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All-New VIP Lounge
Dine & Drink at Oktoberfest Northwest in style as a VIP!
Ticket sales are officially on sale August 2017 for the VIP lounge!
WHEN: Friday, Oct. 6 from 5:00pm - 11:30pm
Saturday, October 7 from 5:00pm - 11:30pm
LOCATION: Oktoberfest Northwest Festhalle near the Main Stage
PARKING: FREE at the Blue Lot (For directions, check out our Getting There section)
Early Bird: $55 (limited spots)
Pre-Event: $60
On-site: $65
Experience includes:
- Same-day Admission
- Exclusive VIP Only Area with Private Bar located right by the Festhalle Main Stage in the main event!
(For VIP guests to use beverage tickets included in VIP lounge or purchased separately)
- Limited Edition German Beer: TBD will be exclusive to the VIP Dinner!
- 'Meet & Greet' with our host Manuela Horn, The Queen of Oktoberfest
- Official Stein with 2 beverage tickets (The tickets can be used for beer, wine or cider)
- Souvenir Oktoberfest lanyard
- VIP-only Hammerschalgen stump
- Live polka music & bar games
- Skip the Beer Ticket Lines! Option to buy additional beer tickets at VIP only line at Cash only ticket booth.
NOTE: VIP Lounge is for 21 & Up Only. VIP guests can arrive any time at Oktoberfest NW, however, the VIP Lounge is open at the set times mentioned above.
Media Sponsor:


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|Message view
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|"Gary Tully (JIRA)" <j...@apache.org>
|[jira] Created: (AMQ-2980) Seeing inflight messages that are not consumed when jmsPriority is enabled and have intermittent durable consumer
|Fri, 15 Oct 2010 12:24:40 GMT
Seeing inflight messages that are not consumed when jmsPriority is enabled and have intermittent durable consumer ----------------------------------------------------------------------------------------------------------------- Key: AMQ-2980 URL: https://issues.apache.org/activemq/browse/AMQ-2980 Project: ActiveMQ Issue Type: Bug Components: Broker Affects Versions: 5.4.1 Reporter: Gary Tully Assignee: Gary Tully Fix For: 5.5.0 With reconnecting durable subs or with small prefetch, out of order priority messages and missing messages can occur. Issues with the kahaDB topic store, message delete and ordered cursor sync and replay. Topic store sd.orderIndex need an exclusive lock and replay from the last ack needs to take ordered cursors into account. Batch replay also needs to maintain ordered cursor state between batches. JDBC store also has some issues in the batch regard. -- This message is automatically generated by JIRA. - You can reply to this email to add a comment to the issue online.
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subset: commoncrawl


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Ethics: This seminar will deal with the history, definition, components and importance of ethics.
It also examines the IMA ethics principles and standards as well as the impact of having an appropriate code of ethics within an organization.
Examples of some ethical dilemmas will be presented to discuss the details of each scenario and the steps for resolving them.
IMA Qatar Chapter Board Election: IMA Qatar Members are invited to nominate themselves for available IMA Qatar Chapter Board positions. Nominations will be received on the night whereby voting and appointments will be made in accordance with the chapter bylaws.
For picture gallery of this event, please click here.
Events >


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Museum Exhibit: Early hominids
''Doubly wise man''
By: Bailey Wielhouwer
Doubly wise man aka homo sapiens sapiens had a high rounded skull and a large brain that is why they knew how to make a lot of tools. They had small teeth and very slender bones.
Doubly wise man lived in Africa, Asia, Antartica, and Europe. In these Continents there is a lot of stone. The hominids used the stone to make tools and they used the tools to hunt or protect themselves which helped them survive.
One of the reasons that this hominid group survived is because of there expertise tool making. They used there tools for many things one of them was to hunt. They would use a tool such as a bow and arrow to kill any animal they could find. Another reason was to from protect themselves from predators.


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News By Tag
Industry News
News By Location
Industry News
Insight Pharma Affiliated Reports Collection Announces Antibody-Drug Conjugates 2011 Report
Antibody-Drug Conjugates 2011 – real breakthrough still to come: a Technology, Stakeholder and R&D Pipeline Analysis Report
This report provides the most complete compilation of information about antibody-drug conjugate (ADC) companies, technologies and products in R&D. A comprehensive analysis of the state of the art and key trends guides the reader through this complex subject. Stakeholders in the field of antibody-drug conjugates are analyzed and their contribution to the growth ADC technology and products is assessed. A critical appraisal of the clinical results of active and discontinued ADC projects and products is provided. ADC technologies and products are challenged for their commercial value and growth potential.
Scope of the report:
• Drugs and Linkers Used in Antibody-Drug Conjugates
• Antibodies Used in Antibody-Drug Conjugates
• Analysis of Stakeholders in Antibody-Drug Conjugates
• Clinical Value of Antibody-Drug Conjugates
• R&D Pipeline Analysis of Antibody-Drug Conjugates
• Commercial Values of Antibody-Drug Conjugates
• Company Profiles
• Executive ADC Profiles
For more information and to purchase this Insight Pharma Report, visit: http://www.InsightPharmaReports.com
About Insight Pharma Reports
Insight Pharma Reports are written by experts in consulting and industry who collaborate with us to provide a series of reports that evaluate the salient issues in pharmaceutical technology, business, and therapy markets. Insight Pharma Reports are used by leading pharmaceutical, biotech, diagnostic, consulting, and financial companies to keep abreast of the latest advances in pharmaceutical R&D, their potential applications and business impacts, and their current and future position in the marketplace. Insight Pharma Reports is a division within Cambridge Healthtech Institute. http://www.InsightPharmaReports.com
Insight Pharma Reports offers our Affiliated Reports Collection which provides a repository of additional scientific and business resources. For more information, visit http://www.insightpharmareports.com/
# # #
Insight Pharma Reports are written by experts in consulting and industry who collaborate with us to provide a series of reports that evaluate the salient issues in pharmaceutical technology, business, and therapy markets.
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It was a pleasant stay with lovely viewsand open fire (it was the only camping site where allow open fire! and lots of wood sticks everywhere around you). Thanks to that, we had great dinner with baked potatoes and sausages! Although the facilities are a bit old they keep them clear. It is a nice place to chill out and relax for few days and hang out with friends. YJ & Insun from South Korea
- Official Description (provided by the hotel):
- Camping * bungalows * pension rooms * youth hostel * swimming pool * restaurant * barbecue * good traffic connections to Budapest (bus, train) * beautiful island with huge trees * free wi-fi * washing machine * bicycle road * bike tours * water sports * thermal bath * near by the centre of the historical Szentendre * sightseeing tours to Budapest * folklore programs * Budapest by night. ... more less


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The Ascension Parish Industrial Group Community Awareness Emergency Response participated in the Ascension Parish Sheriff's Office annual Christmas Crusade for Children last month.
The group has participated in the crusade for more than 15 years, Chairman James E. LeBlanc said in a news release.
"We're just happy to be a part of this event and happy to help our community children have a nice Christmas."
The Community Awareness Emergency Response Committee's membership, which includes chemical and industrial companies in Ascension Parish, works closely with parish government and the Sheriff's Office to define and prepare procedures that would be used during a chemical or industrial emergency, LeBlanc said.


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Today, I puked up an anti-nausea pill. FML
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Keen reader – Level: student ninjaYou have voted for 15% of the entire collection of FMLs to date.
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I agree, my mouse works.200 "I agree" votes is a good start.
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100 kick-ass comments100 of your comments are neither buried or moderated. Popular is your middle name!10%
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Today, I was laying in the grass, staring into the blue sky and watching planes go by. My boyfriend snuggles down next to me; it was a sweet moment. He then told me all about how the planes above are leaving 'chem trails', and that he believes the CIA is out to mind-control us all. Right. FML
Today, I fell asleep in my last period class. When I woke up my teacher said "you missed your bus". I grabbed all my stuff and ran out the room. My class mates were standing outside the class laughing. We still had an hour left in class. FML


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Are you a student or teacher? We have the latest educational apps for your classroom and for learning. We support all Android Phones and Tablets.
Click on the title of this section to expand the list and show you every app in our system!
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We help you search for a Alfreton recorder teacher. Recorder lessons are a great way to learn a fun new hobby, acquire a new skill and gain confidence with recorder. Try our service to find Alfreton recorder teachers and select which best matches your requirements so you can start your recorder tuition in Alfreton immediately!
This is the best place to find Alfreton recorder teachers in the UK, helping you discover Alfreton recorder lessons in your area and Alfreton teachers to help with any instrument such as piano, violin or guitar. We can help you find Alfreton recorder lessons or a Alfreton recorder tutor to prepare for recorder exams and improve your recorder skills! We order Alfreton recorder teachers local to you according to their hourly prices and distance from you.
If you are a recorder tutor wishing to offer your recorder tuition services in Alfreton or anywhere else across the UK, please register with First Tutors: Music or learn about us here. Becoming a Alfreton recorder tutor is a fantastic way to re-affirm your own skills by providing recorder lessons while assisting others, all in the Alfreton area!


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Baden-Baden is a world renowned spa town in the foothills of the
Black Forest. The natural hot springs, which can reach a
temperature of 68 degrees, are the source of the towns 'cure'
Visitors particularly enjoy the natural surroundings, not only the Brenners private park but also the beautiful expanse of the Black Forest. Hiking, climbing and mountain biking are all popular. Touring through historic towns and vineyards is particularly charming in the comfort of Brenners' classic VW Samba.
The city is world famous for its culture. Art lovers will appreciate the prominent collections and the town's famous casino, which is itself a work of art, each room designed in the elegant traditions of a French château. Festpielhaus is Europe's second largest opera house with extraordinary acoustics, a magnificent stage for grand events and regular home to the Berlin Philarmonic.
In May, September and October, guests enjoy the excitement on Iffezheim horse racecourse, where the Brenners Lounge is available for all lovers of a first-class ambiance.


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Already have a VetUK Account?
Don't have an account?
Free delivery on orders with £10 worth of
VetUK own brand products
(click to enlarge)
Manufacturer: James Wellbeloved
James Wellbeloved Senior Dog Duck and Rice has been specially formulated to contain all the wholesome natural ingredients that the senior and/or overweight dog needs to keep fit and healthy without any of the artificial colours, flavours and preservatives.This food is ideal for dogs with loose bowels and skin irritations. It is hypo allergenic, uses activity balanced proteins to calm hyperactive behaviour and contains seaweed, alfalfa and yucca in addition to natural sources of vitamins E and C for their anti oxidant qualities.
Composition:Brown Rice (39.7%), Duck Meal (15.0%), White Rice (14.6%), Naked Oats, Whole Linseed, Duck Gravy (2.9%), Duck Fat (2.4%), Alfalfa Meal, Pea Fibre, Chicory Pulp, Seaweed (0.5%), Omega Oil Supplement*, Potassium Chloride, Sodium Chloride, Parsley (0.125%),Nettles (0.125%), Taurine (0.1%), Chicory Extract (0.1%), Calcium Carbonate, Glucosamine (0.045%),Yucca Extract (0.02%), Chondroitin (0.005%) * From Fish Oils
Typical Analysis:Protein 19 %, Crude Fibres 3.7 %, Fat Content 9.3 %, Crude Ash 4.8 %, Vitamin E 400 Mg/Kg, Omega-3 Fatty Acids 1 %, Omega-6 Fatty Acids 2.1 %


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Download Crazy Toad apk 1.0.0 free for Android smartphone
Posted by [email protected] in Casual | April 3, 2014 | 0 Comments
Apk file size: 9.3 MB
Crazy toad an educational game for all ages. Created by Mr. Wiljun Geresola BSIT 4th year of UI-PHINMA. The game will stir your mind to stretch your eye and brain to hit the opponent. This game was the product of innovation and the fundamentals of game development subject in UI-CITE (College of Information Technology Education) headed by the dean Seth dA. Nono,MSCS. The crazy toad is one of the student projects in Game Development Subject. This is part of the casual game platform. Relax and have fun.
[email protected] part of our Casual and have average installs from 100 to 500. Last Update April 3, 2014. Google play rating is 80.0. Current verison is 1.0.0. Actual size 9.3 MB.


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Infectious Grooves
- Overview
- Biography
- Songs
- Browse by Format
- Browse by Genres
- Similar Artists
|Heavy Metal Pop / Rock
|funk metal funk metal alternative rock
|1990s 2000s
|discography discogs lyrics other databases other databases purchase for download purchase for download wikidata wikipedia
This heavy Los Angeles, USA funk-rock band was founded by the Suicidal Tendencies duo of vocalist Mike Muir (14 March 1964, Venice, California, USA) and hugely talented bass player Robert Trujillo (b. 23 October 1964, Venice, California, USA), with guitarists Adam Siegel (from Excel) and Dean Pleasants and ex-Janes Addiction drummer Stephen Perkins (b. 13 September 1967, Los Angeles, California, USA). The band was deemed more than a side project for Muir and Trujillo, given equal status with Suicidal Tendencies, and the two bands often toured together, necessitating two exhausting sets per night for the pair.
The 1991 debut established an entirely different sound from the parent band, with a heavy, Red Hot Chili Peppers -style funk attack, with Muir, for once, producing lighter lyrical fare. Standout track Therapy featured guest backing vocals from Ozzy Osbourne, who punctuated Muirs vocals with gleeful, manic roars of...
- MatchInfectious Grooves
- 100%Living Colour
- 84%Primus
- 42%Les Claypool
- 35%Faith No More
- 32%Mindfunk
- 30%Extreme


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swades theme tune.mp3 MP3
Swades theme music MP3
The theme music of Swades.............Makes my heart beat a lot faster.
Ye Jo Des Hai Tera [Full Song] Swades MP3
Song - Ye Jo Des Hai Tera Film - Swades Singer - A.R. Rahman Lyricist - Javed Akhtar Music Director - A.R. Rahman Artist - Shahrukh Khan, Gayatri Joshi, ...
Swades - Score - 5. Theme MP3
Movie: 'Swades' Score by A.R.Rahman ( 5. Theme ) *****All content is owned by AGPPL (Ashutosh Gowariker Productions Pvt. Ltd.)*****
Swades OST A Real Indian Theme MP3
Swades soundtrack.
A. R. Rahman, "Yeh Jo Des Hai Tera" (Swades): Berklee Indian Ensemble and Berklee World Strings MP3
A. R. Rahman is an Indian composer, singer-songwriter, producer, multi-instrumentalist and philanthropist, known for redefining contemporary Indian film music, ...
Pal Pal Hai Bhaari [Full Song] Swades MP3
Song : Pal Pal Hai Bhaari Movie : Swades Singer : Madhushree, Vijay Prakash, Ashutosh Gowariker Lyricist : Javed Akhtar Music Director : A.R. Rahman Artist ...
Swades Theme | A.R. Rahman MP3
Recorded at Panchathan Record Inn (C) T-Series.
Yeh Jo Des Hai Tera (Instrumental) ~ Swades MP3
This instrumental version of the original song is extremely beautiful. One of ARR's best. Although, I love all songs of Swades, This small piece of music has a ...
Swades Theme by A R RAHMAN MP3
Powerful Theme by Rahman in Swades, used in Slumdog Millionaire for Salim phone's Ringtone (:D) . I do not own this track, Just a die hard fan wanting to ...
Swades - Shehnai Tune (Yeh Jo Desh Hai Tera) MP3
Swades Music by A.R.Rehman ngelizz has no copyrights of this.
bombay theme original MP3
AR Rahman concert in Los Angeles.
Yeh Jo Des Hai Tera (English Subtitles) - Swades - HD MP3
(Click CC for English Subtitles) Mohan can't keep the thoughts of his motherland out of his head even when back in America. Beautiful, patriotic song featuring ...
"Aahista Aahista (Full Song) | Swades | Shahrukh Khan MP3
Song - Aahista Aahista Film - Swades Singer - Udit Narayan, Sadhna Sargam Lyricist - Javed Akhtar Music Director - A.R. Rahman Artist - Shahrukh Khan, ...
Jeans Theme Music.mp4 MP3
Yeh Jo Des Hai Tera - Swades - A.R.Rahman -- HD *Blu-Ray* Quality MP3
Very emotional track of Swades by A.R.Rahman.. Jai Hind :) ............ Lyrics both in Hindi & English ...
Shakti - The Power (2002) - Hindi Full Movie - Shahrukh Khan - Karisma Kapoor - Nana Patekar MP3
Shekhar (Sanjay Kapoor) and Nandini (Karisma Kapoor) live a harmonious life with their young child Raja in Canada. A series of events lead them to Shekhar's ...
Bombay theme music-A.R.Rahman.wmv MP3
Film:Bombay Composed by: A.R.Rahman http://www.youtube.com/user/Hiddensweetnessshibu.


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What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
Group Registration with all Names ShowingAsked by knaadmin on June 23, 2014 at 01:27 PM
This is for a conference registration.
Is there a way to to show all the names of people who have registered on one credit card?
For example, 10 people are registering as a group with one credit card but I want each individual's name. Is there a way to set a condition for that?
JotForm Support
Yes you can. By following the method described in this user guide
1. You will need 2 forms.
2. In first form, collect all the information (Names of Registrants and registration options)
3. In the second form, pass the payment.
Hope this help. Inform us if you need further assistance doing this.


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Here are photos from the Tour Divide, the 2,700-mile self-supported Canada-Mexico mountain bike race hailed as "the most difficult cycling event in the world." As it took me 27.5 days, here are 27 30 photos representing what I remember most from each of the days.
If you enjoyed this article, please consider receiving my weekly newsletter. I typically write about endurance bicycling, world travel, self improvement, Colorado living, marathon running, and epic adventures.
Articles related to Tour Divide: 27 Days, 27 Photos
- Other posts about Tour Divide


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01326 389272
Find A Cottage
You are here:
Marazion, Cornwall
Photographs courtesy of Marina Rule (see www.marinarule.com)
Marazion lies to the east of Penzance and lies directly in front of St. Michael's Mount, which dominates the landscape in a pleasing fashion. The main high street meanders up the hill and has a range of shops, cafes and pubs. There are lots of crafts on display, including jewellery and paintings.
The long beach is shallow and a great place for a day's swimming and relaxing. Although be warned, the tide does race in at an alarming rate. At low tide there is a causeway which allows access to the Mount itself, but there is also a boat service. Adjacent to the seafront is a large open space perfect for picnicking or kite flying, and an enclosed children's play area.
On the outskirts of the village is the RSPB Marsh nature reserve - home to a variety of commonly viewed birds and some more unusual visitors.
© Copyright 2017 - Above Beach Cottages


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Help me, Ronda: Is Rousey one of the best ever in UFC?
08/03/15 by Rennie Detore
For those who work by the hour, you'd love to be the pace and rate of UFC fighter Ronda Rousey.
She's captivated the mixed martial arts and fighting world with a 12 wins and zero losses record, and now she's gaining even more mainstream publicity after disposing of a so called challenger in a mere 34 seconds.
Yes, half of a minute.
Like this article? You should check out all our Target promo codes!
But that isn't anything new for Rousey who clearly doesn't work by the hour, as she has had few fights that last even a full minute recently. She's about as well rounded of a fighter as you get; if you try to take her down, you'll get popped. When you pay attention to the hands and how she throws them, you'll be on the ground quickly.
So basically, you're in a lose lose situation.
After her win this past weekend in 34 seconds over a seriously competent challenger, Brazilian Bethe Correia, Rousey is starting to find herself on media outlets everywhere, including CNN, MSN and others as being more than just a female fighter that could easily be labeled a novelty in a sport dominated by men.
Now, she's the poster person for Ultimate Fighting Championship.
She's a draw, a legit superstar with enough credibility to carry an entire pay per view with her fight as the headliner. She can be mentioned alongside fight cards with her male counterparts and no one blinks an eye (well, except maybe her opponent here in the next few seconds).
So the debate about Rousey and if she's the real deal hardly is much of a topic of discussion. The answer is an easy yes.
The fact that she's a woman competition shouldn't ever preclude her from being discussed as one of the best in her sport. Yes, she's pretty and in some ways when she's not knocking blocks off in the ring, she's donning sleek, sexy dresses on the "Tonight Show" or doing ESPN's "Body issue" and baring it all.
But Anna Kournikova, this is not.
Kournikova was the teen age dream of tennis fans when she strutted on to the court and the world cared more about her short shorts than her game, which wasn't very good. She was an average player in the sport at best, but her appeal visually gave her career and subsequent spotlight more than it truly was worth.
Rousey is dominant at what she does and isn't showing signs of slowing down any time soon. Like a lot of competitors, she'll get older and lose a fight here and there, but what she's doing now is remarkable and the fans of UFC are reveling in this fighter that is quite simply the talk of the entire sport.
Which is exactly where she should be based on what she's done in the ring.
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Doggie Dolittle: Deciphering your dog filled with many misnomers
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By Paleo Prints
Chapter 3.5: Happy Hearth's Warming, I Don't Want to Fight Tonight
Note: This chapter occurs between 3 and 4. I'll switch the order to reflect that in a week, after the subscribers see it.
Dust-covered glass greeted Cheerilee as she opened the battered chest. Years of partially-sober ornament design parties flooded back as she scrutinized rows of fragile constructions. A Ramanes album cover reproduction scrawled on a piece of wood that could charitably be called a square leaned on a glass ball with "Teecher's Pet" spelled out lovingly, if only approximately, across in graffiti-like hoofwriting. Cheerilee smiled as she pushed aside the rows of crystallized memories.
Her eyes lit up at the checkered pattern sticking out underneath an ancient diminutive blackboard. Picking both up with her teeth, Cheerilee deposited them on the table. Wow, she thought with a deep sigh and a dusty mouth. You know, I bet unicorns never learn to control their saliva for delicate teeth work.
Written across the small chalkboard was the simple statement, "We Love You, Mom & Dad." Next to it was a checkerboard-framed picture of Cheerilee and Lyra at a party. She waved out of the frame at herself, decked out in bangles, frizzy hair, and lightning bolt earrings. Next to her was Lyra, staring at Cheerilee with an admiring gaze and a blush only partly explained by alcohol.
Yeah, after I hung that up was about the time Mom cancelled Lyra's sleep-overs. Cheerilee smiled. At least, the official ones. Thank Celestia for windows.
Long moments past while Cheerilee stared into the past. With a determined start, she trotted into her bedroom. As the click of a latch and a jingling of metal filled the air, Cheerilee heard the door open.
"Ditzy? Ly-Ly? Wait there, I'll be right out! I've got a surprise!"
Cheerilee raced out, a single bright blue lightning bolt dangling from her ear. Her enthusiasm ground to a halt when she met the sardonic, violet eyes of an older unicorn,
"You know," he said as he levitated a package under the tree, "the flannel and the pastel really conflict. Pick one of them and be done with it, dear."
Cheerilee smiled while the inside of her brain called her mouth muscles liars. "Mister Heartstrings! How lovely for you to join us. Is anyone else going to join us?"
He sniffed as he found a kitchen stool and opened a wine bottle. "Here? I doubt you'd have the room. Ballad is staying at her coltfriend's family winter house. It's not like Lyra talks to her sister anyway."
Cheerilee stared as a full wineglass emptied into Jazz. "Um, that's meant-"
"To help me deal with... this," Jazz said as he waved his hoof irritatedly around the room and levitated more wine into his cup.
"And what about Lyra's mom. She's not spending time with her family members?"
A chuckle echoed an empty glass. "No, although depending on her sobriety and faithfulness to medication she may be generating some."
Cheerilee walked to the edge of the counter, grabbing the half-filled bottle in her teeth and depositing it in the fridge. She leaned back against it, crossing her front hooves and frowning.
Jazz smiled. "That's adorable, if useless. I have a horn, you know."
"Try it and you'll pull back a stump." Cheerilee considered this. "Or, gain a stump somewhere logical." She narrowed her eyes, only managing to draw a laugh out of Jazz as he raised his hooves in surrender.
"Enough. Is there is coffee?"
Seconds later caught Cheerilee headfirst inside the refrigerator gazing past preserved muffin experiments and Lyra's ill-saved leftovers on a quest for creamer that Daring Do would give up in favor of something with spiked pits. She pushed aside a pile of hay fries half-wrapped inside a stapled together cling film bag.
"Ly-Ly, you never clean up your messes right," She said softly.
"I agree," came Jazz's voice from behind. It startled her, sending her head into a shelf and nearly tipping over a bowl the last tenants had left when she moved in. Cheerilee straightened the shelf with the side of her face as she reached out a hoof to slide it into its groove.
"Sorry, music instructor's hearing," came the barely apologetic response. "You know, I think I finally have the right perspective to make out what my daughter sees in you."
Cheerilee gently pushed the pretty floral bowl of gelatinous mass to a safe corner and breathed out. With professionally faked cheerfulness, she inquired, "And that would be? From a position of hospitality? Resourcefulness, perhaps?"
Jazz let out an amused chuckle. "The correct term is 'behind,' my dear."
Cheerilee's eye twitched as she pulled her front out of the refrigerator.
"I don't blame her," Jazz continued, obviously to the looming danger, "I've learned many pleasant lessons from my earth pony ex-wife myself. Amazing stamina, that breed."
Cheerilee's mouth slammed a tray of mugs onto the counter, sending spikes of coffee into the air. She moved very close to Jazz, showing a smile that would have made a tooth fairy reach for his wallet. "What do you want, Sir?" Cheerilee said with a rising tone of voice. "One lump, two, or a whole lot?"
Jazz nodded and levitated the unsweetened cup to his lips. "Coffee is drank for utility my dear, not flavor. So, should I just leave Lyra's present under the tree?"
Cheerilee stayed quiet for several seconds as Jazz downed the cup. Finally shrugging, she sat down next to Jazz and took a mug herself. "Tree is fine. What did you get her?"
"A Longnote Orichacum Lyre with adamant sap-treated strings."
Cheerilee had enough presence of mind to aim her mouthful of coffee away from the stallion with the expensive present.
Jazz only smiled. "The towels wouldn't be on the other side of the kitchen, would they?"
Cheerilee returned his gaze as she pulled a rag from a nearby drawer. "You only get one show, 'Sir'." She shook her head. "I haven't heard a single pleasant word from you about your daughter. Why get her something that cost more than my tuition?"
Jazz flashed the grin of somepony who used first-born colts as currency. "Think of it as an investment in her future."
The front door was flung open. "Hey, everypony! I hope you have room for Donut Dan's!"
Ditzy Doo trotted into the room with a yawn and several bags hanging off of her curled feathers. She deposited her bounty on the counter, bleary eyes going wide at Jazz's presence. "Mister Heartstrings! How nice to see you."
Jazz leaned over the counter. "Of course. Your darling father wouldn't happen to be here, would he?"
Ditzy shook her head. Jazz nodded with the relief the beta timber wolf shows when the pack alpha falls into a canyon. "Good," he said as he turned away from Ditzy. "Cheerilee, my daughter needs a rich husband or a career. She has to provide or be provided for."
Ditzy reached her feather's over the counter, brushing Cheerilee's hair out of her eyes and petting her forehead before finally taking a cup of coffee. Cheerilee's shoulders relaxed at the touch.
Cheerilee risked another venture into the minefield of the conversation. "With a teacher's salary and her playing gigs we should be able to make do until she gets her degree."
Jazz snorted. Cheerilee eyes flashed.
Ditzy looked up from her coffee with a frown. "Sir," she said neutrally, "Cheerilee and Lyra both have a lot of talent."
"I know about this one," Jazz said with a leering wink. "I got a show earlier."
Ditzy's blood froze at Cheerilee's embarrassed blush. She carefully put down her cup and folded her wings in front of her. "You know, my father told me he'd be happy with my career regardless of what I chose, as long as I followed my heart."
Jazz rolled his eyes. "Darling, if I was your father I'd agree. I'd be happy if you managed to find yourself anything."
Cheerilee's heart jumped as she fumbled for her falling mug. Ditzy's wings carefully put down her drink before reaching over the counter and pulling Jazz across it by his necktie.
"You've insulted me," she said in a steady tone. "That's okay. I'm used to that. But you seem to be upsetting my friend, and- "
"Let go of me," Jazz choked out of his fabric noose, "you feather-brained - "
"I am talking!" Ditzy shouted. The apartment was dead silent. Jazz looked into Ditzy's eyes, seeing the pony his mind previously filed between the "Target" and "Eye Candy" folders and finding that the shelf of folders lacked one marked "Quiet and Terrifying."
Ditzy released him, Jazz gasping for breath as he fell back in his seat. "Anyway, I think you were just leaving."
Jazz rushed to the door, fumbling at the locks with his horn's glow. He turned back as he got the door cracked open.
"You and your father are both dangerous, violence-prone lunatics, Miss Doo."
Ditzy smiled. "I should introduce you to my great-aunt Daring, then."
Jazz froze. He shivered. He left.
Cheerilee moved to the other side of the minikitchen counter and put a grateful hoof on Ditzy's shoulder. The pegasus sniffed. Cheerilee gave her a kiss on the cheek.
"Ditzy Doo," she said, "you are beyond value. Come on, I'm taking you out for lunch."
Ditzy's wing drew across her eye. "But... I have to get through chapter six today to stay on schedule for my presentation."
Cheerilee lifted DItzy's chin up. "You're my new personal hero. Isn't being a hero worth free cheese hay fries?"
Ditzy thought for a second and sighed. "Not as often as you'd think, actually."
Lyra sat in a relatively spartan office, and this offended her. She felt that a proper professor should have stacks of paper leaning over on her desk near a perpetually cold cup of coffee. Using graduate students to keep a clean office and a regular return of papers to the students somehow seemed to be an abandonment of responsibility.
At the moment, Lyra was as much paying attention to the professor in question as she could dredge up on four hours of sleep spread over a music theory textbook with drool marks.
Chromatic Scale cleaned her glasses telekinetically. She reclined in her chair, her multi-colored hair tied into a tight bun that made mares jealous and stallions eager to hear a breathy statement about overdue books.
"Miss Heartstrings, while your impromptu performances are amazing, you've turned in only half of your required writing assignments. While I can respect enthusiasm, I also must hold everyone to the same high standards I myself went through. This is quite an important part of becoming part of the Canterlot musical hierarchy."
Hair, Lyra thought. Rainbow hair, flowing like waterfalls. Strawberry-smelling locks falling between blueberry-tasting strands and...
"Are you paying attention to me right now, Miss Heartstrings?"
Professor Scale sat patiently.
I think the hair is talking.
Lyra snapped up in her chair. Professor Scale adjusted her glasses and grimaced.
"Miss Heartstrings, you are aware that tonight is Hearth's Warming Eve? I'm in my office today in respect for your father's reputation and your obvious talent. I don't want to waste my time to help another future casualty of society."
Lyra broke out in a cold sweat.
"Professor Scale, I'm sorry if I'm a little out of it. I had a gig last night. I really needed the bits. And I was trying to get through chapter four afterwards."
"Of course, that would be more important that a scheduled emergency meeting with a busy professor on a holiday." Scale sighed.
Lyra swallowed. "Please, Miss, I promise I'm taking this seriously. These textbooks don't pay for themselves, and I have to take care of my roomies, and I need to get presents, and I'm living off of grass."
Scale nodded as she stood up. "I understand your mindset, Miss Heartstrings. When I was young I knew everything."
Lyra stepped in front of the slowly retreating faculty. "Please. Please help me. I want to get my theory papers done, but I don't know where to start. You know I play better than half the students in my class."
Scale snorted. "Half? I think you could adjust that number upward."
Lyra's brain stopped at the surprise compliment. Scale breathed out.
"Listen, Miss Heartstrings, I only want you here if you're willing to put in the work. You could be fantastic, but you really have to decide what you're going to prioritize. This is your turning point, Lyra. It's a fork stuck in the road. At this age life is grabbing you by the hoof and asking you where to go. Be back in my office the day classes start again with your textbooks and decide what is really important."
Five minutes later found Lyra breathing rapidly in front of a restroom mirror. She spread her forelimb on the counter and stared at years of accumulated small lines. She heard a knocking on the door.
"Go away," the preteen answered from her locked personal bathroom.
An impatient tapping sounded on the outside of the door. "Little Ly, come on out," said a voice with good-natured control. "We're late for the restaurant."
Lyra breathed rapidly. "Ballad, my recital is today! All my friends are coming!"
The doorknob briefly glowed and wiggled without opening. "I know, Ly. This is important, though. With this invitation Mom and Dad might double their concerts this season. I promise you we'll reschedule."
Lyra stared into her reflection's eyes. "They've never rescheduled yours."
"Lyra," Ballad said in the voice that told Lyra she was about to utter That Sentence. Lyra started shivering preemptively.
"You have to face it. You can't run."
As usual, the shivering continued.
Ballad sighed. "Be out in two minutes. All smiles, remember? Remember what Mom says."
Lyra slumped over the sink, briefly looking for the toothbrush with the sharp, pointy bottom. It was gone; the maids must have caught on. "All smiles, all grins today. Keep the frowning locked away."
"That's my sister. Two minutes."
Lyra listening to the sound of retreating hoofsteps and stared at her forelimb. In the assuring quiet she bit down with the desperation of a drowning pony gasping for air, screaming as she shook her head. After a few minutes the muffled cries stopped. With practiced efficiency the tearstained towel went into the hamper, the red tissues went into the toilet, and she walked toward her parents with a smile.
Lyra breathed heavily in the college restroom as the knocking pony gave up and wandered off. She had three forms of release in her life, but Cheerilee and her instrument was both elsewhere.
In lieu of a toothbrush, she bit down.
"Raargh," declared Ditzy through the wad of fries shoved in her upper lip. "Nightmare Moon want candy!"
Cheerilee giggled. Tension flowed out of her as Ditzy's answering laugh rung through the nearly empty cafe, the hay fries falling out of her mouth onto Ditzy's plate.
Cheerilee grabbed the basket. "Okay, let me try one." She stuck two fries into her upper lip. "I am a vampire," she declared with her hooves in the air.
"Heh," said the soft voice to their side that made Cheerilee jump and Ditzy squeek. "You gonna bite anyone?"
Cheerilee was staring into reflective purple goggles and seeing nothing but the amused grin below. A nervous-looking pink mare pushed in front of the grin and gave it a reproaching look.
"You weren't supposed to scare them, Vinyl."
Even with the glasses in the way, Cheerilee felt that "Vinyl" was staring straight at her.
Vinyl shrugged. "Vampires are cool. If she's a vampire, she'll be cool with it." Vinyl leaned onto the table, close enough that Cheerilee could smell candy on her breath. "Are you cool, lady?"
Ditzy crossed her forelimbs. "Vampire aren't cool."
Vinyl snorted. "Anyway, my friend here wanted to ask you a question." Vinyl pushed her shivering companion forward.
She stared at Cheerilee and Ditzy for a few seconds. Cheerilee smiled, then waved a hoof towards herself. "Come on. I'm not going to bite."
"Disappointing," said Vinyl.
"Um." The mare carefully placed both hooves on the table. "Are you the mare who danced with her girlfriend on Nightmare Night?"
Ditzy lean forward, her mouth a straight slit as her wings straightened out. "What if she is," Ditzy asked with an edge to her voice. "What of it?"
Cheerilee looked into the strange mares eyes. She nodded.
"Oh." The nervous girl met the non-judgmental gaze of the bowl of fries. "Well, if you ask a girl out and she says yes, and it goes okay... What do you do?"
Ditzy's eyes spun as Cheerilee breathed out.
"Be curious," she finally said. "Explore. Do what she likes. Always consider how she feels."
Vinyl giggled as her friend blushed. Cheerilee tapped her hoof on the table idly. "Vinyl, is it? I thought I saw you with stallions all year."
"What?" Vinyl giggled. "Oh, yeah. No, I'm here as back-up courage. Also, I thought this would be kinda like getting matches."
Cheerilee and Ditzy stared at her.
Vinyl shrugged. "Like in the Colt Scouts, you know? Something you keep just in case." She gently pulled her friend away from the table. "Be prepared for anything, you know. Come on, Daisy. Let's let these girls explore."
As she pulled her friend away, Cheerilee would have sworn that Vinyl winked at her. Ditzy shrugged. "So, what plans do you have for Lyra?"
Cheerilee leaned forward, rubbing her hooves together. "I've been planning for weeks. This Hearth's Warming is going to be perfect."
Ditzy cocked her head. "Why does it need to be perfect?"
Cheerilee raised an eyebrow. "You know, maybe more ponies should do your cute eye thing. You see a lot more than most." She slumped over the table, sipping her straw for a space of time. Ditzy remained attentive. Her sugary thinking break successful, she drew in a deep breath.
"How was Hearth's Warming at your house, Ditzy? I mean, while you were growing up?"
Ditzy chewed on the edge of her hooftip a second. "Awesome!" Ditzy exclaimed as she spread her limbs. "Mom would make huge helpings of food, Dad always helped me on my Commander Hurricane costume, and we'd all tell windigo stories until I fell asleep on the floor."
Cheerilee nodded. "My family doesn't do Hearth's Warming well, Ditzy. If my parents didn't have to go to other ponies' parties to make deals, they'd bring over business friends from out of town to get new contracts. It wasn't horrible, but it was never right. Never just us."
Ditzy nodded. "So, what are you getting Lyra on your special night to be just 'us'?"
Cheerilee shrugged, the weight of consumer culture pushing her shoulders down. "I have no idea what to get her, Ditzy. She's never been the kind of pony to keep things around." She idled pushed around the hay fries bowl. "What kind of pony doesn't like stuff?"
"Someone who's used to running," Ditzy wisely stopped from saying at the last minute. In fact, Ditzy merely leaned across the table and took Cheerilee's hoof in her own. "What she values is you, 'Lee. Plan something special for the two of you." Ditzy's smile was warm and sad simultaneously. "In the end, all that matters is the time you two spend together."
Sighing, Ditzy's wing pulled open her saddlebags and fished out two shiny tickets. "Look, here's two tickets to the Canterlot Castle's Hearthwarming Eve play. I want you to have it."
Cheerilee's eyes widened. "How in Equestria did you ever manage to get those?"
Ditzy stared off, laughing uncomfortably. "Oh, I might have done a favor for someone at the castle at some point." She pushed the tickets forward onto the table, allowing Cheerilee a glimpse at the gold-inlaid filigree show information. Many theater-goers keep tickets as keepsakes, but only one event's were good enough for the venue to sell extras as souvenirs.
"Ditzy," said Cheerilee as her mind reeled. "I have no idea how you could give these up."
Her friend shook her head dismissively. "Oh, I'm already seen it. I've gotten these every year since I got my cutie mark."
"Girl, I wonder what you did to earn these." Cheerilee ran her hoof down the ticket, feeling the raised calligraphy. Her parents were well off, but they never bought a ticket like this. The artistry increased as you neared the stage. A sixth row ticket hung in the Canterlot Art Museum. These were front row seats.
Ditzy nodded, eyes thoughtful. "I do too. I'll find out someday. Anyway, I've been going to the Hearth's Warming plays for a long time. Like, a really, really, really long time. It's your turn."
"Heh." Cheerilee held up the precious paper to her nose, breathing in the possibility. "I remember first going as a kid to one of the Ponyville shows. The used those cheap wooden windigoes that wouldn't fool anyone"
Ditzy thoughtfully sipped her drink before answering.
"Mine… were a lot more realistic at my first time."
Elsewhere and off the campus, Lyra hunched over a bar. It was hard not to feel self-conscious as one of the only five patrons who needed a drink on Hearth's Warming Eve. Her eyes lazily passed over endless unfamiliar pictures of soccer teams as she contemplated her next mood. "All right, give me a double."
"And I'll take that, squared," said the trenchcoated pony who sat down next to her. He ran a chestnut-colored hoof through an unruly mane of spiky hair, jogging Lyra's memory.
As the two ponies (or the pony and the kind of pony, as it were) started drinking, Lyra snorted and turned to her unexpected company. "We're quite a pair, aren't we? Drinking alone on Hearth's Warming Eve."
The Doctor nodded. "Yep. Even though I have someone waiting for me." His eyes went wide, and he looked around furtively before coughing. "Somepony, I mean. Sorry. Amphibian throat thing."
Lyra nodded. "Me too. Even got her a gift."
His eyebrows raised. "Something nice?"
A small felt-covered box levitated out of Lyra's saddlebags, flicking open to reveal a ring that sparkled in the candlelight.
"Yup." She sighed. "I just don't know if I'm a good enough mare to marry yet. Who'd slip a ring down their tail for a failed music student who reads about humans because she can't handle reality?"
"Humans." The Doctor sniffed. "Feh. Not bad, humans. Give me ponies any day." He speculatively tasted his beverage. "If she loves you, keep reading about humans."
Lyra snorted. The Doctor raised an eyebrow.
"I'm serious. Imagine. Everything you do, even the humans, makes the amazing symphony that is you. Each part is a movement she's fallen for. If she loves you, she fell in love with all of that."
Lyra was quiet for a full minute as she looked into her swirling cup. She risked a small, hopeful smile. "You drinking over someone special as well?"
"Yep." The Doctor knocked bank his tankard and pushed it back toward the bartender. "She sees just like a child. She sees just what I want, and she brings me back to life."
If anyone accused Lyra of having a romantic side they would have to quickly answer with raised forehooves, but she was blushing and sighing now.
"That's why I should leave," he said as he destroyed her moment. "I'm bad for her. Too much baggage. Have to find a new place. I might go off to fight in the war."
Lyra's head jerked up. "Wait, what war?"
The Doctor shrugged, gesturing vaguely upwards. "Oh, I don't know. There's always a war going on somewhere. For nebulous duty, generic deity and random geographic location, ooh-rah. It'll all be over by Hogswatch."
She learned on the counter, taking in the gentle eyes and slightly uncoordinated theatrical gestures. "Do you really picture yourself somewhere with a weapon?"
"Weapon?" He blinked. "Don't hold to those. Don't expect to use one."
"Ah. Short war then."
"Yep." He slugged back his drink. "This is swill. Bartender, do you have anything that's more like, I dunno, maybe a brick with a slice of lemon wrapped around it?"
Lyra scooted her stool over. "Go to Ditzy."
"What!" The Doctor looked at Lyra with suspicion. "What are you? Telepath? Shape changer? Thought construct?" He picked up a spoon in his teeth and brandished it in a threatening manner.
Lyra giggled as she levitated the spoon out and dropped it in his drink. "I saw you at a party once."
"Really?" He nodded and took another swig. "Never crossed my mind, that. Highly unlikely."
"Listen carefully, buddy. I've seen the way you two look at each other. If you walk away, you'll regret it for the rest of your life."
He was momentarily still. "Bartender, another two drinks please."
"And don't forget about her," Lyra continued as she snaked a limb around his shoulder. "She's set her whole life around the thought of being near or with or like you. I can't imagine what she'll do if you just disappear. I don't want to think about how that'll affect her."
"Plus," she said after pulling away and downing the latest of a nameless succession of shots, "if you hurt her I will hunt you down, and I will find you."
He swivelled, examining Lyra's eyes for the briefest of seconds. "You know, I believe you just might." He pushed himself you his feet, nearly falling over. "Whoosie woozie! Okay, need to be nober sow. Or something."
The Doctor slapped both his cheeks, mooed like a cow, and blew a raspberry. He closed his eyes for a single second of concentration, then stood up as sober as a chariot-stopping police officer. "Right, off I go then. Maybe I can help you one day, miss. Night!"
"Wait!" Lyra's eyes spread wide as he threatened to run off. "Hey, could you teach me that trick?"
He blinked, waving his hoof in the air as he began a gesture and forgot where it was going to end up. "Yes," he said before disappearing into the night.
Lyra sighed. "Bartender? Two large coffees please."
As the Doctor pulled himself out of the bar his eyes widened at the nearby labelled intersection. "Oh, no. Okay, the college is where exactly? Streets meet in the center, right?" He swivelled toward an outside table and grabbed a nearby bar patron by the shoulders. "I'm rubbish with streets. Where's the college?"
The stallion blinked, his brain never being quick while sober. His date, however, thought she saw an interesting conversation for the first time that night.
"Follow this road until you turn on Sol Street. Hey, you were drinking with the green girl, right? She's that musical deviant, right?"
The Doctor shrugged. "I dunno. Never heard her play."
"C-college is that way," choked out the stallion as the mare rolled her eyes. She pulled closer to the Doctor.
"No, I mean a real deviant." She pushed to the edge of her seat, waiting for the gossip.
"Her?" The Doctor scratched the back of his neck in confusion. "Oh, no. She's nothing, comparatively. You should meet the mathematiphiles of Abbot IV. They date geometrical concepts. Met a girl who married a halved right triangle. She was a bisectual."
He ran off, leaving the couple to add it up on their own.
Ditzy sat at the outside cafe table, staring at the starlight. The wind played through her hair as her eyes moved independently to mark the motion of the falling snowflakes. She idly began searching for patterns in the snowfall. Equations played through her head until she saw a pony well-practiced in running gallop across the campus grounds toward her. Ditzy started bouncing on her stool.
A thousand mares could never reach you, she thought with a smile. How could I have been the one?
The Doctor ran toward Ditzy, his scarf whipping in the wind. He skip to a stop in front of her and bowed. She clapped her mittens together.
"Hello, Doctor. Did you bring me anything?"
"A piece of sky every night, Miss Doo." He winked. "Shall we exeunt, or just simply leave?"
The Doctor extended his hoof and drew Ditzy onto her hooves. As they walked off onto the snowy drift, the Doctor felt the tip of her wing brush against the hourglass on his far flank. He turned, aiming a raised eyebrow at her blushing expression.
"Um." He considered. "What was that?"
She struggled with raising her eyes to his. "Um. I read about it in a novel, Doctor."
He nodded. "Oh. All right, then." He turned away then spun back in place. "What kind of novel?"
Ditzy finally raised her eyes to his. "A romance novel, Doctor."
They stared at each other, the intervening seconds filling with possibilities until the snowball hit Ditzy in the face.
"Dude, look at her. You really dizzyed up the girl."
"I think she came that way."
"Man, how old is he? That's kinda creepy."
The Doctor turned to see three giggling stallions in team jerseys. "Oi, you lot! Why would you possibly do that?"
Two of them looked at each as the third shrugged. "We like having fun at other's expenses?" The Doctor's only response was a growl.
With the Doctor restraining himself to the depths a warrior mare of Volupton's wardrobe can be considered restrained, Ditzy pinched her nose to stop a sneeze. In hindsight, when she and the Doctor would look back on this event while hiding behind a tree forty paces away they both decided that the sneeze was what did it, or in this case what didn't it.
Natural selection would've had a hard time producing more effective protection than Ditzy Doo's sneezes. Ditzy seemed to extrude cuteness as a defensive field, much as infants evolved to be charming to prevent parents from strangling them at three in the morning. Just as certain salamanders keep the traits of their youth (and think themselves "hip" and "edgy"), Ditzy Doo's bodily noises were still arguably adorable.
Whereas her eating noises had greatly eased certain moment in intergalactic diplomacy, her sneezes immediately projected onto the listeners an instant feeling of empathy and desire to embrace and comfort the afflicted. If one could have projected this ability into the past onto some prehistoric eohippus cave pony, the predators of Equestria would have guiltily starved themselves into oblivion hundreds of millennia ago.
If she had only sneezed, it would have deflated and unified the Doctor and the frat boys instantly, quite possibly leading to apologies, laughs all around, and a drunken bonding experience. In another universe, a blitzed physical education major may have embarked on a journey that begins with an inebriated stumble into a time machine and ended with him as on a distant world as a wise philosopher king with a taste for rugby.
But in the end, Ditzy Doo didn't sneeze, and the Doctor got angry. He snorted as he stomped toward the sniggering trio. Two of the not-so-motley crew were nearly doubled over in laughter. The third student had accidentally caught a look at the Doctor's eyes. Deep in his brain, something reptilian shouted that it might not be a bad time to start a lifetime dedication to running away, lest said lifetime turn out considerably shorter.
"Guys, we need to be somewhere," he said as he tried pulling them away.
The Doctor shook his hoof at the trio. "That's right, you should run! Run fast! You have no idea how good I am at running. When I catch you, you'll- "
Turning to Ditzy threw a wrench into the Doctor's mental gears. Her eyes were very nearly focused directly on him. She was quaking in a way few beings sort of galactic dictators had ever inspired in her. The baleful gaze she projected could have stopped a pony's heart; he was absurdly glad for bringing an extra.
"Doctor," she said as she stepped towards him with slow deliberation. "What's one of the most dangerous things I've ever faced?"
Bragging, he thought. I can handle bragging. This is familiar.
"Uh, the robot yetis? Real yetis? Animated storefront dummies?"
Ditzy gave him a reproachful glare that would have made Cheerilee suggest a career in education. "After all this time, did you really think I need the full 'I'm the Big Oncoming Storm' dragged out for my benefit for a snowball?"
The bullies gave each other a look with a meaning that, elsewhere in the multiverse, a Japanese human caught between two rubbery giant monsters would have understood. They knew they were playing well above their food chain level.
"Okay," stammered the terrified one who had locked eyes with the Doctor. "We'll leave you two to sort this out." He dragged his comrades over a snow drift, unconsciously looking for cover.
"Um." The Doctor backpedalled physically and mentally. "What would have been the appropriate response, then?"
Ditzy turned and pushed a wing in front of his face, using the feathers to count off. "Let's see, there's wiping off my nose with a hoofychef, kissing it to make it better, pushing your own nose into mine to share the snow," she said before pausing and lowering her wing. "You, know, anything that would have shown concern for me over macho idiot posturing."
The Doctor's nostril flared. "Idiot? I'm an idiot then, am I?"
Ditzy nodded. "Of course."
He scratched behind his mane. "Yep. Guess I kind of was. Doesn't the 'angry boyfriend' act get any points?"
Ditzy shivered, her eyes unfocused.
"Okay," he said slowly. "I said something, didn't I? I mean, I know I said something, I'm saying something now-"
Ditzy smiled, wings tentatively spreading outward. "Boyfriend, Doctor?"
His brain stopped, rewound, checked to see if there was any way out of this situation, and shrugged.
"Um." He paused. "Um. Hmm. Um. This should count as dating. I mean, we go to diferent dates. We go on dates to dates."
For the first time in centuries, the Doctor was unable to feel the turn of the planet as two warm lips tentatively covered his own. Slowly she pulled back, her face flushed as she watched his brain restart.
"Well. That was scary."
Ditzy smacked him playfully in the shoulder. He fell back on his rump, waving his front hooves around.
"Not that! That wasn't that! I like the lip thing. I meant the hoofballers."
Ditzy nickered. "Scary? Hoofballers with snowballs? Come on, Doctor. I bet that's not even in the top hundred."
"Them? No, no. No! I meant I was scared you were going to run off. I always worrying about this old stallion finally chasing you off."
Ditzy stared into his blue eyes for a second before finding herself. She deliberately and delicately kissed him on the nose.
"I'll never leave you, Doctor. I don't know what I'd do if you ever left me."
She leaned her neck across his mane and closed her eyes. They felt each other's hearts beat as the Doctor looked up at the stars.
Several definitions for insanity have been suggested by ponies over the years. They range from "Claiming to be Starswirl the Bearded" to "Attempting Diplomacy with Custard Products."
The one that generally floats to the top is "Attempting to Do the Same Thing Over Again with Different Results." This seems initially to be a bad definition, since it assumes the sanity of a pony with a firm grasp of cause and effect who yet claims to be a potato. Still, its the one most ponies (even potato ponies) know about.
This is why, despite maintaining a firm rejection of self-vegetableness, Cheerilee's action that night were insane.
She hummed to herself as she buzzed from place to place in the apartment, checking with certainty that all the touches were in order. Snacks and presents were fine. The tree was small, but would suffice. It only just touched the ceiling. Her father was renowned in Ponyville for trees that required renovations to display, even if only the servants were home on Hearth's Warming Eve.
This will do. Cheerilee hid a large book underneath a couch pillow, and patted it . Everything's in place except for me.
When Lyra walked into the dorm twenty minutes later, (slightly favoring her left forehoof), she was stunned to find Cheerilee surrounded by decorations and basking in the light of the fire.
"Well, now," Cheerilee said to her stunned lover as she adjusted her Princess Platinum crown, "do you like what you see, my subject?"
The first word Lyra was able to form was "Fire."
Cheerilee cocked her head. "Yes?"
Lyra crawled onto the couch, briefly noting the fake horn her girlfriend had put on and shivering pleasantly. "Love, we live in a dorm. How do we have a fireplace?"
The response was giggles. "I traded some cookies for a favor from an illusion magic major. The glamour's a little fragile, though. As long as you don't touch it, we've got a fire tonight."
Seconds later found Cheerilee underneath a warm and smiling green pillow. They rested like that for a while before either dared to speak.
"So," Lyra asked, "how'd you know about the 'Princess Platinum' thing?"
Cheerilee laughed. "Doesn't every good unicorn tomboy grow up with a crush on her?"
Lyra breathed out, cheeks reddening. She rolled over onto her back to position her head right under Cheerilee's so that their lips were nearly touching. After about ten minutes in this position she finally managed to get a word in.
"You know, Princess Platinum's wasn't known for lightning bolt earrings, but I like it. What else do we have planned?"
"Well, more of that." Cheerilee laughed. "I have cookies, hidden presents, and holiday costumes. First off, check what's under the pillow. It's your starter gift."
Lyra lifted a limb and wrapped it around Cheerilee's next. "Is it something for the 'special drawer'?"
Cheerilee rolled her eyes. "Later."
"Something practical, I bet." Lyra sniffed. "You never start with the fun stuff, Miss Teacher."
Lyra's horn lifted the pillow, revealing a large book. Immediately, she felt a ripple of pain run down her right forelimb.
"Music Theory for Foals? No."
"Love," Cheerilee said, "everypony uses the 'For Foals' books once or twice. I read the teaching series."
Lyra tried to levitate the book away, but Cheerilee caught it in her teeth. She placed it onto Lyra's chest.
"No," said Lyra. "I don't want it." She barely heard what her lover said as she stared at the cover and saw only a judgemental hair of rainbows.
Cheerilee sighed. "Honey, I'm proud of you but I can tell you need help. You work hard, and you missed so much while you were busking."
Lyra tried to push away the book with her hoof. "I'm not dealing with this tonight."
Cheerilee bit her lip. She searched her mind for the best possible ways to smooth over the moment. Unknowingly choosing the worst words possible, she gave it her all and selected an action that in view of Lyra's previous reactions could charitably called insane.
"You have to face it. You can't run."
Lyra rolled off the couch violently, one hoof pushing off of Cheerilee's stomach. Her horn flared as she through the offending book away with a scream. It impacted into the tree, shaking the branches. There was a sound of something with a checkerboard pattern breaking on the floor.
Lyra stopped. She looked at the mess of needles and ripped tinsel. The book had gone through the tree entirely, upending a mug of something onto its cover as it lay in a corner. Turning to Cheerilee, Lyra saw a scared face breathing quickly.
Stop hurting yourself, Ballad had said. You're going to make ponies think I have a freak for a sister.
Lyra raised a hoof gently towards Cheerilee. "Don't," she whispered. "Don't go."
Cheerilee hadn't heard. She stood up on the couch, shaking with tears. "Not tonight, Lyra. Please. I'll let you say whatever you want tomorrow, Lyra. Don't do this tonight."
Lyra's legs gave out underneath her. Whereas Cheerilee had expected an angry and shouting unicorn, what she got was a sobbing balls of green in a fetal position. Cheerilee stepped closer as Lyra bawled into her hooves.
"I'm sorry. You never should have fallen for a freak. I don't know what's wrong- "
Lyra looked up in time for Cheerilee to kiss her on the nose.
"Shhhh. I hit something inside you, didn't I? Lyra, you can tell me why you did that later. I just want to help you get rid of the tears now."
Lyra pulled herself onto her knees. She lifted one at a sharp touch and frowned.
"That's the Senior Dance picture of us, wasn't it?" Her lips started vibrating.
Cheerilee threw her limbs around Lyra, pulling her into a tight embrace. "It's okay. I don't need the picture. I still have the mare I went with."
Lyra stood up. She wiped her eyes and smiled. "You know, you make me a better pony."
Cheerilee smiled. "That's my job. If I ever stop I get fired, you'll know." I'm going to go clean up. You get back on the couch."
Lyra watched Cheerilee tidy the dorm. She straightened the tree, swept up the glass, and carefully place the intact picture to the side. Lyra started rubbing her forelimb as she saw Cheerilee wiped off the book instead of throwing it away.
"I guess we're not done with that," she whispered to herself.
"Hey, Lyra?"
She turned to Cheerilee, hoping for a distraction for arguments to come. "Yes?"
"Out of curiosity, did anyone ever teach you to salivate less with your mouth open?"
Her answer was a long snort. "You magnificent educator, what is tonight's lesson?"
Cheerilee dropped the dustpan out of her mouth. "Behave. We have a show to be at in an hour. I can't wait to see what you got me."
Lyra looked at her saddlebags. "I'm not sure its ready yet."
Hearth's Warming Eve rolled on. They were together, and as long as no one touched it the fire kept burning.


text:
Cyclists of the World, Large Cycling Poster
Cyclists of the World, Large Cycling Poster
We love all things cycling; particularly the Classics, Grand Tours and all of the evocative paraphernalia that goes with it.
Taken from our original illustration; this giclee art print depicts a selection of riders – resplendent in their national jerseys, representing some of the world's great cycling nations including: the USA, Great Britain, Norway, Germany, Belgium, Australia, Italy, France, Switzerland, Canada and the Netherlands.
This print would make a great gift for your cycling mad friends, family or just as a little treat for yourself.
It is printed with pigment inks onto smooth matt art paper, creating a beautiful high quality art print.
The print measures 50 x 70 cm (27.5 x 19.5 inches approx) and fits a standard size frame from ikea etc...
Your print will be carefully wrapped in acid free tissue paper and packed in a sturdy cardboard tube and as this print is printed to order, we use a trackable mailing service to ensure it reaches you safely and in tip top condition.
N.B. Print sold unframed and unmounted / unmatted.
© gumo 2013. All Rights Reserved


text:
If you can't foster or adopt at this time, please consider helping our Neediest Cases .
Love this breed? NGPR now has a Rescue Store where your purchase goes to help our rescue dogs and neediest cases.
Thank You!
Your message has been sent to National Great Pyrenees Rescue.
You'll receive a copy, too, at to help you keep track of which pets you've inquired about, and which shelters and rescues you've emailed.
NOTE: Some shelters have physical locations you can visit; some of these shelters may only have pets for a limited time, so please do not wait for a reply—just go visit the shelter! Other organizations are rescue groups run by busy volunteers who may take a while to reply. You can find information about the shelter or rescue group caring for this pet, and their adoption procedures, on the pet's details page on Adopt-a-Pet.com.


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- Doctors
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The staff and the doctor act like they are so much better than the people they are treating. They seem to forget they are in Beattyville not New York.
Hands down best doctor around! He actually cares about the patient. Very knowledgable, Extremely nice guy!
Dr. William Jerome G. also comes to a Suboxone clinic in Hazard. He only keeps you on a helpful dose for a few months and then tells you he has to follow DEA regulations and lowers you down twice only within month's. All patients know that Dr. Burnette who owns these clinics keeps his patients on 3 dosages per day for years and he also knows more about addiction and is much more understanding. I know it is up to a patient when its time to taper down because of the psychological effects are the main problem when it comes to addiction. It takes YEARS, not a few months, to get your head back and for the cravings to go away.. I feel as well as all of the other patients that go to the clinic in Hazard that Dr. W. J. G. needs to "learn" more about the psychological effects of addiction, not just the physical effects and the way he does it I only see people rebounding back to drugs since he tapers everyone down much too quickly.. Gotta find a more understanding Dr. I tried submitting my review and received a message to not use the word "g_y" in my review so going to try and resubmit and call him Dr. William Jerome G
Dr. Gay is a very compassionate Dr. He is not only caring but very knowledgeable and has a very good personality. My husband and have both switched to him. So glad he came to our community.
Great doctor, smart and very caring!!! The best doctor in southeast Ky for sure
The most kind and professional doctor that has ever treated me. Spent more time with me than any other doctor. Showed a genuine interest in seeing that my health needs are met. I recommend him above any other doctor in this area.
Went to the doctor out of necessity, and was charged $200.00, just to walk in the door. Utterly ridiculous to abuse a patient who does not have health insurance this way. Normal doctors offices prorate services for people who are willing to pay cash up front. I will never be back, simply because I can not afford it.
The staff were professional, caring and efficient.
Dr. Gay is a compassionate, caring doctor that really works well with his patients. I am so glad that I am now his patient!
Takes his time with you, start are great, So glad I changed doctors
Dr. William J. GAY's Credentials
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Monoclonal antibody 4C5 prevents activation of MMP2 and MMP9 by disrupting their interaction with extracellular HSP90 and inhibits formation of metastatic breast cancer cell deposits
Heat shock protein 90 (HSP90) is a molecular chaperone that is considered a new target for the treatment of cancer. Increasing data reveal an extracellular chaperoning activity for HSP90. Here we investigate the interaction of the secreted isoforms of HSP90 with matrix metalloproteinases (MMP) MMP2 and MMP9. Moreover we examine the role of a monoclonal antibody (mAb) against HSP90, mAb 4C5, regarding these interactions and its value as a potential inhibitor of human breast cancer cell invasion and metastasis.
Our results showed that both HSP90α and HSP90β are secreted by MDAMB453 human breast cancer cells and interact with MMP2 and MMP9. MAb 4C5, while not affecting the secretion of inactive MMPs, inhibits their activation by disrupting their interaction extracellularly with both isoforms of HSP90. The
Both isoforms of HSP90 are secreted by MDAMB453 cells and interact with MMP2 and MMP9. MAb 4C5 prevents MMP2 and MMP9 activation, by disrupting their interaction with HSP90. Finally mAb 4C5 significantly inhibits the metastatic deposit formation of MDAMB453 cells, by preventing their extravasation and infiltration in the lung tissue and therefore it could be used as a potential therapeutic agent for cancer metastasis.
The dissemination of tumor cells from their primary site of growth to distant organs is the major cause of morbidity and death among cancer patients
One well-characterized property of invasive tumors is their ability to accelerate the degradation of the extracellular matrix, by matrix metalloproteinases (MMPs)
The heat shock protein 90 (HSP90) is a molecular chaperone which exists in mammalian cells in two isoforms that share 86% aminoacid conservation (HSP90α and HSP90β). It is one of the most abundant cytoplasmic proteins in unstressed cells, where it performs housekeeping functions, controlling the activity, intracellular disposition and proteolytic turnover of a variety of proteins. Over the past years there has been increasing evidence that HSP90 interacts with a great number of molecules intracellularly, that are involved in the development and/or survival of cancer cells
Taking all the above into consideration together with previous data showing that HSP90α is secreted from fibrosarcoma cells and promotes their invasive capacity through association with MMP2
Both the α and β isoforms of HSP90 are secreted by MDAMB453 breast cancer cells and interact with MMP2 and MMP9
In order to investigate the secretion of the α and β isoforms of HSP90 by MDAMB453 cells, cell lysates and concentrated supernatants derived from the culture of these cells were analyzed by Western blotting using mAb 4C5 which recognizes both isoforms of HSP90
Figure 1
Both the α and the β isoforms of HSP90 are secreted by MDAMB453 cells and interact with MMP2 and MMP9 metalloproteinases
Both the α and the β isoforms of HSP90 are secreted by MDAMB453 cells and interact with MMP2 and MMP9 metalloproteinases. (A) Cell lysates were immunoblotted with mAb 4C5 recognizing both isoforms of HSP90 and serving as positive control. Concentrated supernatants derived from the cell cultures as described in Methods, were analyzed by Western blot using anti HSP90 α and anti HSP90 β antibodies and mAb 4C5. Anti beta actin antibody was used in both fractions. Secretion of the two isoforms of HSP90 was detected in the supernatant derived from MDAMB453 cells. The absence of beta actin in the supernatant demonstrates that there is no contamination of this fraction with the intracellular components of cells during the experimental procedure. (B) Western blot analysis of concentrated supernatants derived from MDAMB453 cell cultures, using anti-MMP2 and anti-MMP9 antibodies showed that both the pro-MMP2 and pro-MMP9 as well as their activated forms are present in the culture medium. Proteins derived from the culture supernatant were immunoprecipitated with anti-MMP2 and anti-MMP9 and bound proteins were analyzed by Western blot with anti-HSP90α and anti-HSP90β antibodies. Both isoforms of HSP90 interact with the two metalloproteinases. Irrelevant IgGs and anti-MMP2 or anti-MMP9 antibodies were used as negative and positive controls respectively. (C) Proteins derived from the MDAMB453 cell culture supernatant were immunoprecipitated with anti-HSP90α and anti-HSP90β antibodies and immunoprecipitants were analyzed by Western blot using the anti-MMP2 and anti-MMP9 antibodies. Irrelevant IgGs and anti-HSP90 α or anti-HSP90 β antibodies were used as negative and positive controls respectively. The reverse immunoprecipitation experiment showed that both isoforms of HSP90 interact with pro-MMP2 and pro-MMP9 and to a lesser extent with the activated forms of the two metalloproteinases. IP immunoprecipitation, WB Western blot.
An important characteristic of invasive tumors is their capacity to accelerate the degradation of extracellular matrix by MMPs
MAb4C5 prevents MMP2 and MMP9 activation and disrupts their interaction with both the α and the β isoform of extracellular HSP90
Based on our observation that presence of both the inactive and mature forms of MMP2 and MMP9 were detected in the concentrated supernatants derived from MDAMB453 cell cultures, we next examined the effect of mAb 4C5, the function blocking anti-HSP90 antibody, on the secretion and activation of MMP2 and MMP9. Analysis of concentrated supernatants derived from MDAMB453 cells, with zymography, showed that when 200 μg/ml of mAb 4C5 were included in the culture medium, presence of the inactive pro-enzymes was not affected, while detection of the activated forms of both MMPs was not obtained (Figure.
Figure 2
MAb4C5 prevents MMP2 and MMP9 activation and disrupts their interaction with both the α and the β isoform of extracellular HSP90
MAb4C5 prevents MMP2 and MMP9 activation and disrupts their interaction with both the α and the β isoform of extracellular HSP90. (A) Metalloproteinases derived from the concentrated supernatants of control and mAb 4C5 treated cultures of MDAMB453 cells were isolated and analyzed by zymography, as described in Methods. Proteolysis was detected as a white zone in a dark field. Metalloproteinases previously isolated as described in Methods were used as markers. Activated MMP2 and MMP9 are absent in the mAb 4C5 treated cultures. (B) Proteins derived from the concentrated supernatants of control and mAb 4C5 treated cultures of MDAMB453 cells, prepared as described in Methods, were analyzed by Western blot using anti-MMP2 and anti-MMP9 antibodies. Presence of mAb 4C5 in the culture medium inhibits activation of both metalloproteinases. (C) Proteins from the above described supernatants were immunoprecipitated with anti-MMP2 and anti-MMP9 antibodies and bound proteins were analyzed by Western blot with anti-HSP90α and anti-HSP90β antibodies. MAb 4C5 disrupts the association of both isoforms of HSP90 with the two metalloproteinases, since anti-MMP2 and anti-MMP9 antibodies did not co-immunoprecipitate any detectable levels of HSP90 in the mAb 4C5 treated cultures, when compared with controls. Western blot analysis of the MMP2 and MMP9 immunoprecipitants, using the corresponding antibodies was performed as positive controls and irrelevant IgGs were used as negative controls. IP immunoprecipitation, WB Western blot.
Consequently and taking into account the previously demonstrated interactions of both isoforms of HSP90 with MMP2 and MMP9, we explored the role of mAb 4C5 in relation to these interactions, using co-immunoprecipitation experiments. To this purpose, concentrated conditioned media derived either from control or mAb 4C5 treated cultures were immunoprecipitated with antibodies against MMP2 and MMP9 followed by Western blot analysis with antibodies against the α and the β isoforms of HSP90. As shown in Figure
MAb4C5 inhibits the metastatic deposition of MDAMB453 breast cancer cells into the lungs of SCID mice
On the basis of previously reported studies using the MDAMB453 cell line
Figure 3
MAb 4C5 inhibits the metastatic deposition of MDAMB453 cancer cells into the lungs of SCID mice
MAb 4C5 inhibits the metastatic deposition of MDAMB453 cancer cells into the lungs of SCID mice. MDAMB453 cells were labeled with the fluorescent dye DiI and injected into SCID mice, in the presence either of 100 μg/ml of mAb 4C5 or of an irrelevant antibody (control), as described in Methods. Evaluation of metastatic deposits was performed several hours later. (A) Macroscopic level: An important number of metastatic deposits (arrow) was observed in control animals as compared to mAb 4C5 treated mice. (B) Microscopic level: Representative cryosections of the lungs of control and mAb 4C5 treated mice. The arrows show MDAMB453 cells stained with DiI present in the lung tissue. A significant decrease in the deposition of cancer cells was observed in the mAb4C5 treated mice. (C) Quantitative effect of mAb 4C5 on the metastatic deposition of MDAMB453 cells into the lungs showed an 86.67% inhibition of the metastatic deposition in the mAb 4C5 treated mice when compared to the control animals. (D) A 3D reconstitution of a cryosection from a control animal: The arrow demonstrates infiltration of metastatic deposits in the lung tissue. (E) MDAMB453 cells restrained in the inner surface of large pulmonary vessels derived from mAb 4C5 treated mice. On the contrary, in the lungs from control mice MDAMB453 cells could rarely be detected stagnating in the inner surface of the pulmonary vessels. However, cancer cells were clearly observed dispersed in the lung tissue. Arrows indicate the pulmonary vessels. (F) Quantitative effect of mAb 4C5 on the retention of MDAMB453 cells in the pulmonary vessels. A 15.4% of the vessels visualized in the control animals showed intravascular cancer cell retention. In contrast in the mAb 4C5 treated mice, cancer cells were observed stagnating in the inner surface of 58.76% of the calculated vessels (p < 0.01 Bar, 40 μm).
Our present findings demonstrate that both the α and the β isoforms of HSP90 are secreted by cultured MDAMB453 human breast cancer cells and interact with matrix metalloproteinases, MMP2 and MMP9. Additionally, we show that a monoclonal antibody against HSP90, mAb 4C5, prevents maturation of the two metalloproteinases
We have previously reported the presence of HSP90α and HSP90β on the cell surface of MDAMB453 breast cancer cells
Additional file 1
Additional figure showing that the antibody against HSP90β does not recognize the HSP90α isoform. The western blot analysis of human recombinant HSP90α and total cell lysates (positive control) derived from MDAMB453 cell cultures using anti-HSP90α (positive control) and anti-HSP90β antibodies.
Click here for file
Additional file 2
Additional figure legend. A file containing the legend of the additional figure.
Click here for file
Controlled degradation of the extracellular matrix is essential for the invasion and metastasis of malignant tumors. In this context matrix metalloproteinases and in particular MMP2 and MMP9 are of crucial significance for tumor development and progression
We have previously demonstrated that mAb 4C5 inhibits the invasive capacity of MDAMB453 breast cancer cells by disrupting the interaction of cell surface HSP90 with the extracellular domain of HER-2, a member of the ErbB family of epidermal growth factor receptors
We have previously demonstrated that mAb 4C5 significantly inhibits melanoma metastasis in C57BL/6 mice inoculated with B16 F10 melanoma cells,
Our present findings combined with recently reported data
MAb4C5 was produced and characterized, as previously reported
Cell cultures
The MDAMB453 human breast cancer cell line was kindly provided by Dr A.Mamalaki from the Hellenic Pasteur Institute, Athens, Greece. The cells were seeded at a density of 2×106 cells per cm2 on plastic dishes as monolayers in RPMI media containing 10% FBS and supplemented with the antibiotic garamycin, (10 mg/ml) in a 5% CO2 humidified atmosphere at 37°C. When cells reached confluence, the initial medium was replaced by RPMI without FBS and the cells were left for 24 hours in starvation conditions. Subsequently they were exposed to 200 μg/ml of mAb 4C5 for 24 h. Control cultures were grown for 24 h either in RPMI medium alone or in culture medium containing 200 μg/ml of an irrelevant IgG2a monoclonal antibody named BM88
Preparation of cell lysates and concentrated supernatants
At the termination of the cultures, cells were immediately washed twice with ice-cold PBS and lysed in 50 μl lysis buffer (137 mM NaCl, 20 mM Tris/HCl pH 7.4, 50 mM HEPES, 5 mM EDTA, 1 mM DTT, 1 %Triton, 10 %Glycerol, 200 mM Na3VO4, 0.5 mM PMSF, 5 μg/ml aprotinin, 5 μg/ml pepstatin and 50 μg/ml leupeptin). Protein lysates were quantified and equal amounts of total protein were subjected to SDS-PAGE and Western blot. Concentrated supernatants derived from MDAMB453 cells, cultured as described above, were prepared as follows: An initial volume of 20 ml of culture supernatant was collected from each experimental case (control and mAb 4C5 treated cultures). At this point it is important to underline that the supernatants were derived from the same number of cultured cells, for all experimental cases. Subsequently 100 fold concentration was performed using ultra centrifugal filter devices (10000 MWCO) obtained from Millipore TM. The concentrated supernatants were used for all the experimental procedures concerning immunoprecipitations and Western blots. Equal volumes of the concentrated supernatants were subjected to SDS-PAGE on 12% acrylamide in order to obtain the best separating conditions for the proteins of interest
Co-immunoprecipitation was performed as previously described
Isolation of metalloproteinases
Isolation of the MMPs from the other proteins present in the concentrated supernatants was performed as previously described
Equal volumes of isolated MMPs derived from control and mAb 4C5 treated cultures of MDAMB453 cells, were denatured and analyzed by gel electrophoresis in a 10% SDS-polyacrylamide gel containing 0.1% (w/v) gelatin. The gel was incubated at room temperature for 2 h in the presence of 2.5% Triton x-100 and subsequently at 37°C over night in a buffer containing 10 mM CaCl2, 0.15 M NaCl, and 50 mM Tris (pH 7.5). The gel was then stained for protein with 0.5% (w/v) Coomassie and photographed on a light box. Proteolysis was detected as a white zone in a dark field. MMPs (proenzymes and active forms) isolated as previously described
Assay of MDAMB453 cell metastatic deposit formation in the lung tissue
SCID mice were originally purchased from Jackson Laboratory, bred and maintained under specific pathogen free conditions at the Experimental Animal Unit of the Hellenic Pasteur Institute. All of the experiments with animals were done in accordance with the guidelines approved by the Ethical Committee of the Hellenic Pasteur Institute. The
Evaluation of tumor cell retention in the pulmonary vessels
In the above mentioned lung sections the total number of blood vessels was calculated and MDAMB453 stagnating cells were visualized and compared between the control and the mAb 4C5 treated animals.
Statistical analysis
For the experimental groups that were statistically analyzed for differences, Student's t test was used, in which
Authors' contributions
DS participated in the design of the study carried out, part of the i.p. experiments, the in vivo experiments and the statistical analysis. Moreover he participated in the drafting of the manuscript. AH performed part of the i. p. experiments and the zymography. EP conceived of the study, oversaw the experimental design and wrote the final draft of the manuscript. All authors read and approved the final manuscript.
We wish to thank Dr A. Aletras for precious advice concerning the zymography experiments and for providing the metalloproteinase markers, Dr A. Mamalaki for providing the MDAMB453 cell line, Dr C. Prodromou for his generous gift of recombinant HSP90α and Dr K. Sidera for critically reading the manuscript. This project was supported by the European Social Fund and National Resources-(EPEAEKII-Archimides).
Dissemination and growth of cancer cells in metastatic sites
Proteolytic and non-proteolytic migration of tumour cells and leucocytes
Matrix metalloproteinases in tumour invasion and metastasis
The hallmarks of cancer
Metastatic potential correlates with enzymatic degradation of basement membrane collagen
Protease degradomics: a new challenge for proteomics
Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion
Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin
Heat shock protein 90 as a molecular target for cancer therapeutics
Pharmacogenomics in cancer drug discovery and development: inhibitors of the Hsp90 molecular chaperone
HSP90 as a marker of progression in melanoma
Extracellular HSP90: conquering the cell surface
Monoclonal antibody 4C5 immunostains human melanomas and inhibits melanoma cell invasion and metastasis
A critical role for HSP90 in cancer cell invasion involves interaction with the extracellular domain of HER-2
Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness
Involvement of cell surface HSP90 in cell migration reveals a novel role in the developing nervous system
Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs
Extracellular heat shock protein-90alpha: linking hypoxia to skin cell motility and wound healing
Transforming growth factor alpha (TGFalpha)-stimulated secretion of HSP90alpha: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFbeta-rich environment during wound healing
Matrix metalloproteinases in tumor invasion
New functions for the matrix metalloproteinases in cancer progression
How matrix metalloproteinases regulate cell behavior
Role of acetylation and extracellular location of heat shock protein 90alpha in tumor cell invasion
Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies
Enhanced metastatic dissemination to multiple organs by melanoma and lymphoma cells in timp-3-/- mice
Identification of a novel neuron-specific surface antigen in the developing nervous system, by monoclonal antibody 4C5
Purification and characterization of neuron-specific surface antigen defined by monoclonal antibody BM88
Molecular Cloning: A Laboratory Manual
Creatine kinase, an ATP-generating enzyme, is required for thrombin receptor signaling to the cytoskeleton
Gelatinolytic and collagenolytic activity in periprosthetic tissues from loose hip endoprostheses
Inhibition of spontaneous breast cancer metastasis by anti-Thomsen-Friedenreich antigen monoclonal antibody JAA-F11


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Three children struck by vehicle in Ashburn driveway
Three children playing in the driveway of an Ashburn home were hospitalized Thursday night – one with serious injures – after a teenager in the midst of a driving lesson with her parent lost control of her vehicle.
One of the three children, a 7-year-old girl, is being treated for life-threatening injures at Inova Fairfax Hospital.
Two others – 8- and 10-year-olds, were taken to the Lansdowne campus of Inova Loudoun for treatment of non-life-threatening injuries.
According to the Loudoun County Sheriff's Office, a 15-year-old girl was driving on Morven Woods Court about 6:45 p.m. when deputies believe she accidentally accelerated, causing the vehicle to jump a curb onto a sidewalk where the children were playing.
The crash is under investigation by the Loudoun County Sheriff's Office Crash Reconstruction Unit.
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Dr. Jay Rhee, MD is a hematology doctor who practices in Annapolis, MD. He is 43 years old and has been practicing for 17 years. Dr. Rhee is affiliated with Anne Arundel Medical Center.
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Question about Gateway FPD1975W 19" LCD Monitor
I just bought a 19" lcd monitor...2 DAYS AGO!!!!!!! Well to day i get on and there's a red tint on the whole screen......i can see some lines going through the background....i've checked the plugins and everything's connected fine. I even tried plugging in the monitor to a different computer...same problem...so i know it's the monitor..just dont know what!!!!!!!!
Posted by luckysgirl11 on
Not rocket science... take it back to the store and get a different one. It does come with warranty.
SOURCE: I have freestanding Series 8 dishwasher. Lately during the filling cycle water hammer is occurring. How can this be resolved
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Seltzer set for England
By Adam Marshall
Last Updated: 01/01/70 1:00am
The highly-rated full back is being tipped to leave Argentinos Juniors in his homeland and join the growing band of his countrymen plying their trade in The Premiership.
Spurs, of course, have close links with the South American country, and former star Ricky Villa has been spotted at White Hart Lane recently.
The 1981 FA Cup final replay hero is acting as an agent for up-and-coming players in Argentina, as previously reported on planetfootball.com, and is believed to have advised his English contacts to pursue an interest in Seltzer.
The 21-year-old defender could be linking up with pals Julio Arca and Nicolas Medina in the English top flight, providing the ever-complicated transfer details can be ironed out.
South American sources claim Spurs are in pole position to land Seltzer, but there could well be interest from rival clubs.
Indeed, Sunderland may be in the market for a new full back, and Peter Reid has made scouting trips in the past to check on potential targets.
Furthermore, the pint-sized player is currently with the same club that sold both Arca and Medina to Stadium of Light boss Reid.
With the economic crisis engulfing the country as a whole, Argentinian players are expected to head for Europe in an even greater number than has previously been the case, with wealthy clubs looking to take advantage of the situation.
Victorio Ocampo-born Seltzer is well known to top scouts after being involved with his country's successful Under-20 side, and seems ready to make a move before the start of next season.