text: Hi all, This is a really weird one and I haven't been able to find a post from anyone else with this problem. I've got a new Hero, running the bog standard 1.5 and it's not rooted. On one of the home screens I created a folder I called "System" and put some app shortcuts into it. On another home screen, I have a folder called "Misc" with a number of shortcuts to various apps. A few days ago, I was certain there were shortcuts to a couple of apps in the System folder that had disappeared. I hadn't manually deleted the shortcuts and hadn't uninstalled the apps. I thought it must be just me and recreated them. Then, I created the Misc folder and I know I had around six or seven shortcuts in the folder when I did it. Today, I opened the folder and there are only two shortcuts in there. Again, the apps are still installed and I know I haven't removed any shortcuts. Even uninstalling software doesn't get rid of shortcuts you create, so it couldn't be that anyway. So, have any of you heard of this happening? It's really weird and I'd put it down to me going mad if it weren't for the fact that it's happened twice now. EDIT: Even stranger! I've just done a google search for "android shortcuts disappearing" and it seems there are others out there experiencing this problem. Looks like an OS bug to me then. Cheers, Jim


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RepairPal is your advocate for car care advice and guidance
Q: CEL, TRAC and VSC comes on at the same time? Anyone know how to fix this problem on 2008 Toyota RAV4
Im somewhat mechanically incline, I dont want to take it to the dealer since they charge you arm and leg. I dont have any diagnostic tool, but i was thinking to get one, just to fix this issue, however if anyone had encounter this problem and know how to fix, i would really appreciate.
| |
You will need a scanner that will access the anti-lock brake and traction control computers in the vehicle. If you're going to get your own scanner make sure it will do this. Most "code readers" will only access federally mandated codes for emissions. I think your best bet is to find a quality independent who can diagnosis this. It will be less expensive in the long run.
Sir, thanks for the information.
Didn't find what you were looking for?

subset: commoncrawl


text:
Moone Moonu Varthai Trailer (2015)
26 June 2015 Comedy, Romance 128 mins
Arjun and Karna, two happy-go-lucky friends who have resigned from their jobs, start a bad news delivery service and one of their assigments ends up in a marriage getting cancelled. And the bride happens to be the sister of Arjun's girlfriend Anjali! Can they undo the damage?
Watch the official Moone Moonu Varthai 2015 trailer in HD below or find more Moone Moonu Varthai videos on Vidimovie.


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Hotel Pineta
Select your stay dates to check availability
Hotel Pineta
About the hotel
Property Location
Located in Vico del Gargano (Gargano Peninsula), Hotel Pineta is close to Abbey of Santa Maria di Kalena and Peschici Castle. This hotel is within the vicinity of Church of Our Lady of Loreto and Nautilus Beach.
Make yourself at home in one of the 40 air-conditioned rooms featuring minibars. Digital television is provided for your entertainment. Private bathrooms with showers feature complimentary toiletries and bidets. Conveniences include phones, as well as safes and desks.
Rec, Spa, Premium Amenities
Enjoy a range of recreational amenities, including a spa tub, an outdoor tennis court, and a seasonal outdoor pool. This hotel also features complimentary wireless Internet access and a television in the lobby. Getting to nearby attractions is a breeze with the area shuttle (surcharge).
Enjoy a satisfying meal at a restaurant serving guests of Hotel Pineta. Quench your thirst with your favorite drink at a bar/lounge. A complimentary buffet breakfast is included.
Business, Other Amenities
Featured amenities include express check-in, express check-out, and dry cleaning/laundry services. A roundtrip airport shuttle is provided for a surcharge (available on request), and free self parking is available onsite.
Hotel Facilities
- Luggage storage
- Airport transportation (surcharge)
- Spa tub
- Free self parking
- Outdoor seasonal pool
- Outdoor tennis court
- Express check-out
- Bar/lounge
- Television in lobby
- Tennis on site
- Free WiFi
- Express check-in
- 24-hour front desk
- Multilingual staff
- Free breakfast
- Elevator/lift
- Coffee/tea in lobby
- Free parking nearby
- Area shuttle (surcharge)
- Dry cleaning/laundry service
- Laundry facilities
- Restaurant
- Total number of rooms - 40
- Number of buildings/towers - 2
- Smoke-free property
Room Facilities
- Desk
- In-room safe
- Sofa bed
- Shower only
- Free toiletries
- Phone
- Hair dryer
- Iron/ironing board (on request)
- Cribs/infant beds (surcharge)
- Air conditioning
- Television
- Minibar
- Rollaway/extra beds available
- Bidet
- Climate control
- Digital TV service
- Private bathroom
Hotel Policy
Know Before You Go
- Cash transactions at this property cannot exceed EUR 999.99, due to national regulations. For further details, please contact the property using information in the booking confirmation.
- This property offers transfers from the airport (surcharges may apply). Guests must contact the property with arrival details before travel, using the contact information on the booking confirmation.
- Guests can arrange to bring pets by contacting the property directly, using the contact information on the booking confirmation (surcharges apply and can be found in the Fees section).
The following fees and deposits are charged by the property at time of service, check-in, or check-out.
- Pet fee: EUR 30 per pet, per week
- Crib (infant bed) fee: EUR 5 per day
The above list may not be comprehensive. Fees and deposits may not include tax and are subject to change.Show all hotel policy Show less hotel policy


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Many people have asked about the items that I started with when I began incorporating movement in my classroom. Now that I am a counselor, I would love to begin stockpiling some of these things so that I had them available for teachers that were wanting to try something different! These items can make such a difference in regards to behavior and academics!
The following are the items that I started with-
Ball Chair with legs, affectionately called "cow chairs", by my kinder kiddos!
I will say that these did not last very long like this! Even with them only at my teacher table, the kids had a hard time managing them, so we let out a lot of air and put them in milk crates. This allowed the students to bounce, but kept the balls from rolling.
This is also a WAY cheaper option! I know many upper grades use these with great success, but for the younger kiddos, I would go with cheap balls in the crates! These are always easy to find and CHEAP at Walmart and you can get the balls there too! I googled milk crate chairs and this amazing blog post came up from Miss V's Kinder Kraziness! Super cool and you should definately check it out! And btw, the saving grace for ball chairs in kinder…ALWAYS KEEP BOTH FEET ON THE FLOOR J!
Pure Fun Kid's mini trampoline – to be utilized prior to beginning assignments, as well as, upon completion, to expel excess energy and to increase focus.
LOVE, LOVE, LOVE this trampoline (you can buy it here!!! It is the PURE FUN Kid's mini trampoline with handrail. Now, I am not gonna lie, it was a bear to put together! (Thank the Lord for a my strong hubbyJ)
I put this with the handle facing in a corner. The rules were… 1) both hands on the bar, 2) only one person touching on the mat a time (more on the mat below) & 3) Chose one patterns in numbers to read out loud, then let someone else have a turn (on the wall in the corner I had number pattern anchor charts)
Balance Boards were utilized by anchor charts with high frequency words and/or phrases. In order to make it easier for the kinder kiddos, one of my teammates had the brilliant idea to put a die-cut had on the counter and we taught them to place one hand on the counter for support, until they could balance! This is the one that we used and it was perfect. The picture makes it looks like it is for really young kiddos, but it was perfect, I might have even used it once or twice 😊. This was another Amazon purchase (again, THANK YOU Toyota of Rockwall!)
Students read and balance, fun, coordination, strength and balance all rolled into one! This is Win-Win!!!
Slant boards – were utilized on the floor as alternate seating. Students would on their stomachs, developing core strength, and eye coordination as their eyes move up and down tracking print. I had these available as a choice during word work The Occupational Therapist on my campus said this was a MUST HAVE and I always listen to those that know more than me!
Puzzle Play Mat was used underneath standing tables to provide support for feet and legs while standing on tile. Being able to utilize another type of alternate work spaces in the classroom, allows for greater growth academically for students.
This was one of my favorite purchases because of its versatility. I used some of it under the trampoline, some under the balance board, some under tables as stated above It provided designated areas for our flex seating and added some fun colors in the processJ.
This is just the starting point! It is so exciting for me to walk around my current building and see so many teachers embracing flexible seating! I used to not be a beleiver, but after seeing it in action and the the academic and behavioral successess that it produced, I have had my mind forever changed inregards to the power of movement in the classroom! Small changes can produce results, but those small changes have to begin with us 😊.
I would love to hear some of the things that you have tried!


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W Hotels + Mixcloud present
The FUTURE RISING platform engages and champions the creative leaders of tomorrow across the artistic sphere--from musicians and DJs, to visual artists and videographers, to creative entrepreneurs and innovators.
At the heart of FUTURE RISING is the ambition to identify and champion future creative leaders, cultivate new talent, foster craft and collaboration, and provide a framework and network for them to succeed on a global scale.
7 Cities. 7 Talks. 7 Parties.
In collaboration with


text: Hello all, I have used LG and Samsung phones mostly. Never a real smartphone either. My current phone is the Samsung Rogue and I love it. But I got a promotion at work and they want me to get a smartphone. They wanted me to switch to AT&T and get an iPhone and I said no thanks. I am interested in the HTC Incredible. I do not like Blackberrys. I think the DroidX is too huge. I think the Samsung Android phones hare too huge as well, although what beautiful screens they have. I like the Droid2, but I think it is a bit bulky and fell the slider keyboard is junk. So I started playing with the HTC Incredible and I like it a lot. I have read some reviews and was a bit concerned though. Someone I read was complaining about the camera. I took a pic and it looked fine to me. I don't expect to be taking very worthy pictures with this, that is what a camera is for. Anyone find any major issues with the camera? I also read something about call quality being quite poor. Is this true? Or perhaps was this somethign fixed in an update? It is after all a phone first for me. Battery Life... Another downfall I have read about. In comparisons with other phones, I have read this one is dismal. If I can get a solid day out of heavy use, I am happy. Any truth to the appetite this phone has for energy? Are there any other known issues that should keep me away from this phone? I text a ton. I will be getting Exchange Email sent to it. I love apps and hope to replce my iPod Touch as much as possible. I am not a novice user either. I have been in the IT business for years, run Ubuntu on an HP Mini, OS X on a Dell Mini, hacked firmware on my PSP, etc etc etc, you get the idea. I am not afraid of a little tweaking. Thanks in advance for any responses!


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GraphicRiver HOME TOWN Logo Templates 3354289
Category: Logo Template | Comment: ( 0 )
GraphicRiver HOME TOWN Logo Templates 3354289
Logo Template \ Buildings
Business \ Real \ Estate \ Properties \ Mount \ Metropolis \ Restriction
Logo Template - HOME TOWN Logo Templates 3354289 by Sandra_Brown12 @ GraphicRiver
Logo Template \ Buildings
Graphics Files Included: Photoshop PSD, Vector EPS, AI Illustrator, Font; Layered: Yes; Minimum Adobe CS Version: CS3; Resolution: Resizable.
Excellent logo,simple and unique.
- Fully editable EPS , Ai and Photoshop PSD.
- Easy to Change Color and Text.
- Used Free Font (Link Included Main Download).
What is included?
- AI CS3 Document.
- EPS CS3 Document.
- PSD CS3 Document.
- Font.
Note: (The mock up file is not included, that's only for preview purpose)!
Please any help you need Contact me and I am at your service at any time.
More of my work.
Thank you
Cloud Barso Logo; Sotamort Logo Templates; Colour Care Logo; Infinity Heart Logo; Star Cube Logo; Studio Eye Logo; Melo Tree Logo.
Keywords: Land Business, architecture, build, building, business, camp, capital, city, constraint, constriction, elegant, engineer, home, house, housing, interior, metropolis, mount, neighborhood, properties, real estate, restriction, roof, town, unique, urban, villa, village.


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Honda CRV
For sale: cars, cars and vehicles in Lagos, Nigeria
Honda CRV
Price in Naira: NGN 5,850,000
Location: Other, Lagos
Last update:
Last update:
0 comments like this listing
Ad description
AWD, Full option with Leather seats
Seller: Chidera Autos Nig. Ltd
City: 164B Obafemi Awolowo way, Ikeja, Lagos
Category: Car
Type: Honda CRV
Color: Metallic chocolate brown
New/Used: Used
Nigeria used/imported: Imported
Fuel type: Petrol
Mileage: Automatic
Year of manufacture: 2012
Price in Naira: 5850000
ATTENTION! Do not make any advance payments to any seller on Mobofree, not even for delivery! You may get scammed by unfair seller. Please report abuse to help us stop scam! To keep yourself safe, make sure to follow our Safety tips!


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person who cannot accept defeat under any circ-mstance and must show their displeasure to everyone by b-tching non stop even though said b-tching won't change a thing.
donalt trump won the presidency but the liberab-tches don't seem to let it go.
Read Also:
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a conversation you get in that one person gets so worked up they hit the table. usually to get someone attention or to show anger. "conversation about rahim is a table pounder." "man if you mention s-xist jokes around her she get so mad she pounds the "table. a conversation that gets you so worked […]
- pulling a scott garland
the act of faking an injuring to not have to partic-p-te in any sports related activities. joe: hey frank i don't think i can make it to the cross country meet. frank: what's the matter dude? joe: i think i twisted my ankle today during pe. frank: come on joe, stop pulling a scott garland.
- marhaen
a useless piece of cr-p that usually moans around roaming and being useless,usually found in the streets finding food in the garbage bin and forever alone, tends to be mad for no personal reason and usually have a disorder and only has 1 ball and 2 d-ck,usually tend to forget that he has a d-ck […]
- hillarying
the act of failing or imploding at something that was, and should have been, all but -ssured. the 2015 warriors are down 3-2 to the cavs? they are totally hillarying these finals.
- tripped on his d*ck
overconfidence that leads to failure or embarr-ssment. jeff thought he could impress those girls at the bar, but when he got over there he tripped on his d-ck and now they won't talk to him. joey didn't think he had to study for his math final but when he went to take the test he […]


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We help you locate a Bromsgrove harmonica teacher. Harmonica tuition are a great method to begin an entertaining new hobby, pick up a new skill and gain confidence with harmonica. Use our service to search for Bromsgrove harmonica tutors and select which best matches your requirements so you can begin your harmonica lessons in Bromsgrove today!
This is the fastest way to locate Bromsgrove harmonica teachers in the UK, helping you discover Bromsgrove harmonica lessons close to you and Bromsgrove teachers to assist with any instrument like piano, violin or guitar. We can help you find Bromsgrove harmonica lessons or a one-to-one Bromsgrove harmonica teacher to prepare for harmonica exams and improve your harmonica skills! We order Bromsgrove harmonica teachers near you by their lesson prices and distance from you.
If you are a harmonica teacher wishing to offer harmonica lessons in Bromsgrove or anywhere else across the UK, please register with First Tutors: Music or learn about us here. Becoming a Bromsgrove harmonica teacher is a great way to re-affirm your own skills through providing harmonica lessons while assisting others, all in the Bromsgrove area!


text: Da Soocha III was the third moon of Da Soocha. AppearancesEdit Republic Commando: True Colors (First appearance) In other languages DeutschEspañol Retrieved from "http://starwars.wikia.com/wiki/Da_Soocha_III?oldid=7241258" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Legends articlesMoons of Da Soocha


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s 19 incredible kitchen islands made from totally unexpected things, kitchen design, kitchen island, repurposing upcycling, Vintage washtub turned storage stunner
How To Create Ottomans from Flea Market Find Tables. I used Old Fashioned Milk Paint.
40 High Style Low-Budget Furniture Makeovers You Could Definitely Do! DIY Vintage Clock Table from a Flea Market Find.
Thrifty storage, add casters and make an awesome side table, night table, towel storage, so many options
LOVE flipping flea market and thrift store items for a profit!
If you are a budget decorator, you probably know your local flea market, thrift store, or yard sale circuit pretty well. If you don't, get familiar. Because flea market flips and other such fairy.
Awesome locker style, cou ld add draw underneath and a shelf at top
living room sets recycled into a beautiful outdoor furniture set.


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The New Chronospace Evo Night Mission From BREITLING
06 Dec 2016 by Pedro Aristes in Ego, Fame, Fashion, General, Gift Guide, Home, Money, Pleasure, Products, Style
If you're looking for a special gift for the watch connoisseur in your life, consider the new Breitling Chronospace Evo Night Mission, a new high-performance instrument in blue and black. By appearing with a sturdy and light black titanium case framing a blue dial with tone-on-tone counters, the electronic Chronospace chronograph from Breitling adopts a strong and original new persona, while maintaining its sterling qualities as an instrument for professionals.
The spirit of performance is immediately perceptible in the sheer power of black satin-brushed titanium, achieved by a high-resistance carbon-based treatment, combined with the original note struck by a deep blue dial.
Beneath its exclusively analog displays, a notable exception in the Breitling Professional range, the Chronospace Evo Night Mission conceals the best of high-tech capabilities, with a SuperQuartz movement ten times more accurate than standard quartz. As with all Breitling watches, the Breitling Chronospace Evo Night Mission is chronometer-certified by COSC (the Swiss Official Chronometer Testing Institute), the ultimate benchmark in precision and reliability.


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In 1929, Edwin Hubble announced the greatest discovery in the history of astronomy since Galileo first turned a telescope to the heavens. The galaxies, previously believed to float serenely in the void, are in fact hurtling apart at an incredible speed: the universe is expanding. This stunning discovery was the culmination of a decades-long arc of scientific and technical advancement. In its shadow lies an untold, yet equally fascinating, backstory whose cast of characters illuminates the gritty, hard-won nature of scientific progress.
The path to a broader mode of cosmic observation was blazed by a cadre of 19th-century amateur astronomers and inventors, galvanized by the advent of photography, spectral analysis, and innovative technology to create the entirely new field of astrophysics. From William Bond, who turned his home into a functional observatory, to John and Henry Draper, a father and son team who were trailblazers of astrophotography and spectroscopy, to geniuses of invention such as Lon Foucault and George Hale, who founded the Mount Wilson Observatory, Hirshfeld reveals the incredible stories and the ambitious dreamers behind the birth of modern astronomy.
"A masterful balance of science, history and rich narrative." (Discover magazine)
"Hirshfeld tells this climactic discovery of the expanding universe with great verve and sweep, as befits a story whose scope, characters and import leave most fiction far behind." (Wall Street Journal)
"Starlight Detectives is just the sort of richly veined book I love to read full of scientific history and discoveries, peopled by real heroes and rogues, and told with absolute authority. Alan Hirshfeld's wide, deep knowledge of astronomy arises not only from the most careful scholarship, but also from the years he's spent at the telescope, posing his own questions to the stars" (Dava Sobel, author of A More Perfect Heaven: How Copernicus Revolutionized the Cosmos and Longitude)
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Experience the discovery of most of the universe.
- Zachary Adams
Telescopes, cameras and Spectographs
I found the history of the characters behind the evolution of the telescope and the camera the most interesting. Although the story behind the spectrograph was surprisingly well told. The reader is perfect.
Louis Daguerre and the invention of the camera. The history behind the modern and old observatories.
- Jeff Parry


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It's coming up to the season of LOVE!! As a pagan, we celebrate a version of Valentine's Day on Imbolc, also known as Candlemas or Groundhog Day as it was made into. We use this day as an excuse to celebrate our love, have a date night and enjoy good food. I like to use the time between Imbolc and Valentine's Day to really celebrate our love together. We try to remember why we have this crazy life and family together. We have two little ones and my husband has a busy work schedule so romance isn't always at the top of our list at the end of the day. This is the perfect reminder that it needs to be and we need to make it a priority.
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Time for a relationship challenge!
I have a challenge for you and your marriage or relationship. I will say marriage, but I'm from Quebec, people don't always get married there but live together for decades and have kids. Some people are in a same sex relationship and may or may not be able to get married. I include everyone, if you are in love and together, this is for all of you!
Starting the first day of February you need to have two of these sheets printed out. Post it on the wall, or fridge, someplace you both can see and appreciate. You need to remember to do it daily, that's the fun of it. Every day you and your partner need to think of a reason you love the other person and write it down, every day from Imbolc to Valentine's Day! It's a great way to show your partner how much you care, and get some affirmation yourself that you are loved too.
Ready to start?
Click the graphic below to print or HERE for the PDF.
Start #ValentinesDay by showing your #partner you love them #affirmation #marriage #relationships Click To Tweet
Are you ready? Pumped? Let's work on our relationships and make our partner know how much we love and appreciate them!!!
Follow Raising Fairies and Knights's board Relationships on Pinterest.
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little talk about the effect an unavoidable increase in interest rates will have on stocks.
As with bonds, there will be some stocks that will do better than others. Namely, companies with modest dividends and the potential for fast growth. History tells us these outperform in an increasing rate market.
A study of past periods when the 10-year Treasury's yield has increased by a half of a percentage point showed large cap stocks with modest dividends and growth potential returned an average of 20% in the 12 months following the increase.
Companies like Schlumberger Limited.(NYSE:SLB), Caterpillar Inc.(NYSE:CAT) and The Walt Disney Company(NYSE:DIS).
Schlumberger has a puny 1.5% dividend and an 18% five-year growth estimate.
Disney yields 1% and is estimated to grow 16% per year.
And Caterpillar, the highest of the payers, has a 2.2% yield with a 12% growth estimate for the next five years.
When rates finally move, it will be a whole new ball game for stocks and bonds. Make the necessary changes before the horse gets out of the barn.
It's Not Different
As long as we are on interest rates, here's one that will really pop your cork.
Spain is paying less to borrow money than the USA.
Yup! You heard me right.
Right now the benchmark 10-year Treasury in the U.S. pays around 2.6% to about 2.8%, and has been in that range since January.
The Spanish 10-year is paying 2.57%. Is Spain really a better credit risk than the U.S.? No! Spain is benefiting from European Central Bank (ECB) easing and no inflation in sight.
But the longer the Fed goes without raising rates, the stronger the economy gets and the greater the chance of real inflation. In that case we will see much higher 10-year yields, and the spread between our borrowing rate and Spain's will be much higher.
In case you're wondering, none of this makes sense. We are in one of the most confusing bond markets of my 30-year career, and it doesn't look to be improving anytime soon.
The EU is pouring money into Treasurys, which is helping to keep rates low, while our own Fed is tapering bond buying and talking rate increases.
Talk about pushing a rope!
But, no matter how upside-down this may seem, it is very foolish to think the Fed will not act and keep rates low indefinitely. It will not, and that is the only definite in this whole mess.
Remember, the markets, bond and stock, will always correct. The longer it takes, the bigger and more exaggerated the correction will be. In the case of bonds, that means to hold only super-short maturities in both individual bonds and especially bond funds.
The old adage "It is different this time" will always come back to bite you on the backside, especially in this market. It is not different and this will resolve itself.
The "Slap in the Face" Award, Italian Style
And finally, the real reason anyone watches this segment… the "Slap in the Face" Award.
This week might be the best "Slap in the Face" Award ever. It may not be the funniest, but it will definitely sting for some time to come.
I'm not sure who the winner is: the EU, Italy, or hookers, pushers and smugglers.
So here it is…
It seems the Italian government, in an effort to boost a chronically weak GDP, will now include in its GDP calculations revenues from prostitution and illegal drug sales.
Oh, and smuggling, too!
This proposal is not coming from a splinter group or a lobbying group for hookers. Nope, it is from the prime minister himself. His thinking is if they get their chronically stagnant economy above $2.1 trillion, he can spend more money.
The EU has restrictions on how large the spread can be between spending and a budget deficit. So, boost the GDP with revenues from hookers, smugglers and dope, and spend more.
Have we really sunk this low?
If these are truly under-the-radar, illegal operations, how do you measure them? Do you now require criminals to submit quarterly reports? That should be interesting.
Can you see the CNBC team anxiously waiting for the heroin numbers to come out?
God, I hope Obama doesn't get wind of this. I'm afraid to think of what a taxer and spender like him could do with this kind of thinking.
Let see… car thefts, burglaries, chop shops, murder for hire. Now we're talking revenues, American style!
The sky could be the limit on this one.
by Steve McDonald, Bond Strategist
Investment U provides cutting-edge research and strategic financial recommendations for all levels of investors through its morning publication Investment U Daily and its related publications.


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GDPR to take effect on May 25, 2018. Are you ready?"
General Data Protection Regulations: what does the new EU data protection law mean for small businesses?
The upcoming reform of the EU data protection will mean a major change to how organizations deal with data processing controls. The GDPR is expected to harmonize data protection across all the EU member states and introduce a number of key measures such as mandatory breach disclosure, the right to data portability, and the right to be forgotten. Breaches of data privacy could lead to fines of up to €20 million or 4% of global annual turnover.
But before we get too carried away by the fear of fines – let's pause and get to terms with how "bad" it really is…
Daunting as it all may seem, small businesses can take comfort in this: as long as they can demonstrate that they've put their best foot forward to meet the requirements of GDPR, regulators will work with them on any problems that might arise. This is not about creating a big brother money making machine – this is about making sure that personal data is kept safe.
So getting educated on the matter – and setting in place initiatives to document process is the best approach. Holding your hands over ears and eyes, pretending this is not relevant to you, is the worst.
At QBS we strive to act as your primary advisor when it comes to your business – so GDPR is a topic we should all get familiar with. This is why we have invited Microsoft Technology Director, Ole Kjeldsen, to do a QBS Talk which gives you the Microsoft perspective on GDPR.
Additional sources of information on GDPR:
Are you interesteded in the QBS Talk about GDPR?
Upcoming QBS Talks
|General Data Protection
Regulations (GDPR)
– a Microsoft perspective


text: Whats up im Wes from Idaho. Ran into this site last night and went to work on 2 hours of sleep because i was surfing the forum all night. Im stoked because i just lost my liscence and a motorized bike would help me out alot. Just dunno what kit to buy and what bike to put it on. Any input would help. thanks


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Vance Hall - located at Burrawang
House, Burrawang
Rated 5 out of 5 stars 43 reviews
Confirmation within 24hr
From $235 per night {{quote.pricing.message}} Total {{quote.pricing.price | format:'currency':'short'}} for
Min 1 - 2 nights stay
Vance Hall is a stylish self contained cottage that offers all the comforts for a relaxing stay away from busy city life.During your stay you are sure to enjoy the comforts of this well appointed property that offers two queen bedrooms, one full bathroom and one ensuite bathroom, open plan kitchen, dining and living room that opens out on to a large deck area. There is a wood fire to add to the atmosphere when the temperature drops, a large tv, dvd player and stereo equipment for when you are relaxing after a day exploring the beautiful Southern Highlands. Breakfast supplies are left for the length of your stay. No smoking inside the property and no pets. Great mid week specials available. One night min mid week two night min weekend stays.
Burrawang, Southern Highlands
Self contained cottage
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Baan Chart
Select your stay dates to check availability at Baan Chart
Baan Chart
About the Hotel
Property Location
With a stay at Baan Chart in Bangkok (Khao San), you'll be minutes from Wat Chana Songkhram and Khao San Road. This hotel is close to Temple of the Emerald Buddha and Grand Palace.
Make yourself at home in one of the 42 air-conditioned rooms featuring refrigerators and plasma televisions. Complimentary wireless Internet access is available to keep you connected. Private bathrooms with bathtubs feature complimentary toiletries and hair dryers. Conveniences include phones, as well as safes and minibars.
Rec, Spa, Premium Amenities
Take advantage of recreation opportunities such as an outdoor pool, or other amenities including complimentary wireless Internet access and tour/ticket assistance.
Satisfy your appetite at one of the hotel's 2 restaurants. Relax with your favorite drink at a bar/lounge or a poolside bar.
Business, Other Amenities
Featured amenities include dry cleaning/laundry services, a 24-hour front desk, and an elevator (lift).
Hotel Facilities
- Poolside bar
- Elevator/lift
- Designated smoking areas
- Outdoor pool
- Breakfast available (surcharge)
- Number of restaurants - 2
- Dry cleaning/laundry service
- Free WiFi
- 24-hour front desk
- Total number of rooms - 42
- Tours/ticket assistance
- Bar/lounge
Room Facilities
- In-room safe
- Air conditioning
- Phone
- Free toiletries
- Free bottled water
- Daily housekeeping
- Shower only
- Minibar
- Bathtub only
- Refrigerator
- Plasma TV
- Hair dryer
- Private bathroom
- Free cribs/infant beds
- Free WiFi
Hotel Policy
Know Before You Go
- No pets and no service animals are allowed at this property.


text: Let´s say i want to rank for 2 keywords and i have only 40% Anchortextlinks. Now the 60% of the links passing only linkjuice/authority/trust but they won´t help for google to find out for what we are ranking. So is it more like we have linkpower and can invest this linkpower one time and after it is gone. Or does it not matter and we get the second keyword "for free"? Practical example: We want to rank for weight loss programs: Title: "We provide You the best weight loss programs that are available" Title2: "We provide You the best weight loss programs for your nutrition diet" In title one we try to rank for "weight loss programs", in title two we try to rank for "weight loss programs" and "nutrition diet". Do we have now lesser chances for ranking for the first keyword in the second version (of course with same backlinkstructure and only Anchortextlinks for the first keyword)? Reason: Sometimes it´s easy to rank also for some no competition where we don´t need any additional backlinks. Thanks


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Viral videos are designed to do two things: pique the audience's interest in a particular film without giving anything away, and simultaneously heighten the mythology of the movie. I feel like this recent viral video for 's Oldboy remake accomplishes both. If you haven't seen the original film, these images are intriguing, but give away absolutely nothing. It also creates a preeminent sense of dread toward these hotel rooms, thereby solidifying the mythology. I really enjoyed 's narration, especially over 's frantic face.
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Guide to the William Hays Simpson Papers, 1915-1938.
William Hays Simpson was a Professor of Political Science at Duke University from 1930 until 1974. His collection includes material concerning credits in North Carolina, which was one of Professor Simpson's research interests. Also includes reports, clippings, and correspondence. The collection ranges in date from 1915-1938.
Collection Details
- Record Group
- Title
- William Hays Simpson papers
- Date
- 1915-1938
- Creator
- Simpson, William Hays, 1903-
- Extent
- 0.5 Linear Feet, 100 Items
- Repository
- David M. Rubenstein Rare Book & Manuscript Library
- Language
- Material in English
Collection Overview
Contains material concerning credits in North Carolina, which was one of Professor Simpson's research interests. Also includes reports, clippings, and correspondence. The collection ranges in date from 1915-1938.
Using These Materials
A majority of collections are stored off site and must be requested at least 2 full business days in advance for retrieval. Contact Rubenstein Library staff before visiting. Read More »
Access to the Collection
Researchers must register and agree to copyright and privacy laws before using this collection.
In off-site storage; 48 hours advance notice is required for use.
Use & Permissions
Copyright for Official University records is held by Duke University; all other copyright is retained by the authors of items in these papers, or their descendants, as stipulated by United States copyright law.
How to Cite
[Identification of item], William Hays Simpson Papers, Duke University Archives, David M. Rubenstein Rare Book & Manuscript Library, Duke University.
Contents of the Collection
1. Container List
Historical NoteBiographical/Historical note
William Hays Simpson was born in Madison Run, Virginia. He married Mary McNab in 1930. He received his A. B. degree from Tusculum College in Greenville, TN and his M. A. and Ph.D. degrees from Duke University. In 1930, he joined the faculty of Duke's political science department where his specialties were the American political system and Southern politics. He retired in 1974. His research interests included the social and economic life of cotton mill workers in Canada, Holland and England as well as consumer credit. He published several books, including The Small Loan Problem of the Carolinas (1941), Life in Mill Communities (1943) and Southern Textile Communities (1948). Professor Simpson died in 1989 at the age of 85.
Related Material
- News Service Biographical Files, 1960-2004. (University Archives, Duke University.)
Click to find related materials at Duke University Libraries.
The William Hays Simpson Papers, were received by the University Archives as a transfer in 1973.
Processing Information
Processed by Archives Staff, September 2006
Encoded by Sherrie Bowser, October 2006
Accession A75-12 is described in this finding aid.


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Repulsive. Ugly. Stupid. Deranged. So many negative words could be used to describe Fede Alvarez's Don't Breathe… It's hard to believe that a film with such a questionable cast of characters could have anything to recommend it, but, despite its nasty core, Don't Breathe is a genuinely good thriller. Sure, there's plot holes the size of Texas, but it's the concept of being caught doing the wrong thing in the wrong place at the wrong time that raises Alvarez's latest feature film to a level one-step above the typical horror genre fare.
Despite the obvious limitations of the premise, Don't Breathe takes every opportunity available to it in an attempt to stretch the plot to breaking point. Take the trio of small-time burglars, all of whom are none too bright. There's Rocky (Jane Levy), Alex (Dylan Minnette) and Money (Daniel Zovatto). Rocky and Money are looking to escape the hard-bitten existence of the once-great Motor City, Detroit. Alex, on the other hand, simply suffers from unrequited love for Rocky and is willing to do anything for her. That includes stealing the keys to houses from his father's security company to help her and Money pull-off break and enters in what's left of the city's well-to-do. Unfortunately for this trio, their misguided beliefs and intentions lead them to seriously underestimate the capability of their latest "mark"; a cash-rich blind man who lives all alone in one of the city's abandoned neighbourhoods.
Jane Levy plays Rocky in Don't Breathe
Don't Breathe takes its time to get going and the viewer is forced to sit through a combination of convoluted and logic-defying actions by our trio of young burglars before Stephen Lang's "Blind Man" crystallises the plot and gives the film a creepy edginess. Take, for example, the manner in which the threesome break into "Blind Man's" home; by smashing a lower story bathroom window. The guy may be blind, but nowhere in the production notes did it say he was deaf! Then there's the general carry-on that goes on for the first few minutes Rocky, Money and Alex are inside the house. They've broken into this guy's home on the assumption that he has several hundred thousand dollars in cash just lying around for them to steal. They've got no plan how to find it and, in their wisdom, try and gas the guy in his bed so they can roam around for any length of time until they stumble upon the money that no one is really sure is there! (At this point in the film, it's difficult to believe the positive word-of-mouth that came about as a result of a number of festival screenings Don't Breathe has had.)
It's at the exact moment that Stephen Lang's "Blind Man" appears in the doorframe of his lounge room that Don't Breathe goes from being run-of-the-mill to creepy, thrilling and disturbing. Lang had no problems demonstrating his hard-ass credentials as Avatar's villain but he takes it to a whole new level in this film. What's especially impressive is that he does it with minimal dialogue, without the use of his eyes and in very limited light. The bulk of the story plays out in the hours between 2 am and daybreak, so there's very little natural light and limited internal light sources as Lang's character has little to no need for it. Alvarez and Cinematographer Pedro Luque do a great job with the innovative way they light scenes and use their rambling, big house setting for maximum cat-and-mouse effect. The only question that viewers may feel entitled to ask is "How can Blind Man do all the things he can?" Alvarez's screenplay, which he co-wrote with Rodo Sayagues, certainly stretches his capabilities to the edge of credibility, but no less so than other great Horror genre icons such as Michael Myers and Jason Vorhees. (These guys were human in their initial outings but possessed by an evil that made them superior in their ability to withstand physical pain and transcend their environment. It's not hard to place "Blind Man" in this same category.)
Stephen Lang plays The Blind Man in Don't Breathe
Stephen Lang is best known to cinema audiences as Colonel Miles Quaritch in James Cameron's 2009 3-D blockbuster Avatar, but his career in film and television dates back as far as 1981. What's really interesting about Lang is his age, he's sixty-four years old! When audiences see him in Don't Breathe it's hard not think that his character is a man in his late 40s, early 50s. It's a tribute to the great physical condition he's in for a man of his age to pull off such a physically demanding role.
Be warned, the longer Don't Breathe goes, the more challenging the story becomes as the full extent of Lang's character's capability is revealed. There are several clever (but disturbing) twists that play out in the film's second half and, unlike so many films in this genre, Don't Breathe doesn't afford the viewer an easy ending. Right up to the last frame of the film there is an all-pervading sense of uncertainty about whether the story is really over. For all its rehashing of genre tropes and convoluted plot points, the "uncertainty concept" that takes the film through to its final frame is what makes Don't Breathe a thrilling breath of fresh air!
Don't Breathe - production images & new poster
A trio of friends breaks into the house of a blind recluse confident of an easy score only to find themselves in a terrifying life-or-death struggle in Don't Breathe, the second feature film from writer and director Fede Alvarez (Evil Dead) and legendary filmmaker Sam Raimi. In his sophomore feature, Alvarez goes for the jugular with an unapologetically brutal and twisted horror-thriller that pits a trio of thieves against an unexpectedly dangerous adversary.


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Petpals Zest Cat Scratcher BoxPP2439 818483011341
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Tolerate your frisky kitty's fervour of sharpening their claws and scraping surfaces with the Petpals Zest Cat Scratcher Box. This nifty pet house is the ideal cat furniture for your feline friends during their leisure sessions.
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- The Petpals Zest Cat Scratcher's external surfacing is matted with sisal fibre for comfort and added resiliency that will withstand minor scrapes and scratches.
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Executive Pay Irks Major Investors
Institutions Feel U.S. Firms Sharply Overpay Leaders, According to New Survey
NEW YORK -- Institutional investors are largely unhappy with the way U.S. executives are compensated, with 90% agreeing that executives are "dramatically overpaid," according to a survey.
The survey results provide a peek into what areas of pay institutional shareholders might target next year, when they are expected to place more focus on how executives are compensated. Already, a number of shareholder groups -- including...


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An epistatic interaction of 5-HTTLPR and BDNF Val66Met polymorphisms has been implicated in the structure of rostral anterior cingulate cortex (rACC) and amygdala (AMY): key regions associated with emotion processing. However, a functional epistasis of 5-HTTLPR and BDNF Val66Met on overt emotion processing has yet to be determined. Twenty-eight healthy, Caucasian female participants provided saliva samples for genotyping and underwent functional magnetic resonance imaging (fMRI) during which an emotion processing protocol were presented. Confirming the validity of this protocol, we observed blood oxygen level–dependent (BOLD) activity consistent with fMRI meta-analyses on emotion processing. Region-of-interest analysis of the rACC and AMY revealed main effects of 5-HTTLPR and BDNF Val66Met, and an interaction of 5-HTTLPR and BDNF Val66Met. The effect of the BDNF Met66 allele was dependent on 5-HTTLPR alleles, such that participants with S and Met alleles had the greatest rACC and AMY activation during the presentation of emotional images relative to other genetic groupings. Increased activity in these regions was interpreted as increased reactivity to emotional stimuli, suggesting that those with S and Met alleles are more reactive to emotional stimuli relative to other groups. Although limited by a small sample, this study contributes novel and preliminary findings relating to a functional epistasis of the 5-HTTLPR and BDNF Val66Met genes in emotion processing and provides guidance on appropriate methods to determine genetic epistasis in fMRI.
The imaging genetics framework provides a methodological approach to examine the impact of genetic variation on the structure and function of brain regions involved in emotion processing (Hariri et al. 2006; Pezawas and Meyer-Lindenberg 2010). Many imaging genetics studies have now examined the roles of serotonin transporter (5-HTTLPR, e.g., Hariri et al. 2005; Hariri and Holmes 2006) and brain-derived neurotropic factor (BDNF Val66Met, e.g., Montag et al. 2008; Mukherjee et al. 2011) genetic polymorphisms – independent from each other – on the structure and function of regions involved in emotion processing. A recent meta-analysis observed that the effect size of 5-HTTLPR is smaller than previously reported (Murphy et al. 2012) and another highlighted the inconsistent effects of BDNF Val66Met (Verhagen et al. 2010). Elucidating an epistatic interaction of the two genes may help to better understand the role of these polymorphisms in emotion processing. While the impact of genetic epistasis on brain structure has been examined (Pezawas et al. 2008), studies remain to examine epistatic effects on brain function. A previous report (Wang et al. 2012) attempted to investigate a potential epistasis; however, analyses were not conducted to allow for an epistatic interaction to be determined. This study also had a variety of other methodological limitations (see Outhred and Kemp 2012 for commentary). Building on previous work, we report the results of a human in vivo functional magnetic resonance imaging (fMRI) study on overt emotion processing, exploring the impact of 5-HTTLPR and BDNF Val66Met polymorphisms and a potential epistatic interaction in a homogenous sample of healthy Caucasian subjects.
Gene–gene epistatic interactions may better explain the complex differential brain and behavior correlates of the 5-HTTLPR and BDNF Val66Met polymorphisms. The impact of 5-HTTLPR polymorphisms may vary depending on BDNF Val66Met variation, such that Met allele reduces sensitivity to 5-HT signaling (Murphy et al. 2003; Martinowich and Lu 2008). Equally, 5-HTTLPR may moderate the effect of BDNF Val66Met: the S allele reduces the capacity for BDNF expression (Murphy et al. 2003; Martinowich and Lu 2008). A structural neuroimaging study (Pezawas et al. 2008) reported that these two genetic polymorphisms interact in amygdala (AMY) and the rostral anterior cingulate cortex (rACC). These regions play a key role in emotion processing: the AMY responds to motivationally salient, exteroceptive sensory stimuli, while the rACC is associated with emotion regulation and response preparation (Lindquist et al. 2012).
Building on previous work (Wang et al. 2012), we examined the impact of 5-HTTLPR and BDNF Val66Met and their epistasis on blood oxygen level–dependent (BOLD) activity in the rACC and AMY during emotion processing in a sample of healthy, unmedicated, female Caucasian participants, thus circumventing the potential for the moderating effects of illness, treatment, sex, ethnicity, and associated factors. Consistent with Wang et al. (2012), we hypothesized that (1) the 5-HTTLPR and BDNF Val66Met polymorphisms would both impact on emotion processing and (2) these polymorphisms would interact in an epistatic manner during the processing of emotional stimuli in rACC and AMY.
A sample of 28 healthy Caucasian females with complete fMRI, genotyping, and questionnaire data sets were recruited for this study in order to exclude effects of gender and impact of ethnicity and to reduce overall sample heterogeneity. Exclusion criteria included history of physical brain injury, neurological or psychiatric disorder, or any other serious medical condition. In addition, participants were excluded if they reported use of psychoactive medications or any psychotherapy within the past 6 weeks. All participants provided written informed consent in accordance with National Health and Medical Research Council guidelines.
DNA was extracted from saliva samples and 5-HTTLPR and rs25531 (given the differential impact of the La and Lg genotypes), and BDNF Val66Met genotypes were determined according to protocols described previously (Joffe et al. 2009; Bryant et al. 2010; Quinn et al. 2012). Genotypes were scored independently by two researchers. The functional 5-HTTLPR genotypes were categorized as "S/S" (n = 6; 21%), "S/L" (n = 14; 50%), and "L/L" (n = 8; 29%), and were found to be in Hardy–Weinberg equilibrium, χ2 < 0.001, P = 0.98. The BDNF genotypes Val/Val (n = 16; 57%), Val/Met (n = 10; 36%), and Met/Met (n = 2; 7%) were also found to be in Hardy–Weinberg equilibrium, χ2 = 0.06, P = 0.80.
In accordance with previous literature (e.g., Pezawas et al. 2008; Bhang et al. 2011), the total of 28 participants were divided into four groups on the basis of their functional 5-HTTLPR genotype and their BDNF Val66Met genotype. Groups were as follows: S and Met group (5-HTTLPR S/S or S/L plus BDNF Val/Met or Met/Met) n = 4, 14%; S and Val/Val group (S/S or S/L plus Val/Val) n = 5, 18%; L/L and Met group (L/L plus Val/Met or Met/Met) n = 8, 29%; L/L and Val/Val group (L/L plus Val/Val) n = 11, 39%.
Participants viewed 90 pictures selected from the International Affective Picture System (IAPS; Lang et al. 2008). With regard to normative ratings of valence and arousal for females, emotional images were grouped into three valence categories: negative, neutral, and positive, with all images high on arousal levels in order to maximize the impact on underlying emotional circuitry. As a result of the high arousal ratings, the neutral category was renamed as "interesting." The inclusion of the interesting category allows for the arousal between valence categories to be controlled such that the emotional images vary across valence, but not arousal. No significant differences were found between any category for brightness and contrast. Stimuli were presented in nine blocks consisting of 10 images of the same valence category. The order of block presentation was pseudo-randomized to avoid consecutive presentation of blocks with similar valence. Each image was presented for 6 sec, followed by a 3-sec fixation cross and a 3-sec nonemotional landscape image. Images were back-projected onto a screen via an LCD video projector and were viewed by subjects through a mirror fixed to the scanner's head coil. Participants were instructed to simply pay attention to the images on the screen and to avoid regulating their immediate response to emotional content.
Imaging was performed using a 3.0 T Siemens Trio scanner. Thirty-six consecutive axial slices (4-mm thickness) parallel to the anterior–posterior commissure covering the whole brain were imaged using a T2*-weighted gradient echo EPI sequence (echo time [TE] = 32 msec; repetition time [TR] = 3000 msec; matrix = 64 × 64; flip angle = 90°). The field of view was 240 mm and the effective in plane functional spatial resolution was 3.75 mm. For each functional run, 360 volumes were collected after discarding the first six. For anatomical reference, high-resolution whole-brain images were also acquired: TR = 1570 msec; TE = 3.22 msec; flip angle = 15°; matrix 512 × 512 × 192 mm. Movement was minimized with padding, and an fMRI compatible eye movement system was used to ensure that participants attended to the stimuli and did not close their eyes during the experiment.
We tested for group differences in age, menstrual phase, hormonal birth control use, handedness, education, and depression (PHQ-9; Kroenke et al. 2001) and anxiety (GAD-7; Spitzer et al. 2006) symptoms. This was performed to ensure sample homogeneity between 5-HTTLPR × BDNF Val66Met groupings and to avoid potential confounding factors. Due to logistical constraints, estradiol and progesterone levels could not be measured. In order to prevent interference of online ratings during emotion processing (see Phan et al. 2003), participants were asked to rate each image on nine-point Likert valence and arousal scales immediately after the scanning session.
The imaging data was preprocessed and analyzed using the image processing routines implemented within the statistical parametric mapping software package, SPM8 (http://www.fil.ion.ucl.ac.uk/spm/software/spm8/; Wellcome Trust Centre for Neuroimaging). Images for each subject were first corrected for susceptibility-by-movement artifacts and then realigned to the first volume of the time series. Realigned images were spatially normalized into a standard stereotactic space (Montreal Neurologic Institute template) and smoothed with a Gaussian kernel (FWHM 8 mm) in order to minimize anatomical differences. The BOLD response at each voxel was modeled with a canonical hemodynamic response function and its temporal derivative.
For each participant, brain activation was examined for the contrasts of the emotional (positive, negative, and interesting) images relative to the nonemotional landscape images: emotional > nonemotional. These individual contrast images were then used in the second-level random effects model in order to determine regional responses for the whole sample. We conducted a whole-brain analysis in order to ensure the emotion processing task activated regions associated with emotional processing, and critically, our regions of interest (ROIs) including the bilateral rACC (operationally defined as the portion of anterior cingulate that lies anterior and superior to the genu of the corpus callosum, with the posterior boundary of y = +30 mm; Bryant et al. 2005) and the left and right AMY (as previously defined; Tzourio-Mazoyer et al. 2002; Maldjian et al. 2003). The rACC was defined bilaterally as clusters on the left or right rACC may be indistinguishable due to low spatial resolution at 3 mm. For all analyses, we employed an alpha level of P < 0.05 (partial volume, FDR-corrected) and a spatial extent of five or more voxels per cluster in order to control for type I error rates associated with multiple comparisons within the ROIs. The bilateral rACC and left and right AMY ROIs were subsequently employed in the analyses examining gene effects.
In order to determine whether there were effects of genotype, an omnibus analysis of variance (ANOVA) on the emotional > nonemotional contrast was performed for the ROIs rACC and AMY. Consequently, a second ANOVA was performed for the emotional > nonemotional contrast in order to determine whether there was an effect of the 5-HTTLPR genotype (S and L/L groups) within the rACC and AMY ROIs. These analyses were then followed up with independent samples t-tests in order to determine the directions of the effects. Similarly, a third ANOVA was performed in order to determine whether there was an effect of the BDNF Val66Met genotype (Met and Val/Val groups) within the rACC and AMY ROIs for the emotional > nonemotional contrast. In order to determine the direction of the effect, this ANOVA was then followed up with independent samples t-tests.
In order to test our a priori hypotheses for the 5-HTTLPR × BDNF Val66Met epistasis, we employed a 2 (S and L/L groups) × 2 (Met and Val/Val groups) ANOVA. The 2 × 2 ANOVA was then followed up with independent samples t-tests in order to determine the directions of the effects across the four cells. We then extracted beta weights from each participant from their whole-brain emotional > nonemotional contrasts in order to inspect the distribution of these beta weights within and between each genotype cell. This data analysis strategy was performed in order to increase our confidence in the findings obtained from the small sample of genetic groupings relating to the interaction effects or genetic epistasis.
In order to examine the relationship between subjective ratings of emotion processing and BOLD activation during emotion processing, a multiple regression was performed in IBM SPSS Statistics version 19. The dependent variable was the individual beta weights extracted from an exemplar ROI – the rACC was selected as its pattern of results was similar to that of the AMY – for the emotional > nonemotional contrasts. The predictors were the IAPS ratings of the valence and arousal ratings from the positive, negative, and interesting images and were entered altogether into the regression.
Participant characteristics and IAPS ratings across 5-HTTLPR × BDNF Val66Met genotype groups are displayed in Table 1. There were no differences between groups in age, stage of menstrual phase, hormonal birth control use, handedness, education, or depression (PHQ-9) and anxiety (GAD-7) symptoms. Participants' ratings of the valence of the stimuli were congruent with the categories of positive, negative, and interesting. Additionally, ratings confirm that participants found the stimuli to be arousing consistent with normative ratings of the stimuli.
Emotional stimuli activated regions including the inferior frontal gyrus, middle temporal gyrus, cuneus, precuneus, superior temporal gryus, middle occipital gyrus, middle frontal gyrus, superior parietal lobule, insula, cingulate cortex, caudate, cerebellum, thalamus, and AMY relative to the nonemotional landscape stimuli in the total sample of 28 participants, consistent with previous meta-analyses (Phan et al. 2002; Wager et al. 2010; Lindquist et al. 2012).
In order to determine whether there are effects of genotype within the rACC and AMY, an ROI analysis on all genotype effects for the total sample (N = 28) was performed. The analysis revealed a significant bilateral rACC cluster (k = 102; peak voxel at [−12, 36, 24], F = 4.02, P < 0.001 [partial volume, FDR-corrected], η2 = 0.56), left AMY cluster activation (k = 47; peak voxel at [−27, −3, −18], F = 3.30, P = 0.003 [partial volume, FDR-corrected], η2 = 0.51), and right AMY cluster activation (k = 30; peak voxel at [21, −3, −18], F = 2.79, P = 0.026 [partial volume, FDR-corrected], η2 = 0.47).
The rACC and AMY ROI analysis on the main effect of 5-HTTLPR (S, n = 9; L/L, n = 19) showed a significant bilateral rACC cluster (k = 370; peak voxel at [15, 39, 6], F = 12.57, P = 0.001 [partial volume, FDR-corrected], η2 = 0.27) and a left AMY cluster activation (k = 21; peak voxel at [−21, 0, −18], F = 8.32, P = 0.021 [partial volume, FDR-corrected], η2 = 0.20). Relative to L/L homozygotes, S carriers showed greater activation in the rACC (k = 231; peak voxel at [−12, 36, 24], t = 4.68, P < 0.001 [partial volume, FDR-corrected], d = 0.94) and a left AMY cluster activation (k = 42; peak voxel at [−27, −3, −15], t = 4.02, P < 0.001 [partial volume, FDR-corrected], d = 0.80). There were no significant activations for L/L homozygotes relative to S carriers.
The rACC and AMY ROI analysis on the main effect of BDNF Val66Met (Met, n = 12; Val/Val, n = 16) showed a significant right AMY cluster activation (k = 21; peak voxel at [27, −3, −15], F = 14.63, P < 0.001 [partial volume, FDR-corrected], η2 = 0.31) and an rACC cluster activation (k = 31; peak voxel at [−9, 36, 15], F = 5.93, P = 0.019 [partial volume, FDR-corrected], η2 = 0.15). Relative to Val/Val homozygotes, Met carriers showed significantly greater activation in the right AMY cluster (k = 21; peak voxel at [27, −3, −15], t = 3.83, P < 0.001 [partial volume, FDR-corrected], d = 0.77) and an rACC cluster activation (k = 109; peak voxel at [−9, 36, 15], t = 2.43, P = 0.009 [partial volume, FDR-corrected], d = 0.49). Conversely, Val/Val showed no significant activations relative to Met carriers.
The rACC and AMY ROI analysis on the 5-HTTLPR × BDNF Val66Met (S and Met, n = 4; S and Val/Val, n = 5; L/L and Met, n = 11; L/L and Val/Val, n = 8) interaction effect, with follow-up comparisons, is displayed in Table 2. Relative to all other groups, the S and Met group had greater activation in the rACC and AMY. Inspection of the distribution of beta weights between 5-HTTLPR × BDNF Val66Met cells demonstrated a clear interaction (as displayed in Fig. 1 with the rACC activation displayed as an exemplar as a similar distribution was found for the AMY). The activity of all the S and Met participants was increased and activity for all the L/L and Met participants was decreased, and the activity of S and Val/Val and L/L and Val/Val participants lay in between that of the former two genetic groupings.
In order to examine the relationship between subjective ratings of emotion processing and BOLD activation during emotion processing, a multiple regression of the IAPS ratings and the distribution of rACC BOLD activation was conducted. The IAPS ratings significantly predicted 43% of the variance (adjusted R2 = 0.268) in BOLD activation of the rACC, F(6, 21) = 2.645, P = 0.045. Ratings of both valence (interesting) and arousal (negative) were significant predictors.
The aim of this study was to determine the functional effects of 5-HTTLPR, BDNF Val66Met, and whether their epistasis impacts on emotion processing. Building on previous research (Wang et al. 2012), the 5-HTTLPR and BDNF Val66Met polymorphisms were found to interact in the rACC and the AMY during overt emotion processing in a homogenous, healthy sample of Caucasian females. The effect of the BDNF Met66 allele was moderated by the 5-HTTLPR alleles such that S and Met carriers displayed the greatest activation of the rACC and AMY in response to emotional images, while L/L and Met carriers had the least. Therefore, the epistasis of 5-HTTLPR and BDNF Val66Met is not only related to structural variation of the rACC, as reported previously (Pezawas et al. 2008), it is also associated with functional variation. Relative to all other groups, participants with S and Met alleles are more reactive to emotional stimuli generally. Findings such as these may have implications for the understanding of affective disorder development and maintenance (Martinowich and Lu 2008; Grabe et al. 2012).
A particularly novel finding obtained in the present study is the observation of a potential epistatic relationship of the 5-HTTLPR and BDNF Val66Met polymorphisms during emotion processing. Our data indicate that the vulnerable effects of the Met66 allele are – at least – partially dependent on 5-HTTLPR polymorphisms, such that the S allele in combination with the Met66 allele is associated with the greatest activation, while the L allele in combination with the Met66 allele is associated with reduced activity (Fig. 1). Therefore, we suggest that the S and Met combination is the most vulnerable against all other combinations, while the L/L and Met may be the least vulnerable. Serotonergic activity is partly due to the modulatory effects on the serotonin transporter (Mössner et al. 2000). Low 5-HTT efficiency in S carriers may reduce BDNF Val66Met gene expression and the less efficient Met66 allele may magnify this effect (Mamounas et al. 2000; Murphy et al. 2003; Martinowich and Lu 2008). This effect may result from impaired neurogenesis of serotonergic neurons (Ren-Patterson et al. 2005) supporting the circuitry underlying emotional experiences (Mukherjee et al. 2011). In contrast, our data suggest that the more efficient L/L genotype may compensate for the effects of the Met66 allele. Our findings further highlight the need for future neurocellular research to consider the impact of 5-HTTLPR and BDNF Val66Met epistasis on the neurogenesis of emotion circuitry.
Our findings indicated that participants with a combination of 5-HTTLPR S and BDNF Met66 alleles display the greatest activity in rACC and AMY in response to high-arousal emotional images relative to nonemotional landscape images. We also found that participant ratings of emotional stimuli were strongly associated with rACC activation during the presentation of the stimuli. This finding further supports the notion that differential rACC activity may be associated with individual differences in adaptive emotion regulation and response preparation (e.g., Roiser et al. 2012). Prior studies have reported that harm avoidance and neuroticism – well-validated, heritable personality measures linked to the risk of affective disorders – are also associated with the S allele of 5-HTTLPR gene (Lesch et al. 1996; Reif and Lesch 2003; Sen and Burmeister 2004), the Met66 allele of the BDNF Val66Met gene (Gatt et al. 2009), and heightened rACC and AMY activity in response to emotional stimuli (Keightley et al. 2003; Bertolino et al. 2005; Pezawas et al. 2005). The epistasis of 5-HTTLPR and BDNF Val66Met influences susceptibility for dysfunctional affective disorder-related personality characteristics (Lang et al. 2005; Ren-Patterson et al. 2005). For instance, the number of risk alleles increases susceptibility for rumination, with those of the S/S and Met/Met genotype at the most risk (Clasen et al. 2011). Our results suggest that individual differences in emotional reactivity may be underpinned, in part, by the epistasis of BDNF Val66Met and 5-HTTLPR polymorphism variants. Future examination of the 5-HTTLPR and BDNF Val66Met epistasis on emotion processing also should consider associated risk factors such as personality traits. This line of enquiry may provide further insights into the development and maintenance of affective disorders.
Our finding that the S and Met group was the most reactive to emotional stimuli – suggesting that it is the most vulnerable group – is consistent with that of Wang and colleagues (2012). Although they did not test for an epistatic relationship or interaction between 5-HTTLPR and BDNF Val66Met, they also found the S and Met group to be the most vulnerable genetic grouping against a combined non-S and Met group. While an earlier structural MRI study (Pezawas et al. 2008) reported the S and Val combination to be the most vulnerable against other combinations, a more recent study (Carballedo et al. 2012) reported the structural connectivity of the ACC and the AMY to be reduced in Met carriers. Within a multimodal MRI framework, future research should integrate the structural and functional lines of enquiry by examining the impact of the epistasis of 5-HTTLPR and BDNF Val66Met polymorphisms on the relationship between the structure and structural connections of regions involved in emotion processing as well as their function and functional connections.
A main effect for 5-HTTLPR was observed for emotional stimuli such that S carriers had greater activation in the rACC and AMY than L/L homozygotes. Together with the extant literature (see Murphy et al. 2012 for a meta-analysis), S carriers are more reactive to emotional stimuli. While there is debate as to the magnitude of the effect of the 5-HTTLPR polymorphism function on AMY function – Murphy et al. (2012) suggest the effect is smaller in magnitude than previously thought (Munafò et al. 2008) – our data demonstrate a moderate effect of this polymorphism on the AMY and a large effect on the rACC. These findings suggest that the effects of 5-HTTLPR may be stronger in the rACC than in the AMY, which in turn impact on AMY reactivity via reentrant feedback.
We also observed a main effect of BDNF Val66Met in the rACC and AMY, with Met66 carriers showing greater reactivity to emotional stimuli than Val/Val homozygotes; a finding consistent with previous fMRI research on emotion processing (Montag et al. 2008; Mukherjee et al. 2011). Additionally, previous behavioral (Beevers et al. 2009; Terracciano et al. 2010), structural (Pezawas et al. 2004; Carballedo et al. 2012), molecular (Chen et al. 2006), and fMRI memory consolidation (Egan et al. 2003) studies have identified Met66 carriers as being more at risk for affective disorders and related traits. Due to the lower neural plasticity associated with lower BDNF levels and impaired memory consolidation processes, it has been suggested that the BDNF Met66 allele reduces capacity for the retrieval of emotional memories (Mukherjee et al. 2011). This impairment consequently impacts the ability to process the present emotional context, and thus to respond to it adaptively (Mukherjee et al. 2011). The overreactivity displayed in BDNF Met66 allele carriers may be also associated with hyperactivity of neurovisceral networks (including the rACC; Lane et al. 2009) involved in the activation and regulation of the autonomic nervous system (Thayer 2006; Gatt et al. 2009), and our results suggest that these networks may be further and partially moderated by 5-HTTLPR status. Therefore, those carrying the BDNF Met66 allele may have a reduced capacity to strengthen networks that regulate reactivity to emotional stimuli through learning in previous emotional contexts.
Due to the infancy of research in this area (Martinowich and Lu 2008), a limitation that is faced by researchers is small sample size, which is then magnified when attempting to examine epistatic interactions. However, the large effects and clear differences between groups at the individual subject level within a homogenous sample are reassuring. Indeed, significant and strong fMRI findings obtained from smaller samples with conservative correction procedures may be true, rather than false, positives and consistent with findings from larger samples (Murphy and Garavan 2004), particularly within the imaging genetics paradigm (Meyer-Lindenberg et al. 2008). As there are known modulatory effects of hormone status (e.g., Felmingham et al. 2012) and sex on gene–brain (e.g., Everaerd et al. 2012) and gene-affective disorder vulnerability (e.g., Sjöberg et al. 2006), our findings are limited to the female sex only. Future studies employing emotion processing paradigms and recruiting larger, homogenous samples of females and males will broaden and increase confidence in findings on the impact of the functional epistasis of 5-HTTLPR and BDNF Val66Met on brain-behavioral correlates of emotion processing.
In conclusion, our preliminary study demonstrates a role for 5-HTTLPR, BDNF Val66Met, and their epistasis on emotion processing. Building on previous findings, our novel contribution to the literature is an illustration of a potential functional epistasis of 5-HTTLPR and BDNF Val66Met polymorphisms on emotion processing. The functional impact of the BDNF Val66Met allele may be partially dependent on 5-HTTLPR alleles, with the emotional reactivity of the rACC and AMY being implicated in this epistasis. Both Wang et al. (2012) and our findings, in independent samples and tasks, provide support for S and Met as a vulnerable genetic grouping. Future research on the epistasis of 5-HTTLPR and BDNF Val66Met should consider both its structural and functional impacts, employing large, homogenous samples of females and males. Working within a gene–brain–behavior framework, future clinical research should consider the potential for a structural–functional epistasis of 5-HTTLPR and BDNF Val66Met that may underpin vulnerability for affective disorders.
The authors T. O. and A. H. K. are supported by an Australian Postgraduate Award (APA) and a National Health and Medical Research Council (NHMRC) Career Development Award Fellowship (571101), respectively. This research was further supported by an Australian Research Council (ARC) Discovery Project (DP0987332) and an NHMRC Project Grant (464863) awarded to A. H. K. DNA was extracted by Genetic Repositories Australia, which is supported by an NHMRC Grant (401184). K. G. is supported by a scholarship from an ARC laureate. G. M. has received research support from AstraZeneca, Eli Lilly, Organon, Pfizer, Servier, and Wyeth. He has been a speaker for AstraZeneca, Eli Lilly, Janssen Cilag, Lundbeck, Pfizer, Ranbaxy, Servier, and Wyeth. He has been a consultant for AstraZeneca, Eli Lilly, Janssen Cilag, Lundbeck, and Servier. We acknowledge Jim Lagopoulos for his technical support in the planning and data collection stages of this research.
None declared.
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