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OUTSTANDING CONDITION MINI COOPER FINISHED IN RARE SPICE ORANGE METALLIC AND COMES WITH £3620 WORTH OF FACTORY OPTIONS INCLUDING UPGRADED ALLOYS, HEATED HALF LEATHER AND HEATED FRONT SCREEN**CALL TO ARRANGE A TEST DRIVE** 12 months MOT, Excellent bodywork, Black Part leather interior - Excellent Condition, SPICE ORANGE METALLIC, ALL OURS CARS COME WITH 12 MONTHS MOT, FULLY SERVICED AND ALL CARS RIGOROUSLY INSPECTED AND COME WITH A CUSTOMER DETAILED REPORT, ALL CARS HPI INSPECTED. ALL THIS TO GIVE YOU COMPLETE PEACE OF MIND., PART EXCHANGE AVAILABLE, GREAT FINANCE DEALS 12--60 TERM, WE GO THAT EXTRA MILE FOR OUR CUSTOMERS ALL MAJOR CARDS ACCEPTED. DRIVE THIS CAR HOME WITH COMPLETE CONFIDENCE AND SATISFACTION., VISIT CARTECMOTORCOMPANY.CO.UK FOR YOUR NEXT CAR., VISIT CARTECMOTORCOMPANY.CO.UK FOR YOUR NEXT CAR., VISIT CARTECMOTORCOMPANY.CO.UK FOR YOUR NEXT CAR, £5,989
This car comes with
Air Conditioning, Manual, DAB Digital Radio, 15in 5 - Star Spooler Light Alloy Wheels, Alarm, Alloy Wheels-15in 5 Star Spooler, Hill Assist, Radio BOOST with Single CD and Aux-In Connection (3.5mm), Tyre Pressure Warning System (TPWS), Window Lifts, Electrical, Including One - Touch Down and One - Touch Up Functions (Drivers and Passengers Side)
- 201804245850282
- 2011
- 11
- £5,989
- 599
- 78,577
- Cars
- UnQsyeyV+lY=
Vehicle summary
|Body style
|Engine size
|1598 cc
|Fuel type
|Number of doors
|Number of seats
|Gearbox type
|CO2 emissions
|127 g/km
|Insurance group
|Standard manufacturer's warranty (miles)
|No details available
|Standard manufacturer's warranty (years)
|0 years
|Standard paintwork guarantee
|2 years
Performance & economy
|Fuel consumption (urban)
|40.9 mpg
|Fuel consumption (extra urban)
|61.4 mpg
|Fuel consumption (combined)
|52.3 mpg
|0 - 60 mph
|9.1 seconds
|Top speed
|126 mph
|Engine power
|122 bhp
|Engine torque
|118.02 lbs/ft
|1407 mm
|Height inclusive of roof rails
|No details available
|3723 mm
|2467 mm
|1913 mm
|Width including mirrors
|No details available
|Fuel tank capacity
|40 litres
|Minimum kerb weight
|1075 kg
|Interior features
|Exterior features
|Interior World Carbon Black
|15in 5 - Star Spooler Light Alloy Wheels
|Interior Lights, Integrated Into Centre Front Headliner (Above Interior Mirror), Luggage-Compartment Light
|Alloy Wheels-15in 5 Star Spooler
|Outside Temperature Indication
|Roof Spoiler Painted in Roof Colour
|Interior Mirror, Mechanical Anit-Dazzle
|Electrically Adjustable and Heated Exterior Mirrors, Aspheric on Drivers Side, Mirror Caps in Body Colour
|Revolution Counter
|Heated Windscreen Washer Jets
|Easy Entry Access to The Rear Seats and Memory Function For Drivers Seat Base
|Rear Window Wiper
|Foldable and Divided Rear Backrest (50% - 50%)
|Mechanical Seat Adjustment Including Seat-Height Adjustment for Drivers Seat
|Ashtray and Cigar Lighter in Front
|Steering-Wheel Colum Adjustment, Mechanically in Height and Length
|Sun Visors with Integrated Vanity Mirror on Drivers and Front Passengers Sides
|Air Conditioning, Manual
|Cloth Cosmos Upholstery
|Storage Options in the Centre Console/Trim Front and Rear Side Panels
|Door Handles Chrome-Plated
|Window Lifts, Electrical, Including One - Touch Down and One - Touch Up Functions (Drivers and Passengers Side)
|Radio BOOST with Single CD and Aux-In Connection (3.5mm)
|Cupholder, Two in Front, One in Rear
|DAB Digital Radio
|Heated Rear Window with Automatic Deactivation
|Trip Distance Recorder
|3rd Brake Light
|Locking System with Central Locking
|Airbag for Driver
|Hill Assist
|Follow-Me-Home Function
|Tyre Pressure Warning System (TPWS)
|Headrests, for All Seats, Manually Adjustable
|Anti-Lock Brake System (ABS) with Cornering Brake Control (CBC)
|Electronic Brake Force Distribution (EBD)
|2 Head Airbags
|ISOFIX attachment, anchorages for up to two ISOFIX child seats on rear seat
|Front Passenger Airbag with Deactivation Switch
|MINI Mobility System (MINI MS)
|Dynamic Stability Control (DSC), including Automatic Stability Control + Traction (ASC+T)
|Power Steering, Electronic Power Steering Speed - Related
|Centre Rear Seat Belt
|Electronic Vehicle Immobiliser (Thatcham CAT1)
|2 Side Airbags
|3-Point Seat Belts in All Seats incl. Belt Stopper, Pyrotechnic Belt Tightener and Belt Force Limiter in Front
Please note
This includes MPG figures which are calculated under European Standards, in test conditions, and will vary under normal driving conditions. The information displayed above describes the typical specification of the most recent model of this vehicle. It is not the exact specification for the actual vehicle being offered for sale which may vary. Specifications for older models may also vary. Please contact us prior to purchase to confirm the exact specification of this vehicle.
Cartec Motor Company Ltd
Based on 29 customer reviews
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Our service model is around the following, which has led to hundreds of satisfied customers across the globe:
Excellent Service: We take the necessary time to understand your needs through not only written communication but personal phone discussions. We engage you via an initial call to ensure we are the right match, followed by a 60-90 Resume Branding & Strategy Session, and several calls throughout the process as needed to deliver a top-notch document.
Honesty & Integrity: While we aim to please you, we are also here to tell you the truth and that sometimes means advising you against misinformation. Often, job seekers are misguided due to the sleuth of experts online who no longer practice the craft but instead rest on their laurels, data collection of the resume writing and job search industry, and on new writers to do all the writing. You can count on our Chief Executive Writer, Rosa to tell you how it really is and respect your final decision once you are informed.
Craftsmanship and Hard-Work: Rosa Elizabeth Vargas has been writing resume for more than 12 years and still writes and intimately designs all the executive resumes that are engineered by Careersteering.com. With a small team behind her (an assistant proofreader and editor, administrative assistant, and a project manager), Rosa's time can be allocated to keeping abreast of the latest job-search demands, conducting personal branding sessions with clients across the globe, and hands-on application of these resume writing strategies, which have become more complex as the job market gets more demanding, global, and digital.
Walmart Executive LinkedIn Recommendation. Click to read more.
Hello Rosa,
I hope you are well. Thank you for the resume work you did for me… it has been very well received. I have accepted & interviewed for roles of President, VP/GM, and CCO.
I have a question… I would like a resume that is targeted to CFO/COO roles as well for future opportunities. Do you think the resume you created is appropriate or would you think it needs to be adjusted?
Please let me know your thoughts.
Thank you,
~ John
I received compliments from both recruiters and hiring managers on the style, look/feel and ease of use.
This was amazing. After we distributed the resume to recruiters via your service, I literally began receiving interest within a week. I ended up having conversations with 8-10 recruiters, moved forward with 4 into the recruiter interview and screening process, moved to the finalist phase with 3 (i.e., conversations with clients/hiring managers), and then ultimately settled on the SVP Marketing/Communications role with [confidential].
The entire process – from the time we distributed to recruiters via your service, to my acceptance of the offer was about 100-115 days. In short, this was the fastest job search/recruiting process I've ever participated in (of three total).
Again, I can't say enough good things about the work you did – the process, the guidance/advice, the products and the services – in the end, delivered a tremendous career opportunity for me that I would not have uncovered otherwise.
Take care and have a great weekend.
~ Steve P., SVP of Marketing and Communications
Thank you for the masterful job you've done creating this resume. I've compared it to resumes I have on my desk from people that have tried to get senior positions from my company in the past. Your high-impact style is light-years ahead of even the best resumes I've seen in the past.
All the best,
~ Steven R., Chief Executive Office
Hi Rosa,
Sorry for the silence but I was slammed…I made changes to the resume. There were only a couple of things. It looks OUTSTANDING!!!!
Thank you for everything.
~ Rhonda, Compliance Attorney
Rosa Elizabeth…
I wanted to email you and let you know I was offered the position shortly after I sent out the resume you drafted for me. When I attended my interview, I had several employees approach me and tell me they were "wowed" and "impressed" by my resume and experience as I had been the talk of the office before I even arrived. They were so impressed with the crafted writing in my resume and offered me the job on the spot after a three-hour interview.
Thanks to you – I landed my first six-figure position with an office overlooking the ocean. Frankly, I wasn't expecting to land such an amazing position.
I want to thank you from the bottom of my heart for your help and hard work in creating a resume masterpiece. This job opportunity allows me to financially secure a future for my children and me.
Thank you so very much, Rosa!
~ Jaime S. Marketing Manager
Darron Watson, Technology Executive
CEO of Consulting Company
VP of Engineering
I first learned of Rosa and Career Steering after doing intensive research and trying to find the best professional resume service that would help me address the following points of concern similar to your own and avoid the resume cookie cutter mills out there:
1.Rebranding of image and creation of artifacts to support experience.
2.Cleanup of a massive resume that had a blend of consulting, executive mgmt & proprietorship of my own business.
Rosa spoke to me and listened based on my individual experiences and strengths to bring my mantra to life; it was refreshing to find a resume writer that remained grounded while understanding how to streamline all of my experience to blend harmoniously with my online presence. It is a challenge understandably to find a resume writer that can take your resume to the next level when you have peaked and are looking to take the next step in your career planning. I assure you Rosa is it and will have your best interests in mind. I hope this helps you as I understand and shared similar concerns before committing to avoid disappointment.
I just want to let you know that I landed a CFO position 3 weeks ago. Various interviewers throughout the process were impressed with my resume and bio. Thanks for your help. I have recommended your services whenever I get a chance.
I'm so thankful that you are helping me…this is so very professional and unique. People send me their resumes quite frequently, but none compare to these drafts. There is no way I could have done this on my own. By the way, I really like my logo!
~ Stephanie M., MD.
Hi Rosa,
I used your services a few months back and will be starting my new job in a couple of weeks. The Chief Lending & Sales Officer of my new company told me I had the best-written resume he had ever seen. Please let me know if I can offer any testimonial regarding my positive experience.
~ Rick T., Vice President, Business Development, XYZ Credit Union
Frank, Head of Risk Management says:
By 2014, I was working for a large Bank in Saudi Arabia for five years. I had reached the limit in my role as there is a 'ceiling' for expatriates. I had built a Risk Management team from scratch and initiated three projects, one of which was related to regulatory governance.
I began searching in February 2014 for a suitable resume writer as I felt mine could use a professional touch. I researched on the web and asked around. I shortlisted Career Steering in the top tier of such service providers. Later, a colleague approached me, and we found that he had independently ranked Career Steering high on his list as well.
I began working with Rosa at Career Steering in March 2014. I had diligently worked on the Career Assessment and Branding Exercises. I also provided all the material that Rosa had requested. My LinkedIn profile was updated. All the career tools had a consistent message and branded look.
By late April I was contacted by a recruiter for several roles. One role that stood out was with a larger multinational Bank in the UAE. I went for the first interview on May 14. At that interview, the CRO was so impressed, that he arranged for a follow-up interview the next day. The next week, they were considering me for a larger role. The week after, I had a phone interview with the CEO and Country Head of the Bank's Egypt operations. This was my fifth interview.
Then began the compensation negotiation. After all the approvals were done, I received the offer letter on July 16. It has been quite the journey. I was impressed with the biographic, cover letter, resume, LinkedIn profile, and Thank You note produced by Career Steering. This made a real difference in securing the interview and during the interview as well.
My advice to others is to do justice to the Career Assessment and Branding Exercises. Lock yourself in a quiet room and chip away at it. The results have been well worth it. I have received a 40% uplift in my total compensation package, increased responsibility, and career satisfaction. What was not achievable due to the imposed ceiling at my current employer was now achieved through hiring a specialist in the personal branding field.
I would highly recommend Rosa and Career Steering if you want to reach your next level.
Greg Kelaart-Courtney, Chief Information Officer says:
I enjoyed working with Rosa, the quality of her work was phenomenal. She had to wade through copious amounts of background data to develop several branding documents. The quality of these documents was outstanding not only in the actual content but also the graphical representation.
Rosa is a very personable and talented individual who diligently 'peels back the onion' to understand you're greatest talents and abilities, she then turns this information into highly polished documentation. I highly recommend Rosa for her work ethic and ability to product branding documentation and resumes of the highest quality, well worth the investment by any executive wishing to take on a new challenge in their career.
Hi Rosa,
Hope all is well with you! I wanted to take a moment to provide you an update from the time we spent working together. You created two awesome resumes for me; both were well received! I applied for one job on my own and passed along my resume to 2 friends. I was called for interviews on all 3 positions and extended offers on 2 of them while being the top candidate for the 3rd position until I had to withdraw for accepting one of the other offers!
I firmly believe I would not have had these opportunities without you and your exceptional talent in resume writing and design.
I know I picked the right person to compliment me. I couldn't have done it without you. To say thank you, and how confident I am in your skills being the game changer, I have recommended you to a former co-worker, and will continue to recommend you to everyone whom may need a resume facelift! 🙂
Take care!
~ Angela Asbury, Product Manager
CIO/COO Spencer says:
After 15 years in the healthcare IT business, I realized my career was at a crossroads where I needed to complete my MBA to proceed to being the Chief Information Officer for larger, more progressive organizations. I decided to step-down and become a "Deputy CIO" while pursuing my graduate degree, but unfortunately, that step left a hole in my resume where I no longer was perceived as an executive.
As I reentered the executive job market, this gap in executive experience had the result of putting me back at the starting gate with organizations that only wanted previous executives to fill the openings on their senior leadership team. I knew that I needed help in re-framing my experience in a way that was honest but also highlighted my previous successes as a Chief Information Officer.
Working with Rosa has been a wonderfully collaborative experience. I was worried that I was going to be paying for an expensive "Word Template," but what I found was that Rosa's tools for collecting my work and experience history, as well as our multiple telephone conversations, made me think of my accomplishments in a different way than I had considered before.
When I received the first draft, I was overwhelmed with how Rosa had taken these volumes of data and distilled the information into three pages of concise, easy to read and compelling information. Within two days of sending my new resume out to nationally recognized corporations, I received numerous calls for interviews. During one of the interviews, I was told that my resume was one of the best and unique the corporation's executive recruiter had ever seen and that he continually kept coming back to my resume during his vetting process.
This kind of insight made me realize that my investment, both in my time and money, was well worth the effort.
~ Spencer Hamons, MSOL, PMP, Chief Information Officer
The above is only a partial list of our testimonials. Most of our clients are conducting a covert job search, and we need to protect their confidentiality. However, you will find more testimonials embedded into different pages on this website and LinkedIn. If you are one of our happy customers, please email your testimonial to firstname.lastname@example.com. We periodically rotate testimonials. Thank you.
Rosa Elizabeth Vargas
Certified Career Management Coach
Certified Master Resume Writer
Nationally Certified Resume Writer
Academy Certified Resume Writer
Award-Winning Resume Writer

subset: commoncrawl


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As a specialist business information consultancy, we have significant experience in delivering focused and in-depth investigative projects providing domestic coverage on political risk and specific reputational due diligence. We act for a range of major clients which include multinational corporations, and banks. The information Waskitasena provides informs our clients' business decisions and mitigates risk.
Our work is informed by privileged insights from an internal network of well-placed, reliable and confidential sources. Our team of due diligence experts provide clients with the insight they need in sectors ranging from mining and construction to financial services and education. We have deep experience of operating effectively and with discretion in the most challenging jurisdictions, while maintaining client confidentiality.
Waskitasena Advisory's information model allows us to manage a flexible network of sources aligned to precise project requirements. Our team includes former diplomats, government officials, bankers, journalists and global geopolitical risk specialists, who are experienced in discreet, information-led investigations.
We advise clients on strategies as they look to enter new markets or deepen their presence in existing locations. We provide market research, political and reputational risk assessment, personality profiling, influence mapping, and identification of legal and regulatory obstacles.
Our clients access Waskitasena Advisory's continuous risk analysis in ways that best suit their needs, including: :
Waskitasena advisory's risk analysis assists in understanding and minimizing risk. At the core of our analysis is the Waskitasena strategic risk assessment methodology. SRA is a risk profiling service that quantifies risk levels for a wide range of indicators, and risk factors relevant to our clients. SRA is the tool with which we capture inbound data and information, which helps clients understand the implications of strategic trends for their operations. SRA is regularly updated by our analysts based in Jakarta and in locations around Indonesia, with regular input from Waskitasena's senior sources on the ground.
The SRA can be customized specifically for client needs, providing forward-looking information, analysis and risk benchmarking. We can provide you with trial access in order to demonstrate our approach and breadth of coverage.
The reports analyze the strategic and tactical risks for companies considering entering or already operating in Indonesia The reports include a strategic outlook, national summary, and political and commercial analysis. They are created by our expert team of advisers in our Jakarta head office, with information supplemented by our nationwide sources on the ground.


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The influx of imported and gourmet-style fruits and vegetables into the American market is exciting. But very few of us know what to do with feijoas. Following is a handy guide to storage and serving suggestions for some of the newest offerings.
Feijoa: Ripen at room temperature. Fruit is ripe when it is as tender as a soft pear. After ripening, store in refrigerator for a day or two. Peel, if desired, before slicing or halve and eat from the shell. Use in fruit salads.


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Here's a quick and super easy way to replicate a steak hoagie at home, with a fraction of the prep time, calories, and fat that comes with a hoagie made from real steak. This is an ovo-lacto vegetarian-friendly meal that comes in at around 750-900 calories (depending on what kind of cheese, bread, and peppers that you use). It's one of those meals that will convince anyone that a vegetarian diet can be totally yummy. I love these with mustard and ketchup. Mike likes to put ketchup or barbecue sauce on his sandwiches. They are also delicious with nothing but the onions and peppers.
- Flame-grilled Boca Burgers (there's 4 in a box)
- 4-slices of low-fat mozzarella (white American) cheese
- 4 sesame seed topped hamburger buns
- 1 tablespoon olive oil
- 1 peeled onion, cut in half and sliced
- a few forkfuls of pickled banana peppers (you may substitute a fresh banana pepper or bell pepper. The important thing to remember is to fix the veggies in the way that you and your family will eat them best. I use pickled banana peppers because I love the flavor. You can also grill or roast the veggies, but the olive oil replicates the grease from a steak hoagie so be sure to include it somewhere. I've found that the best way to introduce meat eaters to vegetarian dishes is to make sure that the veggie dish mimics the real deal as much as possible).
2. Prepare the Boca Burgers according to package directions. I like to cook them just a bit longer than directed. I like for the outside of the burger to get crispy. This helps mimic the texture of meat when you bite into the sandwich.
3. While you're waiting for the Boca Burgers to cook, sort the tops of the hamburger buns from the bottoms. Put the tops on a plate, add a slice of cheese to each top, and zap in the microwave (or oven) for a few seconds (minutes) to melt the cheese.
4. Construct sandwiches and enjoy.


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I freely admit it. Landmarks are lovely, but I also enjoy observing others interacting with their surroundings. And, I like to do my people-watching with my camera at the ready.
Paris in September requires a full suitcase. You could as easily be fumbling for a warm winter jacket as a sundress -or searching out a warm latte versus a refreshing gelato. The weather seems to fluctuate along with the euro, bringing chilly rain some years and summer sun in others. When I last visited, a long stretch of warmth filled the benches and lawns and Seine River quays with Parisians simply enjoying their city. Weekend or work day, we found masses of people savoring the sunshine and delights of outdoor Paris.
While I would have enjoyed the city in any weather, but warmer temperatures seemed to entice more Parisians outdoors, allowing us to soak in a little more Paris energy along with the sun.
More photos on Facebook at Heather Dugan Creative and on Google+Leave a comment


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New Supervalu survey reveals that food brings families together
MINNEAPOLIS — Food is the most important aspect of the holiday season and unites families, according to a new survey conducted by Harris Interactive for retail giant Supervalu.
According to the Supervalu holiday survey, 70% of Americans indicated that food brings their families the most joy during the holidays, followed by baking and decorating (both at 49%); gifts (48%); shopping (32%); and holiday movies (28%). Among those surveyed, 59% of holiday meal hosts did everything themselves when it came to preparing the main holiday meal, and only 34% said they asked guests to bring a dish to share.
Supervalu said its survey underscored how food is an integral part of holiday traditions among families, and that its stores would focus on providing customers "with simple, affordable meal solutions, tasty tips and useful ideas throughout the season," by offering ideas both in-store and online at the company's local stores' websites. Additionally, news about holiday promotions, events, special offers and coupons can be found on store websites and Facebook pages, and can be accessed by mobile phone.
Dollar Tree completes purchase of Dollar Giant assets
CHESAPEAKE, Va. Dollar Tree on Wednesday announced that it has completed its purchase of the assets of 86 Dollar Giant stores for approximately $52 million in cash, plus the assumption of certain liabilities.
This marks Dollar Tree's first expansion of retail operations outside of the United States.
Based in Vancouver, British Columbia, Dollar Giant stores offer a wide assortment of general merchandise, contemporary seasonal goods and everyday consumables, all priced at Canadian $1.25 or less. The stores average 9,000 gross sq. ft. and operate in British Columbia, Ontario, Alberta and Saskatchewan.
"We now have an outstanding platform for significant expansion in Canada, with an experienced team of management and associates," stated Bob Sasser, Dollar Tree president and CEO.
Dollar Tree operates 4,009 discount variety stores across 48 states. The company is one of the few operations in the dollar channel that literally sells everything for $1 or less.
Deloitte consumer spending index drops in October
NEW YORK — Soft housing prices drove down the Deloitte consumer spending index for the month of October, Deloitte said Wednesday.
The index, which is comprised of four components — tax burden, initial unemployment claims, real wages and real home prices — fell to 4.63%, from an upwardly revised gain of 4.84% a month ago.
But Deloitte said that the drop is no reason to give up hope on the holiday season.
"Despite the index's recent weakness, there are signs that consumers are starting to shake off their long-term austerity in time for the holiday season," said Alison Paul, vice chairman and retail sector leader at Deloitte. "Recognizing there is still fierce competition for consumers' wallets this season, retailers should be ready to capture the consumer's interest with renewed focus on their exclusive items, personalized service and targeted promotions."


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Belt conveyor is very widely used in mining production. But in the daily running production, it will also be affected by environmental and materials handling, leading to a series of equipment failures. Common faults of belt conveyor include belt deviation, sprinkle materials, etc. Shanghai Shibang Machinery Co.,Ltd. sorts out a programme of common faults for belt conveyor combined with customer feedback in the recent days to excerpt the treatment for the customers who are facing the most common problems of belt conveyor running.
First, Start with the most common problems, about the treatment of belt deviation generally includes six areas. 1.Adjusting the carrying idlers, belt deflect which side, which side idlers on the belt toward the forward direction forward. 2.Installing of self-aligning idler when the shorter belt conveyor is bi-directional running. 3. Adjusting the position of driven roller and bend roller to ensure that all the rollers must be perpendicular to the centerline of the mounting position for the belt conveyor in the longitudinal direction. 4.Hammer tension bend roller at the upper part of the two should be perpendicular to the length vertical direction and gravity. 5.To avoid the deviation caused by falling materials add the blocking plate at the reprinted point. 6. To solve the two-way operation of belt deviation should be carefully observed the relationship between the direction of movement and tread, then make adjustment.
Secondly, sprinkling materials of belt conveyor is also a kind of common phenomenon and should be treated according to different situations. For reprinted point, you can control the delivery of the ability to solve sprinkling materials; for concave section vacant belt, you can use a larger radius of curvature; for belt deviation, adjusting the belt is a very good way. Of course, for these common problems, adjusting the size of the installation is not enough, routine maintenance is also very important. How to maintain the belt conveyor? Enterprises should train specialized personnel for routine maintenance and cleaning work to avoid excessive disposable feeding, inspect and timely tighten loose bolts tight, regularly do lubrication, etc. These all help to avoid common faults.
Base on decades of years' R&D experience and thousands of clients' production experience, SBM updated our tranditional vibrating feeder and developped the TSW series feeder, which can greatly improve the whole production line capacity.
Hammer crusher machine is developed for both dry and wet crushing of brittle, medium-hard materials for the mining, cement, coal, metallurgic materials etc.
Ball mills are used primary for single stage fine grinding, regrinding, and as the second stage in two stage grinding circuits.
Wharf Belt Conveyor can be used for transferring lump materials in mining.


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By Michelle Nichols
UNITED NATIONS (Reuters) - The United States wants a team of United Nations investigators to determine who is to blame for chemicals weapons attacks in Syria in a bid to pave the way for Security Council action against those responsible, diplomats said on Tuesday.
Russian U.N. Ambassador Vitaly Churkin said the United States had given him a draft Security Council resolution on the proposal on Monday, which he sent back to Moscow for study. Russia is an ally of Syria and has protected President Bashar al-Assad from council action during the four-year civil war.
Syria agreed to destroy its chemical weapons program in 2013, but the Organization for the Prohibition of Chemical Weapons has since found chlorine has been "systematically and repeatedly" used as a weapon. The group is not mandated to lay blame.
Government and opposition forces have denied using chlorine.
"The rationale is clear and understandable and we talked with (U.S. Ambassador to the United Nations) Samantha Power about it a long time ago, that there seems to be a missing link," Churkin said. "People are researching the allegations about the use; but accountability, it's not there."
The Security Council threatened in March to take action if toxic chemicals were used again. Ten days later six people were killed in a chlorine attack in Sarmin village, medics said.
Churkin has said there would need to be strong proof of who is to blame for any attacks before the council could act. Russia is one of the 15-member Security Council's five veto powers, along with China, Britain, France and the United States.
The United States said it was actively engaged with U.N. colleagues on the use of chlorine as a weapon in Syria.
"The Security Council must address the need to determine who is responsible," said a U.S. official. "Doing so is critical to getting justice for the Syrian people and accountability for those who have repeatedly used chemical weapons in Syria."
Chlorine is not prohibited, but its use as a weapon is prohibited under the 1997 Chemical Weapons Convention, which Syria joined in 2013. If inhaled, chlorine gas turns to hydrochloric acid in the lungs, which can cause burning and drowning through a reactionary release of fluids.
"We are looking at the (U.S.) proposal and of course we are firmly opposed to any use of chemical weapons," China U.N. Ambassador Liu Jieyi told Reuters. "It is something that the council will have to take up."
(Reporting by Michelle Nichols)


text: Memphian, former stay-at-home mom chosen to speak for country's best attorneysClark pleads guilty in federal gun caseOpening arguments begin in Mark Giannini trailDefense attorney: Giannini had consensual sex with woman accusing him of rape Victim testifies against accused rapist Mark GianniniJury finds Mark Giannini not guilty on all three counts during rape trialAppeals court rules in favor of death row inmate in Memphis murderHair weave triple murder suspect appears in courtJudge issues gag order in Treveno Campbell murder trialJudge issues gag order in Martoiya Lang case Lorenzo Clark and wife face federal gun charges in officer shootingLorenzo Clark, wife appear in federal court on gun chargesJudge issues gag order in Martoiya Lang caseGag Order Issued For Campbell CaseMan charged in shooting of off-duty officer to be released into federal custodyLorenzo Clark in courtClark's attorney claims self-defenseAccused killer Lorenzo Clark appears in federal courtMPD officers suspended as TBI revisits Officer Martoiya Lang investigationTwo officers relieved of duty following TBI investigation of Officer Martoiya Lang's murder caseTBI investigation in 2012 MPD officer death could alter murder caseTwo Memphis officers suspended as TBI opens investigation in Lang caseJoe McClusky represents man on trial in shooting incident; Accounts of the trial found in the article 'So senseless': Man on trial in shooting death of 17-year-old boyLauren Fuchs make statement in the article The Brady Bunch: District Attorney Amy Weirich's prosecutorial tactics come under fire again in a steamy sex-and-murder trial.Joseph McClusky defends Memphis man in murder trial. Accounts of the trial found in the article Memphis man accused of murder found not guiltyLorna McClusky represents man; results in a not guilty verdict. Accounts of the trial found in the article Jury convicts one, acquits one of murderWilliam D. Massey represents business man; results in release on bond. Accounts of the trial found in the article Mark Giannini allowed out on bond


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There is so much to see in Hakone that it's recommended to stay at least one night to make sure you have enough time to see all the interesting spots. Gora Ichinoyu is a comfortable and cozy Ryokan (traditional Japanese inn), which will make your stay a pleasant experience. The staff speaks English, you can have your own private Onsen on the balcony of your room (outdoor bath with fresh Hot Spring water) and you can enjoy a traditional Japanese tatami room with futon for a very reasonable price. They also have public indoor baths (men and woman baths are separated), vending machines, a restaurant and a small souvenir shop.
The staff are very friendly and will help you if you have trouble finding your way around the area. The Ryokan offers all kind of meals (unfortunately no Vegetarian course available) for a good price, for which you have to make a reservation when booking your room. The Ryokan does not have that many rooms (which makes it nice and quiet), so make sure to make your reservation in advance. All the rooms have a stunning view over Hakone's beautiful landscape.
Ichinoyu is a 10-15 minute walk from Gora station. They recommend you use a taxi. I used a taxi on my way to the Ryokan just to make sure I didn't get lost and walked back to the station the next day. For more information and reservations, check their official website (in English): http://english.ichinoyu.co.jp/gora/


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Police Suspect Suspension of Detention of Secretary General of FUI
MuslimsPost.Com | Wearing a white garment, Al-Khaththath got out of drug custody Polda Metro Jaya (PMJ), Wednesday (12/7) approximately at 18.00 pm.
The secretary general of the Islamic Forum Muhammad who was caught up in the alleged treason case will be a city prisoner after the investigator granted the request to suspend his detention.
"Alhamdulillah, we thank the police for giving us, fulfilling the request of our lawyer Mr. Achmad Michdan, a Muslim lawyer who has filed for arrest," Al-Khaththath said.
Monitoring at Metro Jaya Police Headquarters, besides the family, Al-Khaththath was also accompanied by his lawyer, Achmad Michdan, and Chairman of Parmusi Usamah Hisham.
Upon his exit, Al-Khaththath immediately thanked the police for fulfilling the suspension application he had submitted.
The original man named Muhammad Gatot Saptono was also grateful to the party who had supported him during the period of detention.
Al-Khaththath admitted to being treated well by the police while serving time in prison.


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|NEMA standards
North American plugs and sockets
NEMA* standards are used in the US, Canada and Mexico. Comparable flat blade plugs are used in Japan, various Caribbean islands, parts of South America and some Southeast Asian countries
* National Electrical Manufacturers Association (U.S.A.)
locking devices
dual Amp / Volt types
classic types
heavy duty types
Receptacle is used in American English rather than socket, but for the sake of unambiguity socket is preferred here.
In North America different names and abbreviations are used. Neutral (N) is indicated as W which corresponds to the white wire; the black wire is 'Hot' (L)*. Equipment earth is indicated as Ground. Three phase L1, L2, L3 is in North America indicated as: X, Y, Z.
* Occasionally a single phase hot connection is indicated as X.
Logos and notes on history of manufacturers of material shown on North American plugs and socket pages are given on a separate page.
grounded socket
rated at 15A - 125V. The model corresponds to NEMA 5-15R (NEMA codes are explained below).
Slots for flat
blades may have
a different width. See plug no. 6 for explanation. Manufacturer: Cooper
Electric Supply, New Jersey U.S.
|2, 3
Resistant NEMA
5-15 socket.
Hot and W slots have shutters. From November 2013 new and
renovated residential housings in the U.S. and
have to
be equipped with tamper resistant sockets. Simultaneous plugging in
both power blades pushes the shutter aside. Manufacturer: Pass &
Seymour (part of Legrand Group). {DH}
duplex socket (NEMA 5-15R), with ground fault circuit interrupter
(GFCI). This feature evaluates the current difference between line and
neutral and interrupts the flow of electricity when a sudden difference
is measured.
Manufacturer: Leviton.
plug (top) and
(bottom). For safety reasons, extensions
(indicated by green arrows) prevent the insertion of a grounded, 3 pole
plug in an non-grounded connector. The plug has brass blades of equal
width. Manufacturer: Eagle Electric
difference in
width between hot and neutral (W) blade changes an
essentially non-polarized NEMA 1-15
into a polarized type. Neutral (W)
blades might be nickel
plated rather than standard brass (see left plug, made in Mexico).
The plug at right is unusual, but certified* type; blades do not have circular holes. Most sockets have some type of bump on the contacts which match up with the holes in the plug blades to help increase the plug retention force.
• plug has been made in China and has a very small Underwriters Laboratories Inc. certification mark. {DH}
|7, 8
15A - 125V plug (NEMA 5-15P). The
position of the U-shaped earth pin results in a polarized plug; hot
and neutral are irreversible. The earth pin is 4 mm longer than the W
and X (hot) blades. This safety measure ensures that grounding is
effective before power pins make contact.
The round base plate with pins can be fixed in eight positions with 45ş rotational steps. Image nos 7 and 8 show five of eight positions. The plug has a side cord entry (downwards in plug no. 7). Without the possibility to adapt cord entry orientation it would be impossible to use two of these plugs in a dual socket (socket nos 1, 2 and 4). Orientations 8b and 8d are also useful when a socket has been mounted horizontally rather than vertically. {DH}
The plug has been made in China by WE. Details about the company has not been found. A link between WE and Pass & Seymour has been suggested, but evidence is lacking.
| The
variety in plug and
socket standards is unsurpassed
The National Electrical Manufacturers Association (NEMA, USA) has set standards for configurations that differ depending on current rating (15, 20, 30, 50 or 60 A) and electrical potential (nominal 125, 208, 250, 277, 480 or 600 V)*. This has resulted in more than 35 different straight blade configurations (various grounding systems included). The system rules out accidental intermating of devices and related risks.
* 480 and 600 V are three-phase only. The page on three-phase transformers explains the source of the other voltages.
NEMA codes
Codes consist of two numbers followed by R (receptacle) or P (plug). The first number indicates a class, second number refers to current. Class defines voltage, single, split- or three-phase, and grounded or non-grounded. Locking devices have a code preceded by an L
For example NEMA 5-15R stands for a class 5 (125 Volt, grounded) socket.
Plugs and sockets in Japan
Also Japan uses flat blade plugs and sockets, in part comparable to NEMA types; they are shown on a separate page.
|Locking devices
Besides flat blade plugs and sockets NEMA
has also defined locking devices. Japan has developed a deviant system.
Click here for locking devices.
|Dual Amperage /
Voltage types
Series of sockets exist that can be used for more than one type of plug. Plugs can differ
with respect to amperage and/or voltage.
Click here for dual types.
|9, 10
|NEMA 5-15R socket with isolated ground, also known as clean earth. It has two, separate earth connections – one is connected to the earth pin contacts of the outlets (green wire), and the other connects socket fixing screws to the general building earth. The green wire is connected to an earth reference bar. Read more about clean earth at the page on uncommon British sockets. The green dot indicated that it is a hospital grade socket (see no. 11 for details). Manufacturer: Leviton. {DH}
grade NEMA 5-15 plug, which means that (i) blades are usually solid
instead of folded metal, (ii) the blades are normally nickel-plated,
and (iii) the plug
includes a cable retention device or strain relief to prevent any
stress to the plug's internal connections. Many hospitals prefer that
the plugs be clear so that internal connections can be
inspected visually, but this not an obligation. Hospital grade devices
are marked with a green dot (see inset top right). {DH}
Manufacturer: Ching Cheng Wire Materials, Taiwan.
|Multi-plugs for two blade 15 A plugs (125V). The lower example is a swivel type device, which can be tilted over 180 degrees. Both plugs are protected against attempts to insert plugs with ground pins.
grounded 15 A plugs (125V). Manufacturer: Eagle.
for six,
grounded 15A plugs. This device has to be used in a duplex socket (the
standard configuration, see
no. 1) for providing sufficient stability. No brand name; made in China.
|NEMA 1-15 plug-in
switch tap. Manufacturer: General
Electric (USA).
|Pull chain medium
light bulb socket with two non-grounded outlets. Only the lamp is
on/off by the pull chain; outlets are continuously active. Read also
the historical note about classic
material on the classic plugs and sockets page.
* medium refers to the diameter of the Edison screw base; medium = 26 mm (U.S.), or 27 mm (Europe). Size are also indicated as E26 and E27. The adapter has been made in Colombia
|Two medium size
light bulb
adapters. Left: screw base to 2-pole outlet. Right:
non-grounded 15A, 125V plug to medium light bulb socket.
|Duplex 15A - 125V
grounded power strip with a lighted adapter plug, indicating when power
is on. The top of the adapter has a single grounded outlet. The
indicator light can also be used as a night light. Manufacturers:
Leviton (power strip) and Woods Industries (adapter plug with indicator
light) .
US, Canada
Japan flat blade plugs are also used in many other countries.
The reliability of plugs in some Latin American and Asian countries is
occasionally doubtful. The image shows two examples. Top: Chinese
made 15A
molded flat blade plug. Bottom: Peruvian 15A "mini" connector. The
Chinese plug is the only plug in the museum that fits in the
mini-connector. The blades of standard US plugs are too wide and too
thick. Unlikely that plug and
connector comply with the U.S. safety standards.
Note that plug and connector were (and still are?) used in countries that have a 220 Volt network. {PO}
|Tap-A-Line outlet with elongated slots to
receive the prongs of multiple appliance plugs. Details are given on a separate page.
|Not earthed 15A-125V NEMA 1-15R socket; a nearly 'classic' model. Since 1974 all new outlets must have an earth contact (NEMA 5-15R). NEMA 1-15R is still available, but for repair use only. Manufacturer: Pass & Seymour / Legrand. {DH}
|22, 23
|Leviton Wetguard 5-15R (15A-125V)
connector (image no. 22) and 6-15P (15A-250V)* plug (image no. 23).
watertight straight blade devices are engineered to IP66 and IP67
standards. Manufacturer: Leviton in Melville NY, USA. {FSE}
* Find more U.S. 250 Volt device at the page on dual Amp / Volt page.


text:
Main Street Theater has 2 offerings for families during Spring Break next week: How I Became a Pirate and Ramona Quimby. Both productions are playing in midtown at 3400 Main Street. Pirate plays Monday & Tuesday (March 13 & 14). Ramona plays Wednesday – Friday (March 15 – 17). All shows are at 10:30am. Tickets range from $16 – $20 depending on seating. Ages 3 and up. More details below.
Ramona also has performances March 12 at 12:30 & 3:30 and March 18, 25, and April 1 at 11am and 2pm.
Sensory-Friendly Performance: Sunday, March 12 at 3:30pm
ASL Performance: Saturday, April 1 at 2pm
Pirate also has performances April 22 at 11am and 2pm
Sensory-Friendly Performance: Saturday, April 22 at 11am
ASL Shadow-Interpreted Performance: Saturday, April 22 at 2pm
Photos of both shows are attached:
Ramona photos are by Blueprint Film Co.
Ramona 1: Ramona Quimby (Lauren Ashley Miller) with her sister Beezus (Elizabeth Tinder)
Ramona 2: L-R: Aunt Bea (Whitney Zangarine), Ramona Quimby (Lauren Ashley Miller) and Beezus (Elizabeth Tinder)
Pirate photo is courtesy of Main Street Theater
The cast of How I Became a Pirate
Main Street Theater provides theater experiences for all ages. Founded in 1975, our MainStage produces professional, intimate, literary plays for adults; our Theater for Youth produces professional, engaging productions based on children's literature for families and school groups, both in-house and on tour around Texas; and we offer Education and Outreach programs on-site and at satellite locations around the Greater Houston area for youth aged 4 – high school. We perform locally in 2 facilities: our Rice Village home on Times. Blvd., and as part of the MATCH (Midtown Arts & Theater Center Houston) on Main Street.
AHOY, MATEY! When Captain Braid Beard and his crew invite Jeremy Jacob to join their voyage, it's the swashbuckling time of his life! No vegetables or table manners, and you get to have sword fights whenever you want. But Jeremy soon misses things like getting tucked into bed, goodnight kisses and story time. A heave-ho, blow-the-man-down tale you won't want to miss!
Recommended for Pre-Kindergarten and up.
Children under the age of 3 (including sleeping babies) are not allowed in the theater.
Sign Language Interpreting services courtesy of the University of Houston's ASL Interpreting Program.
When her father loses his job, Ramona Quimby learns that being grown up is hard work. But as her sister Beezus says, "being a kid and trying to become a grown up is even harder." For more than 60 years, kids of all ages have delighted in the hilarious antics of Ramona and the Klickitat street gang in Beverly Cleary's beloved Newbery Honor book series. Based on the books by Beverly Cleary: Beezus and Ramona, Ramona the Pest, Ramona and Her Father, Ramona the Brave, Ramona and Her Mother, Ramona Quimby, Age 8, and Ramona Forever.
Recommended for Kindergarten and up.
Children under the age of 3 (including sleeping babies) are not allowed in the theater.


text:
We don't know who he was because he didn't sign his name.
Was it fear that drove this anonymity in an age of persecution? Or was it humility?
When we studied Hebrews 7, we marveled together at the author's ability to connect the dots between Melchizedek and Jesus, our High Priest forever, based on the power of an indestructible life. Whoever wrote this letter we now refer to as "Hebrews" certainly knew the Old Testament scriptures, and once again in chapter eleven he's connecting the dots between a concept — faith — and the way he sees it lived out in the recorded lives of Old Testament saints.
Hebrews 11:1 provides a two-pronged description of faith:
Now faith is the assurance of things hoped for, the conviction of things not seen.
- The assurance of things hoped for. By faith, we are sure of God's promises and are enabled to…
View original post 638 more words


text:
'enchondromatosis, x-ray'
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text:
According to FICE, the Federation of Spanish Footwear Industries, the value of footwear exports has fallen in the first trimester of the year, compared to similar period in 2016. Volume of exports up by 3.4%
In the first three months of the year, Spain exported 48 million pairs of shoes, with total value of 834.4 million euros, reflecting a 1.1% decline in value and a growth of 3.4% in volume.
The UE markets are still the main destination for Spanish footwear, receiving a total of 37.8 million pairs with a total value of 624.6 million euros and representing 78.8% of total exports. France (158.2 million euros), Italy (114.4 million euros) and Germany (80.5 million euros) make up the top 3 buyers ranking.
Notwithstanding this position, exports to the EU markets fell by 3.8% in value in the period. In the opposite direction, exports to non-EU markets grew by 8.6% in value. Exports to no EU markets already reached 209.37 million euros.
The United States are the main destination outside the EU and the fourth largest market for Spanish footwear, with a share of 7% in total exports. During the first three months of the year, a total of 1.6 million pairs valued at 57.7 million euros were exported to the United States.
Amongst the 40 largest destinations for Spanish footwear, the United States pay the second highest average price per pair (36.58 euros), just behind buyers from Hong Kong (41.97 euros).
By World Footwear…


text:
A quantitative hypothesis for cancer genesis and progression—the endogenous molecular–cellular network hypothesis, intended to include both genetic and epigenetic causes of cancer—has been proposed recently. Using this hypothesis, here we address the molecular basis for maintaining normal liver and hepatocellular carcinoma (HCC), and the potential strategy to cure or relieve HCC. First, we elaborate the basic assumptions of the hypothesis and establish a core working network of HCC according to the hypothesis. Second, we quantify the working network by a nonlinear dynamical system. We show that the working network reproduces the main known features of normal liver and HCC at both the modular and molecular levels. Lastly, the validated working network reveals that (i) specific positive feedback loops are responsible for the maintenance of normal liver and HCC; (ii) inhibiting proliferation and inflammation-related positive feedback loops and simultaneously inducing a liver-specific positive feedback loop is predicated as a potential strategy to cure or relieve HCC; and (iii) the genesis and regression of HCC are asymmetric. In light of the characteristic properties of the nonlinear dynamical system, we demonstrate that positive feedback loops must exist as a simple and general molecular basis for the maintenance of heritable phenotypes, such as normal liver and HCC, and regulating the positive feedback loops directly or indirectly provides potential strategies to cure or relieve HCC.
1. Introduction
Cancer, a generic term for malignant neoplasms, has been recorded for thousands of years [1]. During the long discourse on cancer, many hypotheses have been proposed [1,2]. Nowadays, cancer is thought to be a genetic disease, which suggests that the genesis and progression of cancer are caused by genetic alterations, i.e. carcinogenic factors caused cancer by their damage to normal genomes [3,4]. Nevertheless, there is extensive experimental and theoretical evidence to suggest that the genome is not the whole story [5–14]. Although cancers are often characterized by genetic alteration, it is certainly clear that genetic alterations are not always a prerequisite for the initial genesis of cancer. For example, certain precancerous lesions can develop in vivo without detectable cytogenetic abnormalities [10,11]. On the other hand, genetic alterations are not always sufficient for the initial genesis of cancer. For example, about 50% of hepatocytes (in an adult human) are polyploid, with two, four or even more times the normal diploid quantity of DNA per cell [15]. The facts show that there are no one-to-one relationships between genotype and phenotype, and the biochemical reactions of the endogenous molecular–cellular agents cannot be ignored [16–20]. Thus, in order to understand cancer, we need to include both genetic and complex biochemical reaction information in addition to genomic information. Thus, we have proposed an alternative cancer endogenous molecular–cellular network hypothesis [5,6], which is formulated as follows. The molecular and cellular agents, such as oncogenes and suppressor genes, and related growth factors, hormones, cytokines, etc., interact with each other through signalling transduction and gene regulation to form the endogenous molecular–cellular network. A quantitative description of the endogenous network consists of a set of nonlinear and coupled differential equations. The nonlinear dynamical interactions among the endogenous agents can generate many local attractors with obvious or non-obvious biological functions. We assume that normal tissue and cancer are endogenous attractors underlying the endogenous molecular–cellular network. Related hypotheses have also been proposed by others [21,22].
In light of the present hypothesis, the genesis and regression of cancer is viewed as transitions between normal tissue and cancer attractors passing through saddle points or other attractors. Using hepatocellular carcinoma (HCC) as a working example, we explore the molecular basis which maintains both normal liver and HCC attractors and, by taking advantage of this, seek potential strategies to cure or relieve HCC. Despite the fact that effective therapies are still lacking for most cancers [23], we are motivated to address the issues from both clinical and experimental perspectives. For example, we know that there have been independent reports of the spontaneous regression of cancer; despite it being a rare event [13,14], there is optimism that cancer may be cured or relieved. In fact, tumorigenesis is also a rare event, caused by factors such as oncogenes; however, they have been overexpressed or activated to increase the probability of tumorigenesis. Along the same lines, it is reasonable to assume that we can make rare spontaneous regression of cancer a more probable event by targeting properly defined factors. We also know that this concept has been achieved successfully in acute promyelocytic leukaemia (APL), in which targeted therapy has changed APL from being highly fatal to highly curable [24].
In the following sections, firstly, we will discuss the basic assumptions of this hypothesis and establish a working model according to the hypothesis using HCC as an example [23,25]. Secondly, we quantify the working network by a nonlinear dynamical system and compare the modelling results with clinical and experimental data. We will show that the working model reproduces the main features of normal liver and HCC at both modular and molecular levels, which suggests that the working network may be valid to study normal liver and HCC. Lastly, theoretical and practical implications from the working model are considered. We answer the proposed questions explicitly: (i) specific positive feedback loops are responsible for the maintenance of normal liver and HCC; (ii) inhibiting proliferation and inflammation and simultaneously inducing liver differentiation is predicated as the potential strategy to cure or relieve HCC; and (iii) the genesis and regression of HCC is asymmetric.
2. Biological assumptions and working model
An endogenous molecular–cellular network hypothesis of cancer has been proposed as an alternative means to understand cancer [5,6]. The main assumptions underlying the hypothesis are as follows. Firstly, we assumed that a biological system is built by a set of functional modules and that there is crosstalk between the modules. According to the current understanding of cancer biology [26], a minimal set of core functional modules (figure 1) to describe HCC at the systemic level may include the cell cycle, apoptosis, metabolism, liver-specific function, cell adhesion, immune response and angiogenesis [8,15,25,26]. Furthermore, we assumed that the status of each functional module may be regulated by a minimal set of molecular–cellular agents according to the accumulated molecular biology knowledge of liver [15,25]. The molecular–cellular agents are assumed to be proteins, as proteins are the main cell fate decision-makers via the regulation of signalling transduction and gene expression (figure 1; for a detailed description, see the electronic supplementary material).
Secondly, we assumed that the molecular–cellular agents will interact with each other. The activation/upregulation or inhibition/ downregulation among the agents was summarized from a well-documented gene regulatory network and signalling transduction pathway, which suggest that the interactions have a solid biochemical basis [15,25]. We assume that the agents and interactions among agents form an autonomous and decision-making network, which suggests that the transmission of information is not one way and there is no privileged causality in the network. To emphasize that the network is formed by the interactions of endogenous cellular–molecular agents shaped by evolution, we called it the endogenous molecular–cellular network. The aim of establishing a liver endogenous network is to reveal the core regulatory mechanisms of the liver at the systemic level. A working endogenous network of HCC has been established according to the hypothesis (figure 1; for detailed references see the electronic supplementary material, table S1). As the key molecular–cellular agents that regulate the status of the functional modules and their interactions have been documented and proved to be conserved, it seems that the working endogenous network is reproducible according to the hypothesis.
It is necessary to discuss the gaps between the working endogenous network of liver and real liver. There is no doubt that the real liver has been greatly simplified by the above assumptions. For example, there are far more functional modules than the selected modules here; other molecular–cellular agents, such as microRNA, metabolites and other proteins, are not considered explicitly in the network. Thus, the simplified and incomplete working endogenous network is by no means the only realization and is open to further expansion and revision. However, we will show later that it is one of the simplest variants, which may reproduce the main features of normal liver and HCC tissues at both the modular and molecular levels. Moreover, we will show that solid predications can be reached by careful analysis even in the case of partial knowledge.
3. Quantification of the endogenous network
The quantitative description of the core endogenous molecular–cellular network consists of a set of coupled differential equations [27–30]. We use CyclinD-CDK4/6 as an example to show how to obtain the differentiation equations (figure 1). CyclinD-CDK4/6 was upregulated by transcription factor E2F and Myc and downregulated by C/EBPα, p21 and GSK-3β. Firstly, we assume that the concentration or activity of CyclinD-CDK4/6 under the influence of the protein E2F, Myc, C/EBPα, p21 and GSK-3β takes the following form [27–34]: 3.1Here, [CyclinD-CDK4/6] is the concentration or activity of protein CyclinD-CDK4/6. [E2F], [Myc], [C/EBPα], [p21] and [GSK-3β] have similar meaning. f([E2F], [Myc], [C/EBPα], [p21], [GSK-3β]) is the integrated production rate of CyclinD-CDK4, is the degradation term of CyclinD-CDK4/6, τCyclinD−CDk4/6 is its degradation constant. We further assume that CyclinD-CDK4/6 needs to be activated by E2F or Myc, and at the same time inactivated by C/EBPα, p21 and GSK-3β. Then, the integrated production rate f([E2F], [Myc], [C/EBPα], [p21], [GSK-3β]) is quantified by Hill functions, is the maximal production rate of protein CyclinD-CDk4. n1i are the Hill coefficients, K1i are the dissociation constants, which are biochemical parameters describing the kinetic properties of each protein in regulating the production of CyclinD-CDK4. As it is impossible to obtain all the parameters, we focus on the properties of these interactions which are invariant in the appropriate parameters but depend only on the logical and topological structure of the interactions [29]. We consider the relative concentration or activity of these agents: the content or activity of each protein was normalized to range from 0 to 1, where 0 means minimal content or activity and 1 means maximal. This assumption will not affect validations, because much of the experimental data, such as gene expression data, are also in a framework of relative concentration. The maximal production rate, VCyclinD−CDK4/6, and the degradation rate, τCyclinD−CDk4/6, are normalized, as 1. n1i and K1i values are selected within a reasonable range to grasp the key feature of activation or inhibition, for example n1i = 3 and K1i=1/8 (scanning of parameters is considered in the electronic supplementary material).
The quantitative assumptions provide a general framework to quantify the endogenous network; other proteins in the working endogenous network of liver are quantified in a similar way (see the electronic supplementary material). Thus, the working endogenous network is described by a nonlinear dynamical system, which implies some attractors underlying the endogenous network [5,6,28]. We show that attractors are robust against reasonable parameters by scanning n and K in the Hill function (electronic supplementary material, tables S2–S7). The results suggest that attractors are determined by the emerging property of network topology structure and dynamic logic relationship rather than by selective parameters.
4. Validations at modular and molecular levels
As we have established and quantified the working endogenous network, we now validate this network using the main known features of normal liver and HCC. One of the most important features is that some key functional modules have opposite status between normal liver and HCC [25,26]. We define the status of functional modules using on and off: on means the expression or activation level of the molecular–cellular agents supported the execution of the functional module, whereas off means the expression or activation of these agents did not support the execution of the functional module. We summarize the status of these functional modules, including cell cycle, metabolism, liver-specific function, cell death, cell adhesion, immune response and angiogenesis, in normal liver and HCC from clinical and experimental data (table 1) [25,26].
From the working endogenous network model side, according to the ordinary differential equations, we obtain five attractors, which may have obvious or non-obvious biological functions (see the electronic supplementary material, tables S2–S7). Each attractor is specified by the relative content or activity of these molecular–cellular agents. According to the expression or activation level of these agents, we can judge the status, on or off, of the functional modules in each attractor. We also summarize the status of these functional modules in each attractor (table 1). The results show that two attractors, A and C, obtained from the model have a perfect match with normal liver and HCC, respectively, at the modular level. Thus, we preliminarily conclude that attractors A and C of the model reproduce the clinically normal liver and HCC.
Furthermore, we test this preliminary conclusion at the molecular–cellular level. Firstly, we summarize the relative change of each agent from normal liver to HCC (table 2) according to the experimental data. The experimental results are collected in two independent ways. The first way is expert knowledge, which is obtained from the current study of the mechanism of each agent and its relative change from normal liver to HCC; relative changes of the agents from clinical studies have also been summarized as a double check [15,25] (detailed references are in the electronic supplementary material, table S8). The other way is to analyse the high-throughput microarray data, checking the transcriptional change of each agent from normal liver to HCC [35]. Secondly, according to the modelling result, we summarize the relative change of each agent from normal liver to HCC (table 2). The comparison shows that the modelling results and specialist knowledge have an agreement of 85.7% (table 2) and have an agreement of 61.9%, 76.2%, 71.4% with three independent HCC tissues, respectively (table 2, NCBI ID: GSE33006) [35]. Given the heterogeneous nature of cancer [36] and intrinsic experimental error [37], the accuracy rates suggest a good agreement.
Consistency of the experimental data and model results at both the modular and molecular levels suggests that the present working network of liver reproduces the main known features of normal liver and HCC. It seems quite striking because the molecular–cellular agents and interactions in the working network are added one by one from the knowledge obtained independently and the attractors of the complex nonlinear dynamical systems are far beyond our imagination before analysis, and ultimately experimental data and model results have a good agreement. We want to point out that, despite the good agreement, actually it is neither sufficient nor necessary as an absolute test of the model; and given the heterogeneous nature of cancer and the incomplete working network, experimental results of certain molecular–cellular agents which do not appear to fit this model must be expected.
We also want to point out that as it is impossible to enumerate all the possible attractors of this high-dimensional nonlinear dynamic system, the attractors obtained here are by sampling. By sampling enough times, we confirm that there are at least five attractors. The dynamical system may include limit cycles and chaos; however, at the present stage we have not found limit cycles and chaos. Mathematically, the structure of the endogenous molecular–cellular network model is similar to the Morse–Smale dynamical system [38]: it is structurally stable with a finite number of attractors.
5. Theoretical and practical implications
As real liver has been simplified during the realization of the hypothesis, the present working network should be viewed as what liver might be, not as what it must be. As the endogenous molecular–cellular network is quantified by a nonlinear dynamical system, we shall therefore discuss only the characteristic properties of the nonlinear dynamic system. One of the most characteristic properties of nonlinear dynamical systems is that each attractor of the system is established and maintained by some key molecular–cellular agents and their interactions [33,39]. The present working network reveals that distinct positive feedback loops provide a simple and general strategy for the establishment and maintenance of normal liver and HCC.
The working network reveals that the positive feedback loop HNF4α–C/EBPα–Foxa2 is responsible for the establishment and maintenance of normal liver attractor (figure 2a). Biologically, HNF4α, C/EBPα and Foxa2 are liver-enriched transcription factors, which regulate the synergistic transcriptional activation of hepatocyte-specific genes [25,40]. These liver-enriched transcription factors have mutual activations, which form a positive feedback loop and maintain normal liver tissue [25,40]. Experiments also show that fibroblasts can be induced to function as hepatocyte-like cells by overexpressing liver-specific transcription factors [41]. The activated HNF4α–C/EBPα–Foxa2 loop also affects the status of other functional modules (figure 2a), such as suppressing the hepatocyte cell cycle and related metabolism [42,43], suppressing inflammation [42] and inducing differentiation of hepatocytes [25].
The working network reveals that two positive feedback loops, receptor tyrosine kinases (RTKs)–Ras, Akt, ERK, β-catenin–Myc, HIF and TNF-α, IL-1, IL-6–NF-κB (in Kupffer cells), are responsible for the establishment and maintenance of HCC (figure 2b). Biologically, RTKs–Ras, Akt, ERK, β-catenin–Myc, HIF is a conserved proliferation-related positive feedback loop. Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors, including EGFR, VEGFR, etc. Once activated, RTKs will lead to downstream activation of a number of common signalling molecules [44]. The activation of signalling pathways will change the gene expression profiles, and the changes in gene expression in turn activate the RTK ligands; in this way they form positive feedback loops to support cell proliferation [45,46]. TNF-α, IL-1, IL-6–NF-κB (in Kupffer cells) is an inflammation-related positive feedback loop [47]; pro-inflammatory stimuli, TNF and IL-1β, will activate the IκB kinase (IKK), resulting in IκB phosphorylation and leading to the nuclear entry of freed NF-κB dimers in Kupffer cells. Activated Kupffer cells produce a panel of inflammatory cytokines and growth factors, including IL-1, IL-6 and TNF-α, thus forming an inflammation-related positive feedback loop [48]. The two activated positive feedback loops also affect the status of other functional modules (figure 2b), such as activating cell proliferation and growth [45,46], activating angiogenesis [46] and inhibiting cell apoptosis [45], inducing dedifferentiation [43].
Regulating these positive feedback loops provides strategies to make transitions between normal liver and HCC. Specifically, one predication is that HCC may be cured or relieved by inhibiting the proliferation-related feedback loops RTKs–Ras, Akt, ERK, β-catenin–Myc, HIF and inflammation-related feedback loops TNF-α, IL-1, IL-6–NF-κB (in Kupffer cells), and simultaneously activating differentiated liver-specific-related loop, HNF4α–C/EBPα–Foxa2 (figure 3). In reality, regulating the positive feedback loops can be achieved either by inhibiting or activating these proteins in these positive feedback loops directly or by controlling diet and metabolism, etc., which affects these positive feedback loops indirectly. In short, the working network predicates a potential strategy to cure or relieve HCC by inhibiting proliferation and inflammation, and inducing liver differentiation simultaneously.
The second characteristic property of the working network results from the topology of these positive feedback loops coupling (figure 3). The coupling of the liver-specific, proliferation and inflammation positive feedback loops reveals that the genesis and regression of HCC is asymmetric. This means that normal liver can be induced to HCC by activating the proliferation-related feedback loops, RTKs–Ras, Akt, ERK, β-catenin–Myc, HIF and inflammation-related feedback loops, TNF-α, IL-1, IL-6–NF-κB (in Kupffer cells); however, HCC cannot be induced to normal liver by inhibiting the two positive feedback loops, so we still need to activate the liver-specific positive feedback loop HNF4α–C/EBPα–Foxa2 simultaneously. The ubiquitous HCC relapse and drug resistance may result from this property [49,50]. In short, the results show that, when designing strategies for HCC prevention, cure and care, we need to take these positive feedback loops seriously.
6. Discussion
6.1. Endogenous molecular–cellular network hypothesis and genetic mutation hypothesis
The proposed cancer endogenous molecular–cellular network hypothesis incorporates both genetic information and biochemical reactions among endogenous molecular–cellular agents beyond the genomic information [5,6]. On the genetic information level, the present hypothesis incorporates the hypothesis that cancer is a genetic disease. The gain and loss of functions via genetic mutations can be simply represented by removing and adding molecular–cellular agents or interactions in the endogenous network [3,4]; such manipulation can be handled by standard procedures, which pose no additional conceptual issues [6,28]. Beyond the genomic information, the nonlinear dynamical biochemical interactions among the endogenous agents generate normal tissue attractors and cancer attractors. Owing to the nonlinear biochemical interactions beyond the genomic information, the present hypothesis holds that there are no simple one-to-one relationships between genotype and phenotype in complex diseases such as cancer. Instead, genotype is in general related to phenotype by a very complex network of biochemical reactions [16,17].
6.2. Working endogenous and typical bioinformatics networks
The aim of establishing a liver endogenous network is to reveal the core regulatory mechanisms of HCC genesis and progression at the systemic level. Many other high-throughput-based frameworks, such as the ENCODE project [51], also have been proposed with similar aims. Theoretically, the regulatory mechanism can be deduced from high-throughput data if we have enough data [30]. Nevertheless, in reality, the present genome-wide gene expression and protein interaction information are far from achieving this goal [8,30]. Currently, the analysis of high throughput is based more on statistics, which can deduce the network topology and correlation between these molecular–cellular agents [51]. In the endogenous network construction, we solve this issue by making full use of the well-documented gene regulatory network and signalling transduction pathway, which reflect our accumulated knowledge in the molecular biology of liver.
6.3. Quantitative analysis of the endogenous molecular–cellular network
The endogenous molecular–cellular network should be quantified by a stochastic nonlinear dynamical system [52,53]; recent progress allows us to ignore the stochastic effects at the first step [54,55]. Characteristic properties of nonlinear dynamical systems declare that a distinct positive feedback loop must exist to maintain normal liver and HCC, in the light of the assumption that normal liver and HCC are distinct attractors of the endogenous molecular–cellular network of liver. A vivid and graphical description of the dynamical system is an adaptive landscape, which can depict the robustness of these attractors and the transition between the attractors intuitively [56]. Recent progress allows us to construct the adaptive landscape based on the endogenous molecular–cellular network [55,57].
6.4. Potential strategies for hepatocellular carcinoma cure, prevention and care
The working network predicates a potential strategy to cure or relieve HCC by inhibiting proliferation and inflammation, and simultaneously inducing liver differentiation, which can be checked by experiments. There are three reasons to recommend this combination. Firstly, each has been successfully used to cure cancer [58–62]. Proliferation and inflammation-related proteins have been approved by the US Food and Drug Administration to treat certain human cancers [58,62]. Liver-specific transcription factors that are overexpressed to induce HCC differentiation have shown anti-tumour effects [60,61]. However, the separate treatment strategies may result in dilemmas such as drug resistance [59] or just cannot obtain favourable results in clinical practice [61]. Our predication here reveals that we should use combined therapies, in particular we need to induce HCC differentiation. Secondly, similar strategies have been successfully used in a subtype of APL to turn it from highly fatal to highly curable [24]; our predication suggests that these concepts should be used in solid tumours. Thirdly, clinical cases have independently reported the spontaneous regression of HCC [14]; however, spontaneous regression is a rare event. The predicated combined strategies here may make rare HCC spontaneous regression a more probable phenomenon.
7. Conclusion
Using HCC as an example, we have realized the recently proposed cancer endogenous molecular–cellular network hypothesis. The working network of liver was quantified by a set of nonlinear differentiation equations. We have then demonstrated that the working network reproduces the main features of normal liver and HCC at both modular and molecular levels, as the first set of evidence of the validity of the hypothesis. We explicitly obtained two additional testable predications for further validation. Specifically, (i) the potential strategies to cure or relieve HCC may be inhibiting proliferation and inflammation, and simultaneously inducing liver differentiation; (ii) the genesis and regression of HCC are asymmetric. We explicitly discuss the gaps between the working endogenous network of liver and real liver at each step of the realization, including the basic assumptions, working network construction, quantification, validations and feasibility of the predications. In summary, these predications should be taken seriously when designing strategies for HCC prevention, cure and care. We would also suggest that the endogenous molecular–cellular network hypothesis may provide a suitable candidate, both qualitatively and quantitatively, to understand cancer genesis and progression.
Data accessibility
Gene expression profiles from the HCC tissues can be accessed by NCBI GEO accession: GSE33006.
Funding statement
This work was supported in part by the National Basic Research Program of China no. 2010CB529200 (P.A.), Natural Science Foundation of China no. NFSC91029738 (P.A.).
We thank Dr Gensheng Feng, Dr Leroy Hood, Dr Anning Lin for helpful comments; Bin Li, Site Li, Shuang Tan for discussions; and Xue Lei for comments on the manuscript. X.Z. is grateful for the hospitality of SCSB, which enabled the collaboration.
One contribution of 10 to a Theme Issue 'Computational cell biology: from the past to the future'.
- © 2014 The Author(s) Published by the Royal Society. All rights reserved.


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Mission Viejo: Vehicle Occupant and Sheriff's Deputy Injured in Collision
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Shortly before 5:30 p.m. on Monday, October 21, a vehicle occupant and a sheriff's deputy were injured in a collision in Mission Viejo, reported the Orange County Register. While traveling eastbound on Alicia Parkway, the deputy collided with a motorist who was turning left at Trabuco Road. The deputy, who was responding to a nonemergency call for service at the time of the crash, sustained minor injuries and was transported to a local hospital. Emergency responders transported the occupant of the other vehicle to a hospital to receive treatment for moderate trauma. A Good Samaritan who helped extinguish a fire in the deputy's vehicle was also taken to a hospital for minor smoke inhalation. The CHP is investigating the crash.
Mission Viejo accounted for 1 of the 71 fatalities and 349 of the 17,031 injuries motor vehicle occupants suffered in collisions that occurred in Orange County in 2010, according to the California Highway Patrol's Statewide Integrated Traffic Records System. The California Office of Traffic Safety compares the crash data of cities with populations of a similar size, ranking those with the poorest records the highest, starting with 1st place. That year, Mission Viejo ranked 81st out of 103 cities with populations of between 50,001 and 100,000 for its incidence of fatal and injury collisions.
After a motor vehicle collision, those who were injured may file personal injury claims in order to hold the at-fault parties liable for their recovery-related expenses, such as for medical bills, lost wages, and pain and suffering. For more information on the personal injury claims process after an auto accident, please call 866-981-5596.
Everyone at Allen, Flatt, Ballidis, and Leslie would like to wish a full recovery to the vehicle occupant and the sheriff's deputy who were injured in the collision.
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Owl City aka Adam Young continues to promote his upcoming fifth studio album, titles 'Mobile Orchestra'. Earlier today he released a promotional single was released and it's actually a very lovely song. After the massive success and heavy, heavy radio play of his single 'Fireflies', I think everyone kind of grew a little tired of his sound. With the two songs released from this album thus far, Adam has created a new sound that is much more current and less auto-tuned than his previous records. 'My Everything' is an enchanting little synth-pop love song that includes a very catchy "hallelujah"...more
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Been holding off to share this news as we wanted to share the lead single along with the album announcement. "Fireflies" singer, Owl City, announced his fifth studio album earlier this week. The album, titled "Mobile Orchestra," will be available worldwide July 10, with pre-order going up tomorrow (Thursday). "Mobile Orchestra" has 13 songs, featuring collaborations with artists like Jake Owen, and Hanson. "Verge," the album's lead single's features one of 2014's breakout stars, Aloe Bacc. It will be made available for purchase tomorrow, along with the album's iTunes pre-order. Take a listen below! "Mobile Orchestra" track listing Mobile Orchestra...more


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