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Brit woman stopped in Turkey was 'trying to cross into Syria'
A BRITISH woman has been stopped in Turkey on suspicion of trying to cross into Syria, according to a Turkish official.
The woman, 21, was stopped at a bus stop in the capital Ankara on Monday.
She is being held pending deportation hearings.
It is reported she was attempting to cross into war-ravaged Syria and travel to conflict zones.
Images and messages on the woman's phone strongly suggested she was intending to travel to IS-controlled areas.
The Foreign Office said: "We can confirm the detention of a British National in Ankara and are providing consular assistance."
Last month three teenage girls – Shamima Begum, 15, Kadiza Sultana, 16, and Amira Abase, 15 – crossed into Syria and are now believed to have joined Islamic State (IS).
Brutal terror group IS controls large areas of territory in both Syria and Iraq.
Meanwhile a 16-year-old boy whose two elder brothers have been killed waging jihad in war-torn Syria has been barred by a High Court judge from travelling abroad.
On Tuesday Mr Justice Hayden made the teen a ward of court which bars him from leaving England and Wales.
The judge made the ruling at a hearing in the Family Division of the High Court in London after social services staff in Brighton raised fears he could follow his siblings to Syria.
The youngster cannot be named for legal reasons.


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by Taki S. Raton
Milwaukee High School of the Arts (MHSA) and Golda Meir School social worker Jerrell Braxton earned state recognition when he was named Wisconsin School Social Worker of the Year for 2011-2012 by the Wisconsin School Social Work Association (WSSWA).
He was honored September 29 at the Midwest School Social Work Conference in Indianapolis where he represented Wisconsin. His award presentation was Friday, November 11 at the Heidel House in Green Lake, Wisconsin.
Braxton has been honored with numerous awards and accommodations to include Special Recognition by the Milwaukee Board of School Directors for 2011-2012, the Milwaukee Chapter Top Ladies of Distinction Celebrating Fathers & Mentors Award in 2007, the Milwaukee Common Council City Proclamation in 2003, and the Milwaukee Public Schools Excellence in Education Award in 1995.
His signature contribution to the arena of mentoring and to the positive development of young African American males is his Brothers of Kwanzaa (BOK) program at MHSA. The now 20th year consistent programming of BOK qualifies it as one of the longest running groups of its kind in the United States.
The major focus of BOK is to empower African American male participants to succeed academically, educationally and socially with the long range visioning of succeeding in life. This empowerment/support effort is designed to address issues and lend solutions that are presently fueling the deteriorating status of African American males in Milwaukee and throughout the country.
The group details five social indicators that have become challenging benchmarks to Black teens. These markers are Education, Health, Employment, Crime, and Life Expectancy.
BOK's primary emphasis is the development of critical thinking skills and survival skill training. These tasks are cultivated by promoting students to critique community speakers, review documentaries, participate in group discussions and learn from field trips opportunities.
"We believe that these engagements and other activities such as the arts, jazz and poetry encourages students to cooperatively work together and think about issues that affect their lives today and in the future," says Braxton.
He adds that the Brothers of Kwanzaa is a "self empowerment interactive program that promotes students to help each other gain interpersonal insight, increase motivation and improve academic performance."
Hundreds of young men at the Milwaukee High School of the Arts have been serviced over these 20 years cite Braxton. He reveals that the program has a 99% graduation rate with 85% of these students continuing to higher education, training programs and city service positions.
Mr. Braxton has a deep appreciation for our students and has committed himself to bringing out the best in each young man he works with," says Dena Radtke, Coordinator of School Social Work and School to Work Transition and Community Services for MPS.
For his work with BOK, he has received Special Recognition by the Milwaukee Board of School Directors for 2011-2012, the Brothers of Kwanzaa Leadership Award in 2007, the Brothers of Kwanzaa 15 Year Special Recognition Award in 2006 and was featured in the Milwaukee Magazine writing "First Person-Brothers Keeper" in 2007, and appeared as a guest feature on "Positively Milwaukee" in 1997.
He has been with Milwaukee Public Schools now for 23 years and has presented himself as a proud leadership model for MPS, for Milwaukee High School of the Arts and for our youth.
The Milwaukee community joins in this celebrative recognition of Braxton's proud achievement.

subset: commoncrawl


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Wednesday, 30 September 2015
Top 10 tips for success in Special Ed
Hello friends! I am currently enjoying my term 3 holidays and busily preparing for my wedding day in just 2 days!! Did I just hear you all squeal with excitement!! My hubby to be and I are beyond excited and we cannot wait for our big special day!
Amoungst all of the craziness here I thought I'd share my top tips for success in your Special Education classroom! Sooooo here goes..
1. Self Care- It is number one for a reason friends.. YOU NEED to look after yourselves! If you're not 100% neither will your cherubs be. Find a favourite calming thing to do, colouring in, playing music, going for a walk, etc etc. Find whatever works for you! Be the best YOU that you can be!
2. Unconditional Love- We've all had those bad days right? of course we have! The biggest part of our day to day business is to show children that no matter what, we unconditionally love and care for them because some days, lets face it, they will test the boundaries of our love in the most unloving ways, but the only solution to this is MORE LOVE!!! The tougher the day, the MORE LOVE that is needed... you all think I'm crazy right.... try it, then all me crazy ;)
3. Relationships... Relationships... Relationships- I cannot stress the importance of this one! Is there that one teacher at your school who just seems to 'get' the kids? when they ask any of the kids to do something, they just do it without question, but when you or any other teacher asks you brace for world war 3? Do you want to know their secret? RELATIONSHIPS!! Don't tell anyone (or tell everyone) because this is seriously a magic key to success! If you take the time to get to know the kids, find out what their interests are, find out who their family is etc you will develop a magically heart felt positive relationship. Not only will it help you in your classroom but it will create a positive role model of how to treat others in their lives! Cool Huh!
4. Work as a team- In most Special Education settings we are lucky to have the support of Teacher's Aides, or at my school SLSO. It is super important to value this person in your classroom! They are a big part of your classrooms day to day running. Once you approach the daily tasks as a team everyone will be happy, the kids see a solid, united front of support for them, and your teacher's aide feels valued and supported!! Win..Win!!
5. Build on each strength- "Together we have it all" Each child and adult will bring some different strengths to your classroom. CELEBRATE these!!! In our classroom we know that so and so is really good at maths, but thats great because I am really great at spelling! We can't all be the best at everything and it is so good to know each others strengths so the children know that they can ask so and so for help with maths etc. It builds on excellent collegial classroom and works wonders!!
6. Appreciate all of the positives- Sometimes you will have a bad day... Its bound to happen but take time to appreciate all of the positives, share them during your circle time with your kids! Share them at staff meetings and around the lunch table, this will help build a positive perspective lens for others looking into your classroom. Thank the children for all of their hard work and everything they put in to each day for you, and appreciate them! :)
7. Daily debrief- This is so important in our line of work. It is so important to remember to debrief at the end of each day so you don't take 'school stuff' home. Even if it is a excellent day, it is great to share the success and positives from the day. If you're not lucky enough to have a scheduled daily debrief as a team, find a teaching buddy and check in with each other every day. It will make a big difference!
8. Celebrate your successes- Were all so busy we sometimes forget to celebrate your success! The cherubs I get in my support class have often been disengaged with school for quite some time, I always remember the journey an the celebration of success for each child, that keeps me fresh and its why I love my job so much! Although the children are often the ones making the change, teachers need to take some credit and celebrate this success!
9. Build on your professional repertoire- Everything is always changing so it is super important to stay up to date with the current research. Your daily teaching and learning should be based on best practice, which always changes. It is so important to always read new information, about how the brain works, what courses these behaviours, why is this happening.. There are so many starting points for professional reading that will not only benefit you, but also your entire classroom! If you would like some recommendation, let me know in the comments :)
10. Enjoy! It truely is the best job in the universe! This should of been number one... Enjoy every moment, because learning knows no boundaries!
What tips can you add?
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Miss Smartie Pants
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The data is always recoverable if you're
Willing to pay the price.
First thing will be that you'll loose the Drive as it will be dismantled the platters removed and then coated with some green goup and then put into a special machine and every layer of data ever written to the drive will be recovered. Cost will be several Hundred Thousand $ + or - a bit.
When you say that the Drive is no longer recognised is that in a Windows Environment or in BIOS?
It's possible that the drive is still available but because you haven't used the software correctly that it's unavailable in the Windows Environment. The easiest solution is to reformat the drive and reinstall XP to it after running a Wiping utility like Boot & Nuke over it
And then restore all your data from your existing backup. It's much cheaper to do things that way.
Anyway before you ever use any new software that you haven't used previously you need to do a complete backup of all your data and then test the software ability to do the required job and even better your ability to use that software.
Anything less is both foolish and possibly dangerous.
thanks but that doesnt help
Thanks for your time but that was no help.
There is no backup of this data and I cant afford $1000 to have ADR recover this.
Reformat / nuke and boot? Doesnt sound right
Drive cant be seen in bios or windows
Check the Jumper setting on the HDD
IN a USB Caddy it should have been set to Cable Select but in the computer may need to be set to Master/Slave and also make sure that the jumper is still on the HDD.
It's possible that it's come off while you have been removing it from the USB Caddy and this will cause the drive not to be recognised in either BIOS or Windows though the important thing here is that you can see it in BIOS Windows isn't important as it may or may not be visible in there depending on what Partitions remain intact.
The proper way to do things is Boot & Nuke then Format when installing the OS or if this will be a slave drive go into Computer Management chose Drive Management and then select the 160 GIG HDD and use the Format Option.


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Glenn Martin
Listed by Re/Max Shoreline
Close to major routes, beaches, and golf courses. Unit has been freshly painted and new carpets. Complex has a pool and tennis courts. The unit has had many recent updates. New windows, new slider, new garage door. Interior, new carpets, new appliances, and Kitchen cabinets. Freshly painted as well. Pets are welcome upon Association approval. Limit 1 Dog or 2 cats. See attachment for PAS requirements and WFHM offer submittal information in MLS document section.
Date Showings Begin:
Delayed Showing: No


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Pope's message at funeral of Sister Lucia
A message from the Holy Father to Bishop Albino Mamede Cleto of Coimbra, Portugal, was read out at the funeral of Fatima visionary Sister Lucia. Cardinal Tarcisio Bertone, archbishop of Genoa, Italy, presided at the funeral Mass as the Pope's special envoy. The Pope wrote: "For Lucia, the visit by the Virgin to her and to her cousins Francesco and Jacinta, at Fatima in 1917, was the beginning of a special mission to which she remained faithful to the end of her days. Sister Lucia leaves us an example of great faithfulness to the Lord, and of joyous obedience to His divine will." The Holy Father recalled with emotion his various meetings with Sr Lucia, and "the ties of spiritual friendship which strengthened over time. I felt myself supported by the daily gift of her prayers, especially during difficult moments of trial and suffering. May the Lord give her ample reward for the great and hidden service she offered the Church. "I like to think that Sister Lucia, in her transit from earth to heaven, was welcomed by the One whom she saw at Fatima so many years ago. May the Most Holy Virgin now accompany the soul of this devoted daughter to the beatific encounter with the divine Bridegroom." On the eve of her death, the Holy Father had sent a fax to Sister Lucia in which he expressed his closeness and gave assurances of his prayers that she might "experience this moment of pain, suffering and sacrifice with the Paschal spirit" of death and resurrection. John Paul II met Sister Lucia, a Carmelite nun, on three occasions: on May 13 in the years 1982, 1991 and 2000. The first encounter took place exactly a year after the attempt on the Pope's life in St Peter's Square in which he almost died. On that occasion, the Pope went to Fatima to give thanks to the Virgin Mary for saving him, and ordered that, as a sign of gratitude, the bullet found in his jeep after the assassination attempt be set in the crown of the image of the Virgin of Fatima. The second meeting, in 1991, took place on the tenth anniversary of the assassination attempt. The last occasion on which the Pope and Sister Lucia met personally was on May 13, 2000, when the Holy Father beatified her cousins, the shepherd children Francisco and Jacinta, and Cardinal Secretary of State Angelo Sodano read a message concerning the third secret of Fatima. Source: VIS


text:
Ehlers-Danlos Syndrome:
- Ehlers-Danlos National Foundation
- Ehlers-Danlos Network C.A.R.E.S.
- EDS Today
- Ehlers-Danlos Support UK
Postural Orthostatic Tachycardia Syndrome:
- The Joyful Heart Foundation: "The Joyful Heart Foundation works to foster a community that turns toward the issues of sexual assault, domestic violence and child abuse."
- To Write Love on Her Arms: "A non-profit movement dedicated to presenting hope and finding help for people struggling with depression, addiction, self-injury and suicide."
- NDRI - The National Disease Research Interchange: Donations of tissue, organs or blood can be made for researchers to study rare genetic illnesses. These donations are prearranged and can be done during minor surgeries, major surgeries or postmortem.


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Locations Details
1697 Lower Curtis Rd, Elba, AL 36323
General Manager
Scott Davison
Kelley Foods Plant Manager
Scott Kelley
About Southeast
The City of Elba, Alabama, located in Coffee County in Southeastern Alabama, just 38 miles from the Florida State Line, is what a small town is supposed to be. Its great location with proximity to the nearby Gulf Coast beaches and major transportation routes.
Ben E. Keith and Kelley Foods of Alabama - Expanding to the Southeast from Ben E. Keith Foods on Vimeo.
Related News
Keith Kitchen Essentials 2017 Catalog
Jan 04, 2017
Check out the Keith Kitchen Essentials 2017 Equipment & Supplies catalog.
C.H. Guenther & Son named Ben E. Keith's Supplier of the Year
Oct 05, 2016
C. H. Guenther & Son was named Ben E. Keith Foods 2016 Supplier of the Year at the 33rd Annual Supplier Appreciation Dinner
Keith Kitchen Essentials Q4 2016 Catalog
Oct 04, 2016
Check out our forth quarter 2016 Equipment & Supplies catalog
Ben E. Keith Foods Announces Acquisition of Kelley Foods of Alabama
Sep 08, 2016
Ben E. Keith Foods proudly announces its intent to purchase Kelley Foods of Alabama. The acquisition includes all assets of Kelley Foods including the Elba, AL, distribution center and the manufacturing division, which produces quality sausages and hams, as well as other custom products under the Kelley Foods name. Closing is expected to occur September 30, 2016.


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Herb's Garage & Arman Auto Service Center
ReScore Reviews™ (4)
98% Would Recommend
Latest Review 1 day ago
Review for Herb's Garage & Arman Auto Service Center
Jonathan B. on 09/12/2015
Jonathan said this business goes the extra yard and he really appreciates it. When his girlfriend was in the hospital they drove him home in his vehicle which was very sweet of them. He would like to see them keep up the good work.
Vehicle: Volvo V70
Category: Service
Service Date: 09/11/2015
Review Created: 09/12/2015
This review was collected via phone interview by Customer Research Inc.


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Mau Sep 6, 2012
Watch in HD!
is this xbox of ps?
Xbox since on PS3 it would say Lan Party instead of system link.
oh nice video mate!
i know how to do this its the SLE glitch lol
look closely its say press (A)
that was before i watched the video duhhhhhhhhhhhhh
your meant to comment after you watch the video duhhhh :LOL:
no i like to comment before , after , and sometimes even between..
Separate names with a comma.


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I have been diagnosed with a fatty liver and have high liver enzyme levels. I don't need help quitting and have gone without alcohol for over a week at time. I am about 30 lbs. overweight as well. I have had periods where 2 fingers in my left hand are numb at times but don't know if this is related.
Am I at risk for D.T.'s? I'm 54 and drink 1 bottle of wine/night 4-5 times per week (last 10 years)?
- Asked
- 8 Jul 2014 by Anne5689
- Active
- 9 Jul 2014
- Topics
- obesity, alcohol, nonalcoholic fatty liver disease, wine, liver, diagnosis
Responses (2)
Hi, you may or may not suffer withdrawal symptoms... as you don't drink EVERY day & can have a week alcohol free, you body is used to short periods of abstaining. You may find that you suffer more from psychological withdrawal, and i would suggest you seek support with quitting. Such as AA or SMART groups. I would recommend you ask your doctor his opinion of your physical health with regards to stopping drinking, if he has any concerns about you doing it without a detox?
Further Information
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Discussion in 'Gamers' Pulse' started by JakobwithaK, Jul 12, 2009.
Damn shes fine.
Allison Carroll, just like it says in the video if you had actually watched it
she hot as fuck man
Am I the only one that thinks they couldve picked a better model? If I remember right there was a thread when this set of pics came out and they were all just as ridiculous as this one
WTF indeed. :hsr:
I'd hit it. Still.
i dont get the "wtf" part
ohz noes she doesnt have a tan in every nook of her body, or am i missing something else here
digusting. would not hit.


text:
North Bay Imports
Review for North Bay Imports
AL P. on 06/20/2012
"prompt, professional service; excellent advice, fair prices"
have been using about one year; most impressive operation. chris is great; fair, tells it like it is, delivers on promise at a good price. i trust my A4 to north bay completely; will never return to dealer unless it's a warranty situation.
Vehicle: Audi A4
Service Date: 06/19/2012
Review Created: 06/20/2012 08:07 PM


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The first introductory statistics text written specifically to make statistics accessible for health science students . Assuming no prerequisites other than high school algebra, the authors provide numerous examples from health settings, a wealth of helpful learning aids, as well as hundreds of exercises to help students succeed in the course.
Concepts, principles, and methods at an introductory level. Annotation c. Book News, Inc., Portland, OR (booknews.com)


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Bob Weir announces 'Campfire Tour'
Grateful Dead co-founder Bob Weir has announced a short fall tour across America supporting his first solo album in a decade, titled 'Blue Mountain'. His Campfire Tour kicks off October 7th in San Rafael and plans to visit Oakland, Los Angeles, Upper Darby, Brooklyn (2 shows), Port Chester and Nashville. Weir recently finished a summer tour with Dead & Company which visited 19 cities across the U.S.
Bob Weir will be releasing his new solo album 'Blue Mountain' on September 30th, 2016 through his new label, Columbia/Legacy. It's his first album in 30 years composed of entirely new material and was inspired by his time working at a ranch in Wyoming when he was fifteen. The album features guitarists Aaron Dessner and Bryce Dessner, and bassist Scott Devendorf, plus collaborations with singer-songwriter Josh Ritter on select tracks. Aside from the new album, Weir is also writing a book along with developing a new Grateful Dead TV series.
Bob Weir Concert Schedule
No Events! =(Track Bob Weir!
About Bob Weir Tour Albums
Bob Weir appeared on the Pop / Rock scene with the release of the album 'Gonesville' released on November 30, -0001. The track '' quickly became a success and made Bob Weir one of the fastest growing performers at that time. Later on, Bob Weir came out with the extremely famous album 'Ace' which includes some of the most well-known tracks from the Bob Weir collection. 'Ace' includes the single 'Black-Throated Wind' which has proven to be the most sought-after for music lovers to see during the performances. In addition to 'Black-Throated Wind', many of other tracks from 'Ace' have also become sought-after as a result. A few of Bob Weir's most famous tour albums and songs are displayed below. After 2017 years since releasing 'Gonesville' and making a true impact in the industry, followers continue to head to see Bob Weir in person to perform favorites from the entire catalog.
Bob Weir Tour Albums and Songs
Bob Weir Concert Tour Questions & Comments
Bob Weir Tour and Concert Ticket Information
- Tour dates for Bob Weir is located on top.
- Bob Weir concert schedule has finally been released.
- Tickets for the forthcoming Bob Weir concert can now be purchased.
- Concert schedules for all Bob Weir concerts are revised on a regular basis.
- Backstage passes will not be any concern, we always have top quality tickets.
Bob Weir could be coming to a city near you. Browse the Bob Weir schedule on this page and click the ticket link to view our big selection of tickets. Look through our selection of Bob Weir front row tickets, luxury boxes and VIP tickets. After you track down the Bob Weir tickets you need, you can purchase your tickets from our safe and secure checkout. Orders taken before 5pm are normally shipped within the same business day. To purchase last minute Bob Weir tickets, look for the eTickets that can be downloaded instantly.


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Classic White Porch - 80 Breezy Porches and Patios - Southernliving. Hanging ferns area a classic look for any Southern porch. Container gardens and a lush border add color to this space. Porches: Creating the Space
Make This DIY Wooden Doormat….a fun family project!
Stone Porch - 80 Breezy Porches and Patios - Southernliving. Randomly placed stepping-stones crafted from local granite lead to this front porch's wide steps. Hand-hewn posts and railings, along with (Patio Step From House)
Front Porch Addition Design Ideas, Pictures, Remodel, and Decor - page 4
Potted plants are one of the easiest ways to dress up any space! Be sure to check out these gorgeous porch planter ideas and inspiration front and back porches before sprucing up your own outdoor space.
Christmas on the Front Porch. Vintage Christmas decor ideas for your front porch (Christmas Porch)
balcony with pair chairs side table and garden seat porches amp structures


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Product Description
This item has been discontinued & is a clearance product. All clearance items are sold as-is and are final sale, no returns, exchanges or refunds
These Ladies Compression Socks Pink Argyle from Dr. Seagal's will provide increased circulation, reduced swelling and feature 15-20 mmHG True Graduated Compression Therapy. Features an attractive Argyle Pattern
Material - 75% NYLON / 25% LYCRA / 15-20mmHg / Latex Free
- INCREASES CIRCULATION to help prevent blood clots during long periods of sitting or standing such as travel or work
- REDUCES SWELLING and leg fatigue to give your legs increased energy
- Assists in the prevention of varicose and spider veins for optimal leg health
- Beautiful, comfortable fibers for easy wear
- Latex free
- Special anti-odor properties help eliminate foot odor
- Non restrictive band and toe box for added comfort
- Pink/Grey Argyle
- Refer to sizing chart picture for best fit
Available in Size : B for Women's


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The induction of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a key regulator of mitochondriogenesis, is well-established under multiple physical exercise regimens, including, endurance, resistance, and sprint training. We wanted to determine if increased expression of PGC-1α in muscle is sufficient to improve performance during exercise in vivo. We demonstrate that muscle-specific expression of PGC-1α improves the performance during voluntary as well as forced exercise challenges. Additionally, PGC-1α transgenic mice exhibit an enhanced performance during a peak oxygen uptake exercise test, demonstrating an increased peak oxidative capacity, or whole body oxygen uptake. This increased ability to perform in multiple exercise paradigms is supported by enhanced mitochondrial function as suggested by increased mitochondrial gene expression, mitochondrial DNA, and mitochondrial enzyme activity. Thus this study demonstrates that upregulation of PGC-1α in muscle in vivo is sufficient to greatly improve exercise performance under various exercise paradigms as well as increase peak oxygen uptake.
- exercise capacity
- peak oxygen uptake
- peroxisome proliferator-activated receptor γ-coactivator-1α
peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α) and its closely related family member PGC-1β are coactivators essential for various cellular processes, including mitochondrial biogenesis, oxidative metabolism, and energy homeostasis (24, 26, 46). The PGC-1 proteins partner with a variety of transcription factors, including nuclear receptors such as the PPARs, estrogen-related receptors (ERRs), and hepatocyte nuclear factor 4α, as well as the nuclear respiratory factors (NRFs) and myocyte enhancer factor 2 (MEF2) (23, 27, 29, 40, 42, 46). Several experimental approaches in vitro as well as in vivo have established the role of PGC-1s as key regulators of mitochondrial gene expression, function, and biogenesis (40, 46). Both PGC-1α- and PGC-1β-deficient mice have been generated, and although both models exhibit impaired mitochondrial gene expression, and decreased mitochondrial area, they exhibit only slight changes in mitochondrial respiration during basal conditions (2, 21, 22, 25, 41). Conversely, they exhibit significantly decreased mitochondrial function during states that require increased energy, such as exercise and cold challenge (21, 22, 25, 41). Muscle-specific PGC-1α transgenic mice exhibit an increased expression of multiple markers of slow fiber-type muscle in type 2 muscle fibers, whereas muscle-specific PGC-1α knock-out mice display the converse shift in muscle fibers (11, 23). Furthermore, skeletal muscle from the PGC-1α transgenic mice exhibit a decreased fatiguability ex vivo, while muscle-specific PGC-1α knock-out mice demonstrate decreased exercise capacity (11, 23). Similarly, muscle-specific PGC-1β transgenic mice demonstrate increased mitochondrial gene expression, a fiber-type switch to oxidative myosin heavy chain type IIX fibers, and an improvement in exercise capacity (3). Together, these in vivo models indicate that PGC-1α and PGC-1β are important modulators of mitochondrial function.
Physical training induces muscle remodeling as well as mitochondrial biogenesis within skeletal muscle, resulting in multiple physiological changes, including fiber-type conversion from glycolytic to oxidative fibers, enhanced mitochondrial function, increased oxidative capacity, and improved metabolic flexibility (6, 10, 13). The expression of PGC-1α is induced in muscle following both an acute exercise challenge or following long-term exercise training (4, 18, 32–34, 37). Furthermore, inactivity and denervation are associated with decreased PGC-1α expression (17, 39). However, it is not known if an upregulation of PGC-1α and the subsequent mitochondrial biogenesis is sufficient to improve exercise capacity in vivo. It was recently demonstrated that an inducible, muscle-specific PGC-1α transgenic mouse model exhibited diminished exercise capacity as a result of decreased glycogen utilization (44). Using an independent mouse model, we wanted to investigate if an upregulation of PGC-1α in skeletal muscle of PGC-1α transgenic mice is sufficient to improve exercise capacity during voluntary and forced exercise paradigms. We demonstrate that increased PGC-1α expression in muscle results in an enhanced ability to exercise under various regimens and improves peak oxygen uptake.
Animal studies.
All mice used were maintained on 12:12-h light-dark cycle and cared for in accordance with animal welfare regulations under an approved institutional Animal Care and Use Committee protocol in the Novartis Institute for BioMedical Research animal facility, which is accredited by the Association for Assessment and Accreditation of Lab Animal Care. PGC-1α transgenic mice were rederived before use, and male transgenic and wild-type littermates were used for all experiments (23).
Male PGC-1α and wild-type mice were individually housed and fed a standard chow diet (LabDiet, St. Louis, MO) ad libitum. Body weight and food intake were measured twice weekly. Body composition was determined using MRI, and fat and lean mass measurements were normalized to body weight. Fasting and fed blood glucose concentrations were determined using the OneTouch Ultra Glucometer (Lifespan, Milpitas, CA). To examine glucose tolerance, an oral glucose tolerance test was performed. Mice were fasted for 16 h, orally gavaged with a glucose solution (2 g/kg), and blood glucose readings were measured at baseline, 15, 30, 60, and 120 min following gavage. To examine insulin tolerance, an insulin tolerance test was performed. Mice were fasted for 4 h, injected intraperitoneally with Vetsulin (0.5 U/kg) (Intervet, Millsboro, DE), and blood glucose readings were measured at baseline, 15, 30, 60, and 120 min.
To collect insulin levels, tail blood was collected in EDTA-blood collection vials during a fed state or following a 16-h fast, and insulin was quantitated using an Ultra Sensitive Rat Insulin enzyme-linked immunosorbent assay kit (Crystal Chem, Downers Grove, IL).
Determination of exercise capacity.
To examine voluntary exercise capacity, 4-mo-old male mice were housed in cages equipped with exercise wheels. Mice were placed in a mouse single activity wheel system (Lafayette Instrument, Lafayette, IN), voluntary wheel-running was measured for 72 h, and the data were analyzed using the Activity Wheel Software (Lafayette Instrument).
Before exercise testing, the mice were acclimatized to the treadmill by running the day before the test for 10 min at 10 m/min followed by 2 min at 20 m/min. To determine exercise capacity under an endurance paradigm, 4-mo-old male mice were placed on a six-lane treadmill (Columbus Instruments, Columbus, OH) and run with a fixed slope of 10°. During the first 30 min, the speed was 10 m/min and increased 2 m/min every 15 min thereafter. The protocol is shown schematically in Fig. 1C and is similar to that previously performed (44). Animals ran until exhaustion, which is defined as remaining on the shocker plate for more than 10–15 s. Work performed (J) was calculated as previously described (31).
Exercise capacity during a higher-speed challenge was determined during the peak oxygen uptake (V̇o2) challenge. To determine peak V̇o2, 6-mo-old male mice were placed in an enclosed treadmill (Columbus Instruments) for 5 min at a 0° incline and 0 m/min. The mice were then challenged with 1.5-min intervals of increasing speed at a 15° incline. The protocol is shown schematically in Fig. 1E. The increasing speeds used in the protocol were 10, 14, 18, 22, 26, 28, 30, 32, 34, 36, 38, and 40 m/min. The protocol was performed until exhaustion, as defined above. Relative exercise intensity was derived by calculating the treadmill speed as a percentage of the maximal speed achieved by that genotype at peak V̇o2.
To examine the peak V̇o2 and respiratory exchange ratio (RER) values during exercise, 6-mo-old male mice were subjected to the peak V̇o2 test described above in an enclosed treadmill attached to the Comprehensive Laboratory Animal Monitoring System (CLAMS) (Columbus Instruments). Measurements were collected for 5 min before the exercise challenge, throughout the challenge, and following failure until values approached baseline. Air flow through the treadmill was 0.6 l/min, and V̇o2 and carbon dioxide production (V̇co2) readings were acquired every 15 s. Data analysis was performed using the Oxymax software (Columbus Instruments).
Glycogen content quantification.
The gastrocnemius muscle and liver were harvested from 6-mo-old male mice in an ad libitum state, flash-frozen in liquid nitrogen, and pulverized, and approximately 50–100 mg was used to isolate glycogen. Briefly, samples were incubated with 500 μl of 30% sodium hydroxide and incubated for 30 min at 75°C (liver) or 86°C (gastrocnemius). The samples were cooled on ice, 1 ml of absolute ethanol was added, and incubated overnight at −20°C. The precipitated glycogen was recovered by centrifugation for 20 min at 840 g, washed with absolute ethanol, and incubated for 2 h at −20°C. Following centrifugation for 20 min at 5,000 g, the glycogen was resuspended in 250 μl distilled sterile water, hydrolyzed with an equal volume of 1 N HCl for 2 h at 99°C, and cooled to room temperature. The sample pH was neutralized by the addition of 23 μl of 10 N NaOH, and the glucose concentration was determined using the Amplex red kit (Molecular Probes, Carlsbad, CA).
Analysis of mRNA expression and mitochondrial DNA content.
Six-month-old male wild-type and PGC-1α transgenic mice were euthanized in an ad libitum state, and gastrocnemius and heart muscles were harvested. Gastrocnemius muscle samples were pulverized, and total RNA was isolated using TRIzol reagent (Invitrogen, Carlsbad, CA) and quantified using a spectrophotometer at OD 260 nm. Reverse transcription was performed using the BD Sprint PowerScript kit (Clontech, Mountain View, CA), and quantitative real-time PCR (Q-PCR) was performed using Assay-on-Demand primer probes (Applied Biosystems, Foster City, CA). Average relative mRNA expression values were calculated for each group using 2−ΔΔCt, where Ct is cycle threshold (as described by Applied Biosystems, Foster City, CA) using β-2-microglobulin (B2M) as an endogenous control, and with the expression of wild-type mice normalized to a value of 1. The mRNA expression of B2M is similar for both wild-type and PGC-1α transgenic mice, and the Assay-on-Demand primer probes exhibit similar efficiencies. Statistical significance for each gene was determined using the Student's t-test comparing the transgenic mice with the wild-type controls.
To determine mitochondrial DNA (mtDNA) content, genomic DNA was isolated from 50 mg of pulverized gastrocnemius muscle using the DNAeasy tissue kit (Qiagen, Valencia, CA). DNA was quantitated using a spectrophotometer at OD 260 nm, and 40 ng of genomic DNA was used to amplify cytochrome b (mitochondrial encoded gene) and β-actin (nuclear-encoded gene) using Q-PCR. The β-actin primer probe set was obtained as an Assay-on-Demand, and the cytochrome b primer probe was generated by using the following sequences: forward primer 5′-TTC ACA CCT CAA AGC AAC GAA-3′, reverse primer 5′-GCC CCC AAT TCA GGT TAA GAT AA-3′, and probe 5′-CGC CCA ATC ACA CAA ATT TTG TAC TGA ATC C-3′.
Citrate synthase activity assay.
Gastrocnemius and tibialis anterior muscles isolated from 6-mo-old male mice were pulverized and lysed in RIPA lysis buffer supplemented with a complete protease inhibitor cocktail (Roche, Indianapolis, IN). Total protein content was assessed using the BCA protein assay kit (Pierce, Rockford, IL). Citrate synthase (CS) activity was determined using 2 μg of total protein using the CS assay kit (Sigma, St. Louis, MO).
Data analysis.
Data are presented as means ± SE. All statistical analysis was performed using Prism 4.0 (GraphPad 4, San Diego, CA). Differences between a two-tailed Student's t-test or ANOVA were considered statistically significant if P < 0.05. To determine statistical significance of RER values at relative exercise intensity, an area under the curve (AUC) was performed using the mean RER at rest for each genotype as baseline.
PGC-1α transgenic mice demonstrate increased exercise capacity.
To determine if increased PGC-1α expression in skeletal muscle impacts the ability of mice to perform exercise, we investigated the exercise capacity of PGC-1α transgenic mice under various exercise paradigms. We evaluated the ability of these mice to perform voluntary exercise during a 3-day wheel-running experiment. During the first day housed in the treadmill cages, the mice experienced an acclimation period, resulting in high activity for both genotypes. During the second day, the PGC-1α transgenic mice exhibited greater voluntary exercise, as observed in a significant increase in speed (counts/min) (Fig. 1A). Furthermore, during the course of the experiment, PGC-1α transgenic mice traveled 27% further on the voluntary wheel compared with wild-type mice (Fig. 1B).
To determine if the increased voluntary exercise observed in the PGC-1α transgenic mice translated into increased performance during a forced exercise challenge, we examined their ability to perform a forced treadmill run. We examined the exercise capacity of PGC-1α transgenic mice during a slow, endurance-type running challenge. This challenge consisted of running the mice at a constant speed of 10 m/min for 30 min and then increasing the speed 2 m/min every 15 min (Fig. 1C). The mice were run until failure, which was defined as remaining on the shock-grid for greater than 10 consecutive seconds. During this endurance exercise paradigm, the PGC-1α transgenic mice ran significantly longer distances (Fig. 1D). Similarly, during the exercise challenge, the PGC-1α transgenic mice ran for a duration of 121.9 ± 3.4 min, a significant increase compared with the 88.2 ± 3.3 min the wild-type mice ran (P < 0.0001). Further, the PGC-1α transgenic mice attained a maximum speed of 23.4 ± 0.44 m/min, significantly faster than the 18.85 ± 0.47 m/min that the wild-type mice reached (P < 0.0001). Together, this indicates that increased PGC-1α expression in skeletal muscle results in greater performance during an oxidative challenge.
To determine if PGC-1α expression in skeletal muscle also improves performance during a shorter, more intense exercise paradigm, the PGC-1α transgenic mice and littermate controls were subjected to a treadmill exercise challenge designed to measure peak V̇o2 value. This peak V̇o2 challenge consisted of 1.5-min intervals of increasing speed at a fixed 15° incline (Fig. 1E). Consistent with the endurance challenge, the PGC-1α transgenic mice ran longer distances during this exercise test (Fig. 1F). The PGC-1α transgenic mice also reached a higher maximum speed, 39.25 ± 0.99 m/min compared with the speed wild-type mice achieved, 29.25 ± 0.84 m/min (P < 0.0001). Furthermore, the PGC-1α mice ran for 24.46 ± 0.78 min, whereas wild-type mice ran for 16.88 ± 0.513 min (P < 0.0001). This increased exercise capacity during these different exercise paradigms is consistent with the finding that isolated muscle from PGC-1α transgenic mice exhibits decreased fatigability in response to electrical stimulation ex vivo (23).
PGC-1α transgenic mice demonstrate increased peak oxygen uptake and reduced RER values during exercise challenge.
To investigate the peak oxygen consumption, or oxygen uptake at a whole body level, in PGC-1α transgenic mice, we performed a peak V̇o2 exercise challenge in an enclosed treadmill and acquired real-time respiratory measurements using indirect calorimetry (Fig. 1E). In both groups, V̇o2 values increased linearly as speed increased until the point of failure (Fig. 2A). As mice fail during the exercise challenge, the treadmill is stopped and V̇o2 measurements continue to be taken, resulting in a decrease in V̇o2 values. The curves in Fig. 2A represent the mean V̇o2 profiles and the inflection point corresponds to the mean peak V̇o2 value on failure. Figure 2B illustrates the mean peak V̇o2 during this exercise challenge for PGC-1α transgenic and wild-type mice. The PGC-1α transgenic mice demonstrated a 24% increase (P < 0.0001) in their peak oxygen uptake compared with their control littermates. Comparatively, an 8-wk-long endurance training regimen induces only a 15% increase in peak oxygen uptake in humans (9, 12).
We examined the RER (V̇co2/V̇o2) values during the peak V̇o2 exercise challenge to investigate fuel utilization during exercise. During the beginning of the capacity test, while the mice were either at rest or running at low speed, both wild-type and PGC-1α transgenic mice exhibited low RER values (0.799 ± 0.013 for wild-type mice and 0.806 ± 0.011 for PGC-1α transgenic mice), indicating the utilization of fatty acids for fuel (Fig. 2C). However, as the treadmill speed increases during the capacity test, RER values increase, indicating a switch from fatty acid oxidation to glucose oxidation as the predominate fuel source. In wild-type mice, this increase in RER values occurred at low speeds during the exercise challenge (Fig. 2C). Conversely, the PGC-1α transgenic mice were able to exercise at higher speeds before an increase in RER values was observed. Consequently, at speeds above 10 m/min, the PGC-1α transgenic mice exhibited significantly lower RER values (Fig. 2C). This suggests that PGC-1α transgenic mice were capable of utilizing fatty acids and sparing carbohydrate stores at higher speeds during this exercise challenge. We normalized for the increased exercise performance by PGC-1α mice by examining RER values at similar relative exercise intensities. When the data are presented as the percentage of speed achieved at maximal peak V̇o2, the PGC-1α transgenic mice continue to exhibit significantly lower RER values (Fig. 2D). Together, these data indicate that PGC-1α transgenic mice exhibit lower RER values at either the same absolute exercise intensity (speed), or the same relative exercise intensities (percentage of maximum speed at peak V̇o2).
PGC-1α transgenic mice show no alterations in glucose tolerance or insulin sensitivity.
Poor physical fitness is a known risk factor for developing Type 2 diabetes, whereas exercise training has been shown to improve insulin sensitivity (7, 8, 43). Therefore, we investigated if the increased exercise performance and peak oxygen uptake observed in the PGC-1α transgenic mice influenced whole body glucose homeostasis or insulin sensitivity. Glucose and insulin levels under fed and fasting conditions in PGC-1α transgenic mice did not differ compared with wild-type mice (Fig. 3A and Table 1). During an insulin tolerance test (ITT), PGC-1α transgenic mice exhibit similar insulin sensitivity compared with wild-type mice (Fig. 3B). Further, we also performed an oral glucose tolerance test (OGTT) to examine glucose homeostasis and observed similar glucose excursion curves in PGC-1α transgenic mice compared with their wild-type littermates (Fig. 3C).
To address the impact of enhanced mitochondrial content on additional metabolic parameters, we examined PGC-1α transgenic mice at both 2 mo and at 7 mo of age. We observed no differences in body weight, body composition, or body core temperature between the transgenic and wild-type mice (Table 1). Furthermore, analysis of energy expenditure (V̇o2) and activity revealed no differences between the transgenic and wild-type mice (Table 1). Thus the PGC-1α transgenic mice do not exhibit any differences in multiple metabolic parameters under basal conditions.
Expression of PGC-1α in skeletal muscle induces mitochondrial DNA levels, mRNA expression, and enzyme function.
We performed quantitative real-time PCR (Q-PCR) to examine the expression of the PGC-1α transgene in gastrocnemius and heart muscles. In agreement with a previously published report, we observed a 16-fold increase in PGC-1α mRNA expression in gastrocnemius tissue (see Supplemental Fig. S1, available with the online version of this article) (23). Furthermore, we determined that the PGC-1α transgene is expressed at low levels in the heart (Supplemental Fig. S1). Next, we investigated the effect of increased PGC-1α expression on various mitochondrial pathways. Previous studies have illustrated increased expression of cytochrome c (CYCS), cytochrome oxidase II (COXII), and cytochrome oxidase IV (COXIV) in this mouse model (23). In gastrocnemius muscle of PGC-1α transgenic mice, we observed increased mRNA expression of genes important for the fatty acid transport and oxidation, OXPHOS genes, as well as genes important for the tricarboxylic acid (TCA) cycle, including fatty acid binding protein 3 (FABP3), fatty acid translocase (FAT/CD36), fatty acid transport protein 1 (FATP1), carnitine palmitoyltransferase 1b (CPT1b), medium-chain acyl dehydrogenase (MCAD), long-chain acyl dehydrogenase (LCAD), very long chain acyl dehydrogenase (ACADVL), CYCS, COXIV, ubiquinol-cytochrome c reductase binding protein (UQCRB), and isocitrate dehydrogenase (IDH3a) (Fig. 4A). We also observed alterations in select markers of the muscle fiber type in PGC-1α transgenic mice, consistent with a previously published report (Supplemental Fig. 1) (3). Furthermore, mRNA expression of the reactive oxygen species (ROS)-scavenging genes, superoxide dismutase-2 (SOD2), thioredoxin reductase-2 (TXNRD2) and catalase, were also increased (Supplemental Fig. 1), consistent with the recent finding that PGC-1α null mice exhibit decreased expression of ROS-detoxifying enzymes glutathione peroxidase-1 (GPX1) and SOD2 and are sensitive to multiple oxidative stressors (38). Increased mRNA expression of transcription factors essential for mitochondrial function, ERRα and mitochondrial transcription factor A (TFAM), was also observed (Supplemental Fig. 1).
We investigated mtDNA content by examining the ratio of cytochrome b to β-actin. We found that PGC-1α transgenic mice exhibited a 166% increase in mtDNA compared with wild-type controls (Fig. 4B). We next inspected the activity of CS, an enzyme of the TCA cycle and a well-validated marker of mitochondrial activity. Figure 4C demonstrates that the PGC-1α transgenic mice exhibited greater than twofold increases in CS activity in both the gastrocnemius and the tibialis anterior muscles. To further examine mitochondrial enzyme activity, we investigated the expression of pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial enzyme that controls metabolic substrate utilization. PDK4 induces fatty acid oxidation at the expense of glycolysis through the phosphorylation and inactivation of the PDH enzyme complex (16, 32). We investigated expression of PDK4 in the gastrocnemius muscle of untrained PGC-1α transgenic and wild-type littermates and observed an increase in PDK4 mRNA (Fig. 4A).
Expression of PGC-1α in vitro has been shown to increase complete fatty acid oxidation, resulting in an increased storage of glycogen (17, 30). Consistent with these experiments, PGC-1α transgenic mice exhibited a 57.6% increase in glycogen stores in their skeletal muscle in the fed state (Fig. 4D). There was no difference in liver glycogen content, consistent with the muscle-specific expression of PGC-1α in this model (data not shown). We performed Q-PCR to determine a possible mechanism by which the PGC-1α transgenic mice exhibited increased glycogen content. We demonstrate that the transgenic mice exhibited decreased expression of glycogen phosphorylase but no change in mRNA for other genes important in glucose utilization (Fig. 4E). These data are consistent with a recent report demonstrating that inducible, muscle-specific expression of PGC-1α results in increased glycogen stores through multiple mechanisms (44).
It is well-established that various types of exercise induce PGC-1α expression in rodents and humans (1, 4, 15, 32, 34). This occurs coincident with increases in many aspects of mitochondrial function, including mitochondrial number, enzyme function, and expression of genes critical for mitochondrial function (5, 6, 14). However, at least one study demonstrates the increase in mitochondrial number/function occurs before the induction of PGC-1α (45). Further, skeletal muscle-specific expression of PGC-1α in an inducible manner results in decreased exercise capacity as a result of decreased glycogen utilization (44). Therefore, it remains unclear whether the PGC-1α induction observed on exercise training is sufficient to improve exercise capacity in vivo.
Previous work in PGC-1α transgenic mice demonstrates a fiber-type switch from glycolytic to oxidative muscle fibers and decreased fatigability during an ex vivo electrical stimulation assay (23). Consistent with these data, we demonstrate that these mice exhibit an increase in exercise ability during multiple exercise challenges. Further, the peak V̇o2 challenge demonstrated that expression of PGC-1α in skeletal muscle is sufficient to increase the aerobic capacity by 24% compared with their control littermates; the magnitude of this change is greater than what is observed following an intense exercise training regimen in humans (9, 12). Interestingly, both whole body and skeletal muscle-specific PGC-1α knock-out mice exhibit decreases in both voluntary physical activity levels and exercise capacity during forced treadmill training (11, 22). Furthermore, it has been recently demonstrated that activators of SIRT1, such as resveratrol, increase skeletal muscle mitochondrial content, oxidative capacity, and exercise capacity, through the deacetylation and activation of PGC-1α (19). Together, these data suggest that increased PGC-1α expression and/or activity in skeletal muscle is necessary and sufficient to improve exercise performance and peak oxygen uptake.
The magnitude of improvement in peak V̇o2 in the PGC-1α transgenic mice is suggestive that central factors may contribute to the improved exercise performance. We demonstrate that the PGC-1α transgenic mice exhibit a large increase of PGC-1α mRNA expression in gastrocnemius skeletal muscle, as well as a small increase in the heart (Supplemental Fig. S1). It is unknown if this twofold increase in PGC-1α expression contributes to the improved exercise capacity, as no analysis has been performed to examine cardiac structure or function in this transgenic mouse model. Multiple mouse models demonstrate that high expression of PGC-1α in cardiac muscle results in cardiomyopathy (20, 35). However, until additional experiments are performed to examine cardiac function in these mice, it is not possible to exclude the contribution of twofold increase in PGC-1α expression in heart to the improvements observed in peak oxygen uptake and exercise performance.
A recent report by Wende et al. (44) demonstrates a diminished capacity during a high-intensity exercise challenge in a different PGC-1α transgenic mouse model. Their paper used an inducible transgenic model to examine the consequences of PGC-1α induction for 3–4 wk, whereas the mouse model we utilized expressed PGC-1α constitutively (44). In addition to these temporal differences in transgene expression, the two mouse models likely exhibit differences due to expression levels (23, 44). The unexpected decrease in exercise capacity in the inducible PGC-1α transgenic mouse model is explained by a decreased ability to utilize glycogen during exercise. Wende et al. used forced exercise paradigms at significantly higher speeds to elicit these differences. In comparison, in our mouse model, we demonstrate increased performance both in a voluntary as well as in two forced exercise paradigms. Additionally, we challenged the mice at a slightly older age, and the overall decreased exercise capacity in the control animals at this age may have allowed us to detect a difference in exercise capacity between the genotypes. It is not unprecedented that two independent PGC-1α transgenic mouse models exhibit different phenotypes; the mouse model we examined prevents denervation and fasting-induced skeletal muscle atrophy whereas an independent model results in increased muscular atrophy (28, 36).
Another interesting finding illustrated by this work is that the PGC-1α transgenic mice exhibit lower RER values during a peak V̇o2 challenge. This may be explained by the reduced relative workload (percentage of peak V̇o2) experienced by the PGC-1α transgenic mice compared with wild-type mice. Since the PGC-1α transgenic mice exhibited an increase in peak V̇o2, they experienced a reduced percentage of their peak V̇o2 throughout the challenge compared with wild-type mice. To address this possibility, we examined RER values at the same relative exercise intensity. After comparing the RER values at the same percentage of maximal speed achieved during the exercise test, we demonstrate that the PGC-1α transgenic mice continue to exhibit lower RER values. Therefore, the PGC-1α transgenic mice exhibit lower RER values when examined at either absolute exercise intensity or relative exercise intensity. Although normalizing for relative exercise intensity decreases the divergence, the result is suggestive that the PGC-1α transgenic mice are capable of utilizing fatty acid as fuel for longer periods of time during exercise. Additionally, the RER values in PGC-1α transgenic mice never exceed 1.0 during the peak V̇o2 challenge, suggesting that these mice achieve a more complete oxidation of fuel during exercise. In fact, the PGC-1α transgenic mice may exhibit a greater capacity for utilizing fatty acids as fuel at a molecular level. Consistent with this, we demonstrate increased expression of genes necessary for lipid transport and oxidation, indicating that PGC-1α has pleiotropic effects on lipid utilization. These in vivo results are consistent with in vitro findings that PGC-1α expression stimulates fatty acid oxidation and induces complete fatty acid oxidation at the expense of incomplete fatty acid oxidation (17, 40). However, further studies are required to investigate lipid utilization and lipid flux in a dynamic setting to determine if the PGC-1α transgenic mice demonstrate greater fatty acid utilization in vivo.
Patients with Type 2 diabetes exhibit decreased mitochondrial function and impaired peak oxygen uptake. We demonstrate that the induction of PGC-1α in skeletal muscle is sufficient to increase both mitochondrial function, exercise ability, and peak oxygen uptake in vivo. However, under these circumstances, we were not able to detect any differences in glucose homeostasis or insulin sensitivity in the PGC-1α transgenic mice. It is possible challenging the PGC-1α transgenic mice with a high-fat diet or utilizing a more sensitive detection method such as the euglycemic hyperinsulinemic clamp may be necessary to reveal improvements in insulin sensitivity.
We advanced the characterization of mitochondrial function in the skeletal muscle of PGC-1α transgenic mice by demonstrating increased gene expression of various key mitochondrial pathways, including those involved in oxidative phosphorylation, TCA cycle, fatty acid oxidation, and ROS scavenging. We further demonstrate increased mitochondrial function by illustrating increased mtDNA, as well as enhanced CS activity and mitochondrial gene expression. The increased mitochondrial function shown here suggests that the PGC-1α transgenic mice may be better prepared to handle a metabolic challenge. This is exemplified by the ability of these mice to sustain fatty acid oxidation during the metabolic stress of an exercise challenge. Therefore, as patients afflicted with obesity or Type 2 diabetes are often unable to cope with metabolic stresses, increasing PGC-1α function in skeletal muscle may be a viable therapeutic strategy for the treatment of these patients.
We thank Stacey Shaughnessy for assistance with mouse husbandry, and Valerie Beaulieu, Kerry Pierce, and the Metabolic Profiling and Automation Group for help with the assays described in this study. We also thank Dr. Zhidan Wu for discussion and critical reading of the manuscript.
Parts of the manuscript were presented at the Keystone Symposium on Nuclear Receptor Pathways to Metabolic Regulation held at Steamboat Springs, March 27–April 1, 2007.
Present address of J. Lin: Life Sciences Institute and Dept. of Cell & Developmental Biology, Univ. of Michigan Medical Center, Ann Arbor, MI 48109.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2008 the American Physiological Society


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Brownwood ISD Registration Process
Brownwood ISD has announced the schedule for student registration for the upcoming school year. For students who attended the district in the 2016-2017 year, registration will be completed online this year.
Beginning July 31st, parents of returning students will complete all documentation through their txConnect Parent Portal account (https://brownwood.tx.txeis15.net/txConnect/Login.aspx). Resource documents can be found on the left hand navigation. If anyone requires assistance with the online registration, he/she may attend a registration session for new students, as listed below.
For students who are NEW to BISD this year, registration will take place per the following schedule:
(Note: Students/Parents new to BISD must come in to finalize the process)
Grades PK - 6th @ Brownwood Administration Office
- Monday, July 31, from 7:30 a.m. to 4:30 p.m. or
- Tuesday, August 1, from 11:30 a.m. to 6:00 p.m.
Grades 7 - 8 @ Brownwood Middle School
- Wednesday, August 2, from 7:30 a.m. to 4:30 p.m. or
- Thursday, August 3, from 11:30 a.m. to 6:00 p.m.
Grades 9 - 12 @ Brownwood High School:
- Wednesday, August 2, from 7:30 a.m. to 4:30 p.m. or
- Thursday, August 3, from 11:30 a.m. to 6:00 p.m.
The parent or guardian of each new student must provide the following:
1) Parent/guardian photo ID
2) Child's birth certificate
3) Child's Social Security card
4) Child's up-to-date immunization record
5) Proof of address:
A) If you OWN your home, bring ONE of the following:
- Purchase contract or mortgage with date of possession (not closing date)
- Current electric, water, or gas bill
B) If you RENT your home, bring ONE of the following:
- Signed lease or rental agreement, including move-in date
- Current electric, water, or gas bill
C) If you LIVE WITH ANOTHER FAMILY, the homeowner or renter must accompany the
Parent/Guardian to enroll new students. All of the following must be submitted:
- A BISD Student Residency Statement available at registration
- An electric, water, or gas bill in the owner's/renter's name
6) Information from the last school attended
7) Court documents affecting the parent/child relationship
*NEW PK STUDENTS ONLY - Proof of previous month's income or letter of eligibility for SNAP or TANF benefits must also be presented.
If you have any questions about BISD's registration process, please call 325.643.5644.


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Garrettsville Area Chamber of CommerceThink Local: Live, Shop, and Dine in Historic Garrettsville
Home » Membership Directory » Bars & Taverns
Slim & Jumbo's
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(330) 527-0485 (Business)
Slim & Jumbo's is a member of the Garrettsville Area Chamber of Commerce. Your continued support of member businesses helps promote the local economy, and funds many of the community activities you enjoy.
Become a Chamber Member


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Book: The International Dimension of the American Society of Agronomy: Past and Future, 2010
Published by: American Society of Agronomy
For more than 100 years scientists have made the American Society of Agronomy a force for international change to improve agriculture. Learn the linkages and meet some of the luminaries. The real treasure of this book is its look forward with "viewpoint" essays from leading agronomists who prophesize the future of world agronomy in the context of changing diets, food crises, biofuels, fertilizer trends, the emergence of organic agriculture, the underinvestment in agricultural research, and more.
Table of Contents


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|Yoshi Ruler's Hut
|Greater Location
|Yoshi's Island
|First Appearance
|Super Mario: An Evil Rising
|Current Ruler
|Yoshi Ruler
Super Mario: An Evil Rising
When Waluigi arrives on Yoshi's Island, Yoshi Ruler allows him to live in the hut. Yoshi Ruler gives Waluigi two missions and after Waluigi finds a way home, Yoshi life becomes normal again. Later, when the Mushroom Behemoth is revived and begins a rampage by crushing the island, bits of the hut can be seen flying around.


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One week after I told my class that I thought that either China or India would build infrastructure for hydrogen fuel cell cars before any of the western countries did, the New York Times reports that China is trying to become the world leader in electric cars. So I was close! My reasoning was that hydrogen cars require a fair bit of supporting technology – especially a system of refueling stations – and that it would be much easier to build this infrastructure in an economy where the petrol car system wasn't so deeply embedded. At the same time, you need a reasonably big market to make the whole thing work, which means China or India (or maybe Brazil).
John and I were discussing this issue of economic embeddedness this afternoon with regard to our research on project-based firms, who face a relatively unique set of innovation challenges due to the high level of interdependencies within their work. The same applies a the level of countries – in order to accommodate a new innovation, in many cases ties to previous systems have to be broken first. In the case of cars, there are a whole lot of ties that need to be broken before an entirely new system like electric or hydrogen can be put in place. Consequently, I think there is a very high chance that these technologies will spread widely first in a place with fewer existing ties to break.
I can't take credit for making a correct prediction yet, but if China goes electric, I guess that still leaves India with a great chance to build a hydrogen fuel cell industry! And I'll even take credit for the prediction of Brazil manages it first…
(I first found this story through worldchanging.com – a very good website and blog that is well worth checking out)


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Item description for Terra Madre: 1600 Food Communities by Slow Food Editore...This book describes 1,600 Food Communities in 150 countries: from the hatahata fishermen of Kitaura in Japan to the raisin producers of Herat in Afghanistan; from Ethiopian forest coffee pickers to Mexican vanilla growers. Farmers, shepherds, fishermen, pork butchers, vine-dressers...all people who embody a new idea of agriculture based on taste quality, sustainability and social justice. All they demand is fertile soil, clean seas, sufficient water and the free circulation of information, knowledge and produce. Of these communities, 300 are Slow Food Presidia, developed worldwide to save food products in real danger of extinction.
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e-Boks.dk V 3.0.6 for Android 4.0.3+ With e-Boks you can access your digital mail from public authorities and private companies.
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Providers Should Prepare for RACs Expanding Into Medicaid
As part of the healthcare reform package approved last month, federal government agencies must expand the current recovery audit contractor program to Medicaid and Medicare Parts C and D no later than December 31, 2010.
One initial reaction of this announcement might have someone asking "Isn't that what Medicaid Integrity Contractors (MIC) are for?" Unlike RACs, MICs, which are part of the Medicaid integrity program, do not receive any portion of recoupment funds.
"It is unlikely that this will give providers any relief from the perceived inaccurate payments by the Part C plans as this does not appear to address those payments," says Kimberly Anderwood Hoy, JD, CPC, director of Medicare and compliance for HCPro, Inc. "The Part C RAC provisions appear to focus on CMS payments to Part C RAC contractors rather then their payments to providers."
On the Medicaid side, this will be difficult because instead of four main RACs, there could be 50 different Medicaid RACs, though it remains to be seen how this will be implemented. Perhaps there will be some aggregation of the states, but unlike Medicare, it will be difficult because each state has different Medicaid provisions.
During the RAC demonstration project, which only operated in New York, Massachusetts, Florida, South Carolina, and California, RACs successfully corrected more than $1 billion in overpayments from providers and underpayments refunded to providers. Experts say those figures will surely rise with the implementation of the permanent RAC program and expansion into Medicaid and Medicare Parts C and D.


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|Green City Painters
|Serving New York and surrounding area
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114 Reviews
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Keeping building exteriors and room interiors looking fresh and spruced up can be as simple as adding a new coat of paint – but inexpert painting work can actually devalue a building. What you need is professional painters who really know their stuff. Whether you're looking at home painting, hope to find the best apartment painters or want to keep a commercial building looking smart, finding the right contractors is the first step.
Painting is often not recognized as an actual profession', and a lot of people try to DIY the job, or outsource it to an unskilled handyman, but from prepping your surfaces to choosing the right paints and coatings, there's much more to painting than meets the eye! Getting real professionals in can actually save you money in the long term – let alone mess, fuss and hassle.
The best house painting contractors in NYC are well worth your consideration – and if you embarked on a failed DIY painting project already, they'll come and fix up the mess with ease.
New York City's Industrial and Commercial Painting Contractors
Commercial painters in NYC know how to get the job done quickly, efficiently, neatly and with minimal disturbance to your work activities. They understand the need for you to continue with business as usual. A professional commercial or industrial painter will meet with you before the project begins so that you can discuss how work should be scheduled to minimize its impact on your business day.
For example, interior areas may need to be painted over weekends so that the paint will have dried and the fumes will have dispersed before your workforce arrives for work. You can't give everybody a couple of days off just because their offices are being refurbished! Exterior wall painting is usually a lot easier, but you may have concerns here too, especially if you're running a busy yard with lots of comings and goings.
You may not even have considered the practical implications of your decorating project, but a real professional will know what you should consider and will discuss the details with you so that you aren't confronted with any surprises and won't have to face extensive disruptions to your busy work schedule.
Your painting job improves your business' image – but only if it's properly done. Remember: most of the work lies in proper preparation of surfaces – and after that it's all about a neat and durable finish.
Pricing of Exterior and Interior House Painting Services in NYC
Price is important, but it's not everything. There's more to wall painting than many of us realize. It's not just a matter of deciding on your colors. For example, you might want to know if interior PVA is washable. The best contractors know their products and will be ready to answer your questions.
If you're about to relocate, you may be looking to get house or apartment painters in so that you can either let your property, sell it, or reclaim your full deposit if you're renting. Making wear and tear good before you move out can save you big time – either in deposits recovered or in a better asking price when you rent out or sell your current home.
While you might be looking for cheap prices, you also need to consider issues such as whether your contractors are licensed and insured. After all, accidents happen! What if your apartment painters accidentally spoil your carpet by spilling a can of paint? If you're using professional painting contractors, you should be covered, but if you DIY or get a 'handyman' in to do the job, you aren't! When considering pricing, take these issues into account.
Even when we're looking at outside painting, cost isn't everything. Sure, some lads might be willing to take the task, but what if they break a window or splash paint all over it? Using pros with the right equipment and experience for residential paint jobs is really the only way to go for savvy homeowners.
A gorgeous wooden floor and attractive wooden window-frames are big selling point for any home, but staining them yourself can result in messy finishes, hassle and unnecessary expense. Not only will affordable contractors in New York provide you with affordable prices, they'll also ensure that you get your money's worth!


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Turn On The Taps
Sweat is good. Stink? Not so much. Use your odour to win her over.
Women are more sensitive to body odour than men are, according to a study by scientists at the Monell Chemical Senses Centre. Men and women were asked to rate the strength of underarm odour alone and when fragrances were used to block underarm odour. Male underarm odour was harder to block with fragrances than female underarm odour – suggesting that sweat conveys important information to women, which is why it's so hard to block their perception of body odour. So that doesn't mean you should give up on deo. To tap into sweat's seductive powers, play touch rugby, volley ball or group frisbee on the beach – women find men who take part in team sports as more desirable mates. Mate-attracting pheromones are excreted by scent glands in your skin as you sweat. Neither of you will consciously notice the pheromones, but they register in the part of your brain that controls sexual urges and triggers desire.
READ MORE ON: seduce any woman sweat


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May I quickly remind everyone that when we were first asking Chowhounder's how to build this site, it was made very clear to us that favoritism has no place in Chowhound. Yet, the ability to quickly scan threads to see if their favorite hounds are posting is at the top of almost everyone's wish list.
We'll build the site however you'd like, but I'd appreciate some clarification.


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GraphicRiver 16 Pages Interior Catalog-Template 9475868
Photoshop \ Print Template \ Brochures \ Catalogs
Design \ Interior \ Included \ Photoshop \ Brochure \ Catalog \ Bifold \ Resolution
Print Template - 16 Pages Interior Catalog-Template 9475868 by jillur-milon @ GraphicRiver
Photoshop \ Print Template \ Brochures \ Catalogs
This is a bi-fold interior design catalog.Clean, Stylish and print ready design. You can easily edit color, font, image.
All are PSD layers and smart object.
Photo are not included, download link attached in help file.
File Information.
- Size: 420×148 mm(A5)
- Pages: Bifold(16 page)
- Resolution: 300 dpi
- Color mode: CMYK
- Bleed: 6mm
- Working file: Photoshop cs,
- Files included: Photoshop cs5 (psd)
- Font used.
Open Sans
Layered: Yes; Graphics Files Included: Photoshop PSD; Minimum Adobe CS Version: CS4; Print Dimensions: 420x148.
Business Brochure Template; Square Trifold Business Brochure; Bi-Fold Corporate Brochure; Tri- Fold Corporate Brochure; One Page Clean Resume/CV; Corporate Bifold Brochure; Bifold Brochure-Template.
Keywords: 16 pages, bi-fold, bifold, brochure, brochure template, brochures, business, catalog, clean, corporate, design, editorial, flexible, furniture, interior, letter, marketing, minimalist, modern, multipurpose, print, print ready, professional, template.


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- Please select a date to see the proper prices!
- Meal can be requested on the spot
Best offer
107.78 € / person / night, no meal
Description of the accommodation:
Rooms, services 30 comfortably furnished rooms are offered by Hotel 115 Christchurch to guests looking for accommodation in Christchurch. If you wish to learn more about the exact scope of services provided by Hotel 115 Christchurch (including those available for an extra fee) or about the equipment of the rooms, you can find the complete list on the information sheet below.
Payment For the reservation you may need to provide advance payment by credit card or credit card guarantee, depending on the exact date, room and price.
Arrival, opening hours The personnel can communicate with you in English.
Hotel 115 Christchurch rooms Rooms
- Please select a date to see the proper prices!
Accommodation services


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This season, Y-3 explores parts unknown with a brave, bold, kinetic collection inspired by aviation: its pioneering history and, tantalizingly, its future. Shown during Paris men's fashion week at Couvent des Cordeliers, January 25th, 2015, the collection captured the magic of flight and the possibility of broadening horizons, pairing this message with elegant, sleek, strong sportswear and colorful accessories. Men's and women's pieces debuted side by side in a sharply tailored aesthetic—think peaked shoulders, cinched waists, and masterful outerwear—that at the same time pushed the limits of future tech. Models walked the runway to music by Jiro Amimoto, enjoyed by front-row guests including adidas tennis icons Ilie Nastase and Jo-Wilfried Tsonga, perhaps a glimpse of what's next on Y-3's radar.
From the origins of humanities pursuit of flight to the exciting future of space travel, flight remains an endlessly fascinating subject matter that is eternally relevant. In this collection, Yohji Yamamoto melds these two worlds—the nostalgia for flight's past and the promise of its future—to create clothes that break boundaries. Inspired by pioneers of flight like Amelia Earhart and the Royal Air Force, Yamamoto conjures a classic silhouette realized in futuristic fabrics and with a trailblazing modern spirit. Regal, refined, and elegant, these clothes elevate sport-style to new heights.
The season's silhouette is tailored and slim and arrives in a strict color palette driven by its Royal Air Force inspiration: steel blue, dark navy, cool gray. These sober hues are livened by inventive new interpretations of classic camouflage in bold graphic patterns like a black-and-white chevron. Y-3's ever present signature patterns are more richly applied than ever—not merely printed on top of fabrics but engineered into them. The result is 21st-century camo that is innovative and never obvious. Melding past and future, the collection employs a range of fabrics, from classics like wool flannel, cotton twill, and French terry to innovative materials like Tyvec and neoprene.
Yamamoto's vision for women begins with a brilliant range of essential outerwear executed in a variety of shapes, colors, patterns, fabrics, and techniques. Classic short jackets play intriguingly with oversize details, be they decorative epaulettes, roomy open pockets, or dramatic collars. Long coats indulge Yamamoto's iconic flair for volume—a sleek track jacket pleated on one side, a floor-length parka billowing in shape, or an exquisitely tailored modern redingote. Y-3 essentials round out the women's offering with neat A-line dresses, cropped voluminous capes, and punkish sweaters cleverly adorned in parachute straps and taping.
Y-3 men's follows a similar trajectory, envisioning innovative takes on classic sportswear. Tailored jackets are cropped, sharp and cool, from a blouson inlaid with contrasting fabrics to a military blazer featuring trimmed in dangling straps. The clash of tradition and future becomes evident in a perfectly tailored trench with nipped, belted waist (tradition) and tight, short, shiny leather A-1 flight jacket (future). The men's collection also makes brilliant use of eye-popping three-stripe motifs and humorous graphic slogans based on imagined air traffic control chatter.
As always, Y-3 presents striking innovations in footwear. Boots reign supreme for men and women this season, realized in multiple fabrics and heights but almost always in solid black. For punches of bright colour, the breakthrough Qasa shoe returns in new fabrics and colour ways—the grounding force of a collection inspired by aviation.
[youtube id="C8VAPQ1pa78″ width="610″ height="360″]
Shop New Season Y-3 >>>>>
Shop Y-3 Clearance >>>>>
Tags: Y3, yohji yamamoto


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Not Accepting Guests
- Last login over 5 years ago
Join Couchsurfing to see Alexia's full profile. It's free!
About Me
Travelling all over the word.!
Girl, 22, french, open-minded, curious, interested in everything, responsible. Living for travelling and meeting new people, from other countries and other cultures.
Life isn't about finding yourself.
Life is about creating yourself.
Why I'm on Couchsurfing
At the time, any experience but I'm travelling by Australia this year and it could be a great way to meet people and see how they are living. I prefer inviting my host for some drinks or to a restaurant then paying a room in a hostel!
Art & Photo. I'm totally passionate about Art (specially contemporary art). I love Architecture, Design and Photography too. I'm taking pictures of everything, every little thing which catch my attention, every detail of a place, a face... a feeling.
Music. I can't imagine my life without music, I could listen to music all the time.
Travelling. I can say that travelling is my motor, it's my way to feel alive and to learn so many things about our world and about people.
Sport. I also like sport (I mean watching sport!), tennis is my favourite one (Come on Roger!) but I'm looking at a lot of international events. I'm not really a sportive girl, however, I like hiking, biking and I'd love to try skydiving (maybe in the Great Barrier Reef) and bungee jumping.
Computer. I'm interested in computer and all web stuffs. I'm kind of addicted to internet but I'm trying to live without (or better with less internet, it's so easier with internet for everything!).
- arts
- architecture
- design
- contemporary art
- photography
- drinking
- traveling
- socializing
- music
- cycling
- hiking
- bungee jumping
- skydiving
- sports
- tennis
- study abroad
Music, Movies, and Books
Cinema. I like almost all the movies, ones more then others of course but I'm really not critical about movies. I just can say that I'm not a fan of science fiction or pure action movies. In my favourites you can find : L'Auberge Espagnole (The Spanish Apartment), Garden State, Erin Brockovich, The life of David Gale, Revolutionary Road, Thelma and Louise, A love song for Bobby Long... ans so much more!
Music. About music, that's more or less the same thing, I don't dislike anything, I find good things in all music styles. Preference for pop&rock, reggae, hard-rock, soul, depending on my humor!
Books. For books, it's really more difficult for me, I love some french autors like Amélie Nothomb or Eric-Emmanuel Schmitt but I'm complicated in litterature! I appreciate really strange stories! I'm also used to read a lot about societal topics. I have to confess that sometimes I enjoy relaxing just reading some stupid women's magazine, fashion trends, beauty tips.
One Amazing Thing I've Done
Meeting people from everywhere during my Erasmus experience in Barcelona last year, an incredible meltin-pot in a wonderful city.
Teach, Learn, Share
Teach. I can teach some French and Spanish.
Learn. I definitely want to improve my English, so necessary in our world!
Share. Always very motivated to do some photography trips, just cameras, our feet or a car and the inspiration of the places!
Countries I've Visited
Andorra, Australia, Belgium, Czech Republic, Egypt, Germany, Morocco, Netherlands, Spain, Sweden, Switzerland, Turkey, United Kingdom
Countries I've Lived In
France, Spain


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Trinity revenues benefit from MEN deal
THE Manchester Evening News and its sister titles have contributed revenue of £18.2m and operating profits of £2.7m to their new parent Trinity Mirror.
The quoted newspaper group bought the MEN and 30 other titles belonging to GMG Regional Media in March for £7.4m and the cancellation of a £37.4m printing contract.
Half-year figures from Trinity, which also owns the Daily Mirror, the People, the Liverpool Daily Post and Echo and a string of 150 other smaller titles, show the deal also helped hold up group income whi... For the full story register now for free or login below...


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Defino,1900 arg
I think I might know why the "F" is in lower case rather than capitals. One of the reasons might be that when a woman gets married she keeps her maiden name, however she adopts "de" meaning "of". For example if a woman's maiden name is Teresa Bueno, if shemarriesJose Diaz, her name then becomes Teresa Bueno de Diaz. At least that is the tradition in the Latin-American countries.


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Warwick General Guide by Nishimurason
Not Updated For Current Season
This guide has not yet been updated for the current season. Please keep this in mind while reading. You can see the most recently updated guides on the browse guides page.
Thank You!
Your votes and comments encourage our guide authors to continue
creating helpful guides for the League of Legends community.
Warwick Build
Ability Sequence
Not Updated For Current Season
The masteries shown here are not yet updated for the current season, the guide author needs to set up the new masteries. As such, they will be different than the masteries you see in-game.
This build is very strong in DMG and will kepp you alive and going in even 1v3s. I focus mainly on the on-hit effecs and DMG because Warwick relies on his auto attack as his main source of DMG. Items like Madreds Bloodrazors and Wits End are very important to Warwick because of those on-hit effects. This is my very first build, constructive critism and comments would be greatly appriciated.
Amazing ganker
Great survivability
A very good chaser due to blood scent
Best ingame jungler
Very susceptible to early game counterjungle/ganks
Very mana reliant
Leaves a a teammate in a 1v2 situation
Team dependent
I go with a 21-0-9 because i play Warwick as a dps champion. I pick up the improved smite and the extra magic pen. but besides that its the normal 21-0-9.
Another option is the 0-21-9, this will give you a little more armour, health, and bulkyness in the beginning but the jungling route wont be to intense, so i dont recommend this but it is an option none the less.
These items are very strong on Warwick because he relies on hit effects (Bloodrazor, Malady, Wits End Ect...). The only item I feel i should explain is the Hextech Gunblade. I picked this item because it gives major bonuses it provides Warwick. The lifesteal for obvious reasons, the spell vamp for his bite, the DMG for ult and auto attack, the AP because his bite scales AP, and the Passive Bonus of the item (slow and 600 DMG). It may be substituted for a Bloodthirster, but i believe this to be a better choice.
I go with flat DMG runes marks and Quints (Reds and Bronze), armour seals (Yellows), and attack speed glyphs (Blues) for the sheer hitting power, speed, and survivability in the jugle/laning phase in the beginning. You could substitute the glyphs for mana/sec for even longer jungle/laning duration but I feel they arent neccasary when your getting the Blue Golem almost every chance it spawns.
Skill Combo
I use a R,W,Q repeat combo. This combo is for more of a 1v1 situation because it imobilizes one champion and it focuses on mainly the high burst from ult and sustaned power from the W. Another combo I use is a Q,W,R this is more of a team fight because if you get targeted in the middle you can easily flash out, but if you kill the enemy with your ult it can just serve as a killing blow and you may still flash out.
Summoner Spells
I picked Smite for one very obvious reason, for speed jungling. Speed in the jungle is key to picking up the quick levels and buffs so you may quickly overpower your enemies.
And secondly I picked Flash. Flash is by far the best summoner spell because of its many uses. You can flash to get away from enemies, to engage, to set up ganks, ect...
Ghost is also a viable option as well as exhaust. I say this because in the beginning your blood scent will speed you up but not a significant amount, it will allow you to catch up with them but not use many auto attacks. Ghost and Exhaust can keep you with them so you can keep hitting them and keep bringing them down.
Creeping / Jungling
Ok, so my Warwick Technique is a little odd. I call it periodical jungling because you spend only about 20 percent of your time in the jungle.
The Order- The 2 small golems, lane, when they spawn grab them again, lane more, grab the blue and then the red, and from there on lane and grab any buff on your side of the map anytime it comes up. I do this to get the extra XP from the jungle creeps. As your laning you are sharing XP with another player, but when you jungle you are getting the solo XP. When you are getting the jungle solo XP your teammate is also getting the solo XP, so its very beneficial for you and your teammate.
Ganking and Ult Usage
Ganking is one of Warwicks strongest attributes. ALWAYS gank when the oppurtunity presents itself, the extra gold and kill/assist is very good for you and your teammate.
Ult Usage- Warwicks ultimate can be used as a initiator and a finisher. I personally use it when I engage an opponent so i can get them into low health ASAP to activate blood scent. The other choice is to finish with it, you can auto attack and bite to get them around half health and then use your ult so they put you into blood scent. Chase them and easly net yourself a kill.
Tips and tricks
There are a few key things i always do when i play Warwick, the first being i stay completely passive until level 6. (Excluding the times when your teammate engages and there is a chance you might net a kill.) Another is that if someone comes into turret range have your ult ready to be casted because if they take turret aggro even once you can suppres them in the range and easily pick them off and gain a kill.
This build will hopefully help you become a better Warwick player, and give you those higher scores that everyone looks for. As i said before this is my first build and i would greatly appriacate help,tips, and advice. Thanks.


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Oxford County takes a bold step towards becoming a leader in waste reduction
Oxford County is acting on its Zero Waste objectives of reducing the amount of waste being produced in, and exported out of, Oxford County by maximizing recovery efforts and extending the lifespan of the Oxford County Waste Management Facility.
A series of reports and technical documents have been received by Oxford County Council following a series of Waste Audits and an assessment of Waste Recovery and Reduction Technologies (WRRT).
The waste audits were conducted by AET Group which included:
An assessment of Waste Recovery and Reduction Technologies was completed by SLR Consulting (Canada) Ltd. This included a review of existing approaches to waste reduction and compiled into scenarios and then screened and evaluated using the County's Multi Criteria Analysis Tool (MCA), a resource included in the Future Oxford Community Sustainability Plan to help guide councils, organizations, businesses and others in making decisions that support a sustainable future.
The technologies explored in the assessment include a Materials Recovery Facility, a wet anaerobic digestion plant, and Mechanical Biological Treatment.
Seven scenarios have been presented consisting of different types and combinations of technology that are considered appropriate for Oxford County.
Council Report PW 2017-42 – Advancing Towards Zero Waste
Report cover and table of contents
Executive summary
Approach and methodology
Results and discussion: single family residential curbside audit
Results and discussion: physical landfill audit
Results and discussion: visual landfill audit
Tables, figures and appendices
Table of contents
Executive summary
Introduction, approach and methodology
IC&I sector profile
Estimate of IC&I and C&D waste quantities
IC&I sector survey
Hauler survey results
IC&I model results, conclusions and recommendations
Tables, figures and appendices
Executive summary
Table of contents
Assessment of existing waste recovery technologies
Case studies of implemented technologies
Review of new and emerging technologies
Relationship of EPR and resource recovery to Oxford County
Economic potential of full resource recovery
Statement of limitations
Tables, figures and appendices
Technical memo 1
Technical memo 2
Technical memo 3
Technical memo 4
Technical memo 5
Technical memo 6
Technical memo 7
Technical memo 8
Draft Zero Waste Plan - September, 2016
The Draft Zero Waste Plan has been received by Oxford County Council, opening the strategy document for public review, while seeding $400,000 in funding to begin work on advancing the plan.
The initial funding will allow research to begin with the ultimate goals of reducing the amount of waste being produced in, and exported out of, Oxford County. This includes maximizing recovery efforts from our waste stream and extending the lifespan of the Oxford County Waste Management site to 2100, from the current expected lifespan of 2043. The initial funding for the plan is being financed from the Landfill and Waste Diversion reserve fund.
The first steps in developing the Zero Waste Plan will involve:
Waste reduction is a key component of the Zero Waste Plan; however, beyond reduction, extending Oxford's landfill site lifespan to 2100 will require a dramatic reduction in the volume of material landfilled within the next five years.
Developing a Zero Waste strategy is a key environmental goal in the Future Oxford Community Sustainability Plan and also aligns with provincial strategies like the Ontario Climate Change Action Plan, the Waste Free Ontario Act, 2016 and the Waste Free Ontario Strategy.
Sept. 28 report to Oxford County Council -Read Council Report CAO 2016-14
1. Implementation Status and Outcomes
2. Zero Waste Targets
3. Planning and Orientation
4. Zero Waste Institutionalization
5. Local Stakeholder Engagement
6. Technologies and Activities
7. Buildings
8. Mobility and Transportation of Waste
9. Waste Reduction and Resource Recovery
10. Knowledge Generation
11. Public Engagement
12. Participation in Networks
Strategy for a Waste Free Ontario: Building a Circular Economy
Waste Free Ontario Act 2016
Waste Diversion Transition Act, 2016
Ontario's Climate Change Strategy
Ontario's Climate Change Action Plan
Oxford County Waste Management Strategy 2014


text: Page ContentApplicants for entry to postgraduate research programmes should have at least one of the following qualifications:A Master's degree from a UK university or a degree from a non-UK institution deemed to be of equal standing to a UK degree, orA first class or upper second class Bachelor 'sdegree award by a UK university or a degree of a non-UK institution deemed to be of equal standing to a UK degree, orA professional qualification recognised as equivalent to a good degree, orEquivalent evidence of prior professional practice or learning that meets the University's criteria and guidelines for Recognition of Prior Learning (RPL) (see the relevant documents on our Freedom of information Public Documents page)In addition:Two satisfactory written reports from academic referees;A student is admitted to a Professional Doctorate or Professional Master's programme on the basis of being actively engaged in a profession relevant to the award being sought;For the award of PhD by Works in the Public Domain or the Professional Doctorate by Contribution to Practice, an appropriate number of prior publications or other outputs (this shall be determined on a case by case basis as specified in the programme outlines). These degrees are currently available only to members of staff and to people who have an existing relationship with the University. Download our PGR Programmes Admissions Policy 2015-16