text:
JMM decides to withdraw support to Arjun Munda govt, to meet Governor tomorrow
Top Stories
In the backdrop of conflicting claims about an accord on rotational leadership of the coalition, JMM on Monday decided to withdraw support to the Arjun Munda-led BJP government in Jharkhand, pushing it to a minority and threatening its survival.
JMM leader and Deputy chief minister Hemant Soren said the decision was "unanimous" and was taken after talking to several BJP leaders, including its Jharkhand affairs in-charge Dharmendra Pradhan.
"After a series of meetings, JMM has decided to withdraw support to the (BJP-led) government," Soren said after the party's executive committee meeting.
JMM chief Shibu Soren said the party would hand over tomorrow a letter conveying to Governor Syed Ahmed its decision to withdraw support to Munda government.
In the 82-member state Assembly, BJP and JMM have 18 members each and the Mund government enjoys the support of six members of All Jharkhand Students' Union, two of JD (U), two Independents and one nominated member who has voting right in trial of strength.
Earlier, Munda met JMM chief Shibu Soren and discussed the political situation in the state.
JMM has put before BJP 'over phone' certain issues, including the "ruling by rotation". The 28-month limit for ruling by BJP, according to the tribal, party ends on January 10.
Relations between BJP and JMM have come under strain since Chief Minister Arjun Munda, in a written reply to a letter from JMM on January 3, rejected that there was an agreement between the two parties on "rotation of power" after 28 months in office.
JMM, however, insisted there had been an agreement to share power. Hemant Soren had in a letter to Munda on December 25 asked him to clarify BJP's stand on the issue.
Hemant Soren said "If BJP considers them (the issues) positively, then the JMM can even consider its withdrawal of support."
... contd.


text: > View Product Details Please select the size of the product. Please enter valid quantity. Wyatt helium blue denim 'Anela' boyfriend shorts overview details Retail: $95.00 Bluefly: $68.00 $19.00 color : Helium Blue Whether you're looking to expand your weekend wear or evening wardrobe, you're bound to find your next fashion crush among the many versatile designs of Wyatt. Color: Helium Blue Lightweight stretch denim Zip fly with button closure at belt looped waist Five pocket construction Frayed detail at 20'' opening 8'' rise 2�'' inseam Approximate measurements taken from a size 26W, and may vary by size 42% Lyocell / 33% Cotton / 15% Rayon / 9% Polyester / 1% Spandex; Machine Wash; U.S.A; style#318582004

subset: commoncrawl


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Something about the grill's heat brings out the best flavor in the simplest chicken recipe.
We have over 700 dessert recipes just for summer fun.
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text:
Am I safe to assume that the offset of a data member (
offsetof(mystruct, myfield)) is numerically equal to the raw value of a member pointer retrieved with
&mystruct::myfield, or is it implementation dependent?
Take the 2-minute tour ×
Stack Overflow is a question and answer site for professional and enthusiast programmers. It's 100% free, no registration required.
Am I safe to assume that the offset of a data member (
No; the implementation of a pointer-to-member is not specified, and there is no defined conversion to get the "raw" value.


text: We've just returned from Applecross after a fantastic 3 night stay at this lovely B&B. Alistair and Seonag couldn't have been more accommodating. Seonag made us tea when we arrived and Alistair drove us into the Potting Shed for dinner and even arranged with the manager to call when we needed a lift back! James, their young son, was equally... More


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Solar Energy Materials & Solar Cells
An International Journal Devoted to Photovoltaic, Photothermal, and Photochemical Solar Energy Conversion
Editor-in-Chief: C.M. LampertView full editorial board
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Solar Energy Materials & Solar Cells is intended as a vehicle for the dissemination of research results on materials science and technology related to photovoltaic, photothermal and photoelectrochemical solar energy conversion. Materials science is taken in the broadest possible sense and encompasses physics, chemistry, optics, materials fabrication and analysis for all types of materials.
Of particular interest are:
Solar Cells, covering single crystal, polycrystalline and amorphous materials utilising homojunctions and heterojunctions, Schottky barriers, liquid junctions and their applications. Also of interest is analysis of component materials, individual cells and complete systems, including their economic aspects.
Photothermal Devices, in the broadest sense, including solar absorber devices, heat storage materials, radiative cooling systems and their applications.
Photoelectrochemical and Photochemical Devices, covering photoelectrodes, photocatalysis, photoconversion and solar desalination...
This journal supports the following content innovations
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This application lets readers explore data and other quantitative results submitted with the article, providing insights into and access to data that is otherwise buried in plots.Read More
Altmetrics - Top Rated Articles
- Effects of spectral coupling on perovskite solar cells under diverse climatic conditions
- Soiling of building envelope surfaces and its effect on solar reflectance – Part II: Development of an accelerated aging method for roofing materials
- Perspectives on the pathways for cadmium telluride photovoltaic module manufacturers to address expected increases in the price for tellurium
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- The path towards a high-performance solution-processed kesterite solar cellDavid B. Mitzi | Oki Gunawan | ...
- Polymer solar cells: Recent development and possible routes for improvement in the performanceWanzhu Cai | Xiong Gong | ...
- Co-evaporated Cu 2ZnSnSe 4 films and devicesIngrid Repins | Carolyn Beall | ...
Recent Articles
- A novel thermophotocatalyst of mixed-phase cerium oxide (CeO2/Ce2O3) homocomposite nanostructure: Role of interface and oxygen vacancies
Ranjana Verma | S.K. Samdarshi | …
- Wavelength influence on the photodegradation of P3HT:PCBM organic solar cells
Laura Córcoles | Jose Abad | …
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Z. El Jouad | M. Morsli | …
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- 3D-printed concentrator arrays for external light trapping on thin film solar cellsLourens van Dijk | E.A. Pepijn Marcus | …
- Limit of efficiency for photon-enhanced thermionic emission vs. photovoltaic and thermal conversionGideon Segev | Yossi Rosenwaks | …
- Application and modeling of an integrated amorphous silicon tandem based device for solar water splittingFélix Urbain | Vladimir Smirnov | …
- Enhanced energy conversion of up-conversion solar cells by the integration of compound parabolic concentrating opticsGeorgios E. Arnaoutakis | Jose Marques-Hueso | …
- EMRS 2014 Spring Meeting - Advanced materials and characterization techniques for solar cells IIVolume 135 (2015)
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text:
Get out your wheelbarrows, potting soil and rakes
A new initiative by the town will award Yard of the Month titles to one resident each during the months of April, May and June.
The first winner will be announced at the Rivergate Festival on April 26, Main Street director Lynn Ryals said after the measure was approved unanimously by town aldermen on April 1. The project was proposed by Ward 2's Brad Beach.
The town is also unofficially encouraging residents to "clean up, paint up, fix up" during the month of April. Citizens may call Town Hall at (662) 363-2432 to request extra pick-ups for yard trimmings and other trash.
Latest News
Town, county wait to hear judge's ruling After a half a day...
Board splits over Chandler evaluation On June 10, the Board...
Kirkland tapped for Coaches' Hall of Fame The winningest boys basketball...
Hercules Hampstead Stage players...
New airman proves 'good' comes from Tunica "When the world...
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text: Little but a very clean room with a nice bathroom. It is definitely cheaper than Verbier and at the walkable distance to the ski lifts. We had just a mixed feeling about the breakfast, it was supposed to be served at 8 am and we had to wait for it for at least 20 min to get it. Well, it... More


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0 User Responses
I lived here 9 months. It was OK but nothing special at all. In fact the management does nothing to screen tenants and they don't even run a credit check. I know because I have a FICO score of 391 and I got in with no problem and no extra deposit. There's nothing here, no pool, no laundry, nothing. Very bare bones. Clean, nice maintainance man and yard man but he tries to borrow money all the time from tenants.
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Lenox Woods Apartments2255 Lenox Road Northeast, Atlanta, GA 30324 26 Reviews
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Woodland View Apartments1195 Woodland Avenue NE, Atlanta, GA 30324 10 Reviews
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The Reserve at Lavista Walk Apartments1155 Lavista Road NE, Atlanta, GA 30324 43 Reviews


text:
New Jersey State Police
New Jersey State Police Union Warns Of "Heightened Hostility"
New Jersey's state police union has issued an email alert to the group's 33,000 members warning them to take extra caution after two NYPD officers were murdered.
NJ State Police Want Fugitive Living In Cuba Back In Prison
Cops in the Garden State see plans by the Obama Administration to resume diplomatic relations with Cuba as an opportunity to return a convicted cop killer to prison.
Reward Increased To $5K For Information In Salem County Fatal Hit-And-Run
Anyone with information is asked to contact Woodstown Station at (856) 769-0775.
Amber Alert Cancelled; Baby Boy Found Safe
New Jersey State Police say Steven Ristick was taken from a residence at 338 Fairview Avenue in Greenpoint, New York around 10:45 p.m. Sunday by his father, 21-year-old Jonathan J. Lawrence.
Police: NJ Kids Killed In Murder-Suicide Attempt By Mom
A New Jersey mother shot three of her children, killing two of them, before turning the gun on herself inside the family's home, State Police said.
One Dead In Fiery Crash On New Jersey Turnpike
It happened Tuesday night in the northbound lanes just north of Exit 8 in Cranbury Township.
State Police: 2 Dead, 1 Injured In Pilesgrove Township Crash
It happened around 1:40 p.m. Thursday at Yorktown Road.
Family Speaks Out After Deadly Hit-And-Run In Salem County
New Jersey State Police are asking for the public's help in identifying a driver wanted in connection with a fatal hit-and-run crash in Pilesgrove, Salem County.
Caught On Tape: State Police Cruiser Struck By Hit-Run Driver In NJ
A manhunt is underway for the driver who side-swiped a New Jersey State Police cruiser and kept on going.
Police: Amber Alert Canceled; 5-Year-Old Girl Found Safe
The Amber Alert was canceled.
Cops: Woman Suspected Of DWI Drives Wrong-Way On NJ Turnpike, Crashes At Police Station
It's never, ever a good idea to drive drunk. It's even worse to pull into the parking lot of a police station while driving drunk.
Murder Charges Filed In Deadly South Jersey Street Shooting
State police have arrested a man who allegedly shot and killed another man in Woobine, New Jersey.
6 Women Allegedly Stole Thousands Of Dollars From Chinese Restaurant In South Jersey
New Jersey State Police are on the hunt for a group of women accused of taking cash and other items from a Chinese Restaurant in Atlantic County.
NJ State Troopers Help Deliver Baby On Garden State Parkway
State Police say Trooper Yenier Hurtado removed his uniform shirt and wrapped the boy in it. Hurtado cut the umbilical cord after paramedics arrived and carried the baby to an ambulance.
Protests In Ferguson Raise Questions About Police Department Diversity Nationwide
In 2012, New Jersey State Police graduated only two Black officers out of a class of 85. But the department's last three classes of new troopers have made history.


text:
Watch Movies Online
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10StarMovies.com has the largest database to Watch Movies Online completely free? you can watch movies and even documentaries by streaming video files online.
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Watch X-men Online
Release:July 13, 2000
RunTime:1 hr 44 min
IMDB Rating:7.4/10 (303923 votes)
Director:Bryan SingerActors:Hugh Jackman, Patrick Stewart, Ian McKellen, Famke Janssen, James Marsden(View All)
Description: Watch X-men full movie online for free directed by Bryan Singer produced in 2000. Genres are Action, Adventure, Sci-Fi, Thriller.
Fatal error: Allowed memory size of 33554432 bytes exhausted (tried to allocate 13429487 bytes) in /home/star10/public_html/cache-credits/X-Men_2000.php on line 1


text:
|Students Excel at Competitions
|Board of Visitors Elects New Officers and Members
|Michelle Mendez '08 Wins Young Lawyer Award from the American Immigration Lawyers Association
|Maryland Carey Law's National Trial Team Receives $75,000 Gift from The Law Office of Miguel Palmeiro, LLC
|Baltimore State's Attorney Marilyn Mosby Shares Her Story with City's Youth
|New LL.M. Specialties in Crisis Management in Cybersecurity
|Health Law Collaborator
|A Passion for Advocacy
|Prof. Ertman's New Book Explores How Formal Contracts and Informal Deals Transform Families
|New Business Fellowship Program Announced
|Prof. Greenberger Testifies on Cybersecurity Before U.S. Senate Foreign Relations Subcommittee
|Congratulations, Class of 2015
|Laws to Save Lives
|Maryland Carey Law Congratulates our Graduating Award Winners
|Stephanie Rawlings-Blake '95, Mayor of Baltimore City, to to Deliver 2015 Law School Commencement Address
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Vacuum Cleaner Bags
Vacuum cleaning systems that offer the best cleaning ability – is that what you are seeking? It's also likely that you believe that cleaning ability is related to power or suction. Actually, it's not. While there's no single factor that determines the cleaning ability of the vacuum cleaner you use, understanding how vacuums work and how you can help maintain your vacuum cleaner to perform its best is important. Changing your vacuum cleaner bag is an important step in maintaining the efficiency of your vacuum cleaner. While most vacuum cleaners come with an indicator to help you determine when your cleaner's dust bag needs to be changed, you can perform a check yourself to see if it is over 50% full as that's when you need to replace it. Don't wait until the dust bag in your vacuum cleaner is completely full as it can reduce the suction and cleaning capacity of your vacuum cleaning system. If you use your vacuum cleaner frequently, it is recommended that you change vacuum cleaner bags once a month, especially if you are cleaning a large area over 2000 square feet or if your pet sheds a lot.
What you need the most when you are considering vacuum cleaner bag replacement is a bag that is well-matched with the model of your vacuum cleaning system. You can find original equipment manufacturer (OEM) or replacement type bags online. While both serve the purpose, that is enhancing the cleaning capacity of your vacuum cleaning system and providing you an easy way to get rid of all the dirt that you vacuum cleaner collects, you can choose one according to your budget and cleaning needs. At GoVacuum, we have got a vast range of vacuum cleaner bags from the biggest and the best brands around. You'll find them here at great prices and shipping offers. We are the vacuum cleaning system experts and can recommend the right bag for your existing system all while staying within your budget.
Genuine Smart Choice Carpet Pro 06.153 Upright Vacuum Cleaner Bags to Fit All CPU Models, 3pk.$6.99These are genuine Smart Choice Carpet Pro Premium Filtration vacuum cleaner bags that fit ALL Carpet Pro uprights.These genuine Carpet Pro bags have a special feature named Allerest lining. The interior of the bag is lined with an electrostatically charge Learn More
48 Generic Smart Choice Carpet Pro Upright Vacuum Bags, BULK DEAL 48 Total Bags$79.96This is bulk deal of 48 total Smart Choice Carpet Pro generic upright vacuum bags for all CPU models. Learn More
Carpet Pro SCBP-1 Backpack Vacuum Bags (10pk)$19.99This is a 10 pack of Carpet Pro SCBP-1 Backpack Vacuum cleaner bags for the Carpet Pro, Sanitaire, and Powr-Flite Backpack Model Vacuums. Learn More
CarpetPro CPU 10 Pack Generic Vacuum bags$19.95CarpetPro CPU 10 Pack Generic Vacuum bags use the highest quality Micro-Plus filter media including Melt-Blown inner liner in order to achieve filtration efficiencies up to 99.9%. Learn More
Carpet Pro Vacuum Cleaner Tiny Tank Bags$10.97Carpet Pro vacuum cleaner bags. Fits canister model Tiny Tank SCC1. Also known as part CP1401. Genuine six pack of Carpet Pro vacuum cleaner bags. Learn More
Carpet Pro Replacement Backpack Vacuum Bags C352-2500$21.87Carpet Pro Replacement Backpack Vacuum Bags C352-2500 Learn More
48 Generic Smart Choice Carpet Pro Upright Vacuum Bags, BULK DEAL 48 Total Bags!$44.40This is a mega bulk kit put together for you by GoVacuum. Save substantial money when purchasing these bags in bulk. There are a total of 48 bags (4 x 12 pks.). Each bag has a convenient seal that will allow you to seal the bag shut when changing it, preventing a face full of dust or debris in the process of changing the bag. These bags are designed to fit ALL Carpet Pro upright models including; CPU-75, CPU-75T, CPU-85, CPU-85T, CPU-1, CPU-1T, CPU-2, and CPU-2T. They will also fit Riccar 2000, 4000 series, Simplicity 5000, 6000 series type A, as well as all Fuller Brush upright models. Generic product made by Envirocare. Learn More
Carpet Pro Smart Choice Carpet Pro HEPA Filtration 5 Pack Bundle Package +$49.83These are the best quality bag available for the Smart Choice Carpet Pro upright vacuum cleaners. Rather then using a paper bag, these are a high quality synthetic cloth material. The more efficient HEPA filtration bag will capture more dust particles in the bag, where the paper bags will allow the microscopic particles to escape through the pourus bag, then into the vacuums motor, and finally exhausting back into the air you breathe. Because the HEPA bags retain more of the dust, the vacuums motor is exposed to less dirt, making the motor last longer, and run cooler. These HEPA bags are over 75% more effective at capturing airborne allergens then standard paper bags. Highly recommended for homes with breathing issues such as asthma, as well as allergies. These bags are designed to fit ALL Carpet Pro upright models including; CPU-75, CPU-75T, CPU-85, CPU-85T, CPU-1, CPU-1T, CPU-2, and CPU-2T. They will also fit Riccar2000, 4000 series, Simplicity 5000, 6000 series type A, as well as a Learn More
Genuine Carpet Pro BackPack bags - 10 Pack$17.75Genuine Carpet Pro paper bags for Backpack Vacuums 10 pk Learn More
Carpet ProUpright Vacuum Cleaner Bags 3pk 09-2430-07$10.04Works with: Carpet Pro Heavy Duty, Carpet Pro Commercial, Carpet Pro Standard Household, Carpet Pro CPU-1, Carpet Pro CPU-1T, Carpet Pro CPU-2, Carpet Pro CPU-2T, Carpet Pro CPU-75, Carpet Pro CPU-75T, Carpet Pro CPU-85, Carpet Pro CPU-85T Learn More
06.153 CarpetPro CPU1, CPU2, CPU75 Genuine Upright Vacuum Bags, 3pk.$5.84Carpet Pro Upright Vacuum Bags Learn More
Generic Smart Choice Carpet Pro Upright Vacuum Bags + 12pk$13.71These are generic Smart Choice Carpet Pro micro filtration vacuum cleaner bags made by Envirocare, the leading manufacturer of high quality replacement vacuum bags and filters. Each package contains 12 bags, as well as a convenient seal system that allows you to seal the bag shut before throwing it away, to prevent any dust or debris to exhaust out of the bag. These bags are designed to fit ALL Carpet Pro upright models including; CPU-75, CPU-75T, CPU-85, CPU-85T, CPU-1, CPU-1T, CPU-2, and CPU-2T. They will also fit Riccar 2000, 4000 series, Simplicity 5000, 6000 series type A, as well as all Fuller Brush upright models. Learn More
Carpet Pro Vacuum Cleaner Bags$8.77Carpet Pro Vacuum Cleaner Bags. Fits Carpet Pro vacuum cleaner models Cpu1, Cpu1T, Cpu2, Cpu2T, Cpu75, Cpu75T, Cpu85 and Cpu85T. Also known as part CP1400. Genuine three pack of Carpet Pro vacuum bags. Learn More
Carpet Pro 06.153 / Fb06153 Upright Vacuum Bags For Cpu Uprights- Genuine -3 Pack$5.99Designed to fit all Carpet Pro upright vacuums. 3 bags per pack. Fits: CarpetPro Models CPU-1 CPU-1T CPU-2 CPU-2T CPU-75 CPU75-T CPU-85 CPU-85T Featuring Allerest Liner-caputures particles up to 0.1 micron like pollens, spores, bactria dust mites and allergens. Learn More
Generic Sharp PU-2 Allergen Cloth Vacuum Cleaner Bags - 3pk.$7.95Product Features- Ideal For Homes With Allergies, Asthma, Breathing Issues, and Pets - Advanced Fiber Filtration - 40% Larger then Standard Paper Bags - Guaranteed Not To Tear Open During Use - 30% More Effective in Dust Capturing Then Standard Paper Bags Learn More
Micro-lined PC-2 Canister Vacuum Bags (36pk) for Sharp Vacuum Cleaners$44.95Fits Sharp compact canister vauums using PC-2 bags. Sold 12 packages of 3pk bags (36 bags total). Fits Sharp Modesl EC-7311, EC-FX30, EC-6311 Learn More
Micro-Lined PU-2 Upright Vacuum Bags (36pk) for Sharp Vacuum Cleaners$40.95Fits most every model of Sharp Upright vacuum with Top-Fill bags. Including All current production models. Sold 3 bags per pack.Micro-Lined Bags capture microscopic particles and germs and bacteria as small as 0.1 microns. Sold 12 packages of 3pk bags (36 Learn More
Pack of 10 Generic Sharp Bags for (PU-2)$17.99Pack of 10 Sharp Orginal Bags for (PU-2) Learn More
Sharp PU-2 Microfiltration Dust Bags 3 pack. Sharp EC03PU2$11.99Sharp PU2 OEM vacuum cleaner bags. 3 package of Sharp PU-2 bags. These Sharp PU-2 vacuum cleaner bags are best priced at GoVacuum 074000680487. Learn More
Generic Sharp PU-2 Upright Microfiltration Vacuum Cleaner Bags w/ Seal. 9 Pk.$11.78Sharp PU2 Micro Filtered Vacuum Cleaner Bags. Sharp PU-2 Bags Fit All Sharp Uprights. Our Sharp PU 2 bags are discounted and fit 074000680494, 748167099696 Learn More
Sharp Reuseable Cloth Vacuum Bag. Sharp part # EC01CU1$25.99It's no more paper bags with this reusable cloth vacuum cleaner bag. It fits all Sharp upright models.Gray in color.1 per package.Reusable cloth vacuum bag with slide closure (slide is used to keep the open end closed).Used in place of the paper bags.For Learn More
9 Micro-Lined Sharp PU-2 Upright Micro-Filtration Bags- Generic - BONUS Free Bag! 10 Total MADE IN USA.$10.88These are a generic aftermarket Sharp PU2 Upright Bag designed to fit Sharp EC-PU10 Vacuum Bags. These high quality aftermarket bags by DVC Micro-Lined are 40% more efficient at capturing fine dust then standard paper bags, and are made here in the USA! Unlike most other generic vacuum bag manufacturers, DVC has made a commitment to keep jobs here in the USA, without giving up a single bit of quality. Each package contains 9 Bags, with a limited time special of a bonus bag free with every order! 10 Bags total. Works With: Sharp 12SX3 Sharp 12SX6 Sharp 12TX3 Sharp 12TX3B Sharp 12TX6 Sharp 12TX8 Sharp 12TX8B Sharp 12TXC Sharp TU2603 Sharp TU2608 Sharp 14TX6 Sharp 14TX6B Sharp 14TX8 Sharp TU4606 Sharp 12SX2 Sharp 12SXT4 Sharp 12SXT4B Sharp 12SXT5 Sharp 12TWT4 Sharp 12TXT2 Sharp 12TXT4 Sharp 12TXT6 Sharp 14TXT6 Sharp 12TXT7 Sharp TXT9 Sharp 14TXT7 Sharp 14TXT9 Sharp 12TWT7 Sharp 12TWT9 Sharp TU2607 Sharp TU2609 Sharp 14TWT7 Sharp TU4607 Sharp TU4609 Sharp 12TBC Sharp 12TWC Sharp S2620 Sharp T2630 Sharp T2650 Sharp T4765 Sharp T4770 Sharp TU2807 Sharp TU2809 Sharp TU4707 Sharp TU4711S Sharp T5965 Sharp T5970 Sharp T5980 Sharp TU5907 Sharp TU5909 Sharp TU5910 Sharp TU2007 Sharp TU5007 Sharp TU2111 Sharp TU5111 Sharp S5170 Sharp T5180 Sharp T5180A Sharp T5180B Sharp PU2 Description:Envirocare ReplacementGeneric Brand, 99.7% Microfiltration, 9 Bags In Pack Learn More
Sharp PC-2 Canister Bags - 10 pack$11.51Quantity Per Package: 10 sharp vacuum bags Please note that the Genuine EC-10PC2 bags are no longer available. Your order will be substituted with Envirocare Brand EC-10PC2 vacuum bags. Picture shown above is the stock image. OEM Part Number: EC-10PC2 Fits Models: Sharp EC6311, Sharp EC7311 Canister Learn More
3PK Sharp PU2 Vac Bag$7.173PK Sharp PU2 Vac Bag Learn More
3 Sharp EC-PU2 DVC Micro-Lined Anti-Allergen Premium Filtration Vacuum Bags, Generic 3pk. Made in The USA!$6.94This is a 3 package of replacement DVC Micro-Lined Allergen Sharp PU2 Style Upright Vacuum Bags for all Sharp Upright models made since 1995. These high quality Micro-Lined bags capture up to 40% more dust and debris then standard paper bags do, and come with a manufacturers warranty assuring should you ever have a bag tear while using it, they will replace it at no charge. These high quality generic aftermarket bags are made right here in the United States, in Virginia by Dust Vacuum Corporation (Home Care Industries, aka DVC), who have made a commitment to keep American jobs here, while most all other generic aftermarket, and even most OEM Genuine bags are now made overseas. Support our economy by purchasing Micro-Lined bags, a better quality bag at a competitive, economy stimulating price. Back to the bags now.... Fits all Sharp Upright Vacuum Cleaners, including Sharp Upright models; Micro-Lined Bags capture microscopic particles and germs and bacteria as small as 0.1 microns. Sharp models that use PU2 bags: EC-12TBC, EC-12TWC, EC-12TWT4, EC-12TWT6, EC-12SXT5, EC-TU2607, EC-TU2609, EC-T2640, EC-T2650, EC-TU2807, EC-TU2809, EC-T2860, EC-TU4607, EC-TU4609, EC-TU4707, EC-TU4709, EC-TU4810, EC-TU4840, EC-TU5907, EC-TU5909, EC-TU5910, EC-T5980. Learn More
Sharp Upright Types PU-2 Vacuum Bags Microfiltration with Closure - 9 Pack$8.25Designed to fit all Sharp Uprights. 99.7% Filtration. A MUST FOR ALLERGY SUFFERERS!!! Learn More
Results 1 - 27 of 27


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HSBC "lift" by Grey London
Agency: Grey London
Rating: 5.0
By Joe Thomas, brandrepublic.com, Wednesday, 14 July 2010 09:45AM
Created in partnership with the direct and digital agency, Tullo Marshall Warren, and members of the IAB SMC, the framework has been designed to help advertisers and agencies take on board the complexities of social media measurement.
Using the letters I, A and B as a point of reference, the framework can be downloaded on the IAB SMC blog, and has been designed to be flexible enough to be applied across a broad spectrum of social media platforms.
The 'I' stands for 'intent', with the IAB recommending that no social media activity should take place unless there is a firm motive, or set of objectives, to determine which key performance indicators (KPIs) are most relevant to measure success.
The 'A' stands for 'awareness', 'appreciation', 'action' and 'advocacy'. These are the four main areas within which the KPIs can be set, after the intent has been agreed. 'B' stands for 'benchmark' in which targets can be created based on activity and that of competitors and industry averages, to provide a basis for future planning.
The IAB is hoping for feedback from the wider industry – including other trade bodies with a vested interest in social media – in order for the framework to evolve.
It is also calling for case studies to illustrate how the model applies in practice, and, over the coming months, intends to build a database of results against this framework, so brands can benchmark and forecast new initiatives.
The IAB Social Media Council claims to be Europe's biggest group dedicated to the promotion of social media, with membership comprising site owners, creative, media and search agencies, as well as social specialists and clients.
Richard Pentin, member of the IAB Social Media Council and Group Planning Director at TMW, said: "The days of whimsical experimentation have long gone. Nowadays, marketers have to justify every budget line with robust KPIs, solid business cases or definitive ROI analysis.
"If we genuinely want social media to be taken seriously, it's imperative we start making it much more accountable, and the IAB social media measurement framework is designed to do exactly that."
This article was first published on brandrepublic.com
Before commenting please read our rules for commenting on articles.
If you see a comment you find offensive, you can flag it as inappropriate. In the top right-hand corner of an individual comment, you will see 'flag as inappropriate'. Clicking this prompts us to review the comment. For further information see our rules for commenting on articles.
Agency: Grey London
Rating: 5.0


text:
Canada's Insurance and Risk Magazine
Environment Canada was advising people to monitor weather conditions and listen for updated statements as a result of potentially damaging winds expected to hit parts of Newfoundland and Labrador on Tuesday.
"A low-pressure system over the Labrador Sea will continue to intensify as it drifts eastward today," notes a weather warning for the area of Northern Peninsula East. "Westerly wind gusts reaching up to 110 km/hour are expected in the Canada Bay this morning and will gradually diminish by this afternoon."
In the Postville – Makkovik area of the province, Environment Canada was calling for wind gusts of 100 km/h, with winds expected to slightly diminish this afternoon as the low moves away.
"Strong winds will combine with freshly fallen snow to give reduced visibilities in blowing snow from Nain to Makkovik. The blowing snow is expected to cease tonight as the winds diminish," the warning notes.
Environment Canada reports strong winds will continue behind this system today with the strongest winds expected from Nain to Makkovik, gusting to 100 km/h. Winds are expected to slightly diminish this afternoon as the low moves away.
A similar warning was issued for Hopedale and vicinity.
DisclaimerNote: By submitting your comments you acknowledge that Canadian Underwriter has the right to reproduce, broadcast and publicize those comments or any part thereof in any manner whatsoever. Please note that due to the volume of e-mails we receive, not all comments will be published and those that are published will not be edited. However, all will be carefully read, considered and appreciated.
Learning to Share
Get things straight. Vacation rental operator Airbnb currently has more than 36,000 users in Canada. UberX, the popular app-based ride-sharing service, uses "tens of thousands" of drivers in six cities across the country, reports a spokesperson...
Drought to Deluge
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Publications (57)350.91 Total impact
- SourceAvailable from: Iwona Bujalska[Show abstract] [Hide abstract]
ABSTRACT: Innate immune responses have a critical role in regulating sight-threatening ocular surface (OcS) inflammation. While glucocorticoids (GCs) are frequently used to limit tissue damage, the role of intracrine GC (cortisol) bioavailability via 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in OcS defense, remains unresolved. We found that primary human corneal epithelial cells (PHCEC), fibroblasts (PHKF) and allogeneic macrophages (M1, GM-CSF; M2, M-CSF) were capable of generating cortisol (M1>PHKF>M2>PHCEC) but in corneal cells, this was independent of Toll-like receptor (TLR) activation. While PolyI∶C induced maximal cytokine and chemokine production from both PHCEC (IFNγ, CCL2, CCL3, and (CCL4), IL6, CXCL10, CCL5, TNFα) and PHKF (CCL2, IL-6, CXCL10, CCL5), only PHKF cytokines were inhibited by GCs. Both Poly I∶C and LPS challenged-corneal cells induced M1 chemotaxis (greatest LPS-PHKF (250%), but down-regulated M1 11β-HSD1 activity (30 and 40% respectively). These data were supported by clinical studies demonstrating reduced human tear film cortisol∶cortisone ratios (a biomarker of local 11β-HSD1 activity) in pseudomonas keratitis (1∶2.9) versus healthy controls (1∶1.3; p<0.05). This contrasted with putative TLR3-mediated OcS disease (Stevens-Johnson Syndrome, Mucous membrane pemphigoid) where an increase in cortisol∶cortisone ratio was observed (113.8∶1; p<0.05). In summary, cortisol biosynthesis in human corneal cells is independent of TLR activation and is likely to afford immunoprotection under physiological conditions. Contribution to ocular mucosal innate responses is dependent on the aetiology of immunological challenge.PLoS ONE 04/2014; 9(4):e94913. DOI:10.1371/journal.pone.0094913 · 3.53 Impact Factor
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ABSTRACT: Purpose:Vitamin D3 is a secosteroid mainly synthesized from the conversion of the skin precursor 7-dehydrocholesterol to vitamin D3 by ultraviolet (UV) B sunlight. Extra-renal synthesis of vitamin D3 has been reported in many tissues and cells including barrier sites. This study characterizes the expression of components of vitamin D signaling in human ocular barrier cells. Methods:Human conjunctival epithelial (CCL20.2), human corneal endothelial (HCEC-12), non-pigmented ciliary body epithelial (ODM-2), and adult retinal pigment epithelial (ARPE-19) cell lines and primary human scleral fibroblasts (HSF), were analyzed for the expression of vitamin D receptor (VDR), the vitamin D activating enzymes 1α-hydroxylase (CYP27B1), 25-hydroxylases (CYP27A1 and CYP2R1), the vitamin D inactivating enzyme 24-hydroxylase (CYP24A1), and endocytic receptors cubulin and megalin utilizing a combination of RT-PCR, Immunocytochemistry and EIA. Results:CCL20.2, HSF, HCEC-12, ODM-2, and ARPE-19 express mRNA and protein for all vitamin D synthesizing and metabolizing components. The cell types tested except HSF are able to convert inactive 25-hydroxyvitamin D3 (25(OH)D3) into active 1,25-hydroxyviatmin D3 (1,25(OH)2D3) in the order of HCEC-12>ODM2>CCL20.2>ARPE >HSF. Conclusions: This novel study demonstrates that ocular barrier epithelial cells express the machinery for vitamin D3 and can produce 1,25(OH)2D3. We suggest that vitamin D3 might play a role in immune regulation and barrier function in ocular barrier cells.Investigative ophthalmology & visual science 02/2014; 55(4). DOI:10.1167/iovs.13-13019 · 3.66 Impact Factor
Article: 11β-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects[Show abstract] [Hide abstract]
ABSTRACT: Glucocorticoid (GC) excess adversely affects skin integrity, inducing thinning and impaired wound healing. Aged skin, particularly that which has been photo-exposed, shares a similar phenotype. Previously, we demonstrated age-induced expression of the GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in cultured human dermal fibroblasts (HDFs). Here, we determined 11β-HSD1 levels in human skin biopsies from young and older volunteers and examined the aged 11β-HSD1 KO mouse skin phenotype. 11β-HSD1 activity was elevated in aged human and mouse skin and in PE compared with donor-matched photo-protected human biopsies. Age-induced dermal atrophy with deranged collagen structural organization was prevented in 11β-HSD1 KO mice, which also exhibited increased collagen density. We found that treatment of HDFs with physiological concentrations of cortisol inhibited rate-limiting steps in collagen biosynthesis and processing. Furthermore, topical 11β-HSD1 inhibitor treatment accelerated healing of full-thickness mouse dorsal wounds, with improved healing also observed in aged 11β-HSD1 KO mice. These findings suggest that elevated 11β-HSD1 activity in aging skin leads to increased local GC generation, which may account for adverse changes occurring in the elderly, and 11β-HSD1 inhibitors may be useful in the treatment of age-associated impairments in dermal integrity and wound healing.The Journal of clinical investigation 06/2013; 123(7). DOI:10.1172/JCI64162 · 13.77 Impact Factor
Article: Novel H6PDH mutations in two girls with premature adrenarche: 'Apparent' and 'true' CRD can be differentiated by urinary steroid profiling.[Show abstract] [Hide abstract]
ABSTRACT: CONTEXT: Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase (H6PDH- encoded by H6PD) causes Apparent Cortisone Reductase Deficiency (ACRD). H6PDH generates cofactor NADPH for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 encoded by HSD11B1) oxo-reductase activity, converting cortisone to cortisol. Inactivating mutations in HSD11B1 cause true cortisone reductase deficiency (CRD). Both ACRD and CRD present with HPA axis activation and adrenal hyperandrogenism. OBJECTIVE: To describe the clinical, biochemical and molecular characteristics of two additional female children with ACRD, and to illustrate the diagnostic value of urinary steroid profiling in identifying and differentiating a total of six ACRD and four CRD cases. DESIGN: Clinical, biochemical, and genetic assessment of two female patients presenting during childhood. In addition, results of urinary steroid profiling in a total of ten ACRD/ CRD patients were compared to identify distinguishing characteristics. RESULTS: Case 1 was compound heterozygous for R109AfsX3, and a novel P146L missense mutation in H6PD. Case 2 was compound heterozygous for novel nonsense mutations Q325X and Y446X in H6PD. Mutant expression studies confirmed loss of H6PDH activity in both cases. Urinary steroid metabolite profiling by gas chromatography/ mass spectrometry (GC/MS) suggested ACRD in both cases. In addition, we were able to establish a steroid metabolite signature differentiating ACRD and CRD, providing a basis for genetic diagnosis and future individualized management. CONCLUSIONS: Steroid profile analysis of a 24h-urine collection provides a diagnostic method for discriminating between ACRD and CRD. This will provide a useful tool in stratifying unresolved adrenal hyperandrogenism in children with premature adrenarche, and adult females with PCOS.European Journal of Endocrinology 11/2012; 168(2). DOI:10.1530/EJE-12-0628 · 3.69 Impact Factor
Article: Lack of Significant Metabolic Abnormalities in Mice with Liver-Specific Disruption of 11β-Hydroxysteroid Dehydrogenase Type 1[Show abstract] [Hide abstract]
ABSTRACT: Glucocorticoids (GC) are implicated in the development of metabolic syndrome, and patients with GC excess share many clinical features, such as central obesity and glucose intolerance. In patients with obesity or type 2 diabetes, systemic GC concentrations seem to be invariably normal. Tissue GC concentrations determined by the hypothalamic-pituitary-adrenal (HPA) axis and local cortisol (corticosterone in mice) regeneration from cortisone (11-dehydrocorticosterone in mice) by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, principally expressed in the liver. Transgenic mice have demonstrated the importance of 11β-HSD1 in mediating aspects of the metabolic syndrome, as well as HPA axis control. In order to address the primacy of hepatic 11β-HSD1 in regulating metabolism and the HPA axis, we have generated liver-specific 11β-HSD1 knockout (LKO) mice, assessed biomarkers of GC metabolism, and examined responses to high-fat feeding. LKO mice were able to regenerate cortisol from cortisone to 40% of control and had no discernible difference in a urinary metabolite marker of 11β-HSD1 activity. Although circulating corticosterone was unaltered, adrenal size was increased, indicative of chronic HPA stimulation. There was a mild improvement in glucose tolerance but with insulin sensitivity largely unaffected. Adiposity and body weight were unaffected as were aspects of hepatic lipid homeostasis, triglyceride accumulation, and serum lipids. Additionally, no changes in the expression of genes involved in glucose or lipid homeostasis were observed. Liver-specific deletion of 11β-HSD1 reduces corticosterone regeneration and may be important for setting aspects of HPA axis tone, without impacting upon urinary steroid metabolite profile. These discordant data have significant implications for the use of these biomarkers of 11β-HSD1 activity in clinical studies. The paucity of metabolic abnormalities in LKO points to important compensatory effects by HPA activation and to a crucial role of extrahepatic 11β-HSD1 expression, highlighting the contribution of cross talk between GC target tissues in determining metabolic phenotype.Endocrinology 05/2012; 153(7):3236-48. DOI:10.1210/en.2012-1019 · 4.64 Impact Factor
Article: Genotype at the P554L Variant of the Hexose-6 Phosphate Dehydrogenase Gene Is Associated with Carotid Intima-Medial Thickness[Show abstract] [Hide abstract]
ABSTRACT: The combined thickness of the intima and media of the carotid artery (carotid intima-medial thickness, CIMT) is associated with cardiovascular disease and stroke. Previous studies indicate that carotid intima-medial thickness is a significantly heritable phenotype, but the responsible genes are largely unknown. Hexose-6 phosphate dehydrogenase (H6PDH) is a microsomal enzyme whose activity regulates corticosteroid metabolism in the liver and adipose tissue; variability in measures of corticosteroid metabolism within the normal range have been associated with risk factors for cardiovascular disease. We performed a genetic association study in 854 members of 224 families to assess the relationship between polymorphisms in the gene coding for hexose-6 phosphate dehydrogenase (H6PD) and carotid intima-medial thickness. Families were ascertained via a hypertensive proband. CIMT was measured using B-mode ultrasound. Single nucleotide polymorphisms (SNPs) tagging common variation in the H6PD gene were genotyped. Association was assessed following adjustment for significant covariates including "classical" cardiovascular risk factors. Functional studies to determine the effect of particular SNPs on H6PDH were performed. There was evidence of association between the single nucleotide polymorphism rs17368528 in exon five of the H6PD gene, which encodes an amino-acid change from proline to leucine in the H6PDH protein, and mean carotid intima-medial thickness (p = 0.00065). Genotype was associated with a 5% (or 0.04 mm) higher mean carotid intima-medial thickness measurement per allele, and determined 2% of the population variability in the phenotype. Our results suggest a novel role for the H6PD gene in atherosclerosis susceptibility.PLoS ONE 08/2011; 6(8):e23248. DOI:10.1371/journal.pone.0023248 · 3.53 Impact Factor
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ABSTRACT: Dexamethasone (DEX) is commonly used as a therapeutic agent for various ocular inflammatory diseases; however, its effect on resident naive cells is unknown. In this study, genome microarray and microRNA (miR) analyses were used to evaluate the global gene and miR expression of human corneal fibroblasts (HKFs) in response to treatment with DEX. Primary HKFs from three donors were treated with DEX for 16 hours. Treated and untreated cells were snap frozen for microarray and miR array analyses. Genes with a more than threefold change were classified into gene families using the DAVID web-based classification database, and six of these genes were validated using quantitative real-time PCR. Five miRs were also validated using miR-detection assays. Of the 41,093 genes examined, 261 were upregulated and 123 were downregulated greater than threefold after DEX treatment. Real-time PCR confirmed upregulation of six genes, including oculocutaneous albinism II (OCA2), angiopoietin-like 7 (ANGPTL7), neuron navigator 2 (NAV2), neurofilament light chain polypeptide (NEFL), solute carrier family 16/member 12 (SLC16A12), and serum amyloid A1 (SAA1). Expression of several miR including miR-16, -21, and -29C were upregulated, whereas miR-100 was downregulated in fibroblasts by DEX. DEX can greatly change the global gene and miR profile of HKFs. DEX not only downregulates inflammatory genes, but can also induce expression of angiogenic and inflammatory genes. In addition, DEX may exert posttranscriptional gene regulation through miRs. These data support a complex role for DEX-induced changes in resident cells that may have implications in the clinical management of corneal inflammation with topical glucocorticoids.Investigative ophthalmology & visual science 06/2011; 52(10):7282-8. DOI:10.1167/iovs.11-7463 · 3.66 Impact Factor
Article: Cortisone-reductase deficiency associated with heterozygous mutations in 11β-hydroxysteroid dehydrogenase type 1[Show abstract] [Hide abstract]
ABSTRACT: In peripheral target tissues, levels of active glucocorticoid hormones are controlled by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a dimeric enzyme that catalyzes the reduction of cortisone to cortisol within the endoplasmic reticulum. Loss of this activity results in a disorder termed cortisone reductase deficiency (CRD), typified by increased cortisol clearance and androgen excess. To date, only mutations in H6PD, which encodes an enzyme supplying cofactor for the reaction, have been identified as the cause of disease. Here we examined the HSD11B1 gene in two cases presenting with biochemical features indicative of a milder form of CRD in whom the H6PD gene was normal. Novel heterozygous mutations (R137C or K187N) were found in the coding sequence of HSD11B1. The R137C mutation disrupts salt bridges at the subunit interface of the 11β-HSD1 dimer, whereas K187N affects a key active site residue. On expression of the mutants in bacterial and mammalian cells, activity was either abolished (K187N) or greatly reduced (R137C). Expression of either mutant in a bacterial system greatly reduced the yield of soluble protein, suggesting that both mutations interfere with subunit folding or dimer assembly. Simultaneous expression of mutant and WT 11β-HSD1 in bacterial or mammalian cells, to simulate the heterozygous condition, indicated a marked suppressive effect of the mutants on both the yield and activity of 11β-HSD1 dimers. Thus, these heterozygous mutations in the HSD11B1 gene have a dominant negative effect on the formation of functional dimers and explain the genetic cause of CRD in these patients.Proceedings of the National Academy of Sciences 02/2011; 108(10):4111-6. DOI:10.1073/pnas.1014934108 · 9.81 Impact Factor
Article: Hexose-6-Phosphate Dehydrogenase Contributes to Skeletal Muscle Homeostasis Independent of 11 beta-Hydroxysteroid Dehydrogenase Type 1[Show abstract] [Hide abstract]
ABSTRACT: Glucose-6-phosphate (G6P) metabolism by the enzyme hexose-6-phosphate dehydrogenase (H6PDH) within the sarcoplasmic reticulum lumen generates nicotinamide adenine dinucleotide phosphate (reduced) to provide the redox potential for the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to activate glucocorticoid (GC). H6PDH knockout (KO) mice have a switch in 11β-HSD1 activity, resulting in GC inactivation and hypothalamic-pituitary-adrenal axis activation. Importantly, H6PDHKO mice develop a type II fiber myopathy with abnormalities in glucose metabolism and activation of the unfolded protein response (UPR). GCs play important roles in muscle physiology, and therefore, we have examined the importance of 11β-HSD1 and GC metabolism in mediating aspects of the H6PDHKO myopathy. To achieve this, we examined 11β-HSD1/H6PDH double-KO (DKO) mice, in which 11β-HSD1 mediated GC inactivation is negated. In contrast to H6PDHKO mice, DKO mice GC metabolism and hypothalamic-pituitary-adrenal axis set point is similar to that observed in 11β-HSD1KO mice. Critically, in contrast to 11β-HSD1KO mice, DKO mice phenocopy the salient features of the H6PDHKO, displaying reduced body mass, muscle atrophy, and vacuolation of type II fiber-rich muscle, fasting hypoglycemia, increased muscle glycogen deposition, and elevated expression of UPR genes. We propose that muscle G6P metabolism through H6PDH may be as important as changes in the redox environment when considering the mechanism underlying the activation of the UPR and the ensuing myopathy in H6PDHKO and DKO mice. These data are consistent with an 11β-HSD1-independent function for H6PDH in which sarcoplasmic reticulum G6P metabolism and nicotinamide adenine dinucleotide phosphate-(oxidized)/nicotinamide adenine dinucleotide phosphate (reduced) redox status are important for maintaining muscle homeostasis.Endocrinology 01/2011; 152(1):93-102. DOI:10.1210/en.2010-0957 · 4.64 Impact Factor
Article: Localization, age- and site-dependent expression, and regulation of 11β-hydroxysteroid dehydrogenase type 1 in skin[Show abstract] [Hide abstract]
ABSTRACT: Glucocorticoids (GCs) are highly detrimental to skin integrity and function both when applied topically for anti-inflammatory treatments and during conditions of circulating excess, e.g., Cushing's syndrome. Within target tissues, GC availability is regulated at a prereceptor level, independently of systemic levels, by isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) that interconvert active cortisol and inactive cortisone. Many of the adverse effects of GCs on skin are also reminiscent of the natural aging process. 11β-HSD1 (which activates cortisol), but not 11β-HSD2 (which inactivates cortisol), was expressed in epidermal keratinocytes and dermal fibroblasts in human skin and also in outer hair follicle root sheath cells in murine skin. 11β-HSD1 activity was present ex vivo in both species and increased with age in human skin tissue explants. In primary human dermal fibroblasts (HDF) from both photoprotected and photoexposed sites, 11β-HSD1 also increased with donor age. Additionally, photoexposed HDF displayed higher 11β-HSD1 mRNA expression than donor-matched photoprotected HDF. GC treatment of HDF caused upregulation of 11β-HSD1 mRNA levels independent of donor age or site. The age- and site-associated increase in dermal 11β-HSD1, and the ensuing increased local GC activation, may contribute to the adverse changes in skin morphology and function associated with chronological aging and photoaging.Journal of Investigative Dermatology 01/2011; 131(1):30-6. DOI:10.1038/jid.2010.257 · 6.37 Impact Factor
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ABSTRACT: Hexose-6-phosphate dehydrogenase (H6PDH) has emerged as an important factor in setting the redox status of the endoplasmic reticulum (ER) lumen. An important role of H6PDH is to generate a high NADPH/NADP(+) ratio which permits 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to act as an oxo-reductase, catalyzing the activation of glucocorticoids (GCs). In H6PDH knockout mice 11β-HSD1 assumes dehydrogenase activity and inactivates GCs, rendering the target cell relatively GC insensitive. Consequently, H6PDHKO mice have a phenotype consistent with defects in the permissive and adaptive actions of GCs upon physiology. H6PDHKO mice have also offered an insight into muscle physiology as they also present with a severe vacuolating myopathy, abnormalities of glucose homeostasis and activation of the unfolded protein response due to ER stress, and a number of mechanisms driving this phenotype are thought to be involved. This article will review what we understand of the redox control of GC hormone metabolism regulated by H6PDH, and how H6PDHKO mice have allowed an in-depth understanding of its potentially novel, GC-independent roles in muscle physiology.Molecular and Cellular Endocrinology 12/2010; 336(1-2):213-8. DOI:10.1016/j.mce.2010.12.004 · 4.24 Impact Factor
Article: Cerebrospinal Fluid Corticosteroid Levels and Cortisol Metabolism in Patients with Idiopathic Intracranial Hypertension: A Link between 11β-HSD1 and Intracranial Pressure Regulation?[Show abstract] [Hide abstract]
ABSTRACT: The etiology of idiopathic intracranial hypertension (IIH) is unknown. We hypothesized that obesity and elevated intracranial pressure may be linked through increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. The aim was to characterize 11β-HSD1 in human cerebrospinal fluid (CSF) secretory [choroid plexus (CP)] and drainage [arachnoid granulation tissue (AGT)] structures, and to evaluate 11β-HSD1 activity after therapeutic weight loss in IIH. We conducted in vitro analysis of CP and AGT and a prospective in vivo cohort study set in two tertiary care centers. Twenty-five obese adult female patients with active IIH were studied, and 22 completed the study. Intervention: Fasted serum, CSF, and 24-h urine samples were collected at baseline, after 3-month observation, and after a 3-month diet. Changes in urine, serum, and CSF glucocorticoids (measured by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry) after weight loss were measured. 11β-HSD1 and key elements of the glucocorticoid signaling pathway were expressed in CP and AGT. After weight loss (14.2±7.8 kg; P<0.001), global 11β-HSD1 activity decreased (P=0.001) and correlated with reduction in intracranial pressure (r=0.504; P=0.028). CSF and serum glucocorticoids remained stable, although the change in CSF cortisone levels correlated with weight loss (r=-0.512; P=0.018). Therapeutic weight loss in IIH is associated with a reduction in global 11β-HSD1 activity. Elevated 11β-HSD1 may represent a pathogenic mechanism in IIH, potentially via manipulation of CSF dynamics at the CP and AGT. Although further clarification of the functional role of 11β-HSD1 in IIH is needed, our results suggest that 11β-HSD1 inhibition may have therapeutic potential in IIH.The Journal of Clinical Endocrinology and Metabolism 12/2010; 95(12):5348-56. DOI:10.1210/jc.2010-0729 · 6.31 Impact Factor
Article: Low energy diet and intracranial pressure in women with idiopathic intracranial hypertension: prospective cohort study[Show abstract] [Hide abstract]
ABSTRACT: To observe intracranial pressure in women with idiopathic intracranial hypertension who follow a low energy diet. Prospective cohort study. Outpatient department and the clinical research facility based at two separate hospitals within the United Kingdom. 25 women with body mass index (BMI) >25, with active (papilloedema and intracranial pressure >25 cm H(2)O), chronic (over three months) idiopathic intracranial hypertension. Women who had undergone surgery to treat idiopathic intracranial hypertension were excluded. Stage 1: no new intervention; stage 2: nutritionally complete low energy (calorie) diet (1777 kJ/day (425 kcal/day)); stage 3: follow-up period after the diet. Each stage lasted three months. The primary outcome was reduction in intracranial pressure after the diet. Secondary measures included score on headache impact test-6, papilloedema (as measured by ultrasonography of the elevation of the optic disc and diameter of the nerve sheath, together with thickness of the peripapillary retina measured by optical coherence tomography), mean deviation of Humphrey visual field, LogMAR visual acuity, and symptoms. Outcome measures were assessed at baseline and three, six, and nine months. Lumbar puncture, to quantify intracranial pressure, was measured at baseline and three and six months. All variables remained stable over stage 1. During stage 2, there were significant reductions in weight (mean 15.7 (SD 8.0) kg, P<0.001), intracranial pressure (mean 8.0 (SD 4.2) cm H(2)O, P<0.001), score on headache impact test (7.6 (SD 10.1), P=0.004), and papilloedema (optic disc elevation (mean 0.15 (SD 0.23) mm, P=0.002), diameter of the nerve sheath (mean 0.7 (SD 0.8) mm, P=0.004), and thickness of the peripapillary retina (mean 25.7 (SD 36.1) micro, P=0.001)). Mean deviation of the Humphrey visual field remained stable, and in only five patients, the LogMAR visual acuity improved by one line. Fewer women reported symptoms including tinnitus, diplopia, and obscurations (10 v 4, P=0.004; 7 v 0, P=0.008; and 4 v 0, P=0.025, respectively). Re-evaluation at three months after the diet showed no significant change in weight (0.21 (SD 6.8) kg), and all outcome measures were maintained. Women with idiopathic intracranial hypertension who followed a low energy diet for three months had significantly reduced intracranial pressure compared with pressure measured in the three months before the diet, as well as improved symptoms and reduced papilloedema. These reductions persisted for three months after they stopped the diet.BMJ (online) 07/2010; 341(jul07 2):c2701. DOI:10.2307/20734830 · 16.38 Impact Factor
Conference Paper: PROSPECTIVE EVALUATION OF THE EFFECT OF WEIGHT LOSS ON INTRACRANIAL PRESSURE IN IDIOPATHIC INTRACRANIAL HYPERTENSIONABN Joint Annual Meeting/Spanish-Society-of-Neurology; 11/2009
Article: The Role of 11 beta-Hydroxysteroid Dehydrogenase 1 in Adipogenesis in Thyroid-Associated Ophthalmopathy[Show abstract] [Hide abstract]
ABSTRACT: Thyroid-associated ophthalmopathy (TAO) is a sight-threatening autoimmune disease in which de novo adipogenesis has been identified as a fundamental pathogenic mechanism. 11beta-Hydroxysteroid dehydrogenase 1 (11beta-HSD1) increases cortisol bioavailability and is pivotal in mediating glucocorticoid responses in adipose tissue and inflammation. In this study we characterize 11beta-HSD1 as a determinant of the adipogenic and inflammatory pathways in TAO orbital fat (OF) compared with normal OF. OF was harvested from 46 TAO and 44 control patients undergoing orbital surgery. Samples were examined by a combination of immunohistochemistry, real-time RT-PCR, primary cell culture, specific enzyme assays, colorimetric proliferation assays, and bead-based ELISA. Glucocorticoid (glucocorticoid receptor-alpha,11beta-HSD1, hexose-6-phosphate dehydrogenase) and inflammatory cytokines (IL-1beta, IL-1 receptor, IL-6, TNF-alpha, TNF-alpha inductible protein, TGF-beta2) target genes together with markers of late adipocyte differentiation (fatty-acid-binding-protein-4, glycerol-6-phosphate-dehydrogenase) were highly expressed in TAO whole OF (P < 0.05) compared with controls. Primary cultures of TAO OF stromal cells demonstrated greater 11beta-HSD1 oxoreductase activity (P < 0.05), which was regulated by cytokines, most notably TNF-alpha (P < 0.01), compared with controls. Activity increased across differentiation, and this was most marked in TAO cells (P < 0.01). Similarly, stromal cell proliferation was limited by incubation with cortisol in TAO cells only. Furthermore, cortisone decreased IL-6 (P < 0.005), IL-8 (P < 0.05), and macrophage chemoattractant protein-1 (P < 0.05) production by cultured TAO cells only, an effect that was abrogated by inhibition of 11beta-HSD1. Induction of 11beta-HSD1 activity and expression by inflammatory cytokines (TNF-alpha, IL-6) may enhance orbital adipocyte differentiation (adipogenesis) and limit proliferation in TAO. 11beta-HSD1 may also have a role in regulating the local orbital inflammatory response.The Journal of Clinical Endocrinology and Metabolism 10/2009; 95(1):398-406. DOI:10.1210/jc.2009-0873 · 6.31 Impact Factor
Article: NMR-based metabolomic analysis of cerebrospinal fluid and serum in neurological diseases--a diagnostic tool?[Show abstract] [Hide abstract]
ABSTRACT: We sought to evaluate the diagnostic accuracy of metabolomic biomarker profiles in neurological conditions (idiopathic intracranial hypertension (IIH), multiple sclerosis (MS) and cerebrovascular disease (CVD) compared to controls with either no neurological disease or mixed neurological diseases). Spectra of CSF (n = 87) and serum (n = 72) were acquired using (1)H NMR spectroscopy. Multivariate pattern recognition analysis was used to identify disease-specific metabolite biomarker profiles. The metabolite profiles were then used to predict the diagnosis of a second cohort of patients (n = 25). CSF metabolite profiles were able to predict diagnosis with a sensitivity and specificity of 80% for both IIH and MS. The CVD serum metabolite profile was 75% sensitive and specific. On analysing the second patient cohort, the established metabolite biomarker profiles generated from the first cohort showed moderate ability to segregate patients with IIH and MS (sensitivity:specificity of 63:75% and 67:75%, respectively). These findings suggest that NMR spectroscopic metabolic profiling of CSF and serum can identify differences between IIH, MS, CVD and mixed neurological diseases. Metabolomics may, therefore, have the potential to be developed into a clinically useful diagnostic tool. The identification of disease-unique metabolites may also impart information on disease pathology.NMR in Biomedicine 01/2009; 23(2):123-32. DOI:10.1002/nbm.1428 · 3.56 Impact Factor
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ABSTRACT: Data are presented on the urinary corticosteroid metabolic profile of the mouse strain 129/svJ. Through the use of GC/MS we have characterized, or tentatively identified corticosterone (Kendall's compound B) metabolites of both the 11beta-hydroxy and 11-carbonyl (compound A) series in urine. Full mass spectra of the methyloxime-trimethylether derivatives of 15 metabolites are included in the paper as an aid to other researchers in the field. Metabolites ranged in polarity from tetrahydrocorticosterone (THB) to dihydroxy-corticosterone with dominance of highly polar steroids. We found that prior to excretion corticosterone can undergo oxidation at position 11beta, reduction at position 20 and A-ring reduction. Metabolites retaining the 3-oxo-4-ene structure can be hydroxylated at position 6beta- as well as at an unidentified position, probably 16alpha-. Saturated steroids can be hydroxylated at positions 1beta-, 6alpha-, 15alpha- and 16alpha. A pair of hydroxy-20-dihydro-corticosterone metabolites (OH-DHB) were the most important excretory products accounting for about 40% of the total. One metabolite of this type was identified as 6beta-hydroxy-DHB; the other, of similar quantitative importance was probably 16alpha-hydroxy-DHB. The ratio of metabolites of corticosterone (B) to those of 11-dehydro-corticosterone (A) was greater than 9:1, considerably higher than that for the equivalent "human" ratio of 1:1 for cortisol to cortisone metabolites. Results from this study allowed the evaluation of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity in mice with deleted glucose-6-phosphate transporter (G6PT). These mice had attenuated back-conversion of A to B resulting in an increased ratio of A-metabolites to B-metabolites [Walker EA, Ahmed A, Lavery GG, Tomlinson JW, Kim SY, Cooper MS, Stewart PM, 11beta-Hydroxysteroid dehydrogenase type 1 regulation by intracellular glucose-6-phosphate, provides evidence for a novel link between glucose metabolism and HPA axis function. J Biol Chem 2007;282:27030-6]. We believe this study is currently the most comprehensive on the urinary steroid metabolic profile of the mouse. Quantitatively less steroid is excreted in urine than in feces by this species but urine analysis is more straightforward and the hepatic metabolites are less subject to microbial degradation than if feces was analyzed.Steroids 11/2008; 73(11):1066-76. DOI:10.1016/j.steroids.2008.04.004 · 2.72 Impact Factor
Article: 11beta-Hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets.[Show abstract] [Hide abstract]
ABSTRACT: Exposure to excess glucocorticoid is associated with pancreatic beta cell damage and decreased glucose-stimulated insulin secretion (GSIS). Inactive glucocorticoids (cortisone, 11-dehydrocorticosterone) are converted to active cortisol and corticosterone by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which requires NADPH as cofactor, which is generated by hexose-6-phosphate dehydrogenase (H6PDH). We investigated the localisation and activity of 11beta-HSD1 within pancreatic islets, and determined its functional role in the regulation of insulin and glucagon secretion. mRNA expression of 11beta-HSD1 (also known as HSD11B1), glucocorticoid receptor and H6PDH (also known as H6PD) in human pancreas and murine islets was examined by real-time PCR. 11beta-HSD1 protein levels were examined by immunohistochemistry and immunofluorescence. 11beta-HSD1 activity was assessed in intact tissue and isolated islets of wild-type (WT) and both 11beta-Hsd1- and H6pdh-null mice. Glucagon secretion and insulin secretion were analysed by RIA and ELISA respectively in isolated murine islets incubated with dexamethasone. 11beta-HSD1 co-localised with glucagon in the periphery of murine and human islets, but not with insulin or somatostatin. Dexamethasone, 11-dehydrocorticosterone and corticosterone induced a dose-dependent decrease in GSIS and glucagon secretion following low glucose stimulation. Reduction of 11beta-HSD1 activity with specific inhibitors or in experiments carried out in H6pdh-null mice reversed the effects of 11-dehydrocorticosterone, but had no effect following treatment with corticosterone. Local regeneration of glucocorticoid via 11beta-HSD1 within alpha cells regulates glucagon secretion and in addition may act in a paracrine manner to limit insulin secretion from beta cells.Diabetologia 10/2008; 51(11):2003-11. DOI:10.1007/s00125-008-1137-2 · 6.88 Impact Factor
Article: Elevated cerebrospinal fluid (CSF) leptin in idiopathic intracranial hypertension (IIH): evidence for hypothalamic leptin resistance?[Show abstract] [Hide abstract]
ABSTRACT: The aetiology of idiopathic intracranial hypertension (IIH) is not known, but its association with obesity is well-recognized. Recent studies have linked obesity with abnormalities in circulating inflammatory and adiposity related cytokines. The aim of this study was to characterize adipokine and inflammatory cytokine profiles in IIH. Paired serum and cerebrospinal fluid (CSF) specimens were collected from 26 patients with IIH and compared to 62 control subjects. Samples were analysed for leptin, resistin, adiponectin, insulin, IL-1beta, IL-6, IL-8 (CXCL8), TNFalpha, MCP-1 (CCL2), hepatocyte growth factor, nerve growth factor and PAI-1 using multiplex bead immunoassays. CSF leptin was significantly higher in patients with IIH (P = 0.001) compared to controls after correction for age, gender and body mass index (BMI). In the control population, BMI correlated with serum leptin (r = 0.34; P = 0.007) and CSF leptin (r = 0.51; P < 0.0001), but this was not the case for the IIH population. Profiles of other inflammatory cytokines and adipokines did not differ between IIH patients and controls once anthropometric factors had been accounted for. IIH was characterized by significantly elevated CSF leptin levels which did not correlate with BMI. We suggest that CSF leptin may be important in the pathophysiology of IIH and that obesity in IIH may occur as a result of hypothalamic leptin resistance.Clinical Endocrinology 10/2008; 70(6):863-9. DOI:10.1111/j.1365-2265.2008.03401.x · 3.35 Impact Factor
Article: Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency[Show abstract] [Hide abstract]
ABSTRACT: Cortisone reductase deficiency (CRD) is characterized by a failure to regenerate cortisol from cortisone via 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), resulting in increased cortisol clearance, activation of the hypothalamic-pituitary-axis (HPA) and ACTH-mediated adrenal androgen excess. 11beta-HSD1 oxoreductase activity requires the reduced nicotinamide adenine dinucleotide phosphate-generating enzyme hexose-6-phosphate dehydrogenase (H6PDH) within the endoplasmic reticulum. CRD manifests with hyperandrogenism resulting in hirsutism, oligo-amenorrhea, and infertility in females and premature pseudopuberty in males. Recent association studies have failed to corroborate findings that polymorphisms in the genes encoding H6PDH (R453Q) and 11beta-HSD1 (Intron 3 inserted adenine) interact to cause CRD. Our objective was to reevaluate the genetics and steroid biochemistry of patients with CRD. We analyzed 24-h urine collection for steroid biomarkers by gas chromatography/mass spectrometry and sequenced the HSD11B1 and H6PD genes in our CRD cohort. Patients included four cases presenting with hyperandrogenism and biochemical features clearly indicative of CRD. Gas chromatography/mass spectrometry identified steroid biomarkers that correlated with CRD in each case. Three cases were identified as homozygous (R109AfsX3, Y316X, and G359D) and one case identified as compound heterozygous (c.960G-->A and D620fsX3) for mutations in H6PD. No mutations affecting enzyme activity were identified in the HSD11B1 gene. Expression and activity assays demonstrate loss of function for all reported H6PDH mutations. CRD is caused by inactivating mutations in the H6PD gene, rendering the 11beta-HSD1 enzyme unable to operate as an oxoreductase, preventing local glucocorticoid regeneration. These data highlight the importance of the redox control of cortisol metabolism and the 11beta-HSD1-H6PDH pathway in regulating hypothalamic-pituitary-adrenal axis activity.Journal of Clinical Endocrinology & Metabolism 10/2008; 93(10):3827-32. DOI:10.1210/jc.2008-0743 · 6.31 Impact Factor
Top Journals
University of Birmingham
Birmingham, England, United Kingdom
- • School of Immunity and Infection
- • Centre for Endocrinology, Diabetes and Metabolism (CEDAM)
- • School of Clinical and Experimental Medicine
- • Institute for Biomedical Research
The Queen Elizabeth HospitalTarndarnya, South Australia, Australia
University of Texas Southwestern Medical Center
Dallas, TX, United States
- Department of Internal Medicine
Queen Elizabeth Hospital BirminghamBirmingham, England, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, England, United Kingdom
- Department of Medicine


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Joe Tordy posted 859 days ago
Great idea! If it turns out that the Ravens choose not to use the exclusive tag, that would definitely generate some buzz!
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