Being a student should be one of the most memorable and productive times of your life. This is the period to gain knowledge, skills and experiences to help you compete well in life. Such periods are not without challenges. Our dedicated academic support department provides a personal and practical support to college and university students to manage their learning and other academic demands.
We're able to provide you with support that is tailored to your needs such assistance with personal care, mobility, meals preparation and nutritional support as well as with academic work and other tasks. We have carefully selected support workers and personal assistants with university and college life experience to support you to attend lectures and social events to enable you gain exciting and memorable experiences at this stage of your life.
We're here to help you at a time that you require assistance, contact our dedicated team which is led by Andrew Malcolm who was previously a Head of student support of a local university to discuss your requirements. Call us today on 0203 643 5295 or request a call back and we'll return your call.
Verity Healthcare Academic Support team are at hand to provide extra help such as one-to-one sessions or more complex care to students with dyslexia, dyspraxia and other physical and learning difficulties whilst studying at college or university. The support services are flexible and tailored around your needs and to help you to enjoy and make the most of your time at college or university.
Our dedicated nurses, personal assistants, care and support workers and academic tutors have many years of experience in providing a wide range of provide support in most situations, covering long and short term, live-in care or daily care.
Our staff are carefully chosen to ensure their skills and expertise are well matched to your personality and care needs.
We find an initial conversational assessment to understand the wide range of needs and support required is the foundation to providing you with first class services. Even more importantly, we offer uninterrupted and steady service by assigning a main personal assistant or support worker who will attend to your needs consistently with a backup staff who will step in when your regular personal assistant is on leave or unable to attend. Receiving care from the same personal assistant and support worker is vital in enabling you to receive exceptional assistance to make your college or university life special and meaningful.
When you contact us, you'll be assigned a dedicated academic support manager who is an experienced educational nursing staff. This manager will work with you to assess and establish the type of support you require, the college or university personal assistant or support worker you're looking for and the kind of support or care you need. The assigned manager will have oversight responsibility for your care package from start to finish.
We implement a care or support plan which is reviewed and where necessary revised to ensure that the care and support you receive meets your changing needs so that you have complete peace of mind no matter your needs. All our services are managed by highly qualified care manager and regulated externally by regulatory bodies such as Care Quality Commission to ensure that the services that you receive are exceptional and tailored to your personal needs.
As part of the assessment process, your dedicated manager will communicate with social services and your college or university to identify the facilities that will be suitable to your needs and take the best advice on the appropriate accommodation that will be suitable to your needs. Your assigned managed will ensure that that the right assistive technology facilities including mobility aids are available before you arrive.
Your personal assistant or support worker will be available to support you throughout the academic year and time at college or university. You'll have the cover personal assistant to support you if the main personal assistant goes on holidays and breaks. You can be assured that the same routines will be maintained and the same familiar face will be by your side.
Our dedicated academic support services team are available to support you. Contact the team today to discuss your requirements. Call 0203 643 5295 or email us.
We are capable of providing academic support services to students at college and university – undergraduate and postgraduate students throughout the UK. Past students who used our services have expressed their great appreciation for quality of services received from our college support workers and university personal assistant and how these services have helped with their education and social life.
We're able to organize bespoke services to suit your specific needs.
Get in touch to discuss your academic support needs on 0203 643 5295 or request a callback and we'll surely return your call immediately.
From experience, we've found that it is always essential to arrange for academic support and personal care for college university ahead of time and as early as possible. You may have to plan a year or more in advance of college and university admissions and entry. This is to ensure that funding support for your personal and academic needs are in place.
We can help your to arrange your needs and to get referral from a healthcare professional. There after we can help you with the assessment process to identify the kind of support you need and also to identify the most suitable support worker or personal assistant to suit your needs and preferences.
University or College provide support for students with disability to ensure that they start out well with further and higher education. You may contact the learning support department of you college or university and speak with the learning support coordinator or disability advisor about disability allowance and any other needs and the type of support they provide. You're only allowed to contact and apply for Disabled Student Allowances when Student Finance England has asked you to do so. This is why it is absolutely essential that you contact Student Finance England as soon as possible and let them know your circumstances.
The Disabled Students' Allowances (DSA) can offer students extra financial support up to about £25,000 based on the nature of course or course intensity. You're strongly advised not to buy any equipment until you've been assessed by Student Finance England – you won't be reimbursed for it.
If you'd like us to help in contacting the relevant institutions and persons on your behalf, please contact us today.
Here's what our clients say about the quality of academic support they receive.
We'd love to hear from you so we can support you achieve your life dreams and educational aspiration. If your require further information on Academic Support Services, or any of our services, please contact one of our advisors on 0203 771 5653 or email us: info@verityhealthcare.co.uk.
We're available throughout the week 24/7 to talk through the academic support services and any other options available to you. Call 0203 643 5295 or request a call back and we will return your call.


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Keith Miles
New album available now!
New review from Rootstime
Thanks to Freddy Celis for this wonderful review. Excuse the google translation from the Dutch.
Then in 2006 we met with Keith Miles from his album "What It Was They Became" We already had a suspicion that the latter would not be what we would hear this storyteller from Nashville, rhythmically beating heart of country music.
Of course that sound is also reflected in his new CD "Beyond The Headlights" with a variety of local musicians were included. Producer of the album is Jack Sundrud which itself is primarily known as bassist for the legendary country rock group "Poco". It is ultimately an eleven containing songs, smooth album with nine songs that the listener's own undeniably a comparison with artists like John Prine or Guy Clark will make do.
The first song "Road I'm On" is an uptempo country song about leaving the past behind. Then follows a banjo and played bluegrass-inspired song "7 Cent Cigar Blues". Despite the fact that his daily activities consist mainly of office work Keith Miles has always made some time to compose their own songs and narrative lyrics to write. The intensely beautiful ballad "The South" on this CD is typical of his beloved song style.
In "Sweet Waters" he also shows some of the jazz music in his songs like vibrafoontje through the process and this number is highly contagious. The only real cover of "Beyond The Headlights" is the song "Them Dance Hall Girls", a traditional sounding song from 1971 of the folkduo Fraser & DeBolt. There is also a clever adaptation of an old traditional "Samson and Delilah" we still know the ancient version of The Grateful Dead '.
Keith Miles is a musician who is very expressive way his whole heart and soul into his songs and explains that is made clear again in songs like "I Like To Drive" and "Iowa" and in the final full emotional masterpiece "Memories Of You". Craftsmanship would be a good term for the review of this CD to close.
About the songs
Jack Sundrud and I wrote The South as an homage to the place and the literary history it evokes. We included nods to Mark Twain, Thomas Wolfe and Margaret Mitchell. The orginal song did not have a bridge, and Jack and I wrote that prior to going into the studio. That's the section that talks about "look homeward all you angels."
Angela Primm and Gale Mayes did an outstanding job on the back-up vocal, harkening the spiritual feel the song demanded.
I played a Martin Ditson guitar on this cut. The Diston has a really deep body and sound.
Cool albums reconsidered 2
Cool Albums Reconsidered . Peter Rowan
In 1993, Peter Rowan released "Awake Me In the New World," an absolutely stunning musical reconsideraton of Derek Wolcott's book "Omeros." which was in itself a reconsideration of Homer's Odysseus.I recall that the album affected me for almost a full year. Every time I listened, I heard something new. To my mind, it is one of the coolest concept albums I've listened to. I'm sure you have had an album affect in you in a similar way.
Cool albums reconsidered
…from my MySpace blog in 2006…
Cool Albums Reconsidere 3/4 Walter Hyatt, Rickie Lee Jones
Walter Hyatt's King Tears was released in 1996. Hyatt had performed for years in the super Texas group, Uncle Walt's Band. If you like great vocals, check out Walter Hyatt. He only released two solo albums before he was killed in an airplane crash in Florida. Picking a favorite Rickie Lee Jones album is like deciding which finger you like best. But since I'm in the 90s here, I'm going with Pop Pop, a collection of old standards and movie tunes. As always, the Duchess of Coolsville was cool before it was cool.
Copyright © 2022 Keith Miles

redpajama_set_name: RedPajamaCommonCrawl


Welcome you all to Drink Beer, Neglect Family! Today, what is your core objective during this fun and splendid game? The answer will be revealed right after you press the Start button!
So, what's up? The game's requirement is little different from others! Yes, players are assigned to a special mission of helping a disillusioned man drink beers as many as possible. That's because he feels disappointed in his family. Thus, please assist him in forgetting his beloved for a while! A lot of challenging stages are now ready to be solved in this interesting game. Try to bring the man to the final round while achieving the high score! Once he drinks a cup of beer, something negative will happen (blinking eyes, throwing up, restricting the movement ability, etc.) Hence, be careful! Always stay focused, since all of such the effects aren't good. The man will surely tumble down the platforms if he feels dizzy.
Staying away from any obstruction along the way is one of the effective ways to conquer Drink Beer, Neglect Family! Good luck!


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Pom Poko
Studio Ghibli Collection
Parental Guidance Recommended
Parental guidance is recommended for younger viewers.
NOTE: Low Level Violence
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"So amazing"
Review by Jordyn on 17th December, 2013
This film is certainly another amazing Studio Ghibli film, filled with fun, action, adventure and many morals that are interlaced through many of Studio Ghibli's other films.
The way in which the movie is done is quite ingenious, with it being from the Raccoons point of view rather than that of the humans in the film, and the mischief the Raccoons get up to in an attempt to save their home from advancing human interference will have you in stitches with laughter.
It's certainly a feel good family film with aspects that will appeal more to adults as well, as any good family film has.
Review by Nurul on 9th February, 2007
The cover may not look very cool. But this movie contain an important message…
A strong message…Care for the Nature's creature… Not to mention, this is such a fun and funny movie to watch!
Quite like the soundtrack…classic nippon music…
U learn quite alot of japanese/asian culture from here…in the sense of what they believe in. :)
Everyone needs to watch this!
Pom Poko (Heisei Tanuki Gassen Ponpoko) is a 1994 Japanese animated fantasy film, the eighth written and directed by Isao Takahata and animated by Studio Ghibli.
POM POKO is a tale of the clash between modern civilization and the natural world. The Raccoons of the Tama Hills are being forced from their homes by the rapid development of houses and shopping malls. As it becomes harder to find food and shelter, they decide to band together and fight back. The Raccoons practice and perfect the ancient art of transformation until they are even able to appear as humans. In often hilarious ways, the Raccoons use their powers to try to scare off the advancement of civilization. But will it be enough? Or will the Raccoons learn how to live in balance with the modern world?
Celebrate the magic of the forest and the beauty of the creatures who live among us in POM POKO – on DVD for the first time ever. From the Studio Ghibli Collection.
Feature Length Storyboards
Original Trailers
Studio Ghibli Trailer Reel
Won Mainichi Film Concours Award, Best Animated Film (1995)
Won Japanese Academy Award, Special Award (1995)
Pom Poko Movie Reviews
"Director of the powerful animated film Grave of the Fireflies, Takahata Isao, went in a different direction for his 1994 Studio Ghibli outing with Pom Poko. The fantastical story with its roots in Japanese mythology and hints of Orwell's Animal Farm, is set in the booming suburbs of Tokyo in the 1960s. Following a group of magical, shapeshifting raccoons who come together to fight of the encroachment of human expansion into their habitat, the film is comedic, sentimental, and environmentally driven at the same time. The story, hitting at a time when Japan's economy was in slump, the film used the 1960s urban boom to turn a mirror on he unabated greed and unrestricted environmental destruction of Japan's corporate world…Pom Poko won the award for Best Animated Feature Film at the 1995 Annecy International Animated Film Festival." 4 out of 5 stars Blu-rayDefinition.com
"A posse of shape-shifting raccoons wage war on humanity to protect their land in Studio Ghibli's strangest adventure. While elements of environmental fable and Japanese folklore share kinship with Hayao Miyazaki's work, the subversive humour and anarchic animation are writer/ director Isao Takahata's own. Whether staging freakish parades or attacking foes with their voluminous testicles, these raccoons are truly wild. So is the film; while its undisciplined story is stitched together by voiceover, the ambition is bracing as Takahata fires off potent asides about societal progress and revolutionary movements en route to a deeply moving conclusion." 4 out of 5 Stars, Total Film
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Video Game Brainwaves Used to Fight ADD Researchers studying Attention Deficit Disorder (ADD) are lauding the development of video games that reward focus and concentration by using electrodes to monitor players' brainwaves. Many clinicians are embracing the technology as a useful treatment tool for young patients suffering from ADD.
Video Game Brainwaves Used to Fight ADD
July 24, 20061:00 PM ET
Heard on Day to Day
Laura Sydell
Researchers studying Attention Deficit Disorder (ADD) are lauding the development of video games that reward focus and concentration by using electrodes to monitor players' brainwaves. Many clinicians are embracing the technology as a useful treatment tool for young patients suffering from ADD.
Stanley Yang's company, Neurosky, has developed its own brain wave reading technology for playing video games. Laura Sydell, NPR hide caption
Laura Sydell, NPR
Stanley Yang's company, Neurosky, has developed its own brain wave reading technology for playing video games.
NOAH ADAMS, host:
It's DAY TO DAY. I'm Noah Adams. In a few minutes, one writer's story of her struggle with the highs and lows of mental illness. But first, if you really put your mind to it you can make it happen. That is increasingly true in the world of video games. There are new games in which the intensity of a player's concentration and focus can virtually lift a table or send a car racing faster. While these games may be fun, as NPR's Laura Sydell reports, they are also helping people with Attention Deficit Disorder.
LAURA SYDELL reporting:
Scientists have been studying human brainwaves since the 1920s. By putting electrodes into certain parts of the scalp it is possible to measure the electrical activity of the brain. The resulting signal can be measured on paper or by computer. Eight-year-old Julia Mather(ph) is playing a commercially available game called Splashdown on her Sony Playstation. Hooked up to the game console and to Julia is another technology made by a company called CyberLearning. Julia wears a cap with electrodes on it that measure brainwaves, which indicate how closely she's paying attention. She has attention deficit disorder, or ADD. Julia plays the game with a normal handheld controller, but when her mind wanders...
Ms. JILL MATHER (Julia's Mother): The first thing that happens is you lose your steering control, and then if you can't pull it together pretty fast, you lose your speed.
SYDELL: That's Jill Mather(ph), Julia's mother. She and her other two daughters also have ADD. For the last six months, the family has been working closely with a doctor who prescribed the CyberLearning technology. Mather says playing these games for 45 minutes several times a week has changed all of their lives.
Ms. MATHER: In six months, the kids are off their meds, I'm off my meds. This one is reading. I didn't think she'd be able to read. It was a horrible, horrible nightmare. And she's reading.
SYDELL: Not only is she reading, but she and her sisters are having a good time treating their ADD.
Ms. MATHER: It's sit down and we're going to do our neurofeedback. And it's not painful.
SYDELL: The CyberLearning technology costs just under $600, but it's thousands of dollars more to work with a clinician who monitors the exercises. The computer interface, used by CyberLearning, was originally developed by NASA to measure the astronauts' concentration. Dr. Alan Pope, a research scientist at NASA knew that similar technology known as neurofeedback have been useful to individuals with ADD. He wondered if neurofeedback technology would be more effective if it was hooked up to games. A study proved him right.
Dr. ALAN POPE (Research Scientist, NASA): We also noticed that there were dropouts in the group that had to put in 40 sessions of training with simple graphic displays and no dropouts in the video game treatment group.
SYDELL: Playing games using brainwaves is so much fun that now other companies are looking to market similar technology for entertainment.
Mr. STANLEY YANG (CEO, NeuroSky): Wipe everything away from your mind, relax, and take a deep breath.
SYDELL: That's Stanley Yang, CEO of NeuroSky, a Silicon Valley startup that's developed its own brainwave reading technology for playing video games. Yang is talking to me. I've got electrodes on my scalp hooked up to a computer and I'm trying to raise the level on a meter that gets higher the more relaxed I am.
I guess I'm jut not relaxed, am I?
Mr. YANG: No, you're not. What you're doing is you're paying attention to the meter.
SYDELL: The brainwave measurement won't replace the handheld gaming controls, but NeuroSky's CEO Stanley Yang thinks it will add another dimension to game playing.
Mr. YANG: If you're in a Harry Potter game where you try to expel the Dementor, but you have to have happy memories in your head, so how does a computer know if you have happy memory or if you're happy in your head or not.
SYDELL: In fact, a good question might be how much can a computer know? Scientists within NeuroSky and other researchers are still trying to determine the meaning of particular brainwave activity. Yang believes we've just scratched the surface.
Mr. YANG: Eventually, maybe we will achieve a way of complete interface between the human mind and the computer somewhere down the road. Like the complete Matrix style lifestyle maybe, you know, some 50 years from now.
(Soundbite of movie The Matrix)
Mr. LAURENCE FISHBURNE (Actor): (As Morpheus) You have to let it all go, Neo. Fear, doubt and disbelief. Free your mind.
Mr. KEANU REEVES (Actor): (As Neo) Whoa.
SYDELL: Well, for now, mind reading computer games are meant to be fun. NeuroSky expects the first games using its technology to be out next year. Laura Sydell, NPR News, San Francisco.
Related NPR Stories
The Marketplace Report: ADHD Skin Patch April 7, 2006
FDA Probes Safety of Attention-Deficit Drugs Feb. 9, 2006
Dealing with ADHD as an Adult July 12, 2005
Study Links TV, Attention Disorders in Kids April 5, 2004
Report: Use of Ritalin Higher in Boys Feb. 3, 2003
Ritalin Debate Dec. 17, 2001
Neural Feedback Info and Equipment at SmartBrainGames.com
Neurosky.com


Our customer is a major automobile builder and manufactures its major engine components in-house. These forged camshafts needed to be de-flashed and de-scaled prior to turning. The method in use at the time was a hand operation using a coated abrasive disc on a hand grinder to knock down the parting line, followed by high pressure blasting with steel shot to remove the iron oxide scale. This system was difficult to quantify and hard to control, in addition to being very labor intensive. CDMC deburring engineers consulted with our customer and devised a highly productive and predictable solution to all their needs.
We applied our extensive knowledge of brushes to this application, incorporating seven brush heads at five work stations to perform a complete de-flash and de-scaling. Our customer insisted that all the iron oxide scale be trapped and collected in a container that was safe and easy for operators to empty. A large Torit collection unit mounted to the top of the machine filtered the fine particles and separated the heavier particles into a metal container accessible from the shop floor. CDMC developed a new urethane impregnated brush core specifically for this application.
The part is first de-flashed by a massive four-head brush array fitted with the newly developed brush cores, aggressively reducing the parting line. At the next four stations a rising and falling single-head wire brush further reduces the parting line and removes the last traces of scale.
Our customer specified a very close tolerance for parting line projection, beyond which the turning tools would wear too fast. As you can see from the After part picture below, not only was the line knocked down below spec, it was virtually eliminated. The parts are rotated on the holding spindle at each brushing station to insure uniform de-flashing. An on-site robot loads and unloads parts.


my thoughts and prayers are with you and your town. i, too, have little separation from you and feel what you feel. deep breaths, clearing the mind, cup of tea before bed. be strong. . .
We must be neighbors, because I live in the same small town. My son is too old to have known Rachel but I have a friend who's kids knew her. It is horrific; and has plagued my mind ever since I heard the news. A parents worst nightmare. Such a beautiful young sweet girl, with a small baby. There is no justice strong enough for anyone who would do this.
We probably have. It truly is a small world.
All of us are joined as one when something like this happens.


Please note the responses to the FAQ below are provided for general information only. Please read our standard terms and conditions, which form part of our contract with you, for the definitive information.
The entry price for our standard experience is £2,750.00. This 30-minute experience (minimum 20 minutes airborne) can be extended by purchasing additional flight time. See our website booking facility for further details.
If you are considering other suppliers, when comparing packages, it is important to make sure exactly how much FLIGHT (airborne) time is included within your experience.
We will be pleased to arrange bespoke packages. These can include the opportunity to fly in formation with another Spitfire, Hurricane or both aircraft.
We also have a limited selection of merchandise available including commemorative mugs and books.
Some passengers choose to fly generally straight and level, whilst others enjoy a more dynamic flight. Subject to suitable weather conditions, all passengers are offered the opportunity to experience aerobatic manoeuvres in the Spitfire, including a Victory Roll.
Am I able to take the controls?
Subject to the approval of your pilot, you will be permitted to handle the controls once the aircraft is established in level flight and away from the ground.
Can I get to the coast in 20 minutes?
Twenty minutes is sufficient flight time to go to the Thames Estuary and towards the Weald of Kent. If you extend your trip by an additional 15 minutes, this will allow you to get to Beachy Head where you can see the famous lighthouse and white cliffs. An additional 25 minutes will take you to the white cliffs of Dover.
We fly all year round everyday of the week except Mondays and selected bank holidays. Schedule dates can be found online, if your preferred date isn't listed please call us as we can usually arrange extra days by arrangement. All dates are subject to Weather.
Why should I fly at Biggin Hill?
There is no more iconic a location than Biggin Hill, a crucial RAF Sector Station in the Battle of Britain and synonymous with Spitfires and Hurricanes. The Heritage Hangar where the flights take place is the world's leading Spitfire restoration centre. The knowledge, experience and care available here is unrivalled. The other factor to consider is that Biggin Hill has tarmac runways which means that as soon as it stops raining, flying is back on, it does not get water-logged like a grass airfield can.
Are there any age, weight, height or medical restrictions?
The minimum age to fly in the Spitfire is 18. There is no minimum height but a maximum of 6ft 6 inches (198cm). The maximum weight is 230lb (16 stone 6lbs) (105 Kg). You will be weighed and measured on the day.
Further to the above restrictions, your physique must be such as to permit free movement of the controls. This will be checked by the pilot on the day, and exceptionally, some of those fulfilling the basic requirements above, may still be unable to fly.
You need to be physically agile enough to climb into and out of the aircraft and safely experience the dynamic nature of the flight – if you have any concerns over your suitability you should consult your GP. You should not participate if you are medically precluded from holding a driving licence, suffering from a cold, are pregnant or suffering from any condition affecting your breathing or consciousness.
I am concerned about the maintenance of the aircraft – who does it?
We operate from the Biggin Hill Heritage Hangar, which is the largest Spitfire restoration and maintenance facility anywhere in the world. At any time we typically have 10-15 Spitfires, Hurricanes and other aircraft on site.
We have our own CAA approved maintenance organisation, with licenced engineers on site, who have access to one of the largest Spitfire spares holdings in existence.
What can we do during the flight?
The content of the flight is very much determined by the passenger. Some like to fly generally straight and level and soak up the experience whereas others like to do some manoeuvring and aerobatics. You will get an opportunity to discuss your flight and what you would like to do with the pilot before you depart.
Yes gift flights are available and can be bought via the website without a date booked. The recipient can book their own date with us.
How long should I allow for the experience?
While four hours is usually sufficient to cover briefings and the flight, it is recommended that you make as much of the day available as possible to cover unforeseen delays such as weather.
The actual duration of most flights is around 30 minutes from engine start to shut down. This provides approximately 20 minutes airborne. Exact timings depend on external factors such as the runway in use and air traffic control requirements. Please allow plenty of time at the venue to cover pre-flight briefings, Q&A sessions with the pilot, photography time, and for any weather delays.
You can arrive in normal everyday clothes, but you will be kitted out with your own personal protective equipment consisting of a flight suit worn over your clothes plus helmet and gloves. You will need to provide your own footwear which should provide a good grip.
Can I bring friends and family along with me?
Accompanying friends and family are welcome, but limited to a maximum of four guests per passenger. While we would like to be able to welcome additional guests we do not have the facilities to accommodate significant numbers. Great viewing facilities exist with a balcony offering panoramic airfield views. Guests other than the four permitted can spectate from the Lookout Coffee Shop at the airfield entrance.
Can I bring a someone in a wheelchair?
Unfortunately, our viewing facility is elevated which provides an excellent view of the activity at Biggin Hill. Access is by a flight of stairs. However, the facility has wheelchair friendly access and an alternative waiting area, albeit with no view of the airfield.
We have vending machines available on-site providing snacks, tea and coffee. There are several cafes within a short drive.
If your flight has to be postponed due to poor weather you will be offered an alternative date or dates. We will attempt to contact you the day before your flight if the weather is looking unsuitable. If you hear nothing, please arrive for your scheduled report time.
What happens if the aircraft becomes unserviceable?
If your flight has to be postponed due to a technical fault with the aircraft, you will be offered an alternative date or dates.
Can I take a camera or is there an in-flight video available?
As you are not able to take a camera up with you, we provide a video recording of your flight free of charge. No technology is 100% reliable and as such the content of the recordings cannot be guaranteed, however they have been very successful in virtually all cases.
Can you take a deposit or can I pay by instalments?
No, we take the full amount when you make a booking. Places cannot be reserved without full payment. Credit and debit cards are accepted.
In what order do passengers fly?
Passengers usually fly in the order in which they were booked, however the order can sometimes be changed to suit operational requirements, or altered by request, subject to the agreement of your fellow passengers.
We use a number of highly experienced pilots to fly our passengers. All our pilots hold a commercial flying licence and a valid medical certificate. They come from a wide variety of backgrounds, both civil and military, but all share a great enthusiasm for flying these historic aircraft.
Unfortunately, pets are not allowed as this is a working hangar environment on a live airfield.
Is there a discount if I book more than one trip?
Unfortunately, we are unable to provide a discount. Each passenger is carried separately there is no saving to be made for multiple bookings.
Hangar Tours - are they suitable for kids?
How do I view my SD Card Videos?


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8 Social Media Profiles You Should Be Following for Financial Advice in 2018
Meredith Simonds
January 3, 2017February 5, 2018Apps & Financial ResourcesBig Money Decisions, Budgeting & Expenses, Featured, Spend Less923Meredith Simonds
Whether you're hopeful or discouraged about your personal finances in 2018, give yourself some daily motivation to do better. For a regular dose of inspiration, follow these personal finance experts on all things money management.
1. Deacon Hayes, @WellKeptWallet
With a brand new car and two condos, it looked like Deacon Hayes and his wife had their financial house in order. That changed the day Deacon sat down to look at their finances more closely.
The Hayes were deep in debt and, with more money going out than coming in, they wouldn't be getting out of it anytime soon. Determined to get a handle on things, the Hayes took a personal finance class, read books, and talked to money-savvy people.
Doing their homework paid off, literally — the Hayes managed to pay off $52,000 in just 18 months.
Expertise: Debt management
Best platforms to follow: Twitter and Facebook
2. Erin Lowry, @BrokeMillennial
Despite the name of her blog and book, Broke Millennial-founder Erin Lowry wants you to know that she's not actually broke.
On the contrary, this millennial has mastered her money since she graduated from college — not because her first job paid a ton of money, but because she was able to graduate debt-free.
Attending her first-choice school would have meant $80,000 in student loans. She opted for a different college, which offered enough scholarship money for her to graduate debt-free.
Expertise: Financial independence
Best platforms to follow: Twitter and Instagram
3. Suze Orman, @SuzeOrmanShow
While working as a waitress after college, Suze Orman decided to open her own restaurant. When the customers she'd been waiting on for six years learned of Orman's dream, they collectively offered to loan her a whopping $50,000.
Orman went straight to the bank to open a money market account that would keep her money safe and growing. "Just sign here on the dotted line and we'll see what we can do," said the broker. What he didn't say was that he actually put Orman's money into a riskier investment strategy. After three months, her account was wiped out.
It was this devastating experience that inspired Orman to became a broker herself. (She also sued and won back all the money she'd lost.) Instead of opening that restaurant, Orman became one of the world's most trusted voices in personal finance.
Expertise: Investing, budgeting, debt management
Best platform to follow: Twitter
4. @MrMoneyMustache
This anonymous blogger retired with his wife at 30 years old. That didn't happen because Mr. Money Mustache was born into money or because he or his wife made millions.
His secret (and advice to you)? Cut your expenses and save at least half of your income. Mr. Money Mustache says they saved 66 percent of theirs: "In under ten years, we woke up and realized we didn't have to work for a living anymore."
Expertise: Budgeting and saving
5. David Ning, @MoneyNing
David Ning's approach to personal finance education is an empowering one: "There's really two basic goals in building a solid net worth — make more income and save more of it … It's time to learn how to maximize your efforts and channel your desire of reaching financial freedom into results."
When you need a motivational boost, you'd be hard-pressed to find a better-curated collection of personal finance quotes than the ones in Ning's Twitter feed.
6. Dave Ramsey, @DaveRamsey
When he was just 26 years old, Dave Ramsey was already making $250,000 a year with a net worth of over one million dollars. Unfortunately, he was also in a lot of debt. It turned out to be too much to overcome and, within a few years, he and his wife had lost everything.
It was this loss that inspired Ramsey to figure out how money really works. "I came to realize that my money problems, worries, and shortages largely began and ended with the person in my mirror," says Ramsey. "I also realized that if I could learn to manage the character I shaved with every morning, I would win with money."
Expertise: Investing, real estate, budgeting, debt management
7. Jason Vitug, @Phroogal
Accomplished at work but unsatisfied, Jason Vitug quit his job and sold everything he owned to backpack through 20 countries in 12 months. He was living the life he wanted and realized he wanted to help others do the same.
Vitug's website combines search and social through an ask-and-answer platform on all things personal finance. He and his team have also hosted dozens of events across the country on Phroogal's "Road to Financial Wellness" campaign.
Best platforms to follow: Twitter, Pinterest, and Instagram
8. Liz Weston, @LizWeston
Liz Weston bought her retirement property when she was just 26 years old. The only problem is she bought it in Alaska, 80 miles from the nearest road. She had the right intention, but the wrong direction.
Today, Weston is one of the most widely read personal finance columnists online and the author of several books. Check out her Ask Liz section on her website; your question could be featured in a future column.
Expertise: Credit, debt management, budgeting
What are you hoping these personal finance experts will help you accomplish in 2018? No matter your goal, there's a right and a wrong way to set your intention. Learn the psychology of successful New Year's resolutions, and how you can accomplish your goals this year.
Previous: 5 Ways to Be More Mindful With Your Money in 2018
Next: Dry January Doesn't Just Improve Your Health, It Helps Your Wallet Too
Published in Big Money Decisions, Budgeting & Expenses, Spend Less


text:
Annotated Volcano: A Spectacular View of Tenerife From the ISS
Author: Erik KlemettiErik Klemetti
Tim Peake/ESA
On Wednesday, astronaut Tim Peake (currently on the International Space Station) posted a stunning image of Tenerife, the largest of the Canary Islands. In it, you can clearly see the tallest peak in the Atlantic Ocean (Teide), but also the giant Las Cañadas caldera along with the long volcanic rifts that splay off like arms of the Canary's biggest volcano.
The Canary Islands are likely caused by an upwelling of hot mantle material called a hot spot (or mantle plume), creating a chain of volcanoes as the African Plate moves (much like how the Hawaiian Islands are formed). However, there is still debate about whether the inferred plume actually exists.
Tenerife is one of the seven large islands in the Canary Islands. It is a complex of volcanic material, with the ancestral volcanoes of the Teno (~5-6 million years old) and Anaga Massif (4-5 million years old) on the northwestern and northeastern corners of the island. (Anaga is not visible in the ISS shot.) The younger volcano straddles the middle of the island, joining the older relict shield volcanoes. The main edifice you can see on the island is the youngest area: Teide, the adjacent Pico Viejo and the NW and NE rift zones.
From the floor of the Atlantic Ocean around the island to the top of Teide is a remarkable 7.2 kilometers (~24,000 feet) of relief. The two cones of Teide and Pico Viejo sit inside the Las Cañadas caldera that is 10 by 17 kilometers (bigger than Crater Lake or Kilauea's caldera). We still don't know exactly how the caldera formed, as both a collapse of the land surface in an explosive eruption or landslides could have carved the feature.
The two volcanically-active rift zones head off 13 kilometers (8 miles) to the northwest and 10 kilometers (~6.2 miles) to the northeast from the caldera. A third rift that heads south has only experienced seismicity but no known eruptions.
Now, although Teide is the highest point on the island it isn't the location of the most recent volcanism on Tenerife. The last eruption on the island was in 1909 and it came from a cinder cone (Chinyero) on the NW rift, which has historically been the most active area on the volcano. That eruption lasted 10 days and was a rift eruption that coalesced into a single cone—similar to what we saw during the Kamoamoa eruption of Kilauea.
In 1798, a small eruption occurred on the flanks of Pico Viejo, but you need to go back to ~800 AD (plus or minus 150 years) to find evidence of an eruption from Teide itself. The 1706 eruption of Montaña Negra from the NW rift destroyed the town of El Tanque and its harbor in less than 15 hours when lava flows overran the region. A week later, more lava flows did in two more towns.
About 2,000 years ago, Tenerife unleashed a surprising large explosive eruption for this kind of shield volcano. Volcanoes like Tenerife and Kilauea are hot spot volcanoes that tend to have eruptions that produce lava flows, but in ~80 AD, Pico Viejo produced an explosive eruption that released ~0.3 cubic kilometers of pumice and ash, along with some small domes, totally a VEI 4 eruption.
This change in eruption style came from a change in the magma, from basanite (low silica, runnier) to phonolite (higher silica, stickier). Now, Tenerife hasn't produced another eruption like this since, but a paper by Ablay and others (1995) suggested that there could be more of the explosive phonolite magma lurking underneath the caldera.
The biggest threat to the ~900,000 people on Tenerife today doesn't come from a potential explosive eruption but rather the lava flows and cinder cones that could erupt on the NW rift zone. These eruptions could spread some ash across the island and start fires on the slopes of Tenerife. It even seems that activity from Teide has been on the decline over the last 30,000 years, so another eruption from the peak might be increasingly unlikely.
Occasionally a small earthquake swarm will occur under Tenerife (including a notable one in 2004). These swarms are likely business-as-usual at Tenerife, with magma rising from ~7-10 kilometers under the island. However, right now, things seem quiet under the island. The Canary Islands were home to an impressive eruption of El Hierro in 2011-12.
Check out the previous Annotated Volcanoes here: Cerro el Condor and Nabro
#remote sensing
#volcanoes


text:
CO Chipset Consumes Little Space
Staff | Sep 01, 2002
The latest member of the CopperFlite central office (CO) chipset family, the CopperFlite LX chipset is said to be the industry's smallest while significantly reducing power consumption on a per-port basis. The LX chipset is comprised of two chips that together consume less than one square inch per port. Similar to other chipsets in the family, it includes the company's eXtremeDSL features, such as eXtremeRate and eXtremeReach. The eXtremeRate allows rates up to 12 Mb/s and the eXtremeReach claims to increase potential service areas by more than 50%. For further information and prices, contact CENTILLIUM COMMUNICATIONS INC., Fremont, CA. (510) 771-3647.
Company: CENTILLIUM COMMUNICATIONS INC.


text:
Q: How to zero pad a matlab array? What is the easiest way to (zero) pad a matlab array?
i.e. given [1,2,3,4] and length 6 return [1,2,3,4,0,0]
Background
I have a data array which I would like to apply a windowing function to before running fft on the data.
I use to pass data directly to fft which would zero pad to the next power of 2, but now I need it zero padding before the fft so I can multiply by the window function.
fs = 100;                          % Sample frequency (Hz)
t = 0:1/fs:10-1/fs;                % 10 sec sample
x = (1.3)*sin(2*pi*15*t) ...       % 15 Hz component
  + (1.7)*sin(2*pi*40*(t-2)) ...   % 40 Hz component
  + (2.5)*randn(size(t));          % Gaussian noise;

m = length(x);          % Window length
n = pow2(nextpow2(m));  % Transform length
w = barthannwin( n );   % FFT Window

y = fft(data, n);       % DFT

windowed_data = x*w ; % Dimensions do not match as x not padded
y = fft(windowed_data, n); % DFT

I am aware of padarray as part of the Image Processing Toolbox, which I do not have.

A: EDIT
This method is probably even better for vectors as it does not break when they are transposed, note that it will change the original vector which may not be desirable:
myVec = 1:7;
myVec(end+3)=0

Alternately you can just concatenate zeros and the vector that you have and create a new variable with it.
myVec = 1:7;
requiredpadding = 10-7;
myVecPadded=[myVec zeros(1,requiredpadding)]

A: There is no built in function to do padding, but here is a little function to pad vector x given a minimum length n.
function y = pad(x, n)
y = x;
if length(x) < n
    y(n) = 0;
end

A: this should pad it with zeros to the nearest power of 2 for an array a:
a(2^ceil(log2(length(a))))=0;

A: The image-processing toolbox of Matlab has a built-in function to pad arrays padarray(A,dim,value
For your example:
A = [1, 2, 3, 4];
dimension = [0 1]; % pad with extra columns
size = 2; % how much to pad
B = padarray(A,size*dimension,'post') % 'post' says to pad at the end
% just for demonstration, let's pre-pad the first dimension (rows)
dimension = [1 0];
C = padarray(A,dimension,'pre') % just as an example
% or pad in both directions
dimension = [1 2];
D = padarray(A,dimension) % by default, it will pad both pre and post

returns
B =

 1     2     3     4     0     0

C =

 0     0     0     0
 1     2     3     4
D =

 0     0     0     0     0     0     0     0
 0     0     1     2     3     4     0     0
 0     0     0     0     0     0     0     0

You can also use this for multi-dimensional arrays, the dimension vector just needs to be extended correspondingly, i.e. dimension = [0 0 1] will extend in the 3rd dimension.

redpajama_set_name: RedPajamaStackExchange


14-1: Explain the role of networks in building social capital.
Networks provide social capital such as access to sources of financing, information, expertise, and support; and networks can be excellent sources for loyalty. They allow for learning and information exchange; and social capital enables access to a range of resources, including venture capitalists, angel investors, advisors, banks and trade shows.
14-2: Demonstrate the value of networks for entrepreneurs.
Relationships are key to business success, and entrepreneurs in particular will need to skillfully interact with a vast array of stakeholders. Networks provide entrepreneurs with access to private information, diverse skillsets, and power. Networks can also be relied on for personal and emotional support.
14-3: Describe different ways of building networks.
Building a network extends beyond socializing with friends and acquaintances, and it often involves active participation in organized networking events. In a new relationship, it is better to give value to get value; value is a two-way game.
14-4: Illustrate the benefits of virtual networking.
Social media sites and other forms of virtual networking provide additional channels to meet or interact with stakeholders from the world over. Entrepreneurs have a number of different virtual communities in which they can participate, with many communities offering access to a specific subset of interests in entrepreneurship. Common social media platforms like Facebook also contain groups that are similar in fashion to online entrepreneurship communities.
14-5: Explain how networking can help to build the founding team.
One of the most valuable things an entrepreneur can do is connect with individuals who serve as great complements on a founding team. Research even suggests that team-started ventures are more successful than solo-founded ventures. Networking skills can often be relied on as the means to that end.


This article is about the year 1905. For the film, see 1905 (film).
Year 1905 (MCMV) was a common year starting on Sunday (link will display full calendar) of the Gregorian calendar and a common year starting on Saturday of the 13-day-slower Julian calendar.
As the second year of the massive Russo-Japanese War begins, more than 100,000 die in the largest world battles of that era, and the war chaos leads to a revolution against the Tsar. (Shostakovich's 11th Symphony is subtitled "The Year 1905" to commemorate this.) Canada and the U.S. expand west, with the Alberta and Saskatchewan provinces and the founding of Las Vegas. 1905 is also the annus mirabilis of Albert Einstein, publishing papers which lay the foundations of quantum physics, introduced the special theory of relativity, explained Brownian motion, and established mass-energy equivalence.
January 2 – Russo-Japanese War: The Russian Army surrenders at Port Arthur, China.
January 22 (January 9 O.S.) – The Bloody Sunday massacre of Russian demonstrators, at the Winter Palace in Saint Petersburg, helps trigger the abortive Russian Revolution of 1905.
January 26 – The Cullinan Diamond is found near Pretoria, South Africa at the Premier Mine.
February 16 – At Haulbowline Base in Ireland, two explosions on board HM Submarine A5, due to petrol fumes after refueling, kill six of the eleven crew.
February 17 – At Fremantle, Western Australia, the R.M.S. Orizaba is wrecked, but all 160 passengers and the mail are saved.
February 19 – Russo-Japanese War: The Battle of Mukden begins in Manchuria.
March 4 – U.S. President Theodore Roosevelt begins a full term.
March 14 – Chelsea FC is founded.
March 17 – Albert Einstein publishes his paper On a heuristic viewpoint concerning the production and transformation of light, in which he explains the photoelectric effect using the notion of light quanta.
March 31 – German Emperor Wilhelm II asserts German equality with France in Morocco, triggering the Tangier or First Moroccan Crisis.
April 4 – In India, the 1905 Kangra earthquake hits the Kangra valley, kills 20,000, and destroys most buildings in Kangra, Mcleodganj and Dharamshala.
May 15: Las Vegas, Nevada is founded with auction of 110 acres (0.45 km2).
May 11 – Albert Einstein submits his doctoral dissertation On the Motion of Small Particles..., in which he explains Brownian motion. In the course of the year, Einstein publishes four papers, formulates the theory of special relativity and explains the photoelectric effect by quantization. 1905 is regarded as his "miracle year".
May 13 – Mata Hari debuts in Paris.
May 15 – Las Vegas, Nevada is founded when 110 acres (0.45 km2), in what later becomes downtown, are auctioned off.
May 17 – Kappa Delta Rho is founded in in room 14 of Old Painter Hall at Middlebury College in Middlebury, VT.
June 30 – Albert Einstein publishes the article On the Electrodynamics of Moving Bodies where he reveals his theory of special relativity.
July 22 – Taft-Katsura Agreement.
August 25 – 'Ancient Order of Druids' initiate neo-druidic rituals at Stonehenge in England.
September 27 – Albert Einstein submits his paper Does the Inertia of a Body Depend Upon Its Energy Content? in which he develops an argument for the famous equation E = mc2.
October 1 – Galatasaray SK is founded.
October 2 – HMS Dreadnought is laid down, revolutionizing battleship design and triggering a naval arms race.
October 16 – Russian Revolution of 1905: The Russian army opens fire in a meeting on a street market in Tallinn, killing 94 and injuring over 200.
October 30 – Tsar Nicholas II is forced to grant Russia's first constitution, conceding a national assembly (Duma) with limited powers.
October - The Fauvist artists, led by Henri Matisse and André Derain, first exhibit, at the Salon d'Automne in Paris.
November 4 – The application of the infamous and, from the Finnish perspective, unconstititional, February Manifesto, subordinating the local legislation of the autonomous Grand Principality of Finland to Imperial Russian legislation, is interrupted in the November Manifesto. The Senate of Finland is also ordered to prepare a proposition for a new unicameral representative organ elected in accordance to universal and equal suffrage to replace the outdated Diet of the Estates.
Women are given the vote and admitted to the practice of law in Queensland.
This page uses content from the English language Wikipedia. The original content was at 1905. The list of authors can be seen in the page history. As with this Familypedia wiki, the content of Wikipedia is available under the Creative Commons License.
200 people were married in 1905.
There were 0 military battles in 1905.


The digital camera industry is constantly evolving and as a result of that today there is a variety of camera models available on the market, including point and shoot cameras, DSLR cameras, SLR cameras and others, each one with its own distinctive features. However, since not everyone needs the same kind of camera, in this article we decided to present the advantages and disadvantages of the two most popular types, DSLR and point and shoot cameras, so that you choose the one that suits your needs best.
The main advantage of these cameras is their great image quality. Because they have a bigger sensor, they capture images with much less noise (the grain you often see in a picture). Less noise also means that you can shoot in very dim environments and take photographs that would be impossible to take with a point and shoot camera. Moreover, they have a reflex mirror which enables you to look through the lens instead of a see-through hole in the camera and see what you shoot. They also have a lot of buttons and controls, so once you learn how to use them, you will have a bunch of settings to experiment with. DSLR cameras enable you to use different lenses to shoot specific types of photos. There is a range of these camera tools available on the market, from telephoto to super wide angle, so choose some of these according to your needs.
One of the downsides of these cameras is their higher price tag. Plus, they are also more complex to work with as you will need some time to learn their features and find out what all the buttons serve for.
One of the greatest advantages of point and shoot cameras is their size and their light weight which allow you to simply slip them into your pocket and take them anywhere you want. This consequently eliminates the need for buying extra camera tools for transporting it. Since these cameras generally cannot separate background from foreground, they bring everything together making the scene look sharp. This can be a good and a bad thing at the same time. Moreover, they are relatively inexpensive which is another advantage.
When it comes to disadvantages, point and shoot cameras come with a smaller size sensor than DSLR, which delivers a low image quality. And since they put the entire scene in focus, there is not much you can do to isolate your subject from the background. With these cameras, you won't be able to change lenses or mount an external flash. Plus, the variety of external tools is limited to the make and brand of the device.


At the Golden Globes last night, Meryl Streep accepted the Cecil B. DeMille Lifetime Achievement Award. And she used her acceptance speech to repeatedly attack President-elect Donald Trump.
It's refreshing to FINALLY have a leader who isn't afraid to stand up to Hollywood A-listers, and others in power.
SHARE this article if you stand with the next President of the United States: Donald J. Trump!


text:
AbstractIntroductionResultsDiscussionConclusionsMethodsSupplementary MaterialsReferencesCopyright
Big Data and Network Biology 2015
Xueying Chen, Min Zhao, Hong Qu, "Cellular Metabolic Network Analysis: Discovering Important Reactions in Treponema pallidum", BioMed Research International, vol. 2015, Article ID 328568, 8 pages, 2015. https://doi.org/10.1155/2015/328568
Cellular Metabolic Network Analysis: Discovering Important Reactions in Treponema pallidum
Xueying Chen,1 Min Zhao,1 and Hong Qu1
1Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China
Academic Editor: Md. Altaf-Ul-Amin
Received13 Mar 2015
Revised19 May 2015
Accepted30 May 2015
Published01 Oct 2015
T. pallidum, the syphilis-causing pathogen, performs very differently in metabolism compared with other bacterial pathogens. The desire for safe and effective vaccine of syphilis requests identification of important steps in T. pallidum's metabolism. Here, we apply Flux Balance Analysis to represent the reactions quantitatively. Thus, it is possible to cluster all reactions in T. pallidum. By calculating minimal cut sets and analyzing topological structure for the metabolic network of T. pallidum, critical reactions are identified. As a comparison, we also apply the analytical approaches to the metabolic network of H. pylori to find coregulated drug targets and unique drug targets for different microorganisms. Based on the clustering results, all reactions are further classified into various roles. Therefore, the general picture of their metabolic network is obtained and two types of reactions, both of which are involved in nucleic acid metabolism, are found to be essential for T. pallidum. It is also discovered that both hubs of reactions and the isolated reactions in purine and pyrimidine metabolisms play important roles in T. pallidum. These reactions could be potential drug targets for treating syphilis.
As data for molecular interactions and sequenced genomes in microorganisms are increasing rapidly, network analysis provides a novel perspective for studies on the metabolism of microorganisms. When it comes to human beings, the study of pathogens is highly related with the treatment of and drug development for infectious and inflammatory diseases. Recent studies have revealed important facts about the metabolisms that microorganisms, especially pathogens, have developed mechanisms to escape from the prevention process of the elaborate network of the human immune system [1, 2]. In this paper, T. pallidum, the causative agent of syphilis, is analyzed as a successful demonstration.
T. pallidum is a spirochete as well as a phylogenetically ancient and distinct bacterial group. Despite its discovery almost a century ago, T. pallidum continues to be an enigma. The problem confronted by syphilis researchers is their failure in cultivating T. pallidum in artificial medium [3]. For years, although many scientists attempted to cultivate syphilis spirochete, only nonpathogenic treponema was found, while the virulent treponema still escapes cultivation [3, 4]. It is discovered that the failure in cultivation results from the limited biosynthetic capacity and tolerance for the environmental stress of T. pallidum that utilizes glycolysis for energy production. It lacks the tricarboxylic acid cycle and oxidative phosphorylation pathways. In addition, it is unable to synthesize enzyme cofactors, fatty acids, and most amino acids [5]. Further research about Treponema denticola (T. denticola) and T. pallidum reveals that many genes and metabolic capabilities present in T. denticola, which enable this bacterium to replicate in vitro, are absent in T. pallidum rendering the latter incapable of sustained replication under similar conditions. Due to these frustrating facts, it is aspiring to perform an analysis of T. pallidum's metabolic network in silico.
Systems biology, which provides us with an efficient way to exploring the biological mechanisms, would facilitate the study of T. pallidum. Recently, many studies have found numerous important properties of the metabolic networks such as the scale-free topology [6], network robustness [7], and a hierarchy of modules [8]. However, the limitation of computing capability restrains further exploration on the level of the whole organism. It results in attempts to find subnetworks or to cluster the network nodes. Questions about the differences and similarities among subnetworks and how the behaviors change when subnetworks are separated and grouped together are also raised. In spite of topological and graph analysis, many network models and analysis tools have been developed: biochemical reaction network and statistical influence models network [9–14] and constraint-based reconstruction and analysis [15], among which Flux Balance Analysis has been applied to many theoretical analyses [16] because in general all reactions in a system are maintaining a steady state flux. It not only gives the solution space but also provides a quantifiable method to examine various vast reactions.
It is promising to identify the virulence determinants in T. pallidum by cellular metabolic network analysis. Previous work only identifies a small number of virulent determinant genes based on the biological functions related to pathogen-host interaction [5]. Interestingly, nearly all of the T. pallidum metabolic enzymes genes are not annotated to be virulent factors because the traditional angle for virulent genes is more focused on housekeeping and pathogen-interaction processes. However, accumulated evidences link the metabolic enzymes as virulence factors in the pathogens [17, 18]. Thus reannotation of T. pallidum metabolome by comparative genomics strategy may provide further insight into the metabolic virulent factor [3, 5, 19].
Syphilitic gastritis is the case of chronic active gastritis which involves T. pallidum and H. pylori together [20]. In clinical practice, it is also necessary to demonstrate T. pallidum in gastric lesion to confirm the diagnosis [21]. So, in order to further confirm our analysis, we also investigate H. pylori as a comparison to find out differences between organisms, especially the factors which are important to their artificial cultivation.
In this paper, we cluster all reactions in T. pallidum and group them into different types based on both the Flux Balance Analysis and topological analysis. By computing the stoichiometry matrix's null space, reactions are represented quantitatively and further classified. In addition, critical reactions are identified through minimal cut set calculation. Analysis of H. pylori follows as a comparison. This paper closes with a discussion.
2.1. Clusters of Reactions and the Role Type of Reactions in T. pallidum
According to the hierarchical clustering result of 341 reactions in T. pallidum obtained from KEGG database, the network has a "hub-structure" (shell-type ordering): there is one or two clusters consisting of a large number of reactions (more than 85 reactions) while the other clusters have only a few reactions (less than 8 reactions) (Figure 1). This type of structure is associated with robust operation and efficient communication in microorganisms.
Structure of clusters of T. pallidum and H. pylori. -axis represents the number of clusters that contain the percentage (indicated by the value on -axis) of reactions.
The role type distributions in Figure 2 imply that most reactions fall into the first three types. According to the definition, reactions in the first three types are closer to their cluster center but far away from the other clusters. This phenomenon indicates a separate functional mechanism in the metabolism. There are 61, 112, 97, 20, 6, and 26 reactions in type 1, type 2, type 3, type 4, type 5, and type 6, respectively. Therefore, reactions of type 2 take the most part in all reactions; reactions of type 4 take the least part. Also, the first three types are much more than the last three types. It could be seen from the results that there are many isolated reactions; most reactions are more connected within their own clusters but have a few reactions linking them to other clusters.
The distribution of role type of the reactions for T. pallidum and H. pylori. -axis indicates the type of reactions; and -axis indicates the percentage of reactions in the corresponding type.
2.2. Calculation of Minimal Cut Sets for T. pallidum
It is known that reactions in nucleotide, purine, and pyrimidine metabolisms play an important role in T. pallidum. Here, reactions that take part in minimal cut sets are considered to be crucial to the metabolism [22]. According to our results, 28 reactions that compose 582 minimal cut sets in combination stand out. The overall average cut set size is 11.3127 and the cut set size histogram is shown in Figure 3. These 28 reactions spread in 19 clusters and all of them are type 1 or type 6 reactions except 3 type 2 reactions and 2 type 4 reactions. It means the hutches of reactions and isolated reactions have larger impact on the pathways.
The distribution of the cut set size. -axis indicates the number of reactions in one minimal cut set; and -axis indicates the number of minimal cut sets that have that amount (indicated by -axis) of reactions.
The degree distribution for the subnetwork shown in Figure 4 exhibits the combination possibilities for each reaction. All reactions are essential in purine and pyrimidine metabolisms. These combinations further make a distinction among these reactions in minimal cut sets by their significance. For example, we notice the fact that only two upstream reactions (R00300 (D-glucose: NAD+ 1-oxidoreductase) and R00335 (GTP phosphohydrolase)) and one downstream reaction (R02372 (dUTP: cytidine 5′-phosphotransferase)) distinguish themselves since they participate in most minimal cut sets.
The paths and degrees of reactions in minimal cut sets. (a) Rectangle nodes indicate reactions in purine metabolism; circular nodes indicate reactions in pyrimidine metabolism. The directed edges show the distinct pathways in the minimal cut sets which cannot be reduced further towards the objective reaction. (b) -axis indicates the reactions' ID in KEGG; -axis indicates the degrees of reactions.
2.3. Comparison with H. pylori
To further explore the functions that the reactions of each role type perform, another microorganism, H. pylori, is analyzed.
As a basic comparison, there is a clear similarity between cluster structures of T. pallidum and H. pylori (see Figure 2), one huge cluster and many small and isolated clusters. This nonuniform distribution meets the recent findings about the scale-free property of cellular networks. It is also related to the highly heterogeneous centrality distribution [23]. Moreover, the similarity of the role type distribution for those two microorganisms (Figure 1) tells that in both organisms' reactions in the same cluster are more likely to be involved with the same metabolites. Thus, the large clusters represent metabolites that have high degrees in the metabolic networks or participate in a lot of reactions and a few nodes with a great number of links, which are often called hubs, hold other nodes together.
In addition, we investigated the role type of reactions that participate in the minimal cut sets and found out that type 4 reactions occur in both microorganisms. However, type 1 and type 6 only exist in H. pylori while type 2 and type 5 only exist in T. pallidum (Figure 5). The complementarity appears in all role types except types 3 and 4. It leads to the conclusion that if H. pylori contaminates the medium where T. pallidum grows, biocide that disturbs type 2 and type 5 reactions would be a nice choice since it helps to kill H. pylori without affecting T. pallidum. In contrast, if T. pallidum is the target, impairment of type 1 and type 6 reactions could be a goal to achieve. However, type 4 reactions are essential for both microorganisms which may be untouched in purification but could be a potential target for efficient broad spectrum antibiotic.
Role type of minimal cut sets in two species. -axis indicates the role type; and -axis indicates the number of reactions in minimal cut sets of the corresponding role type.
The structure of cellular networks underlying the cellular functions and regulation appeals to researchers to reveal their relationship. Here, we analyze all metabolic reactions in one microorganism by both topological and quantitative methods to discover critical reactions. Although further experimental and clinical verification is still needed, computer simulation and analysis, along with traditional bioinformatics approaches, have frequently been proposed to significantly increase the efficiency of metabolism study of microorganism.
It is worth noticing that all the 28 reactions which are essential to T. pallidum are in nucleotide metabolism: 11 (rectangle nodes) take part in purine metabolism and the others (circular nodes) participate in pyrimidine metabolism (Figure 4(a)). This discovery is in concert with the previous work [5, 24]. As mentioned above, T. pallidum lacks enzymes that are responsible for the synthesis of fatty acids, amino acids, and so forth. Baseman et al. and the genome analysis both confirmed that T. pallidum did not take up the tritiated thymidine and lacked a thymidine kinase (EC 2.7.1.21) but synthesized DNA from uridine nucleotides [5, 24]. Both uridine kinase and uridylate kinase (the gene IDs in KEGG are TP0667 and TP0099, resp.) are present as well as thymidylate kinase (the gene id in KEGG is TP0354). T. pallidum possesses the necessary enzymes to synthesize DNA. Among these genes, TP0667 and TP0354 are responsible for 16 reactions (R00513, R00517, R00962, R00964, R00968, R00970, R01548, R01549, R01880, R02096, R02097, R02098, R02327, R02332, R02371, and R02372) in the minimal cut sets, giving strong evidence that both genes and reactions found here are critical in the metabolism of T. pallidum.
The purine and pyrimidine metabolism are indispensable constituents critical for synthesis of DNA and RNA and relevant metabolic regulation to all organisms. The mutations of these enzymes often cause lethal effect on the newborn. In total, at least 19 inborn disorders are related to purine and pyrimidine metabolism in human [25]. According to our results from minimal cut set, those reactions related to purine and pyrimidine metabolism tend to be the hub nodes in the entire metabolic network. Previous studies on the biological network revealed that the hubs with large number of interactions are associated with lethality [26]. With the important genetic function, numerous essential enzymes are identified in purine and pyrimidine metabolism. Moreover, many enzymes that catalyze these essential reactions are missed in host human. For example, one of the upstream enzymes glucose 1-dehydrogenase (NAD) not only participates in the majority of minimal cut sets, but also is missed in human. Thus, this enzyme will be one of the best candidates for the follow-up pathogen treatment experimental design.
This method leads us to view the metabolism of microorganism in a new perspective. Topological analysis has been used for drug target selection [27]. Calculated elementary modes of human parasite Trypanosoma brucei find out that all three modes obtained are in agreement with experimental observations. Klamt and Gilles have verified the relationship between elementary modes and minimal cut sets [22]. However, interpreting topological calculation, we should keep in mind that this kind of analysis tends to be confined to several determined reactions because the results represent idealized situations. By defining the role type of each reaction, we extend the potential reactions and determine that nucleic acid metabolism is extraordinary important, which could be verified by syphilis pathogenesis. It is reported that virtually every gene in T. pallidum is expressed during testicular infection of rabbits [28]. Previous research indicates that the number of DNA recombination and repair genes of T. pallidum takes the least part of its DNA sequence. So, once destroyed or interrupted, it is less likely that T. pallidum could repair its DNA or RNA to survive [4]. Moreover, Leschine and Canale-Parola [29] discover that treponemal RNA polymerases are resistant to rifampicin but rifampicin is toxic to H. pylori [30]. All the results are in agreement with our findings about T. pallidum and H. pylori.
One of the great current challenges in bioinformatics is to correlate the simple linear world of nucleotide sequence with the nonlinear world of cellular function [31]. In this paper, minimal cut set analysis with FBA provides us with a new combined method. The cell can be approached from top to the bottom, starting from the network's scale-free and hierarchical nature and moving to the organism-specific molecules. By clustering the reactions, we characterize each reaction and determine their importance according to the topological calculation of minimal cut sets. On the other hand, time is also an appealing parameter that should be taken into consideration. As the concentrations or fluxes always change, more questions could be answered under the sense. Thus, it is necessary to extend our cellular metabolic analysis in both space and time.
The failure in identifying virulent determinant or drug targets of T. pallidum results from its "complex" metabolism. The problem is extended to questions about the importance of reactions and the roles of reactions in the metabolism. This paper is concerned with the related questions. The first question is addressed by calculating the minimal cut sets under the frame of whole metabolism. In concordance with the previous biological findings, nucleotide metabolism contains all 28 reactions in minimal cut sets. The question regarding the reaction role is harder since we do not have a universal definition or classification about the reactions. Here, we use a novel way to deal with the difficulty. The reactions are first quantified by Flux Balance Analysis. Then they are clustered through hierarchical clustering analysis. Given the cluster structure of the reactions, different reaction patterns show up with respect to the within-cluster and out-cluster distances. We associate the reactions in minimal cut sets with their role types and thus extend the concept of essential reactions to essential role types. Furthermore, by analyzing H. pylori as a comparison, we discover that different types of reactions have various importance in diverse microorganisms.
5.1. Description of the Dataset
Data used here were obtained from Kyoto Encyclopedia of Genes and Genomes (KEGG) LIGAND database [32]. For each organism, the LIGAND database contains chemical substances, reactions, and enzymes. However, carrier metabolites such as water and ATP were removed manually.
For each organism, only reactions catalyzed by enzymes were considered.
5.2. Flux Balance Analysis and Null Space Determination
In most metabolic network analysis, metabolites are treated as nodes while two metabolites are connected if a biochemical reaction exists. However, to explore the connection between reactions directly, we treated each reaction as a node. Reactions are linked by reaction compounds.
Flux Balance Analysis (FBA) [33, 34] provides a way to estimate the flux distribution of reactions in an organism. More importantly, it assigns every reaction a value that is unique to the reaction. In general, the steady state is common for organism; that is, all reactions in the metabolic system are maintaining a steady state flux. So the concentrations of metabolites and reaction rates are constant. Therefore, a principle equation is achieved. Assume that there are metabolites with concentrations (), reactions with fluxes (), and is the stoichiometry matrix with element to be coefficient for metabolite in reaction :In a matrix notation, where .
The mass balance equation above represents the principle constraint of FBA. Additional constraints or objectives are added to maximize the growth in terms of glucose, acetate, glycerol, and so forth, with excess energy production in form of ATP. The physicochemical constraints represent a set of linear equations: , where is defining the weights of fluxes: fluxes that produce glucose, acetate, glycerol, and ATP have weight 1, fluxes that consume glucose, acetate, glycerol, or ATP have weight −1, and the others have weight 0. Combining these constraints, FBA can be presented as a linear programing problem:where is the stoichiometry matrix and defines the weights of fluxes in the objective function. To solve this linear programming problem, it is noticed that all stationary flux distributions lie in the right null space of stoichiometry matrix. It can be further derived that the null space could be spanned by its kernel which is indicated by matrix , assuming that the rank of kernel is . Thus, the kernel represents the basis of the steady states of an organism [35]. In addition, each row of the kernel is associated with a reaction which is a crucial fact to quantify the reactions. However, there are infinite representations of the kernel because vectors in the null space are linearly correlated. Given this drawback, constraining the kernel to be an orthogonal matrix may be a solution. It could be proved that the orthogonal matrix is unique for each stoichiometry matrix. Denote by the column vectors of the orthogonal kernel. Then any flux in the steady state can be written as a linear combination of the basis; that is, , where 's are coefficients. Among all the fluxes which satisfy the steady state condition, those with the largest growth rate are the desired states. In other words, the boundary surface of the null space depicts the fluxes that achieve the cellular objective. Depending on the collinearity between the weight matrix and the stoichiometry matrix, the boundary surface could be a set of fluxes or a subspace of the null space. In the latter case, the subsets of the orthogonal basis that span the subspace are the fluxes that quantify the reactions.
5.3. Hierarchical Clustering of Reactions
As the flux of a reaction is correlated with its reaction rate, the value of the flux could be used to cluster reactions based on their reaction rates. Here, hierarchical clustering is used to group the reactions.
Firstly, find out the similarities between each pair of reactions according to their "distance." If two reactions are associated with vector and vector , respectively, the distance is defined bellow: where and .
Therefore, when the two reactions are negatively correlated, meaning that the correlation between associated vectors is −1, distance reaches the maximum value of 2; when the two reactions are positively correlated implying that correlation between associated vectors is 1, distance reaches the minimum value of 0.
Secondly, group the reactions into a hierarchical tree with regard to the distances. The distance between two clusters is defined by the smallest distance between points in the clusters. Suppose there are reactions in cluster and reactions in cluster . Denote by the th reaction in cluster and denote by the th reaction in cluster . The distance between clusters and iswhere is defined above (4).
Then treat a cluster as a new point to group and so on until we eventually get only one cluster and the hierarchical tree of reaction nodes.
Finally, it is reasonable to cut the tree at the middle level when we need to determine where to cut the hierarchy tree into clusters. In fact, it is shown that there is a wide range of cutoff levels leading to the same results.
5.4. Minimal Cut Set Calculation
Elementary mode can be defined as the smallest subnetwork enabling the metabolic system to operate in steady state [25]. It enables us to get insight into cell functions. Elementary mode analysis has been used to predict phenotype and gene expression ratio [36]. It is a "forward" way to model and investigate. On the other hand, analyzing the minimal cut sets (MCS) is an opposite perspective [22]. Klamt and Gilles defined a cut set as a set of reactions (with respect to a defined objective reaction) if after the removal of these reactions from the network no feasible balanced flux distribution involves the objective reaction.
So, for the purpose of finding critical reactions to a specific microorganism, we calculated the minimal cut sets in an organism because the removal of all reactions contained in an MCS could result in a dysfunction of the objective reaction from a perspective of the network structure; and removing a complete MCS from the network could also repress certain functioning. However, other pathways might still be active [22]. These properties of minimal cut sets help to find out species-specific reactions that are essential for pathogen but do not affect the hosts, which could be promising drug targets. We use FluxAnalyzer [37] to do the calculation and use Medusa [38] to draw the map of minimal cut sets.
In addition, to identify important reactions, we pay attention to the degree distribution of reactions in this particular subnetwork formed by reactions that compose minimal cut sets. The total degree is defined as the number of links that a node has. In a directed map for a certain node, an incoming degree is the number of links that point to the node while an outgoing degree is the number of links that start from it. Degree distribution would help us to gain insight into the global structure of the subnetwork.
5.5. Role Identification
From the perspective of distance, reactions have different connections either within their own clusters or outside their own clusters. As the reactions have been grouped into different clusters, we further classified reactions into six types.
If is the vector associated with reaction belonging to cluster , is the average of for all reactions in cluster ; that is, . The within-cluster distance of reaction is defined as . Moreover, if there is only one reaction in the cluster, the within-cluster distance is defined to be 0, which is in concert with the former definition.
Suppose there are clusters in all and the average for each cluster is , respectively. The out-cluster distance for reaction is defined as .
Then each reaction is classified according to their scores: and . To classify the reactions, assume that reactions of the same type have similar connectivity in the subnetwork. Reactions in the clusters that only contain one reaction are isolated reactions which form a stand-only type. The other reactions are classified by the order of magnitude of the within-cluster distances. As seen in the left panel of Figure 6, the within-cluster distances are well separated and have significant differences in order. Reactions in the clusters which have large within-cluster distances are hubs while reactions in the clusters with small but nonzero within-cluster distances are nonhubs or peripheral nodes. Any typical classification method such as -means would classify the reactions into three groups: one with the order around −30, one with the order around −5, and one with the order above −4. For clusters with within-cluster distances larger than or equivalently with the order larger than −4, the order of within-cluster against the out-cluster distances relationship is shown in the right panel of Figure 6. The plot shows clear pattern of three well-separated groups: one has relatively smaller within-cluster distance and two with the largest within-cluster distances. The two groups with the largest within-cluster distances are further classified by the out-cluster distances: provincial hubs which have larger out-cluster distances and connection hubs which have smaller out-cluster distances. Therefore, all reactions other than isolated reactions are further classified into 5 groups. For convenience purpose, integer thresholds are used in the classification but it is worth noting that the classification is quite robust against the specific numerical thresholds. In summary, if , reaction belongs to type 1; if , reaction belongs to type 2; if , reaction belongs to type 3; if , reaction belongs to type 4; if and , reaction belongs to type 5; if and , reaction belongs to type 6.
Distributions of within-cluster distances and out-cluster distances for T. pallidum. (a) Distribution of the order of magnitude of within-cluster distances. (b) Scatterplot of the order of magnitude of the within-cluster distances against the out-cluster distances for reactions with large within-cluster distances.
Authors' Contribution
Xueying Chen and Hong Qu carried out all analyses and helped write the paper. Min Zhao and Hong Qu conceived the analysis and helped write the paper.
This work was supported by the National Natural Science Foundation of China (no. 31171270).
Below is a list of reaction identifiers of T. pallidum and H. pylori in the KEGG LIGAND database. Each reaction identifier represents a chemical reaction occurs in the microorganism. For example, R00086 is ATP phosphohydrolase which defined by ATP + H2O ⟺ ADP + Orthophosphate.
N. R. Cooper, "Complement evasion strategies of microorganisms," Immunology Today, vol. 12, no. 9, pp. 327–331, 1991. View at: Publisher Site | Google Scholar
K. A. Joiner, "Complement evasion by bacteria and parasites," Annual Review of Microbiology, vol. 42, pp. 201–230, 1988. View at: Publisher Site | Google Scholar
J. D. Radolf, B. Steiner, and D. Shevchenko, "Treponema pallidum: doing a remarkable job with what it's got," Trends in Microbiology, vol. 7, no. 1, pp. 7–9, 1999. View at: Publisher Site | Google Scholar
D. L. Cox and J. D. Radolf, "Metabolism of the Treponema," in Pathogenic Treponema: Molecular and Cellular Biology, pp. 71–72, Caister Academic Press, 2006. View at: Google Scholar
G. M. Weinstock, J. M. Hardham, M. P. McLeod, E. J. Sodergren, and S. J. Norris, "The genome of Treponema pallidum: new light on the agent of syphilis," FEMS Microbiology Reviews, vol. 22, no. 4, pp. 323–332, 1998. View at: Publisher Site | Google Scholar
A.-L. Barabasi and R. Albert, "Emergence of scaling in random networks," Science, vol. 286, no. 5439, pp. 509–512, 1999. View at: Publisher Site | Google Scholar | MathSciNet
E. Meir, G. Von Dassow, E. Munro, and G. M. Odell, "Robustness, flexibility, and the role of lateral inhibition in the neurogenic network," Current Biology, vol. 12, no. 10, pp. 778–786, 2002. View at: Publisher Site | Google Scholar
E. Ravasz, A. L. Somera, D. A. Mongru, Z. N. Oltvai, and A.-L. Barabási, "Hierarchical organization of modularity in metabolic networks," Science, vol. 297, no. 5586, pp. 1551–1555, 2002. View at: Publisher Site | Google Scholar
N. Friedman, "Inferring cellular networks using probabilistic graphical models," Science, vol. 303, no. 5659, pp. 799–805, 2004. View at: Publisher Site | Google Scholar
N. D. Price and I. Shmulevich, "Biochemical and statistical network models for systems biology," Current Opinion in Biotechnology, vol. 18, no. 4, pp. 365–370, 2007. View at: Publisher Site | Google Scholar
I. Shmulevich, E. R. Dougherty, S. Kim, and W. Zhang, "Probabilistic Boolean networks: a rule-based uncertainty model for gene regulatory networks," Bioinformatics, vol. 18, no. 2, pp. 261–274, 2002. View at: Publisher Site | Google Scholar
J. M. G. Vilar, C. C. Guet, and S. Leibler, "Modeling network dynamics: the lac operon, a case study," Journal of Cell Biology, vol. 161, no. 3, pp. 471–476, 2003. View at: Publisher Site | Google Scholar
M. Zhao and H. Qu, "Human liver rate-limiting enzymes influence metabolic flux via branch points and inhibitors," BMC Genomics, vol. 10, supplement 3, article S31, 2009. View at: Publisher Site | Google Scholar
M. Zhao and H. Qu, "High similarity of phylogenetic profiles of rate-limiting enzymes with inhibitory relation in human, mouse, rat, budding yeast and E. coli," BMC Genomics, vol. 12, supplement 3, article S10, 2011. View at: Publisher Site | Google Scholar
N. D. Price, J. L. Reed, and B. Ø. Palsson, "Genome-scale models of microbial cells: evaluating the consequences of constraints," Nature Reviews Microbiology, vol. 2, no. 11, pp. 886–897, 2004. View at: Publisher Site | Google Scholar
E. Almaas, B. Kovács, T. Vicsek, Z. N. Oltvai, and A.-L. Barabási, "Global organization of metabolic fluxes in the bacterium Escherichia coli," Nature, vol. 427, no. 6977, pp. 839–843, 2004. View at: Publisher Site | Google Scholar
P. Pilo, E. M. Vilei, E. Peterhans et al., "A metabolic enzyme as a primary virulence factor of Mycoplasma mycoides subsp. mycoides small colony," Journal of Bacteriology, vol. 187, no. 19, pp. 6824–6831, 2005. View at: Publisher Site | Google Scholar
S. R. Schmidl, A. Otto, M. Lluch-Senar et al., "A trigger enzyme in Mycoplasma pneumoniae: impact of the glycerophosphodiesterase GlpQ on virulence and gene expression," PLoS Pathogens, vol. 7, no. 9, Article ID e1002263, 2011. View at: Publisher Site | Google Scholar
J. D. Radolf, K. R. O. Hazlett, and S. A. Lukehart, "Pathogenesis of syphilis," in Pathogenic Treponema: Molecular and Cellular Biology, pp. 197–236, Caister Academic Press, 2006. View at: Google Scholar
E. L. Rank, S. A. Goldenberg, J. Hasson, R. W. Cartun, and N. Grey, "Treponema pallidum and Helicobacter pylori recovered in a case of chronic active gastritis," American Journal of Clinical Pathology, vol. 97, no. 1, pp. 116–120, 1992. View at: Google Scholar
K. Y. Chung, M. G. Lee, C. Y. Chon, and J. B. Lee, "Syphilitic gastritis: Demonstration of Treponema pallidum with the use of fluorescent treponemal antibody absorption compliment and immunoperoxidase stains," Journal of the American Academy of Dermatology, vol. 21, part 1, no. 2, pp. 183–185, 1989. View at: Publisher Site | Google Scholar
S. Klamt and E. D. Gilles, "Minimal cut sets in biochemical reaction networks," Bioinformatics, vol. 20, no. 2, pp. 226–234, 2004. View at: Publisher Site | Google Scholar
H. Jeong, S. P. Mason, A.-L. Barabási, and Z. N. Oltvai, "Lethality and centrality in protein networks," Nature, vol. 411, no. 6833, pp. 41–42, 2001. View at: Publisher Site | Google Scholar
J. B. Baseman, J. C. Nichols, and S. Mogerley, "Capacity of virulent Treponema pallidum (Nichols) for deoxyribonucleic acid synthesis," Infection and Immunity, vol. 23, no. 2, pp. 392–397, 1979. View at: Google Scholar
W. L. Nyhan, "Disorders of purine and pyrimidine metabolism," Molecular Genetics and Metabolism, vol. 86, no. 1-2, pp. 25–33, 2005. View at: Publisher Site | Google Scholar
X. He and J. Zhang, "Why do hubs tend to be essential in protein networks?" PLoS Genetics, vol. 2, no. 6, article e88, 2006. View at: Publisher Site | Google Scholar
S. Schuster, T. Dandekar, and D. A. Fell, "Detection of elementary flux modes in biochemical networks: a promising tool for pathway analysis and metabolic engineering," Trends in Biotechnology, vol. 17, no. 2, pp. 53–60, 1999. View at: Publisher Site | Google Scholar
D. Šmajs, M. McKevitt, J. K. Howell et al., "Transcriptome of Treponema pallidum: gene expression profile during experimental rabbit infection," Journal of Bacteriology, vol. 187, no. 5, pp. 1866–1874, 2005. View at: Publisher Site | Google Scholar
S. B. Leschine and E. Canale-Parola, "Rifampin as a selective agent for isolation of oral spirochetes," Journal of Clinical Microbiology, vol. 12, no. 6, pp. 792–795, 1980. View at: Google Scholar
S. Fujimura, S. Kato, T. Kawamura, and A. Watanabe, "In vitro activity of rifampicin against Helicobacter pylori isolated from children and adults," Journal of Antimicrobial Chemotherapy, vol. 49, no. 3, pp. 541–543, 2002. View at: Publisher Site | Google Scholar
S. Schuster, D. A. Fell, and T. Dandekar, "A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks," Nature Biotechnology, vol. 18, no. 3, pp. 326–332, 2000. View at: Publisher Site | Google Scholar
M. Kanehisa and S. Goto, "KEGG: kyoto encyclopedia of genes and genomes," Nucleic Acids Research, vol. 28, no. 1, pp. 27–30, 2000. View at: Publisher Site | Google Scholar
J. S. Edwards, M. Covert, and B. Palsson, "Metabolic modelling of microbes: the flux-balance approach," Environmental Microbiology, vol. 4, no. 3, pp. 133–140, 2002. View at: Publisher Site | Google Scholar
J. M. Lee, E. P. Gianchandani, and J. A. Papin, "Flux balance analysis in the era of metabolomics," Briefings in Bioinformatics, vol. 7, no. 2, pp. 140–150, 2006. View at: Publisher Site | Google Scholar
M. G. Poolman, C. Sebu, M. K. Pidcock, and D. A. Fell, "Modular decomposition of metabolic systems via null-space analysis," Journal of Theoretical Biology, vol. 249, no. 4, pp. 691–705, 2007. View at: Publisher Site | Google Scholar | MathSciNet
J. Stelling, S. Klamt, K. Bettenbrock, S. Schuster, and E. D. Gilles, "Metabolic network structure determines key aspects of functionality and regulation," Nature, vol. 420, no. 6912, pp. 190–193, 2002. View at: Publisher Site | Google Scholar
S. Klamt, J. Stelling, M. Ginkel, and E. D. Gilles, "FluxAnalyzer: exploring structure, pathways, and flux distributions in metabolic networks on interactive flux maps," Bioinformatics, vol. 19, no. 2, pp. 261–269, 2003. View at: Publisher Site | Google Scholar
S. D. Hooper and P. Bork, "Medusa: a simple tool for interaction graph analysis," Bioinformatics, vol. 21, no. 24, pp. 4432–4433, 2005. View at: Publisher Site | Google Scholar
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