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When it comes to flying, the ability to navigate the friendly skies fits like hand and glove to 20-year-old pilot Jonathan Strickland.
So much so, that the young aviator's love of flying is attributed to being focused to the point that he says: "I do not know what I would be doing today if I were not for aviation."
"I've been flying since the age of eight and ever since then, I have always loved the freedom that comes with piloting an aircraft. The feeling that you are in 100% control of the operation is incredible," Strickland told EURweb via e-mail. "All I ever wanted to do was to fly airplanes. With that said, it was not 'difficult' to stay focused on that goal. In addition to this, I also had great support from my mother, father, as well as grandparents in looking for any opportunity that would help me making my dream of being a pilot a reality."
Reality is one filled with major accomplishments for Strickland, who transformed the sky into a home away from home with his first general aviation plane flight in the Experimental Aircraft Association's Young Eagles youth program in Torrance Ca. and lessons learning how to fly helicopters.
Strickland's hard work ultimately paid off with him becoming the youngest person to solo a helicopter and airplane on the same day as well as the youngest African-American to solo a helicopter, fly a helicopter round-trip internationally and solo six airplanes and one helicopter in the same day. Add to that, a current job flying the Bombardier CRJ 700 regional jet for United Airlines Express based in Chicago's O' Hare International and it's safe to say that dreams do come true for the young man who grew up in Inglewood, CA.


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Dallas: There are several ways to share files within the same platform; iOS devices make use of AirDrop whereas Android has Android beam for sharing files. But the problem arises when you think of sharing files across platforms (from iOS to Android or vice versa).
Earlier, we used to follow many ways like emailing the file or uploading it to the Dropbox so that it can be downloaded on the phone later. But now, fortunately we have a lot of applications which are designed to solve the problem of sharing files across platforms. There are different options out there, out of which the most favored one is the app called Zapya which is available both on iOS and Android platforms.
Zapya is a local file sharing application which makes use of wireless networks to connect two different devices. It just uploads the files on one device and lets you download it on the other; it is as simple as the chatting on Facebook. Not only that, Zapya also allows you to share applications between the devices.
This is how Zapya works:
Zapya lets you share files easily using Wi-Fi network, so file transfer will obviously be faster when compared to cloud services. As you are not uploading or downloading anything, it doesn't use up your data limit or cost you anything. Of course, it is slower when compared to USB file transfer method, but it is certainly beneficial for getting files out of an iOS device, which could be cumbersome or even impossible in some cases.
Zapya also has certain limitations associated with it. In case of an iOS device, you're confined on the contents you can send. In order to share a photo or a video, you need to open the particular file using corresponding apps and then you can tap on share icon to send the file to Zapya first which can later be downloaded on an Android device. This often makes the app to crash. But in Android device, as it has an open file system, you can just browse the file you want to send and share them with iOS devices. Later you can just tap the file and select "open in" option to open the required app.
Fortune Innovations Dallas, a front-runner in mobile application development, offers consulting and outsourcing solutions to the clients all over the globe. Our developers excel in the latest development technologies and are competent in building astonishing mobile applications. Contact us for any requirements on Android or iPhone application development.

subset: commoncrawl


text:
|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|Steven Noels <stev...@outerthought.org>
|Re: JSF CarStore Sample
|Fri, 17 Sep 2004 11:15:29 GMT
On 17 Sep 2004, at 12:56, Vadim Gritsenko wrote: > You acknowledge that this software is not designed, licensed or > intended for use in the design, construction, operation or > maintenance of any nuclear facility. > --> > > Just want to confirm, we can not add this carstore sample to the > Cocoon's Faces block, right? Or we do have some option here? This is just BSD-style-with-required-credits with the nuclear thing added. I wouldn't be bothered too much with it - it's at the discretion of the nuclear end-user to acknowledge the fact that this demo is going to melt his core. </Steven> -- Steven Noels http://outerthought.org/ Outerthought - Open Source Java & XML An Orixo Member Read my weblog at http://blogs.cocoondev.org/stevenn/ stevenn at outerthought.org stevenn at apache.org
|View raw message


text:
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Texturized rose gold plated collar necklace. Adjustable. By Karen LondonRose Gold Plated PewterMade in the USAApproximately 6" drop, 1 1/4" wide (at widest)
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text:
Athens: Greece's World Cup players have turned down their World Cup bonus and called for the money to be used to build a national training centre in the cash-strapped country, reports said yesterday.
Greece's Theofanis Gekas (centre) is consoled by teammates. Pic/Getty Images.
The team wrote to Greek PM Antonis Samaras saying they did not want the promised bonus.
Catch all the FIFA World Cup 2014 action here
Costa Ricans rejoice in San Jose
"We do not want the extra bonus. We only play for Greece and its people," their letter was quoted as saying. "But we ask you to support our effort to find a land plot in order to create the training center that will house our National team."


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According to a poll done in Britain, four out of 10 Muslims want sharia law enforced. PLEASE TAKE NATIONAL POLLS AND PETITIONS. YOUR OPINION MATTERS Results Are Sent To Congress - Let Congress Hear Your Voice
Results Are Sent To Congress - Let Congress Hear Your Voice
The ICM opinion poll also indicates that a fifth have sympathy with the "feelings and motives" of the suicide bombers who attacked London last July 7, killing 52 people, although 99 per cent thought the bombers were wrong to carry out the atrocity.
Overall, the findings depict a Muslim community becoming more radical and feeling more alienated from mainstream society, even though 91 percent still say they feel loyal to Britain.
The results of the poll, conducted for the Sunday Telegraph, came as thousands of Muslims staged a fresh protest in London yesterday against the publication of cartoons of Mohammed. In Libya, at least 10 people died in protests linked to the caricatures.
Although the individuals polled were in Britain, it is a good indicator as to how Muslims may feel around the world.
What is your opinion?
H/T: Telegraph


text:
What breed do you think my new puppy is?
By Omar from San Francisco, CA
Add your voice! Click below to answer. ThriftyFun is powered by your wisdom!
Your dog looks like it might have a bit of pitt bull in it to me. My sister had a pit bull pup that looked very much like your dog only it was a darker color. From the photo it looks like it has the rounded head you see on boxers but boxers have short, blunt snouts. To me your dog looks more in the range of pit bull. Cute puppy!
I agree. She looks like she has a lot of pit in her.... her coloring is brindle. I recently rescued one that looked a great deal like her. She could have something else mixed in, but my guess is, she has a lot of pit.
I think i see some Dane. Pit-maybe Lab, lots of devotion. I can see it in her eyes. What a beauty. You are so blessed.
Could be an American Staffordshire Terrier mix. I have one just like that. Only with standing ears.
I think it's a American Staffordshire Terrier mixed with Pit bull. Go to dogchannel.com to look at the dog breeds. So cute.
Not sure about yours. Anyone have any idea on ours. The rescue organization said he was a golden retriever/boykin spaniel mix. I don't see any boykin in him. Thoughts? Thanks.
This baby looks to be a Brindle Staffordshire Terrier and may have a little lan in there if it full grown. But may be full blooded if is a puppy. Pretty dog!
Add your voice! Click below to answer. ThriftyFun is powered by your wisdom!
By Tebbie R from Pierre Part, LA
Don't know, sorry but I just have to say that is the cutest little girl!
By KC W. from Chicago IL


text:
|New Wounds
|Their Cuts
|Old Scars
can you help me sleep again - Perfect Imperfection
May 2009
can you help me sleep again
its about 3 in the morning, and i just got home from san marcos. i needed to get away to clear my head. the past week has been hectic. pledge induction for phi kappa psi were last sunday and our tests have been non-stop. my pledge brothers have been adding extra stress to my papers and tests this week and ive just been emotionally drained. we're not supposed to drink or be alone for 8 weeks. insane. major change for me, i dont even want to party now. oh well, its really late and i am craving my queen.
Current Mood: nostalgic
Current Music: The Office - Season 2
|New Wounds
|Their Cuts
|Old Scars


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Shark Dad St. Louis, Missouri
"...one of the best things to happen to garage rock in a long time."
-- Beach_Sloth
"[a] refreshing break from the rigmarole of modern rock and radio" "F**king classic." -- Zach Valladon
"Classy hooks can be found here, and you don't need to dig very deep to find them."
-- "Riverfront Times"
Shark Dad is :
Jason - vocals
Kevin L - drums
Krash - bass
Jeremy E - guitar ... more
Streaming and Download help


text:
Mazda joint venture partner, FAW Car, a listed subsidy of FAW Group, booked an 88% fall in 2011 net profit to only CNY217m due to slow sales and the high value of the Japanese yen.
Get full access to all content, just $1 for 30 days
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And now there's just-auto plus, our premium membership that gives you exclusive component forecast data, company profiles and extended news coverage - just for premium members.
Today I can offer you 30 days access for $1 - and that includes just-auto plus.
Dave Leggett, editor of just-auto
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text:
2016 WGC Executive Committee
- Alison Canning, Chair
- Kim Agnor, Treasurer
- Danelle Buchman, Secretary
- Dee Athey, Chair, Grants Committee
- Colleen D'Agrosa, Chair, Communications Committee
- Courtney Workman, Chair, Youth Development Committee
- Megan Bruno, Immediate Past Chair
View the full WGC Advisory Board
Mailing Address
10630 Little Patuxent Parkway; Century Plaza, Suite 315; Columbia, MD 21044.
Grants: The function of the Grants Committee is to design and implement the grant making process. It determines eligibility criteria, the grant cycle, the selection of grantees and grant evaluation.
Donor Development: The Donor Development Committee is responsible for working with the WGC's existing donors and reaching out to prospective donors.
Communications: The Communications Committee is responsible for external communications including monthly WGC eNewsletter and WGC website and promoting the WGC through the media.
Leadership: The Leadership Committee is responsible for identifying WGC donors to assume leadership positions on the Advisory Board.
Youth Development: The Youth Development Committee is responsible for supporting and mentoring the Young Women's Giving Circle (YWGC) and promoting philanthropy among the young women of Howard County through various activities and events.


text: I'm going snowboarding on monday, I have a weight allowance of 20kg for my hold luggage and a further 12kg for my winter sports equipment bring me to a total allowance of 32kg. The question is if my sports equipment weighed 8kg then would I be able to go slightly over my weight allowance for my hold luggage to lets say 22kg? The easyjet website says that if your equipment weighed 20kg and your hold luggage weighed 12 kg then that is fine, but I'm just not sure if the rule applied the other way round. Thanks for the help! Jonny.


text:
American Girl Kanani Doll
- Sold for: Start Free Trial or Sign In to see what it's worth.
- Item Category: Toys, Dolls, Games & Puzzles
- Source: eBay
- Sold Date: Nov 27, 2015
- Channel: Auction House
Doll is in very good condition. Doll's hair became very easily tangled, so there is some damage to the ends. There are a few snips in her hair which I've tried to display in the photos. Doll is able to stand on its own. Includes doll, brush, skirt and tank top, and 3 floral rings/leis. From a smoke-free home.


text:
KIM LANDERS: If you're in chronic pain, could some tasty food help ease it?
It was a question on a few people's lips at a recent conference in Adelaide.
The gathering featured 600 of the world's top pain therapists, who were told that good food can work where medicines may not.
It's a sentiment backed up by a well known Australian chef who reached a similar conclusion after a stint in hospital.
Tom Nightingale caught up with Ian Parmenter and Oxford University's Charles Spence.
(Sound of café)
TOM NIGHTINGALE: At a hospital in suburban Adelaide, a cafe is busy with the lunch rush.
For those eating hospital food, it's rarely an enjoyable meal.
Chef Ian Parmenter has spent decades promoting good food on television.
He says he was dismayed during a recent stay in hospital.
IAN PARMENTER: I had a hip replacement in a hospital in Perth. And I was in there longer probably - we had a bit of a complication - I was in there longer than I really wanted to be there. And I just found that in spite of the fact that this was a private hospital the food was so disappointingly bland.
TOM NIGHTINGALE: He's in Adelaide at the moment, directing the Tasting Australia Festival.
When in hospital, he persuaded the management he could cut food costs.
But he says his real mission was to improve the culinary quality.
And he says it got results.
IAN PARMENTER: The young woman, seriously ill, and she got in touch with me because she found I was involved with the hospital and she said, I can't tell you how much pleasure it's given me, and how much meaning it's given me to actually be able to enjoy food and its presentation. I look forward to the food coming in, it makes me feel better.
TOM NIGHTINGALE: Oxford University's Professor Charles Spence is also in Adelaide for an international seminar on chronic pain.
He says the use of food to treat pain is getting more and more creative.
CHARLES SPENCE: Everything from the kind of the heel prick pain of a newborn baby when given an injection, they're very often given sugar, sweet tastes in the mouth in order to stop them crying so much, to reduce pain. And you find the same thing in adults.
And one of the things that are of particular interest to us is even smells that are sweet, things like vanilla and strawberry, for kind of a western diner, we've learnt through our taste experience that those smells usually come with sugar. And so if you have somebody with their arm in a painful situation, you can actually, they'll can actually, will have less pain with that sweet smell.
TOM NIGHTINGALE: Professor Spence says people in Australia and Europe are starting to catch on to Asian concepts of linking food and pain treatment
CHARLES SPENCE: They don't really make a distinction between medicine and food whereas in the west it's very much you go to one place to buy your food and another place to buy the medicine. And I'm starting to see that transition in western market place that now you have foods that improve your mood, foods that improve your intelligence and you sort of wonder how long it will be before somebody starts selling food that could potentially reduce pain.
TOM NIGHTINGALE: Both men think it'll become a more common trend in the next few years
IAN PARMENTER: I would just like to think that if we do more to make the whole enjoyment of food more special, then it's going to make a positive difference to all of us.
TOM NIGHTINGALE: Could you see it getting bigger though, getting more sort of main stream recognition I suppose, the use of food?
CHARLES SPENCE: Use of food? I think around the world now people are either through their own experience of being in hospitals and seeing how bad the food is, or through those working in the health sector realising the sort of poor nutrition in those who are suffering from pain. Either because they have to increase the salt levels, you imagine that six times more to 12 times more salt just to overcome the effects of medication, that's got huge health consequences and people are thinking how can we deal with that?
IAM PARMENTER: And also the aromas, the aromas of food. When it's fresh - when it is fresh herbs it's so, you know, it just makes you feel better.
KIM LANDERS: Chef Ian Parmenter ending that report from Tom Nightingale.
The full story...
Could food heal chronic pain?
Tom Nightingale reported this story on Monday, April 30, 2012 12:50:00
KIM LANDERS: If you're in chronic pain, could some tasty food help ease it?


text:
Well [wel]: a hole drilled or bored into the earth to obtain water. I love how that definition describes the picture below! The well (el pozo) at the Casa del Buen Trato Hovde in Huánuco, Perú is now approximately 46 feet deep and they hope to hit water soon! I really get so excited to bring you these updates! 🙂
Did you know that we will be returning to Perú in 2014 either in late July or early August? If you would like to come with us and see the new well, and serve the beautiful people that live at the Casa del Buen Trato Hovde, please send me an email below.


text:
The National Institute of Building Sciences Building Seismic Safety Council (BSSC) will host the fifth webinar in its 2017 series sponsored by the Federal Emergency Management Agency (FEMA). The free webinar, "Design of Seismic Force-Resisting Systems in Wood Light-Frame Buildings," will be held Friday, July 7, 2017, from 2:00 pm to 3:00 pm ET (11:00 am to 12:00 pm PT).
The webinar series highlights the National Earthquake Hazards Reduction Program (NEHRP) 2015 NEHRP Recommended Seismic Provisions for New Buildings and Other Structures, as well as its supporting materials, FEMA P-1051 Design Examples and FEMA P-1052 Training Materials.
This webinar will provide an introduction to the design of seismic force-resisting systems in wood light-frame buildings, intended to complement the wood design problems in Chapter 14 of FEMA P-1051. Presenter Kelly Cobeen, a member of BSSC's Provisions Update Committee (PUC) and chair of PUC Issue Team 9: Rigid Wall Flexible Diaphragm and Alternate Provisions for Diaphragm Design, will introduce wood light-frame terminology, design and construction; shear wall concepts and example design calculations; diaphragm concepts and example design calculations; and discuss special seismic provisions for anchorage of concrete and masonry walls.
Cobeen is an associate principal with Wiss, Janney, Elstner Associates in their San Francisco office, and is a registered civil and structural engineer. Her work experience includes a wide range of project types, sizes and construction materials, with a special interest in seismic resistance of light-frame construction. She has been involved in numerous code development, research and educational activities, including updates to the NEHRP Recommended Provisions; the American Society of Civil Engineers (ASCE)/Structural Engineering Institute (SEI) 7-10: Minimum Design Loads for Buildings and Other Structures; numerous Applied Technology Council publications; and International Building Code and International Residential Code development. Cobeen is coauthor of the Design of Wood Structures textbook.
Attendees who are engineers are eligible to earn one Professional Development Hour (PDH) for the webinar, code officials are eligible to earn 0.1 Continuing Education Units (CEUs) and architects are eligible to earn one health/safety/welfare (HSW) CEU. People are encouraged to watch the webinar together as a group or a firm, but all viewers must sign up individually to receive learning unit verifications.
Sign up now to attend the free "Design of Seismic Force-Resisting Systems in Wood Light-Frame Buildings" webinar on July 7. Space is limited, so don't wait. Register today!
Want to see what other topics BSSC has arranged for the 2017 webinar series?
View the schedule.
7/31/2017Upcoming NCS Webinar Will Look at BIM Implementation
7/24/2017August 25 BSSC Webinar Will Look at Seismic Design of Masonry
7/24/2017 Don't Miss the Chance to Present at BEST5, Deadline August 1
8/25/2017BSSC Webinar: Seismic Design of Masonry with the 2015 NEHRP Provisions
9/10/2017 » 9/17/2017Association of Environmental & Engineering Geologists (AEG) 60th Annual Meeting
9/14/2017BSSC/SEAOC Workshop
10/17/2017Introduction to Cybersecuring Building Control Systems Workshop
10/18/2017Advanced Cybersecuring Building Control Systems Workshop


text:
The casino is like a new road. A dirt road. After it has been traveled on a while it will get smoother. When I am in Vegas, I always tip my waitress. I see them more often then.
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text:
Listen to free music played by octoberland
Blip.fm is internet radio made social. It's easy to search for, play, and discover free music recommended by real people. Join today to create your own free station and start listening to @octoberland.
octoberland took the midnight train going anywhere.
Journey – Don't Stop Believin'| play
octoberland not quite there... but close.
Cat Stevens – Another Saturday Night| play
octoberland heh. this is enjoyable. particularly if you watch the video.
octoberland mixed on these guys, but this one is a definite #QA@octoberland
Super Furry Animals – Northern Lites| play
octoberland there might be a theme here... #QA@octoberland
Super Stereo – Superhero (Plejs Remix)| play
octoberland there might be a theme here... #QA@octoberland
Stereolab – Super-Electric| play
octoberland inspired by @quitecontrary --- i was thinking of this group the other day. thanks for reminding me!
Stereo Total – Supercool| play
octoberland @TaraBusch: "@williamorbit - Here, happily one of yours with a rather lovely, marshmallow-y bassline..!" --- just heard you. already a fan :) (reblip)
William Orbit – Water From a Vine Leaf| play
octoberland for my mom. RIP 6/5/09
Floyd Cramer – Music Box Dancer| play
octoberland @peterhick: "@mammara" --- glad to see other brave musical souls out there :) (reblip)
Piano Magic – Theory of Ghosts| play
octoberland @DigitalJEdwin -- thanks for rubbing that one in :P this will be me soon enough! enjoy the day to come.
TV On The Radio – Staring at the Sun| play
octoberland this song is so joyful. i love the instruments and rhythm. makes me think i might be in the eastern europe countryside. sort of like a movie, maybe ;)
octoberland inspired by @joechapman -- nearly forgot this band.
Afro Celt Sound System – Persistence of Memory| play
octoberland @philkirby if i saw you at a club it'd be awesome to hear this ;)
Nouvelle Vague – Dancing With Myself| play
octoberland wonderful choice! nowhere i'd rather be. (reblip)
The Cure – Underneath The Stars| play
octoberland blip blip bop beep. #QA@octoberland
octoberland shoutin out friday! good glitch / IDM here. #QA@octoberland
To Rococo Rot – Freitag| play
octoberland brilliant glitch here. #QA@octoberland
Lali Puna – Faking The Books| play
octoberland top shelf electronica here #QA@octoberland
Calix, Mira – Shadenfreunde| play
octoberland maybe a little random. great background noise without fading away.


text:
Dear Parents and Guardians,
Welcome to the 2016-2017 School Year ! Your school information Welcome Back Letters and forms can be found on this page. In addition, hard copies can be found at Door #6.
District Welcome Back Letter, please click here
Middle School Welcome Back Letter, please click here
Elementary School Welcome Back Letter, please click here
- Monthly School Calendars and Monthly Breakfast and Lunch Menus can be found under CALENDARS
Student Emergency Information
You are able to update your own contact information and emergency contacts in our student information system, Genesis, using Parent Portal. The instructions are provided below. Please note that a Parent Portal account is needed to access Genesis, and is different than a school fusion account. Please e-mail Carole Lyons at email@example.com for any account-related issues.
URL https://parents.ncs-nj.org
URL https://parents.ncs-nj.org
District Flyers
- T-Pass
- School Security Drills
- Advertised School Budget 2016-17
Our district's 2016-2017 Advertised Budget is available for download here. In addition, our 2016-2017 User Friendly School Budget is available for download here.
- Parent Assessment Information
- Latex Letter
- Parent Teacher Organization (PTO) Welcome Letter
- T-Shirt Design Contest for September 2017
- Integrated Pest Management (IPM)
- District and School Summaries for all incident categories and the full report may be accessed here
- BYOD (Bring Your Own Device) Policy
Elementary School Flyers
- Back-To-School Nights 2016-2017 - PLEASE NOTE the Visitor and Volunteer Training times
- Dismissal Approval Form 2016-2017 - Please complete and send to school on the first day of school
- AM ARRIVAL and PM DISMISSAL PROCEDURES, TIMES, and DOOR LOCATIONS 2016-2017
- School Map for Drop-off and Pick-up 2016-2017
- Kindergarten 2016-2017 Welcome Packet
- Kindergarten 2016-2017 Supply List (All supply lists can be found on the Elementary School web page)
- Dismissal Procedures 2016-2017
- Absences and Homework Request Procedures 2016-2017
- Lunch Schedules, School Hours, and Attendance Information 2016-2017
- 2016-2017 REPORT CARD Dates
- Day 1-5 Yearly Calendar 2016-2017
Middle School Flyers
- Back To School Nights 2016-2017
- Absences & Homework Requests
- Dismissal Procedures
- Classroom Supplies
Student After-School Child Care (SACC) Program Packet:
Free and Reduced School Lunch Forms:


text:
Welcome to the Instructor Resource Center
SilverSneakers and Prime Fitness' parent company, is now Tivity Health™
We are excited to announce a new corporate brand and new name that better represents our commitment to helping people thrive, no matter their age or stage. Our new brand, Tivity Health, evokes the tangible benefits that our products deliver - a focus on physical activity, improved productivity, strong connectivity, and spirited creativity, all with a sense of positivity.
Tivity Health will continue to focus on our SilverSneakers, Prime and WholeHealth Living™ products.


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Neural-glial signaling in the spinal cord may underlie pain and sensitization after peripheral injury. Here we test the role of a glial activator, the chemokine CCL2 on mechanical hypersensitivity following plantar incision in a rat model of postoperative pain.
Twenty four hours after hindpaw incision rats were intrathecally administered an anti-CCL2 neutralizing antibody (3 μg and 10 μg) or control IgG (10 μg). Mechanical hypersensitivity was assessed acutely and for several days following administration of anti-CCL2 antibody using von Frey filaments. Immunohistochemical analysis was conducted on spinal cord sections to examine the effects of treatment on measures of microglial activation including levels of ionized calcium binding adaptor molecule 1 (IBA1) and phosphorylated p38 mitogen activated protein kinase.
Neutralization of spinal CCL2 acutely reversed mechanical hypersensitivity within 30 minutes in a dose dependent manner. A single administration also produced a sustained decrease in mechanical hypersensitivity 48 and 72 hours following incision. Anti-CCL2 antibody reduced microglial activation as measured by the levels of IBA1 immunoreactivity and the number of microglia containing phosphorylated p38 mitogen activated protein kinase 48 hours following incision but not within 30 minutes of administration.
These results provide evidence that CCL2 contributes to the maintenance of mechanical hypersensitivity following plantar incision and establishes a role for neural glial signaling in postoperative pain. The long term effects of anti-CCL2 treatment correlate with reduced microglial activation. Spinal blockade of CCL2 may serve as a useful therapy for the treatment of certain aspects of postoperative pain.
An estimated 23 million people in the United States and 234 million worldwide undergo surgical procedures each year 1. Despite increased preclinical and clinical research on pathological mechanisms of postoperative pain and recent advances in analgesic therapies, many patients do not receive adequate analgesic support during the postoperative setting. Clinical reports indicate that 50-70% of patients experience moderate to severe pain after surgery 2-4.
Preclinical models of acute postoperative pain have been developed involving surgical incision of the skin, muscle and fascia which leads to evoked and non-evoked pain-related behaviors that mirror the symptoms observed in patients undergoing surgery 5-7. It is now widely recognized that activation of spinal glial cells including microglia and astrocytes are involved in central sensitization and mechanical hypersensitivity in acute and persistent pain states8-11. However, the contribution of glial cells to postoperative pain states has just begun to be investigated. Following surgical incision, spinal microglia upregulate the cell surface molecules CD11b (recognized by OX42 antibody) and the ionized calcium binding adaptor molecule 1 (IBA1) in lumbar dermatomes ipsilateral to incision 9,12,13. Further, phosphorylated p38 mitogen activated protein kinase (p-p38 MAPK)14 and cyclooxygenase 1 15,16 are upregulated in microglia within hours of surgical incision. These data suggest that microglia may serve as sources of proinflammatory cytokines and prostaglandins which could maintain central sensitization after incision. In support of this idea, intrathecal injection of the glial metabolic inhibitor fluorocitrate dose dependently reversed mechanical hypersensitivity 24 hours after incision 9 and spinal administration of agents that target microglial mediated signaling including p38 MAPK inhibitors 14 and the COX1 preferring inhibitor ketorolac 16,17 also partially reverse or prevent the development of mechanical hypersensitivity post incision. Recently, it has been shown that the cannabinoid receptor type 2 agonist JWH015 reduced microglial activation and mechanical hypersensitivity following surgical incision in rats 18.
What has not been determined is what factors activate glial cells in the postoperative setting. Several factors that activate glial cells in the spinal cord have been identified in neuropathic pain states including adenosine triphosphate, tumor necrosis factor-α, CCL2, fractalkine (CX3CL1), and toll like receptor agonists 19. As part of the current study, we investigated the effects of spinal blockade of the chemokine CCL2 on mechanical hypersensitivity and spinal markers of microglial activation including IBA1 and p-p38 MAPK following surgical incision.
Male Sprague–Dawley rats (Harlan Industries, Indianapolis, IN), weighing 250–275 g, were used for experiments. All studies conformed to the Wake Forest University Guidelines on the ethical use of animals, and studies were performed under Animal Care and Use Committee (Winston-Salem, NC) approval. Animals were housed under a 12-h light–dark cycle, with food and water ad libitum.
Plantar incision was performed as previously described 5. In brief, animals were anesthetized with inhalational isoflurane (2%) in oxygen, and the plantar aspect of the left hindpaw was prepared in a sterile manner with a 10% povidone-iodine solution. A midline incision (1 cm) was made using a No. 11 blade on the left hindpaw starting 0.5 cm from the heel. The plantaris muscle was elevated and incised longitudinally. The wound was closed with two 5.0 nylon mattress sutures. For sham procedures, animals were anesthetized with inhalational isoflurane (2%) in oxygen and the plantar aspects of the left hindpaw were prepared in a sterile manner with 10% povidone-iodine solution.
Rats that received plantar incision were intrathecally administered CCL2 neutralizing antibody (goat anti-mouse CCL2/MCP-1/LE 15 μl at 200ng/ml or 15 μl at 667 ng/ml for 3 and 10 ng total, respectively) or the same amount of goat anti-mouse IgG (Both antibodies from R&D Systems, Minneapolis, MN). Anti-CCL2 antibody and control IgG were prepared in 0.9% saline solution as the vehicle. The goat anti-mouse CCL2/MCP-1/LE neutralizing antibody used for this study also recognizes rat CCL2 20. Percutaneous intrathecal injections were performed between the L5 and L6 vertebrae of the spine using a 30 gauge ½ inch needle under 2% isoflurane/O2 anesthesia. Successful puncture of the dura mater was assumed by the presence of a tail flick.
Paw withdrawal thresholds to mechanical stimuli were determined using von Frey filaments as previously described 21. Briefly, rats were placed in individual Plexiglas chambers with a plastic mesh floor and allowed to acclimate to the test apparatus at least 30 minutes prior to testing. Filaments were applied to the bending point for 6 s, and a brisk paw withdrawal was considered a positive response. Withdrawal threshold was determined using an up–down statistical method 21. Individuals conducting behavioral assays were blinded to the treatment.
Rats were anesthetized with sodium pentobarbital (intraperitoneal injection; 100 mg/kg), the thorax was opened, and 0.1 M phosphate buffered saline (PBS, pH 7.4) followed by fixative (4% paraformaldehyde in 0.1 M PBS, pH 7.4) was perfused through the left ventricle with a peristaltic pump (20 ml/min). The spinal cord was removed, immersed in fixative for 12 hours at 4° C followed by immersion in 30% sucrose at 4°C for cryoprotection until ready to be sectioned. Spinal cord cross sections (40 μm) were cut on a cryostat and every fourth section was processed for immunohistochemistry for a given marker. For single labeling of microglia an antibody against IBA1 (rabbit anti-rat IBA1, Wako Chemicals, Richmond, VA) was used. Spinal cord sections were processed free floating and incubated over night at 4°C with primary antibody. Antibodies were diluted in a solution consisting of PBS containing 1% normal donkey serum and 0.1% Triton X-100. Sections were washed in 0.1 M PBS solution and incubated in rabbit biotinylated secondary antiserum (1:500, Jackson Immunoresearch, West Grove, PA) for 2 hours at room temperature. The Elite Vectastain ABC kit (Vector Laboratories, Burlingame, CA) was used to link the antigen-antibody complex to horseradish peroxidase which was then visualized with 3, 3-diaminobenzidinetetrahydrochloride histochemistry. Finally, the sections were washed thoroughly in PBS, mounted on plus-slides, air-dried, dehydrated in ethanol, cleared in xylene, and cover slipped with DPX mounting media (Sigma-Aldrich, St. Louis, MO)
For double immunofluorescense labeling, sections were incubated with a mixture of primary antibodies rabbit anti p-p38 MAPK (1:500, Cell Signaling Technologies, Danvers, MA) antibody and mouse monoclonal antibody against the microglial specific cell surface receptor CD11b (clone OX-42,1:250, Serotec Ltd, Raleigh, NC) overnight at 4 ° C. The sections were washed in 0.1 M PBS and incubated in a mixture of CY3-conjugated donkey anti-rabbit IgG (1:600, Jackson Immunoresearch) and CY2-conjugated donkey anti-mouse IgG (1:200, Jackson Immunoresearch) for 2 hours at room temperature. Then sections were washed in PBS mounted on plus –slides air-dried, dehydrated in ethanol, cleared in xylene, and cover slipped with DPX.
Sections were examined with brightfield illumination and images were captured with a CCD digital camera attached to the microscope using a 10× objective at a resolution of 1,600 × 1,200 pixels. Images of ipsilateral and contralateral L4-5 dorsal horn of sham operated and incision rats were captured. A square with a fixed area (250 × 250 μm2) covering the region of laminae I-II was randomly positioned in the middle one third of the mediolateral extent of the spinal cord dorsal horn. The number of pixels occupied by IBA1 immunoreactive cells within a defined threshold was measured using image analysis software (Image J; NIH Image, National Institutes of Health, Bethesda, MD). Immunodensity measurements were obtained from a minimum of 5 spinal cord sections/rat and averaged.
For assessment of spinal levels of p-p38 MAPK, images of p-p38 MAPK immunoreactivity and OX42 immunoreactivity within ipsilateral and contralateral L4-5 dorsal horn of sham operated and incision rats were sequentially captured using a 20× objective for each section by alternating between filter sets to capture in separate overlapping images CY3 and CY2 labeling, respectively. A square with a fixed area (250 × 250 μm2) covering the dorsal medial aspects of the spinal cord was randomly positioned in the dorsal horn of the spinal cord images. The number of p-p38 MAPK immunoreactive cells was counted on six randomly chosen sections from each animal and averaged for each animal. The microglial phenotype of p-p38 MAPK immunoreactive cells in each section was confirmed by overlaying the p-p38 MAPK images with the OX42 image. The observer quantifying the sections was blind to the condition of the sample being quantified.
Statistical analysis was conducted using Sigma Plot (Version 11.0, Systat software Inc, San Jose, CA) software. The effects of treatment on withdrawal thresholds were examined at each time point using the Kruskal-Wallis test. Significant effects were followed by pairwise comparisons of the mean ranks of the treatment groups at each time point using Student Newman Keuls post hoc test. The effects of treatment over time on withdrawal thresholds were examined using Friedman repeated-measures analysis of variance on ranks test. If significant effects were found pairwise comparisons of the mean ranks at each time point within a treatment group were conducted using Student Newman Keuls post hoc test. If group sizes were not equal Dunn's test was conducted for post hoc analysis. Immunocytochemical data was analyzed using a two way ANOVA assessing for effects of treatment and side followed by Bonferroni post hoc tests for pairwise comparisons. To examine whether markers of microglial activation (p-p38 MAPK immunoreactivity and IBA1 immunoreactivity) were associated with measures of mechanical hypersensitivity following sham procedure or plantar incision linear regression analysis was conducted using a nonparametric Spearman's rho test. The criterion for statistical significance for all analysis was P< 0.05.
To examine the contribution of endogenous CCL2 to mechanical hypersensitivity following surgical incision, we measured the acute behavioral effect of intrathecal anti-CCL2 neutralizing antibody (10 ng, 3 ng) on mechanical withdrawal thresholds when administered 24 hours following plantar incision. Withdrawal thresholds were significantly reduced 24 hours following incision compared to baseline values (P<0.05) in all groups examined (Figure 1A.) Both doses of anti-CCL2 antibody significantly attenuated mechanical hypersensitivity compared to control IgG treated rats at 30, 60, 90 and 120 minutes post administration. At 30 minutes post administration the higher dose of anti-CCL2 antibody (10 ng) increased paw withdrawal thresholds significantly greater than the 3 ng dose indicating a dose dependent attenuation of mechanical hypersensitivity at this time point (Figure 1A, P<0.05).
Because single spinal administration of exogenous CCL2 has been shown to induce long term persistent changes in microglial activation and pain facilitation 20,22, we examined the ability of anti-CCL2 neutralizing antibody to reduce mechanical hypersensitivity at later time points post administration. In a separate group of rats, a single administration of 3 ng or 10 ng anti-CCL2 IgG or control IgG was administered intrathecally one day following incision and rats were assessed for mechanical hypersensitivity on day 2, 3 and 7 post incision (Figure 1B). Both doses of anti-CCL2 IgG significantly reduced mechanical hypersensitivity day 2 and 3 post incision (1 and 2 days post administration) compared to control IgG (P<0.05, Kruskal-Wallis followed by Dunn's test). The difference in the median values of the treatment groups 7 days post-incision was not significantly different compared to values from control IgG treated rats (P=0.264, Kruskal-Wallis).
Spinal microglia are activated following plantar incision as indicated by increases in the cell surface protein CD11b (OX42), upregulation of the microglial specific protein IBA1 and increased levels of phosphorylated p38 MAPK. Immunohistochemical staining of IBA1 was significantly greater in the spinal cord dorsal horn ipsilateral to plantar incision compared to the ipsilateral dorsal horn of rats with sham surgery 24 and 48 hours following surgery (Figures 2 and and3,3, P<0.05). Rats with plantar incision had significantly greater number of IBA1 immunoreactive pixels in the ipsilateral spinal cord dorsal horn 1 day and 2 days postoperatively compared to contralateral values (Figure 3, P<0.05). Microglia in the spinal cord of incised rats exhibited characteristic morphology of activation including larger cell bodies and thicker processes compared to the thin and highly ramified processes of microglia within the spinal cord of rats that underwent sham procedure (Figure 2). We examined the short and long term effects of blocking spinal CCL2 on the number of IBA1 immunoreactive pixels beginning 24 hours postoperatively following plantar incision. Rats treated with anti-CCL2 IgG via percutaneous lumbar intrathecal injections had similar number of IBA1 immunoreactive pixels in the ipsilateral dorsal horn as in control IgG treated incision rats 30 minutes following administration (Figure 3A). Conversely, when IBA1 was examined 24 hours following spinal anti-CCL2 treatment the number of pixels was significantly reduced in the ipsilateral dorsal horn compared to incision vehicle treated rats (Figure 3B). At this later time point the IBA1 immunoreactive pixel values from ipsilateral dorsal horn of CCL2 treated rats were not significantly different compared to contralateral CCL2 treated values (P=0.832) or values from rats that underwent sham procedures (P=0.226)
We also examined the number of p-p38 MAPK immunoreactive microglia. Spinal cord sections were labeled with antibodies against p-p38 MAPK and the microglial cell surface antigen CD11b (OX42, Figure 4). Immunohistochemistry for both markers was performed in the same sections to confirm co-labeling of p-p38 MAPK in microglia (Figure 4C, F, I) and allow for cell type specific quantification. Incision increased the number of p-p38 MAPK microglia ipsilateral to surgery compared to sham operated rats and compared to the contralateral side 24 and 48 hours following incision (Figure 5; P<0.05). Anti-CCL2 IgG did not alter the number of p-p38 MAPK microglia in the ipsilateral dorsal horn 30 minutes following administration on the first postoperative day compared to vehicle (Figure 5A). Likewise the number of p-p38 MAPK microglia were significantly greater in ipsilateral versus contralateral spinal cord sections of anti-CCL2 treated rats 30 minutes post treatment (Figure 5A). Twenty four hours following treatment the number of p-p38 MAPK immunoreactive microglia were significantly reduced in the ipsilateral dorsal horn of anti-CCL2 treated incision rats compared to control IgG treated incision rats, although not to the levels in rats that underwent sham procedures treated with control IgG (Figure 4 D,G; Figure 5B).
In a separate group of rats, we conducted behavioral analysis and collected spinal cord tissue 48 hour following plantar incision or sham operation and 24 hours following spinal treatment with anti-CCL2 antibodies or control IgG. We observed a strong correlation between the number of p-p38 MAPK immunoreactive microglia in the ipsilateral spinal cord and the degree of mechanical hypersensitivity in rats with plantar incision or sham procedure based on linear regression analysis (Figure 6A). There was also a strong correlation between number of IBA1 immunoreactive pixels in the spinal cord and mechanical hypersensitivity at this time point (Figure 6B).
In the current study, we provide behavioral evidence that endogenous spinal CCL2 contributes to mechanical hypersensitivity following surgical incision. First, we demonstrate that acute blockade of spinal CCL2 with a neutralizing antibody partially reverses mechanical hypersensitivity within minutes of administration independent of effects on microglial activation. Second, we demonstrate that a single spinal administration of anti-CCL2 antibody attenuates mechanical hypersensitivity for days following incision by inhibiting microglial activation and p38 MAPK signaling. These results carry implications for the mechanisms of neural glial signaling in pain facilitation after incision and for postoperative pain treatment.
CCL2 also known as monocyte chemotactic protein 1 is a small 14 kDa protein which signals through the G-protein coupled receptor CCR2. CCL2, similar to other chemokines, was initially identified as an immunomodulatory factor that regulates activation and migration of peripheral immune cells. Recently, it has been shown to have a neuromodulatory role in spinal nociceptive processing (For review see 23). CCL2 messenger RNA and protein are constitutively expressed in a population of predominantly small and medium sized neurons within the dorsal root ganglia (DRG) 22. CCL2 immunoreactivity colocalizes with markers of peptidergic 20,22 and non-peptidergic 20,24 primary afferents in the DRG and their central terminals within the dorsal horn of the spinal cord 25. Under normal conditions, CCL2 is not present at detectable levels within non-neuronal cells including microglia and astrocytes of the rat spinal cord22,26,27. However, CCL2 may be upregulated in sensory neurons of rats following peripheral nerve injury and inflammation 20,22,25-29 and has also been shown to be upregulated within spinal cord astrocytes following chronic constriction injury of the sciatic nerve in mice 30.
CCR2 receptors have been localized in the spinal cord based on autoradiographical binding studies that reported dense binding of radiolabeled CCL2 in the dorsal horn (laminae I-IV)29. There is some debate regarding the cell type expression of CCR2 within the spinal cord and immunohistochemical and transgenic approaches have provided evidence of CCR2 on predominantly microglia and macrophage 31,32 while other studies report it predominantly in second order neurons and terminals of primary afferents30,33. Therefore, in the context of postoperative pain state primary afferent derived CCL2 may have actions on both neuronal as well as non-neuronal cell populations within the spinal cord.
In the current study, we provide evidence that endogenous spinal CCL2 contributes in part to mechanical hypersensitivity following surgical incision in the rats. In support of our findings, there is substantial evidence that endogenous CCL2 and CCR2 are involved in the development of mechanical hypersensitivity in acute and persistent pain states. CCR2 antagonists attenuate mechanical hypersensitivity in neuropathic pain models 20,28,30 and transgenic mice lacking CCR2 do not develop mechanical hypersensitivity following partial sciatic nerve ligation 32. In two recent studies, intrathecal administration of a CCL2 neutralizing antibody attenuated ipsilateral mechanical allodynia for several days following chronic constriction injury in rats 20 and transiently reversed mechanical hypersensitivity following spinal nerve ligation in mice 30. In acute inflammatory pain states, CCR2 knockout mice exhibited decreased phase II formalin induced nociceptive behavior and a modest attenuation of mechanical allodynia induced by hindpaw injection of complete Freund's adjuvant. Spinal administration of exogenous CCL2 in naïve rats induces mechanical allodynia which is sustained for several days following single injection 20,22 suggesting long term effects of CCL2 on spinal pain processing.
In the current study, we provide evidence that microglial mechanisms may be relevant to CCL2 induced central sensitization in the postoperative pain setting. We observed a reduction in IBA1 immunoreactivity and a reduced number of p-p38 MAPK immunoreactive microglia in the ipsilateral spinal cord of rats with plantar incision 24 hours following administration of neutralizing anti-CCL2 antibody. Consistent with our findings, there is substantial evidence in support of a microglial mediated mechanism contributing to CCL2s pro hypersensitivity effects. A causal relationship between microglial activation and CCR2 mediated signaling was initially suggested based on observations that upregulation of CCL2 in primary afferent nerve terminals correlates with the spatial and temporal profile of activated microglia within the spinal cord following peripheral nerve injury 27 and exogenous administration of CCL2 in the spinal cord of naïve rats induces extensive spinal microglial activation at the site of injection 20 as indicated by increased OX42 immunoreactivity. Additionally, spinal CCR2 antagonists attenuate microglial activation (reduce OX42 immunoreactivity) following peripheral nerve injury 20 and CCR2 knockout mice have a reduced number of p-p38 MAPK positive microglia following partial sciatic nerve injury compared to wild type controls 32. Similar to our results, Wen et al. observed a significant increase in the number of p-p38 MAPK immunoreactive microglia one and two days post hindpaw incision in rats. In their study, a single intrathecal injection of the p38 inhibitor ZR167653 prior to incision attenuated mechanical hypersensitivity and reduced the number of p-p38 MAPK microglia following incision. These results and our findings demonstrating a strong correlation between measures of mechanical hypersensitivity and the number of p-p38 MAPK microglia in the ipsilateral spinal cord of treated rats suggest that microglial signaling via p38 MAPK is important for the persistence of mechanical hypersensitivity following surgical incision. In contrast to our findings, Ito et al. reported that single systemic administration of the microglial inhibitor minocycline only slightly attenuated mechanical hypersensitivity when administered acutely one day after plantar incision 38. In the same study, intrathecal administration of the p38 inhibitor SB203580 one and three days after incision was without effect. Chronic administration of minocycline twice daily for three days after surgical incision failed to attenuate mechanical hypersensitivity despite producing a reduction in OX42 immunoreactive microglia. While these data suggest microglia may have a minor role in postoperative pain, it is also possible that the systemic doses of minocycline and p38 inhibitor used in this former study were insufficient to block phosphorylation of p38 MAPK which appears to be essential for the development and maintenance of mechanical hypersensitivity in this postoperative pain model 14. The effect of preemptive systemic minocycline on mechanical hypersensitivity and levels of p-p38 MAPK were not examined in the former study. This may be an important distinction as OX42 immunoreactivity does not parallel the development of mechanical hypersensitivity following incision unlike the upregulation of p-p38 MAPK and IBA1 in microglia which has been observed as early as one to 24 hours following plantar incision, respectively. Several studies suggest that microglial changes in IBA1 immunoreactivity or levels of p-p38 MAPK in microglia may be a more functionally relevant marker of microglial activation particularly in acute pain states 10,34,35.
Interestingly in the current study, spinal neutralization of CCL2 rapidly attenuated mechanical hypersensitivity within 30 minutes of administration but failed to reduce the number of p-p38 MAPK immunoreactive microglia or IBA1 immunoreactivity at this acute time point. There are several explanations for the lack of acute effect on microglial activation. First, it is possible that the immunohistochemical approaches used in the current study are not sensitive enough to detect acute effects of treatment. However, several studies have observed acute effects of pharmacological agents on p-p38 MAPK immunoreactivity in the peripheral and central nervous system 36. Another possibility is that CCL2 contributes to mechanical hypersensitivity at early time points by direct actions on spinal cord neurons in addition to the delayed effects on microglia that we observed at 48 hours following incision. There is increasing in vitro and in vivo evidence that CCL2 directly excites or sensitizes neurons in the superficial laminae of the spinal cord and DRG. Spinal administration of exogenous CCL2 in vivo induces phosphorylation of the mitogen activated protein kinase pERK in neurons within the superficial dorsal horn and in vitro following application to spinal cord slices 30. Patch clamp recordings of lamina II spinal cord neurons have been conducted in slice preparations to examine direct functional effects of CCL2. Bath application of CCL2 increased excitatory synaptic transmission as indicated by an increased frequency and amplitude of spontaneous excitatory postsynaptic currents 30. Whole cell patch clamp recordings of cultured spinal neurons demonstrated that CCL2 inhibits gamma amino butyric acid (GABA) induced currents suggesting a neuromodulatory role for this chemokine 29. The presence of CCL2 in primary afferents fibers and localization of CCR2 on sensory neurons suggest that CCL2 may act in an autocrine or paracrine manner on the central terminals of primary afferent fibers to promote the release of neurotransmitters into the spinal cord. In support of this, CCL2 has been shown to trigger the release of calcitonin gene related peptide from cultured DRG neurons 37 It is not known if similar mechanisms occur following surgical incision. Clearly, additional research is warranted to more precisely define the mechanisms by which CCL2 modulates nociceptive processing in the context of postoperative pain.
In summary, we administered a CCL2 neutralizing antibody beginning one day following plantar incision in the rat after the postoperative pain state was established. Using this post-treatment paradigm, we observed that spinal blockade of CCL2 attenuated mechanical hypersensitivity within minutes of administration an effect that was sustained for several days. These findings establish a role for spinal CCL2 mediated signaling in the maintenance of mechanical hypersensitivity following surgical incision and suggest that spinal CCL2 antagonists may have utility for treating postoperative pain.
Source of funding: This work was supported from grant GM48085 from the National Institute of General Medical Sciences (Bethesda, Maryland) and an Individual Postdoctoral Ruth L. Kirchstein National Research Service Award 1F32GM089076-01 from the National Institute of General Medical Sciences and the National Institutes of Health (Bethesda, Maryland).
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Recent Developments
•With oil prices staying firm, along with rising government capital expenditure and new investment in infrastructure, the Saudi economy is expected to maintain an annual average growth rate of around 5% in 2012-2016.
•In response to the supply interruptions resulting from the decline in Libyan oil exports due to the Arab Spring, Saudi Arabia has raised oil production to partially compensate the export loss, with Saudi production expected to remain at high levels, particularly in light of the US-led import boycotts on Iranian oil.
•Saudi Arabia is Hong Kong's third largest export market in the Middle East (after the UAE and Israel). In the first four months of 2012, Hong Kong's total exports to Saudi Arabia grew 33.9% year-on-year (YoY) to US$229 million and its imports from the country fell 20.3% YoY to US$226 million.
Current Economic Situation
Oil plays an important role in Saudi Arabia's economy, accounting for about 90% of exports and 80% of government revenue. Production and refinery of oil are the pillars of the Saudi economy, which account for about 45% of the country's GDP. While Saudi Arabia continues to be a leader in crude oil exports, it is also stepping up natural gas production. It is expected that gas output of the country will rise by 40% by 2014. The Saudi government is keen to develop alternative energy sources such as nuclear energy and solar energy to reduce its oil use in future. 16 nuclear reactors are planned to be built over the next 20 years. Apart from that, the Kingdom aims to generate one-third of its electricity with solar energy by 2032.
In the beginning of 2011, the Jasmine Revolt originated in Tunisia swept through the Middle East and North Africa (MENA) region in what is known as the Arab Spring, leading to changes of government in Tunisia and Egypt. This was followed by a Libyan civil war which badly affected its oil production and exports (pushing it down from the pre-war level of around 1.6 million barrels per day (bpd) to almost a halt at certain points). With the Gaddafi regime removed, Libyan oil production has resumed, yet slowly. To compensate for the supply interruptions in Africa, and to an extent, the import boycott on Iranian crudes led by the US, Saudi Arabia has increased its oil production rapidly. The increase in Saudi oil export and firm international oil prices are expected to help the Kingdom retain a trade surplus.
With oil prices staying firm, along with rising government capital expenditure and new investment in infrastructure, the Saudi economy is expected to maintain an annual average growth rate of around 5% in 2012-2016. However, Saudi Arabia's medium-to-long-term prospects will hinge on the government's success in economic reforms. Economic reforms stress the need for promoting economic diversification and an active role of the private sector in the Saudi economy. To this end, the Saudi government encourages the development of industrial sectors such as production of chemicals, petrochemicals, aluminium and plastics. Prince Sultan bin Salman also underscores the role of tourism in economic reforms for job creation, with 670,000 people hired in the sector in 2011. In order to gain easier access to the Saudi market, foreign investors invariably partner with Saudi companies. According to the World Bank's Doing Business 2012 Survey, Saudi Arabia ranked 10th out of 183 countries, the best performer in MENA.
Saudi economic growth received a substantial boost in the wake of the two massive fiscal spending packages announced by King Abdullah in 2011 amid the MENA unrest. Amounting to US$130 billion, the fiscal packages account for about 30% of the 2010 GDP of the country and are aimed at raising social spending, including salary rises and unemployment benefits, which should help stimulate private consumption. Furthermore, King Abdullah decreed in September 2011 to allow women vote and run in local elections in 2015. Since May 2012, Saudi women no longer require male consent to work, marking a big leap forward for the country.
The consumer price rose 5% in 2011, down slightly from 5.4% in 2010. The surge in international food prices had a relatively small impact on Saudi Arabia, partly due to the government's food subsidy. On the other hand, rents are expected to ease after more new housings come on stream in coming years.
Attracting foreign investment forms a vital part of Saudi Arabia's economic policy. With effect from June 2000, Saudi investment law allows 100% ownership of projects by foreigners, and relaxes rules for sponsoring foreign employees. The law also permits foreign ownership of property, and lowers corporate taxes.
Similar to the UAE, Saudi Arabia has ambitious plans of infrastructure expansion. The main difference between the two countries of the six-member GCC (consisting of the UAE, Saudi Arabia, Kuwait, Qatar, Bahrain and Oman) is that the UAE puts more emphasis on commercial development, while Saudi Arabia focuses on a wider range of infrastructure and building projects: oil and gas facilities, water and electricity plants, residential and commercial buildings, and roads and railways. The country's mega projects include the construction of six economic cities in Medine, Hail, Tabuk, Jizan, Ras Al-Khair and Rabigh.
Trade Policy
In December 2005, Saudi Arabia became the 149th member of the WTO after over 12 years of negotiations. Saudi Arabia's tariff commitments will be introduced in six phases until 2015. In 1993, when Saudi Arabia first applied for membership of the General Agreement on Tariff and Trade (GATT), the predecessor of the WTO, 75% of Saudi's tariffs on imports were at 12%.
In April 2008, Saudi Arabia started to decrease or exempt voluntarily import duties over six years on 180 goods, which had attracted import duties ranging from 12% to 25%. In 2009, Saudi Arabia's average MFN applied import tariff rate was 4.8%, with average rates of 5.6% for agricultural products and 4.7% for non-agricultural products respectively. In 2010, the number of tariff-free goods reached 763 and constituted 23% of import value in 2010.
Saudi Arabia has not imposed tariff quotas, applied seasonal tariffs, and other duties and charges on imports. There are no VAT, excise duties or any other internal tax or charges on domestically produced or imported products as well.
Saudi Arabia's WTO commitments provide for foreign participation in its wholesale and retail trade. Upon accession, Saudi Arabia allowed foreign companies to hold up to 51% of the equity in a wholesale or retail business. The limit has been increased to 75% since January 2009.
However, some products remain restricted from entering Saudi Arabia for religious, health or security reasons. Prohibited items include alcoholic beverages, pork, non-medical drugs, non-Islamic religious materials, weapons and weapon-related electronic equipment. In addition, foreign companies that are deemed to support Israel in one way or another are blacklisted because of the Arab League boycott of Israel, to which Saudi Arabia is a participant. 98.6% of Saudi tariff lines are applied on an ad valorem basis.
The tie between Saudi Arabia and its fellow members of the GCC is strong. In November 1999, the GCC agreed to form a customs union. The customs union took effect from 1 January 2003. The accord establishes a single tariff of 5% on 1,500 imported items from non-member countries. It also provides a list of other essential items that can be imported duty-free. Under the accord, goods imported into the GCC area can be freely transported subsequently throughout the region without paying additional tariffs. Saudi Arabia is a member of the Pan-Arab Free Trade Area too, with almost all trade barriers among its members eliminated from January 2005.
There are health and sanitation regulations for all imported foods. Saudi Arabia has however agreed to take on the obligations of the WTO Agreement on Sanitary and Phytosanitory Measures. Under the agreement, Saudi Arabia has to apply science-based safety standards to all agricultural goods.
Saudi Arabia maintains regulations on product labelling and country of origin marking. In addition, there are safety regulations on toys, and product standards regulations for electrical and electronic goods.
Imports for exhibition purposes have to be accompanied by an invoice with the value of the goods endorsed by the local chamber of commerce, and a certificate of origin. The invoice should show clearly that the goods are imported for exhibition purposes, and will be re-exported. Saudi Customs requires a deposit, which is refundable, for these goods.
While the Saudi Riyal is pegged to the US dollar, Saudi Arabia is committed to the planned Gulf Monetary Union, along with three other members of the GCC, to work towards a single currency. Nonetheless, Oman withdrew from the monetary union in 2006, followed by the UAE in May 2009. Although a joint monetary council has been set up since December 2009 with a view to setting up a single GCC currency in the future, the Eurozone sovereign debt problem is seen as deterring GCC members from proceeding.
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New Delhi, Nov 9: Delhi Chief Minister Sheila Dikshit has exuded optimism that Congress would storm back to power for a third consecutive term, riding on the plank of stability and development achieved by her government.
''We go to the electorate with absolute confidence as Delhi has witnessed unprecedented progress in the past ten years. What people will call it anti-incumbency, it will be pro-incumbency for us,'' Ms Dikshit said in an interview with UNI.
''I have a dream of making Delhi a world class city. This is an unfinished agenda which we hope to complete after we come back to power. The opportunity has come in the form of the Commonwealth Games for which the infrastructure has to be developed on a massive scale,'' she said.
Terming stability as one of the major achievements of the ten-year rule of the Congress in Delhi, she said Delhi under the BJP in mid 90s was an epitome of instability. ''The regime had seen as many as three Chief Ministers. Power and water situation was in a total shambles,'' the Chief Minister said, adding that ''What a mess!'' While listing out the various achievements of her government in transport, health and education, Ms Dikshit admitted that the law and order problem could not be tackled by the government as it did not have control over policing.
On tackling terrorism, she said not just Delhi but the entire country was affected by terror attacks. ''As far as ensuring security is concerned, one state government could not take entire responsibility as it is too sophisticated matter.
Delhi is far more sensitive to terrorism than other states.'' Responding to the Opposition's criticism on her handling of the law and order, the 70-year-old Congress leader, who has been the Chief Minister for two consecutive terms since 1998, said when other states which have police under their jurisdiction could not control terror attacks, how could her government handicapped by the lack of control over land and policing, be expected to do so.
''Police is totally out of our hands. Neither DDA nor MCD are with us. Delhi government should at least have representation in Delhi Development Authority and MCD (which are under the Centre),'' said Ms Dikshit.
Asked about her government's efforts on grant of full statehood to Delhi, she said full statehood for Delhi, like that enjoyed by other states, was not possible, as it is the capital of the country.
Reacting to the Opposition's tirade against her government on price rise, the Chief Minister said '' Inflation in Delhi has been the least among all the metros. We have undertaken measures to check the price rise of essential commodities, like conducting raids on hoarders. Delhi is giving two dals and oil in ration shops for BPL families.'' Admitting that there has been a slight rise in prices of commodities, she said that if the prices have increased, so has the income level.
Highlighting the achievements of her government in the transport sector, she said,''In the last ten years, we have changed the face of transport in Delhi--brought in the Metro, high capacity low floor buses and AC buses. About 47 to 57 flyovers were built and more are in the pipeline.'' On BJP chief ministerial candidate V K Malhotra's allegation that there was a major scam in the purchase of low floor buses, Ms Dikshit outrightly denied it.
Mr Malhotra had alleged that while the low floor buses in Chennai had cost Rs 16 lakh, it was Rs 42 lakh in the capital.
To this, Ms Dikshit said the Chennai buses were medium floor and not low floor and he was only referring to the cost of its chasis and not the bus.
Ms Dikshit said that in the last ten years, her government made rapid strides in the fields of education, health, environment, power, water supply and social sector.
''In the education sector, on the one hand we have built two schools per month in the last ten years while on the other, there has been a sharp improvement in performance of government schools, from 35-36 per cent in 1998 to 85 per cent at present.
In higher education, the government has set up four new universities- while the Bhimrao Ambedkar University is to start in April next, there is a college of pharmaceuticals, a Law college and an IIIT started in association with G B Pant Hospital'', the Delhi Chief Minister stated.
Ms Dikshit added, '' In the health sector, from five to six hospitals ten years ago, Delhi now has 30 to 35 hospitals besides 50 small hospitals and 300 plus dispensaries. In the social sector, we have undertaken a scheme to built housing for the poor who live in the jhuggis. Nearly three to four lakh applications have already been recieved. 13 to 14000 houses are ready.
Under the JNNURM, we plan to build low cost houses for nearly four to five lakh people in the next four to five years.'' On her government's achievement in the field of environment, Ms Dikshit said,''Delhi today is much greener compared to what it was ten years ago. From two per cent in 1999, the green area in the city has increased to 20 per cent today, despite the large number of infrastructural development in the city.'' In terms of power situation too, Ms Dikshit said,''power consumption in Delhi has gone up from 1900 MW in 1998 to over 4000 MW today. Besides, we are also planning for the future which includes setting up a 1500 MW gas based power plant in Bawana, a 750 MW plant in Bamnauli and a 750 MW coal-based power plant in Jhajjhar in partnership with Haryana government.'' On the water front, she said the situation had improved considerably, thanks to the coming up of 140 MGD Sonia Vihar water treatment plant.
On the Opposition's charge that granting of provisional certificates of regularisation to unauthorised colonies was a pre-election ploy to gather votes, the Chief Minister vehemently dispelled the criticism, saying ''These were all legally notified documents.
We have been fighting on this issue for several years even when the NDA government was in power. The certificates were issued after a notification by the Union Urban Development Ministry. So the contention that we are fooling the people is wrong.'' UNI


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Paul Walker Fiery Crash at 3:30 Illuminati Freemason Symbolism. The Great Deception is coming. . TheGroxt1·285 videosPosted: December 1, 2013 in Illuminati
Tags: Army, crash, day of the Lord, devil, fast and furious, fireball, furious, hollywood, man of perdition, obama, Paul Walker, vin disel
Is Obamacare The Mark OF The BEAST????Posted: November 3, 2013 in NWO
Tags: 666, anti-christ, end times, health, obama, obamacare, revelations, taxes, US
Samsung Hooded Figures- HalloweenPosted: October 31, 2013 in Music, NWO
Tags: aliens, candy, end times, grace, halloween, hooded figure, iphone, Jesus, mercy, nwo, pillars world system, Revelation, samsung, satanist, Saves, sony, the judge, trick or treat, witches
5.0 earthquakes hitting all over the Pacific Rim in the last weekPosted: October 31, 2013 in Earthquake
Tags: Alaska, chile, China, earthquakes, Japan, pacific, pacific rim, us.gov
Strange, Glowing Orb Is Seen Hovering Over Indian OceanPosted: October 20, 2013 in unexplained
Tags: Atlantic, beacon of truth, cable, communist, end times, falcon, grand slam, heathen, hippie, India, missle, money, nwo, ocean, orb, pacific, patriot, rocket, stocks, tree huggers, tv, ufo, vandenburg, weather satellite, yippie
More on Comet IsonPosted: October 17, 2013 in Bible
Tags: anti-christ, endtimes, gravity, mars, moon, nwo, Paul Begley, planet, regulus, Revelation, space, speed, stars, sun, Tom Hanks


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Congressman Todd Akin, Chairman of the Seapower & Expeditionary Forces Subcommittee and member of the House Budget Committee, released the following statement in response to Secretary of Defense Robert Gates' "efficiency" proposals:
"I appreciate Secretary Gates' effort to find inefficiencies and waste in the DOD budget. Congress and the Administration must work together to ensure that every single tax dollar is spent wisely. There are certainly wasteful and inefficient parts of the DOD that should be cut. At the same time, I find it stunning that the Obama Administration thinks cutting almost $80 billion from our defense budget while we are at war is a responsible course of action. I have a number of concerns about the specifics as well as the overall priorities this action reveals. If Secretary Gates wants Congress to even consider supporting any of these proposals, he must personally ensure that Congress receives the information we need, rather than stiff-arming the Congress as has been the norm for the last few years.
"First, I think this announcement shows the liberal priorities of this Administration. The only department undertaking a serious budget cutting exercise is the Department of Defense. Where are the similar reviews at any other executive department? Our military is at war, and our military is the only department asked to seriously tighten its budget?
"Second, President Obama's budget shop has already shown an interest in "harvesting" even the reinvested savings and applying them outside the Department of Defense, rather than letting the military use these funds for other priorities as Secretary Gates has proposed. I am worried that Gates will propose these cuts, walk out the door, and leave the military with a constricting budget and little political support to oppose an even larger cut.
"Third, many of these cuts seem to have been decided upon in a vacuum, ignoring the strategic situation our nation is in, and the capabilities we need to fight and win today and tomorrow. For example, do we as a nation think that the Marine Corps should be able to get from ships to the shore in a battle? If so, cutting the EFV is absurd. If the President and the Secretary of Defense want to get rid of the Marine Corps, they should come out and say that directly.
"While my concerns are significant, and these proposals will require serious oversight from the Armed Services Committee, I do think elements of the reinvestments make sense. In particular, buying more F/A-18's to fill the gap created by the JSF delays makes a lot of sense and is something that I have championed for years. These Super Hornets will help address the Navy's strike fighter shortfall and are a great deal for taxpayers. I look forward to hearings on every aspect of this proposal."
Source: http://akin.house.gov/index.php?option=com_content&task=view&id=1591&Itemid=74


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wooga is a social network game developer located in Berlin, Germany.[1] The company develops free-to-play browser-based games for social networks like Facebook and is currently the largest European social games developer and also the world's 8th biggest game developer (by monthly active users) on the Facebook platform as of June 2010.[2]
The name "wooga" is a contraction of the sentence "world of gaming" and is written without capital letters.[3]
wooga was founded in January 2009 by Jens Begemann (CEO) and Philipp Moeser (CTO).[3]
In July 2009 wooga launched its first game, Brain Buddies. The game reached 5 million monthly players 3 months after launch.[4]
The company received EUR €5 million in a round of funding led by Balderton Capital in November 2009. [5] Holtzbrinck Ventures, which had provided funding earlier that year, also participated in this round.[6]
In February 2010 wooga launched its second game, Bubble Island, which reached 4 million monthly players in 8 weeks.[3]
In May 2010 wooga launched its third game, Monster World.[7]
According to AppData, in late June 2010 wooga had a total of ca. 9.7 million monthly active users and 1.2 million daily active users.[8]
- ↑ "Contact wooga." Retrieved on June 9, 2010.
- ↑ "Appdata Developer Leaderboard by MAU." Retrieved on June 9, 2010.
- ↑ 3.0 3.1 3.2 "About wooga." wooga.
- ↑ "Facebook Game "Brain Buddies": Five million monthly users." Retrieved on June 9, 2010.
- ↑ "Following the Playfish exit, social games developer wooga secures a further €5 million funding." TechCrunch.
- ↑ "wooga secures €5m ($7.5m) in funding led by Balderton." wooga.com
- ↑ "Wooga Goes Facebook Farming with Monster World." Inside Social Games.
- ↑ "wooga - world of gaming." AppData, Retrieved on June 22, 2010.
- ↑ 9.0 9.1 9.2 "Appdata.com - wooga." Retrieved on June 9, 2010.


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Backstage at the 57th annual Emmy Awards in Los Angeles Sunday night, the star of the CBS sitcom "Everybody Loves Raymond" told The Early Show national correspondent Hattie Kauffman, "You could look at it and say, 'You did the right thing, you went when you're still on top,' or you can also look at it and say, 'You didn't do the right thing, 'cause you're still winning awards.' So you can't win."
"Wanna come back," Kauffman kidded Romano.
"Can I?" he kidded back.
Last season was the last for the long-running "Raymond."
Doris Roberts, who played Raymond's mother, won for the fourth time for Supporting Actress in a Comedy Series, and she was dancing in the aisles.
"When people stop me on the street, they always say the same thing: 'I love you and thank you for the laughter you brought into my home.' What a great thing to hear," she observed to Kauffman.
Brad Garrett took a laidback approach to his third win as Best Supporting Actor in a Comedy Series.
"You must be used to winning these: You put it on the floor. Everyone else is holding it close to the heart," Kauffman remarked.
Responded Garrett, "I'm not about the bling-bling. If I was in charge of the academy, I would make them out of wicker."


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NewswireToday - /newswire/ -
Mount Kisco, NY, United States, 2005/07/19 - I-FlowerDelivery.com recently announced the launch of a new website, which provides comprehensive information about same day, next day, international, online, and cheap flower delivery in various regions..
People have been giving flowers as gifts for generations. According to I-FlowerDelivery.com, flowers can represent many things, ranging from friendship to love, and are given for many occasions including birthdays, anniversaries, births, and deaths.
While offline flower delivery has been popular for decades, online flower delivery has become increasingly popular. According to I-FlowerDelivery.com, online flower deliveries witness double-digit growth last year.
I-FlowerDelivery.com recognized a need to answer questions about various services and products available both on and offline, and responded to this demand by creating a comprehensive online guide to flower delivery.
According to I-FlowerDelivery.com, the busiest times for florists are the major holidays, including Mothers Day and Valentines Day.
The new website provides detailed explanations of various services, including same and next day delivery, as well as international delivery and cheap or discounted flower delivery services. I-FlowerDelivery provides information relevant to most audiences, but also focuses on specific high-demand markets, such as Chicago, Los Angeles, Philadelphia, New York and Washington D.C.
I-FlowerDelivery.com will be constantly updated about flower delivery to help educate readers about what products and services might be best for them.
About i-flowerdelivery.com
Flower Delivery provides information on same day, next day, international, and online flower delivery in various regions.
Written by / Agency / Source: Growthink, Inc.
Availability: All Regions (Including Int'l)
Traffic Booster: [/] Quick Newswire Today Visibility Checker
Distribution / Indexing: [+]


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Hello, I'm Donnie'sDarko, and I'm a new user here. I have been on this wikia for about the last 2 years (?), and I love reading original pastas. I've never really been a fan of Cliched writings, like Jeff The Killer, or Slender Man (not to knock the authors), because I find it lacks originality. I recently decided to make an account because I love to write, especially darker stories, and short thrillers. I would love to post, but am a bit shy about my work. If any of you have any pointers for me, I'd love it. :) I'd also wouldn't mind making a few buddies on here, if possible. I can't wait to get reading y'all's writings, and writing my own. Thanks for reading through this post. :)
(extra info, AKA a little about me)
I've always enjoyed writing, and I love pastas. I also draw a lot. As you can tell from my name, I love the cult classic DONNIE DARKO. Horror and creepiness is my speciality, and I hope this is the community for me. BTW, I have read the Rules and Guidelines and such, thank you for those pointers.


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Question: Evaluate the marketing situation for one of the following companies
Evaluate the marketing situation for one of the following companies or brands. What makes this company (brand) unique and what is its differential advantage(s) compared to the primary competitors? Based on what you know of this company (brand) and what you see or hear in terms of marketing communications, develop a positioning strategy statement for the company (brand). a) Samsung b) Target c) H& M d) Doritos e) Gatorade
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Answer to relevant QuestionsUsing a company or brand of your choosing, examine the relationship between its name, logo, and advertising slogan. Are these brand and communications ele-ments permanently entwined or can any of them change in order to ...Ad campaigns should have focus and aim toward an overall goal. Identify and briefly explain three specific goals a campaign may try to achieve. Clip an ad that catches your attention from a magazine in your household. After assessing the ad, try to determine the advertising objective, the creative objective (key benefit statement), and the creative strategy (appeal ...Briefly describe how the timing and amount of spending vary in the following media schedules: pulse, skip, blitz, and build- up. Given the nature of Canada's population and where the bulk of the population is located, when is it practical to implement a national media campaign? When do regional media campaigns or key market media campaigns make ...
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Data from: Marine communities on oil platforms in Gabon, West Africa: high biodiversity oases in a low biodiversity environment
Date Published: August 7, 2014
DOI: http://dx.doi.org/10.5061/dryad.9p91h
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Most Helpful Girl
Yeah, I'm a fan. Pink is unapologetic about her imperfections and feelings and that's what I love about her music. Whether she's singing a song about her crazy feelings like in Please Don't Leave Me, or shouting out So What she never holds back. She's real. She knows that she can get a littlw crazy and a little loud and be kind of a mess, but she doesn't care because she's not looking for anyone's approval. That's what makes Pink a good role model for girls. Girls face so many challenges in life. We're constantly worried about being labeled a slut, a prude, a bitch, too loud, too quiet, bossy, a doormat, crazy, over emotional and more. Pink just does not care, and I respect that. She doesn't care if she comes off as the crazy ex-girlfriend, or the party girl, or the drunken mess, or the badass rebel because she knows who she is and she won't let anyone else define her. That's real empowerment!21|10|0


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Grab yourself a slice of the action at the Premier Inn Hotel Caerphilly (Corbetts Lane) - a great choice whether you're in the area for big business, top entertainment or world-class heritage.
Please note: the Premier Inn Breakfast is not served at this hotel. Guests can enjoy breakfast, lunch and dinner at the neighbouring Carvery restaurant.
This hotel has 1 newly opened meeting room, which can hold up to 14 delegates.
Exit M4(J32) towards Merthyr Tydfil on A470. Exit junction with A468 to Caerphilly. Continue on A468 to Penrhos roundabout, take 2nd exit to Newport. Continue to the Trecenydd roundabout, go straight across. Take 3rd exit at roundabout. Hotel is behind the Cedar Tree pub.


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Pairon Talle Trailer
"Pairon Talle (Soul of Sand)" is an upcoming Hindi drama, thriller film written & directed by Sidharth Srinivasan. Movie produced by Reel Illusion Films. The "Pairon Talle (Soul of Sand)" movie includes Dibyendu Bhattacharya, Saba Joshi, Avtar Sahni & Geeta Bisht in lead roles. Movie releasing on 5th October 2012.
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Rush Movie Trailer
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Verdi has broad interest in capital markets research in accounting and finance. His past research investigates the economic consequences of financial reporting quality to investment efficiency and to the cost of capital. He also has studied the interaction between accounting information, voluntary disclosure, and market efficiency. Overall, Verdi's research provides insights into the role of accounting information in corporate finance decisions and in capital markets behavior.
Verdi holds a PhD from the University of Pennsylvania.
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