text:
Our news - Profit was delayed repair AdvCash Payment System Added
We accept:Perfectmoney,Advcash,Payeer,Bitcoin
online: 288 days
Yes. 5 Investment LTD is officially registered . Name & Registered Office: 5 INVESTMENTS LIMITED 10 SILVESTER ROAD BILSTON UNITED KINGDOM WV14 6NN Company No. 10410408
Our incorpuration number:10410408 . Verify our status: click here.
One of our strongest advantages over competitors is that we provide legal share certificate for all investors with any amount of deposit. We also offer our clients with best management as well as risk control system to ensure that their funds are being handled efficiently and they are getting higher levels of safety.
You have to be at least 18 years old before you're allowed to become a member. In addition to this, you must agree to our Terms of Service. Anybody from anywhere in the world can join. Even if you live in the desert, as long as you have an internet connection, you're free to join.
No more than one account is allowed per person. Multiple account openings is against our internal users policy and might result in membership termination, however you can share IP with other members, but each account should contact valid persons info.
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The idea behind our affiliate program is to provide more earning opportunity to members who refer other people to our investment project. Not much work is needed from you; just share your referral link, which is made available in your account, with friends, and you'll earn 5% from their active deposit. You can even earn 10% when you apply for a Representative status with our company.
No, no active deposit is required to earn commission as an affiliate.
The Representative program is very similar to the normal affiliate program. The only difference is that the earning potential is larger - 15%, compared to the 10% of the normal affiliate program. However, the Representative program is not open to everybody. For you to become a Representative of CCML, you need to have the ability to promote and support our investment project in your region through various means, like online/offline presentations, meetings with clients, a personal blog, etc. However, notes that we never support SPAM nor any form of illegal promotion of our project. If you think this is 'right up your alley', then send your personal details; full name, phone number, username, country, city, email and messenger ID to firstname.lastname@example.com, and we will respond within 24 business hours. You don't need to have an active deposit to be a Regional Representative.
The main difference is that Regional Representatives earn twice as much (15%) compared to standard affiliates. Plus, as a Regional Representative, you must have the ability to promote our project in your region.
Firstly, you need to have an account with us. To do this, simply click on 'REGISTER' at the top of our pages, you will be redirected to a page where you fill all your information and electronic payment account such as Perfect Money, Payeer,AdvCash and Bitcoin. Upon successful registration, you will be allowed to access our program by login into your newly created account with your username and password chosen during registration. Now, to make deposit, simply click on 'Make a Deposit' under the Account Navigation section of your Account Dashboard, select an investment plan of your choice, such as; Baby Plan, Crawler Plan or Walker Plan, enter the deposit amount you want to make, choose payment processor and click Proceed with Deposit.
Your account will be updated as fast, as you deposit. Bitcoin deposit will add after confirmations from blockchain.
We accept Perfect Money, Payeer, Bitcoin,AdvCash
To withdraw your funds, please go to the withdrawal section of your personal account and request a withdrawal.
Your withdrawal will process instant. But if withdrawal not process instant (Goldcoders or server problem) then we will process it manually within 1 to 2 hours.
No, this is technically not possible. However, you can have multiple deposits.
No, you can have as many deposits as you deem fit.
You can deposit any amount from only 3$ and up to 50,000$ through any payment system. You can withdraw any amount not less than 0.1$. and maximum withdraw is Unlimited.
CERTAINLY NO! We can ONLY process your withdrawal request into the same type of e-currency/digital currency account wallet you make deposit from.
Our customer service are open 24/7 to help and answer all your inquiry.


text:
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subset: commoncrawl


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Skål: Scandinavian Spirits
On view January 28-September 17, 2017
We are excited to announce the opening of our next special exhibition Skål: Scandinavian Spirits, which explores the drinking culture and traditions of Scandinavia. Some claim that the word skål has a root in the skulls of the vanquished, from which Viking warriors would drink to celebrate their victory. But this is a grisly tale, and most likely just a story. Most agree that skål, which is the word for bowl in Danish, Swedish and Norwegian, harkens back to a time when wooden bowls, sometimes elaborately decorated, would be filled with beer and passed from person to person at community gatherings like weddings or festival days. From that tradition of passing the bowl, the term Skål is now also a toast – "Cheers!"
The history of imbibing on special (and not so special) occasions predates the proliferation of Christianity in Scandinavia. The Norse god Odin was credited with teaching humans how to brew beer, and drinking beer could take the form of worship and offering to the deities. The Norse sagas mention drinking beer, especially in celebration of battle victories, and sometimes in the form of drinking challenges. When harvests were small, however, beer brewing was restricted in order to reserve enough grain for food preparation.
Around the 1500s, the strong stuff made its way into society when brännvin (brændevin in Danish / brennevin in Norwegian), a term for vodka or distilled liquor, became known through Scandinavia. It was primarily distributed as medicine, but we can see that a wider use had become common by 1551 when King Christian III of Denmark-Norway attempted to ban serving brännvin on holidays to prevent people from attending church while drunk. By the 1600s, brännvin was widely available through home-based distilling, though the results often tasted awful, which led to adding herbs and other plants to improve the flavor. These selective infusions became what we now know as aquavit, which is regularly served with herring at any decent smörgåsbord.
King Gustav I Vasa of Sweden was fond of a German drink called Glühwein, which was a sweet mixture of wine, sugar, honey, cinnamon, ginger, cardamom and cloves. It was later named glödgad vin in 1609, which meant "glowing-hot wine." The word glögg is a shortened form that first appeared in print in 1870. Swedes consume glögg from the beginning of Advent through the New Year, as the beverage is almost exclusively reserved for the Christmas season. Swedish glögg is a souped-up version of the German drink consisting mainly of red wine, brandy, and port infused with spices, and then raisins and blanched almonds are added to the cup. Glögg is preferably served in a special little mug with a handle. While it's not so typical to "Skål!" while holding an adorable cup of glögg, it can and does happen and everyone enjoys the ritual:
Raise your glass.
Say "Skål!" with gusto.
Look your companions in the eye.
Take a drink.
Look your companions in the eye again.
Set down your glass.
Discover more about these and other fun, boozy histories when ASHM opens the exhibition Skål! Scandinavian Spirits. This exciting travelling exhibition focuses on the heritage of beer and aquavit through stories, traditions, and recipes. Over 50 historic and contemporary artifacts related to Scandinavian drinking traditions will be on display from the Museum of Danish America, American Swedish Institute, Swedish American Museum, the Nordic Heritage Museum, and the Vesterheim Norwegian-American Museum. It may be the first collaborative project to involve such a broad spectrum of Scandinavian-American museums; it is as if we all gathered around the table—Skål!
Skål! Scandinavian Spirits opens on Saturday, January 28, 2017 and will be on view through September 17, 2017.
Presented by Aalborg and Linie Aquavits, organized by Tova Brandt of the Museum of Danish America, Elk Horn, Iowa.
It is presented at ASHM through the generosity of the Swedish Council of America, SWEA New Jersey, SWEA Philadelphia, the ASHM Auxiliary, Barbro Osher Pro Suecia Foundation, George C. and Esther Ann McFarland Foundation, Midsommarklubben, and an anonymous foundation. Support provided in part by the Philadelphia Cultural Fund. Funding for the American Swedish Historical Museum is supported by a grant from the Pennsylvania Historical and Museum Commission, a state agency funded by the Commonwealth of Pennsylvania.
Fact and Fiction: Getting to Know Sweden's Authors
In a small exhibition located in the Kalm-Seaborg Gallery on the second floor, ASHM examines Swedish authors whose works have leaped across culture lines to impact the American literary landscape. From Carl Linnaeus's writings about scientific taxonomy in the 1700s to the socio-political themes explored by crime novelist Stieg Larsson in the 21st century, this "mini" exhibit features objects and images that illuminate the life and times of some of Sweden's best-known authors.
A Common Thread: Tradition and Trend in Swedish Textiles
Whether they are created for function or fashion, Swedish textiles are well-crafted, colorful, and full of detail. A Common Thread uses the museum's collection to explore the themes of technique, style and material employed to create Swedish clothes, weavings, embroidery, and other handiwork. The exhibition looks at the ways in which Swedish textiles communicate class, gender, cultural identity and social trends. Highlights from the collection include examples of Saami outerwear, Swedish provincial costumes, household linens, decorative wall hangings, tools and modern examples of Swedish style. A hands-on table with wool, linen, silk, leather and fur, is available for visitors to handle and explore textile materials on their own.
Where the Children Sleep, Opens October 2017
To view more information about past exhibitions at ASHM click here>>


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I have a Hyper-V Server 2008 R2 Data Center with 2 On-Board GB NIC's and 2 Quad Port GB Nics. I see lots of inbound traffic on each of the different nics, but the outbound traffic flows out the default route of the Server ie the first NIC. I have been searching for options to tell each NIC to handle it's own traffic, but I am not seeing anything other then to setup different subnets. This means that I would need to setup each Host NIC in it's own subnet and I would rather not do that. This is all internal traffic. Right now the nics are all in the same subnet.
Am I missing something simple?
17 Replies
Nov 25, 2011 at 5:38 UTC
how do you have the nics setup?
are they teaming or have they all got their own config,
and if so do they all have the same gateway?
are your vm's configured to bridge though a nic and is that a different nic than you notice is taking the load?
Nov 26, 2011 at 6:45 UTC
how do you have the nics setup?
are they teaming or have they all got their own config,
and if so do they all have the same gateway?
are your vm's configured to bridge though a nic and is that a different nic than you notice is taking the load?
I have a Virtual Network Setup for Each Nic. I then connect anywhere from one to three VM's to the Virtual Networks. The connection type is External.
The NIC's are not teamed they are each config.
They all ave the same gateway IP because they are all on the same subnet.
I am not using bridging.
I did notice that the nic's have a check box to allow management operating system to share this network adapter. Is that a contributor to my issues?
Nov 26, 2011 at 7:11 UTC
are your virtual networks interconnected?
as long as they are seperated the traffic flow should be seperated aswell.
perhaps one of your vm's is just generating more traffic than the others?
another possibility, are the physical nics configured to use load balancing service?
Nov 26, 2011 at 8:19 UTC
they are not interconnected.
I just included a snapshot of my NIC activity from Task Manager to show has the iSCSI traffic is working but they are on different subnets. But all the other nics are on the same subnet. It looks like it is flowing everything thought the one NIC "Broadcom 1". Both in and out.
Nov 26, 2011 at 8:22 UTC
This is a view showing the VM -> Virtual Switch -> NIC -> out.
Nov 26, 2011 at 10:02 UTC
so the busy card is used for iscsi?
then it seems a bit more normal as iscsi is being ran by the host so it goes over the preconfigured nic. it's seperate communication from hyperv.
perhaps i misunderstand.
Nov 26, 2011 at 10:21 UTC
Intel 5 - VT -ISCSI & Intel 1 - ET iSCSI are showing correct traffic and it's the iSCSI traffic between the Host and the VHD storage. The part that I am trying to figure out is Broadcom 1 shows all of the server traffic between the clients and the VM Servers. This should be spread out across all of the other NIC' s based on which servers are assigned to which virtual switches which in turn are assigned to the different NIC's. But from this view it is showing all of the traffic for all the Servers is running though Broadcom1 so I am not getting the befit of having my additional NIC' s in the server.
Hope that makes it a little clearer.
Nov 26, 2011 at 3:43 UTC
I cannot see whats running on that nic from the graphs.
nor whats on the intel 8,7, 6 and 4
broadcom 2 shows what I assume is a gateway or proxy, and sql development server and a terminal server.
Any chance those are in less demand as some of your other servers?
If you want it spread out evenly you should consider nic teaming.
Honestly I'm guessing here as I cannot see the full setup, but I'm sure there is a logical explanation for this.
Nov 28, 2011 at 5:35 UTC
This is a more current graph of the adapters sorted in descending order by Bytes Sent. You will see that Intel 5 & Intel 1 are the ISCSI Adapter. They are on different subnets so they are routing traffic as expected and I an not concerted with them. The other NIC's
Intel 8 - VT
Broadcom 1
Broadcom 2
Intel 2 - ET
See how the traffic for Sent keeps dropping. It's like the system is routing all traffic to Intel 8 - VT then if that gets full then it's dropping to Broadcom 1 etc. The traffic on Intel 2 - ET and below can be attributed to ARP broadcast. This host has been up and running for over 400 days.
I have no load balancing going on. Since I have the different Virtual Machines setup to us different switches etc. Network Card Intel 2 - ET has a server supporting 300+ users so I would expect allot more traffic on that NIC. This just does not make sense unless their is some setting that Hyper-V is sending all traffic out the Default Route of the hyper-v host server and not the NIC's assigned to the Hyper-V Virtual Server.
What am I missing? I want the Guest Servers to both Send and Receive on the NIC that is assigned to the Virtual Switch that the Guest is connected with not the default gateway of the Hyper-V host itself.
Nov 28, 2011 at 5:52 UTC
That is weird indeed,
I initially thought it might be the load that the individual servers pull.
but it doesn't add up.
It's not by hyper-v design so it must be something in the configuration.
I'd have to see it to be able to figure it out.
Sorry but I'm afraid I cannot trouble shoot this one without access to the server.
Nov 28, 2011 at 6:16 UTC
I am going to keep searching and when I turn up the solution I will post it. I am expecting to get a new Hyper-V host in the next few months so I will have a little time to do some testing. This server is in production so I cannot do too much with it. But I agree that it's very weird. I was hoping that I had just missed something simple.
I am getting this exact some type of traffic flow on all of my hyper-v servers and it just does not make sense other then I have consistently configured them wrong ;-). Thanks for your time.
Nov 28, 2011 at 6:22 UTC
You're welcome,
And I'm sorry I couldn't bring you closer to a satisfying fix.
Nov 28, 2011 at 8:31 UTC
Are you sharing your hyper-v network cards with the management OS?
Best advice would be to have 1 (possibly dedicated NIC) for the host OS then all NIC's used by gestes should not be shared with management, this will at least clarify the lines of communication.
At first glance it would appear there's a mistake somewhere in the setting up of virtual nic's and assigning them to guest VM's
Do the guest VM's just show 1 nic available per guest?
Nov 28, 2011 at 11:38 UTC
Are you sharing your hyper-v network cards with the management OS?
Best advice would be to have 1 (possibly dedicated NIC) for the host OS then all NIC's used by gestes should not be shared with management, this will at least clarify the lines of communication.
At first glance it would appear there's a mistake somewhere in the setting up of virtual nic's and assigning them to guest VM's
Do the guest VM's just show 1 nic available per guest?
Am I sharing - Yes on all of them.
According to my Network View I show anywhere from 1-3 VM to a Virtual Switch and the VM' sonly show the name of the virtual switch in the VM settings.
On my host I have a Virtual Network that is setup one for Each NIC. The connection type is "External" adn the allow management operating system to share this network adapter is set on all of them. I am wondering if the "share" might be my issue.
I also notices that on one of my serers all of the traffic is going out a Network Card assigned to a virtual switch that does not have ANY VM's assigned to it. So it should not be getting any traffic. It's like that one is getting almost all of the traffic.
All of the NIC are on the same subnet except for the iSCSI traffic which seems to be running fine.
What else can I tell you?
Nov 29, 2011 at 3:32 UTC
OK I can't see a logical reason why it should affect it, but I would remove the sharing of the virtual NIC's with the OS - this should ensure a direct relationship between the vm's and the nic
You only need to share the NIC with the management OS on the NIC that you want to use for remote access to the server.
In the interests of not changing everything at once, could you test by removing the sharing on one of the NIC's and seeing how that affects traffic from the linked guests?
Nov 29, 2011 at 5:37 UTC
Updated Notes: I spoke with Dell Tech support and their comment was that the information shown under Networking in the Windows Task Manager does not reflect the correct information for network traffic due to how the virtual switch works under Hyper-V. For iSCSI that is not used by Hyper-V it was reporting correctly.
I removed the Allow management operating system to share this network adapter and a few interesting things happened. The Virtual Switch NIC's no longer show in Windows Task Manager and they do not show under Network Connections on the Hyper-V Host. The Nic still shows as bound to the virtual switch but the virtual switch is not visible to the Hyper-V host which I am pretty sure is how its designed. I can also see the NIC in the Virtual Network Manager. I am going to do some monitoring at my switch level to see if traffic increases at the switch level over the next day.
Nov 29, 2011 at 5:48 UTC
Yes - when you stop sharing the virtual nic with the OS the nic does disappear from the host (it's still actually there, but IP configuration is removed)
This discussion has been inactive for over a year.
You may get a better answer to your question by starting a new discussion.


text:
The wonderful and croaky blare of your eupnoeic not simply irritates your better half who is sleeping beside you but too is a plate of promise worries beside your health. In effect, it can be seen as a word commemorative inscription and it is something that you would be sagacious to try and annihilate. Normally, the group who noise have greater bias of hypertension, viscus irregularities and snoozing disorders.
Here is some simplex snoring suggestion for those who are going done the eccentricity.
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text:
|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|"Sean Qiu" <sean.xx....@gmail.com>
|Re: [announce] Java ME contribution
|Thu, 17 Apr 2008 07:40:22 GMT
Great news. "Harmony" will make java a harmony world. :) 2008/4/16, Bartek Teodorczyk <email@example.com>: > Hi all, > > I'm happy to announce contribution part of the Microemulator > (http://www.microemu.org/) project to Apache Harmony. Microemulator is > a Java ME implementation but also emulation layer that allows to > execute CLDC/MIDP applications (MIDlets) on standard Java SE. > > I've been involved into that project for almost 7 years, not always > full time though. In the latest release we achieved quite good > coverage of implemented JSRs: CLDC, MIDP2, JSR-75, JSR-135 and others. > It is however far to complete and of course we've never been able to > even touch the TCK to verify our implementation. > > Unfortunately, we are not able to contribute whole the project but > only parts that meet the Harmony ACQ requirements. That makes > potential integration with Harmony much more difficult, current > contributed code doesn't even compile successfully. I hope you'll find > it useful though, and I'm always open to answers any questions > concerning the Microemulator (as far as I'm allowed to). > > Regards, > Bartek Teodorczyk > -- Best Regards Sean, Xiao Xia Qiu China Software Development Lab, IBM
|View raw message


text:
Listing information
- Beds: 2
- Total Rooms: 5
- New Construction: No
- Lot Area: 0.03
- County: Summit
- Style: Ranch/1-Story
- Baths: 2 (Full: 2 3/4: 0 1/2: 0 Other: 0)
- Stories: 1
- Foreclosure: No
- Estimated Annual Taxes: $1,499
- School District: Nordonia Hills Csd
- Year Built: 1970
- Status: Sold on 4/13/2017
- Parking Type Description: Detached 1 car
- Total Square Footage: 1,206 ($49.49 per sq. foot)
- Association Fee: $255
- Subdivision: Oak Knolls Condo
Amenities Exercise Room, Laundromat, Park, Playground, Pool, Tennis Courts
Appliances Equipment Dishwasher, Range, Refrigerator
Basement Detail None
Basement Y/N No
Cooling Type Central Air
Disability Features Y/N No
Driveway Paved
Dwelling Type Attached
Exterior Vinyl
Exterior Features Patio
Financing Conventional
Fixer Upper No
Garage Features Detached
Heating Fuel Gas
Heating Type Forced Air
HOA Fee Includes Association Insurance, Exterior Building, Garage/Parking, Landscaping, Property Management, Recreation, Reserve Fund, Snow Removal, Trash Removal
HOA Y/N Yes
House Faces West
Lot Description Wooded/Treed
Maint Fee Includes Association Insurance, Exterior Building, Garage/Parking, Landscaping, Property Management, Reserve Fund, Snow Removal, Trash Removal
Maint Fee Y/N Yes
Other Full Baths Lower - 0, Full Baths Main - 2, Full Baths Upper - 0, Half Baths Lower - 0, Half Baths Main - 0, Half Baths Upper - 0, Unit Floor Num Of - 3
Possession Negotiable
Property Subtype Condominium
Restrictions Pets Allowed
Roof Asphalt/Fiberglass
View Description Wooded
Warranty Y/N No
Water Sewer Public Sewer, Public Water
Bedroom First
Dining Room First
Kitchen First
Living Room First
Master Bedroom First
Listing Courtesy of Berkshire Hmserv. Simonsalhany


text:
Commercial property: Invest NI needs a lesson in reality
I've been known to liken government strategies to the mistake made in Australia when the cane toad was introduced to tackle the problem of cane beetles.
In principle it was a good idea, but in practice it became Australia's largest environmental mistake. To this day the cane toad remains a pest and one of the few animals that residents are actively encouraged to eradicate.
The analogy's reference point to Northern Ireland business remains the 'modern government lease' and the detrimental effect it has had on office and investment values alongside creating a scenario where development of new facilities is simply not viable. In a recovering economy, one which is heavily based on inward investment and attracting service companies to locate here, why are we seeing no development?
Invest NI is being rightly lauded for its encouragement of and success in attracting service sector jobs to Northern Ireland - over 6,000 were announced in the year to March, but there is a serious flaw in the plan. Where are these firms going to locate? There is currently only one office development under construction and we will be waiting at least a couple of years before anything sizeable comes out of the ground in the city centre.
Delivering a viable Grade A project requires a minimum rental level of around £18 per sq ft, and yet on the Invest NI website I find the following statement: "Prime office rents are among the lowest in Western Europe. New, purpose-built and fitted-out office space costs are easily affordable with Northern Ireland maintaining the lowest net-rent in the UK. Office space is going for £12-50 per sq ft in the Greater Belfast area."
This is simply ludicrous and highlights limited commercial understanding within the public sector. Until it wakes up and realises that development is required, accepts that rental levels need to be viable and that quality product must be delivered, many of the previously announced job opportunities will be slow to come on stream.
Martin McDowell is managing director of Osborne King commercial agents
Belfast Telegraph


text:
Catch-up Premium
Year 7 literacy and numeracy catch-up premium
The literacy and numeracy catch-up premium gives schools additional funding to support year 7 pupils who did not achieve the expected standard in reading or maths at the end of Key Stage 2. All state-funded schools with year 7 pupils receive this funding of £500 per year.
Funding for Financial Year 2016-17
In 2016 to 2017 schools will receive the same overall amount of year 7 catch-up premium funding they received in 2015 to 2016, adjusted to reflect the percentage change in the size of their year 7 cohort, based on the October 2016 census.
Eligible students at Fort Pitt
In 2015/16, one student at Fort Pitt was eligible for this funding based on her KS2 Maths level, where she just missed Level 4. The fund was used to provide intensive one-to-one tuition and as a result, she has made excellent progress and is now above average in the subject.
In 2016/17, we have one student who is eligible for this funding based on her KS2 score primarily in Maths. We have invested in both one to one tuition and in IT intervention software for this student who is showing a positive impact in terms of progress and attainment evidenced through rigorous testing.
Please contact the office (click here) if you have any question or comments about this premium.


text:
$1,000.00 1 year ago
$1,000, Three female college students
Brieana, F, 20 Brunswick, GA, United States $1000 USD per month Looking for entire place We are three female college students that are currently looking for a townhome/home for rent, we will not rule out an apartment but we prefer a home or townhome. We have two pets, a small male cat and a mixed breed female dog. Ideally, we would like for the area to have a patio of some sort, and a large backya
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Brunswick, GA
$600.00 1 year ago
$600, 2br, Natural life
2 bedroom single family house for rent, off street parking, unit has fresh paint, very clean. First months rent and security deposit to be paid in full prior to move in date. Amherst St,31520 google map | yahoo mapBedrooms: 2Rent: $600 --Cats Ok --Dogs Ok
1 year ago
Brunswick, GA


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Dropbox is one of the most popular cloud storage services and it is always interested in bringing new services to its customers. The company has recently announced that it will be adding the ability to edit Microsoft Office documents to its free iOS client. And now it seems that the update has been released.
By using the free Dropbox app for iOS (follow the link at the end), iPhone and iPad users can edit Word, Excel and PowerPoint documents directly on the cloud. Here's how the official announcement sounds like:
"The new Dropbox and Microsoft Office integrations are here! Now it's easy to work on the Office files you've stored in Dropbox even when you're on the go — you can edit them from the Dropbox app, and access them directly from the Office apps. The new features are available today for Android phone and iOS users."
Microsoft CEO Satya Nadella recently said that Dropbox integration in mobile Office apps and the new Office support in Dropbox provides "our shared customers with flexible tools that put them at the center for the way they live and work today."
The update to the iOS app will be slowly rolling out in the coming weeks, so if you don't see it today, this means you have to wait for a few more days. This is a great feature not only for Dropbox owners but for those who have to deal with a lot of Office files.
Source: iTunes
Dropbox Starts Rolling out the Ability to Edit Microsoft Office Documents on iPhone, iPad
Discussion in 'Apple iPad News' started by RaduTyrsina, Nov 26, 2014.
Discussion in 'Apple iPad News' started by RaduTyrsina, Nov 26, 2014.


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Call of Duty Lessons
I will teach you how to be someone that owns the shit out of other players when they play online. You won't be the person getting served anymore. You'll BE THE PERSON SERVING. This is for people who want to learn how to own in public matches. I am NOT a competitive call of duty player so I can't help you with competitive play, but I have been a long time successful player in pubs.
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I've been in the second standard deviation of call of duty players for years. Despite that most will lie to you about it, I can honestly prove to you that my public kill death ratio has been hovering around 1.5 since I stared playing call of duty at Black Ops 1. I'm not the best player in the world and I'm not even close. But if you're struggling to get better than most, I can help you out.
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I'm free all days besides Tuesday's and Thursday's.
Reviews of Avi
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From Dirty Rotten Scoundrels - Digital Sheet Music
Product InformationDirty Rotten Number from Dirty Rotten Scoundrels - Digital Sheet Music
from Dirty Rotten Scoundrels
Dirty Rotten Number digital sheet music. Contains printable sheet music plus an interactive, downloadable digital sheet music file.
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Family travel guide to Brazil
Breathtaking natural wonders, iconic cities and the world's greatest rainforest, Brazil is a holiday destination that takes some beating. It's little wonder the country's popularity has soared over the past decade, with the country ideal for families with older children looking to combine a city break with a jungle adventure.
Direct flights are available from the UK, with wider options available for those willing to take a stop-over in Lisbon en-route. Visas are not required for British nationals and healthcare in major cities is excellent.
Do keep in mind the sheer size of the country – two weeks travelling here is not comparable to a fortnight's road trip through France. If you're combing any city break with a trip to the Amazon you will be covering 1000 of miles and will find yourself combining flights and bus rides, with off road vehicles and a jaunt on a canoe.
Still tempted? Read on for the first instalment of our guide to Brazil looking at three major cities.
Rio de Janeiro
- Flying time: 11 hours direct from London Heathrow with British Airways and TAM. TAP Portugal offers flights via Lisbon
- Time difference: GMT -3 hours
- Best time to visit: Easter, July and August. Avoid the heat of December where temperatures are in the 40s
Samba, carnival, beaches and favelas – Rio is a breathtaking city that contrasts natural beauty and a laidback beach lifestyle with gritty reality. Whilst inequality and poverty remain part of everyday life, much has been done to curb crime and violence over the past few years, although precautions should be taken as you would in any major city.
Where to stay
- The city is divided by a mountain range into two areas: the North Zone and the South Zone, with the South Zone opening onto the ocean and being home to the majority of the tourist attractions
- Typically most tourists stop in the South Zone, with popular locations here being Copacabana, Ipanema, and neighbouring Leblon. Both are upmarket areas, with Leblon's beaches attracting a lively surfer crowd
- For a more authentic stay, airbnb has a vast choice of private rooms or entire apartments available
- If you are travelling in the warmer months and planning a quick dip to keep everyone cool, it's worth remembering the seas at the city's beaches can be quite rough so, if you can, choose a hotel with a pool
What to do
- Top up your tan and people watch on the city's famous Copacabana and Ipanema beaches. All of Rio's beaches are family friendly, although the currents can be strong. Set up camp near the life-guards and pay attention to any signs
- Ascend Corcovado to stand under Cristo Redentor (Christ The Redeemer) and take in the stunning 360 degree views
- Take the cable car up Sugarloaf Mountain for equally stunning views. Both Corcovado and Sugarloaf are reasonably buggy friendly. A visit to watch the sunset is well worth jostling the crowds for
- Spend some time in the city's historic centre, with museums, street cafes, markets and the impressive Theatro Municipal
- Visit the famous Maracana football stadium in the north zone – if you can get tickets for a match you'll be in for a treat
- Head to Santa Teresa for a wander around some galleries and an al fresco coffee
- Escape the pace of the city and head for the city's Parque Nacional da Tijuca – a hand-planted rainforest in the city and great place for hiking and monkey spotting
- Lose yourself in the city's Botanical Gardens
- Choose a responsible company for a guided tour of a favela. With the rather ethically suspect practice of 'slum tourism' we urge you to choose a responsible company, with guides from the community and revenues invested back into the community. UK-based tour operator Sumak comes highly recommended
- Take a samba lesson and then dance the night away
São Paulo
- Flying time: 11.5 hours direct from UK with British Airways and TAM
- Time difference: GMT -3 hours
- Best time to visit: São Paulo has a rather tropical, mild climate, generally with good weather, although the seasons are not well defined. Avoid the heat of the summer months.
São Paulo is big - really big. It's the largest city in Brazil and the 7th largest by population in the world. It's the business heart of Brazil and a city with a rich history, a diverse multi-cultural population, great restaurants and some fascinating museums and galleries. It will be a host city for the 2014 World Cup and is home to the Interlagos F1 Grand Prix circuit.
Where to stay
- Two popular locations are downtown or in the western region. Downtown is the birthplace of the city and as such home to most of the historical sites. The western district is home to the Government and international businesses.
- Vila Madalena is a trendy area with a buzzing cafe/bar culture and is a popular choice. Ibirapuera and Jardins are two of the city's most prestigious neighbourhoods with Jardins home to designer stores, fine restaurants, shopping malls and museums
What to do
- Grab a map and your comfy walking shoes and explore downtown
- Eat! There are more than 12000 restaurants located in the city and as a real melting pot of nationalities the choice of cuisines is vast
- Make like cool kids and visit Augusta Street – billing itself as the hippest street in the city, offering bars, clubs, eateries, clothes shops and general vibes
- Visit the city's zoo which is home to some 3,000 animal species, and also includes a petting zoo area for children
- Escape the city into Ibirapuera Park. Most Sunday mornings there is a free music concert to enjoy
- Head to one of the city's museums. The choice is vast with museums covering immigration, sacred art, Japanese history in São Paulo, science, football and image and sound, to name just a few
- Don't miss the Museu de Arte de São Paulo - MASP – home to perhaps the best collection of modern art in South America, impressionists and Brazilian contemporary artists. Work includes Gauguin, Van Gogh, Picasso, Degas and Portinari
- Trek Pedra Grande in Cantareira State Park, located in the north zone about 20mins from the city centre. The trail is a 9.5km round trip and you'll be rewarded with great views of the city below
- Head to Interlagos and visit the Formula 1 circuit
- Flying time: no direct flights – you'll need at least one stop in Lisbon with TAP or if you prefer to fly the longest leg first, fly to Rio/San Paulo and connect
- Time difference: GMT -3 hours
- Best time to visit: Brazil's north-west coast is warm year-round with temperatures ranging from upper 20s to mid 30s. June and July can be slightly wetter months.
Salvador is a gorgeous coastal city famed for its numerous outdoor parties and festivals, and was the former capital of the New World colony. Divided into the upper and lower towns (Ciadade Alta and Ciadade Baixa), the brightly-coloured city is home to one of the most beautiful beaches in the world, the Porto de Barra. It's also one of the host cities for the 2014 World Cup.
Where to stay
- Consider staying in Barra, which is very near to all the main beaches in the south. It's very popular with tourists and also has plenty of picturesque scenes like the Farol da Barra Lighthouse
- The Aram Yami hotel in the heart of Salvador's old town – or Cidade Baixa – has plenty for families. If you prefer, the Hotel Casa do Amarelindo is right in the centre of the historic area making it a great base from which to explore the whole of Salvador
What to do
- Sign up for a private tour with one of the many island tour guides so you can learn the history behind the beautifully-painted streets of the old town
- Take an excursion by boat and see Salvador from the waves
- Sign your children up for surfing lessons at the Centro de Terapiaem Surf
- Visit the spectacular Sao Francisco Church and Convent, packed with marvellous designs intricately picked out in gold and silver
Last updated: over 1 year ago


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Can you Wii U owners feel the anticipation? Not only has The Wonderful 101 launched on Sunday, The Legend of Zelda: Wind Waker HD (WW HD) comes out in digital form this Friday, the 20th. Since it's eShop only until Oct. 4'th, there will be a contingent of people who will play it early for this locking the game to their Wii U. I've been checking out the reviews, and they've been very positive. So, what are the things I can't wait to dig into with WW HD:
1.) Nothing: I'm not going to buy it, at least not right away.
2.) Save my money for later: If I recall, WWHD will retail at $50. That's a Nintendo-charged premium when you consider Sony has been doing HD ports of their PS2 classics for $40. True, those do less remastering than WW HD does, but they still qualify as re-releases. I'm all set for Pokemon X and Y, thanks.
3.) Dream of a Zelda game tailor-made for Wii U: It is well-known in many circles that WW HD only exists as a gap filler for the Wii U, albeit one with a purpose. Eiji Aonuma has said that WW HD is a means to experiment with what the future of the Zelda series could be on Wii U. Not only would it be original to the system, but I'm holding out for his vision of a radically-different Zelda to become reality. Probably in 2015, anyway.
4.) Play the GameCube original I already have: There are purists out there, who will forever value the deliberate toon-shading, not to mention pacing, of the 2002 original. I don't mind the changes of the new remake, per say. But, the changes made are so subtle that I may as well replay the original anyway. I've found Wind Waker the most difficult Zelda to replay, and the sailing and Triforce quests have something to do with it. Might as well suck it up and deal.
5.) Sleep soundly at night: Trollololo!
But, seriously... I may or may not play this remake down the line. After all, I signed up immediately for Ocarina of Time 3D back in 2011. This remake doesn't change things quite as radically as that one did, but what was brought in makes it worth replaying Wind Waker again. Also, it's content for the struggling Wii U, so that can only be good news.
Alt. Opinion: Just because GTA V is dominating the gaming landscape, that doesn't mean we can't have whimsy and grand adventure, free of violence. Just like Wind Waker HD does so well.


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Did you have a baby shower for your second baby?
I'm not sure why this is a debate, to me all babies deserve to be celebrated! But there are people out there that think a baby shower should only happen for the first baby. I don't get it.
Did you have a baby shower for your second baby? If you only have one child, do you think it's weird to have a shower for a second baby?
I didn't have one with my first. Lol but I think it's fine to have one with more than just your first.
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Van Fox Photography Photographer
Gabriel GagliardoniModel Male Los Angeles, California, US
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About MeHi im new in the page. My name is Gabriel Gagliardoni im from Venezuela and im 21 years old. Im a profesional model in my country but im moving to Los Angeles in January 2014 to study acting in the NYFA wich is my dream. Im a very responsable person, dedicate and i love what i do so if someone is interested in working with me it will be great you can contact my through the private message. Thanks for your time if you just take this one minute to read my bio. My Instagram is @ggagliardoni
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|Message view
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|Jukka Zitting <jukka.zitt...@gmail.com>
|Re: race conditions in commit hooks/editors
|Thu, 25 Apr 2013 11:27:39 GMT
Hi, On Thu, Apr 25, 2013 at 1:23 PM, Marcel Reutegger <email@example.com> wrote: > I'd be interested to hear what people think about this problem. > should we retry commits when these kind of conflicts where > introduced by hooks or editor or do we require the latter to > take care of this and only manipulate content in a non-conflicting > way? Note that the SegmentMK is designed to avoid this problem; it can guarantee that the commit hooks get run against the latest state of the repository and thus can't possibly conflict. More generally though the best approach here is probably to combine the approaches you mention. Commit hooks should generally try to avoid creating conflicts (like what the p2 index is already doing), but if doing so is not possible or too expensive (as it in many cases may be) it would be best if the commit could fail and be retried after rebasing. BR, Jukka Zitting
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JOHCM All Europe Dynamic
Growth Fund EUR
The investment objective of the Fund is primarily to achieve capital growth through investment in those European equity markets which are included in the definition of Recognized Market (which, for the avoidance of doubt, include emerging European markets). The provision of income will not normally be a major consideration unless this is considered to be in the interests of the Fund.
The investment policy of the Fund is to look for companies that will deliver superior medium-term cash earnings growth, where this is not reflected in the current valuation. This will be achieved by bottom-up stock picking focused on identifying change in companies across all industry sectors. The Fund will invest across all market capitalization levels but it is expected to invest primarily in companies with a market cap in the region of USD 1- 10 billion. Furthermore, the Fund will look to invest in companies which are experiencing an improving outlook for revenue and profit growth. Where considered appropriate, the Fund may utilize techniques and instruments such as futures, options, equity index swaps and currency forwards, for efficient portfolio management purposes only. Minimum Investment is in GBP. AUM reflects the aggregate of the various share classes and is denominated in GBP.


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IS Productions presents "Eating out at an Indian restaurant (white people vs brown people)" starring Inder Singh and Preet Kaler Eating out at an Indian ...
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On the Shelf
The Bard Blazed, and Other NewsBy Dan Piepenbring
- Shakespeare scholars are reeling from a discovery so major, so irrefutably epochal, that it sets the entire field on its head: four clay pipes found in his Stratford-upon-Avon garden contain cannabis residue. Historians may never know for certain if Shakespeare composed his masterworks among purple plumes of the dankest kush, but for the sake of sensationalism, we of the media have no choice but to assume he did. T-shirts featuring the Bard ripping tubes, smoking bowls, and otherwise enjoying a good old-fashioned toke will be available in novelty shops near you by C.O.B. today. I had nothing to do with them.
- A 1991 letter from Elena Ferrante to her Italian publisher, Sandra Ozzola, lays out her approach to promotion with the utmost candor: "I've already done enough for this long story: I wrote it. If the book is worth anything, that should be sufficient. I won't participate in discussions and conferences, if I'm invited. I won't go and accept prizes, if any are awarded to me. I will never promote the book, especially on television, not in Italy or, as the case may be, abroad … I believe that books, once they are written, have no need of their authors. If they have something to say, they will sooner or later find readers; if not, they won't."
- In which Avies Platt, "an art mistress at Wellingborough County High School for Girls in Northamptonshire," has a stirring encounter with an aging W. B. Yeats: "she met the seventy-two-year-old Yeats at an open meeting of the Sex Education Society, a group headed by controversial sexologist Norman Haire … As the evening progressed it became obvious that the elderly poet's interest in Platt went further than conversation—she mentions him sitting outside the Athenaeum club in Pall Mall and expressing his regrets at 'the stupid rule that we may not take ladies in after midnight.' "
- Let's talk about trolling, and while we're at it, let's throw some existentialism in there, too: "If the Internet was predicated on everyone co-existing on a level playing field, able to distribute and share knowledge without the previous gatekeepers of status or affiliation to slow things down (perhaps one of the main benefits of having user names rather than real names), trolling takes that utopian possibility and throws it by the wayside … trolling is a destructive way of addressing the ambivalent state of being that is life online, that is, being connected to millions and even billions of people simultaneously, but being incredibly isolated, separated from the nuance of subtle body language, body odor, touch, taste, et cetera."
- Today in new applications for 3-D printing: haute couture. At Paris Fashion Week, Chanel presented a version of its classic two-piece suit: "Using selective laser sintering—a high powered laser fusing together tiny particles—much of the suit vest was sculpted, appearing boxlike, with no sewing necessary … With endless possibilities in shape, texture and transparency, the experimentation of 3-D printing techniques and materials has a worthy place on the cutting edge of couture. But fashion designers must learn how to generate computer files and complex computer-aided drafting techniques for the printing process to work."


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It was the fourth successive time that the two teams clashed in the final and India have emerged victorious on all four occasions.
Electing to bat first after winning the toss, India was helped by some good batting performances by Asha Rawat, who was fell short of a well-deserved century, and captain Mithali Raj, who scored a well-compiled 66 to post a formidable target of 261 for Sri Lanka.
However, the Indian bowlers did not give Lankans any chance to make a match out of it. The hosts were finally bundled out for a paltry 83 inside the 37th over. Pujare Seema and Neetu David picked up three wickets each.
At the start, India were off to a poor start as opener Jaya Sharma failed to open her account and departed in the second over.
Rawat then combined well with Kavita Jain (28) to stitch the innings before the latter was out with India at 75. Mithali then joined Rawat and both added a massive partnership and almost batted the hosts out of the game.
Rawat's 114-ball knock was studded with 12 fours and a six while her skipper hit six fours in her 72-ball essay.
At the end of the innings, Amita Sharma made a quick-fire 50 off 31 balls as India finally scored 260 for seven in their 50 overs.


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Amplitude distribution of stochastic oscillations in biochemical networks due to intrinsic noise
Intrinsic noise is a common phenomenon in biochemical reaction networks and may affect the occurence and amplitude of sustained oscillations in the states of the network. To evaluate properties of such oscillations in the time domain, it is usually required to conduct long-term stochastic simulations, using for example the Gillespie algorithm. In this paper, we present a new method to compute the amplitude distribution of the oscillations without the need for long-term stochastic simulations. By the derivation of the method, we also gain insight into the structural features underlying the stochastic oscillations. The method is applicable to a wide class of non-linear stochastic differential equations that exhibit stochastic oscillations. The application is exemplified for the MAPK cascade, a fundamental element of several biochemical signalling pathways. This example shows that the proposed method can accurately predict the amplitude distribution for the stochastic oscillations even when using further computational approximations.
PACS Codes: 87.10.Mn, 87.18.Tt, 87.18.Vf
MSC Codes: 92B05, 60G10, 65C30
1. Introduction
Oscillations are a widely occurring phenomenon in the dynamics of biological systems. On the intracellular level, oscillations occur for example in the activity of various genes or signalling proteins. To gain more insight into the processes related to these oscillations, mathematical models for the underlying biochemical and genetic networks are commonly constructed. Such models have proven helpful in connecting the underlying biochemistry with the temporal characteristics of emerging oscillations and the associated biological function. Examples for this type of results include the intracellular circadian clock
In dynamical models for biological systems, oscillations are due to limit cycles or more complex attractors in deterministic frameworks, or may emerge from various stochastic effects in stochastic frameworks. Concerning the biological function, one would not expect that it makes a significant difference whether oscillations are due to a deterministic limit cycle or arise from stochastic effects. For the biological function, rather the temporal characteristics of oscillations are relevant, such as their frequency or amplitude. For deterministic limit cycle oscillations, these characteristics are easily computed by a numerical simulation of the model. For stochastic models, computing the temporal characteristics of oscillations is much more involved. Two approaches are common for solving stochastic systems. In the first approach, the so called chemical master equation (CME) is used
In this paper, we develop a new method to compute the amplitude distribution for systems exhibiting stochastic oscillations. We thereby focus on systems where the deterministic part has a weakly stable equilibrium point (EP), typically with damped oscillations, and the stochastic effects induce sustained oscillations around this EP. In such systems, we can distinguish two mechanisms by which stochastic oscillations occur. For the first mechanism, the system needs to have the property that a certain small perturbation away from the equilibrium point leads to a large excursion in the state space before the system returns to the proximity of the EP
For the second mechanism, it is of interest to compute the amplitude distribution of the stochastic oscillations. Several methods to solve this problems were developed previously. In
In this article we focus on biochemical systems that can be modeled as a set of interconnected, possibly nonlinear, stochastic differential equations (SDEs). With the help of the Fokker-Planck equation (see e.g. [3, p. 193 ff.] or [10, p. 120 ff.]), we calculate the stationary density distribution in the state space. We provide a theorem allowing to calculate the amplitude distribution with only the knowledge of the density distribution and the corresponding SDE. The theorem allows not only to consider linear, but also a wide class of non-linear systems and therefore makes it possible to analyze not only systems with oscillations being of low amplitude compared to average concentrations but also of intermediate and high amplitudes. Although stochastic oscillations are a mainly two dimensional effect, we show that they also occur in higher order systems and give an example on how to analyze them then. As far as we are aware of, this paper introduces for the first time a method to analytically analyse higher order possibly non-linear systems being affected with intermediate to high amounts of noise, and thereby showing stochastic oscillations.
The paper is structured as follows. To give an easily accessible introduction to the material, we first present our results on the calculation of the amplitude distribution of stochastic oscillations and afterwards state the underlying assumptions and theorems. Then we explain the application of our theory by calculating the amplitude distribution of a simple example, the damped harmonic oscillator in the presence of additive noise, to get a first insight into the reasons for stochastic oscillations. We want to remark that this example simplifies, due to its structure, the necessary calculations significantly. As a more realistic example, we discuss oscillations in the MAP kinase cascade with an incorporated negative feedback with limited amounts of entities of each molecular species. For this system, the stationary probability distribution can be estimated by a linear approximation, or it can be computed numerically. We compare the amplitude distributions predicted by our method, based on these two approaches, to an "experimental" amplitude distribution obtained from a long-term stochastic simulation.
2. Results and Discussion
2.1. Amplitude Distribution of the Stochastic Oscillations
In this article we develop a method to derive the amplitude distribution of stochastic oscillations from the knowledge of the stationary density distribution of a stochastic differential equation (SDE). Here we first give a short outline of our results for which we present the corresponding theorems and proofs in the next sections.
Biochemical networks with stochastic dynamics can be modelled by the Langevin equation
with the state vector x ∈ ℛ2, the system's dynamics f = (
Let us denote the stationary density distribution of the system (1) by
The product on the right hand side of (2) represents the steady state flux of reactions through a certain state
The apparent complicated definition of
To normalize the probability distribution
Simple models may have additional properties allowing us to simplify (2). For linear systems the speed
We want to emphasize here that (2) allows to analytically or numerically calculate the amplitude distribution only from the knowledge of certain properties of the SDE describing the biological system without the necessity to run numerical simulations. The formula yields a good approximation for a wide class of nonlinear problems and can be used to calculate the amplitude distribution even for certain systems having more than two dimensions as we demonstrate in the second example of this paper.
2.2. Derivation of the Results
To derive the results presented in the proceeding section we analyze nonlinear SDE systems of order two as given by (1), with an asymptotically stable equilibrium point and damped oscillations in the deterministic part. We restrict our analyis to two dimensional systems, because many higher dimensional systems can be reduced to two dimensions for the purpose of analysing stochastic oscillations. In the derivation we assume w.l.o.g. that we want to compute the amplitude of the oscillations in the positive direction of
We establish an angular phase relationship of the state vector x(
We make the following assumptions on the system (1):
1. There exists a stationary density distribution
2. The deterministic formulation (
which has to be small for almost all x ∈
3. In addition we require that the average speed
Assumption 3 is obviously not satisfied in a small area around the EP where for most systems
With the help of these assumptions we are able to formulate a theorem for the calculation of the amplitude distribution of stochastic oscillations. For the formulation of the theorem let us define
i.e. the unit vector
Figure 1
Definition of
Definition of
The variable
Figure 2
Visualization of the variables
Visualization of the variables. Visualization of the variables needed to calculate the amplitude distribution of stochastic oscillations.
With the help of these definitions we can formulate the following two lemmas and a theorem, which characterizes the amplitude of the stochastic oscillations.
Lemma 1
Lemma 2
Lemma 2 is derived by considering the flux of realizations through an infinitesimaly small region around the state
Figure 3
Flux through unit cell
Flux through unit cell. The fluxes through the edges of an infinitesimal small unit cell around a state x ∈
Theorem 1 (Distribution of amplitudes)
Our results for the calculation of the amplitude distribution
2.3. Remarks
• To check if the assumptions necessary for the application of Theorem 1 are fulfilled, one can calculate
• It may be possible to relax the assumption that the curvature of the level curves does not change its sign globally. Intuitively it seems to be sufficient for most systems that the curvature does not change its sign only locally around the states
• If the Lie derivative
2.4. The Damped Harmonic Oscillator in the Presence of Additive Gaussian White Noise
2.4.1. Equations and Properties of the System
In this section we give a motivational example for the application of Theorem 1 by discussing the behavior of the damped harmonic oscillator in the presence of additive Gaussian white noise. The oscillator satisfies the following Langevin equation:
with Γ
It is easy to show that the deterministic system (
are at λ1,2 = -
2.4.2. Calculation of the Density Distribution
with Σ the matrix of the noise terms of (1). We call (11) linear if ∀
For the system (9),
with ⟨ x ⟩ the mean value of x and Ξ the matrix of the second moments of P, which is the solution of the equation AΞ + ΞA
2.4.3. Determination of the Amplitude Distribution
To get the amplitude distribution
After some calculations we obtain
Due to the linearity of the oscillator (9) and the symmetry of the harmonic oscillator, we can determine the amplitude distribution by utilizing formula (5) as
Figure 4
Amplitude distribution of the oscillations of the damped harmonic oscillator
Amplitude distribution of the oscillations of the damped harmonic oscillator. Amplitude distribution of the oscillations of
This easy example was discussed to give an insight into the reasons for stochastic oscillations. In the next section, we show the practical applicability of our algorithm by predicting the amplitude distribution of a complex biochemical system and therewith give an example of a more biologically relevant application for the results of the paper.
2.5. Oscillations in the MAP Kinase Signaling Cascade
In the following section we apply the algorithm developed in this paper to a realistic example from biochemical signal transduction. A frequent module in many eucaryotic cells from yeast to mammals is the mitogen activated protein (MAP) kinase signaling cascade. MAPK cascades are typically activated by extracellular stimuli such as growth factors, and regulate the activity of various genes, thereby provoking a cellular response to the applied stimulus. Many important cellular functions such as differentiation, proliferation and death are controlled by MAPK cascades
Figure 5
Schematic view on the MAP kinase signaling cascade
Schematic view on the MAP kinase signaling cascade. Schematic view on the MAP kinase signaling cascade. The species with the stars (*) are the phosphorylated versions of the species without stars. MAPKKK* catalyzes the phosphorylation of MAPKK, MAPKK* in turn catalyzes the phosphorylation of MAPK. A negative feedback is given by the repression of the activation of MAPKKK by MAPK*.
2.5.1. The Deterministic Model
For this example, we use a basic ODE model of the MAP kinase signaling cascade. The model contains a negative feedback interconnection from the last kinase MAPK to the activation of the first kinase MAPKKK
we get the deterministic description of the system using mass balancing with Michaelis-Menten reaction kinetics:
with the reaction rates given by
The parameter sets for the phosphorylation (
Table 1
Parameter Set for the MAP Kinase Signaling Cascade
The biochemically relevant equilibrium point x0 of the system is computed as
We can determine the local stability of this EP by analyzing the Jacobian
and thus the deterministic system is locally asymptotically stable.
2.5.2. The Stochastic Model
For validation purposes and to get a first insight into the system's dynamics, we did stochastic simulations of the biochemical network model of the MAPK cascade as described by (19). We used the stochastic simulation software Dizzy by the Institute for Systems Biology
Figure 6
Oscillations of the MAP kinase signaling cascade
Oscillations of the MAP kinase signaling cascade. Plot of the oscillations of the MAP kinase signaling cascade. The plot is the result of a stochastic simulation via the Direct Gillespie approach with Dizzy.
As discussed in
with Γ
2.5.3. Transformation and Model Reduction
The theoretical results in this paper have been developped for two-dimensional systems only. In higher order systems stochastic oscillations may appear on a two dimensional manifold in the state space. Such a system can be reduced to an order two system by computing the slow manifold, making use of a time scale separation
The transformation needs to be done in such a way that the absolute values of the real parts of the eigenvalues of
The two eigenvectors with non-zero imaginary parts,
with the transformation matrix T = (e1, e2 + e3, (e2 - e3)·
Because all of the eigenvalues (22a)-(22b) have non-zero real parts, the Hartman-Grobman theorem states that there exists a local transformation z = H(
Because in the
We substitute (31) in
Table 2
Parameter Set of the Slow Manifold of the MAP Kinase Signaling Cascade
Figure 7
Slow Manifold of the MAP kinase signaling cascade
Slow Manifold of the MAP kinase signaling cascade. Slow manifold of (20) calculated up to the order of four. The black curve is a representative trajectory of the deterministic system.
The slow manifold is attractive enough so that realizations of the stochastic system (25) will stay close to it. Due to this, it is sufficient to just take the oscillations on the slow manifold into account and therewith simplify the problem to two dimensions. We substitute the formula of the slow manifold (31) in the differential equations for
to which Theorem 1 can be applied.
2.5.4. Calculation of the Density Distribution
As a first approach to obtain the stationary density distribution
The linear approximation of the reduced system (32) is given by
with the system matrix
and Γ the vector of the disturbances Γ
From the coordinate transformation
where diag(
Following the same approach as in the previous example, the stationary density distribution is obtained as
for a cell with a volume of
Figure 8
Linear distribution of the state of the MAP kinase signaling cascade
Linear distribution of the state of the MAP kinase signaling cascade. Linear density distribution of the MAP kinase signaling cascade on the slow manifold as calculated in (37). Because we linearized the system, the distribution is Gaussian.
2.5.5. Determination of the Amplitude Distribution
With the preliminary work of the preceding sections we are now able to calculate the amplitude distribution according to Theorem 1. We consider the states xχ = (
The probability of the amplitude
under the constraint that z
The resulting amplitude distributions in each of the three original coordinate directions
Figure 9
Linear amplitude distribution of the oscillations of the MAP kinase signaling cascade
Linear amplitude distribution of the oscillations of the MAP kinase signaling cascade. Linear amplitude distribution of the oscillations of the MAP kinase signaling cascade. The solid curve corresponds to data determined by stochastic simulation of the nonlinear system (24), the dashed curve is the prediction according to the calculations in this section.
As can be seen in Figure
We also want to mention that we compare the results obtained from our method to stochastic Gillespie simulations, and not to realizations of the Langevin equation (24). The reason herefor is that Gillespie simulations better predict the behavior of biochemical networks and are thus the method of choice. However in the derivation of the amplitude distribution we approximated the stochasticity of the system using white noise terms. The results of both methods to describe the intrinsic noise of the system may under certain circumstances lead to different results, which may be a further explanation of the small bias between the measured and the theoretical predicted amplitude distribution in Figure
2.5.6. Numerical Approach
Sometimes it is not adequate anymore to analyze the linearized system and one has to analyze the original nonlinear one. Although there might be several special cases where the probability distribution
To calculate the density distribution of the nonlinear system we have to solve the nonlinear Fokker-Planck equation (11). We therefore applied the algorithm developed in
Figure 10
Nonlinear Distribution of the state of the MAP kinase signaling cascade
Nonlinear Distribution of the state of the MAP kinase signaling cascade. Density distribution of the MAP kinase cascade on the slow manifold (31).
From the density distribution
Figure 11
Nonlinear amplitude distribution of the oscillations of the MAP kinase signaling cascade
Nonlinear amplitude distribution of the oscillations of the MAP kinase signaling cascade. Nonlinear amplitude distribution of the oscillations of the MAP kinase signaling cascade in the negative
3. Conclusion
We introduce a method to determine the amplitude distribution of a wide class of linear and nonlinear stochastic systems given by (1), which display sustained stochastic oscillations. The method is applicable to systems where a stationary density distributions exists and can be computed either analytically or numerically.
The method is based on computing the flux density of realizations for the states where the tangent on the level curve of the density distribution is normal to the direction in which the oscillations are measured. We showed that under certain conditions this flux density is directly proportional to the probability of an oscillation with an adequate amplitude to occur. Our results can be used in the analysis of systems being influenced by strong internal or external noise, as we often find them in biophysical problems.
As already discussed at the end of the second example, for certain systems the calculated amplitude distribution may contain a small bias depending on the exact structure of the system and on how well the the assumption necessary for the application of our method are satisfied. For the wide class of nonlinear systems analyzed we could obtain as a result that realizations being at state
Stochastic oscillations may occur in biological systems not only as a disturbing side effect, but also in a constructive manner
Proof for Lemma 1
In this section we give a short proof for Lemma 1. We therefore consider the level curve defined by
In the following we argue that there exists a
After substituting the definitions made in the equations (8) and utilizing the knowledge that
If we stay on a level curve, it must hold that
Because the coefficients of
This means that we may approximate a level curve of the density distribution locally by a parabola. For small deviations and small times
We can rewrite the norm of the first row elements of
which can be easily validated by the definitions of
Putting everything together we get a one dimensional Wiener process for the movement of (1) in the direction of
with Δx(
Because the stochastic part of (49) may be neglected (see Assumption 4), we can get a linear one dimensional stochastic equation for the movement of (1) in the direction of
It can be shown [10, p. 129 ff.] that the variance of (51) evolves as
We may think of the solution of (51) as a growing Gaussian distribution moving along the trajectory of the deterministic system (see Figure
We can now calculate
For a Gaussian distribution it is true that 68.3% of all realizations stay in an area around the average displacement determined by the standard deviation. This means that only
In the same way it can be shown that 95.5% of all realizations have an amplitude lower than
Proof for Lemma 2
Assume a small unit cell with the edge lengths
By letting
Proof for Theorem 1
Because the density distribution
From the condition
Because of Lemma 2 we know that the flux density
Although we do not know the exact shape of Ω (
For small
Numerical Solution of the Fokker-Planck Approximation of the Chemical Master Equation


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