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What Are The Best Cardio Machines For Burning Calories?
Let's start with a simple question: What is a cardio machine?
Technically an endless-path machine, a cardio machine is a piece of mechanical equipment used for the improvement of human health. Its user follows a repetitive motion (often against resistance); doing so raises the heart rate and boosts blood flow around the body.
The first cardio machine was patented in 1913, believe it or not: A treadmill used to test for signs of heart and lung disease.
You will find one or two cardio machines installed for a specific purpose in hospitals, physio clinics, schools, businesses, sports shops and training centres. Astronauts even use a modified treadmill on the International Space Station.
And while there are a lot of medical applications for cardio machines we are going to look at how they have impacted the world of fitness.
We are especially interested in cardio machines that burn the most calories. After all, what concerns us here at SCI-MX is how well a cardio machine can aid our fitness regime.
Because, when you arrive at a gym and you see a gargantuan variety of cardio machines, the decision about what one to use becomes yours to make… And with many of them promoted by their makers as being the next generation of calorie-busting device it is hard to know which cardio machines REALLY burn the most calories.
What are the benefits of cardio machines?
Cardio-vascular (CV) gym equipment mimics movement in one direction or another along a plane and simulates common activities such as running or cycling. The benefits to health arising from their use have been noted by doctors for years.
Cardio machines promote loss of weight and reduce mental stress.
A rowing machine may not bring the same enjoyment as rowing across a still river on an early morning in July but its convenience cannot be denied. Furthermore, the resistance of most cardio machines can be adjusted to suit, the ambient air is usually 'comfortable' and (especially for the rowers) you won't be nagged by the thought of the return journey.
There are a number of other reasons to prefer the indoor machine. Read on to find out what they are and, of course, which gym equipment burns the most calories.
Of most articles centred on cardio-machine 'likeability', preferences are often swayed by the bloggers point of view, and results tend to be written accordingly, but that's not the case here.
So, the stats that you will read about here of eight popular cardio machines are brought together from various sources completely objectively. We are about to give you definitive results.
Cardio-Vascular Exercise Explained
Cardio exercise is any exercise that raises your heart rate. When it's beating fast, the heart's muscle health increases and that presents us with a basic fact: it will beat for longer than one which is not exercised regularly.
Cardio exercise also works on muscular development; it removes the stodginess of your veins and arteries by forcing something called vasodilation (allowing blood to pump faster around your body).
What's more:
By delivering more oxygen to your organs, CV exertion also improves your overall health by lowering the amount of bad cholesterol in your system.
Types Of Cardio Machine
The stair-mill consists of a repeating set of stairs up which you will walk. It offers a great cardio workout and spikes muscle growth of the lower portion of your body. All-in-all, the stair-mill:
- Uses big muscle groups of the lower body repeatedly
- Utilises stabilising muscle and builds core strength
- Builds endurance and concentration
- Employs glutes, hamstrings, quadriceps and calves
- Applies little wear and tear of ligaments and tendons
The rowing machine engages your entire body and improves coordination and strength. The rower:
- Uses upper and lower muscles repeatedly
- Utilises coordinating muscle and builds core strength
- Builds endurance
- Employs the shoulders, trapezii in the upper back and the lower back
- Applies little wear and tear of ligaments and tendons
Spin Bike
The Spinner provides a challenging workout, and Spinner classes are hugely popular and great fun. There's a real sense of comradery at a Spinner class, as well as the sense of being completely exhausted. The Spin bike:
- Builds lean muscle and affords supreme weight loss
- Builds core strength
- Builds endurance and mental strength
- Employs glutes and hamstrings
- Applies little wear and tear of ligaments and tendons
The treadmill is the oldest of the cardio machines and arguably the easiest to use. It is a great health investment when it comes to home-based exercising. The treadmill:
- Uses lower body muscle repeatedly
- Utilises stabilising muscle and builds core strength
- Builds endurance
- Employs your calves, backside and quadriceps
- Applies little wear and tear of ligaments and tendons
Static Bike
Often seen as a wise choice at the very start of a weight loss programme, the static bike affords some results with relative ease. Even moderate activity can boost hormone and opioid production. The static bike:
- Provides a good start to a weight-loss journey
- Builds core strength
- Builds endurance and mental strength
- Employs glutes and hamstrings
- Applies little wear and tear of ligaments and tendons
Although limiting the amount of natural movement, the cross-trainer is still a popular choice for those looking to condition their bodies. The cross-trainer:
- Uses all muscle groups repeatedly
- Improves general core strength and stability
- Builds endurance
- Employs glutes and hamstrings
- Applies little wear and tear of ligaments and tendons
Arc Trainer
The Arc trainer is similar dynamically to the cross-trainer but more adequately reduces stress on the ankle, knee, and hip joints. It is also better suited to taller people than the cross trainer is. The Arc trainer:
- Uses big muscle groups of the lower body repeatedly
- Utilises core strength
- Builds endurance
- Employs a wide variety of muscles (according to angle settings)
- Applies little wear and tear of ligaments and tendons
Recumbent Bike
The recumbent bike is sometimes seen as the poor relation of the cardio machines. It may not work the upper body and core, but it is as effective at conditioning the lower body as a static upright bike. The recumbent bike:
- Uses big muscle groups of the lower body repeatedly
- Boosts your heart rate if exercise is vigorous
- Builds endurance
- Engages glutes and hamstrings
- Applies little wear and tear of ligaments and tendons, especially of the knee
Comparison Of Calorie Burn Per Minute
The time is right for us to compare these machines in terms of their potential to burn calories. To do this we have taken data from various sources - including self.com and shape.com - and calculated data results for both men and women weighing between 135 and 160 lbs (9 - 11 stone).
Important, the figures shown are from vigorous exercise:
Treadmill: 13.43 calories per minute
Rower: 12.90 calories per minute
Static bike: 12.88 calories per minute
Spin bike: 12.35 calories per minute
Stair-mill: 10.95 calories per minute
Arc trainer: 10.80 calories per minute
Cross-trainer: 8.22 calories per minute
Recumbent bike: 7.66 calories per minute
It terms of which are the cardio machines that burn the most calories the clear winner is the one that has been around for 105 years: the treadmill.
How To Approach A Cardiac Workout
Now that we've gauged which gym equipment burns the most calories, we can plan our cardiac workout more confidently. After all, it's not worth heading to a gym without a clear purpose, nor the right nutrition and supplementation!
Should your day's normal routine force you to visit the gym only in the morning, it is best to load up with carbs and protein before leaving the house. Failure to do so will not break the catabolic state in which your body lay throughout the night (when more protein was broken down than was ingested). A protein drink or high-protein meal about an hour before your workout will suffice.
It is important to remember that if you want to use cardio machines to help you lose weight, a high intensity workout is the very best course of action.
But be careful if you also want to build strength and condition your physique. Should your cardio workout be any longer than about 20 minutes, your muscles will begin to cry out for protein. There will then be little point for further training unless you are prepared to break and refuel.
Hydration and nutrition are most important during vigorous exercise, for obvious reasons.
What you take in after your cardio session is a matter of personal choice. If you feel you were sufficiently loaded with protein prior to your exercising you should perhaps focus on refilling your body with fluids, especially if your time on the machine was intense. Experts suggest after a 20- to 30-minute vigorous cardio session you should drink at least eight ounces of water.
When To Head For A Cardio Machine
Listen to your body. Only YOU know what it wants…
Although many online fitness routines (and personal trainers) advocate such things as interval training, pre-workout cardio sessions and post work-out cool downs, when all is said and done YOU must decide what will work and what will make you feel like you are making progress.
Most fitness buffs agree with the notion that a brief spell of CV before strength training or conditioning is a must, if nothing more than to loosen up your joints and muscles and increase your heart rate.
But when it comes to an intense cardio session, there are those who opine that this should come after weight training or an instructed workout.
To have used your reserves of carbohydrate (glucose/glycogen) prior to your CV exercise your body will be urged to look elsewhere for its energy and when freely available carbs have depleted, your body fat is next to be pulverised.
Other Ways To Burn Calories
It isn't just cardio machines that burn the most calories (although as we have seen there is one clear first among equals). Take some time to consider all of the other forms of exercise to supplement your regimen.
Remember: the calorie expenditure we have outlined here largely depends on the intensity of your workout and the duration of your session. Sitting in a pool talking to your friends is NOT going to burn that many calories (although it will burn more than if you were sat in a pub!)
Here are some alternatives to cardio machines that are worth considering because of their calorie burning ability:
- A strict calorie-controlled diet
- Weight training
- Swimming
- Calisthenics
- Yoga
- Dance
- Walking briskly
- Pilates
So, which is it?
Clearly, the treadmill should be first choice for someone looking to get the most from their cardio workout. But the key to any results from cardio machines is intensity.
We may have shown here that a calorie burn by vigorous exercise on a treadmill surpasses that of other machines, but do keep in mind that should you choose to merely walk while on a treadmill you will achieve far fewer losses than you would from a high-octane Spinner class.
The truth of the matter is that most people don't maximise their cardio workouts. This will not do. You have to input strength, endurance and The Push to achieve results from any gym equipment, not just the cardio machines. It will hurt. It has to hurt!
If you find a certain machine easy then turn the dial on the bike or rower, or find some gym equipment that burns the most calories for you. As they say: no pain, no gain.


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BET Networks Acquires "Hollywood Hearts" Starring Bobby V., DC Young Fly, Lyfe Jennings And More And Release Much Anticipated Movie Trailer. Tier 2 Films have teamed up with Blu Kolla Dreams to produce Hollywood Hearts, a romantic drama set to release on BET networks on October 8, 2016 at 8:00PM ET/ 7:00C.
>Award winning singer/ performer, Bobby V, leads the cast in a complicated love story that is all too real to many who come-of-age in the world of entertainment. Hollywood Hearts is about a music artist who's engrossed with his music industry lifestyle and finds it difficult to give up his ways for the woman that he loves, the life he wants to build and the ego he can't let go of. However, after a tragic turn of events and real friend interventions, he finds himself realizing that the industry will come and go but true love doesn't come around but once in a lifetime. Hollywood Hearts is Directed, Written and Executive Produced by African-American visionaire Tangie B. Moore of Tier 2 Films. Since co-founding Tier 2 Films, Tangie has been able to ink several deals and placements with Discovery Studios, WEtv, EOne, Sprite, BET Entertainment/Viacom & Samsung.
The films cast includes: Bobby V, DC Young Fly, Lyfe Jennings, Benzino, Carl Payne and more. Tune in to BET on Saturday, October 8, 2016, at 8:00PM/ 7:00C to view Hollywood Hearts. To join the viral conversation follow @BET @BobbyVshow #HollywoodHeartsFilm #BluKolla #Tier2Films
- Tangie B. Moore
- Ric Atari
- Tangie B. Moore
Lead – Bobby V – Bobby VLead – Walnette Santiago – JamiePatrice Fisher – IndiaWillie Hyn – HynBenzino – BenzinoCarl Payne – RickAsia Sparks – Hunter MayoLyfe Jennings – DakariDC Young Fly – Wonder-the-Truth
- Ric Atari
- Tangie B. Moore
- Bobby V.
- Courtney Stewart
Jazzlyn Kirkland
"What we long for is free, and what we stand for is to be."
+COOKiE VALENTiNE+
Part time party girl and full time line stepper. Vegas is where I call home. I have a heart for music and an eye for fashion and would love to hear from you. See something cute, hear something juicy... send it to me at firstname.lastname@example.com

subset: commoncrawl


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Jun 25, 2015Conference recording: Caroline McCarthy-Stout, Head of Strategy & Reporting at Lloyds Banking Group talks to the RBS 2015 audience on day two about engaging employees with your strategy and building pride
May 2015, London, United Kingdom
Europe's leading meeting place for corporate leaders delivering sustainable business. 12+ C-Suite and over 300 attendees will address some of the key issues and opportunities, including: sustainable innovation, collaboration, and resource efficiency and brand strategies
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6153 Kenzie Lane
Sales Consultant
Brandie Dauer - (614) 596-4165
More About This Home
This custom ranch features open entertaining and living areas and 10' ceilings and 8' doors.
The spacious great room and master bedroom both have raised ceilings. A private study includes double doors from the formal foyer. The gourmet kitchen with a walk-in pantry, and the master bedroom with an extended vanity, huge shower, and a spacious closet, all complete this beautiful home.
- Raised Ceilings Great Rm, Master
- On Slab for Easy Access
- Master w/Extended Vanity
- Covered Patio
Community - Coffman Park
School District - Dublin Schools
Location - Dublin
Lot - 25
Square Ft - 1,966
Bedrooms - 2
Bathrooms - 2
Garage - 2


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Unique tool-less half-twist detachment system that allows the spray gun to be attached/detached by simply turning the handle 180 degrees. The spray gun is now ever easier to use than before.
Low Volume Medium Pressure Gun is designed fine atomization and high transfer efficiency with much less air consumption that those of conventional guns and HVLP guns. Furthermore, the T-AGPV is a uniquely designed detachable gun. Hoses and tubes are connected not directly to the gun, but to the mounting plate where the gun is easily attached/detached by simple turning a handle 180 degrees. This new design greatly simplifies the disconnection process, resulting in significantly reduced line suspension time for replacement and/or maintenance.
T-AGPV Automatic LVMP Detachable Spray
LVMP Low Volume Medium Pressure
Spray Gun CATALOGUE for Asia
T-AGPZ-F158/F159/F208/F209/S8/S9 COMPACT AUTO. GUN Operation Manual
T-AGPV-868,869,878,879 LVMP Partslist


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Welcome to Ephicacy!
Ephicacy is a niche provider of consulting services and functional sourcing for the life sciences industry with focus on Biostatistics, SAS Programming, Data Migration, CDISC Data Conversion and Clinical Data Management across all phases of clinical trials.Read More...
Employee Speak
"After spending years in the US, it has been a thrilling five years working at Ephicacy with a similar pedigree of customers & colleagues. The company makes continued investments in the technology Infrastructure and is also expanding the range of services to customers. A very exciting place to work which nurtures leadership and fosters Innovation".
Tyagrajan SwaminathanMS, Applied Statistics, Bowling Green State University, M.Sc. Statistics, University of Mumbai. Previously with Myrexis Pharmaceuticals, USA)
"Ephicacy has helped me enrich my technical capabilities by providing ample opportunities in the programming arena-both statistical and CDISC standards. The mentorship, support of colleagues and management here is the magic potion of success".
Rajasekhar Mudugu(Previously with D E Shaw India Software Pvt.Ltd.)
"Five separate fingers are five independent units. Close them and the fist multiplies strength. This is Ephicacy to me as an organization-a closely knit family".
Anu Sivanesan(Previously with Cognizant Technology Services Pvt. Ltd)
"In a span of one year I have learnt to handle the entire recruitment process. This exposure, mentoring and learning has moulded me as a better individual professionally".
Sivasubramanian Renganathan(Previously with Allegis Services India Pvt. Ltd)
"Our policies and practices are pro-people. Ephicacy involves its employees in decisions pertaining to people practices. This has helped us build a culture where people feel recognized and valued".
Divya Cetlur(Started her career at Ephicacy)
"Over the last 7 years of my association with Ephicacy, I have seen Ephicacy evolve as a talent-rich organization in its domain of expertise. We have always valued competency over experience. I am proud to say that our employee compensation & benefits are one of the best in the industry".
Sunanda Subramanyam(Previously with Sasken Communication Technologies Ltd.)
"I have been with Ephicacy for over eight years and have been part of the company's Global Mobility program, moving from the USA to India. The company maintains a consistent culture and professionally I have hardly noticed the Geographical relocation. Ephicacy has outstanding long-term customer relationships reflected by the fact that I worked with one Tier 1 Global client for over six years."
Vindhya M.S.M.S.Bio Medical Engineering, Wayne State University
- A CDISC - Gold member
- ISO 9001:2015 & 27001:2013 Certified
- 21 CFR part 11 compliant
- A well-knit team of biostatisticians and statistical programmers
- Well established procedures for all business functions
- Secure and audited infrastructure with facilities to serve geographically distributed customer base
- Robust recruitment engine to provide competent resources
- Systematic capacity building
- Employee friendly culture
Grow with Us
As you nurture your career at Ephicacy, you will get an opportunity to deal with the world's foremost bio-pharmaceutical and CRO companies.Read More...


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Anyone hear what happened at the new strip club in Gladstone street Fyshwick on Anzac Day?
Went past about 1.30pm and police hat taped off the area in front and carpark of the place and there were those yellow things with numbers on them spread out on the ground.
Police were taking photo's too.
Police were still there at 5pm too.


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Ultra-Light Acoustic Standard
(Gloss Black)
When we say "compact," we mean it.
Fits in airline overhead bins.
Under 3 pounds, less than 2.5 feet long.
The Ultra-Light comes equipped with an acoustic piezo pickup and a standard 1/4 inch output jack. Plug it into your favorite amp, recording device, or headphone amp and practice anyplace, anytime.
Traveler Guitar's innovative and space-saving in-body tuning system eliminates the need for a headstock. And because all Ultra-Lights are full-scale, there's no compromise in the playing experience you're used to on your full-size axe.
Like all Traveler Guitars, the Ultra-Light comes standard with a sturdy gig bag so you can throw it over your shoulder and be ready to rock anytime, any place.
- Full 24 3/4" scale acoustic/electric travel guitar
- Fits in airline overhead bins
- One-piece Eastern American hard maple neck-through-body design
- Detachable laprest
- 2 lbs. 14 oz.
- 28" long
- Piezo pickup with standard 1/4" output
- Includes gig bag
- Audio Output: STANDARD 1/4 IN. JACK
- Batteries: N/A
- Body: EASTERN AMERICAN HARD MAPLE
- Body Thickness: 1.5 IN.
- Body Width: 5.25 IN. (LAP REST DETACHED)
- Construction: NECK-THROUGH-BODY
- Electronics: PASSIVE ELECTRONICS
- Fingerboard: MAPLE
- Finish: BLACK GLOSS FINISH
- Frets: 22 MEDIUM
- Gig Bag LxWxH: 30 X 6.5 X 3 (IN.)
- Hardware: CHROME CLOSED GEAR
- Headphone Amp: NONE
- Instrument Input: NONE
- Model #: ULAS BKGMP
- Neck: EASTERN AMERICAN HARD MAPLE
- Neck Radius: 15.75 IN.
- Neck Width at Nut: 1.75 IN.
- Overall Depth: 2 IN.
- Overall Length: 28 IN.
- Pickup(s): TRAVELER PIEZO
- Scale Length: 24.75 IN
- Strings: D'ADDARIO EJ15
- Weight: 2 LBS. 14 OZ.
- Weight in Gig Bag: 3 LBS. 12 OZ.


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Global provider of retail solutions implements SAP IS-Retail.
The client is top 5 provider of retail solutions globally offering a full range of integrated solutions.
The Client
The client is top 5 provider of retail solutions globally offering a full range of integrated solutions across various selling touch points such as PoS, Mobile, BYOD, eCommerce and IT managed services.
The Challenge
- Development of Rapid deployment solutions for SAP IS-Retail implementation with POS.
- Integrations for key business process.
- Merchandize Lifecycle.
- Supply chain management.
- Store and Multi channel.
- Implementation of Phase 1 – IS-Retail solutions for Discount Retailer.
- Responsible for Integration Testing of SAP IS-Retail Solution for a high street Discount Retailer implementation.
The Solution
- Development of SAP IS-Retail implementation using "client's Retail Template" for its Retail Customers.
- End-to-End SAP IS-Retail implementation.
- Integration testing of IS Retail solution implementation for the client.


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In this area we will feature some good friends of Reliable Gun.
"These are people with the heart of a teacher, that are KNOWLEDGE and SERVICE centered.
They act as mentors to better our community and are people that you should feel comfortable
reaching out to, with any question that you might have."
~Nicholas Chee
About Us
Firearms safety is serious, but learning doesn't need to be done in an intimidating environment. Let Silvercore show you how learning how to safely control and use a firearm can be enjoyable.
With locations across the Lower Mainland and Vancouver Island, Silvercore provides excellent resources to all skill levels and experience.
Services Provided
~CFSC/CRFSC (Canadian Firearms PAL and RPAL Courses)~
~CORE (BC Hunting)~
~Various Live Fire Courses(Excellent Hands-on Courses For All Levels of Shooter)~
~Bear & Predator Defense~
~$49 Yearly Membership allows for ATT Purposes including $10 million in North America wide liability insurance for all hunting and shooting activities~
And Many More...
To Find Out More Please Visit Them At www.Silvercore.ca
As hunters we have a deep respect for the animals we harvest and the process of the hunt. We all started somewhere, we learned, we adapted and absorbed everything we could to be our personal bests. Some of our close friends have created a new tool in mentorship. Howtohunt.com was created as a database of hunter knowledge, to help us share that knowledge. Very proud of these guys and honored to be a part of it. Please like, share and follow these wonderful people!
The EatWild team is passionate about their food. Sharing their tradition of hunting and gathering with a new generation. We are not just about game meat, but about community, slow food and a harmony with nature. Click to learn more about our team! http://www.eatwild.ca/
Whether you want to begin your journey to become a hunter or are an experienced old bugger looking to share that knowledge and join a like minded community. EatWild brings people and traditions together.
For more info: http://www.eatwild.ca/
Learn to hunt with EatWild. CORE Vancouver and PAL Vancouver Certifications, fun events and workshops. EatWild represents the modern food movement, slow food and healthy, ethical meat.
Learn many useful and fun skills with our workshops. Learn how to butcher an animal, make sausages, tan a hide and many other fun, practical skills. Enjoy an enjoyable evening with like minded people and walk away with a new skillset.
Participate in a three-day field skills development workshop in the heart of BC's Grassland country. Immerse yourself in the hunting lifestyle with experienced hunters to help you learn skills. Learn navigation, game hunting, survival, butchering, shooting and other skills neccessary to harvest your own meat!
Please check out their website Eatwild.ca and follow them on all social media!


text: Jesus was one of the most brilliant and profound teachers and preachers of all time. However, not everything he said and did makes sense 2,000+ years later. Cursing a fig tree? Claiming that the poor will always be with us? Telling us to pluck out our eyes? WHAT?! Join us as we explore some of the bizarre and shocking things that came out of Jesus' mouth!


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Don't dare to miss the children's HALLOWEEN EVENT of the year on SATURDAY OCTOBER 27th from 12:00PM (Noon) to 4:00PM.
Enjoy 3 floors of Spooktacular fun and games!
Come out and enjoy a GHOST TRAM, a HAUNTED TUNNEL (Ages 5-11), an ENCHANTED DIVE (Ages 1-5), SWASHBUCKLING GAMES with prizes, a TREASURE HUNT, Arts & Crafts, Face Painting, Costume Parade, Balloon Artist and exciting entertainment by Jackson School and In Motion and so much more!
HOT DOGS and HAMBURGERS and BAKED GOODIES will be on sale at the Buccaneer Bake Sale! PARKING IS FREE and the event WILL HAPPEN RAIN OR SHINE!
Members: $2.50, Non-Members: $5 (Children under 3 are FREE).
ALL NEW MEMBERSHIPS ARE 50% OFF on this day!
Call 294-0204 or email email@example.com for more information.


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By: Jacob Elyachar, jakes-take.com
If it were not for J.K. Rowling and Harry Potter, I would not become the ferocious reader that I am today.
I was first introduced to this wizard by my fifth grade teacher, Mrs. Cynthia Johnston, at Indian Valley Elementary School in Overland Park, Kansas. While she only read a portion of the first book to my class, I was determined to find out about what happened to Harry, Ron Weasley, Hermione Granger, Professor Dumbledore, et al. In 2007, Harry Potter and the Deathly Hallows was released and I eagerly anticipated reading the book when I got back from Israel.
On July 31, 2016, Rowling, John Tiffany, and Jack Thorne released the final part of Harry Potter story: Harry Potter and The Cursed Child. The book was actually a rehearsal script that followed the adventures of an adult Harry and his middle son, Albus Severus. The play started previews at the Palace Theatre in the West End on June 7, 2016 before officially opened in July 30, 2016.
The play was a smash! The London production received 11 Olivier nominations and won over nine awards at the 2017 Olivier Awards. The awards that the play received included Best New Play, Best Actor for Jamie Parker (Harry Potter), Best Supporting Actor for Anthony Boyle (Scorpius Malfoy), and Best Supporting Actress for Noma Dumezweni (Hermione Granger).
When it was announced that Harry Potter and the Cursed Child would be opening at the renovated Lyric Theatre in New York City, I knew that I had to get tickets to this play. On May 24 and May 25, I had the impeccable opportunity to see both parts. While I kept a solemn vow, to "Keep the Secrets," I can give you some insight on what you can expect from this outstanding show.
Acting Performances
What made this show so special is that seven actors from the original London company (Boyle, Sam Clemmett [Albus Potter], Dumezweni, Poppy Miller [Ginny Potter], Parker, Alex Price [Draco Malfoy], and Paul Thornley [Ron Weasley]) helped premiere the American version of this production. While it may hard for some Potter fans not seeing Daniel Radcliffe, Emma Watson, Rupert Grint, et cetera reprise their iconic roles, the five actors made their mark on these classic characters.
Parker perfectly brought The Boy Who Lived into adulthood as he struggles with his ability to balance parenting his youngest son, while working at the Ministry of Magic. Meanwhile, Dumezweni delivered an impeccable performance as Hermione Granger and secured her spot as a significant contender to win the Best Performance by a Featured Actress in a Play award. Both Boyle and Clemment produced superb character growth arcs for both Scorpius Malfoy and Albus Potter throughout the four acts.
Other standouts in the acting ensemble include Jessie Fisher (Delphi Diggory), Geraldine Hughes (Professor McGongall), Edward James Hyland (Albus Dumbledore), Price, and Thornley.
The Production Team
Behind Harry Potter & The Cursed Child's success is an astonishing production crew. The audience will be amazed with spectacular magical illusions that Jamie Harrison created and that Martin Lowe helped arranged through the play's four acts. In addition, Christine Jones and Katrina Lindsay brilliantly brought the Wizarding World of Harry Potter to the Broadway stage through their splendid sets and excellent costumes respectively. Finally, Carole Hancock transformed these actors through her excellent make-up, hair, and wigs designs.
Final thoughts and grade: Harry Potter and The Cursed Child is a spectacular theatrical experience that every Harry Potter fan should see. This production brilliantly pays homage to J.K. Rowling's spectacular literary legacy. The play also introduces audiences to a new generation of performers who brilliantly brings our favorite wizards and witches to life. Currently, the production is nominated for 10 Tony Awards and eight Drama Desk Awards. I hope that this show wins every award that is nominated for because it was a spectacular theatrical experience. A


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After analyzing the issue of downloadable content from the developer's perspective, as well as how to escape the plateau, Novriltataki and the Chemical Lovers are back with episode 19 of their "Exploring Fighting Games" series, this time tackling the subject of properly understanding tier lists.
When Street Fighter II first introduced a unique cast of 8 distinct playable characters back in 1991, Capcom created an inevitable power gap between the fighters, as their unique and individual gameplay styles meant that they could not all be truly equal in power when matched up against one another. As natural competitive spurt began to grow among the community, players began to try and decide which characters were the absolute best in the game, giving birth to character rankings known as tier lists.
Though lists are ideally created with the use of a calculated and researched match-up chart, displaying which warriors have the best and worst individual spread across the entire cast, most players simply create them off of personal feeling and power estimation — making them fallible, since it is not always based off pure battle data.
Norvil examines what determines a match-up score, as well as using titles such as Marvel vs. Capcom 2 and Super Street Fighter II Turbo to explain the differences between games with both tight and spread-out gaps in character strength, as well as advising players on how they should approach tier lists and theory in order to use them constructively.
You can see the full video below. (Upcoming Episode 20 of EFG will focus on which type of controller to use for your favorite fighting game.)
Source: Novriltataki


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As a champion for children, you're now a part of something big. A global movement of passionate, caring people committed to a singular vision: Ensuring every child has the best chance for success.
We'll champion key issues to ensure children's voices are heard and their needs are addressed – so their futures are secured.
In times of crisis , when children are at their most vulnerable, we'll be there. Doing whatever it takes to save their lives, and we'll stay to ensure that their childhoods continue.
Donate Foundation, build innovations in child health, education and protection, we achieve remarkable results for children. In fact, we are the leading expert on children in Italy and around the world.
Investing in Childhood


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We've created a posting element on this website in order to, as a community, share, clarify, and gather stories and histories of Dummerston. If you have a story to tell, or if you'd like to ask a question of the community about an event, landmark, artifact or other piece of Dummerston history, we hope you might post here. Please be respectful, and always, if you wish to ask a question of the DHS directly, please reach us is via email or to come to one of our meetings.
Town Meeting, 1969 [Bob George]
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In a world where easy access to content and files is becoming more and more important, there are many applications available to help people stay on top of the daily grind. One such application is Microsoft OneNote, which is among the best collaboration software out there today.
This breakthrough productivity software allows several people to collaborate on projects at the same time by collecting notes, pictures, drawings, audio commentaries, screenshots, and other data that they can easily share with one another on one easy-to-use platform.
OneNote used to only be available if you had the Microsoft Office Suite of tools. However, Microsoft has since turned it into a stand-alone application that comes with Windows 10. While the Windows 10 version is free, there is another version of OneNote that is web-based and part of the Office Online software that allows you to edit files using a web browser.
OneNote is packed full of cool features that make it one of the most used applications for both business and personal use. Let's look at some of the reasons people are turning to productivity software like OneNote to help them optimize their day-to-day activities.
1.) Ease of Use Is a True Attribute of the Best Collaboration Software Around
If you are already accustomed to using the Microsoft Suite of tools (Word, Excel, Access, PowerPoint, and Outlook), you'll notice that the interface for OneNote is very similar. Just like the other Microsoft applications, OneNote has a horizontal navigation bar at the top of the page which provides easy access to editing a document or note, designing a new page, or changing the page layout.
This makes it easy to use and so virtually any part of your team – whether a millennial or Baby Boomer, a brand-new addition or a seasoned member of the team – can jump right in with little to no issue.
Since it looks and feels like something they've used before, and particularly user-friendly to start with, team members are less likely to get stuck and take up other people's time asking for help. (Since we're on the topic of productivity, you might want to take a peek at how we calculate downtime when it comes to employee efficiency.)
2.) OneNote Seamlessly Integrates with Microsoft Outlook
If you use Microsoft Outlook, you'll especially enjoy OneNote because the two applications go hand-in-hand. When you use Outlook to store details about upcoming meetings, you can pull the information into OneNote. You can even include your notes about the meeting directly into the Appointment feature within OneNote so you don't have to email a separate file containing the meeting's agenda!
Plus, you can take advantage of this fantastic productivity software by writing out a to-do list using OneNote and then transferring it to Outlook so you won't miss completing any task. And if you don't want to transfer your list to Outlook, you can check off each item on your to-do list within the OneNote interface and continue to edit the list during the day as new things come about that must be completed.
3.) Versatility of Use By So Many Different Organizations
Many businesses are now making use of Wiki pages to keep their employees in the loop about what's going on within the company. But besides internal use, Wiki pages are also being published to the internet so outsiders who are outside the company can learn more about what the business stands for and how it runs.
OneNote provides an avenue for creating a Wiki page that everyone can access and contribute to, with one person or a handful of people being given the role of editor to make changes to the page when the need arises.
And when it comes to a specific document that has been uploaded into OneNote, all employees with access to it can see who has worked on the document and what changes they've made to it.
Another reason OneNote is among the best collaboration software is that it can also be used by a business to create surveys and opinion polls. The survey questions can be written and uploaded to one central document within the application, which takes away the need to send out a link to a separate online survey page. OneNote allows each person with access to the survey or poll to write out their thoughts and opinions all in one place, so everyone can easily see how each person feels.
Interestingly enough – but not surprisingly – schoolteachers have even begun using OneNote to create lesson plans and homework for their classes, accessible in one easy-to-reach spot for every student in the class. There are so many other types of organizations and industries utilizing all that OneNote has to offer that we cannot simply try to list them out here. If you're curious as to how productivity software and other great tips and strategies can be customized to any business's particular needs, check out how we helped an engineering firm become more efficient.
4.) Productivity Software Must Be Chock-Full of Great Features
One of the biggest advantages of OneNote is that you can click anywhere within the document to create a text box. Plus, the software will automatically save your work instead of you having to manually save your creation like you would have to do if you were using a traditional word processing program like Microsoft Word.
Also, the files created in OneNote are saved as pages with sections that can be made into notebooks, and pages can easily be moved around within the notebook. You can even draw on your created pages with a stylus pen as well!
Another fun feature that will quickly help OneNote become your favorite productivity software is that it has numerous built-in templates for many different uses, such as meeting notes and project agendas – or you can even create your own template to use as you see fit.
And if your bookmarks page within your regular web browser is becoming too cluttered and hard to keep organized, you can turn to OneNote to create a page with hyperlinks to your favorite sites, a page that is also fully searchable.
5.) The Best Collaboration Software Should Be Widely Available
OneNote is available on computers, tablets, and mobile phones, so users can take part by means of their preferred devices, and the ways you can use this productivity software are virtually unlimited. OneNote has a mobile app, too, to help you complete tasks while on the go so you don't have to feel the need to be attached to your computer all the time!
And, OneNote has a specific app for mobile phones called OfficeLens, which acts as a scanner by using your phone's camera to download receipts and other types of documents. It will also scan business cards and create new contacts on your phone from the information on those business cards.
By Now You Know OneNote Is the Way to Go
If you're looking for the best collaboration software that has an immensely diverse set of helpful features, then OneNote is the right choice for you and your team.
Whether you want to collaborate with your business colleagues or just make a searchable document for your own personal use, OneNote fits the bill and can get the job done with ease, every time.
As IT professionals, we would be glad to answer any questions regarding this productivity software, recommend applications for other needs, or for more ways the tech world can be navigated for the betterment of your company in the long run!


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Rumours continue to circulate around Paul Pogba's current situation at Manchester United, with his relationship with manager Jose Mourinho becoming strained in recent weeks.
Injuries have also hampered his chances this season, as well as a reported falling out with manager Mourinho.
The manager's response to his side's shock elimination from the Champions League was to announce that he needed to sign some new players. Mourinho has reportedly put in a plea to sign sign four players in the summer, but is battling with the club's board over how much he will be able to spend.
The Metro are claiming that one way the problem of budget could be solved is if United offered swap deals for their proposed transfer targets. One sensational swap which is apparently being considered would involve Pogba and Paris Saint-Germain midfielder Marco Verratti.
The Italy international is reportedly one of Mourinho's four transfer targets for the summer, with Tottenham's Toby Alderweireld and Barcelona's Samuel Umtiti also being considered as the Red Devils boss aims to strengthen the spine of his team.
Pogba only returned to Old Trafford in the summer of 2016, for a then-world record fee of £89m. United's priority is said to be to try and ensure that the 25-year-old fulfils his potential at Old Trafford, but has so far fallen below the mark. Alternative plans for Pogba are also being considered in case his relationship with Mourinho continues to deteriorate.
Both Pogba and Verratti are represented by agent Mino Raiola, giving both clubs an easy line of communication to discuss the deal, but United would likely want a return on their record-breaking investment into Pogba and are expected to focus on getting him at his best before trying to move him on.


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Welcome to the University of Southampton Library blog. We want to share news about everything that is happening in your University Library with you.
As with our Twitter andFacebook feeds, we will continue to make the Library even more accessible in as many ways as possible. Expect to hear from different contributors about all aspects affecting your library experience: resources, services, events, initiatives and tackling issues you tell us are important to you. Get in touch with the community on Facebook and Twitter and the next post could be on a topic you always wanted to know more about.
Watch this space.


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This is our collection of livestock shelters. We can also custom design one for you and provide a quote.
Local delivery is available for an additional fee. We realize that most people who need a coop built also need delivery. Our delivery fee is meant to be reasonable and fair for that service. In general, expect $50-100 plus $1.75 per mile from our location, depending on the size of the structure.


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We started our journey to learn Ancient Greek when my boys were 6 and 4. I purchased the first book in the Hey Andrew Teach Me Some Greek series. It came with a CD, workbook, and reader. We slowly went through the first book over the course of 2 years before moving on to the 2nd book in the series. After that I decided to split my boys up. Purchasing two sets of the Greek materials each year was going to be expensive. At that point I moved my oldest child who was then in 4th grade to a free curriculum found at inthebeginning.org while my younger son continued with Hey Andrew using the 3rd book. A couple months into that school year, I realized that I had to abandon both options. The free curriculum was difficult to use and my younger son was no longer learning with the Hey Andrew curriculum.
I went searching and found Athenaze. It is a ancient Greek curriculum designed for high school. During that school year we started Athenaze and have been slowing going through the book since then. We intersperse formal Greek with times reading the Bible in Greek and informal games with Greek vocabulary words. Athenaze has been a little difficult in spots. The grammar isn't always easy, but studying the Greek grammar has improved my children's knowledge of English grammar.
If you are considering learning Greek and starting at a young age I would recommend:
- Hey, Andrew! Teach Me Some Greek! Level 1 Workbook with the song and reader as a gentle way to learn the alphabet.
- Song School Greek. I haven't used this one yet, but I will be starting my daughter on it next year. It would have been a better choice for us instead of continuing with Hey Andrew.
- Athenaze – Going slowly at first and finishing the two books so there is time to read ancient Greek works in high school. If you choose this option, you will find the teacher's manual at Rainbow Resource Center.
- The inthebeginning.org website has a pdf file that will print out all the upper and lowercase letters along with their names. I've printed them all out and have them posted near the ceiling like an English alphabet banner.
If you are considering learning Greek and starting at an older age I would recommend:
- Greek Alphabet Code Cracker – I have heard great things about this curriculum. It helps your child learn the alphabet, but I chose Hey Andrew because I thought it was more suitable for my 5 year old.
- Elementary Greek or Athenaze – I haven't used Elementary Greek, but I've heard some good things about it. I thought the reading approach of Athenaze would be a better fit for my kids.
- The inthebeginning.org alphabet banner can be used for all ages.
Reading some new Greek vocabulary words


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New at BOP:Movie Review: DesperadosReview: GreyhoundReview: HamiltonThe #1 Movie in AmericaReview: Ella FitzgeraldThe 400-Word Review: My SpyMovie Review: ShirleyNew Trivia QuestionAll site updatesShare & Save
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Our first two big surprises of the box office year are upon us, as American Sniper leverages strong limited play, Clint Eastwood's name, and a long weekend, to turn the January box office record book on its head. Blackhat, the $70 million thriller does the opposite, and bombs ugly this weekend.What a big weekend it is, with three brand new wide releases and American Sniper platforming from four screens last weekend to an ultra-wide 3,555 venues this frame. Add to that 11 films expanding in one form or another following Oscar nominations and last weekend's big opener, Taken 3, having another helping this weekend. New films this weekend include The Wedding Ringer, the latest buddy comedy with Kevin Hart, Paddington, the British import that had already earned more than $120 million before opening on our shores, and Blackhat, the new film from Michael Mann that stars Thor himself, Chris Hemsworth. Our number one film of the weekend – by a mile – is American Sniper, the Clint Eastwood war flick starring Bradley Cooper. Analysts were looking for $40 million over four days, and instead American audiences turned out in droves, and the Warner Bros. release ended up earning more than double that amount in three days. This was another success story that was telegraphed by Thursday preview gross, as Sniper took in a surprisingly strong $5.3 million from preview screenings starting at 7 p.m. Taken 3 took in $1.6 million on Thursday on its way to a $39.2 million opening, and Interstellar earned $3.5 million on its way to $47.5 million. The Thursday preview figure remains elusive at targeting weekend grosses, but $5.3 million for American Sniper indicated big things were coming.


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Head of Rail Baltic: First trains from Tallinn to Poland to take to the tracks in 2025 ({{contentCtrl.commentsTotal}})
The first trip on the high-speed railway between Tallinn and the Lithuanian-Polish border should take place in 2025, said Baiba Rubesa, head of the board at RB Rail, the joint-Baltic company set up to oversee the multi-billion-euro project.
"If everything goes according to plan, then the first train traveling to the Lithuanian-Polish border will start from Tallinn around 2025," she said, LETA reported.
Speaking about the track from the Polish-Lithuanian border to Berlin, Rubesa said that should take five years to construct, adding that before that, plans must be harmonized and contracts for that route must be signed.
She said Poland must become an active member of the Rail Baltic project as the aim of the project is to create a new transit corridor in Europe, which will link Europe from Helsinki to Berlin.
Editor: J.M. Laats


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QuoteFacebook said that if a person currently checks in at a respective company's store or "likes" a brand page, the action often gets lost amid all the other content that a user's friends may see. Sponsored Stories solves that problem for advertisers by plucking valuable content from user news feeds and making it more readily noticeable to others.
The Sponsored Stories, which kicked off yesterday for Facebook's "premium" advertisers, will be labeled and viewable only to the content creator's friends, Facebook noted. The service will respect a person's privacy settings. However, Facebook users won't be able to opt out of the service. That's somewhat surprising, since Facebook users can modify their inclusion in the company's existing Social Ads by letting their social actions be includedin a marketer's ad on the site and be shown to friends--or opt out.
QuoteYahoo! Inc. , a leading global Internet company, announced today that it will begin a limited test of Google Inc.'s AdSense for Search service, which will deliver relevant Google ads alongside Yahoo!'s own search results. The test will apply only to traffic from yahoo.com in the U.S. and will not include Yahoo!'s extended network of affiliate or premium publisher partners. The test is expected to last up to two weeks and will be limited to no more than 3% of Yahoo! search queries.


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Tom Hardy leaves Suicide Squad, Doctor Who guest stars announced and Nintendo Direct's slew of announcements.
Dark Knight Rises actor Tom Hardy has dropped out of the Suicide Squad movie, originally set to play team 'leader' Rick Flagg, the actor has had to drop the role after his project with Leonardo DiCaprio The Revenent has run over schedule. The good news is that Jake Gyllenaal (Nightcrawler) seems to have stepped in to fill his boots.
Theories surfaced a few days ago that Black Widow, played by Scarlett Johansson, would be the one to bite the Whedon bullet in Avengers 2 Age of Ultron. But that's probably not the case now, since Johansson will return in Captain America Civil War, alongside Mackie and Evans (and everyone else who's involved in the superhero registration act.)
Teenage Mutant Ninja Turtles Michael Bay's most recent attempt at nostalgia/explosion fever, has a sequel on its way. TMNT 2 will begin filming in April, and is set to release in 2016.
The BBC has announced a bunch of guest stars for Doctor Who season 9, which started production in Autumn last year, you can check some of them out here.
Some promo images for The Flash's return (which will rush to our screens on the 20th of January) have arrived. The episode 'Revenge of the Rogues' will see the return of Captain Cold and his new heat inspired sidekick, as can be seen from these images.
More promo images! This time its for Arrow's return; Left Behind, all I can gather is that Ray Palmer (Brandon Routh) will be fiddling with something on his wrist an awful lot.
Sid Meier's Civilization: Beyond Earth is free on steam right now, until Sunday night. If you like what you play the game is currently reduced by 40% too.
Bungie's newest weekly update for Destiny has also announced the Hard Mode for the newest raid; Crota's End has a release date, it's next Wednesday.
For all those Nintendo fans who missed the Nintendo Direct on Wednesday, you can catch all 45 minutes here, but if you just want to browse through the announcements, Nintendo Life has you covered.


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Atlanticare Red Dress Event 2019
The Heart Institute at AtlantiCare Regional Medical Center (ARMC) hosted its twelfth annual Red Dress/Red Tie Reception on February 6. The American Heart Month event took place at the Smithville Inn in Historic Smithville. This years event filled the Inn with over 320 guests all decked out in their red in support of a worthy cause.
Event proceeds benefit the ARMC Heart Heroes Program, an AtlantiCare Foundation-funded program that places automated external defibrillators (AEDs) in the community. Donated on behalf of the Heart Institute at AtlantiCare Regional Medical Center, the AEDs can restore a normal heart rhythm during cardiac arrest.


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Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review)
- Authors:
Affiliations: Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA
- Published online on: January 18, 2017 https://doi.org/10.3892/or.2017.5387
- Pages: 1291-1300
This article is mentioned in:
Introduction and structure of GPC-3
The glypicans, a family of proteins classified as HSPGs, have been shown to interact with a number of growth factors and modulate growth factor activity (1) and are linked to the extracellular side of cell membrane by a glycosylphosphatidylinositol (GPI) anchor (2). Members of this large family of transmembrane proteins have been identified in both mammals and drosophila: 6 glypicans (GPC-1 through GPC-6) in mammals, and two others in the fly (2). Glypicans have a core protein size of ~60–70 kDa and express an N-terminal secretory signal peptide along with a hydrophobic domain that is used for the addition of the GPI anchor at the C-terminus. Another characteristic that is shared by all glypicans is the location of the insertion sites for the heparan sulfate chains (HSC), which seems to be restricted to the last 50 amino acids in the C-terminus, placing the chains close to the cell membrane. Additionally, the position of 14 cysteine residues is conserved, further strengthening the structural relationship of the proteins within the family (2).
Much of the literature on GPC-3 stems from its proposed role in vivo as well as in vitro in cancer models. Multiple studies have shown a correlation between GPC-3 and hepatocellular carcinoma (HCC) due to the nature of the protein being expressed during normal cellular growth and movement in hepatocytes (1,3–6). In patients who received surgical treatment for HCC, a decrease in GPC-3 protein was observed (3). In addition, in cells derived from hepatocellular carcinoma GPC-3 has been observed to be secreted into culture media (7). GPC-3 does not seems to be expressed by other liver cell types (hepatic stellate cells, kupffer cells, bile duct cells, endothelial cells and fibroblasts) but it appears to be expressed exclusively by hepatocytes. It is well known only that its expression from hepatocytes influences the activity and function of non-parenchymal liver cells.
GPC-3 was initially hypothesized to interact with insulin-like growth factor in selected cell types, though this notion has been challenged as this may not be the case in all cell types (8). In a study done on the loss-of-function mutation of GPC-3 in embryonic development, researchers observed an overgrowth of organs in fetal and postnatal development, known as Simpson-Golabi-Behmel overgrowth syndrome (9). This evidence cast GPC-3 into a strict role as a tumor suppressor. In another study looking at the metastatic adenocarcinoma mammary LM3 cell line, GPC-3 was shown to inhibit the canonical Wnt signals involved in cell proliferation and survival. In the same study, GPC-3 was also observed to play a role in activating the non-canonical Wnt pathway, which directs cell morphology and migration (8). Furthermore, GPC-3 was also found to act as a potential tumor suppressor in lung tissue (10). This has re-opened the case of GPC-3 as a strict suppressor of cell growth and introduced the possibility of its role in stimulating growth and even tumorigenesis in a tissue-dependent manner in some cell lineages.
This being said, certain key elements have been observed which give reason for upregulation of GPC-3 in certain cell types and not others. GPC-3 is able to bind Wnt and Hedgehog (Hh) signaling proteins and was also shown to have the ability to bind basic growth factors such as fibroblast growth factor 2 (FGF2) through its heparan-sulfate glycan chains (11). Additionally, expression of sulfatase 2 (SULF2), another tumor marker expressed in hepatocytes, was found to be correlated with increased expression of GPC-3. When GPC-3 was decreased, FGF2 binding was decreased in SULF2 expressing hepatocellular carcinoma cells. SULF2 expression in resected HCC tissue was also shown to have a worse prognosis and a higher rate of recurrence after surgery (12).
Herein we synthesize the literature on GPC-3, including its structure, expression in normal tissues, as well its role as a serum marker as well as possible therapeutic target. The review also includes current knowledge on GPC-3 expression as a prognostic marker in HCC and its role in liver regeneration post partial hepatectomy (PH). In addition, we discuss embryonic and adult tissue expression of GPC-3. Lastly, we report the interactions of GPC-3 with CD81 as CD81 has been shown to interact with GPC-3 as a binding partner (13,14).
Expression pattern of GPC-3 in human and mouse
Embryonic expression of GPC-3
Embryonic expression of GPC-3 differs greatly from the expression map seen in health adult tissues. In most embryonic tissues and organs, there is positive expression of GPC-3 as illustrated by immunohistochemistry (IHC) in humans and in situ hybridization (ISH) in mice. Organs or tissues that display positive expression in human embryonic tissues include: tissues of the digestive tract, the gonads, kidney, limb buds, liver, nerve tissue, oral cavity, pancreas, respiratory syndrome, tongue, and vertebrae (15). In pancreatic tissue, positive expression was seen in exocrine glands, while endocrine glands showed negative expression. In contrast, IHC revealed negative expression of GPC-3 in human embryonic skin tissue (15). Additional detail regarding location and description of GPC-3 expression in human embryonic tissue can be seen in Table I.
Organs or tissues that displayed positive GPC-3 expression in mouse embryonic tissues include: digestive tract, gonads, kidney, limb buds, liver, oral cavity, respiratory system, skin, tongue, and vertebrae (9,15). In contrast, ISH revealed negative expression of GPC-3 in mouse nerve tissue. Pancreas expression in mice was not reported in this study. While GPC-3 expression across mouse and human embryonic tissue appears consistent in most organs, there are some tissues that differ. While nerve tissue shows positive expression in humans, in mice it is not expressed. On the other hand, human tissue is negative for expression of GPC-3 in skin, but this same tissue is positive for the protein in mice (9). Additional detail regarding location and description of GPC-3 expression in mice embryonic tissue can be seen in Table I.
Studies have also shown decreased GPC-3 expression in the SGB overgrowth syndrome, causing a spectrum of congenital defects such as macrosomia, congenital heart disease, conduction defects, supernumerary nipples, diastasis recti/umbilical hernia, diaphragmatic hernia, renal dysplasia/nephromegaly, cryptorchidism/hypospadias, and hand anomalies (brachydactyly, cutaneous syndactyly, polydactyly) (16). This change in expression and resulting defects are due to a mutation that causes sequence variants as well as multiexon/whole gene deletion in 37–70% of male cases (16,17). Table I gives a summary of the SGB syndrome abnormalities found in various organs and tissues as a result of the GPC-3 loss of function mutation (15,16,18). In these cases, GPC-3 acts as a regulator for normal embryonic development and is only found to cause problems in embryonic tissue when it is mutated (Table I).
Expression of GPC-3 in normal adult tissue
Table II summarizes GPC-3 expression in adult tissues normal versus tumor, while Table I summarizes expression of GPC-3 in embryonic tissue in human and mice. As is shown in Table II, the current literature has some contradictions which must be further evaluated to better understand the expression of GPC-3 in tissue types. The tissues represented as having two or more sources contradicting one another in normal tissue (expressed/not expressed) are: gastric glands, kidney tubules, testicular germ cells, breast tissue, gall bladder, and ovary (19–27). In addition, there are also sources reporting no expression, trace amounts, or scarce expression in normal tissue. These tissues are: liver, brain, colon, esophagus, fat tissue, heart, lung, lymph, mouth and associated glandular tissues, pancreas, prostate, skeletal and smooth muscle, small intestine, thyroid and parathyroid, thymus, bladder, and uterus (2,19,21,22,28–33). In Fig. 1, expression of GPC-3 in normal tissue was constructed based on Table II. Different grey shades were used to differentiate GPC-3 expression in various tissues.
Figure 1.
Expression of GPC-3 in normal tissue. The above image was constructed based on Table II. Different grey shades were used to differentiate GPC-3 expression in various tissues. Opacity and transparency of tissues or organs were adjusted for maximized visualization of all organs and their coloring, while retaining anatomical positioning. In organs or tissues colored in light grey (opaque and transparent), GPC-3 is not expressed. In organs or tissues colored in medium grey (opaque and transparent), we found the literature inconsistent regarding GPC-3 expression in those tissues. Table II and its citations for each organ should be referenced for further detail on the nuances of GPC-3 expression in these tissues. Organs or tissues in white (opaque and transparent), expression of GPC-3 was unknown or unfound in the literature. Lastly, the dark grey coloring of the body is simply intended to show the silhouette of body and does not represent any expression of GPC-3.
Expression of GPC-3 in cancer tissue
GPC-3 expression in various types of cancer is not fully understood, though the variance may be due to the specific type of cancer being studied. Table II lists the reported expression of GPC-3 in cancer in various tissue types. Expression of GPC-3 was found in the following cancers: liver, gastric carcinoma, melanoma, high-grade urothelial carcinoma, testicular, and some uterine and vaginal cancers (1,3–6,23,28,33–35). GPC-3 expression was also reported in some non-CNS tumors of the brain (36). In various other tissue types such as colon, lung, anal, esophageal, mouth mucosa, pancreas, skin, thyroid, bladder, uterus, and vulvar tissue GPC-3 expression varied based on the type, and origin, and grade of cancer [i.e. squamous cell carcinoma (SCC) versus mesothelioma of the lung] (1,10,11,19,28,31–33,37–40).
In some cancerous tissues, reduced or even silenced expression of GPC-3 was found; namely renal cell carcinomas, as well as cancer of the breast, ovaries, penis, prostate, and gallbladder (10,11,24–26,33,38,41,42). Similarly, infrequent expression of GPC-3 was reported in some cancers of the kidney, invasive ductal and tubular carcinomas of the breast, some brain tumors, adenocarcinomas of the gall bladder, prostate, and small intestine, squamous cell carcinoma of the penis, rhabdosarcomas and leimyosarcomas of the skeletal and smooth muscle, adeno- and small cell carcinomas of the submandibular glands, among other cancerous tissues depending upon grade and location within the tissue (19,33,36). For more detail regarding GPC-3 expression in these tissues, refer to Table II.
In human breast cancer, GPC-3 has been shown to be silenced due to hypermethylation of its promoter region. The data also suggest that GPC-3 can act as a negative regulator of breast cancer growth as well a downregulator in mesotheliomas and ovarian cancer (25). Xq26 is a region frequently deleted in advanced ovarian cancers and is where the GPC-3 gene is located.
In ovarian cancer, GPC-3 expression was lost in cell lines analyzed which was also due to hypermethylation of the promoter region. Expression of GPC-3 was restored with the treatment of 5-aza-2′-deoxycytidinem, a demethylating agent. Ectopic GPC-3 expression inhibited the growth of ovarian cancer cell lines and results show that GPC-3 is frequently inactivated in a subset of ovarian cancers which may suggest that it functions as a tumor suppressor in the ovary (27).
In 15% or more of studied cases, GPC-3 was expressed in tumor types of hepatocellular carcinoma, squamous cell carcinoma of the lung, liposarcoma, testicular nonseminomatous germ cell tumor, cervical intraepithelial neoplasia (grade 3), malignant melanoma, adenoma of the adrenal gland, schwannoma, malignant fibrous histiocytoma, adenocarcinoma of the stomach (intestinal subtype), chromophobe renal cell carcinoma, invasive lobular carcinoma of the breast, medullary carcinoma of the breast, squamous cell carcinoma of the larynx, small cell carcinoma of the lung, invasive transitional cell carcinoma of the urinary bladder, mucinous carcinoma of the breast, and squamous cell carcinoma of the cervix (19).
GPC-3 as a serum marker for early detection of HCC
GPC-3 may be a potential serum marker in diseases such as HCC in which expression of GPC-3 is markedly increased (20,21). Capurro et al examined GPC-3 protein expression and serum levels using immunohistochemistry and ELISA in HCC patients, as well as serum levels in healthy donors and patients with hepatitis and liver cirrhosis. Results revealed increased GPC-3 expression levels in patients with HCC, but not in healthy hepatocytes. GPC-3 serum levels were significantly elevated in HCC patients, but undetectable in the serum of healthy and hepatitis-infected patients (22).
Discussing where this protein is cleaved, the cleaved portion of the NH(2)-terminal was found to be between Arg(358) and Ser(359) of GPC-3. In addition to this, it was observed that soluble GPC-3 can be specifically detected in the sera of patients with HCC using N-mAbs (23). Unfortunately, the cleavage events and other post-translational modifications are understudied. It is necessary to investigate in terms of function and cellular localization the cleavage events on GPC-3. Focusing on serum marker it is necessary to understand if the protein is cleaved and which portion is secreted improving the knowledge of secretory pathways involved in its sorting in and out of the cells, with major attention on exosomal cargos.
GPC-3 was also identified as a novel diagnostic marker for human melanoma it its early stages. In patients with melanoma, GPC was detected. However, the protein was not found in the sera of healthy patients, or those with benign skin lesions (large congenital melanocytic nevus). It was also detected in the serum of patients with stage 0, in situ melanoma (28).
In another study carried out to observe biomarkers for HCC, preoperative serum GPC-3-N (sGPC-3N) levels were measured alongside with serum AFP in patients with HCC. It was observed that high serum AFP corresponded with a high sGPC-3N level. The study states that sGPC-3N may serve as an independent prognostic biomarker in HCC patients (24).
Serum α-fetoprotein is the common diagnostic marker to detect HCC. Several studies showed that the combination of α-fetoprotein and GPC-3 increase significantly the sensitivity of diagnostic value compared to their sensitivity analyzed independently (43). Several markers are under investigation to ameliorate the sensitivity and specificity of HCC detection such as: des-γ carboxyprothrombin, lens culinaris agglutinin-reactive α-fetoprotein, Golgi protein 73 (43,44). However, GPC-3 seems to be more specific due to its peculiar expression in hepatocytes as showed before, and this represents the main advantage for its use in HCC detection even if its mechanism of transport in the serum is still unknown. For its peculiar localization and post-translational modifications GPC-3 could represent an ideal target for antibody therapeutic approach with the possibility to bind its membrane form thus inhibiting its activity. Moreover, a chemical approach could obtain the cleavage events that determine GPC-3 functional modulation and cellular localization. Consequent to its expression in pre-neoplastic hepatocytes, this offers the unique advantage of allowing an early and specific therapeutic approach.
GPC-3 in resection, regeneration and liver diseases
Few studies have demonstrated the expression of GPC-3 pre- and post-hepatic resection. Due to hepatic progenitor cells expressing cytokeratin 19 (CK19) and GPC-3 at varying phenotypes, cell samples were analyzed from patients who had a liver resection and were statistically compared with each phenotype of expression in Table III. It was found that CK19+/GPC-3+ HCC was the most aggressive subtype, followed by the CK19−/GPC-3+ HCC and finally with the CK19−/GPC-3− HCC subtype being the least aggressive from the subtypes observed (45). Therefore, a poorer prognosis may be associated with patients undergoing a hepatectomy who have the expression of both CK19 and GPC-3.
Liu et al, on the other hand, described transgenic GPC-3 mice, which were under the control of the albumin promoter gene, overexpressed GPC-3 and actually had a suppression of hepatocyte proliferation and liver regeneration following partial hepatectomy (30,46). These mice developed normally and the authors claim that GPC-3 may play a negative regulatory role in hepatocyte proliferation, showing a contrasting role of GPC-3 in the hepatocytes. Further investigation using models post-PH is needed to uncover various important aspects of GPC-3 expression such as the density and location of GPC-3 expression (i.e. the cut margin or other location). This research may be instrumental in further elucidation of the role and mechanisms of GPC-3 in liver growth and regeneration post-resection and even injury (mechanically, inflammatory, or otherwise). However, limited studies have been conducted on the regeneration of the liver.
At this time there is no evidence on a possible function and presence of GPC-3 in other liver diseases such as fibrosis, fatty liver disease or liver cirrhosis. The peculiarity of its expression in neoplastic hepatocytes makes GPC-3 not only a unique HCC marker but also a possible therapeutic target. However, studies in cirrhotic livers without HCC are necessary to rule out the role of GPC-3 or the presence in these circumstances.
GPC-3 as a therapeutic target for HCC
Therapeutic targets are especially important in the treatment of various types of cancer. GC33, which is a humanized monoclonal antibody, was shown to bind human GPC-3. GC33 has been observed to contain antitumor properties and targets GPC-3 specifically. It was noted that GC33 was well tolerated in advanced HCC and provided some benefit in the clinical treatment (47). In addition, human (MDX-1414 and HN3) and humanized mouse (GC33 and YP7) antibodies that also target GPC-3 are under different stages of clinical development and could also aid in the treatment of HCC (21). miR-219-5p is a microRNA (miRNA) which could exert tumor suppression on hepatic cells expressing GPC-3. miR-219-5p reduced both the mRNA and protein levels of GPC-3 and exerted tumor-suppressive effects in HCC (48). Finally, nanoparticles are also under development to target and bind GPC-3 in cells that could provide useful for further imaging and targeting of GPC-3 (49).
Research has also been conducted in regards to peptide sequences which bind GPC-3. Feng et al described a 12-mer peptide sequence (DHLASLWWGTEL) which was able to act as a probe and bind GPC-3 for HCC detection (21). The peptide allows visualization of the specific sequence via near-infrared fluorescence (50). Another therapeutic target on GPC-3 is mir717, a miRNA, which is located on intron 3 of GPC-3 on the X chromosome. It has been shown to play a regulatory role in renal osmoregulation. mir717 might be connected in some way with obesity regulation, one of the risk factors of HCC (51,52).
It has been proposed that GPC-3 acts as a negative regulator in the Hedgehog signaling pathway during development and as a result, a non-functional GPC-3 protein could be the cause of overgrowth or a GPC3 modified by post-translational modifications. GPC-3 has also been associated with the binding of Wnt to its signaling receptor, Frizzled (53–56). Both the Hh and canonical/non-canonical pathways of Wnt could be potential therapeutic targets as GPC-3 may play a role in proliferation and/or growth suppression, depending on the type of tissue and the stage of development (8,57). In addition, the peptide sequences Arg-Leu-Asn-Val-Gly-Gly-Thr-Tyr-Phe-Leu-Thr-Thr-Arg-Gln and Tyr-Phe-Leu,Thr-Thr-Arg-Gln showed selective binding of GPC-3 (58) which could provide useful for a target that is needing to bind onto GPC-3 for regulation.
GPC-3 and co-receptors
GPC-3 has been observed to interact with a number of co-receptors that further modulate cellular expression. Liu et al showed that GPC-3 and CD81 levels were significantly upregulated in general in the transgenic mice following partial hepatectomy (30,46). They showed that the negative regulatory role was somehow associated with GPC-3 and CD81 and that there is enhanced association between GPC-3 and CD81. GPC-3 and CD81 have both been associated as binding partners in which expression could influence the Hh (13). Co-localization of GPC-3 and CD81 was also shown to occur 2–6 days after hepatectomy (30). In contrast, another study observed that GPC-3 binds to members of the Hh pathway and prevents their interactions with the patched-1 receptor. There was decreased binding of GPC-3 with Hh and CD81 following PH and GPC-3/CD81 may play a role in the termination of liver growth following liver regeneration (14,46). Dysregulation of the association between GPC-3/CD81, which may occur during hepatitis C infection can result in dysregulated signaling and proliferation in infected hepatocytes (59). The structure and character of GPC-3 as a transmembrane protein, in conjunction with the current literature, lends itself to the strong possibility of many associations or interactions with other co-receptors and proteins, not only in hepatocytes, but possible in other normal or cancerous tissue types. It is important to emphasize again the paucity in the current literature in regard to this, and many other aspects of GPC-3.
GPC-3 is a molecule that is still not fully understood in its role in the proliferation and suppression of cell growth in normal and abnormal or cancerous tissue and also in structural and post-translational modifications. The question still remains as to why it is normally expressed in some tissues, while remaining silenced in others. Future research that looks into the upstream and downstream cell signaling pathways and how GPC-3 may be involved could provide further answers. In addition, studies investigating a more complete picture and analysis of GPC-3 structure are warranted, as glycosylation, sulfonation, or other structural components of the protein may be important in understanding its regulatory function within differing tissue types. In this same vein, continued insight into the cleavage of GPC-3 and the function of the cleaved versus non-cleaved form of the molecule could lead to a more complete comprehension of function. Other research paths may include developing the theory of GPC-3 as a dual tumor suppressor and oncogene, as dependent upon its structure. With exosome research brightening the horizons, more attention and detail must be paid to uncover the importance of exosomal GPC-3 as a serum marker or as possible therapeutic target in HCC. GPC-3 is a molecule that could further connect the missing links in liver cancer research and lead to an abundance of new intercellular relationships to reveal important aspects of the biology of this disease.
cytokeratin 19
fibroblast growth factor 2
hepatocellular carcinoma
hepatic progenitor cell
heparin sulfate chain
heparan sulfate proteoglycan
in situ hybridization
partial hepatectomy
sulfatase 2
serum glypican-3 N-terminal
squamous cell carcinoma
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Please Note: This blog was edited on 5th March 2018 to reflect corrections to the NUS delegate election.
Ballots stations have closed and an incredible 5,735 students turned out to vote. After two weeks of passionate campaigning, we're delighted to announce the new officer team:
Full Time Officers 2018-19 (from July 2018)
Union President: James Durcan
Academic Officer: James Hare
Student Activities Officer: Finn Judge
Community & Wellbeing: Steph (Effy) Hayle
York Sport President: Zac Sheppard
Part Time Officers (from summer term 2018)
Working Class Officer: Connor Drake and Sean Price-Regan
BAME Officers: Nayomi Karthigesu & Hannah Joseph-Asikhia
Disabled Students Officer: Chloe Hann & Scarlett Bacchus-O'Callahan
Environment & Ethics Officer: Oscar Bentley
Mature Students' Officers: Hanna Bryszewska
RAG Officers: Elina Kukk and Lucy Waldren
LGBTQ Officer: Gem Card
Women's Officers: Nadine Smith and Sophie Meehan
Other roles
Student Trustees: Maryam Taher and Christian Stickles (from 21 June 2018)
Policy Coordinator: Josh Mackenzie (from summer term 2018)
Faculty Rep - Sciences: Zoe Disley
Faculty Rep - Arts and Humanities: 'RON'
NUS Delegates: (Four places) Maryam Taher, James Everyman, Jack Galea, Lucas North
Candidates were not fielded for the following positions which means a by-election will now be run to elect the following positions:
International Students' Officer
Faculty Rep Social Sciences
Volunteering Officer
A by-election will also be run for the following positions, in which voters selected to Re-Open Nominations:
Faculty Rep for Arts and Humanities
Please contact email@example.com if you are interested in standing.
Congratulations to all the candidates. We're looking forward to working with you over the next year. And thank you to every student that took the time to vote.


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SAN DIEGO - A record field of more than 700 athletes will converge on Mission Bay Park in San Diego, Calif., for Saturday's USA Cross Country Championships. Six races are scheduled to decide national champions for masters men and women; junior men and women; and open men and women.
In addition to the national titles, open and junior men and women will qualify to represent Team USA at the IAAF World Cross Country Championships in Edinburgh, Scotland on March 30. The 2008 USA Cross Country Championships will be televised in association with the AT&T USA Indoor Track & Field Championships February 24, from 5-7 p.m. on ESPN 2.
This year's field includes six U.S. Olympians and eight former USA Cross Country Championship titlists, including Elliot Heath (Winona, Minn.) and Jordan Hasay (Arroyo Grande, Calif.), the defending champions in the junior men's and women's events.
The open men's race will see Ryan Hall (Big Bear, Calif.) and Dathan Ritzenhein (Eugene, Ore.) face each other for the first time since the U.S. Olympic Team Trials - Men's Marathon on November 3, 2007, where both men punched their ticket to Beijing, China for the 2008 Olympic Games. Though Hall dominated the Olympic Trials in New York, the 12 km distance could prove to be more favorable for Ritzenhein when considering his personal best for 10,000 meters of 27:35.65 versus Hall's 28:07.93.
With a men's field that includes seven men who have run faster than 28:00 for 10,000 meters, Hall and Ritzenhein are likely to see challenges from a variety of contenders including recent USA Half Marathon champion James Carney (Boulder, Colo.), 2004 Olympian at 10,000 and the marathon Dan Browne (Portland, Ore.), Olympic steeplechaser Anthony Famiglietti (New York, N.Y.), former NCAA Cross Country champions Jorge Torres (Boulder, Colo.) and Josh Rohatinsky (Portland, Ore.).
Also vying for team positions for Edinburgh will be former U.S. cross country squad members Max King (Eugene, Ore), and Andrew Carlson (Minneapolis, Minn.), Matt Gabrielson (Minneapolis, Minn.) and Jason Lehmkuhle (Minneapolis, Minn.).
The women's field will feature American Record holder Shalane Flanagan (Pittsboro, N.C.), a two-time USA Cross Country 4 km titlist (2004, 2005). Flanagan will face 2006 USA 10 km champion on the roads Katie McGregor (Minneapolis, Minn.), who will look to make her sixth USA Cross Country team. Additional contenders for the title and team berths include Nicole Aish (Gunnison, Colo.), Blake Russell (Monterey, Calif.), Sara Slattery (Lafayette, Colo.) and two-time USA Cross Country Champion (2004, 2005) Colleen De Reuck (Boulder,


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