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The father of a 15-year-old boy and the teen's godfather are accused of handcuffing him for days—beating him, pouring buckets of iced water on him and spraying him with cold water, the Chicago Sun-Times reports.
Jose Quilambaqui and Carlos Quizhpi were ordered held on $90,000 bonds after they appeared in court Thursday on kidnapping charges, according to the Cook County State's Attorney's office.
The incident allegedly began on June 14 when the teenager took money from his godfather, and Quizhpi contacted the boy's father, 40-year-old Quilambaqui, to tell him what the boy had done, prosecutors said.
The next day, Quizhpi brought the teen to a barber shop he owns and, that evening, he and the teen's dad handcuffed the boy with his arms behind his back and forced him to sleep in the basement of the shop, prosecutors told Judge James Brown.
The next morning, Quizhpi, 53, allegedly made the teen strip down to his underwear and sprayed the boy with water from a hose while the teen washed himself with a bar of soap.
Then Quizhpi and Quilambaqui "struck victim with a belt while he was forced to kneel and ask for forgiveness," prosecutors allege.
After that, the teen worked throughout the day for his godfather, only to be handcuffed again that night, prosecutors said. The next morning, he was hosed again, prosecutors said. This time his dad allegedly watched.
Then both men "poured buckets of ice water on victim as he was kneeling on the ground," prosecutors said.
The teen then worked again and was handcuffed again later that night.
This time though, he was handcuffed to a miter saw and slept on a piece of drywall using an unidentified witnesses' sweater as a pillow.
The two men allegedly continued pouring ice water and spraying the teen on different, unspecified dates, prosecutors said.
The teen was handcuffed every night until he escaped June 23 with the help of the witness, who worked for Quizhpi as a contractor/handyman, prosecutors said.
The witness helped the teen by "leaving the back door, which had been screwed [shut], unscrewed so victim could get out," prosecutors said.
The teen was taken to a hospital, treated and released.
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Graham Webb Super Silk Reconstructive Shampoo is a gentle, reconstructive conditioning shampoo that replenishes hair with moisture and flexibility. Leaves hair soft, shiny and silky with extraordinary body. Formerly called "Graham Webb Silk Repair Super Silk Shampoo"
Trending Beauty Brands: Ardell, Proraso, Solano, Toppik, Pharmagel, Denman Hair Brush, La Viola

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Springfield police say a stabbing victim walked into Mercy Medical Center in the city around 7:30 Friday night.
Police believe the stabbing happened on Carew Street, and detectives are headed there to investigate.
CBS 3 Springfield has a crew on the way and will update this story as it becomes available.
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Relegation ends Tooting & Mitcham's suffering (From Streatham Guardian)
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Relegation ends Tooting & Mitcham's suffering
2:17pm Thursday 12th April 2012 in Tooting and Mitcham By Graham Moody, Sports Reporter
Tooting & Mitcham's four-year stay in the Ryman Premier League finally came to its inevitable end on Easter Monday.
A 3-0 defeat at Carshalton Athletic, where former Terrors hero Paul Vines scored a hat-trick, confirmed relegation to Ryman Division One South with four games to go.
It followed Friday's 2-1 defeat to AFC Hornchurch at Imperial Fields – where Connor French's goal had briefly looked like causing an upset before the promotion-chasers scored twice late on to snatch the win.
Tooting have now lost their last nine matches as their fight against relegation petered out in the final months of the campaign.
Questions will now be asked about the future of both manager Kenny Brown, who took over from Mark Beard midway through the season, and the first team – who have had their wages slashed in recent weeks.
Former West Ham ace Brown was tasked with avoiding relegation but, despite twice overhauling the playing squad, could not drag the club away from the drop.
Tooting will look to regain pride this Saturday when they host Margate before games against Wealdstone, Hendon and Bury Town.
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text: Love Font Mug by 3 Blonde Bears £12$22.32€15.61$20.76 In stock £1.75$3.25€2.27$3.02 mainland UK delivery - Order now and receive this item on or before Monday 8 September £1.75$3.25€2.27$3.02 mainland UK deliveryEstimated delivery: 2-5 days £6.70$12.46€8.71$11.59 Express Next Day - Order now and receive this item on or before Thursday 4 September Express delivery available International delivery available print colourprint colour (required)Red Blackprint colour (required)Red Blackprint colour (required)Red Blackprint colour (required)Red Black mug sizemug size (required)10 oz mugTravel mug (+ £2)Latte Mug (with handles) (+ £3)mug size (required)10 oz mugTravel mug (+ $3.72)Latte Mug (with handles) (+ $5.58)mug size (required)10 oz mugTravel mug (+ €2.60)Latte Mug (with handles) (+ €3.90)mug size (required)10 oz mugTravel mug (+ $3.46)Latte Mug (with handles) (+ $5.19) quantity by 3 Blonde Bears Location: West Sussex, GB read seller's profile see seller's complete range more items from this seller Love Font Cushion £22$40.92€28.62$38.07 Love Font Placemat £10$18.60€13.01$17.30 Love Font Mug £12$22.32€15.61$20.76 Personalised Name Cushions £24$44.64€31.22$41.53 Personalised Love's Travel Mug £16$29.76€20.81$27.68 Personalised Love's Mug £15$27.90€19.51$25.95 view all you may also like PRODUCT DETAILS DELIVERY RETURNS gift wrapping available exclusive ask seller a question One of our favourite household items, this Love Font Mug is for the truly stylish hot drink drinker in your life. We literally LOVE these super stylish Love Font Mugs. A great way of showing that special someone how you feel about them. Why not take them a cuppa in bed on the big day! The mugs are great for any gifting occasion, from Valentines day right through to wedding gifts on a couples special day. We have two colours to choose from, Red or Black. Scroll through the images to see them. There are several types of mug to choose from: Standard 10oz mug £12 Travel mug with a silicon lid £14 Large latte mug (with handle) £15 made from: The mugs are microwave and dishwasher safe. The mugs are packed in postal boxes. We can hand write a message of your choice on an off white gift tag. To discuss your corporate gift needs, enquire about product personalisation and place your order please contact our corporate gift service team on 0844 745 9626 or by submitting a 'contact me' form on the corporate gifts page. dimensions: 10oz mug H 9cm Travel mug H 12cm Latte mug H 13 cm Copyright and all intellectual property rights of the Personalised '...is for Mugs' concept and all designs are strictly owned 3 Blonde Bears Ltd. product code: 305788 This product is dispatched to you by 3 Blonde Bears. MAINLAND UK order now and receive this item on or before price Standard Delivery Monday 8 September £1.75$3.25€2.27$3.02 Two Day Delivery Friday 5 September £5.70$10.60€7.41$9.86 Express Next Day Thursday 4 September £6.70$12.46€8.71$11.59 NON-MAINLAND UK estimated delivery price Highlands & Islands of Scotland 2-5 daysfrom dispatch £1.75$3.25€2.27$3.02 Northern Ireland 2-5 daysfrom dispatch £1.75$3.25€2.27$3.02 Other UK Islands 2-5 daysfrom dispatch £3.95$7.34€5.13$6.83 INTERNATIONAL DELIVERY estimated delivery price Western Europe 2-5 daysfrom dispatch £4.45$8.27€5.79$7.70 Rest of Europe 5-10 daysfrom dispatch £4.45$8.27€5.79$7.70 USA & Canada 5-10 daysfrom dispatch £6.95$12.92€9.04$12.02 Far East & Australasia 5-10 daysfrom dispatch £6.95$12.92€9.04$12.02 Rest of the world 5-14 daysfrom dispatch £6.95$12.92€9.04$12.02 You have 28 days, from receipt of cancellable goods, to notify the seller if you wish to cancel your order or exchange an item. Please note: goods that are personalised, bespoke or made-to-order to your specific requirements, perishable products and personal items sold with a hygiene seal (cosmetics, underwear) in instances where the seal is broken are non-refundable, unless faulty. Read more about our returns policy.Should you choose to return or exchange your order you will need to deliver the item(s) to the UK, where this seller is based. 3 Blonde Bears's return policy


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First Person Teacher Resources
Find First Person educational ideas and activities
Showing 1 - 20 of 2,204 resources
In this personal narratives worksheet, students are given 4 writing prompts for a personal narrative and are directed to write about a time they spent with family members, or write about a time they learned to do something new, or write about something they do for fun. Students then answer 5 fill in the blank questions where they provide first person pronouns to complete sentences.
Part of the Read 180 curriculum for English language learners, this plan prompts writers to sharpen their skills. They select one of four listed personal narrative writing prompts to complete and respond to six questions that require them to review how to write with a first person point of view.
Analyze photographs and make inferences about the lives of the people depicted in them. Individuals will exhibit their understanding of first-person narratives when they then use this information as a basis for writing a children's story from the perspective of an inanimate object. Creative and engaging way to practice first-person writing!
Fourth graders identify the point of view. In this point of view lesson students compare and contrast the point of view from third person omniscient and first person. Students rewrite a paragraph in an alternative point of view.
Students read a New York Times article to examine strong first person voice in essays about reading. They write their own first person essays about some aspect of reading, participate in peer review, and re-writing.
Students read and discuss a chapter from the book "A Dog's Life," focusing on the point of view of the dog in the story. They explore dog rescue organization websites, and play the online game "Bone Travels On," creating a story map and telling their version of the story from a first-person point of view.
"First-Person Narratives of the American South," a collection of primary source materials, offer class members a chance to compare the views of two women who experienced Major General William Tecumseh Sherman's March to the Sea. Using the provided worksheet, groups focus their comparisons on the women's views on slavery, their experience of the march, or their beliefs. For the male perspective of this event a link to the journal of George Washington Baker is provided.
Fifth graders identify first and third person points of view in literature. In this point of view lesson students compare the point of view in different pieces of literature, some telling the same story. Students write a first-person narrative about an event in their life. Students also write a third-person narrative about an event that happened to one or two other people.
The words I, me, and my are the first clues learners will use as they are introduced to identifying first person point of view. First the class charts word clues that usually indicate first person, then they read a story as a class and practice identifying point of view, and finally they complete a point of view worksheet to reinforce the concept.
In this writing worksheet, learners focus on first person point of view as the read a selection entitled, "Tornado." They underline and record sentences from the selection that show first person point of view. They write ideas for a personal story that will be written in the first person.
Don't just teach your ELA class about point-of-view, get them writing! Read the illustrated book I, Doko: The Tale of a Basket to your class and discuss how the story is told from the first-person point of view of an inanimate object: a basket. Use the included worksheets, pictures, and research activities to get your class further exploring this style of creative writing. By the end of these four days of planned activities, your young writers will be able to tackle their own first-person narrative!
In the Time of the Butterflies by Julia Alvarez is written from many points of view. Discuss the unique way she reveals the plot as well as the general benefits and downfalls of various points of view. Next, have class members write their own pieces, playing with point of view as they narrate a personal experience.
Students examine perspectives of the Civil War. In this Civil War lesson, students read first person narratives of the Civil War from 2 women on the homefront. Students compare and contrast the narratives of the women with one another. Students may also compare them their points of view with that of a male.
Ever wish you had a packet that would support your learners as they prepare to write a narrative text? This comprehensive and well-scaffolded packet provides multiple support ideas for engaging learners in the narrative writing process. It includes ideas to write about, a five-day breakdown of the writing process, an editorial checklist, and two worksheets. The worksheets focus on using details to support a main idea and organizing a story by outlining the beginning, middle, and end. Just print it and use it!
Sixth graders explain what a point of view is. They list two different types of examples of third person point of view and identify the difference between a third person limited and third person omniscient . Additionally, they read a piece of a story and identify the point of view and record reasoning how they found it. Materials to support are included.
Students identify a pivotal event in world history that they would have liked to have witnessed. They then research this event and write a first-person account of it as if they had been present. Their first-prerson account is modeled after an article they read by Richard Berstein on events in Afghanistan.
Start kids thinking about point of view and autobiographies by telling them a short story about your morning (first person), and then asking a volunteer to re-tell the story to you (second person). There are tips to help you tie this anticipatory activity into the nonfiction genre, and kids explore six types of autobiographies using a graphic organizer. They learn about how to identify a book as an autobiography using book features like the back cover summary. There are sample covers included that you can display or hand out, asking kids to look for genre clues. Writers synthesize these concepts by using one of four sentence starters to write a memoir of their own, taking on one of the autobiography types that resonated with them. There are six sample autobiography excerpts included for guided practice. Which words clues readers in to the genre?
Learners define first, second, and third person point of view. They listen to the same poem written from the first and then the third person point of view, and identify common words and features apparent in each version. Then, they independently read poetry and label the point of view of each poem.
In this subjective pronouns learning exercise, students determine singular and plural pronouns referring to first person, second person, and third person nouns. Students complete fifteen activities.
A creative spin occurs when one pupil acts as author Ann M. Martin. Using a Q & A at the back of her book A Dog's Life, other classmates ask the "author" questions. They discuss the reasons why they know the book is from a first-person perspective. Next, individuals write a tale told from an animal's point of view. They then create a computer-generated story using what they've written.


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Univision Nets Gold Cup Rights As Part of Expansive CONCACAF PactDeal covers Spanish, Portuguese multimedia rights to popular biennial event from 2013-21 10/29/2012 03:17:01 PM Eastern
In the second major soccer pact in as many days, Univision Deportes has signed a 10-year deal with CONCACAF, encompassing an array of competitions highlighted by rights to the Gold Cup.
The deal, the longest in the history of the Confederation of North, Central American and Caribbean Association Football, which represents FIFA in this part of the world, gives Univision Deportes the Spanish- and Portuguese-language multimedia rights to the Gold Cup, the biennial competition that has grown to a dozen nations across the region. The Gold Cup, Copa Ora, will be held next year, as well as in 2015, 2017, 2019 and 2021.
Fox Sports Media Group holds the English-language rights to the event.


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Appendix C
Hand-Washing Recommendations to Reduce Disease Transmission
From Animals in Public Settings
Hand washing is the single most important prevention step for reducing disease transmission. Hands should always be washed upon exiting animal areas and before eating or drinking. Venue staff should encourage hand washing as persons exit animal areas.
How to Wash Hands
- Wet hands with running water; place soap in palms; rub together to make a lather; scrub hands vigorously for 20 seconds; rinse soap off hands.
- If possible, turn off the faucet by using a disposable paper towel.
- Dry hands with a disposable paper towel. Do not dry hands on clothing.
- Assist young children with washing their hands.
Hand-Washing Facilities or Stations
- Hand-washing facilities should be accessible and sufficient for the maximum anticipated attendance and configured for use by children (low enough for them to reach or equipped with a stool), adults, and those with disabilities.
- Hand-washing stations should be conveniently located in transition areas between animal and nonanimal areas and in the nonanimal food concession areas.
- Maintenance should include routine cleaning and restocking to ensure adequate supply of paper towels and soap.
- Running water should be of sufficient volume and pressure to remove soil from hands. Volume and pressure might be substantially reduced if the water supply is furnished from a holding tank. Therefore, a permanent pressured water supply is preferable.
- The hand-washing station should be designed so that both hands are free for hand washing by having operation with a foot pedal or water that stays on after turning on hand faucets.
- Hot water is preferable, but if the hand-washing stations are supplied with only cold water, a soap that emulsifies easily in cold water should be provided.
- Communal basins, where water is used by more than one person, do not constitute adequate hand-washing facilities.
Hand-Washing Agents
- Liquid soap dispensed by a hand or foot pump is recommended.
- Alcohol-based hand sanitizers can be used if soap and water cannot be made available and are effective against multiple common disease agents (e.g., shiga toxin-producing E. coli, Salmonella, and Campylobacter). However, they are ineffective against certain organisms (e.g., bacterial spores, Cryptosporidium, and certain viruses).
- The U.S. Food and Drug Administration recommends using an alcohol-based hand sanitizer with a concentration of 60% or higher to be effective against common disease agents.
- Hand sanitizers are less effective if hands are visibly soiled. Therefore, visible contamination and dirt should be removed to the extent possible before using hand sanitizers.
Hand-Washing Signs
- At venues where human-animal contact occurs, signs regarding proper hand-washing practices are critical to reduce disease transmission.
- Signs that are reminders to wash hands should be posted at exits from animal areas (exit transition areas) and in nonanimal areas where food is served and consumed.
- Signs should be present to direct all visitors to hand-washing stations upon exiting animal areas.
- Signs with proper hand-washing instructions should be posted at hand-washing stations and restrooms to encourage proper practices.
- Depending on the setting, hand washing signs might need to be available in different languages.
Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of
Health and Human Services.
References to non-CDC sites on the Internet are provided as a service to MMWR readers and do not constitute or imply endorsement of these organizations or their programs by CDC or the U.S. Department of Health and Human Services. CDC is not responsible for the content of pages found at these sites. URL addresses listed in MMWR were current as of the date of publication.
All MMWR HTML versions of articles are electronic conversions from typeset documents.
This conversion might result in character translation or format errors in the HTML version.
Users are referred to the electronic PDF version (http://www.cdc.gov/mmwr)
and/or the original MMWR paper copy for printable versions of official text, figures, and tables.
An original paper copy of this issue can be obtained from the Superintendent of Documents, U.S.
Government Printing Office (GPO), Washington, DC 20402-9371;
telephone: (202) 512-1800. Contact GPO for current prices.
**Questions or messages regarding errors in formatting should be addressed to email@example.com.


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Kern County Raceway Park, fueled by Monster Energy, returns to action after a one week break with the return of the NASCAR Pro Late Models to highlight a busy night of racing.
The second round of champions have been crowned by Kern County Raceway Park Saturday night.
Kern County Raceway Park will be presenting a triple-header on the half-mile track, the championship finales for the INEX Legends and Bandoleros as well as the Faster Pastor races for Saturday's "Faith & Family Night".
Brian Richardson took his second NASCAR CITGO Lubricants Late Model win in a race with David Mayhew at Kern County Raceway Park's KUZZ Night at the Races.
KERN COUNTY RACEWAY PARK -News Bulletin
David Mayhew won his 14th and 15th races on Saturday in the NASCAR CITGO Lubricants Late Model 35 lap events on the half-mile speedway at Kern County Raceway Park.
The SPEARS SRL Southwest Tour returned to Bakersfield on Saturday after eight years.
Ross Strmiska became the eighth Pro Late Model winner this year along with David Mayhew who scored his 13th victory in a banner year as the points leader at Kern County Raceway Park's Budweiser night on Saturday.
A NASCAR Late Model doubleheader will be hosted by Kern County Raceway Park, sponsored by Monster energy on Budweiser night on Saturday.
David Mayhew, leader of the NASCAR CITGO Lubricants Late Model points, scored his ninth and tenth wins this year on Saturday night at Kern County Raceway Park.
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BPL Community Profile
Greg Mihalik (greg23) - BPL Premium Member
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All Forum Posts by Greg Mihalik
Showing 3641 - 3650 of 5083 | Page: 1 ...356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 ...509
What Color is Cuban Breen/Stealth ?
I'm trying to find an image of Breen/Stealth Cuban. I want to see what it looks like compared to white. Can anyone point me to a comparative photo showing what this looks like? Or comment...
Re: Re: Caravans/Rv's as a Basecamp
Kimberly, Catalina State Park? g.
An Exped Pillow Pump and a Stephenson DAM
I received my Exped Pillow Pump today and I am a happy camper! The Exped "business end" of the Pillow Pump is smaller than the receiver of the DAM. However, Exped includes somethi...
Re: conduit and canister
Ben, I always use a drysack - a Granite Gear eVent Sil Drysack to be specific - to keep my crucial gear dry, but I have seen other posts here that suggest not even using a stuff sack. I like ...
Re: Re: Re: Neo in a box
I think they are seconds...cosmetic issues, stray hairs ... you know...
Re: Toes getting beat up
"...2nd to 5th toes and in particular the 3rd through 5th ones on each foot ... seem to get beat up (as in small blisters and sometimes nail damage)..." Small blisters where? Top, end...
Re: Lunar Duo Doors
Well, my Duo had a door on each side. As for your mental status.....
Re: plantar warts
"...could the way i am forced to walk and hike b/c of the plantar wart be good for me?..." IMHO - Not good! "Use is outside the design specification." OTOH, if you were r...
Re: just curious about floor
It means the silnylon floor is attached to the top by a "rim" of netting. If you used a ground sheet it would slide underneath the floor.
Recording Thermometer - Brunton ADC Wind
Brunton ADC Wind The temperature range is -25°C to 60°C (-13°F to 140°F) It records the hour average, for the past 24 hours. It does Not have a computer interface. You click forward...
All Reader Reviews by Greg Mihalik
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Therm-a-Rest Neoair
This rating reflects use below 40° F. For summer use it could go much higher. I have wanted to try the Therm-A-Rest Neoair (72"), hoping it would be both light and warm. I've been thr...
Petzl e+LITE
Just to get my experience into this thread here is a ...
Alpkit CarbonLite
Poor packing on my part resulted in a TD 12-10 stove getting a little squashed. I straightened it out as best possible and continued to use it for 8 more days, with no discernable loss of functionali...


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I have incorporated my watercolor arts, into a booklet outline for pricing and ordering of said items. My Original Watercolors can now be mounted on canvas print. I hope you will check them out.
About the AuthorMelody Koert
Yapsalot2 Lelystad, Netherlands
I've been living in Netherlands for 10 years, since I married Marcel Koert. I am an American, born in New Boston Ohio, but spent most of my life in Florida. I can't think of a better place to live, than my city of Lelystad. There are a lot of drawbacks to living in Netherlands, "Expenses", "High Taxes", "Space" etc., but it's well worth it. The beauty cannot be beat. My dutch is terrible, but thank goodness 80% or more Nederlanders, speak and understand English. I'm living like I'm on a vacation everyday. I never get tired of seeing all the places and sites. It's history is everywhere, on every corner, in every street. I'm enjoying myself to the MAX!
Publish Date August 12, 2007
Dimensions Small Square 22 pgs Standard Paper
Category Arts & Photography
Tags Animal Art, Flower Art, Holland Art, Landscape Art, Miscellaneous Art, Netherlands Art, Portrait Art, Scenery Art, Seasonal Art, Watercolor Art, Art
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Oracle Plans to Talk up Sun Hardware
We've been wondering aloud for months now about what might happen to Sun's hardware once (and if, I guess) the deal finally finishes (we're waiting on EU approval now).
Guru Tips For The Linux Road Warrior
What is your impression of the Linux road warrior?
|Page 164 of 172
The Linux Foundation is a non-profit consortium dedicated to the growth of Linux.
Join / Linux Training / Board


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Hobbs' Food Poisoning and Food Hygiene, Seventh EditionTaylor and Francis 2012; US$ 44.95
This unique textbook takes a holistic approach to food poisoning and food hygiene, explaining in clear and non-technical language the causes of food poisoning with practical examples from 'real-life' outbreaks. Now in its seventh edition, the book retains its longstanding clarity, while being completely revised and updated by a new team of editors... more...
Complete Biographical Encyclopedia of Pulitzer Prize Winners 1917 - 2000De Gruyter 2002; US$ 182.00
This informative series gives access to Pulitzer Prize-winning material and a comprehensive, systematic listing of materials and select reprints. Each volume is devoted to one prize category. Chronological coverage includes analyses, provided by the prize administration, of the factors behind awarding each prize. more...
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Manufacturing Handbook of Best PracticesTaylor and Francis 2001; US$ 164.95
Manufacturing Handbook of Best Practices: An Innovation, Productivity, and Quality Focus gives you a working knowledge of today's cutting edge tools - preparing you for the way you will be doing your job tomorrow. With contributions from seasoned manufacturing experts, the book provides a single-source reference to what's currently happening in modern... more...
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Scum AirwaysMainstream Publishing 2011; US$ 11.53
Football is big business and it doesn't come much bigger than Manchester United - commercial giants and the richest club in the world. But in the shadow of Old Trafford a black economy is growing to rival the commercial power of the official sales channels. Scum Airways is an inside investigation of the Manchester grafters - touts, black marketeers... more...
Evaluation of Certain Veterinary Drug Residues in FoodWorld Health Organization 2001; US$ 18.00
This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of veterinary drugs within the terms of reference of... more...
The Business of FoodGreenwood Publishing Group 2007; US$ 85.00
The business of food and drink is for better and worse the business of our nation and our planet, and to most consumers how it works remains largely a mystery. This encyclopedia takes readers as consumers behind the scenes of the food and drink industries. The contributors come from a wide range of fields, and the scope of this encyclopedia is broad,... more...
Chocolate FortunesAMACOM 2009; US$ 3.99
Could there be a more intriguing East-meets-West story than one about the introduction of chocolate?that very symbol of Western indulgence?to legendarily austere China? more...
The British on HolidayChannel View Publications 2011; US$ 25.00
This book is the only in-depth ethnographic study of British charter tourists. It is based on several months of participant observation of British charter tourists on holiday in Palmanova and Magaluf on the Mediterranean Island of Mallorca. With a focus on space, the body, and food and drink practices, the book explores the experiential nature of touristic... more...


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Look of the Day: Good Clean Fun
by POPSUGAR Fashion 39 Reactions 0 Shares Print
No crazy patterns or colors here - just a light white top and high-waisted blue jeans. krystinabell is ready for some good clean fun with an outfit that makes me think "effortless perfection." And, as an afterthought: those high-waisted jeans look great on her - "mom jeans" doesn't enter my mind when I see this.
Here's what she's wearing:
- Shirt: Peepshow
- Jeans: Grey Ant
- Belt: Linea Pelle
- Earrings: Joyce Leslie
Congrats to krystinabell!
Everyone else, submit your looks today and I just might feature you on FabSugar! If you live overseas and have a fab outfit to share, join the Overseas Fashionistas Group and to submit a Look in this group learn how to post a blog.
Read More High-waisted JeansLook Of The Day
marryd2nordstrom 6 years
i love the high-waisted pants and delicate top. so cute!
whtevjenny 7 years
soo incredibly flattering on you!
kh312 7 years
whats wrong with me today?? i mean- totally something i would wear.
kh312 7 years
very,very nice.total something i would wear.
catmousebird 7 years
I LOVE THIS! I love the high waisted denim. I love the waist of the shirt. Oh, I just love this outfit. The colors are minimal, but there's a lot of fun cuts.
DulceKisses 7 years
its really bonita!
DulceKisses 7 years
its really bonita!
JustPlainJane 7 years
Great outfit, beautiful
JustPlainJane 7 years
Great outfit, beautiful
Chalii911 7 years
Wow this is so pretty and feminine! Yet classy! I really like it! She pulled it off really good! =)
krystinabell 7 years
Thanks so much everyone! This totally made my whole week!!!
sbshoulda 7 years
Super simple, super clean, super sexy, and super cool!
leeluvfashion 7 years
Love the look!
leeluvfashion 7 years
Love the look!
kkay 7 years
nothing beats a simple white top with jeans! so cute!
sandra-werner 7 years
Absolutely stunning! Congratulations Miss Krystina!!! :)
shini 7 years
Congrats, I LOVE this fasihon!!! :D you deserve this look of day ...great style!
seespotrun 7 years
Looks great but can't really see the jeans well. Wish we could get a clearer picture.
Vannuccia 7 years
Understated, yet stylish :)
Vannuccia 7 years
Understated, yet stylish :)
PrissyLilBadAss 7 years
OMG, this is my favorite look ever!!! I need that top!
ariel784 7 years
This is the best look ever! I LOVE that top! As a matter of fact, where can I get one so I can look FAB too?? Anyone?
nyaradzom2001 7 years
I hate you lol for looking so fabulous.
JBlondie 7 years
Looks great!
JBlondie 7 years
Looks great!
Lala77 7 years
love the whole outfit , just gorgeous :)
nybella 7 years
i really love the jeans
nybella 7 years
i really love the jeans
zc 7 years
love it..very simple yet stunning...well done.
angeldevilwings 7 years
I love it, always was a fan of clean and simple look but I'm still not gonna wear the high waist pants.
CestLaVie 7 years
Looks great, top is adorable and simple earrings were a nice choice.
christiana30 7 years
wow tina how you do this? nice..very nice
vienvien 7 years
Seraphim 7 years
this is probably the first time i've thought something was cute!!! woohoo CUTE :)
Seraphim 7 years
this is probably the first time i've thought something was cute!!! woohooCUTE :)
pipette1110 7 years
i really love it! it's simple but so beautiful. We don't have that kind of clothes in Belgium...
HuongStar 7 years
This is probably the best outfit featured yet! Very current without looking contrived, such a well put-together look that is flattering to her shape. I especially love that top!
any 7 years
is cute!:D
any 7 years
is cute!:D
Link Love
- The star poses for the first public issue of Herring & Herring — Fashionista
- 5 solid reasons to go faux when it comes to leather — HuffPost Style
- Here's some Gwyneth-approved jewelry to adorn yourself with — InStyle
- This is neither a blazer nor a cardigan, but you need it — Lucky
- You don't even realize you're making these major style mistakes — Who What Wear
- This designer's making a foray into the tech world — The Cut
- Hillary Clinton's pantsuits are more powerful than you think — Racked
- This is what designers think of #FashionWeek — The Fashion Spot
- If she knows a chic runway, Nina Garcia knows a chic home — Domaine Home


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Enjoy a safe and happy Summer Break!
Target Range Family,
We ask for your cooperation to extend a courtesy to our surrounding school neighbors living on South Avenue, Gunsight Court, and Clements Avenue. If you have school business, school events, dropping off or picking up your children, please park in the school parking areas that are provided on our campus.
Thank you very much for your cooperation.
If you do not have the handicapped designation on your vehicle, please be courteous and stop your vehicle in a different location. In addition, please do not pull into handicapped parking areas even when you are just "dropping off" or "picking up" students. More Information


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The 10 Worst Things About Rick Perry (And Why It Would Be Really Bad If He Runs for President)
Continued from previous page
8. Drill, baby, drill
Obviously the governor of Texas has some oil connections. But with Perry as a candidate, we're almost certain to have more of the sort of pro-oil, anti-environment rhetoric that suffused Sarah Palin's tenure on the Republican ticket.
After all, when the BP spill was still churning oil into the Gulf of Mexico, Perry called it "just an act of God" and warned against any "knee-jerk reaction" that might include things like halting deepwater drilling until the dangers could be assessed. Unsurprisingly, Perry also got $129,890 from the oil and gas industry for his last reelection campaign.
Increases in oil prices tend to be good for Texas—bringing jobs and a rise in GDP for the state—but they're a drain on the rest of the country. And the last thing the country needs is a president who's more interested in maintaining oil profits than preventing more oil-related disasters.
9. Flip-flopping on immigration
Texas' population has grown 20 percent during Perry's time in office, and much of that growth has been immigration from Latin America. Up until he began toying with the idea of a presidential run, Perry was a moderate on immigration.
Even last year, he criticized Arizona's SB 1070, and way back in 2001 he signed the state DREAM Act into law. So why the sudden change?
Shani O. Hilton at ColorLines writes:
"...Perry's apparently positioning himself to be a social conservative darling. On immigration, he recently revived a bill that would crack down on so-called 'sanctuary' cities — localities where the government prohibits police officers from asking about the immigration status of legally detained residents."
The sanctuary cities bill would allow police to inquire about immigration status of any person arrested or detained—even at a routine traffic stop.
It's worth noting that Perry's big business buddies oppose this legislation—and that his willingness to make them angry might just be the clearest sign yet that he's aiming for the national stage.
10. Executing an innocent man
Rick Perry has presided over the execution of 232 people, more than any other governor in history. (The previous record, 152, was held by George W. Bush.) Most of those are forgotten, but a few of them stick out.
Liliana Segura wrote:
"Outside of Texas, the name Cameron Todd Willingham did not mean much to most people until the fall of 2009. In a 17-page article published by The New Yorker magazine, a curious and brave woman, a brilliant fire expert, and an investigative journalist re-opened the case against this man who was put to death for killing his children. The 'classic arson case' was picked apart, revealed to have been based on junk science and a misguided sense of expert intuition. Proof of the flawed fire investigation had been rushed to Rick Perry and the Texas Board of Pardons and Parole before the execution, to no avail. Five years later, the article uncovered new evidence to all but confirm what a number of people had suspected for years: That the state of Texas had executed an innocent man."
Perry's utter lack of interest in examining the evidence of Willingham's innocence shows us something about the man, of course. (It won't be the first time a presidential candidate faces down a questionable execution on the campaign trail. Bill Clinton, back in 1992, interrupted his campaign in New Hampshire to fly home to Arkansas, where a severely mentally challenged man sat on death row. Clinton wasn't going back to stop the execution, though. He was going to preside over it. And one of George W. Bush's first acts as governor of Texas was to reject clemency for a man who had severe brain damage and an IQ of 60. He was executed the evening of Bush's inauguration.)
Stay up to date with the latest headlines via email


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Kitchen Jobs in Vancouver
Related Jobs: Kitchen Designer, Kitchen Helper, Kitchen Installer, Kitchen Manager, Kitchen Assistant
Japanese (kitchen) cook
Asa Sushi Japanese Restaurant - Vancouver, British Columbia
Prepare and cook various types of Japanese foods including u-don, tempura, katsu-don, donburi, teriyaki and other Japanese dishes Working Hours: 8hrs/day, 40hrs/week Kitchen Work careers Vancouver... Permanent, Full Time... $16.50 Hourly
from: workbc.ca - 20 days ago
Japanese (Kitchen) cook
Asa Sushi Japanese Restaurant - Vancouver
Preparing various types of Japanese foods including u-don, tempura, katsu-don, donburi, teriyaki and other Japanese dishes; Company Address: 2178 West 41st Avenue, Vancouver, BC V6M 1Z1 Position: Cook Kitchen careers Vancouver... Full Time...
from: Allstarjobs.ca - 20 days ago
Kitchen Manager (Lower Mainland)
WHITE SPOT RESTAURANT - Vancouver, British Columbia
White Spot is a great place to visit for any meal occasion and it is a wonderful place to work. In fact, we are currently looking for Kitchen Managers for various Lower Mainland locations. - Ensuring all standards and policies are followed, including... Indian Kitchen Helper in Vancouver...
from: workopolis.com (+1 source) - 27 days ago
Full-time Kitchen Chef (Asian cuisines)
Sushigo Food Ltd. dba. Sushigo - Vancouver
Salary: $3,820/monthly ($1,910/semi-monthly)/ 40 hours a week *Improve food service and tasty. Education: completion of high school Kitchen Helper in Vancouver...
from: Allstarjobs.ca - 20 days ago
Line Cook/Kitchen Helper
Vancouver, Canada Area
That being said....if you don't have a lot of experience, but know the basics of how a restaurant or pub kitchen are run....then let us know! We still may have a spot for you! Wages depend on experience. Medical and Dental provided Kitchen Designer in Vancouver... Full Time...
from: linkedin.com - 27 days ago
Kitchen and Bath Sales associate
Home Depot Canada - Vancouver, British Columbia
Working here is about more than helping customers choose the right product. Its about making a difference in their lives. We call it "unleashing your inner orange" and its the ability to tap into our inner potential to help customers create a space worth... School Kitchen... Part-Time...
from: swistic.com - More than 30 days ago
Full Time Restaurant Line Cook - Earls (Fir & Broadway)
EARLS KITCHEN & BAR - Vancouver, British Columbia
There are many different stations on the Line: panfry, salads, desserts and more. All of these stations contribute to deliver irresistible food that wows our guests and leaves them craving another visit. We train our Line Cooks to learn each station,... Kitchen Installer in Vancouver bc... Full Time...
from: workopolis.com - 28 days ago
Full Time Restaurant Prep Cook - Earls (Fir & Broadway)
EARLS KITCHEN & BAR - Vancouver, British Columbia
There are multiple roles on our Prep Cooks: from Produce and Protein to Sauces and Bake, our Prep Cooks are integral to setting each restaurant up for success. We train our Prep Cooks to learn each station, slowly building their skills in the kitchen... Kitchen Industry... Full Time...
from: workopolis.com - 28 days ago
Food Safety & Brand Standards Specialist Job
Ecolab - Vancouver, BC
EcoSure, a division of Ecolab, provides industry leading, customized programs for food safety, brand protection and business enhancement. These programs help our chain customers meet their specific quality standards through on-site evaluations and custom... Packer Kitchen Helper in Vancouver...
from: Ecolab - 11 days ago
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Part Time Hostess/Host - Earls (Hornby & Smithe)
EARLS KITCHEN & BAR - Vancouver, British Columbia
At Earls, our Hostesses/Hosts are the "quarterbacks" of our service team, responsible for creating the flow of guests into our restaurant and making sure that there is a rhythm to ensure our kitchen and servers can deliver fantastic service. This is a... Kitchen jobs in Hamilton... Part-Time...
from: workopolis.com - 28 days ago


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World Cup 2014: Will Spain bounce back in clash with Chile today? (From Bournemouth Echo)
When news happens text pix and video to 80360. Start your message with BE then leave a space.
World Cup 2014: Will Spain bounce back in clash with Chile today?
11:55am Wednesday 18th June 2014 in News By Steven Smith, Chief Reporter
AFTER their disastrous result in their first match against the Netherlands, Spain will be looking to get back on track in their second Group B game today.
Kicking off at 8pm, it won't be an easy task, with their opponents Chile buzzing on the back of their 3-1 win against Australia last Friday.
And the Aussies are bound to be fearing the Dutch in their 5pm game after they hammered Spain 5-1 in a repeat of the 2010 final.
Holland were in scintillating form, sweeping aside the nation that beat them to lift the trophy four years ago.
Half-Spanish Darren Rodriguez, who lives in Bournemouth, said: "Well, after the unexpected tonking we got against the Dutch, the media have been full of whether the 'tiki taka' period of success we've had is over.
"The Dutch played very well but Spain were awful, especially in defence.
"Ramos, Pique and Casillas, the backbone for so many years, creaked like an old barn door. It could have been Casillas last game perhaps?
"Xavi looked old and costa up front didn't do anything to warrant his place.
"I feel (manager) Del Bosque may make changes, especially as Pedro, Fabregas, Mata, and Cazorla were all on the bench. Still fancy Spain to bounce back, a 1-0 win is my prediction."
The day ends with the Group A encounter between Cameroon and Croatia at 11pm, with both sides looking to bounce back from defeats to Mexico and Brazil respectively in their first matches.
All our stories on the World Cup, plus fixtures and results, group tables and more in our World Cup section
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Nigeria's main opposition party, All Progressives Congress, APC, has demanded the immediate trial, by the International Criminal Court
NVS Welcomes your articles and viewpoints.
Disclaimer: Statements and opinions expressed in articles, reviews and other materials herein are those of the authors. NVS will not be held responsible for any claim, loss, damage or inconvenience caused as a result of any information within these pages or any information accessed through this site.
BREAKING: Hand over Sheriff, Ihejirika to ICC, APC tells Jonathan
Plateau 2015: Why not another Berom?
While in many other climes in the Nigerian polity, religion and party affiliation would play a role, the two former will play very little roles given the dynamics in Plateau state.
Nigerians holed up in their disguise
He is not that " beautiful" man among the present set of people harloting around with the "God sent me", "I know I can solve the nation's problem", "I will continue with the reforms" and similar lines, that is different.
61% of Nigerians approve Jonathan's performance – Survey
The latest governance poll conducted by the NOIPolls Limited indicated that 61 percent of adult Nigerians have approved the job performance of President Goodluck Jonathan last month, especially in the area of improved electricity supply to some house
Combating the Spread of Ebola through Compulsory Reporting
After the reported incident in Port Harcourt that resulted in the death of a doctor, the government must now as a matter of urgency require every hotel and guest house up and down the country to take and keep a temperature reading of EVERY guest.
Marilyn Ogar: Becoming The News
In my view, on that occasion, Ms Ogar did quite well speaking for the Department of State Security (DSS) and for Nigerian security agencies in general. Oh, she veered off into non-answer and banalities once or twice


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I've chatted with security wonks who work for the feds, and they're as sharp as anyone when it comes to hacking. It's the other cops who are the problem. All it takes is one weak link, and your entire op is compromised.
Anonymous knows this better than anyone. And now the whole world has been apprised.
In other hacking news: Somebody also pwned the home page of the Susan G. Komen Foundation last night. Earlier this week SGK stepped into an Internet hornets' nest when the news broke that it had rescinded nearly $700,000 worth of funding to Planned Parenthood because the group was under "investigation" by Congress.
I won't get into all the issues here (The Atlantic Wire has been doing a great job of following the story). But many people were displeased by what they saw as an attempted hijacking of the anticancer group by right-wing ideologues.
Among those people: The hackers who made a subtle change to the section of the site titled "Susan G. Komen Marathon for the Cure." Instead of saying "Help us get 26.2 or 13.1 miles closer to a world without breast cancer," for a few minutes the page read "Help us run over poor women on our way to the bank."
Bowing to pressure, Komen reversed itself this morning, saying it would continue to fund Planned Parenthood. The hack probably didn't have that much to do with that decision. But the Internet had everything to do with it.
Who else, if anyone, deserves to be hacked? Cast your predictions below or email me: email@example.com.
This article, "Tinker tailor coder spy? Anonymous strikes again," was originally published at InfoWorld.com. Follow the crazy twists and turns of the tech industry with Robert X. Cringely's Notes from the Field blog, and subscribe to Cringely's Notes from the Underground newsletter.


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Ben Zobrist
CBSSports.com: Fantasy Baseball Week 18 Starts And Sits
The fantasy baseball experts at CBSSports.com break down who to start and who to sit for the upcoming week.
10 Players Who Could Get Traded At MLB Trade Deadline
With the MLB trade deadline just two weeks away, it's time to see who could potentially be on the move in late July.
CBSSports.com: Fantasy Baseball Week 10 Starts And Sits
The fantasy baseball experts at CBSSports.com break down who to start and who to sit for the upcoming week.
Who's The Evil Empire Now? Rays Say Rule Gives BoSox Right To Force Doubleheader
The big winner in all this could figure to be the Yankees, who will host a tired Tampa Bay squad for a three-game set starting Friday.
Fantasy Baseball Preview: Shortstop
CBS Local Sports breaks down the top players at shortstop for your fantasy baseball draft.
Fantasy Baseball Preview: Second Base
CBS Local Sports breaks down the top players at second base for your fantasy baseball draft.
Keefe To The City: Joe Girardi To Blame For Yankees' Bad Start
Neil Keefe brings back "The Joe Girardi Show" for a third season after the Yankees' manager made a series of questionable decision in the opening weekend.
Hartnett: Wild Card Wednesday Produces Difficult Path For Yankees
The outcome of 'Wild Card Wednesday' has made the Yankees' playoff match-ups the toughest possible. Verlander and the Tigers are no easy task and the Rays are built for playoff success.
Yankees Do Red Sox No Favors; Soriano Serves Up Game To Rays
Russell Martin has had a unique two days. The Yankees catcher homered and also hit into a triple play in New York's 5-3 loss to the Tampa Bay Rays on Tuesday night.
Jeter's 2,998th Hit Only Highlight Of Yankees' Loss To Rays
Jeff Niemann gave up Derek Jeter's 2,998th hit but little else, B.J. Upton homered and drove in three runs, and the Tampa Bay Rays beat the New York Yankees 5-1 on Thursday night.
Sweeny Says: Heeeere's Johnny Damon
A little quality time with Johnny Damon is always fun. While he'll always be remembered as a key member of the 2009 World Series Champs, he has also led a bit of an itinerant lifestyle as a baseball player.


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This invention provides a method of improving a transplantation of hematopoietic cells from a donor to a recipient to treat a hematopoietic cell tumor in the recipient comprising immunizing the donor's hematopoietic cells with an antigen specific for the recipient's hematopoietic cell tumor, and transplanting the donor's immunized hematopoietic cells to the recipient. Also provided is a composition comprising purified hematopoietic cells primed to produce an immunological response to foreign tumor specific antigen. Also provided is a method of treating a tumor by the transplantation of hematopoietic cells from a donor to a recipient to treat the tumor in the recipient comprising immunizing the donor's hematopoietic cells with an antigen specific for the recipient's tumor, and transplanting the donor's immunized hematopoietic cells to the recipient.
1. A method of improving a transplantation of hematopoietic cells from a human donor to an allogeneic recipient to enhance cellular immunity to treat a hematopoietic cell tumor in the recipient comprising:
a. immunizing the donor's hematopoietic cells with an antigen specific for the recipient's hematopoietic cell tumor; and
b. transplanting the donor's immunized hematopoietic cells directly to the recipient, such that an antigen specific effector T cell immune response to the hematopoietic cell tumor is transferred to the recipient, the donor's transplanted and immunized hematopoietic cells thereby improving the transplantation of the hematopoietic cells to treat the hematopoietic cell tumor in the recipient.
2. The method of claim 1, wherein the antigen comprises an immunoglobulin idiotype.
3. The method of claim 2, wherein the immunoglobulin idiotype further comprises the entire immunoglobulin molecule.
4. The method of claim 2, wherein the immunoglobulin idiotype is an IgG kappa.
5. The method of claim 1, wherein the antigen is conjugated to an immunogenic molecule.
6. The method of claim 5, wherein the immunogenic molecule is keyhole limpet hemocyanin.
7. The method of claim 1, wherein an adjuvant is administered with the antigen.
8. The method of claim 1, wherein the hematopoietic cell tumor is a B-cell malignancy.
9. The method of claim 1, wherein the hematopoietic cell tumor is selected from the group consisting of a myeloma, a lymphoma and a leukemia.
10. The method of claim 1, wherein the donor's hematopoietic cells are bone marrow cells.
11. A composition comprising purified hematopoietic cells primed to produce an effector T cell immune response to a foreign tumor specific antigen, wherein the tumor specific antigen comprises an immunoglobulin idiotype.
12. The composition of claim 11, wherein the immunoglobulin idiotype further comprises the entire immunoglobulin molecule.
13. The composition of claim 11, wherein the imrnmunoglobulin idiotype is an IgG kappa.
14. The composition of claim 11, wherein the hematopoietic cells are bone marrow cells.
15. A method of treating a hematopoietic cell tumor by the transplantation of hcmatopoietic cells from a human donor to an allogeneic recipient to enhance cellular immunity to treat the hematopoietic cell tumor in the recipient comprising:
a. immunizing the donor's hematopoietic cells with an antigen specific for the recipient's hematopoietic cell tumor; and
b. transplanting the donor's immunized hematopoietic cells directly to the recipient, such that an antigen specific effector T cell immune response to the hematopoietic cell tumor is transferred to the recipient, the donor's transplanted and immunized hematopoietic cells thereby treating the hematopoictic cell tumor in the recipient.
16. A method of improving a transplantation of hematopoietic cells from a human donor to an allogeneic recipient to enhance cellular immunity to treat a tumor in the recipient comprising:
a. immunizing the donor's hematopoietic cells with an antigen specific for the recipient's tumor; and
b. transplanting the donor's immunized hematopoictic cells directly to the recipient, such that an antigen specific effector T cell immune response to the tumor is transferred to the recipient, the donor's transplanted and immunized hematopoietic cells thereby improving the transplantation of the hematopoietic cells to treat the tumor in the recipient.
17. A method of treating a tumor by the transplantation of hematopoietic cells from a human donor to an allogeneic recipient to enhance cellular immunity to treat the tumor in the recipient comprising:
a. immunizing the donor's hematopoietic cells with an antigen specific for the recipient's tumor; and
b. transplanting the donor's immunized hematopoietic cells directly to the recipient, such that an antigen specific effector T cell immune response to the tumor is transferred to the recipient, the donor's transplanted and immunized hemopoietic cells thereby treating the tumor in the recipient.
The development of a vaccine against human malignancies has been a long-sought goal which has yet to be achieved. Many of the efforts toward this end have been frustrated by the lack of identification of a tumor-specific antigen which would allow tumor cells to be distinguished from normal cells. Conceptually, such an antigen could be used as a vaccine to induce the host's immune system to reject cells bearing that antigen.
Immunoglobulin (Ig) molecules are composed of heavy and light chains, which possess highly specific variable regions at their amino termini. The variable regions of heavy and light chains combine to form the unique antigen-recognition site of the Ig protein. These variable regions contain determinants (molecule shapes) that can themselves be recognized as antigens, or idiotypes (Id).
B-cell malignancies are composed of clonal proliferations of cells synthesizing a single antibody molecule with unique variable regions in the heavy and light chains. B-cell lymphomas and myelomas are neoplasms of mature lymphocytes which generally express and/or secrete synthesized Ig. The idiotypic determinants of the surface Ig of a B-cell lymphoma or myeloma can thus serve as a tumor-specific marker for the malignant clone.
Studies in experimental animals, as well as in man, have demonstrated the utility of the Ig idiotype as a tumor-specific antigen for the study of the biology of B-cell lymphoma in vitro and as a target for passive immunotherapy in vivo (1-3). Furthermore, active immunization against idiotypic determinants on malignant B-cells has been demonstrated to produce resistance to tumor growth in a number of syngeneic experimental tumor models, as well as specific anti-tumor therapy against established tumors (4-). Furthermore, preclinical studies in subhuman primates demonstrated that optimal immunization with human lymphoma-derived Id required conjugation of the protein to an immunogenic protein carrier (keyhole limpet hemocyanin (KLH)) and emulsification in an adjuvant (15). These results, taken together, provided the rationale for testing autologous tumor-derived idiotypic surface Ig (Id) as a therapeutic "vaccine" against human B-cell malignancies.
The mainstay of therapy for advanced stage myeloma patients with symptoms and signs of progressive disease remains systemic chemotherapy, particularly with alkylating agents and steroids. There is still some controversy regarding the superior efficacy of multiagent intensive chemotherapy regimens, such as the M2 or alternating combination chemotherapy regimens described by the Southwest Oncology Group and Medical Research Council, but most randomized trial results demonstrate only a modest incremental advantage in long-term overall survival compared with standard melphalan and prednisone, with no significant numbers of long-term disease-free survivors (16-23). Thus, although partial remissions of up to 60% are obtained with a variety of regimens, the median survival of about 30 months has remained constant for the last 30 years.
A more aggressive approach with intensive high dose chemoradiotherapy with either autologous or allogeneic bone marrow transplantation (BMT) is currently being explored by several groups of investigators. These protocols have improved initial response rates, although it remains to be seen whether these remissions are maintained with longer follow-up periods (24-28). Regardless of the initial responsiveness rates, the vast majority (>90%) of patients currently treated by these methods experience an eventual relapse of the tumor.
Many groups have described monoclonal B-cell populations in the peripheral blood as well as in the bone marrow of patients with myeloma, and these cells bear the myeloma protein idiotype on their surface as evidence of the clonal identity with the malignant plasma cells (29-37). As the removal of malignant plasma cells by chemotherapy does not appear to deplete the malignant stem cell (38), eradication of these precursor B-cells may ultimately be necessary for successful treatment of this disease.
The goal of the specific strategy described herein was to attempt to transfer tumor antigen-specific immunity induced in a bone marrow donor to a sibling BMT recipient with myeloma, as a means to enhance the therapeutic efficacy of allogeneic BMT. The transfer of induced antigen-specific humoral immunity to viral and other pathogens from immune donors has been explored in BMT patients as a potential therapeutic approach to the problem of increased host susceptibility to infection following the BMT procedure (39-42). A recent report also suggested the possible transfer of Varicella Zoster Virus specific cellular immunity from immune marrow donors to BMT recipients (43). This report, however, was inconclusive as to the origin of the cellular immunity response due to the immunization of both the donor and the recipient. Moreover, the literature reports that transfer of specific cellular immunity cannot be achieved in the context of transplantation (40).
Until this invention only a small percentage (<10%) of investigators had succeeded in eradicating a myeloma through BMT. This percentage is even smaller in the case of patients in the advanced stages of myeloma. The literature does not show that an immune response, and specifically a cellular immune response to a tumor specific antigen, could be transferred exclusively from an immunized donor in a BMT. Thus, donor immunization with myeloma Id represents a very important strategy for enhancing the specific anti-tumor effect of allogeneic marrow grafts.
The present invention provides a method of improving a transplantation of hematopoietic cells from a donor to a recipient to treat a hematopoietic cell tumor in the recipient comprising immunizing the donor's hematopoietic cells with an antigen specific for the recipient's hematopoietic cell tumor and transplanting the donor's immunized hematopoietic cells to the recipient. The donor's transplanted hematopoietic cells improve the transplantation of the hematopoietic cells to treat the hematopoietic cell tumor in the recipient.
Additionally, the invention provides a composition comprising purified hematopoietic cells primed to produce an immunological response to foreign tumor specific antigen.
The present invention provides a method of improving a transplantation, ie. an adoptive transfer, of hematopoietic cells from a donor to a recipient to treat a hematopoietic cell tumor in the recipient comprising immunizing the donor's hematopoietic cells with an antigen specific for the recipient's hematopoietic cell tumor and transplanting the donor's immunized hematopoietic cells to the recipient. The donor's transplanted hematopoietic cells improve the transplantation of the hematopoietic cells to treat the hematopoietic cell tumor in the recipient. Moreover, the method transfers antigen-specific antitumor immunity from an immunized donor to the recipient. Thus, the treatment of any tumor which is treated by donor to recipient hematopoietic cell transplantation can be enhanced using this invention.
Additionally, the invention provides a composition comprising purified hematopoietic cells primed to produce an immunological response to foreign tumor specific antigen. As used herein, "purified" means substantially removed from the presence of naturally occurring proteins, cells or tissues with which the antigens naturally occur. As also used herein "foreign" means the cells are primed to an antigen introduced from a non-self source. The foreign tumor specific antigen can, for example, be derived from an allogeneic tumor, an isogeneic tumor, a syngeneic tumor, or a xenogenic tumor. Therefore, the immunological response can be obtained, for example, from a tumor of an individual of the same species. For example, the tumor can be obtained from a sibling.
In a preferred embodiment the invention also provides that the hematopoietic cells can be T-cell precursors. T-cell precursors contemplates undifferentiated or immature hematopojetic cells which will mature into immunologically competent T-cells. In a more preferred embodiment the hematopoietic cells are bone marrow cells.
The invention also provides that the immunological response to which the cells are primed is a proliferation of peripheral blood mononuclear cells. The invention also contemplates that the immunological response is the production of anti-tumor specific antigen antibodies and cellular immune responses. Furthermore, additional genes, such as those encoding for growth factors, may be introduced into the donor's immunized hematopoietic cells to enhance the immunological response and effectiveness of the present method and composition.
The appropriate tumor specific antigen used in the donor immunization naturally depends on the tumor type being treated. For example, when the tumor is a B-cell myeloma the tumor specific antigen can comprise an immunoglobulin idiotype. This immunoglobulin idiotype can, for example, further comprise the entire immunoglobulin molecule, a Fab, F(ab)2, or the like. For example, the immunoglobulin idiotype can be IgG kappa.
The present invention contemplates the use of various other hematopoietic tumor cell specific antigens. For example, Ras oncoproteins and p53 from leukemia cells may be used to immunize the donor. The present invention contemplates immunizing the donor's hematopoietic cells against solid tumor specific antigens. Such examples of solid tumor specific antigens include carcino-embryonic antigen (CEA) from a colon tumor, Raf oncoprotein from an adenocarcinoma, and GD2 and GD3 from a melanoma. The effectiveness of the particular antigen can be determined following the methods set forth in the Example.
Tumor specific antigens can be obtained, for example, through isolation and purification of immunoglobulins, or immunogenic portions thereof, from naturally occurring B-cell surfaces or from blood plasma. For example, whole cells can be irradiated, sonicated and centrifuged to yield plasma suspended immunoglobulins. The immunoglobulins can be produced either in vivo or in vitro. The immunoglobulins can be produced by growth stimulated cells, genetically engineered cells, or monoclonal antibody producing hybridoma cells. For example, the idiotype can be identified or produced through the use of regional consensus primers and PCR amplification and/or cloning followed by gene expression.
Non-idiotype containing antigens can be obtained following known procedures or are commercially available. See generally, The Oncogene Handbook, T. Curran, E. P. Reddy, and A. Salka (ed.), Elsevier Science Publishers, The Netherlands (1988). Alternatively, appropriately treated, such as by irradiation, whole tumor cells may be used to comprise a tumor specific antigen. Furthermore, the donor's hematopoietic cells may be genetically engineered or recombined with genes encoding other immunological stimulants, such as cytokines, to enhance the present methods and compositions.
In a preferred embodiment, the invention provides that the tumor specific antigen can be conjugated to an immunogenic molecule, for example keyhole limpet hemocyanin (KLH). Other suitable immunogenic molecules include heat shock proteins, cholera toxin, bovine serum albumin, tetanus toxoid, thyroglobulin, and cytokine molecules. The immunogenic molecule can be optimized using standard immunological techniques. Such immunogenic molecules can be conjugated using standard techniques.
In a further preferred embodiment, an adjuvant is administered with the antigen, for example SYNTEX adjuvant formulation 1 (SAF-1) composed of 5 percent (wt/vol) squalane (DASF, Parsippany, N.J.), 2.5 percent Pluronic, L121 polymer (Aldrich Chemical, Milwaukee), and 0.2 percent polysorbate (Tween 80, Sigma) in phosphate-buffered saline. Other suitable adjuvants are well known in the art and include Freund's adjuvant, alum, aluminum phosphate, aluminum hydroxide, N-acetyl-muramyl-L-threonyl-D-isoglutamine (thr-MDP), N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine (CGP 11637, referred to as nor-MDP), N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2-(1'-2'-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy)-ethylamine (CGP 19835A, referred to as MTP-PE), and RIBI, which contains three components extracted from bacteria, monophosphoryl lipid A, trealose dimycolate and cell wall skeleton (MPL+TDM+CWS) in 2% squalene/Tween 80 emulsion. The effectiveness of an adjuvant may be determined by measuring the immune response directed against the antigen using standard procedures.
Furthermore, the invention provides that the hematopoietic cell tumor can be a B-cell or T-cell malignancy, eg. a myeloma, a lymphoma or a leukemia. A B-cell or T-cell malignancy contemplates a monoclonal gammopathy of undetermined significance (MGUS) and premalignancy conditions.
In a preferred embodiment, the donor's hematopoietic cells are bone marrow cells. However, the donor's hematopoietic cells may also be peripheral or lymphoid cells. These peripheral or lymphoid cells can be obtained for example from the blood through leukapheresis.
The donor's hematopoietic cells may be immunized against the recipient's tumor specific antigen either in vivo or in vitro. The in vitro immunization may be accomplished, for example, by exposing the donor's cells to tumor specific antigen in a culture plate (14).
The immunogenic composition can be administered to the donor orally, parenterally (e.g., intravenously), by intramuscular injection, by intraperitoneal injection, topically, transdermally, or the like, although subcutaneous injection is typically preferred. Immunogenic amounts of the antigen can be determined using standard procedures. Briefly, various concentrations of a putative specific immunoreactive epitope are prepared, administered to an animal and the immunological response (e.g., the production of antibodies) of an animal to each concentration is determined. (Arnon, R. (Ed.) Synthetic Vaccines I:83-92, CRC Press, Inc., Boca Raton, Fla., 1987). The exact amount of such compounds required will vary from subject to subject, depending on the species, age, weight and general condition of the subject, the severity of the disease that is being treated, the particular compound used, its mode of administration, and the like. Thus, it is not possible to specify an exact amount. However, an appropriate amount may be determined by one of ordinary skill in the art using only routine experimentation given the teachings herein.
Generally, the dosage will approximate that which is typical for the administration of vaccines, and will be in the range of about 5 to 1000 ug/dose, and preferably in the range of 50 to 500 ug/dose. The number of doses is in the range of 1 to 10, and preferably in the range of 2 to 5. The frequency of dosages for immunization of the donor is in the range of 1 to 10 weeks, and preferably in the range of 2 to 4 weeks. The time elapsed after donor immunization until administration to the recipient is in the range of 1 day to 10 weeks, and preferably in the range of 2 to 4 weeks.
The compositions, as noted above, will include, as noted above, an effective amount of the selected antigen in combination with a pharmaceutically acceptable carrier and, in addition, may include other medicinal agents, pharmaceutical agents, carriers, adjuvants, diluents, etc. By "pharmaceutically acceptable" is meant a material that is not biologically or otherwise undesirable, i.e., the material may be administered to an individual along with the selected antigen without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington's Pharmaceutical Sciences (45).
Parenteral administration, if used, is generally characterized by injection. Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. A more recently revised approach for parenteral administration involves use of a slow release or sustained release system, such that a constant level of dosage is maintained. See, e.g., U.S. Pat. No. 3,710,795, which is incorporated by reference herein.
Isolation and Conjugation of Myeloma Idiotype Protein.
Process Overview. Since a B-cell malignancy myeloma expresses a unique idiotype, the vaccine must be developed on a customized basis from the plasma of each myeloma patient which contains Id in large quantities. The isotope of the circulating paraprotein for this patient was IgG kappa.
Purification of Idiotype
Water Dialysis. As an initial purification and concentration step, plasma containing myeloma Id was dialyzed against sterile water for injection (WFI). The resultant reduction in salt concentration in the plasma caused preferential precipitation of immunoglobulin. The resulting precipitate was collected by centrifugation and resuspended in an appropriate volume of 0.01M Tris.
DEAE Chromatoaraphy. A DEAE Chromatography gel, DE 52, was immersed in 0.5M NaOH and washed 3 times with WFI. The DE 52 gel was then stirred into an equal volume of 0.1M Tris, and the step was repeated until the resulting supernatant had the required pH of 8�0.2 and conductivity (�0.02 mMhos) of the starting buffer. The gel was then equilibrated with 0.01M Tris and packed into a column.
The actual chromatography procedure was performed at 4� C. in an environmentally controlled cold room. The concentrated plasma precipitate was loaded onto the DE 52 column and washed with two gel volumes of 0.01M Tris. The Id was eluted with a stepwise gradient from 0.01M Tris, pH 8.0 (�0.2) to 0.1M Tris, pH 8.0 (�0.2), using absorption at 280 nm to monitor the protein effluent. The protein peak was collected in 1 ml fractions, and based on SDS-PAGE, selected fractions were pooled.
Sodium Sulfate Precipitation . In a laminar flow hood in the clean room, the selected pooled fractions were transferred to sterile pre-rinsed dialysis tubing and dialyzed against 10 volumes of 20% Na2 SO4 for 16-20 hours. When dialysis was complete, the dialysate was aseptically transferred to sterile centrifuge tubes and the precipitate collected by centrifugation. The pellet was resuspended in sterile 0.9% normal saline. The resuspended pool was then dialyzed against 20 volumes of 0.9% normal saline for 16-20 hours. The final material was filtered through a 0.2 micron filter and adjusted to a final concentration of 1 mg/ml.
Conjugation of Idiotype to KLH
Preparation of KLH. KLH was obtained from Calbiochem, San Diego, Calif. (Cat. #374805). The KLH was supplied in a lyophilized form containing more than 60% protein in BES buffer and magnesium sulfate. The protein purity, which is determined by the vendor, was greater than 90%.
Prior to conjugation, the KLH was passed over a Pyrosorb endotoxin removal matrix (Cuno, Inc., Cat. #7503101 PS). The binding capacity of the support is >107 EU endotoxin per cartridge. Repeated passage of the KLH over the columns reduced the endotoxin to an acceptable level. The gel was regenerated with 1.0M NaOH.
Conjugation of Idiotype to KLH. Equivalent amounts of Id and KLH (equal weights and volumes) were mixed together, and glutaraldehyde, (Sigma, St. Louis, Mo.) was added to a final concentration of 0.1%. The mixture was slowly stirred for 4 hours at room temperature. A 1.0M glycine in PBS solution was added to the mixture to a final concentration of 0.1M glycine to block residual glutaraldehyde, and the mixture was stirred an additional 15 minutes. Unconjugated glycine and glutaraldehyde were removed by dialysis in sterile sodium chloride for injection, USP.
Vialing. The final product was aseptically filled into sterile depyrogenated containers under a laminar flow hood. The final fill volume to be delivered was 1 ml which yielded a patient dose of 0.5 mg of Id.
Pluronic Polymer-Based Adjuvant
Id-KLH was mixed with a Pluronic polymer-based adjuvant. This vehicle formulation contains materials already authorized for use in pharmaceutical and cosmetic formulations and had been shown to be safe in the 12 patients observed in the phase I trial (15). The components were 5% squalane (w/v), 2.5% Pluronic L121 and 0.2% Tween-80 in phosphate buffered saline. All three components were obtained from commercial vendors and were sterilized by filtration or autoclaving before use.
The Pluronic polymer-based adjuvant was prepared 24 hours in advance of each immunization, and each lot was tested for sterility. One ml of adjuvant was produced by mixing Tween (0.4%)/PBS (0.85 ml), L121 (0.05 ml), and squalane (0.1 ml) to produce an emulsion. Immediately prior to vaccination of the donor, this emulsion was mixed (vortexed) with 1 ml Id-KLH to produce a final injection volume of 2 ml.
Immunization and Transfer of Immunity
The BMT donor was a healthy 47 year-old white male sibling whose human lymphocyte antigens HLA type was identical to that of the patient. The patient (BMT recipient) was a 45 year old woman, who was previously noted in April of 1987 to have an increased total protein. Two years later she was noted to have a monoclonal protein of 2.4 grams on serum protein electrophoresis and 12% plasma cells in the marrow. By immunofixation the protein was monoclonal IgG kappa. Skeletal survey was normal and plasma cell labeling index was less than 1%. A diagnosis of monoclonal gammopathy of undetermined significance (MGUS) was made. No treatment was given, but by fall of 1991 she began to note back pain and the IgG level had risen to 4.2 grams per deciliter. Treatment was not initiated until fall of 1992 when a skeletal survey was done demonstrating multiple lytic lesions involving the lumbar spine, pelvis and proximal femurs. At that time the IgG level had risen to 4.5 grams per deciliter. She received local radiation therapy in December of 1992 from T4 to T7, total dose 2600 cGy. In January of 1993 therapy with VAD was initiated but because of the development of ileus, vincristine was deleted and she received two more cycles of adriamycin and dexamethasone. Although there was a modest reduction in the monoclonal protein to a level of 3.1 grams, back and pelvic pain increased dramatically. The patient was given a cycle of thioTEPA 100 mg/m2 and received 2200 cGy irradiation from T2 to T6. In February of 1993 there was modest pain improvement but the M protein spike increased to 3.9 grams per deciliter.
The HIA identical brother was identified and the patient was transferred to Fred Hutchinson Cancer Research Center in Seattle, Washington for further treatment. The 47 year-old male HLA-matched sibling donor was immunized with two s.c. injections of 0.5 mg myeloma IgG, purified from the plasma of the BMT recipient, conjugated to keyhole limpet hemocyanin (KLH), and emulsified in the previously described Pluronic polymer-based adjuvant, at one week intervals before bone marrow transplantation (BMT). The injections were administered on March 30 and Apr. 6, 1993. Donor toxicity consisted only of mild reactions at injection sites. Successful donor immunization was demonstrated by serum antibodies which bound specifically to patient-derived myeloma IgG and specific proliferation of peripheral blood mononuclear cells (PBMC) to the IgG in vitro.
On the fifth of April, the patient began a bone marrow transplant conditioning regimen consisting of busulfan 3.5 mg/kg/day in four divided doses given daily for four consecutive days followed by cyclophosphamide 50 mg/kg per day intravenously over three consecutive days. After one day of rest, bone marrow from the immunized, HLA identical brother was infused. The nucleated cell count per kilogram body weight was 3.4�108. GVHD (graft-vs.-host disease) prophylaxis consisted of methotrexate given on days 1, 3, 6 and 11 and cyclosporine 3 mg/kg beginning on day 1 and continuing through day 150. The patient was herpes simplex and cytomegalovirus sero-positive and was given acyclovir prophylaxis 250 mg/m2 intravenously q12 hours and weekly intravenously immunoglobulin 500 mg/kg. The patient was in poor physical condition and was essentially bed ridden from mid-January 1993 until mid-July 1993. The early post-transplant course was complicated by urine culture that was culture positive for coagulase negative staphylococcus on Apr. 16, 1993, requiring treatment with clindamycin. Engraftment to a neutrophil count greater than 500/μl , occurred on day 14 and platelet transfusion independence on day 21. Skin rash developed on approximately day 28 and required the addition of prednisone 2 mg/kg added to the cyclosporine on day 40. On day 38 the patient was transferred out of the bone marrow transplant unit to the intermediate care unit for rehabilitation.
The BMT recipient was a 45 year-old white female with advanced refractory myeloma (multiple bony lesions, 50% marrow plasma cells, and 3.9 gm/dl M-protein) progressing on therapy. Analysis of her pre-BMT serum and PBMC, respectively, revealed no detectable humoral or lymphoproliferative response to autologous IgG idiotype. Engraftment was normal and accompanied by grade 2 skin GVHD responsive to therapy. 60 days post-BMT, recipient PBMC proliferated both to the KLH control protein (stimulation index S.I.! 48.3 at 50 mcg/ml) and to Id (S.I. 4.8) when assayed independently in 5 day in vitro cultures. An Id-specific T-cell line has also been established from recipient PBMC. Specificity was demonstrated by the lack of proliferation to a panel of isotope-matched Ig of unrelated idiotypes. No humoral anti-idiotypic response has been detected in the recipient. The recipient demonstrated an ongoing clinical response, including declining M-protein, 0.4 gm/dl, and absence of dysplastic marrow plasma cells at day 100. As of mid-November of 1993, no myelomic relapse had been detected in the recipient.
The preceding examples are intended to illustrate but not limit the invention. While they are typical of those that might be used, other procedures known to those skilled in the art may be alternatively employed.
Throughout this application various publications are referenced by numbers. Following is a complete citation to the publications. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
1. Stevenson, G T, Stevenson F K. Antibody to molecularly defined antigen confined to a tumor cell surface. Nature, 1975, 254:714-6.
2. Stevenson G T, Elliott E V, Stevenson F K. Idiotypic determinants on the surface immunoglobulin of neoplastic lymphocytes: a therapeutic target. Fed Proc, 1977, 36:2268-71.
3. Miller R A, Maloney D G, Warnke R, Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med, 1982, 306:517-22.
4. Sirisinha S, Eisen HN. Autoimmune-like antibodies to the ligand-binding sites of myeloma proteins. Proc Natl Acad Sci USA, 1971, 68:3130-5.
5. Jorgensen T, Gaudernack G, Hannestad K. Immunization with the light chain and the VL domain of the isologous myeloma protein 315 inhibits growth of mouse plasmacytoma MOPC-315. Scand J Immunol, 1980, 11:29-35.
6. Daley M J, Gebel H M, Lynch R G. Idiotype-specific transplantation resistance to MOPC-315: Abrogation by post-immunization thymectomy. J Immunol, 1978, 120:1620-4.
7. Bridges S H. Participation of the humoral immune system in the myeloma-specific transplantation resistance. J Immunol, 1978, 121:479-83.
8. Freedman P M, Autry J R, Tokuda S, Williams R C, Jr.
Tumor immunity induced by preimmunization with BALB/c mouse myeloma protein. J Natl Cancer Inst, 1976, 56:735-740.
9. Sugai S, Palmer D W, Talal N, Witz I P. Protective and cellular immune responses to idiotypic determinants on cells from a spontaneous lymphoma of NZB/NZWF1 mice. J Exp Med, 1974, 140:1547-58.
10. Stevenson F K, Gordon J. Immunization with idiotypic immunoglobulin protects against development of B lymphocytic leukemia, but emerging tumor cells can evade antibody attack by modulation. J Immunol 1983, 130:970-973.
11. George A J T, Tutt A L, Stevenson F K. Anti-idiotypic mechanisms involved in the suppression of a mouse B-cell lymphoma, B C L1. J Immunol 1987, 138:628-634.
12. Kaminski M S, Kitamura K, Maloney D G, Levy R. Idiotype vaccination against murine B-cell lymphoma. Inhibition of tumor immunity by free idiotype protein. J Immunol, 1987, 138:1289-1296.
13. Campbell M J, Esserman L, Byars N E, Allison A C, Levy R. Idiotype vaccination against murine B-cell lymphoma. J Immunol, 1990, 145:1029-1036.
14. Kwak L W, Campbell M J, Czerwinski D K, Hart S, Miller R A, Levy R. Induction of immune responses in patients with B-cell lymphoma against the surface immunoglobulin idiotype expressed by their tumors. N Engl J Med, 1992, 327:1209-1215.
15. Campbell M J, Esserman L, Byars N E, Allison A C, Levy R. Development of a new therapeutic approach to B-cell malignancy: the induction of immunity by the host against cell surface receptor on the tumor. Int Rev Immunol, 1989, 4:251-70.
16. Oken M M, Tsiatis A, Abramson N et al. Comparison of MP with intensive VBMCP therapy for the treatment of multiple myeloma (MM) (abstr.) Proc Am Soc Clin Oncol, 1984, 3:270.
17. Pavlovsky S, Saalavsky J, Tezanos P M, et al. A randomized trial of melphalan and prednisone versus melphalan, prednisone, cyclophosphamide, MeCCNU, and vincristine in untreated multiple myeloma. J Clin Oncol, 1984, 2:836-840.
18. Hansen O P, Clausen N T, Drivsholm A, et al. Phase II study of intermittent 5-drug regimen (VBCMP) versus intermittent 3-drug regimen (VMP), versus intermittent melphalan and prednisone (MP) in myelomatosis. Scand J Haematol, 1985, 35:518-524.
19. Palva I P, Ahrenberg A, Almquist K, et al. Aggressive combination chemotherapy in multiple myeloma. A multicentre trial. Scand J Haematol, 1985, 35:205-209.
20. Kildahl-Anderson P, Bjark P, Bondevik A, et al. Multiple myeloma in central Norway 1981-1982: A randomized clinical trial of 5-drug combination therapy versus standard therapy. Scand J Haematol, 1986, 37:243-248.
21. Durie B G M, Dixon B, Carter S, et al. Improved survival duration with combination chemotherapy induction for multiple myeloma: A Southwest Oncology Group study. J Clin Oncol, 1986, 4:1127-1237.
22. MacLennon I C M, Kelly Krys R A, Crockson E H, et al. Results of the MRC myelomatosis trials for patients entered since 1980. In Proceedings of British Myeloma Workshop, Blenheim Palace, London, England, October 14-16, 1987.
23. Blade J, Miguel J S, Alcala A, et al. A randomized multicentric study of comparing alternating combination chemotherapy (VCMP/VBAP) and melphalan-prednisone in multiple myeloma. Blut, 1990, 60:319-322.
24. Gahrton G, Tura S, Ljungman P, et al. Allogeneic bone marrow transplantation in multiple myeloma using HLA-compatible sibling donors-an EBMT Registry Study. Bone Marrow Transplant, 1991, 7 Suppl. 2:32.
25. Gahrton G, Tura S, Ljungman P, et al. Allogeneic bone marrow transplantation in multiple myeloma, European Group for Bone Marrow Transplantation. N Enql J Med, 1991, 325:1267-1273.
26. Angelucci E, Baronciani D, Lucarelli G, Galimberti M, Polchi P, Filippetti A, Filocamo M, Donati M. Long-term complete remission after allogeneic bone marrow transplantation in multiple myeloma. Bone Marrow Transplant, 1991, 8:307-309.
27. Attal M, Huguet F, Schlaifer D, Payen C, Laroche M, Fournie B, Mazieres B, Pris J, Laurent G. Intensive combined therapy for previously untreated aggressive myeloma. Blood, 1992, 79:1130-1136.
28. Topolsky D, Crilley P, Leasure N, Bulova S, Lrodsky I. Syngeneic marrow transplantation in multiple myeloma. Leuk Res, 1992, 16:415-416.
29. Abdou N I, Abdou N L. The monoclonal nature of lymphocytes in multiple myeloma. Effects of therapy. Ann Intern Med, 1975, 83:42.
30. Kubagawa H, Volger L, Capra J H D, et al. Studies on the clonal origins of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation. J Exp Med, 1979, 150-792.
31. Bast E, van Camp B, Reynaert P, et al. Idiotypic peripheral blood lymphocytes in monoclonal gammopathy. Clin Exp Immunol, 1982, 47:682.
32. Mellstedt H, Holm G, Pettersson D, et al. Idiotype bearing lymphoid cells in plasma cell neoplasia. Clin Haematol, 1982, 11:65.
33. Berenson J, Wong R, Kim K, et al. Evidence for peripheral blood B lymphocyte but not T lymphocyte involvement in multiple myeloma. Blood, 1987, 70:1550.
34. Boccadoro M, Omede P, Massaia M, et al. Human myeloma: Several subsets of circulating lymphocytes express plasma cell-associated antigens. Eur J Haematol, 1988, 40:299.
35. King M A, Nelson D S. Tumor cell heterogeneity in multiple myeloma: Antigenic, morphologic and functional studies of cells from blood and bone marrow. Blood, 1989, 73:1925.
36. Jensen G S, Mant M J, Belch A G, et al. Selective expression of CD45 isoforms defines CALLA+ monoclonal B lineage cells in peripheral blood from myeloma patients as late stage B-cells. Blood, 1991, 78:711.
37. Pilarski L M, Jensen G S. Monoclonal circulating B-cells in multiple myeloma. A continuously differentiating, possible invasive, population as defined by expression of CD45 isoforms and adhesion molecules. Hematol Oncol Clin North Am, 1992, 6:297-322.
38. Barlogie B, Alexanian, R. Second international workshop on myeloma: Advances in biology and therapy of multiple myeloma. Cancer Res, 1989, 49:7172.
39. Starling K A, Falletta J M, Fernback D J. Immunologic chimerism evidence of bone marrow graft acceptance in an identical twin with acute lymphocytic leukemia. Exp Hematol, 1975, 3:244.
40. Lum L G, Munn N A, Schanfield M S, Storb R. The detection of specific antibody formation to recall antigens after human bone marrow transplantation. Blood, 1986, 67:582.
41. Lum L G, Seigeuret M C, Storb R. The transfer of antigen-specific humoral immunity from marrow donors to marrow recipients. J Clin Immunol, 1986, 6:389.
42. Wimperis J Z, Prentice H G, Karayiannis P, Brenner M K, Reittie J E, Griffiths P D, Hoffbrand A V. Transfer of a functioning humoral immune system in transplantation of T-lymphocyte-depleted bone marrow. Lancet, 1986, 1:339.
43. Kato S, Yabe H, Yabe M, Kimura M, Ito M, Tsuchida F, Tsuji K, Takahashi M. Studies on transfer of varicella-zoster-virus specific T-cell immunity from bone marrow donor to recipient. Blood, 1990, 75:806.
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Metering, AMR & Data Management
American Electric Power Ohio is asking permission to charge customers $31.80 a month if they choose not to have a "smart meter" installed and continue to have their electric meter read manually.
Consumers Energy is accelerating its plan to provide updated electric meters to homes and businesses across Michigan. By the end of 2017 -- two years earlier than scheduled originally -- 1.8 million electric meters will be updated along with 600,000 natural gas meters for customers who also have Consumers Energy electric service.
Duke Energy Indiana is filing a plan today with Indiana state utility regulators to modernize its aging electric grid that delivers power to more than 800,000 Hoosier homes, businesses and industries.
Part of the women-in-energy article series
"As Kayak is to travel, Choose Energy is to electricity," said Kerry Cooper, CEO of Choose Energy when I asked how she described her gig to people outside of the industry. But even people inside of the industry might be a little confused at what Cooper does. An "energy marketplace" really isn't the norm in most states.
Duke Energy Florida is reviewing options to help customers adversely affected by changes in its meter-reading system and may have an announcement as early as today about possible remedies.
TCS reveals step one
"The Internet of Things, empowered consumers, stringent regulations and digitization have changed the approach towards data in utility industry," said Sudheer Warrier, vice president and global head of utilities for Tata Consultancy Services. "Utilities all over the world have more data than ever." Here's how you deal with that.
We talk a lot about the tool of analytics in this issue full of big data fishing metaphors---from our own Utility Analytics Institute to better analytics in energy forecasting to examining sensor data to how utilities are grappling with it all. Plus, I'll tell you the story of my Snoopy fishing pole, which I miss just terribly. Dive right in. The water's fine.
In this sneak peek inside our July/August big data print issue, we talk with Mark Browning about how Exelon's three big utilities (with a combination of 8 million customers) tackles those numbers. After all, when looking for details about big data, Exelon is the big daddy.
Survey reveals trends
A recent enterprise analytics initiative went live this spring at BGE (a subsidiary of Exelon). The technical aspects of this project are certainly eye-catching, but the real differentiator is that this enterprise platform puts BGE on the path to business transformation.
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Gajanan and Diane- ithank you both very much for taking the time to read and comment. You are so appreciated. (Report) Reply
Theodora (Theo) Onken
My Seattle~
It was a Seattle mist that fell here today
Swallowed up by the states giant size and parched ground
A desert of a place on the edge of the Panhandle
It left me longing for Mt. Rainer and Puget Sound;
Where miles and miles of flat land & oil wells make up the scenery
Where the lakes and their water are a muddy- red
Where Rattle snakes & Scorpions take up residency
It's like Hell- almost- like sleeping in the Devils bed;
But it was a Seattle mist that fell here today
So unlike the sizzling sun that usually comes 'round
Baking the land & our skin into beyond done
Making me long even more for Mt. Rainer & Puget Sound;
For Lake Washington and the Space Needle
For fresh seafood instead of a Texas steak
For Woodland Park Zoo & the Public Market
For the ever true blue colour of my favorite lake;
It was a Seattle mist that fell here today
Making me realize just what my heart has known all along
Home is truly where ones heart's abides
And from m heart- i will always sing- my Seattle song;
B, Theodora Onken
April 4,2013
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Comments about this poem (My Seattle~ by Theodora (Theo) Onken )
Theodora Onken (4/22/2013 5:09:00 PM)
Diane Hine (4/22/2013 5:18:00 AM)
I enjoyed the structure of the poem which really conveyed your feelings beautifully. (Report) Reply
Gajanan Mishra (4/4/2013 1:43:00 AM)
home is where ones heart abides. good poem. thanks. (Report) Reply
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text:
duskullofficial asked:
But it's Wednesday?tgif
duskullofficial asked:
ravsy answered:
I'M REALLY STRUGGLING TO DECIDE. I think Yes.
This video is what convinced me to vote yes, it's a Better Together Campaign ad with added text:
A hydra is a snake right? So basically Nick fury is trying to get hydra off the helicarrier right? Does that mean he's trying to get those motherfucking snakes off his motherfucking plane?
#I CANNOT FUCKING BELIEVE#THAT IT HAS BEEN NEARLY TWO MONTHS#AND THIS IS THE FIRST FUCKING TIME I'VE SEEN ANYONE MAKE THIS JOKE#FOR THE LOVE OF GOD#I CAN'T BELIEVE IT'S BEEN TWO MONTHS AND *I* DIDN'T MAKE THIS JOKE#I'M DISAPPOINTED IN ALL OF US#cap 2 (x)