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June 10, 2002
SAN BRUNO, Calif. - Santa Clara women's soccer player Danielle Slaton and Gonzaga men's basketball player Dan Dickau earned the 2002 West Coast Conference female and male Scholar-Athlete of the Year awards, Commissioner Michael Gilleran announced.
Slaton became the second straight honoree from Santa Clara, following women's basketball standout Annie Garrison from last year, but only the second women's soccer player to receive the award, joining SCU alumnae Margaret Krawiec. Dickau became the sixth Gonzaga athlete to receive the honor, all members of the basketball team, including Academic All-American Hall of Famer John Stockton.
The WCC's highest honor is selected by a vote of the league's institutional representatives to recognize the finest accomplishments in athletics, academics and community service by individuals who have completed their conference eligibility.
Slaton finished her Bronco career with a number of accolades and a national championship trophy held above her head. As a four-time NSCAA first team All-American, Slaton has lived one of the most storied careers in collegiate soccer history. In 2001, the SCU defender was the 2001 College Cup Defensive MVP, the WCC Defensive Player of the Year and earned All-WCC honors for the fourth consecutive season. Slaton was a finalist for the Hermann Trophy and the MAC Player of the Year twice during her tenure on the Mission Campus. Not only was Slaton's accomplishments recognized by the league with her selection as one of the WCC's 50 Greatest Scholar-Athletes, but she was the only active scholar-athlete selected.
Slaton's dedication on the soccer field translated into her commitment in the classroom. Slaton earned a 3.72 grade point average while double majoring in Psychology and Biology at Santa Clara. Among her academic accolades, Slaton was named the 2001 NSCAA, Black Issues in Higher Education and San Jose Sports Authority Scholar-Athlete of the Year. Slaton finished her college career as the top pick in this year's WUSA draft by the Carolina Courage.
Dickau was the WCC's men's baketball Player of the Year and two-time WCC tournament MVP during his two seasons in Spokane. The Vancouver, Wash., native compiled a long list of accolades during his senior season, including first-team AP All-American, first-team Verizon Academic All-American, and finalist for the John Wooden and Naismith awards, honoring the nation's best college basketball player. Dickau's play on the court placed him in the media spotlight throughout 2002, which is where the point guard would like to be in his career following basketball. Dickau recorded a 3.40 grade point average while majoring in Broadcasting at Gonzaga, earning a spot on the WCC All-Academic team two consecutive years. Dickau also found time to volunteer for the Children's Miracle Network, visiting kids at Shiner's Hospital and assisting with the annual telethon.


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Allie is the proud MoM of mirror image identical twin boys, Nathaniel and Tyler (7) and Bradley (2).
What made you decide to start a blog?
I had tried different ways of recording moments in the twins lives that meant something to me, but nothing ever seemed to work. I have an old journal, and a couple of different computer files that have maybe three or four "moments" in them each. After we had a momentous night at a baseball game, I decided that I had to find another way to write down all of their moments before I forgot them all. This sparked the idea for the blog – and happily, it has been easy to keep up with.
How did you react to finding out you were having twins?
Although I was shocked of twins, that emotion was overshadowed by the fact that I was not losing yet another pregnancy. I had gone in for the ultrasound after some spotting, for the second time in a week. I was so afraid that something was wrong, I felt like having twins was just making up for all that I had lost.
Your boys are mirror image, can you talk about having mirror image twins?
Mirror image twins just add a different spin on the world of twins. In addition to being identical, all of their traits are mirror image of each other. One is left handed, the other right. The swirls on the back of their heads, are on opposite sides, and go in opposite directions. In our daily life, it doesn't affect the things we do, other than having assigned seats at dinner as to not knock elbows. What I enjoy is watching them take pictures or react to a situation. While their reactions may be exactly the same emotion and mannerism, the mannerism itself will manifest in mirror image. If they shake a fist at you, it will be the opposite fist or opposite eyebrows will get raised. I enjoy watching them sometimes, just because it amazes me.
Since your boys are school age, did you keep them in the same class or separate them? How did you come upon that decision?
Whether or not to put them in the same class in school was probably one of the most thought out decisions we've made thus far in parenting. Our school allows the parents to chose whether our kids are in the same class or split up, so it was left completely up to us.
I started looking for answers when they were only 4 years old. I talked to their preschool teacher, who happened to be a retired elementary school teacher. She told me I should separate them to help them establish their own personalities and friends. I read books that said I needed to be careful of the fear of separation that a lot of twins go through (including ours). I talked to a family friend who is a psychologist , who said I should keep them together the first year. All this advice varied across the spectrum.
I knew that every child makes it through the first day of school, and that twins are lucky enough to be able to share parts of it with each other. I knew they needed to develop their own friends and personalities, but they were doing that pretty well together in preschool. Ultimately, it came down to an incident I saw occur one day. I watched as they were working on writing their numbers and Nathaniel didn't know the answer, he just looked to his brother for it. Of course Tyler gave him every answer he needed. I realized, together they would not learn as well as they would separately. Tyler, excelling in math, would just let Nathaniel latch on, and the opposite would happen in reading. I wanted them to be able to stand on their own feet in the world and not have to rely on each other.
I wrote a letter to the principal asking that they be placed in separate classes, but also where the teachers worked closely with one another. This helps me at night when we are doing homework, because I don't have to go over two completely different concepts. It was a little scary for them at first, but they were right next door to each other and saw each other throughout the day. Now that they are in the second grade, they are happy to be in separate classes, and enjoy having a break from the brother, they can't ever get away from.
Do they play tricks on the teachers, or you?
They've attempted to trick Mommy and Daddy a few times. The only time it ever worked was when they had on Spiderman masks and I really couldn't tell who was who.
They only tried to trick their teachers once that I know about, and a friend gave them away. Their teachers have never been able to tell them apart (even though they are currently sporting different haircuts), and rely on them to be honest majority of the time. I am waiting for the day when I get a phone call because one of them is in the wrong class.
What are some of your favorite activities to do as a family?
I am a big advocate of experience over having stuff. We love to play outdoors or go places or do things that give us time together. In the cold winter, when we don't' get out as much, we really enjoy game nights. The twins got Monopoly for Christmas and it has been a hit at our house. So far, Mommy has only managed to win once, and Daddy hasn't won yet at all.
What question do you have for the other MoMs and Dads in the community?
What do you do when it is cold outside and you don't want the television on?
Be sure to leave your answer to Allie's question in the comment section and head over to 3 Boys + 1 Hubby and leave some bloggy love!

subset: commoncrawl


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What are your associations with the number 500? We now have one – and a very important one – it's how many students were registered and participated in the Legal HR Fair.
The largest fair of legal vacancies was held on November 24 at the Ukrainian House at the initiative of the UBA Students' League. Since we are always ready to support talented youth, our company has been an exclusive partner of the event.
Charisma, ambitions and, topmost, talent – this is what distinguishes students of our times. And it really was very pleasant for us to get acquainted with the future "sharks" of the legal market, with rising high-quality specialists.
Head of HR Irina Chegrintseva shares her professional impressions:
"Students of the first and second year, despite their young age and the beginning of a very difficult educational path, are already thinking about where they will be doing an internship and where they want to work in the future. Now they know, "how to choose and how we are chosen" – this was the topic of my master class. I would like to remark – it was quite active, thanks to great feedback from the students, who willingly participated in the discussion, asked questions, offered interesting solutions."
The agenda was diverse and interesting, and colleagues from leading law firms shared with the youth valuable practical information that you will not find in the textbooks. It's really great – to gather a lot of potential employers and professionals to-be at one place, it is very important to feel the demand to be able to make a proper offer. For us, it is a competitive advantage – to offer decent working conditions and growth, to be in a trend and even to set this trend. This is especially important in the millennials' era – time of youth distinguished by its type of thinking and high competencies, proactive life position and talent. Olena Lazareva, Head of BD and PR, spoke about this during Public talks section.
"The competition of tomorrow shifts from the biggest ones to the most agile ones. We are entering an interesting period of alternation of generations in business life, in the legal sphere as well, when ignoring the needs and targets of the younger generation becomes dangerous for business. According to various studies, from 1/3 to 60% of the labor force by 2025 will be made up of representatives of millennials generation with a completely different set of values and priorities. And if today we teach them what and how much they should know in order to succeed in the profession – tomorrow they will tell us what we should become to be interesting for them to develop business rather than seek to realize their talents in more adaptable companies or in their own startups. The new generation is focused on comprehensive personal development, not just obtaining of professional knowledge. We can help them in this, but first we should give them the feeling that a person with unique set of skills which we can help turn into talents, is most valuable for us.
Talent is important. And people with cultivated talents will drive business further. The question is whether this will be our business or of someone else."
We believe that Legal HR Fair will mean a fantastic start of a brilliant career.
Hope to see you at Legal HR Fair next year!


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The Contest is now OVER.
The lucky winner of this incredible $1,299 Tamron lens is: #2367 – Mira Crisp.
Congratulations. Make sure to check out the Tamron 24-70mm lens. This fall for another great lens contest – this time for a telephoto lens. You never know when your number will be the lucky one. The chances are a lot better than the Powerball 🙂
You have the chance to win a brand new Tamron 24-70mm lens {$1,299 estimated street price}
I love this lens for its flexibility, sharpness, and vibration compensation. I used it in Australia, Alaska and in Michigan on images of people, landscapes, and product shots. And I've used it while standing still, as well as on a moving boat, in a float plane and even in a helicopter. Tamron is showcasing the work of a number of photographers using this lens, including mine in a gallery of images here.
So are you ready to try to win a Tamron Lens?
Start by doing one or more of the first three entries. Once you do that, you can do as many bonus entries as you want of the remaining four. Remember to qualify, we do need to know that you did one of the first three though.
Shortcut links for Entries 4-7:
The Prizes:
Tamron 24-70mm VC Lens (for full frame and crop sensors too). The winner picks their choice of a Canon, Nikon or Sony mount (Sony cameras have image stability so there is not vibration compensation built into that mount).
Contest Rules:
The contest ends Sunday, May 19th at 8pm eastern time and winner will be picked via random drawing, and announced on the top of this post on the MCP Blog. You can enter between 1-7 times based on how many entry items you participate in. Odds are winning are 1-7/# of entries. Valid only where permitted by law.
Tamron USA Inc, the sponsor of this contest, is responsible for sales and marketing in the USA, therefore, they cannot ship outside of the USA. BUT if you reside outside the United States, the lens will ship to MCP Actions, and we will ship it to you. In this case, you will be responsible for the international shipping costs as well as any duties, taxes, or tariffs.


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A man has been arrested following a Peterborough shop theft where the offender was stark naked.
The theft is said to have happened at the JJ News store in Donaldson Drive, Paston yesterday.
A Cambridgeshire police spokesman said: "We were called at about 3.50pm yesterday afternoon (Monday, March 14) with reports of a naked man committing an indecent act in Donaldson Drive, Paston.
"It was also reported that the same man stole cigarettes from JJ News, also in Donaldson Drive.
"A 50-year-old man from Peterborough was arrested on suspicion of theft and indecent exposure. He is currently in custody at Thorpe Wood Police Station."


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A quick search for Vancouver sight-seeing, day trips, or Vancouver suspension bridges inevitably yields Capilano Suspension Bridge as one of the city's must-see. It's certainly impressive, but our vote for the best suspension bridge in Metro Vancouver is in Lynn Canyon, easily accessible by transit or car in the District of North Vancouver. Since there is no entry fee to Lynn Canyon Park, save yourself the whopping $42.95 (2017) charge to visit the Capilano Suspension Bridge and get high above the tree tops with your need-to-know guide to the Lynn Canyon Park & Suspension Bridge.
Lynn Canyon Park, home of the Lynn Canyon Suspension Bridge, first opened in 1912 and boasts over 600 acres of forest trails, swimming holes, and gorgeous natural landscape waiting to be explored. With a forest of west coast evergreen trees averaging 80-100 years old a mere 25 minutes from the city, a day trip to Lynn Canyon Park is city escapism at its finest.
Numerous trails connect the Lynn Canyon Suspension Bridge with 30 Foot Pool, Twin Falls Bridge, and the Ecology Centre. See them all within an hour's walk. For those looking to head out a little further afield, the 48km Baden Powell Trail flanks the east side of the park and provides a challenging yet simple to navigate out-and-back hike of any duration you choose.
Getting There
15km by road from downtown Vancouver, Lynn Canyon Suspension Bridge is accessible by car via the Lions Gate Bridge or the Second Narrows Bridge to Vancouver's North Shore. There is free parking on site, though on busy days you may need to park outside the main park's entrance and walk in.
For those without a vehicle, catch the SeaBus across beautiful Vancouver Harbour to Lonsdale Quay, and hop on the #229 or #228 bus to Lynn Valley Centre – a 15 minute walk from the Lynn Canyon Park's main entrance. If you would rather save your steps, the #227 bus will connect you from Lynn Valley Centre to the Lynn Canyon Park's main entrance so your walking shoes are ready to go inside the park.
The park is open summers from 7:00am to 9:00pm PST, spring and autumn from 7:00am to 7:00pm PST, and in the winter from 7:00am to 6:00pm.
As with any forested outdoor activity, be sure to keep your visit well within dawn-to-dusk hours.
Lynn Canyon Suspension Bridge
The park's main attraction, the Lynn Canyon Suspension Bridge, remains a locals' true hidden gem. It's narrow, springs a little with each step, and gives breathtaking views of the waterfalls and forests below. You will be 50m (164ft), or about 16 stories, above the raging river so take your camera and get ready to capture some incredible shots!
If the suspension bridge is your only priority in Lynn Canyon Park, it is easily accessible off the paved parking area for those visitors who are less mobile.
What to Bring
The trails at Lynn Canyon Park are a combination of wood plank boardwalk and dirt trail. Wear your day hikers as Vancouver is notoriously rain-city, so the trails may be wet. We believe there are no bad days, only bad gear, so with a decent rain coat and shoes you'll be set no matter what the day's weather brings.
There are numerous swimming holes in Lynn Canyon, though we're talking mountain-top runoff and very fresh water… so it tends to be chilly! Even so, on a summer's day a crystal-clear fresh water swim just can't be beat so pack a towel, picnic, drinking water and snacks and you'll have everything you need to enjoy a full day in west coast paradise.
Any of the accessible swimming locations are a minimum 15-20 minute walk from the carpark / suspension bridge. Mind the signs pointing out the swimming locations and do not jump a fence. It's incredibly steep in some locations with unforeseen drop offs. Stay safe, and enjoy the park!
The Lynn Canyon Ecology Centre offers young visitors of any age the opportunity to learn about the variety of plants and animals they may see in the park. There are numerous galleries to explore and with only a $2 suggested donation for entry, is easy on the pocket book.
No doubt you'll be ready for a bite after your visit to the Lynn Canyon Suspension Bridge, so we've compiled a few of our favourite North Shore vegan and vegetarian friendly hotspots for a great post-hike meal on your way back to the city.
- Tao Organics Café. Raw/Vegan. 210-150 Esplanade West, North Vancouver
- Burgoo. Soups/Stews/Comfort Foods. 3 Lonsdale Ave, North Vancouver
- The Workshop. Vegetarian Japanese. 296 Pemberton Ave, North Vancouver
- Bluehose Market & Cafe. Organic/Local. 4342 Gallant Ave, North Vancouver
Did we miss your go-to veggie friendly restaurant? Be sure to let us know in the comments below.
Baden Powell Trail Marker
We hope you enjoy your day at the beautiful Lynn Canyon Suspension Bridge as much as we do! It's a locals' hidden gem, and unlike the Capilano Suspension Bridge, visiting is completely free. So grab your shoes and camera and head out for a gorgeous west coast adventure just half an hour from the city lights. Bon voyage!


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3 things to do in London next week at Infosecurity Europe
London will be a hotbed of InfoSec activity next week with Infosecurity Europe (@infosecurity, #Infosec11) and B-Sides London (@SecurityBSides, @BSidesLondon, #BSidesLondon) happening from 4/19-4/21. In preparation for the excitement, we've put together a short list of events not to miss if you're going be in town, as well as resources for those of us who won't be there in person but would still like to take part in the conversation! Thank you, social media!
1. "The Cost of Compliance" Session at Infosecurity Europe 2011 (4/19)
Dwyane Melancon, head of Products at Tripwire will be presenting on 'The Cost of Compliance' on 4/19 at 13:20-13:45 in the Business Strategy Theater at Infosecurity Europe. He will discuss best practices to adopt to instantiate security and compliance together in your organization, techniques to achieve far greater security with far less effort, and concrete data to take back to your management to justify security and compliance expenditures in your organization. Check out this 2 minute sneak peek into his talk:
Social media:
- Follow: @cindyv on for live Twitter coverage of this event
- Speakers: @ThatDwayne
- Hashtags: #compliancecost, #Infosec11
2. B-Sides London (4/20)
The first ever B-Sides London will take place on Wednesday, 4/20 in a parallel InfoSec universe (Skills Matter eXchange, 116-120 Goswell Road, London, EC1V7DP 7DP London). According to Matt Summers (@dive_monkey), founder of Security B-Sides London and organizer of this year's London conference, B-Sides London had the fastest sell-out in Security B-Sides history. There is a good chance that they will accept walk-ins as space allows since most people are not there all at the same time (This has been the case at past Security B-Sides events).
Social media:
- Follow: @SecurityBSides, @BSidesLondon
- @cindyv will be live-tweeting from B-Sides London sessions
- Hashtag: #BSidesLondon
- Session list: http://www.securitybsides.com/w/page/27749044/BSidesLondon
3. Tripwire booth (4/19-4/21)
Visit us at our booth located at E31 on the show floor of Infosecurity Europe! We'll be giving away some great prizes like Apple gift cards for £15 and £500, as well as a SONY 40″ HDTV!
Come by the booth or follow us on Twitter at @TripwireInc to find out how to play and win!
We look forward to seeing you there or on Twitter!


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The Gotebo Gazette. (Gotebo, Okla.), Vol. 10, No. 17, Ed. 1 Friday, December 2, 1910
Description: Weekly newspaper from Gotebo, Oklahoma that includes local, state, and national news along with advertising.
Date: December 2, 1910
Creator: Stewart, A. H.
Item Type: Refine your search to only Newspaper
Partner: Oklahoma Historical Society


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Crowdsourcing Change: Applying the Social Web to Some Philly Nonprofits
Philadelphia, PA
On November 12, Philly Net Tuesday will feature our signature "Crowdsourcing Change" format. (NOTE the change of date — since our usual "first Tuesday of the month" is Election Day.) Here's how it works: Two or three local nonprofits share how they're using online marketing and social media/networking to achieve their goals and objectives. Then the crowd (that's you!) participates in a facilitated discussion about how each organization might use the social web to even greater effect.
We're pleased to announce two local organizations eager to receive the wisdom of the crowd will be:
- The Agatston Urban Nutrition Initiative (http://www.urbannutrition.org).
Presenter: Ashley Gripper, Administrative Coordinator.
The Agatston Urban Nutrition Initiative (UNI) works to sustain healthy communities by promoting food education, good nutrition and physical fitness in West Philadelphia. UNI's organizes hands-on learning opportunities for more than 10,000 students and their families at 20 public schools and community centers in Philadelphia.
- The West Philly Coalition for Neighborhood Schools (http://westphillyschools.org).
Presenters: Amara Rockar, Board President and Erin McLeary, Board Vice President
The West Philly Coalition for Neighborhood Schools (WPCNS) is focused on a core belief that public education is a social justice issue. Its members, many of whom are parents from a wide range of ethnicities, income brackets, and educational backgrounds, share a vision of a neighborhood strengthened by its school and a school strengthened by its neighborhood.
The event will be held at the Friends Center, 1501 Cherry Street. Doors open at 6:00 PM on the evening of Tuesday, November 12. Light fare will be available, and RSVP's are appreciated for planning, but not required.
Whether you're a social media expert or an interested citizen your perspectives and opinions are welcome and valuable. So, come and join the crowd with your questions, insights and reactions, and help these local organizations more effectively use social tools to achieve their important objectives. This is a great learning and sharing opportunity – not only for the presenting organizations, but for all participants!
Thanks to the American Friends Service Committee for sponsorship.


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Canberra Olympic have qualified for a second successive Westfield FFA Cup Round of 32 spot, beating Tuggeranong United 2-0 at Deakin Stadium.
The PlayStation 4 NPL Capital Football ladder leaders put in a dominant performance, and Robbie Cattanach's brace saw Frank Cachia's squad come out on top to put them into the Round of 32.
After a high intensity start from both sides, Olympic fired the first warning shot, with Tom McLachlan sending in a curling effort that didn't test Tom Barton in goals. Sean Murphy's side looked to absorb Olympic's high pressing game, as Tuggeranong searched for space in behind the NPL leaders using the pace of Aisosa Ihegie and Nikolaos Kalfas on the counter attack.
A strong Olympic side continued to apply pressure, and after a disallowed goal from Stephen Domeneci in the 12th minute, last year's qualification final winners broke the deadlock after 15 minutes, as Robbie Cattanach snuck a perfectly struck free kick just inside the left post to put his side ahead.
League top scorer Stephen Domeneci continued to trouble the Tuggeranong defence, but the attacker was ruled offside for yet another disallowed goal after 23 minutes.
Tuggeranong's best chance came in the 28th minute following a number of set pieces for the side, as Andrew Slavich went up for a close range header and was denied only by the Olympic crossbar. Moments later, Daniel Roberts fired in a well-struck long range effort, but Konstantinou pulled out a top-draw save to preserve Olympic's lead.
The second half began with both sides looking to get an early hold after the break, but it was Olympic who continued to hold sway, frustrating their opponents with their build up play through the middle of the field.
After a number of missed opportunities, Cattanach popped up again, linking up with Jeremy Habtemariam with a silky one-two and calmly taking the ball past Barton; firing home to hand his side a two goal cushion in the 81st minute and put Olympic back into the FFA Cup National round for the second year in a row.
Frank Cachia's side will now look forward to the Round of 32 draw, as Olympic hope to build on the legacy left from last year's cup run, when they finally bowed out to Sydney FC 3-0 in the semi-final.


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EXCLUSIVE! Tia Carrere Says Karina Smirnoff Left 'DWTS' Because Of Her Ex!
Hey, wouldn't YOU hate having to go to work and face your ex-boyfriend every day?
Yeah, we would too.
When Dancing With the Stars return next season, it's going to have a very different feel now that it's lost one of it's key players, Karina Smirnoff. But why would the dancer leave such a sweet gig? Season 2 contestant Tia Carrere thinks she knows the reason: Karina couldn't bear working with her ex-fiance, Maksim Chmerkovskiy!
"She's probably trying to get over Maksim." Tia, 43, told Hollywoodlife.com exclusively at the "Get Lucky for Lupus" event in West Hollywood Feb. 25. She added, "Well, they were engaged and they broke up, so I don't know, it's what I'd do."
Karina, 32, began dating fellow DWTS dancer Maksim, 30, in July 2008 and became engaged a quick six months later. At first, there was nothing but love between the two as Karina planned a gigantic fairytale wedding, but as things turned sour following their joint Broadway show, Burn the Floor, last summer, the couple ultimately split in September, 2009.
Poor Karina! Hell, it's awkward enough to run into an ex if you see them walking down the street or bump into them with their new girlfriend, but to have to see them every single day at work. Horrific.
How would you feel if you had to see your ex in the office every day? Would you want to quit your job, too?


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Weight Loss Doesn't Have to Be a Solo Endeavor
Losing weight is a process that takes dedication, patience, and plenty of will-power. However, weight loss does not have to be a solo endeavor. With help from The Fountain Clinic in the Cleveland, OH area, you can find a method of weight loss that fits you and your lifestyle. Learn more about how you can lose weight with help from Dr. Curt Birchall.
The Diet Science Program in Cleveland
The Diet Science Program is a diet customized for each individual patient based on how much weight they wish to lose. Developed by Dr. Birchall, the Diet Science Program can help patients lose weight regardless of if they have 10 or 100 pounds to lose. The program is supervised by Dr. Birchall, a weight counselor, a personal trainer and a dietician to provide lasting results and keep you healthy during the weight loss process.
The process begins with testing to determine if you are a good candidate for the Program. Various testing tells the Fountain staff if you are in good general health and fit to undergo the Diet Science Program safely. If so, the initial physical examination and weigh-in take place. From there, you will receive your customized diet plan. You may receive prescription medications or supplements to work alongside the diet itself. Dr. Birchall can help you determine what treatment plan is best for you.
Other Weight Loss Procedures at The Fountain Clinic
In addition to the Diet Science Program, The Fountain offers other cosmetic weight loss procedures to remove fat and tighten the skin as you go through your weight loss journey. The Exillis procedure melts body fat and tightens the skin in problem areas such as the arms, love handles, neck and thighs. Treatments last around 45 minutes with no downtime afterward. Most patients require four to six treatments. The Fountain also offers Skintyte laser skin tightening procedures to firm the skin on the neck and face.
For more information on weight loss in the Cleveland, OH area, please contact Dr. Birchall at The Fountain Clinic. Call (216) 503-8517 to schedule your appointment today!


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As part of our ongoing commitment to providing the best GIS location analysis tool on the market, we have updated Z ..
28 Jan 2016
As part of our ongoing commitment to providing the best GIS location analysis tool on the market, we have updated Z ..
05 Jan 2016
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04 May 2015
Economic development websites are constantly improving, as are the online strategies that make organizations successful. ..
25 Mar 2015
What do site selectors and investors look for on an economic development website? It's an important question, and one tha ..
04 Mar 2015
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They say imitation is the sincerest form of flattery. If this is true, we at GIS Planning feel deeply complimented. A ven ..
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We are proud to announce that all GIS Planning websites are now stored on Amazon Web Services (AWS). That means your Zoom ..
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Last night, in the midst of a homework project, my 11-year-old daughter asked me how people used to do research before th ..
11 Aug 2014
(http://lbi.sizeup.com)We've made some important updates to our SizeUp Local Business Intelligence (LBI) tool to improve ..


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A lot of what makes images such an unimaginable craft is the truth that expert photographers can carry a way of permanence to what would in any other case be a fleeting second. Pictures is one ability that revels within the thought of stasis. It's considered one of few strategies by way of which we will problem the relentless march of time.
However what if we might seize the essence of that onward march with out using movement photos? What if we might illustrate the passage of a day in a single nonetheless picture? Acclaimed photographer Stephen Wilkes got down to reply these questions a number of years in the past, and the ensuing collection is a everlasting interpretation of life's transience.
To realize this impact, Wilkes images the identical location from a set angle 1,500 instances over the course of 24 hours.
America's Cup, San Francisco, 2013
He then chooses the best photos from each session and blends them together seamlessly into one image.
Central Park View from Essex House, New York City, 2014
The transition from day to night and back again dictates much of the human experience. Because this is a shared phenomenon, Wilkes decided to choose subjects that people around the world could relate to in a similar way.


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Platinum agents are the backbone of cancer chemotherapy. Recently, we identified and replicated the role of a single nucleotide polymorphism (SNP, rs1649942) in predicting platinum sensitivity both in vitro and in vivo. Using the CEU samples from the International HapMap Project, we found the same SNP to be a master regulator of multiple gene expression phenotypes, prompting us to investigate whether rs1649942-mediated regulation of miRNAs may in part contribute to variation in platinum sensitivity. To these ends, 60 unrelated HapMap CEU I/II samples were used for our discovery-phase study using high-throughput genome-wide miRNA and gene expression profiling. Examining the relationships among rs1649942, its gene expression targets, genome-wide miRNA expression, and cellular sensitivity to carboplatin and cisplatin, we identified 2 platinum-associated miRNAs (miR-193b* and miR-320) that inhibit the expression of 5 platinum-associated genes (CRIM1, IFIT2, OAS1, KCNMA1, and GRAMD1B). We further replicated the relationship between the expression of miR-193b*, CRIM1, IFIT2, KCNMA1, and GRAMD1B, and platinum sensitivity in a separate HapMap CEU III dataset. We then showed that overexpression of miR-193b* in a randomly selected HapMap cell line results in resistance to both carboplatin and cisplatin. This relationship was also found in 7 ovarian cancer cell lines from NCI60 dataset and confirmed in an OVCAR-3 that overexpression of miR-193b* leads to increased resistance to carboplatin. Our findings highlight a potential mechanism of action for a previously observed genotype-survival outcome association. Further examination of miR-193b* in platinum sensitivity in ovarian cancer is warranted. Mol Cancer Ther; 11(9); 2054–61. ©2012 AACR.
Platinum agents, including carboplatin and cisplatin, are the backbone of classic chemotherapeutic regimens. They are used in the treatment of a wide array of cancers (1); however, interindividual variation in response to these agents is observed frequently without a clearly understood mechanism of resistance. Recently, utilizing a genome-wide cell-based approach, we have identified a set of germline genetic variations in the form of single nucleotide polymorphisms (SNP) and copy number variants that predict platinum sensitivity (2–4). Importantly, several of these cell-based findings have been validated in clinical patient samples (5, 6).
In particular, a SNP (rs1649942) was found to be associated with both carboplatin and cisplatin sensitivity in vitro (3, 5). Notably, this SNP was, in addition, found to be associated with progression-free survival and overall survival in 377 nonhispanic white ovarian cancer patients who had undergone carboplatin and taxol treatment (5), although the association was not supported in a (putatively more) heterogeneous set of patients (5), and with decrease in platelet counts in head and neck cancer patients who were treated with platinum-based induction therapy (6). Our group has shown that rs1649942 is a master regulator of multiple gene expression traits in a comprehensive genome-wide expression quantitative trait loci (eQTL) study (7). Many of these expression targets of rs1649942 are also correlated with platinum sensitivity. Interestingly, all observed SNP-gene expression relationships are trans relationships, suggesting a possible indirect SNP effect on gene expression mediated by other (intermediate) transcriptional regulators.
miRNAs, a class of noncoding small RNA molecules that play an important role in the posttranscriptional regulation of gene expression, are predicted to target a third of all human mRNAs (8, 9). Recent studies have shown the role of miRNAs in diverse cellular, developmental, and pathological processes (10). Specifically, it was reported that miRNAs are potential mechanisms of resistance to cytotoxic anticancer therapy (11). Therefore, in this study, we sought to evaluate the role of miRNAs in mediating the effect of rs1649942 on platinum sensitivity. The identification of such miRNAs promises to not only improve our understanding of the role of this important class of noncoding RNAs in mediating pharmacologic traits but also to provide potential biomarkers or druggable targets for platinum resistance.
Materials and Methods
Cell lines and drugs
Unrelated International HapMap lymphoblastoid cell lines (LCL; 60 CEU Utah residents with northern and western European ancestry; HAPMAPPT01) were purchased from Coriell Institute for Medical Research for genome-wide discovery; we refer to these cell lines as discovery-phase samples. Fifty-eight unrelated HapMap CEU III (HAPMAPPT06) LCLs were obtained from the same resource and used for replication experiments; we refer to these LCLs as replication samples. One benefit of the use of these cell lines for pharmacogenomic studies is that extensive genome-wide genotype and gene expression data are publicly available, which enables us to conduct genotyping assays on randomly chosen cell lines using randomly selected SNPs to authenticate the cell lines. This genotyping assay is regularly done in our Pharmacogenomic of Anticancer Agent Research (PAAR) cell line and genotyping core; furthermore, the cell lines have undergone extensive genetic studies by the International HapMap Consortium (12) and the 1000 Genomes Project (13). LCLs were maintained in RPMI 1640/1% l-glutamine plus 15% FBS as previously described (14). Ovarian cancer cell line OVCAR-3 was purchased from American Type Culture Collection. Carboplatin, cisplatin, and DMSO were purchased from Sigma-Aldrich, Inc.
mRNA and miRNA expression quantification
In the discovery-phase samples, global baseline gene expression on 87 CEU LCLs were quantified using the Affymetrix GeneChip Human Exon 1.0 ST array (Affymetrix exon array) as previously described (ref. 15; GEO accession No: GSE7761). Baseline miRNA expression was evaluated in 53 CEU HapMap LCLs using Exiqon miRCURY LNA arrays v10.0 (Exiqon array). After normalization and filtering, 201 miRNAs were found to be expressed in these samples (16).
In the replication samples, quantitative PCR (qPCR) methods were used to measure the expression of 5 genes (CRIM1, IFIT2, OAS1, KCNMA1, and GRAMD1B) and 2 miRNAs (miR-193b* and miR-320a). All miRNA primers were purchased from Exiqon whereas Applied Biosystems Taqman primer/probe sets were used to quantify mRNA expression. Real-time PCR was conducted using an ABI Vii7 thermocycler (Applied Biosystems). Details for total RNA isolation, cDNA conversion, and PCR condition were described in our previous publication (17).
Cellular sensitivity to platinum agents
Both discovery and replication LCLs were treated with increasing dosage of either carboplatin or cisplatin for 72 and 48 hours, respectively. Cellular growth inhibition was measured using an Alamar Blue assay as described previously (14). Drug concentration required to inhibit 50% of cellular growth is defined as IC50 and was used to characterize individual cellular sensitivity to platinum agents. The cellular sensitivity to carboplatin and cisplatin in various HapMap LCLs including those studied here was reported elsewhere (14, 18) and all data as well as genome-wide SNP association results with these data have been made publicly available (19).
Data analysis
The overall workflow in the discovery phase is illustrated in Fig. 1. In the discovery-phase samples, linear regression was done between the rs1649942 genotype, assuming an additive model, and the 201 miRNA expression levels obtained through Exiqon arrays. Only those miRNAs that were associated with rs1649942 at P < 0.05 were further examined for (negative) correlation with the expression of 39 genes that were expression targets of the SNP as an eQTL (7). The ExprTarget database (20), which was constructed to integrate various bioinformatic prediction tools along with our Exiqon and exon array experimental data, was queried to identify the negative correlation relationships between the miRNAs and mRNAs of interest [both 0.05 (for screening) and 10−4 (false discovery rate (FDR) < 0.05, for multiple testing correction; ref. 21) cut off were examined]. Furthermore, the relationship between mRNA expression levels and sensitivity to carboplatin or cisplatin were queried through PACdb (19), another publicly available database we constructed to host results of SNP associations with chemotherapeutic agent sensitivity or with gene expression. Linear regression analysis was carried out between miRNA expression and log2-transformed carboplatin or cisplatin IC50 with P < 0.05 as cutoff. Linear regression was also used to evaluate the SNP-miRNA-mRNA-platinum sensitivity relationships in the replication samples with P < 0.05 used as cutoff. In the discovery-phase samples, the nominal threshold P < 0.05 was used to filter for relationships (among the SNP, miRNAs, and related mRNAs) to carry forward for replication and for additional functional studies.
Functional annotation enrichment analyses
We evaluated the Pearson correlation coefficient between gene pairs for those genes whose expression levels are correlated with miR-193b* and with sensitivity to both platinating agents. We found an enrichment of highly correlated genes (in particular, positively correlated genes) compared with the genomic background, which was derived from 1000 randomly selected pairs of genes from the genome (Supplementary Fig. S1). This finding suggests that genes associated with both miR-193b* and platinum sensitivity may share the same biological pathway. Additionally, we carried out functional annotation enrichment analyses using DAVID (22, 23) with 3 lists of genes. First (level 1), we examined the 39 target genes for the eQTL rs1649942 in order to reveal novel pathways important for cellular sensitivity to both platinum agents. Second (level 2), we considered all potential gene targets of miR-193b* as predicted by ExprTarget (ref. 20; 668 from miRanda and 512 from the LCL-based expression data) and carried out functional enrichment analysis to reveal pathways affected by a specific miRNA (miR-193b*). Finally (level 3), we carried out pathway analysis on the 10 genes whose expression levels are negatively correlated with miR-193b* and also correlated with sensitivity to both platinating agents. We report functional terms that meet the nominal threshold P < 0.05.
Role of candidate miRNAs in platinum sensitivity in NCI60 tumor samples
The expression of the miRNAs and −log10platinum GI50 data from the NCI60 dataset were queried using CellMiner (24). Linear regression analysis was carried out between miR-193b* expression [quantified using Agilent Human miRNA (V2)] and −log10GI50 of either platinum agent, independently for all 60 NCI60 samples as well as for a subset of 7 ovarian cancer cell lines.
Functional validation for miR-193b*, its targets and platinum sensitivity
To functionally validate the role of miRNAs in regulating gene expression and in conferring platinum sensitivity, we conducted miRNA overexpression experiments for miR-193b* in 2 randomly selected HapMap CEU samples (GM07055 and GM07056) as well as in an ovarian cancer cell line (OVCAR-3). Specifically, miRNA mimic (catalog no. MSY0004767) for miR-193b* and scrambled control (AllStars Negative control, catalog no. 1027292) were purchased from Qiagen. Detailed methods of the overexpression and inhibition experiments in LCLs were described previously (17). In OVCAR-3, miR-193b* mimic was transfected in using DharmaFECT 3 transfection reagent with existing Dharmacon DharmaFECT General Transfection protocol. miR-193b* and the gene expression levels of its targets were quantified through qPCR 5, 24, and 48 hours posttransfection. A Student t test was carried out between mimic treatment and controls at each time point. Cellular sensitivity to both carboplatin and cisplatin was measured using the method described above 24 hours post-miR-193b* mimic transfection in LCLs and with CellTiter-Glo luminescent cell viability assay (Qiagen) 48 hours after mimic transfection in OVCAR-3. Cellular growth inhibition curve was plotted after increasing concentrations of carboplatin or cisplatin treatment. Two-way ANOVA was conducted to compare the cellular growth inhibition effect by platinum after treating the cells with either miR-193b* mimic or scramble control. P < 0.05 was used to define statistical significance.
miRNAs associated with rs1649942 genotype play a role in platinum sensitivity via their effects on target gene expression
We found that rs1649942 is associated (P < 0.05) with 89 miRNA expression phenotypes (of 201 tested) in the HapMap CEU LCLs discovery-phase samples (see Materials and Methods). Examining the relationship between these miRNAs and the 39 expression targets (mRNAs) of the same SNP (7), we selected for downstream analysis 61 of these miRNAs, for which higher expression resulted in reduced expression of at least one target gene (at nominal P < 0.05) of rs1649942. There were 27 such target genes (Fig. 1, left branch using a nominal threshold for screening).
When a miRNA or mRNA is nominally associated (P < 0.05) with the IC50 of both carboplatin and cisplatin, we refer to the miRNA or mRNA as platinum associated. Of the selected 27 expression targets of rs1649942, 14 (52%) were found to be platinum associated. Three of the 61 miRNAs are platinum associated and, in addition, negatively correlated (at nominal P < 0.05) with at least one of the 14 platinum-associated target genes of rs1649942 (Fig. 1 left branch). These 3 miRNAs are miR-193b*, miR-320a, and miR-424. A summary of these SNP-miRNA-mRNA-platinum sensitivity relationships can be found in Table 1.
For multiple testing correction (on the miRNA–mRNA inverse relationships), we used an FDR approach (21). At FDR < 0.05 (corresponding to P < 10−4) for the (negative) correlation between rs1649942-associated miRNAs and mRNAs, we found that 2 miRNAs (namely, the platinum-associated miR-193b* and miR-320a) are significantly correlated with 5 platinum-associated genes (CRIM1, IFIT2, OAS1, KCNMA1, and GRAMD1B; bold data in Table 1, Fig. 1 right branch and Supplementary Fig. 2).
To replicate these findings, we used 58 unrelated HapMap CEU III samples, for which the rs1649942 genotype and data on cellular sensitivity to the platinum agents are publicly available (18, 19). Indeed, the SNP was found to be significantly or suggestively associated with platinum sensitivity in these replication samples (P = 0.03 and 0.07 for carboplatin and cisplatin IC50, respectively). Note that the additional G allele is associated with platinum resistance in both the discovery-phase and replication samples. We also quantified the expression of miR-193b* and miR-320a along with their 5 putative-binding targets in these samples using qPCR method. The expression of miR-193b* was found to be platinum associated in the replication samples (P = 0.03 and 0.02, for carboplatin and cisplatin, respectively; see Fig. 2). Increased expression level of miR-193b* conferred greater platinum resistance. Furthermore, we replicated the negative correlation between miR-193b* and 2 of its putative targets (CRIM1 and IFIT2; Fig. 3). These 2 genes, along with GRAMD1B and KCNMA1 (Table 2; which were identified to correlate with the expression of miR-320a and with miR-424 to a lesser degree), were found to be platinum associated in the separate (replication phase) dataset just as in the discovery-phase samples. On the other hand, we did not replicate the relationship between miR-320a expression and platinum sensitivity.
Functional annotation enrichment analyses
Using DAVID, we found enrichment of certain Biological Functional annotation terms such as immune response from the level 2 analysis regardless of the method used to obtain the miR-193b* target genes (enrichment P value = 0.01 and 0.00001 for predicted target genes derived using miRanda and the genome-wide gene expression datasets in LCLs, respectively) and from the level 3 analysis (P = 0.046 using the 10 miR-193b*- and platinum sensitivity-related genes).
Functional validation of the role of miR-193b* in platinum sensitivity
Using 2 randomly selected CEU LCLs treated with miR-193b* mimic, we found that the addition of miRNA mimic yields higher intracellular miR-193b* expression at 5, 24, and 48 hours posttransfection in both cell lines. This increase in miR-193b* expression also led to decreased expression of CRIM1 at 5 hours posttransfection. We did not observe decreased expression of IFIT2 at these time points. More importantly, cells became more resistant to both carboplatin and cisplatin treatment when compared with treating them with scramble control (P < 0.0001 with two-way ANOVA for both drugs; Fig. 4A and B).
Role of miR-193b* in cancer cell lines
We queried the NCI60 dataset through CellMiner and found that increased miR-193b* expression conferred greater platinum resistance in 7 ovarian cancer cell lines (Supplementary Fig. S3). Furthermore, we conducted miR-193b* overexpression experiments in an OVCAR-3 ovarian cancer cell line. The addition of miR-193b* mimic (overexpression) resulted in increased expression of miR-193b* (compared with control, t test, P < 0.0001), decreased expression of CRIM1 (compared with control, t test, P = 0.07 at 24 hours and P = 0.02 at 48 hours) and increased cellular resistance to carboplatin in OVCAR-3 cell line (P < 0.0001 with two-way ANOVA; Fig. 4C).
By triangulating a SNP (that has been shown to be associated with carboplatin and cisplatin sensitivity in lymphoblastoid cell lines and in patient samples) with miRNAs and their putative mRNA targets, we identified the potential role of miR-193b*, miR-320a, and miR-424 in platinum sensitivity. Replication and overexpression experiments confirmed the role of increased miR-193b* expression in conferring platinum resistance in both LCLs and cancer cell lines. Our study integrated genetic variation, miRNA expression, and transcriptome expression to characterize interindividual variation in cellular sensitivity to platinating agents. The identified miRNAs and genes may serve as potential targets for platinum resistance.
miR-193b has been shown to play an important role in several types of cancers, acting like a tumor suppressor in some (25–27), while showing overexpression in others (28). miR-193b has also been found to downregulate estrogen receptor alpha in breast cancer cell lines (29). More recently, a SNP in the miR-193b precursor-flanking region (rs30236) was found to potentially associate with non–small cell lung cancer survival, a disease that is commonly treated with platinum agents (30).
In our study, the expression of miR-193b*, a miRNA on the opposite arm of miR-193b of the same pre-miRNA hairpin structure, along with 2 of its putative targets (CRIM1 and IFIT2) were shown to be platinum associated in the HapMap CEU discovery and replication samples. Checking publicly available drug-induced cellular sensitivity phenotype data (19), including etoposide and daunorubicin, we found the effect of miR-193b* and the 2 targets to be specific to the platinum agents. In addition, overexpression of miR-193b* resulted in decreased CRIM1 expression and increased carboplatin and cisplatin resistance in LCLs. This supports the role of miR-193b* in platinum sensitivity. Furthermore, higher miR-193b* expression was observed to result in greater platinum resistance in 7 ovarian cancer cell lines that are a part of the NCI60 dataset. Our miR-193b* overexpression experiment in OVCAR-3 shows that increased miR-193b* expression in this ovarian cancer cell line results in increased resistance to carboplatin.
CRIM1 encodes cysteine-rich transmembrane BMP regulator 1 (chordin like) protein. The encoded protein may play a role in tissue development though interactions with members of the transforming growth factor beta family, such as bone morphogenetic proteins (31). Various miRNAs have shown their regulative effect on CRIM1 expression, resulting in diverse biological functions. For example, 5 downregulated miRNAs were shown to subsequently affect CRIM1 protein expression and affect neuronal lineage differentiation in unrestricted somatic stem cells (32). miR-20b was found to enhance osteogenesis by repressing CRIM1 in human mesenchymal stem cells (33). Unfortunately, miR-193b* was not among those miRNAs evaluated in these studies. Interestingly, a recent study showed the role of CRIM1 in drug resistance in myeloid leukemia cell lines (34). Another putative target of miR-193b*, IFIT2 (interferon-induced protein with tetratricopeptide repeats 2), whose expression is also correlated with platinum sensitivity in our study, was recently reported to induce apoptosis via a mitochondrial pathway (35). Furthermore, platinum-induced cellular apoptosis was also reported to be a useful pharmacogenomic trait (36).
In our study, 2 of miR-320a targets (namely, GRAMD1B and KCNMA1) were found to correlate in expression with platinum sensitivity in both the discovery and replication samples; however, we did not replicate the role of miR-320a in platinum sensitivity. Since various other miRNAs have shown correlation with these 2 genes (e.g., miR-424), it is possible that these genes may be affected by other miRNAs that directly or indirectly affect platinum sensitivity. Interestingly, these 2 gene expression-drug sensitivity relationships are not unique to the platinums, with observed relationships to etoposide and daunorubicin as well.
In summary, a genetic variation that predicts platinum sensitivity led to the discovery of the role of miR-193b* in conferring platinum sensitivity. Our data support that increased expression of miR-193b* and the subsequent effect on its gene targets contribute to variability in platinum resistance.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Authors' Contributions
Conception and design: D. Ziliak, R.S. Huang
Development of methodology: D. Ziliak, E.R. Gamazon, R.S. Huang
Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): D. Ziliak, B. LaCroix, Y. Wen, R.S. Huang
Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): D. Ziliak, E.R. Gamazon, B. LaCroix, H.K. Im, R.S. Huang
Writing, review, and/or revision of the manuscript: D. Ziliak, E.R. Gamazon, Y. Wen, R.S. Huang
Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): R.S. Huang
Study supervision: R.S. Huang
Grant Support
This study was supported by NIH/NCI grant R21 CA139278 and by NIH/NIGMS grant UO1GM61393. R.S. Huang received support from NIH/NIGMS grant K08GM089941, University of Chicago Cancer Center Support Grant (#P30 CA14599) and Breast Cancer SPORE Career Development Award.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
We are grateful for Mr. Viren Makhijani for assistance in RNA isolation from the replication samples and Dr. M. Eileen Dolan's lab in generating and depositing the platinum sensitivity data.
Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).
- Received February 27, 2012.
- Revision received June 13, 2012.
- Accepted June 14, 2012.
- ©2012 American Association for Cancer Research.


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