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Explore the Entrepreneurship.org Resource Center to find resources. Designed with entrepreneurs in mind, our resource center allows you to find materials to grow great ideas.
Mentors help us confront adversity, seize opportunity, learn from mistakes, understand our strengths and grow as leaders. Learn how to be an effective mentor to other entrepreneurs. (Published Oct 2002)
Entrepreneurs loath to seek mentoring should take at least one piece of advice: try it, you'll like it, writes the author who built a business by accepting help from smarter and more experienced founders. Included is a look at the workings of her relationship with her current mentor. (Originally Published October 2002)
Don Grimm spreads his giving back around through nonprofit and for-profit boards to tech transfer and angel investing.
Pittsburg, Kansas and Pittsburg State University benefit from the broad generosity of Gene Bicknell, who gives because "it's the right thing to do."
Joan and Stephen Carter's small company gives back to entrepreneurship in a big way through the Junior Achievement program.
Through university lectures and financial support, Maxine Clark is giving the next generation of entrepreneurs a leg up.
Vicki Wu's passion for her business and philanthropic activities have caused her to seek convergences between the for- and non-profit worlds.
A media entrepreneur advises joining and utilizing peer-to-peer groups that are selective to build the human capital that enables the building of companies.
Nancy Richards could have taken an easier route with her business, but instead chooses to help small, talented companies get established by creating partnerships with them.
Jack Stack gives back to entrepreneurship in a variety of ways, but one of his main contributions has been through delivering a consistent message: employees at all levels of a company should think and act like they own it.
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June 21, 2012
LOGAN, Utah - Utah State senior distance runner Daniel Howell was named to the 2012 Capital One Academic All-America® Division I Men's Track & Field/Cross Country first team, as selected by the College Sports Information Directors of America (CoSIDA) Thursday.
This marks the second-straight year that Howell has received CoSIDA Capital One Academic All-American honors as he was also named to the third-team in 2011.
Howell, a Manti, Utah native, joins Miles Batty of BYU as the only men from the state of Utah to be named to the CoSIDA Academic All-American teams as both athletes were named to the first team. Howell is also the only Western Athletic Conference male to receive the honor. Idaho's Hannah Kiser represented the WAC on the women's side on the second team, while Nachelle Mackey of BYU (first team) and Sarah Callister of Weber State (third team) were the only women from the state of Utah to receive the accolades.
Additionally in his career, Howell has also received academic all-district honors from the United States Track & Field and Cross Country Coaches Association (USTFCCCA) in 2010 and 2011, along with being an 11-time academic all-WAC honoree.
Howell has a 3.963 GPA majoring in wildlife sciences and rangeland resources. He is a 14-time first-team all-WAC honoree during his Utah State cross country and track career as he won the 3,000m and 5,000m at the 2012 WAC Indoor Championships, while also capturing the 3,000m steeplechase and 5,000m titles at the 2012 WAC Outdoor Championships. Howell also placed fourth at the 2011 WAC Cross Country Championships.
At the first round of the 2012 NCAA Outdoor Championships, Howell competed in two events placing 21st in the 3,000m steeplechase with a time of 9:03.38 as well as finishing 45th in the 5,000m 15:12.85.
To be eligible for Academic All-America® consideration, a student-athlete must be a varsity starter or key reserve, maintain a cumulative G.P.A. of 3.30 on a scale of 4.00, have reached sophomore athletic and academic standings at his/her current institution and be nominated by his/her sports information director.
Since the program's inception in 1952, CoSIDA has bestowed Academic All-American honors on more than 15,000 student-athletes in Divisions I, II, III and NAIA, covering all NCAA championship sports.
For more information about the Academic All-America® Teams program, fans can visit www.cosida.com.
Fans can follow Utah State Athletics, including USU track & field and cross country, at http://twitter.com/USUAthletics or on Facebook at http://facebook.com/USUAthletics.
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Utah State cross country faces tough competition Saturday, Sept. 27 at the 29th annual Roy Griak ...09/26/2014
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In This Section
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Audibility of a CD-Standard A/DA/A Loop Inserted into High-Resolution Audio Playback - September 2007
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Sound Board: Food for Thought, Aesthetics in Orchestra Recording - April 2015
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Reflecting on Reflections - June 2014
4 comments
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Articles about reggae music, reviews, interviews, reports and more...
How very nice that Heartbeat Records' series of Deluxe Edition reissues includes this gem from Johnny Osbourne, a primarily roots-and-culture artist who started out as a lead and harmony singer with The Sensations in the late '60s before relocating to Canada. He was back in Jamaica by 1979, right about the time Clement Dodd was upgrading his studio from 4 to 16 tracks and in the process of enhancing some of his past classic riddims with new instrumentation and recruiting fresh voices to sing over them. With his clear, rich mid-range singing, Osbourne was ideal for the resurgent Studio One sound, widely considered to be the roots of dancehall.
The songs that first appeared on Truths and Rights nearly 30 years ago- including such socially and spiritually conscious offerings as the title track, the sublime "Jah Promise" and the plainspoken "We Need Love" along with breezier fare like "Sing Jay Stylee," -have lost none of their impact. Familiar riddims crackle with new life and lyrical sentiments regarding the futility of war and the like could have been written yesterday. As for the added tracks that make this Deluxe Edition deluxe, there's a previously-unreleased-on-CD "Jealousy, Heartache and Pain" that shows Osbourne's lover's rock side, a trio of extended mixes plus dub and deejay takes on a couple of the originals.
As a release among several that marked a new beginning for one of reggae's most renowned producers and for Johnny Osbourne himself while reggae was taking a new turn, Truths and Rights is truly and rightly a classic.
Interview: Tiken Jah Fakoly (2014)
By Franck Blanquin
Interview: The Philosophy of Anthony B
By Angus Taylor
Interview: Protoje (2014)
By Angus Taylor
Tarrus Riley in Cergy
By Franck Blanquin
The 20 Best Reggae Songs of the first half of 2015
By Erik Magni
Aysha Lorén album launch in London
By Angus Taylor
Morgan Heritage in Oakland
By Lee Abel
Capital Letters - Vinyard
By Gerard McMahon
Jah Cure at Red Stripe Beer Wednesday
By Steve James
© 2007-2015 United Reggae. All Rights Reserved. Reproduction in whole or in part is prohibited. Read about copyright
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|Amazon Price
|New from
|Used from
|Disc: 1
|1. First Of The Gang To Die
|2. In The Future when Alls Well
|3. I Just Want To See The Boy Happy
|4. Irish Blood, English Heart
|5. You Have Killed Me
|6. That's How People Grow Up [NEW]
|7. Everyday Is Like Sunday
|8. Redondo Beach
|9. SuedeHead
|10. The Youngest Was The Most Loved
See all 15 tracks on this disc
|Disc: 2
|1. The Last of the Famous International Playboys
|2. The National Front Disco
|3. Let Me Kiss You
|4. Irish Blood, English Heart
|5. I Will See You in Far-off Places
|6. First of the Gang to Die
|7. I Just Want to See the Boy Happy
|8. Life is a Pigsty
|9. That's How People Grow Up (U.S. EXCLUSIVE)
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I really enjoyed this album but I would've preferred if the track listing would be much different. Most of the tracks are from his albums released in 2004 and 2006. Read morePublished 13 months ago by Connor Burnett
I am a fan of Morrisey and this is a good bundle of his music.Published on April 5, 2010 by Gustavo Lopez
Greatest Hits being Morrissey's 2008 release and is an amazing collection of his hits, i.e. "Irish Blood, English Heart", "The Last of the Famous International Playboys" and "The... Read morePublished on March 2, 2010 by Bjorn Viberg
I don't know why, but 75% of the songs on this compilation are from the last 5 years. What happened to the late 80s, early 90s work?!Published on June 2, 2008 by Tyler B.
para quien no posee los anteriores discos solistas de morrissey, este puede ser un gran comienzo, es una buena recopilacion, quizas deberia repartirse mejor en toda su carrera, ya... Read morePublished on May 27, 2008 by Altieri Benitez Juan Andres
The greatest hits relates to number of records sold not to quality of song writing so classics like 'November Spawned a Monster' are missing. Read morePublished on April 26, 2008 by B. P. Shearn
I bought this, and while I'm not ashamed as I am a bottle of Open Pit shy of Waco for all things Mozzer, in comparison with the first best of, the heavy reliance of his past two... Read morePublished on April 2, 2008 by epsteinsmutha
|From this Discussion
yes there are too many best-ofs for Morrisey and The Smiths each. but how do you know "Suedhead" will be on this one as once again no track listings are available? I know the disc hasn't been released yet, but the songs on the disc certainly can't be a mystery at this point. however,... Read More
Jan 25, 2008 by Yule Ooloo | See all 5 posts


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Originally written on RealGM | Last updated 7/28/13
The Atlanta Hawks have claimed Gustavo Ayon off waivers, a league source told RealGM. Ayon was released by the Milwaukee Bucks on Thursday with their glut in the frontcourt, but the 6-foot-10 big man received heavy interest due to his inside presence and reasonable contract worth $1.5 million next season. Ayon is expected to get a fair trail to earn a spot in a Hawks rotation that has lacked a young, developing center alongside Al Horford. Ayon, 28, has averaged 4.8 points and 4.3 rebounds in two NBA seasons. The Hawks will be his fourth team.
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HREC® - Hospitality Real Estate Counselors® is a leading national hotel and casino advisory firm specializing in property sales, debt financing, consulting, appraisal and litigation support.
Focused exclusively on the hospitality industry, HREC® offers unparalleled expertise in hotel property sales, hotel and hospitality property mortgage services and is an industry leader in hotel brokerage.
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Attending: Mike Armstrong, Hank Wolpert, Steve Strenk
Date: Thursday, August 6th, 2015
Location: Hyatt Regency DFW Airport - Dallas, Texas
Speaker: Geoff Davis
Date: Tuesday, August 11th, 2015
Location: The Magnolia Hotel


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Dominique Benoit
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- An intervention study on interprofessional practice in intensive care: effects on conditions, processes, and competence orientation
- Dual disseminated infection with Nocardia farcinica and Mucor in a patient with systemic lupus erythematosus: a case report
Year in review in Intensive Care Medicine 2013, I: acute kidney injury, ultrasound, hemodynamics, cardiac arrest, transfusion, neurocritical care, and nutrition
2014) INTENSIVE CARE MEDICINE. 40(2). p.147-159 Mark(
Year in review in Intensive Care Medicine 2013, II: sedation, invasive and noninvasive ventilation, airways, ARDS, ECMO, family satisfaction, end-of-life care, organ donation, informed consent, safety, hematological issues in critically ill patients
2014) INTENSIVE CARE MEDICINE. 40(3). p.305-319 Mark(
Year in review in Intensive Care Medicine 2013, III: sepsis, infections, respiratory diseases, pediatrics
2014) INTENSIVE CARE MEDICINE. 40(4). p.471-483 Mark(
Acute respiratory distress syndrome in patients with malignancies
2014) INTENSIVE CARE MEDICINE. 40(8). p.1106-1114 Mark(
- Inappropriate care in European ICUs confronting views from nurses and junior and senior physicians
Validity analysis of a unique infection surveillance system in the intensive care unit by analysis of a data warehouse built through a workflow-integrated software application
2014) JOURNAL OF HOSPITAL INFECTION. 87(3). p.159-164 Mark(
Long-term outcome and quality of life in ICU patients with acute kidney injury treated with renal replacement therapy: a case control study
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- Determinants of procedural pain intensity in the intensive care unit: the Europain study


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Cheesy Sun Crisps
11 Dec 2009
Cheesy sun crisps is a two cheese baked oat and sunflower seeds recipe. Prepared with margerine and seasoned with salt, the cheesy sun crisps is combined with flour and and baked as cookies in the oven. Cooled and stored, the cheesy sun crisps are snacky and delightful.
|Shredded cheddar cheese
|8 Ounce (2 Cups)
|Grated parmesan cheese
|1⁄2 Cup (8 tbs)
|Sunflower oil
|1⁄2 Cup (8 tbs)
|1 Tablespoon, softened
|3 Tablespoon
|All purpose flour
|1 Cup (16 tbs)
|1⁄4 Teaspoon
|Quick oats
|1 Cup (16 tbs), uncooked
|Roasted salted sunflower seeds
|2⁄3 Cup (10.67 tbs)
Beat cheeses, margarine and water in bowl until blended.
Mix in flour and salt.
Stir in oats and sunflower seeds until combined.
Shape into 12-inch-long roll; wrap securely.
Refrigerate about 4 hours or up to 1 week.
Preheat oven to 400°F.
Lightly grease cookie sheets.
Cut roll into 1/8 to 1/4 inch slices; flatten each slice slightly.
Place on prepared cookie sheets.
Bake 8 to 10 minutes or until edges are light golden brown.
Remove immediately; cool on wire rack.
Recipe Summary
Difficulty Level:Easy
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Cheesy Sun Crisps Recipe


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Dyme-A-Duzin - "That Chicken"
Don't play around with mine.
Don't play around with mine.
Off the Brooklynite's Hip-Hope project.
Off the Brooklynite's Hip Hop project.
A 2Dope premiere off the Brooklyn emcee's Hip Hope project.
Beats & rhymes.
Adventures in Inglewwod.
Hip Hope is out now.
One of Brooklyn's finest releases his long-awaited new project.
Produced by Harry Fraud.
His new album, Hip Hope, finally has a release date.
Produced by Urban Rockstarz.
La Musica de Harry Fraud.
As a part of the Puma Shoestring Experience.


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Kristen O'Connor: Collection of stories about her "American Idol" journey
Former American Idol contestant Kristen O'Connor is slated to perform at Capt Hiram's April 28. The restaurant will not be charging admission for the concert.
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Brian: We Will Rock You (Asteroid Version) / 51 Degrees North Event Q&A
Roger Live! Wintershall 2011
Roger will be performing 20 minute slot at the Wintershall Charity Concert on Saturday June 4th.
He will be joined by Spike Edney (keyboards), Steve Stroud (Bass), his son Rufus (Drums) and Jason Falloon (Guitar), plus Jeff Beck has also promised to join Roger onstage for a couple of numbers!
Roger will also be guesting the Band Du Lac, which is Gary Brooker's house band for a couple of songs.
Click here to buy tickets!
Tickets for this very special black-tie event are £135 each and can be purchased by telephone from 01483 892167 (Monday to Friday 9AM to 5PM - UK) or via email from email@example.com.
This year's concert will benefit stroke research. Gates to the estate will open at 4PM and music will begin at 6PM, concluding with fireworks at midnight. Those attending are invited to bring picnics to enjoy by the lakeside.
Other musicians also taking part this year Eric Clapton, Gary Brooker, Lulu, Paul Carrack, Georgie Fame and Daniele de Niesse.
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The Official Queen Podcast: Episode 14 - Steve Coles Interview
Watch Brian Test His Own Queen Knowledge on Play The Game App!
Freddie Mercury Official Birthday Party Update: Live Entertainment Announced - Unrisen Queen Confirmed


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With Minnesota's population growing older, credit unions must be prepared to handle the changing needs of their members.In order to assist with the care and needs, many members are relying upon the support of a loved one to manage their day-to-day decisions, including their finances. Minnesota law provides three legal relationships for persons in need of this assistance: powers of attorney; conservatorships and guardianships. Each of these relationships grant a designated person a different level of control over a protected person. Depending on how these documents are constructed, the designated person's powers may range from very limited to complete control over a member's assets. Credit unions must be aware of the differences in these documents to ensure the designated person exercises proper control over the member's assets and to avoid situations involving elder abuse, theft and fraud.
To assist credit unions in understanding these protective relationships, the Minnesota Credit Union Network is hosting a webinar focused on account compliance for conservatorships, guardianships and powers of attorney. This session will detail what a credit union must consider when presented with a legal document establishing one of these relationships.
Specifically, the webinar will highlight:
Participants will receive login instructions and handout materials via email prior to the webinar. In addition after the session, registrants will receive a web link to the recorded webinar.
Time: 10 a.m.-11 a.m.Cost: $89Deadline: Friday, Dec. 14


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Need to Know: The Redskins practiced in the rain on Day 8 of training camp and it's really no big deal to the players.
Redskins Talk
Virginia Governor Terry McAuliffe stopped by Redskins training camp on Friday.
With New England coming to town for a scrimmage next week, Redskins head coach Jay Gruden says they're as good a blueprint as there is for building a winner.
The Redskins are slated to practice against the Patriots on Monday, but will rain ruin the plans? Jay Gruden hopes not.
How much will the Redskins benefit from having referees at training camp this week?


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Baylor/RGIII's pro day on ESPNU today. I'm DVR'ing it. Yeah, that's what it's come down to. I'm recording a dude's draft workout. LOL
Baylor/RGIII's pro day on ESPNU today. I'm DVR'ing it. Yeah, that's what it's come down to. I'm recording a dude's draft workout. LOL
Watch this video breaking down Luck vs. RGIII.
I actually believe that the Colts could take RGIII and leave us with Luck.
I'm pretty sure the Colts will take RG3. It's just our luck, too. NPI.
I'm all for RGIII but I won't be crushed if we have to settle for Luck.
Agreed. We could get 'stuck with' Luck.
The Colts may find RGIII is the equal player but far less demanding in contract negotiations.
The rookie salaries are now slotted so there really is no negotiating. I just think that they'll believe RGIII is the better player.
I'm hopelessly head-over-heels in love with RGIII myself, but it's comical that we're all worried about getting "stuck" with Andrew Luck, whom most people have considered the best QB prospect since Peyton Manning, or even John Elway.
If we have the good fortune of drafting Andrew Luck, we'll end up with one of the top 5-7 QB's (if not higher) within 3 years of his first game. He'll easily be the most gifted QB that Mike Shanahan has worked with since Elway.
LOL, Stuck with Luck. I'd be thrilled! Actually, I'd be a little sad since I have admitted man crush on RGIII. But I would get over it rather quickly.
Last edited by JonBlaze; 03-21-2012 at 08:41 PM.
i'm kinda sick with the amount of green in here. it almost feels like we lost an avatar bet to the eagles forum
I don't have a signature. You're imagining reading this right now. You should really see a mental health professional about this.
Part of USA TODAY Sports Digital Properties.


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Zac Farro
Brand New Eyes Chapter 6
POV: Hayley "Sam sit down for a sec, I gotta tell ya something." She listen to me and sat down. "You two look
Unexpected Love (Chapter 8)
So I've been meaning to update sooner since the last chapter, and read more updates, but so much has happened this week and weekend: First
One Sumemer (Chapter 7)
So it's been a really long time..... Yep areally long time. Anyways I'm back, and I'm here to post again and of course read you
Incite My Riots Chapter 5
"You guys are late for soundcheck! Hayley, I know you're usually fifteen minutes late or whatever, but 45 minutes? Josh, you should know better, you're
Incite My Riots Chapter 4
"I can't believe you forced me into this." Josh grumbled as he tightened the skates around his ankles. "Hey, you didn't have to come and spend
Unexpected Love (Chapter 7)
So it's only been like a week, and yay I'm updating again. Hopefully I can keep it up, and possibly update more. Seriously I remember
One Summer (Chapter 6)
Can't believe I haven't updated in like a month, I can't tell you how awful I feel, but hey I think I've sort of
~Unexpected Love~ (Chapter 6)
So as I promised here's 'Unexpected Love' Hope you'll enjoy the drama > ;) (Hayley's P.O.V) "Uhmmm… Hayley…" Josh starts but pauses as he was now
One summer (Chapter 5)
So once again it takes me fore ever to update, I won't bore you with a long explanation. Anyways last time I checked, "One Summer&rdquo
One Summer (Chapter 4)
So once again I've taken forever to update again, but hopefully you'll all forgive me. Anyways school starts in another week from now for me
~One Summer (Chapter3)~
So here's chapter three, sorry it's taken me so long to update. For some reason I just had a hard time with the chapter. Anyways
Unexpected Love (Chapter 5)
So here's the next installment, wonder what will happen at Josh's apartment? Hope you'll enjoy and thank you the comments on the previous chapter ;) I
~One Summer (Chapter2) ~
So first off I want to say I'm extremely sorry for not updating in a while, but I really haven't had time. My life is
Unexpected Love (Chapter 4)
So I'm kind of updating a little late than I intended today, were all in different parts of the world, so I hope it's not
~One Summer (Chapter1) ~
So finally here's chapter 1, the first chapter is always a bit boring, but I promise it'll pick up quicker once Hayley's actually in Cali


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|Would locked out Celtics consider signing overseas?
|07.08.11 at 5:16 pm ET
Almost 50 years after The Beatles led The British Invasion of rock bands into the popular culture in the United States, none of the self-proclaimed Heatles have committed to participate in what increasingly appears to be an invasion of NBA players into basketball leagues overseas.
But that's not to say none of the NBA's superstars aren't (triple negative!) considering overseas options while the league's owners have locked out the players with the absence of a collective bargaining agreement. A different wrinkle in this Eurasian Invasion pops up almost every day.
Nets point guard Deron Williams is leading the charge of superstars attempting to create leverage for the players, as he reportedly agreed in principal to a one-year, $5 million deal with Turkey-based (get it?) Besiktas should the NBA's lockout last through the summer. Upstart Canadian National Basketball League has already extended invites to the likes of Dirk Nowitzi and LeBron James. Imports like Zaza Pachulia, Andrei Kirilenko, Marco Belinelli, Patrick Mills and Carlos Delfino are all considering returning overseas. Free agent veterans like Sonny Weems and undrafted free agents like David Lighty have already agreed to deals that will keep them in Europe even if there is a 2011-12 NBA season. And Lakers superstar Kobe Bryant has discussed the possibility of leading a group of players represented by his agent, Rob Pelinka, on an exhibition tour of China.
It's hard to believe that Nenad Krstic started this trend, snubbing the Celtics and other free-agent center pursuers to sign with CSKA Moscow for two years and $9.8 million. With new rumors emerging every day, are the Celtics in danger of losing any other members of the 2010-11 roster overseas?
Let's examine the potential for Celtics to explore options abroad …
|Austin Rivers dunks twice on Rasheed Wallace
|07.08.11 at 3:23 pm ET
Duke University's No. 1 basketball recruit and son of Celtics coach Doc Rivers, Austin Rivers put on a show in his debut at the SJG Greater NC Pro-Am (a.k.a. "The Rucker of the South"), dunking not once but twice on former Celtic Rasheed Wallace — thanks to some vintage Sheed defense (or lack thereof).
|Shaq video chronicles gruesome cast removal
|07.08.11 at 1:56 pm ET
For anyone who might think Shaquille O'Neal exaggerated the right Achilles tendon injury that kept him from all but 12 minutes of the 2010-11 NBA Playoffs, take a look at the foot-long surgical incision on his leg in the embedded video — pieced together from a series of videos he posted on Tout.
Apparently, Shaq underwent surgery on the Achilles in the month and change since he informed the Celtics that he would retire from the NBA after 19 seasons. He now sports a supportive boot, complete with a chrome lining.
During his retirement press conference, Shaq announced his final nickname — The Big AARP — laying his Superman, The Big Shamrock and countless other monikers to rest. Of course, he only lasted a little over a month before declaring yet another nickname as a result of the surgical staples you can see being removed from his calf and ankle: The Big Staple Center.
Both Shaq and girlfriend Nicole "Hoopz" Alexander hinted at more to come. First, Shaq said he'll be hiding his removed cast somewhere and will provide clues to its location soon. And then Hoopz tweeted that she and Shaq will be driving to the West Coast and back in an RV. Kinda like "On the Road" but with Jack KerouShaq.
Let's just hope Yao Ming follows a similar post-career path after Yahoo! Sports broke news of his retirement.
|Mickael Pietrus: 'Celtics are interested in me'
|07.07.11 at 10:10 am ET
Four months after the Celtics could have used his services — and possibly avoided trading Kendrick Perkins for Jeff Green — Suns swingman Mickael Pietrus is claiming the C's are interested in him, according to French newspaper L'Ãquipe (via HoopsHype).
Phoenix didn't use me, but that's their problem. I'm going to continue working. The only thing I care about is winning a title. … A lot of teams are interested in me, like the Lakers or the Celtics. This came from the best player in the world: Kobe Bryant. He told me two months ago that he would like to see me with the Lakers.
It's unclear whether the curiosity coming from Boston is new or just an aftereffect from the rumors that circled around Pietrus and fellow Suns swingmen Grant Hill and Jared Dudley before this past NBA trade deadline.
|Report: Von Wafer wouldn't rule out Celtics return
|07.06.11 at 1:29 pm ET
In order to break his streak of starting with a new team each time he enters an NBA training camp, Von Wafer is reportedly opening to returning to the Celtics if and when the 2011-12 season begins, according to a report by ESPN.com's Chris Forsberg. Here's what Wafer's agent, Terrance Doyle, told Forsberg:
"Von would love to be back. He's never gotten that opportunity to go back with a team."
But do the Celtics want Wafer back? Especially considering they gave Wafer's No. 12 to their first-round pick (Purdue's JaJuan Johnson) and drafted a shooting guard with their No. 55 pick (Purdue's E'Twaun Moore) in addition to signing another undrafted guard (Pittsburgh's Gilbert Brown). Not to mention the number of quality shooting guards expected to be available via free agency — including Delonte West.
In just 9.5 minutes per over 58 games — no thanks in part to a calf injury — Wafer averaged 3.2 points on 42.1 percent shooting from the field (26.9 from 3-point range). Unless you count his preseason brawl with West, Wafer didn't exactly provide the firepower off the bench the Celtics had hoped from a guy who scored 9.7 points on 44.7 percent shooting (39.0 from 3) during his 2008-09 campaign in a Rockets uniform.
While Wafer's defensive deficiency improved under the tutelage of Doc Rivers & Co., he only reached double-digit scoring just six times during the season. Two of those performances came in the final two games of the regular season, when the starters rested, and two more came in 15-point blowouts. Chances are the Celtics could find somebody to provide better punch on both ends of the floor — even at the bottom of the salary barrel.
|Is Wyc Grousbeck willing to lose entire NBA season?
|07.01.11 at 9:30 am ET
The NBA officially entered a lockout at 12:01 a.m. on Friday, and while positive signs are emerging from the NFL camp, more and more questions are developing about whether NBA owners and players can negotiate a collective bargaining agreement before the league starts losing games.
In fact, some owners are willing to lose the entire 2011-12 NBA season in order to get what they want, and Celtics owner Wyc Grousbeck is among them, according to Yahoo! Sports columnist Adrian Wojnarowski:
Back in the labor talks of 2005, Celtics owner Wyc Grousbeck would say over and over in the negotiating sessions: The lockout is an investment.
Grousbeck smartened up, kept that thought to himself, but rest assured the mindset hasn't changed. He's one of the owners believed to be willing to lose the next season, along with Phoenix's Robert Sarver.
While the Celtics are thought to be one of the few teams that could actually benefit from a shortened season — considering the aging legs of Paul Pierce, Kevin Garnett, Ray Allen and Jermaine O'Neal — only Grousbeck would benefit from a lost season, as $31.2 million worth of Garnett and Allen would come off the books. That is, unless you think Dwight Howard is wearing green if and when the 2012-13 season comes around.
|Celtics free-agent options at shooting guard
|06.30.11 at 12:15 pm ET
We're 12 hours and counting from the NBA lockout, but that doesn't mean we can't examine who will be available to the Celtics through free agency for the (fingers crossed) 2011-12 season once commissioner David Stern and players association executive director Billy Hunter hash out their differences. Since we have already analyzed the centers, we'll move on to the C's next-greatest need: Shooting Guards.
Just as the Celtics seemingly solidified the center position prior to the 2010-11 season, the same could be said for two-guards. They featured a Hall of Fame starter (Ray Allen) along with a tough combo guard (Delonte West), a lengthy swingman (Marquis Daniels) and a shoot-first scorer (Von Wafer). The latter three are unrestricted free agents this offseason, and there's a chance any of the trio could return.
As we've noted before, the Celtics have six players under contract in 2011-12 for a combined $64.3 million (Kevin Garnett, $21.2; Paul Pierce, $15.33; Ray Allen, $10; Rajon Rondo, $10; Jermaine O'Neal, $6.23; Avery Bradley, $1.53), and Jeff Green is due at least another $5.91 million this offseason.
However, unlike the center situation, there will be a ton of quality available shooting guards. As a result, Celtics president Danny Ainge can more easily upgrade the team as a whole by dedicating what little money he'll have available to a two-guard once the collective bargaining agreement is in place.
Without further ado, let's take a look at the options that should be available to the Celtics at shooting guard, separating the current free-agent players into four categories '¦
Latest from Bleacher Report
- Austin Ainge Offers Window to C's Pre-Draft Process
- Trade Possibilities for C's with Draft Approaching
- Latest Buzz Surrounding Jamal Crawford, Kristaps Porzingis, Celtics'...
- Latest NBA Trade Rumors, Buzz
- Ranking Celtics' Biggest NBA Draft Needs
- Buzz Surrounding Ty Lawson, Celtics Draft Plans and More
- Realistic Targets for Celtics to Chase During Offseason


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Blind Melon
by Blind Melon
Released: Sep 1992
Label: Capitol Records
Blind Melon got lost in the shuffle after their big 1992 hit "No Rain" faded and that's a shame. Shannon Hoon's fatal OD in 1995 didn't help, either. This debut is anything but an effort befitting a one-hit wonder -- not one bad song, a range of brainy influences emerge and Hoon's lost outsider lyrics put it way beyond the trendiness of the grunge wave they were riding.


text:
Capital Markets
Company Overview of Promark Global Advisors, Inc.
Company Overview
767 Fifth Avenue
New York, NY 10153
United States
Founded in 1990
Key Executives for Promark Global Advisors, Inc.
Promark Global Advisors, Inc. Key Developments
Promark Global Advisors, Inc. Presents at Pension, Foundation and Endowment Conference, Jun-05-2014 11:00 AM. Venue: New York, United States. Speakers: Jason Glass.
Promark Global Advisors, Inc. Presents at The Hedge Fund Operational Due Diligence Forum, Oct-22-2013 03:30 PM. Venue: The Princeton Club, 15 West 43rd Street between 5th and 6th Avenues, New York, NY 10036, United States. Speakers: Randy Klein, Head of Operational Risk.
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Our data partners will research the update request and update the information on this page if necessary. Research and follow-up could take several weeks. If you have questions, you can contact them at firstname.lastname@example.com.


text:
July 5, 2015
John Calvin Stevens' paintings at University of New England
The architect who shaped Portland was an impressive painter, too.
July 5, 2015
Society Notebook: Ball thrown for animal lovers
Supporters of the Animal Refuge League bring in $60,000 for the care of thousands of furry and feathered future family members.
July 5, 2015
Schwarzenegger embraces his aging Terminator
The 67-year-old actor plays a kinder, gentler cyborg in his fourth role in the 'Terminator' franchise.
July 5, 2015
Aasif Mandvi bridges East-West gap on 'Daily' basis and now HBO
Born in India, raised in Florida, he both writes for and stars in 'The Brink.'
July 5, 2015
Biography tracks life of record-industry revolutionary
At one time, Allen Klein was the manager of both the Beatles and the Rolling Stones.
July 5, 2015
New on DVD
July 5, 2015
Book review: 'Project Puffin' explores complicated return of Maine coastal icon
The memoir recounts the impressive restoration of a colony on Eastern Egg Rock and the conservation questions it raised.
July 5, 2015
New shows open at Gleason Fine Art
The Boothbay Harbor gallery exhibits the work of Kevin Beers and Jean Swan Gordon through July 28.
July 5, 2015
Take Heart: A conversation in poetry
"Island Transport" by Elizabeth Garber
July 5, 2015
Bates Dance festival features new work about the AIDS crisis
Choreographer Sean Dorsey hopes 'The Missing Generation' helps people remember.
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telecommutingA term coined by Jack Nilles in the early 1970s to describe a geographically dispersed office where workers can work at home on a computer and transmit data and documents to a central office via telephone lines. A major argument in favor of telecommuting over vehicular commuting is that it does not produce air pollution. In addition, many people are more productive working at home than in an office. For others, however, the contrary holds true.
From secure messaging to document editing, our top free must-have apps have been rated, reviewed and named the best free Android apps of 2015. Read More »The Five Generations of Computers
Learn about each of the five generations of computers and major technology developments that have led to the current devices that we use today. Read More »Cloud Computing Market Leaders, 2015
If not for AWS, Microsoft would dominate the cloud. The race to capture market share will grow ever more fierce in the years ahead. Here's a look... Read More »
From wacky alarm clocks to lecture hall tools and after class entertainment, these Android apps are a good fit for a student's life and budget. Read More »Network Fundamentals Study Guide
A network is a group of two or more computer systems or devices, linked together to share resources, exchange files and electronic communications.... Read More »Computer Architecture Study Guide
This Webopedia study guide describes the different parts of a computer system and their relations. Read More »
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text:
Cameo Tension Shower Rod - Bronze
Item #: 081492785712 Stock Status: In Stock
$11.99 - $15.99
The Cameo Bronze Tension Rod is a must have in any home. This sturdy metal tension rod hangs your curtain with ease. Easy to install.
Product Dimensions Additional Product Info
- Cameo Bronze Tension Rod Features:
- Use this tension rod to hang a shower curtain, window treatments or clothing in a closet (use added support)
- Large expands 50 to 87 inches
- Medium expands 43 to 75 inches
- Small expands 25 to 43 inches
- Additional Information:
- Ground shipping only.
- Gift wrapping not available for this item.
Product Dimensions Additional Product Info


text:
Narrow your search
PayPal lets you easily make purchases and sell goods on eBay and thousands of other stores. It also supports international transactions and peer-to-peer payments, making it the friendliest way to exchange funds online.
Access this service from the vendor's Web site
San Francisco is both the home of the tech industry and the epicenter of the gay rights movement. Now the city is throwing its biggest party of the year, just after the Supreme Court legalized same-sex marriage.
The e-tail giant will be separating its online payment and commerce companies in mid July. Shares will be split, tax-free, right down the middle for current shareholders.
The digital payments firm says it didn't live up to its own standards when it updated its user agreement with a confusing and controversial policy on autodialed calls and texts.
The digital-payments company has faced criticism over its amended user agreement that allows it to direct automated calls and texts to customers.
The New York attorney general's office wants some clarification on the companies' new policies over concerns that they may violate US law.
The Consumer Financial Protection Bureau claims PayPal signed up consumers to its credit service, PayPal Credit, without their permission.
The payment company, which has been spun off by eBay, will trade on the Nasdaq under the same ticker symbol it used more than a decade ago.
On July 1, the payment-services company will start offering buyer protections for services, e-books, software downloads, digital music and much more.
The e-commerce pioneer's overall results hid the differing paths of eBay's two main businesses, with PayPal growing and eBay.com floundering.


text:
Decision quality instrument for treatment of hip and knee osteoarthritis: a psychometric evaluation
1 General Medicine Division, Massachusetts General Hospital (MGH), Harvard Medical School (HMS), Boston, MA, USA
2 Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI) and Faculty of Health Sciences, University of Ottawa (U of O), Ottawa, Canada
3 Center for Shared Decision Making, Dartmouth-Hitchcock Medical Center, Lebanon NH USA
4 General Medicine Division, MGH, HMS, Boston, MA, USA
5 Center for Survey Research, University of Massachusetts Boston, MA USA
6 Division of Orthopaedic Surgery, The Ottawa Hospital and U of O, Ottawa, Canada
7 Department of Orthopedic Surgery, MGH Boston MA, USA
8 General Medicine Division, MGH Boston MA, USA
9 Department of Orthopedic Surgery and Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, HMS, Boston, MA USA
10 The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Medical School (DMS), Lebanon, NH, USA
11 Department of Orthopedic Surgery, MGH, HMS, Boston, MA, USA
12 Clinical Epidemiology Program, OHRI and Department of Epidemiology and Community Medicine, U of O, Ottawa, Canada
13 Department of Orthopedic Surgery, DMS, Lebanon, NH USA
14 Department of Medicine, Ottawa Hospital; Senior Scientist, OHRI, Ottawa, Canada
15 Foundation for Informed Medical Decision Making, Boston, MA USA
BMC Musculoskeletal Disorders 2011, 12:149 doi:10.1186/1471-2474-12-149Published: 5 July 2011
A high quality decision requires that patients who meet clinical criteria for surgery are informed about the options (including non-surgical alternatives) and receive treatments that match their goals. The aim of this study was to evaluate the psychometric properties and clinical sensibility of a patient self report instrument, to measure the quality of decisions about total joint replacement for knee or hip osteoarthritis.
The performance of the Hip/Knee Osteoarthritis Decision Quality Instrument (HK-DQI) was evaluated in two samples: (1) a cross-sectional mail survey with 489 patients and 77 providers (study 1); and (2) a randomized controlled trial of a patient decision aid with 138 osteoarthritis patients considering total joint replacement (study 2). The HK-DQI results in two scores. Knowledge items are summed to create a total knowledge score, and a set of goals and concerns are used in a logistic regression model to develop a concordance score. The concordance score measures the proportion of patients whose treatment matched their goals. Hypotheses related to acceptability, feasibility, reliability and validity of the knowledge and concordance scores were examined.
In study 1, the HK-DQI was completed by 382 patients (79%) and 45 providers (58%), and in study 2 by 127 patients (92%), with low rates of missing data. The DQI-knowledge score was reproducible (ICC = 0.81) and demonstrated discriminant validity (68% decision aid vs. 54% control, and 78% providers vs. 61% patients) and content validity. The concordance score demonstrated predictive validity, as patients whose treatments were concordant with their goals had more confidence and less regret with their decision compared to those who did not.
The HK-DQI is feasible and acceptable to patients. It can be used to assess whether patients with osteoarthritis are making informed decisions about surgery that are concordant with their goals.


text:
The party may already be over for Sarah Palin
Story | Jun 12, 2009
The party may already be over for Sarah Palin
Story | Jun 12, 2009
The stem-cell decision: Obama's not Mr. Sensitivity
Column | Mar 11, 2009
As he lifted the ban on federal funding for embryonic stem-cell research Monday, President Barack Obama proclaimed that scientific decisions now will be made "on facts, not ideology." This sounds good, but what if there were other nonideological facts...
CNN taps Eliot Spitzer and Kathleen Parker for new roundtable debate show
Story | Jun 23, 2010
CNN announced Wednesday that it had hired former New York Gov. Eliot Spitzer and conservative columnist Kathleen Parker to helm a new point-counterpoint show in the key 8 p.m. ET hour, recruiting two headstrong political figures in a bid to...
'Parker Spitzer' has a rough first week in the ratings
Story | Oct 12, 2010
Kathleen Parker and Eliot Spitzer evidently aren't what the ratings doctor ordered for struggling CNN. The new team, in its premiere week, ran a weak fourth in the 8 p.m. time slot in cable news. Fox News Channel's Bill O'Reilly remains the king of


text:
Professor Andrew Ferguson was interviewed on Your Public Radio (WYPR) and on Southern California Public Radio (KPCC) about what jury duty is truly
like and why it matters for our justice system. Prof. Ferguson also
published a new book with NYU Press about the same subject titled, "Why Jury Duty Matters."
Listen to the full interviews at WYPR and KPCC.
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7/1/2015UDC Signs Historic Agreement With Cuba's Oldest University
7/13/2015Tex. Dept. Housing and Comm. Affairs v. Inclusive Communities Project
9/10/2015Edgar Cahn Social Justice Award
UDC David A. Clarke School of Law
4340 Connecticut Ave NW
(Mailing: 4200 Connecticut Ave NW)
Washington, DC 20008
Phone: (202) 274-7400
Fax: (202) 274-5583
Connect with the School of Law


text:
SPECIAL OFFERTake An Extra 20% Off This Item, Discount Taken in Cart. See details
Extra 20% Off Tires And Pumps: Offer valid 6/30/15 - 7/1/15 at PerformanceBike.com and by phone only. Extra 20% off applies to tires and pumps only. Some brand and/or item exclusions may apply. Visit Terms and Conditions for details. Offer cannot be combined with any other coupons. Additional 20% off does not apply to previous purchases, sales tax or other merchandise.
- Overview
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- Reviews
Spin Doctor Aftershock Suspension PumpWhen the valve on your suspension fork doesn't feel quite right, you need the expert quality and efficiency of the Spin Doctor Aftershock Suspension Pump. This high pressure pump inflates your front and rear shocks up to 300 PSI for optimal off-road performance. Swivel hose allows easy access in tight spots and pressure bleed valve guards against accidental negative pressure.
- Easily inflates up to 300 PSI
- Pressure bleed valve allows fine-tuning of shock pressure
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- Aluminum and steel construction for lightweight strength and durability
- Suitable for front and rear shocks
Spin Doctor Aftershock Suspension Pump
- bleed valve:
- Yes
- max. psi:
- 300
- weight:
- 199g
- rating:
- 4.5


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Golden Beach Apartments - Algarve
The hotel is within walking distance of the best nightlife area, restaurants, shops, and supermarkets. The 2-story structure is a complex of 54 apartments with balconies, 42 with fantastic views over the sea, which will give visitors all the comfort during their stay. Water sports are popular in the area and you can spend your days fishing, swimming, sailing, parasailing, water skiing, or cruising in a banana boat.
The building has an outdoor swimming pool with pool umbrellas and chaise longues, which is a lovely place to relax and spend the afternoon sunbathing and swimming. You can also simply return to your fully serviced apartment for a pleasant evening in private. No matter which you decide, you will truly enjoy your stay.
Business services and a computer station are available. Additional amenities include wired and wireless Internet access for an extra charge. Bicycle rental is available on site. For an extra charge, this property can arrange child care or a roundtrip airport shuttle (available on request). Guests can find peace of mind with the safe deposit box located at the front desk.
Please note that this complex is open from April 1st to October 31st.
Our second visit to this complex and this time we stayed at one of the recently…
Location was terrific close to shops, beach, restaurants - everything you need for a…
Enter dates to check prices
Hotel Info: 1-844-302-2248from $116
- Villa, 3 Bedrooms
- Superior Duplex, 3 Bedrooms, Sea View
- Studio
- Standard Apartment, 1 Bedroom, Garden View
- Duplex, 3 Bedrooms, Sea View
- Superior Apartment, 1 Bedroom, Garden View
- Standard Apartment, 1 Bedroom, Sea View
- Basic Room
- Superior Apartment, 2 Bedrooms, Sea View
- Superior Apartment, 1 Bedroom, Sea View
Recommended hotels
At a glance
Key facts
Hotel size
- This hotel has 54 rooms
- This hotel is arranged over 2 floors
- Check-in time starts at 3 PM
- Check-out time is noon
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
- Babysitting/childcare *
- Pets not allowed
- Wired Internet access in public areas *
- Airport shuttle (available on request) *
- Free self parking
- Free nearby parking
- Theme park shuttle *
In the hotel
- Poolside bar
- Outdoor pool
- Pool sun loungers
- Pool umbrellas
- Computer station
- Front desk (limited hours)
- Tours/ticket assistance
- Luggage storage
- Safe-deposit box at front desk
- Garden
- Terrace
In the room
- Blackout drapes/curtains
- Private bathroom
- Shower/tub combination
- Rainfall showerhead
- Bidet
- Satellite TV channels
- Phone
- Refrigerator
- Microwave
- Kitchen
- Stovetop
- Cookware, dishware, and utensils
- In-room safe
Special features
On Site
- Bicycle rentals on site
- Parasailing on site
- Scooter/moped rentals on site
- Water skiing on site
- Golf lessons available nearby
- Golfing nearby
- Scuba diving nearby
- Skydiving nearby
- Snorkeling nearby
Golden Beach Apartments - Algarve's small print
For transfers, guests must contact the property 72 hours prior to arrival at the number on the booking confirmation.
The name on the credit card used at check-in to pay for incidentals must be the primary name on the guestroom reservation.
Mandatory fees
Cash deposit: EUR 50 per stay for guests under 21 years old
Optional extras
Safes in guestrooms can be used for EUR 1.5 per night
High-speed Internet access (wired) is available in public areas for EUR 3 per hour (rates may vary)
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.


text:
Aaron Hernandez in New Letter to Fan: I Had to Hear My Little Girl Say "Dada" From JAIL!
Suspected murderer Aaron Hernandez has written a new jailhouse letter, and in it, he bemoans the fact that he cannot be with his baby daughter.
He had to hear her say "Dada" for the first time from behind bars.


text:
Hotel Everest, Mumbai
- Free continental breakfast, free WiFi, and free parking
Main amenities
- 11 guestrooms
- 24-hour room service
- Airport shuttle
- 24-hour front desk
- Coffee/tea in the lobby
- Air conditioning
- Daily housekeeping
- Laundry service
- Free newspapers in the lobby
- Tour/ticket assistance
- Lobby TV
What's around
- In Colaba
- Gateway of India (1.4 mi / 2.2 km)
- Prince of Wales Museum (1.5 mi / 2.4 km)
- Rajabai Tower (1.5 mi / 2.4 km)
- Flora Fountain (1.8 mi / 2.9 km)
- St. Thomas Cathedral (1.8 mi / 3 km)
I have stayed in over 100 hotels of varying star ratings to qualify that I'm not over…
Enter dates to check prices
Hotel Info: 866-539-8117from $22
- Standard Room, Shared Bathroom
- Super Deluxe Room
- Deluxe Room, 1 Double Bed
Recommended hotels
At a glance
Key facts
Hotel size
- This hotel has 11 rooms
- This hotel is arranged over 1 floor
- Check-in time starts at noon
- Check-out time is noon
Required at check in
- Cash deposit required
- Government-issued photo ID required
- Minimum check-in age is 18
- Local laws may restrict unmarried guests from sharing a room
Travelling with others
- Pets not allowed
- Free WiFi in public areas
- Free WiFi in rooms
- Airport shuttle (available on request) *
- Free self parking
Nearby Two Star Mumbai hotels
In the hotel
- Free continental breakfast daily
- 24-hour room service
- Coffee/tea in the lobby
- 24-hour front desk
- Tours/ticket assistance
- Dry cleaning/laundry service
- Free newspapers in lobby
- Number of buildings/towers - 1
- Elevator/lift
- Television in lobby
In the room
- Air conditioning
- Ceiling fan
- Private bathroom
- Rainfall showerhead
- Shower only
- Free toiletries
- 21-inch TV
- Premium TV channels
- Free newspaper
- Free WiFi
- Phone
- Daily housekeeping
- In-room safe
Top Mumbai hotels
Recently reviewed hotels in Mumbai
- Four Seasons Hotel MumbaiFrom
"amazing hotel with excellent hospitality and service. Everyone is attentive and focus on getting the extra little things right which make all the difference. Definitely recommend…"Jun 18, 2015
- JW Marriott Hotel MumbaiFrom
"Nice hotel and very good breakfast buffet"Jun 14, 2015
- ITC Grand Central, MumbaiFrom
"It was a wonderful stay at ITC grand central. Great service and good hospitality."Jun 9, 2015
- The OrchidFrom
Hotel Everest, Mumbai's small print
Also known as
- Everest Mumbai
- Hotel Everest Mumbai
Only registered guests are allowed in the guestrooms.
For transfers, guests must contact the property 24 hours prior to arrival at the number on the booking confirmation.
Optional extras
Airport shuttle service is offered for an extra charge of INR 500 per person (one way)
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.


text:
Are you Sudha Ananth?Claim your profile
Publications (28)119.91 Total impact
- SourceAvailable from: PubMed Central
Article: Retinal expression of the serine protease matriptase-2 (Tmprss6) and its role in retinal iron homeostasis[Show abstract] [Hide abstract]
ABSTRACT: Matriptase-2 (also known as TMPRSS6) is a critical regulator of the iron-regulatory hormone hepcidin in the liver; matriptase-2 cleaves membrane-bound hemojuvelin and consequently alters bone morphogenetic protein (BMP) signaling. Hemojuvelin and hepcidin are expressed in the retina and play a critical role in retinal iron homeostasis. However, no information on the expression and function of matriptase-2 in the retina is available. The purpose of the present study was to examine the retinal expression of matriptase-2 and its role in retinal iron homeostasis. RT-PCR, quantitative PCR (qPCR), and immunofluorescence were used to analyze the expression of matriptase-2 and other iron-regulatory proteins in the mouse retina. Polarized localization of matriptase-2 in the RPE was evaluated using markers for the apical and basolateral membranes. Morphometric analysis of retinas from wild-type and matriptase-2 knockout (Tmprss6(msk/msk) ) mice was also performed. Retinal iron status in Tmprss6(msk/msk) mice was evaluated by comparing the expression levels of ferritin and transferrin receptor 1 between wild-type and knockout mice. BMP signaling was monitored by the phosphorylation status of Smads1/5/8 and expression levels of Id1 while interleukin-6 signaling was monitored by the phosphorylation status of STAT3. Matriptase-2 is expressed in the mouse retina with expression detectable in all retinal cell types. Expression of matriptase-2 is restricted to the apical membrane in the RPE where hemojuvelin, the substrate for matriptase-2, is also present. There is no marked difference in retinal morphology between wild-type mice and Tmprss6(msk/msk) mice, except minor differences in specific retinal layers. The knockout mouse retina is iron-deficient, demonstrable by downregulation of the iron-storage protein ferritin and upregulation of transferrin receptor 1 involved in iron uptake. Hepcidin is upregulated in Tmprss6(msk/msk) mouse retinas, particularly in the neural retina. BMP signaling is downregulated while interleukin-6 signaling is upregulated in Tmprss6(msk/msk) mouse retinas, suggesting that the upregulaton of hepcidin in knockout mouse retinas occurs through interleukin-6 signaling and not through BMP signaling. The iron-regulatory serine protease matriptase-2 is expressed in the retina, and absence of this enzyme leads to iron deficiency and increased expression of hemojuvelin and hepcidin in the retina. The upregulation of hepcidin expression in Tmprss6(msk/msk) mouse retinas does not occur via BMP signaling but likely via the proinflammatory cytokine interleukin-6. We conclude that matriptase-2 is a critical participant in retinal iron homeostasis.Molecular vision 04/2014; 20:561-574. · 2.25 Impact Factor
Article: Regulation of the cholesterol efflux transporters ABCA1 and ABCG1 in retina in hemochromatosis and by the endogenous siderophore 2,5-dihydroxybenzoic acid[Show abstract] [Hide abstract]
ABSTRACT: Hypercholesterolemia and polymorphisms in the cholesterol exporter ABCA1 are linked to age-related macular degeneration (AMD). Excessive iron in retina also has a link to AMD pathogenesis. Whether these findings mean a biological/molecular connection between iron and cholesterol is not known. Here we examined the relationship between retinal iron and cholesterol using a mouse model (Hfe(-/-)) of hemochromatosis, a genetic disorder of iron overload. We compared the expression of the cholesterol efflux transporters ABCA1 and ABCG1 and cholesterol content in wild type and Hfe(-/-) mouse retinas. We also investigated the expression of Bdh2, the rate-limiting enzyme in the synthesis of the endogenous siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA) in wild type and Hfe(-/-) mouse retinas, and the influence of this siderophore on ABCA1/ABCG1 expression in retinal pigment epithelium. We found that ABCA1 and ABCG1 were expressed in all retinal cell types, and that their expression was decreased in Hfe(-/-) retina. This was accompanied with an increase in retinal cholesterol content. Bdh2 was also expressed in all retinal cell types, and its expression was decreased in hemochromatosis. In ARPE-19 cells, 2,5-DHBA increased ABCA1/ABCG1 expression and decreased cholesterol content. This was not due to depletion of free iron because 2,5-DHBA (a siderophore) and deferiprone (an iron chelator) had opposite effects on transferrin receptor expression and ferritin levels. We conclude that iron is a regulator of cholesterol homeostasis in retina and that removal of cholesterol from retinal cells is impaired in hemochromatosis. Since excessive cholesterol is pro-inflammatory, hemochromatosis might promote retinal inflammation via cholesterol in AMD.Biochimica et Biophysica Acta 01/2014; 1842(4). DOI:10.1016/j.bbadis.2014.01.010 · 4.66 Impact Factor
Article: L-2-oxothiazolidine-4-carboxylic acid attenuates oxidative stress and inflammation in retinal pigment epithelium[Show abstract] [Hide abstract]
ABSTRACT: Oxidant- and inflammation-induced damage to retinal pigment epithelial (RPE) cells is central to the pathogenesis of age-related macular degeneration (AMD). Thus, developing novel strategies to protect these cells is important. We reported previously on the robust antioxidant and therefore cell-protective effects of the cysteine pro-drug L-2-oxothiazolidine-4-carboxylic acid (OTC) in cultured human RPE cells. New reports citing a novel anti-inflammatory role for OTC in addition to the known glutathione-stimulating and antioxidant properties emerged recently; however, this role has not been evaluated in RPE cells or in intact retina. Given the crucial causative roles of oxidative stress and inflammation in AMD pathogenesis, knowing whether OTC might exhibit a similar benefit in this cell and tissue type has high clinical relevance; thus, we evaluated OTC in the present study. ARPE-19 and primary RPE cells isolated from wild-type, Gpr109a(-/-) , or Slc5a8(-/-) mouse eyes were exposed to TNF-α in the presence or absence of OTC, followed by analysis of IL-6 and Ccl2 expression with real-time quantitative polymerase chain reaction or enzyme-linked immunosorbent assay. Cellular and molecular markers of inflammation and oxidative stress (i.e., IL-1β, TGF-β, ABCG1, ABCA1, reduced glutathione, and dihydroethidium) were evaluated in Ccl2(-/-)/Cx3cr1(-/-) double knockout mice on rd8 background (DKO rd8) treated with OTC (10 mg/ml) in drinking water for a period of 5 months. OTC treatment significantly inhibited the expression and secretion of IL-6 and Ccl2 in TNF-α-stimulated ARPE-19 cells. Studies conducted using DKO rd8 animals treated with OTC in drinking water confirmed these findings. Cellular and molecular markers of inflammation were significantly suppressed in the retinas of the OTC-treated DKO rd8 animals. Subsequent in vitro and in vivo studies of the possible mechanism(s) to explain these actions revealed that although OTC is an agonist of the anti-inflammatory G-protein coupled receptor GPR109A and a transportable substrate of the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8), these properties may play a role but do not explain entirely the anti-inflammatory effects this compound elicits in cultured RPE cells and the intact mouse retina. This study represents, to our knowledge, the first report of the suppressive effects of OTC on inflammation in cultured RPE cells and on inflammation and oxidative stress in the retina in vivo.Molecular vision 01/2014; 20:73-88. · 2.25 Impact Factor
Article: The Niacin/Butyrate Receptor GPR109A Suppresses Mammary Tumorigenesis by Inhibiting Cell Survival[Show abstract] [Hide abstract]
ABSTRACT: GPR109A, a G-protein-coupled receptor, is activated by niacin and butyrate. Upon activation in colonocytes, GPR109A potentiates anti-inflammatory pathways, induces apoptosis, and protects against inflammation-induced colon cancer. In contrast, GPR109A activation in keratinocytes induces flushing by activation of Cox-2-dependent inflammatory signaling and, the receptor expression is upregulated in human epidermoid carcinoma. Thus, depending on the cellular context and tissue, GPR109A functions either as a tumor suppressor or a tumor promoter. However, the expression status and the functional implications of this receptor in the mammary epithelium are not known. Here we show that GPR109A is expressed in normal mammary tissue and, irrespective of the hormone receptor status, its expression is silenced in human primary breast tumor tissues, breast cancer cell lines, and in tumor tissues of three different murine mammary tumor models. Functional expression of this receptor in human breast cancer cell lines decreases cAMP production, induces apoptosis, and blocks colony formation and mammary tumor growth. Transcriptome analysis revealed that GPR109A activation inhibits genes, which are involved in cell survival and anti-apoptotic signaling, in human breast cancer cells. In addition, deletion of Gpr109a in mice increased tumor incidence and triggered early onset of mammary tumorigenesis with increased lung metastasis in MMTV-Neu mouse model of spontaneous breast cancer. These findings suggest that GPR109A is a tumor suppressor in mammary gland and that pharmacological induction of this gene in tumor tissues followed by its activation with agonists could be an effective therapeutic strategy to treat breast cancer.Cancer Research 12/2013; 74(4). DOI:10.1158/0008-5472.CAN-13-1451 · 9.28 Impact Factor
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ABSTRACT: SLC5A8 is a putative tumor suppressor that is inactivated in more than 10 different types of cancer, but neither the oncogenic signaling responsible for SLC5A8 inactivation nor the functional relevance of SLC5A8 loss to tumor growth has been elucidated. Here, we identify the oncogenic HRAS (HRAS(G12V)) as a potent mediator of SLC5A8 silencing in human non-transformed normal mammary epithelial cell lines and in mouse mammary tumor through DNMT1. Further, we demonstrate that loss of Slc5a8 increases cancer-initiating stem cell formation, and promotes mammary tumorigenesis and lung metastasis in HRAS-driven murine model of mammary tumor. Mammary gland-specific overexpression of SLC5A8 (MMTV-Slc5a8 transgenic mouse) as well as induction of endogenous Slc5a8 in mice with inhibitors of DNA methylation protect against HRAS-driven mammary tumor. Collectively, our results provide the tumor-suppressive role of SLC5A8 and identify the oncogenic HRAS as a mediator of tumor-associated silencing of this tumor suppressor in mammary gland. These findings suggest that pharmacological approaches to reactivate SLC5A8 expression in tumor cells have potential as a novel therapeutic strategy for breast cancer treatment.Molecular and Cellular Biology 08/2013; DOI:10.1128/MCB.01702-12 · 5.04 Impact Factor
Article: Induction of the Cystine/Glutamate Exchanger SLC7A11 in Retinal Pigment Epithelial Cells by the Antipsoriatic Drug Monomethylfumarate[Show abstract] [Hide abstract]
ABSTRACT: Oxidative stress is a common pathological factor in degenerative retinal diseases; therefore, identifying novel strategies for its limitation is critically important and highly relevant clinically. Along these lines, our present goal was to evaluate the effect(s) of the fumarate ester and antipsoriatic agent monomethylfumarate (MMF) on the expression and functional activity of the cystine/glutamate exchanger SLC7A11 (system x), a transport system critical to potentiation of antioxidant signaling in retina. ARPE-19 and primary mouse RPE cells were cultured in the presence or absence of varying concentrations of MMF (0-5000 μM) for 0 to 24 hours. MMF (10 mM) was also delivered intravitreally to mouse eyes. RT-PCR, radiolabeled uptake, Western blotting, and glutathione (GSH) assays were then used to evaluate the effects of MMF on endogenous antioxidant machinery. MMF induced system x, Nrf2, and hypoxia-inducible factor 1α (Hif-1α) in cultured RPE cells. Additionally, the compound was recognized as a transportable substrate by the Na-coupled monocarboxylate transporter SLC5A8 (SMCT1). In vivo these factors were evidenced by a significant increase in retinal levels of GSH. MMF stimulates multiple pathways in retinal cells that potentiate cellular events leading to the upregulation of genes/mechanisms that function to protect retina against various forms of insult; upregulation of system x is one such consequence. To our knowledge, this is the first report that fumarate esters, compounds already employed clinically for other indications, are effective in retina via x induction. This novel, hitherto unknown mechanism helps to explain the antioxidant feature of these compounds and highlights their therapeutic potential in retina.Investigative ophthalmology & visual science 03/2013; 54(3):1592-602. DOI:10.1167/iovs.12-11289 · 3.66 Impact Factor
Article: GPR109A as an Anti-Inflammatory Receptor in Retinal Pigment Epithelial Cells and Its Relevance to Diabetic Retinopathy[Show abstract] [Hide abstract]
ABSTRACT: Retinal pigment epithelium (RPE) expresses GPR109A, a receptor for the vitamin niacin and the ketone body β-hydroxybutyrate (β-HB). Because diabetes results in elevated levels of β-HB, here we studied expression of the receptor in diabetic retina. We also investigated its functional relevance in RPE. Retinal expression of GPR109A in diabetic mice and postmortem human eyes was evaluated by quantitative PCR (qPCR). ARPE-19 cells and primary wild-type and Gpr109a(-/-) mouse RPE cells were exposed to TNF-α in the presence or absence of niacin or β-HB, followed by analysis of IL-6 and Ccl2 expression via real-time qPCR and ELISA. GPR109A expression was increased in diabetic mouse and human retina. TNF-α increased the expression and secretion of IL-6 and Ccl2 in ARPE-19 cells. Niacin and β-HB suppressed these effects, implicating GPR109A as the target responsible for mediation of the observed effects. Primary RPE cells from wild-type mice behaved similarly. In contrast, GPR109A ligands failed to suppress TNF-α-induced expression and secretion of IL-6 and Ccl2 in primary RPE cells from Gpr109a(-/-) mice, confirming that the observed anti-inflammatory effects were mediated specifically by Gpr109a. GPR109A plays an anti-inflammatory role in RPE and its expression is upregulated in diabetes. Inflammation is a key causative factor in the pathogenesis of diabetic retinopathy. We speculate that the increased expression of GPR109A and elevation of its ligand β-HB in diabetes are mechanisms by which the tissue attempts to fight inflammation in this disease. Pharmacological activation of GPR109A may therefore have therapeutic potential in clinical management of diabetic retinopathy.Investigative ophthalmology & visual science 03/2012; 53(4):2208-17. DOI:10.1167/iovs.11-8447 · 3.66 Impact Factor
Article: Transport of the synthetic opioid peptide DADLE ([D-Ala2,D-Leu5]-enkephalin) in neuronal cells.[Show abstract] [Hide abstract]
ABSTRACT: The sodium-coupled oligopeptide transporters 1 and 2 (SOPT1 and SOPT2) transport peptides consisting of at least five amino acids and show potential for the delivery of therapeutically relevant peptides/peptidomimetics. Here, we examined the expression of these two transporters in the retinal neuronal cell line RGC-5. These cells showed robust uptake activity for the synthetic pentapeptide DADLE ([D-Ala(2),D-Leu(5)]-Enkephalin). The uptake was Na(+) dependent and saturable (K(t), 6.2 ± 0.6 μM). A variety of oligopeptides inhibited DADLE uptake. The uptake of the competing oligopeptides was directly demonstrated with fluorescein isothiocyanate-labeled Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys in RGC-5 cells and primary mouse retinal ganglion cells. The characteristics of DADLE uptake matched those of SOPT2. We then examined the expression of SOPT1 in these cells with deltorphin II (Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH(2)) as the substrate and found that RGC-5 cells also expressed SOPT1. As it is already known that SOPT1 is expressed in the neuronal cell line SK-N-SH, we investigated SOPT2 expression in these cells to determine whether the presence of both oligopeptide transporters is a common feature of neuronal cells. These studies showed that SK-N-SH cells also expressed SOPT2. This constitutes the first report on the functional characterization of SOPT1 and SOPT2 in retinal neuronal cells and on the expression of SOPT2 in nonretinal neuronal cells.Journal of Pharmaceutical Sciences 01/2012; 101(1):154-63. DOI:10.1002/jps.22733 · 3.01 Impact Factor
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ABSTRACT: Haemochromatosis is a genetic disorder of iron overload resulting from loss-of-function mutations in genes coding for the iron-regulatory proteins HFE (human leucocyte antigen-like protein involved in iron homoeostasis), transferrin receptor 2, ferroportin, hepcidin and HJV (haemojuvelin). Recent studies have established the expression of all of the five genes in the retina, indicating their importance in retinal iron homoeostasis. Previously, we demonstrated that HJV is expressed in RPE (retinal pigment epithelium), the outer and inner nuclear layers and the ganglion cell layer. In the present paper, we report on the consequences of Hjv deletion on the retina in mice. Hjv-/- mice at ≥18 months of age had increased iron accumulation in the retina with marked morphological damage compared with age-matched controls; these changes were not found in younger mice. The retinal phenotype in Hjv-/- mice included hyperplasia of RPE. We isolated RPE cells from wild-type and Hjv-/- mice and examined their growth patterns. Hjv-/- RPE cells were less senescent and exhibited a hyperproliferative phenotype. Hjv-/- RPE cells also showed up-regulation of Slc7a11 (solute carrier family 7 member 11 gene), which encodes the 'transporter proper' subunit xCT in the heterodimeric amino acid transporter xCT/4F2hc (cystine/glutamate exchanger). BMP6 (bone morphogenetic protein 6) could not induce hepcidin expression in Hjv-/- RPE cells, confirming that retinal cells require HJV for induction of hepcidin via BMP6 signalling. HJV is a glycosylphosphatidylinositol-anchored protein, and the membrane-associated HJV is necessary for BMP6-mediated activation of hepcidin promoter in RPE cells. Taken together, these results confirm the biological importance of HJV in the regulation of iron homoeostasis in the retina and in RPE.Biochemical Journal 09/2011; 441(2):599-608. DOI:10.1042/BJ20111148 · 4.78 Impact Factor
Article: SIRT1 Is Essential for Oncogenic Signaling by Estrogen/Estrogen Receptor alpha in Breast Cancer[Show abstract] [Hide abstract]
ABSTRACT: The NAD-dependent histone deacetylase silent information regulator 1 (SIRT1) is overexpressed and catalytically activated in a number of human cancers, but recent studies have actually suggested that it may function as a tumor suppressor and metastasis inhibitor in vivo. In breast cancer, SIRT1 stabilization has been suggested to contribute to the oncogenic potential of the estrogen receptor α (ERα), but SIRT1 activity has also been associated with ERα deacetylation and inactivation. In this study, we show that SIRT1 is critical for estrogen to promote breast cancer. ERα physically interacted and functionally cooperated with SIRT1 in breast cancer cells. ERα also bound to the promoter for SIRT1 and increased its transcription. SIRT1 expression induced by ERα was sufficient to activate antioxidant and prosurvival genes in breast cancer cells, such as catalase and glutathione peroxidase, and to inactivate tumor suppressor genes such as cyclin G2 (CCNG2) and p53. Moreover, SIRT1 inactivation eliminated estrogen/ERα-induced cell growth and tumor development, triggering apoptosis. Taken together, these results indicated that SIRT1 is required for estrogen-induced breast cancer growth. Our findings imply that the combination of SIRT1 inhibitors and antiestrogen compounds may offer more effective treatment strategies for breast cancer.Cancer Research 09/2011; 71(21):6654-64. DOI:10.1158/0008-5472.CAN-11-1446 · 9.28 Impact Factor
Article: Transport via SLC5A8 (SMCT1) Is Obligatory for 2-Oxothiazolidine-4-Carboxylate to Enhance Glutathione Production in Retinal Pigment Epithelial Cells[Show abstract] [Hide abstract]
ABSTRACT: To evaluate the role of SLC5A8 in the transport of 2-oxothiazolidine-4-carboxylate (OTC) and to determine whether OTC augments glutathione production in RPE cells, thereby providing protection against oxidative stress. SLC5A8-mediated transport of OTC was monitored in Xenopus laevis oocytes by electrophysiological means. Saturation kinetics, Na(+)-activation kinetics, and inhibition by ibuprofen were analyzed by monitoring OTC-induced currents as a measure of transport activity. Oxidative stress was induced in ARPE-19 cells and primary RPE cells isolated from wild type and Slc5a8(-/-) mouse retinas using H(2)O(2), and the effects of OTC on cell death and intracellular glutathione concentration were examined. Heterologous expression of human SLC5A8 in X. laevis oocytes induced Na(+)-dependent inward currents in the presence of OTC under voltage-clamp conditions. The transport of OTC via SLC5A8 was saturable, with a K(t) of 104 ± 3 μM. The Na(+)-activation kinetics was sigmoidal with a Hill coefficient of 1.9 ± 0.1, suggesting involvement of two Na(+) in the activation process. Ibuprofen, a blocker of SLC5A8, inhibited SLC5A8-mediated OTC transport; the concentration necessary for half-maximal inhibition was 17 ± 1 μM. OTC increased glutathione levels and protected ARPE-19 and primary RPE cells isolated from wild type mouse retinas from H(2)O(2)-induced cell death. These effects were abolished in primary RPE isolated from Slc5a8(-/-) mouse retinas. OTC is a transportable substrate for SLC5A8. OTC augments glutathione production in RPE cells, thereby protecting them from oxidative damage. Transport via SLC5A8 is obligatory for this process.Investigative ophthalmology & visual science 04/2011; 52(8):5749-57. DOI:10.1167/iovs.10-6825 · 3.66 Impact Factor
Article: Expression and Iron-Dependent Regulation of Succinate Receptor GPR91 in Retinal Pigment Epithelium[Show abstract] [Hide abstract]
ABSTRACT: GPR91, a succinate receptor, is expressed in retinal ganglion cells and induces vascular endothelial growth factor (VEGF) expression. RPE also expresses VEGF, but whether this cell expresses GPR91 is not known. Excessive iron is also proangiogenic, and hemochromatosis is associated with iron overload. Therefore, we examined the expression and iron-dependent regulation of GPR91 in the RPE. GPR91 expression was examined by RT-PCR and immunohistochemistry. Hemochromatosis mice, cytomegalovirus (CMV) infection of retina, expression of CMV-US2 in RPE, and exposure of RPE to ferric ammonium citrate (FAC) were used to examine the iron-dependent regulation of GPR91 expression. VEGF expression was quantified by qPCR. Knockdown of GPR91 in ARPE-19 cells was achieved with shRNA. GPR91 was expressed in RPE but only in the apical membrane. Retinal expression of GPR91 was higher in hemochromatosis (Hfe(-/-)) mice than in wild-type (WT) mice. Primary RPE cells from Hfe(-/-) mice had increased GPR91 expression compared with WT RPE cells. Iron accumulation in cells induced by CMV infection, expression of CMV-US2, or treatment with FAC increased GPR91 expression. VEGF expression in the Hfe(-/-) mouse retina was increased at ages younger than 18 months, but the expression was downregulated at older ages. The involvement of GPR91 in succinate-induced expression of VEGF in RPE cells was confirmed with GPR91-specific shRNA. GPR91 is expressed in the RPE with specific localization to the apical membrane, indicating that succinate in the subretinal space serves as the GPR91 agonist. Excessive iron in the retina and RPE enhances GPR91 expression; however, VEGF expression does not always parallel GPR91 expression.Investigative ophthalmology & visual science 02/2011; 52(6):3751-8. DOI:10.1167/iovs.10-6722 · 3.66 Impact Factor
Article: Transport of hepcidin, an iron-regulatory peptide hormone, into retinal pigment epithelial cells via oligopeptide transporters and its relevance to iron homeostasis[Show abstract] [Hide abstract]
ABSTRACT: Retinal pigment epithelial cells (RPE) express two transport systems (SOPT1 and SOPT2) for oligopeptides. Hepcidin is an iron-regulatory peptide hormone consisting of 25 amino acids. This hormone binds to ferroportin, an iron exporter expressed on the cell surface, and facilitates its degradation. Here we investigated if hepcidin is a substrate for SOPT1 and SOPT2 and if the hormone has any intracellular function in RPE. Hepcidin inhibited competitively the uptake of deltorphin II (a synthetic oligopeptide substrate for SOPT1) and DADLE (a synthetic oligopeptide substrate for SOPT2) with IC50 values in the range of 0.4-1.7 μM. FITC-hepcidin was taken up into RPE, and this uptake was inhibited by deltorphin II and DADLE. The entry of FITC-hepcidin into cells was confirmed by flow cytometry. Incubation of RPE with hepcidin decreased the levels of ferroportin mRNA. This effect was not a consequence of hepcidin-induced ferroportin degradation because excessive iron accumulation in RPE, which is expected to occur in these cells as a result of ferroportin degradation, did not decrease but instead increased the levels of ferroportin mRNA. This study reveals for the first time a novel intracellular function for hepcidin other than its established cell surface action on ferroportin.Biochemical and Biophysical Research Communications 02/2011; 405(2):244-9. DOI:10.1016/j.bbrc.2011.01.018 · 2.28 Impact Factor
Article: Diclofenac-induced stimulation of SMCT1 (SLC5A8) in a heterologous expression system: A RPE specific phenomenon[Show abstract] [Hide abstract]
ABSTRACT: SMCT1 is a Na+-coupled monocarboxylate transporter expressed in a variety of tissues including kidney, thyroid, small intestine, colon, brain, and retina. We found recently that several non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the activity of SMCT1. Here we evaluated the effect of diclofenac, also a NSAID, on SMCT1. SMCT1 cDNA was expressed heterologously in the human retinal pigment epithelial cell lines HRPE and ARPE-19, the human mammary epithelial cell line MCF7, and in Xenopus laevis oocytes. Transport was monitored by substrate uptake and substrate-induced currents. Na+-dependent uptake/current was considered as SMCT1 activity. The effect of diclofenac was evaluated for specificity, dose–response, and influence on transport kinetics. To study the specificity of the diclofenac effect, we evaluated the influence of this NSAID on the activity of several other cloned transporters in mammalian cells under identical conditions. In contrast to several NSAIDs that inhibited SMCT1, diclofenac stimulated SMCT1 when expressed in HRPE and ARPE-19 cells. The stimulation was marked, ranging from 2- to 5-fold depending on the concentration of diclofenac. The stimulation was associated with an increase in the maximal velocity of the transport system as well as with an increase in substrate affinity. The observed effect on SMCT1 was selective because the activity of several other cloned transporters, when expressed in HRPE cells and studied under identical conditions, was not affected by diclofenac. Interestingly, the stimulatory effect on SMCT1 observed in HRPE and ARPE-19 cells was not evident in MCF7 cells nor in the X. laevis expression system, indicating that SMCT1 was not the direct target for diclofenac. The RPE-specific effect suggests that the target of diclofenac that mediates the stimulatory effect is expressed in RPE cells but not in MCF7 cells or in X. laevis oocytes. Since SMCT1 is a concentrative transporter for metabolically important compounds such as pyruvate, lactate, β-hydroxybutyrate, and nicotinate, the stimulation of its activity by diclofenac in RPE cells has biological and clinical significance.Biochemical and Biophysical Research Communications 02/2010; 394(1-394):75-80. DOI:10.1016/j.bbrc.2010.02.109 · 2.28 Impact Factor
Article: Identification of a Novel Sodium-Coupled Oligopeptide Transporter (SOPT2) in Mouse and Human Retinal Pigment Epithelial Cells[Show abstract] [Hide abstract]
ABSTRACT: A sodium-coupled oligopeptide transporter (SOPT1) was described originally in ARPE-19 cells. The transporter is inducible by HIV-1 Tat. Recent studies of conjunctival epithelial cells have identified a second oligopeptide transporter (SOPT2). This study was conducted to determine whether the newly discovered SOPT2 is expressed in ARPE-19 cells, to examine whether the new transporter is also inducible by HIV-1 Tat, and to find out whether this transporter is expressed in primary RPE cells. The transport activity of SOPT2 was monitored in control and Tat-expressing ARPE-19 cells and in primary mouse and human fetal RPE cells by the uptake of the synthetic opioid peptide DADLE ((H-Tyr-D-Ala-Gly-Phe-D-Leu-OH) and by its susceptibility to inhibition by small peptides. Substrate selectivity was examined by competition studies and kinetic parameters were determined by saturation analysis. ARPE-19 cells express DADLE uptake activity that is inhibited by small peptides, indicating expression of SOPT2 in these cells. The activity of SOPT2 is induced by HIV-1 Tat. SOPT2 accepts endogenous and synthetic opioid peptides as substrates, but nonpeptide opiate antagonists are excluded. An 11-amino-acid HIV-1 Tat peptide also serves as a high-affinity substrate for the transporter. Primary cultures of mouse and human fetal RPE cells express SOPT2. The transporter is partially Na(+)-dependent with comparable substrate selectivity and inhibitor specificity in the presence and absence of Na(+). ARPE-19 cells as well as primary mouse and human fetal RPE cells express the newly discovered oligopeptide transporter SOPT2, and the transporter is induced by HIV-1 Tat in ARPE-19 cells.Investigative ophthalmology & visual science 08/2009; 51(1):413-20. DOI:10.1167/iovs.09-4048 · 3.66 Impact Factor
Article: GPR109A Is a G-protein-Coupled Receptor for the Bacterial Fermentation Product Butyrate and Functions as a Tumor Suppressor in Colon[Show abstract] [Hide abstract]
ABSTRACT: Short-chain fatty acids, generated in colon by bacterial fermentation of dietary fiber, protect against colorectal cancer and inflammatory bowel disease. Among these bacterial metabolites, butyrate is biologically most relevant. GPR109A is a G-protein-coupled receptor for nicotinate but recognizes butyrate with low affinity. Millimolar concentrations of butyrate are needed to activate the receptor. Although concentrations of butyrate in colonic lumen are sufficient to activate the receptor maximally, there have been no reports on the expression/function of GPR109A in this tissue. Here we show that GPR109A is expressed in the lumen-facing apical membrane of colonic and intestinal epithelial cells and that the receptor recognizes butyrate as a ligand. The expression of GPR109A is silenced in colon cancer in humans, in a mouse model of intestinal/colon cancer, and in colon cancer cell lines. The tumor-associated silencing of GPR109A involves DNA methylation directly or indirectly. Reexpression of GPR109A in colon cancer cells induces apoptosis, but only in the presence of its ligands butyrate and nicotinate. Butyrate is an inhibitor of histone deacetylases, but apoptosis induced by activation of GPR109A with its ligands in colon cancer cells does not involve inhibition of histone deacetylation. The primary changes in this apoptotic process include down-regulation of Bcl-2, Bcl-xL, and cyclin D1 and up-regulation of death receptor pathway. In addition, GPR109A/butyrate suppresses nuclear factor-kappaB activation in normal and cancer colon cell lines as well as in normal mouse colon. These studies show that GPR109A mediates the tumor-suppressive effects of the bacterial fermentation product butyrate in colon.Cancer Research 05/2009; 69(7):2826-32. DOI:10.1158/0008-5472.CAN-08-4466 · 9.28 Impact Factor
Article: Expression and localization of GPR109A (PUMA-G/HM74A) mRNA and protein in mammalian retinal pigment epithelium[Show abstract] [Hide abstract]
ABSTRACT: GPR109A has been identified as a G-protein-coupled receptor for niacin. beta-hydroxybutyrate (beta-HB) is a physiologic ligand for the receptor. beta-HB, the predominate ketone body in circulation, is an important energy source for neurons, including retinal neurons, under various physiologic and pathologic conditions. The identification of GPR109A as the receptor for beta-HB suggests additional, hitherto unknown, functions for this metabolite. The circulating levels of beta-HB increase in diabetes. Since retinopathy is a serious complication associated with diabetes, we investigated GPR109A expression in retina and in different retinal cell types to determine if the receptor may have a role in the pathophysiology of diabetic retinopathy. RT-PCR, fluorescent in situ hybridization, and immunofluorescent techniques were used to analyze GPR109A expression in mouse retina and in three transformed retinal cell lines: ARPE-19 (RPE), RGC-5 (ganglion), and rMC-1 (Müller). Activation of GPR109A by niacin and beta-HB was demonstrated in ARPE-19 cells by cAMP assay. Studies conducted using mouse retinal tissues demonstrated that GPR109A is expressed in retina with its expression restricted to RPE, where it differentially polarizes to the basolateral membrane. These results were confirmed with cell lines, which demonstrated GPR109A expression in ARPE-19, but not in rMC-1 and RGC-5 cells. Primary cultures of mouse RPE also showed robust expression of GPR109A. cAMP assay demonstrated that GPR109A expressed in RPE is functional. These data represent the first report on GPR109A expression in retina. The exclusive expression of GPR109A in RPE basolateral membrane, which has access to beta-HB in blood, may have biologic importance in diabetic retinopathy.Molecular vision 02/2009; 15:362-72. · 2.25 Impact Factor
Article: Functional Identification of a Novel Transport System for Endogenous and Synthetic Opioid Peptides in the Rabbit Conjunctival Epithelial Cell Line CJVE[Show abstract] [Hide abstract]
ABSTRACT: To investigate whether conjunctival epithelial cells express transport processes for opioid peptides. We monitored the uptake of [(3)H]deltorphin II and [(3)H]DADLE, two hydrolysis-resistant synthetic opioid peptides, in the rabbit conjunctival epithelial cell line CJVE and elucidated the characteristics of the uptake process. CJVE cells express robust uptake activity for deltorphin II and DADLE. Both opioid peptides compete with each other for transport. Several endogenous and synthetic opioid peptides, but not non-peptide opioid antagonists, are recognized by the transport process. Though various peptides inhibit the uptake of deltorphin II and DADLE in a similar manner, the uptake of deltorphin II is partly Na(+)-dependent whereas that of DADLE mostly Na(+)-independent. The transport process shows high affinity for many endogenous/synthetic opioid peptides. Functional features reveal that this transport process may be distinct from the opioid peptide transport system described in the retinal pigment epithelial cell line ARPE-19 and also from the organic anion transporting polypeptides, which are known to transport opioid peptides. CJVE cells express a novel, hitherto unknown transport process for endogenous/synthetic opioid peptides. This new transport process may offer an effective delivery route for opioid peptide drugs to the posterior segment of the eye.Pharmaceutical Research 10/2008; 26(5):1226-35. DOI:10.1007/s11095-008-9709-x · 3.95 Impact Factor
Chapter: Vitamin C Transporters in the Retina12/2007: pages 437-450;
Article: Cloning and functional characterization of human SMCT2 (SLC5A12) and expression pattern of the transporter in kidney[Show abstract] [Hide abstract]
ABSTRACT: Recently, we cloned two Na(+)-coupled lactate transporters from mouse kidney, a high-affinity transporter (SMCT1 or slc5a8) and a low-affinity transporter (SMCT2 or slc5a12). Here we report on the cloning and functional characterization of human SMCT2 (SLC5A12) and compare the immunolocalization patterns of slc5a12 and slc5a8 in mouse kidney. The human SMCT2 cDNA codes for a protein consisting of 618 amino acids. When expressed in mammalian cells or Xenopus oocytes, human SMCT2 mediates Na(+) -coupled transport of lactate, pyruvate and nicotinate. The affinities of the transporter for these substrates are lower than those reported for human SMCT1. Several non-steroidal anti-inflammatory drugs inhibit human SMCT2-mediated nicotinate transport, suggesting that NSAIDs interact with the transporter as they do with human SMCT1. Immunofluorescence microscopy of mouse kidney sections with an antibody specific for SMCT2 shows that the transporter is expressed predominantly in the cortex. Similar studies with an anti-SMCT1 antibody demonstrate that SMCT1 is also expressed mostly in the cortex. Dual-labeling of SMCT1 and SMCT2 with 4F2hc (CD98), a marker for basolateral membrane of proximal tubular cells in the S1 and S2 segments of the nephron, shows that both SMCT1 and SMCT2 are expressed in the apical membrane of the tubular cells. These studies also show that while SMCT2 is broadly expressed along the entire length of the proximal tubule (S1/S2/S3 segments), the expression of SMCT1 is mostly limited to the S3 segment. These studies suggest that the low-affinity transporter SMCT2 initiates lactate absorption in the early parts of the proximal tubule followed by the participation of the high-affinity transporter SMCT1 in the latter parts of the proximal tubule.Biochimica et Biophysica Acta 12/2007; 1768(11):2690-7. DOI:10.1016/j.bbamem.2007.06.031 · 4.66 Impact Factor
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Georgia Regents University
Augusta, Georgia, United States
- Department of Biochemistry and Molecular Biology
Georgia Health Sciences University
Augusta, Georgia, United States
- Department of Biochemistry & Molecular Biology


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YIELD: Makes 4 sandwiches
Preheat oven to 375° F.
Cut eight 1/2-inch-thick slices from center of sourdough loaf. In a small bowl toss together pepper Jack and coriander.
Make sandwiches on bread with pepperoni, roasted peppers, and cheese mixture. Bake sandwiches on a baking sheet in middle of oven until cheese is melted, about 5 minutes.