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32 year old woman | Woodland Park, CO, USA | Seeking men 28-35 within 20 miles
Short, blonde and funny. I think.
I love animals, the outdoors, sports and music. I work hard but also like to get out and play. Family is important to me, though most of my family are friends and pets. I am getting to the age when it would be nice to settle down and have kids, not getting any younger I suppose. Just looking for someone who enjoys the same along with the simple things in life. I'm mildly annoyed about being on this site, but since I work 6 days a week and live in a mountain town where everyone is married and over 40, I think I'm in trouble as far a meeting someone. I'd like to have kids, get married and live on a spread of acreage full of animals in the future...but a year or two down the road. I have so many things I want to see and do before I'm caring for tiny people of my own. I love football, NFL mainly. I love camping, the great outdoors, fishing, ATVing, road trips, movies, snowboarding, movies, riding horses, concerts, etc. Playing in mud is great. I can be a tom boy, grew up on a farm. I like to dress up now and again but you'll likely find me wearing jeans and cowboy boots most often. I'm independent so if you're looking for a clingy girl, I'm not it. But I love goofy stuff like Family Guy and Star Wars, so I think that makes me appealing, lol. I have given up on the bar scene and the like..tired of wasting time on guys that think love is a game and commitment is a waste. I'm actually not a cynic and can be deceiving as far as my interests...I'm a farm girl but one who likes to think and talk about books, pop culture, history and the like. Or I can eat jelly beans and Red Bull and go into a sugar fit where I can be dared to do just about anything a 7 year old might agree to. My animals are a pretty big part of my life, they're my kids after all. If ya don't like animals or animals in the house, hmmm, suspect. I'm pretty laid back, sarcastic (sorry), love to laugh and would die to meet someone who can appreciate that.
Camping , Fishing/Hunting , Movies/Videos , Music and concerts , Exploring new areas , Performing arts , Playing sports , Travel/Sightseeing , Volunteering , Watching sports
Auto racing / Motorcross, Billiards / Pool, Football, Martial arts, Other types of exercise, Skiing, Weights / Machines
I exercise 3-4 times per week.
I have Cats, Dogs, Fish
I like Birds, Exotic Pets, Horses
I have a 58 lb dog, two cats and a fish named Sly Stallone. I love my pets. Yes, they sleep with me. I doubt that will change. There are days when they're the only ones I care to hang out with!
I don't get to travel much (unfortunately) but love Yellowstone & Jackson Hole. Anyplace with mountains...someday hope to see the ocean. Yep, never have.
The Ohio State University, Columbus, OH
I was raised on country music so it's def my soul, but I love just about any kind of music, except death metal. I have the most eclectic music collection...ever.
In the winter, I'm an avid snowboarder. My summer months are also spent outdoors. I love anything that involves nature, animals and music. Horses, atv's, and snowboards are my seasonal modes of transportation.
"Lonesome Dove" by Larry McMurtry and currently re-reading "All Quiet on the Western Front"...one of my all time faves ever.
Z{{Cta}} {{#if HasMoreInfo}} ?{{CtaSecondary}} {{/if}}
|What she is looking for
|5'3" (160cms)
|5'8" (172cms) to 6'2" (187cms)
|Body type:
|About average
|About average, Athletic and toned, A few extra pounds, Stocky
|No preference
|Black, Light brown, Dark brown, Blonde, Salt and pepper, Silver, Dark blonde, Grey, Platinum, Bald
|No Way
|No Way, Yes, but trying to quit
|Social Drinker
|No preference
|Medical / Dental / Veterinary / Fitness
|No preference
I work with animals and I love it. I hope to make a bigger, more successful career out of it one day, once I finish college.
|Less Than $25,000
|No preference
|Never Married
|Never Married, Widow / Widower, Divorced
|Have kids:
|No preference
|Wants kids:
|No preference
|White / Caucasian
|No preference
Scotch, Cherokee Indian and Irish. And, I swear like it.
|Spiritual but not religious
|No preference
I hold pretty strongly to a lot of Native American values like, right vs. wrong, respect nature, elders, etc.
|Some college
|No preference


text:
Book Search
Public Debt Sustainability in Developing Asia
Addressing the global financial crisis has required fiscal intervention on a substantial scale by governments around the world. The consequent buildup of public debt, in particular its sustainability, has moved to center stage in the policy debate. If the Asia and Pacific region is to continue to...
Published December 30th 2014 by Routledge
Routledge Handbook of South Asian Economics
The Routledge Handbook of South Asian Economics addresses the recent economic transformation in South Asia. Leading experts in the field look at the major economic achievements and challenges for the region and examine why economic development across the South Asia region has diverged so...
Published June 14th 2011 by Routledge
Modern Public Economics Second Edition
Series: Routledge Advanced Texts in Economics and Finance
In recent times not only have traditional areas of public economics such as taxation, public expenditure, public sector pricing, benefit cost analysis, and fiscal federalism thrown up new challenges but entirely new areas of research and inquiry have emerged. This second edition builds upon the...
Published October 13th 2009 by Routledge
Environmental Sustainability
A Consumption Approach
Series: Routledge Explorations in Environmental Economics
With globalization fast becoming an irreversible process, it is necessary to pay increased attention to the implications for environmental sustainability. However, the so-called environmental Kuznets curve (EKC) argument implies that rapid economic growth in many developing countries should be...
Published March 25th 2009 by Routledge
Macroeconomics for Developing Countries
2nd Edition
Series: Routledge Advanced Texts in Economics and Finance
This comprehensively revised and updated edition develops the themes contained in the first edition. Students and teachers who are familiar with the book will notice that half of the chapters are entirely new, with the other half having changed significantly to take into account the changes that...
Published March 13th 2003 by Routledge
Modern Public Economics
This wide-ranging, up-to-date and detailed account of all aspects of public economics covers topics as varied as: * classical theorems of welfare economics* the theory of public expenditure* the effects of taxation on savings, labour supply investment and risk-taking* commodity, income...
Published December 25th 1997 by Routledge

subset: commoncrawl


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portrait of beautiful young woman with wine glass, black and white retro stylization
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Feature...CNU 23DALLAS/FORT WORTH 4/29-5/2/2015»»»
climate change
The Convenient Truth: Cities and SustainabilitySubmitted by tbellino on Fri, 05/02/2008 - 4:44pm
Description: The relationship between cities and climate change seems little understood, even as the world awakens to global warming and exploding urban populations. New Urbanism must show that compact connected cities and suburbs with efficient bui... read more »
Green Council Working SessionSubmitted by Filmanowicz on Fri, 05/02/2008 - 4:04pm
Description: Saturday, April 5, 2008 9:45 AM - 12:30 PM As a follow-up to the Green Council held in Alexandria, Va., this working session builds on work laid at this historic event. John Norquist presents a slideshow documenting how urbanism is a co... read more »
Urbanism and Climate Change in the U.S.Submitted by Filmanowicz on Wed, 04/04/2007 - 11:31am
Description: As we continue to confront global climate change, the role of Urbanism – new and old - will become increasingly central to the sustainability of our environment. A big share of the green house gases that contribute to rising global t... read more »


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How To Be The Champion
As my high school history teacher Tom "Moto" Pile used to challenge we students: He used to goad… Do you have what it takes? Do you have MOX….ie?! Are you gonna suck it up, or are you too LA…zy!? You gotta have GUMP…shun! You gotta want it! In re-telling, he sounds mean. But, it was actually good, tough love. Moto …Read More
5 Clever Business Lessons From The Sport Of Orienteering
Ever heard of Orienteering? Orienteering is an outdoor sport where you have to figure out where to go based on figuring out where you are. Running a business in today is a lot like Orienteering. I figure there are Orienteering lessons we can apply to Marketeering. Here's what I found… In Orienteering, competitors race through unfamiliar (and often rugged) terrain …Read More
Brainstorming: Sponge Versus Sieve
One of the reasons we find brainstorming intimidating is that some people are better than others in squeezing ideas out of their heads. These people – while amazing because they seem to have magical powers and some conduit to divine inspiration – make the rest of us feel stupid and doubt our creative ability. Why can't I pop out ideas …Read More
Productive or Active?
This sticky note has been stuck to my computer monitor for a while. Now I have a smaller note that states "busy ≠ productive." Often we're merely active in what we're doing. Activity feels busy. But it's not necessarily productive. Are you keeping yourself busy to avoid a project? Or have you fallen into the trap of doing busy work …Read More
Participants versus Attendees
I don't think I've shared this story with you. One of my great bosses at Starbucks marketing used the expression, "The price of admission is participation." What she meant was, if you want the privilege of being in the meetings the price you paid was adding value with thoughts and suggestions. One way to make meetings more efficient is to …Read More
The Five Stages Of Idea Acceptance
The book What A Great Idea! 2.0 by Chic Thompson is chock full o' bits of wisdom that help with creativity and creating new ideas. One bit Chic writes about, is how new ideas are often struck down with "killer phrases." These phrases reflect the lack of acceptance of something new or different. We're all aware of these killer phrases, …Read More
Put A Smile In Your Voice
The image below is a relic from my first out-of-college job with the Disney Company. A page from a "While You Were Out" message pad. (I re-discovered this as a bookmark in my copy of George Orwell's 1984). I was a marketeer at the Disney Vacation Club (Disney's non-timeshare timeshare) when it first launched in '92. We call …Read More
Taking Action: 8 Ways to Classify Ideas
A fair amount of writing about brainstorming emphasizes not judging ideas too soon. A plethora of criticism about brainstorming argues it isn't critical enough. No matter how you think-up ideas, eventually they must prove themselves worthy of helping you meet your objectives. A great way to evaluate your ideas is by categorizing them into what Edward de Bono in his …Read More


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Free Software News Archives
Samba 4.0.0 Officially Released
At long last Samba 4.0.0 has seen the light of day. Samba 4.0 was officially released today as the major rewrite of this widely used SMB/CIFS implementation.
11 December 2012 - Woohoo - 8 Comments
SparkleShare 1.0 Released For Git-Based File Sharing
SparkleShare is an open-source file synchronization and collaboration tool that's powered by Git. After being in development for a long time, SparkleShare 1.0 was released on Sunday.
10 December 2012 - SparkleShare - 5 Comments
A New Project To Run Mac OS X Binaries On Linux
While there is the Wine project to run native Windows binaries on Linux (and other platforms), there's a new open-source project that's emerging for running Apple OS X binaries on Linux in a seamless manner.
8 December 2012 - Darling - 58 Comments
A Deep Look Into GPUs & Linux Graphics Drivers
Martin Peres, the developer who has been a longstanding contributor to the Nouveau graphics driver project, delivered two presentations at a recent French Linux event where he provided an introduction to graphics processors and the Linux graphics driver stack. The second talk focused upon GPUs and Linux drivers in much greater detail.
7 December 2012 - Martin Peres - 5 Comments
Lima GPU Driver Faces Changes, Advancements
There are significant driver changes to report on for the reverse-engineered open-source Lima graphics driver project for providing ARM Mali graphics support.
7 December 2012 - Lima Driver Shake-Up - 9 Comments
Enlightenment E17 Goes Into Beta
After pushing out eight alpha releases in a feverish pace, Enlightenment E17 is now into a beta state after being in active development for the past decade.
7 December 2012 - E17 Beta - 10 Comments
DarkTable 1.1 Supports OpenCL For Images
DarkTable is an open-source photography workflow application and RAW developer that provides a virtual light table and dark-room. The 1.1 release of this leading free software program for dealing with RAW images now supports utilizing OpenCL plus other new features.
6 December 2012 - DarkTable - 5 Comments
A New Build Of Qt 5.0 Surfaces For Testing
Digia has put out a new Qt 5.0 package for those interested in testing out this major tool-kit update that will hopefully be released before month's end.
4 December 2012 - Qt 5.0 Digia - 1 Comment
Git 1.8.1 Adding New Features, Fixes
One month after Git 1.8.0 was released, Git 1.8.1 is now being prepared with several new features as well as fixes.
4 December 2012 - Git 1.8.1
FlashFire: Buffer-Based Write Reordering For SSDs
FlashFire is a buffer-based write reordering layer for SSDs on Linux, which can lead to greater disk performance for flash-based storage devices.
3 December 2012 - Write Reordering Layer - 3 Comments
Qt 5.0 Release Still Planned By Year's End
Lars Knoll has laid out his plans for branching the Qt 5.0 code-base and seeing the long-awaited update to the popular open-source toolkit see the light of day before year's end.
28 November 2012 - Qt 5.0
Enlightenment E17 Alpha 6 Packs Many Changes
It's time yet again for another Enlightenment E17 Alpha release. It's only been four days since E17 Alpha 5 but there is now already E17 Alpha 6 with a huge number of changes.
28 November 2012 - E17 Alpha 6
LibreOffice 4.0 Alpha 1 Is Freed For Testing
For those interested in testing out a new open-source office suite this holiday weekend, LibreOffice 4.0 Alpha 1 was quietly tagged this week.
24 November 2012 - LibreOffice - 54 Comments
Enlightenment E17 Alpha 5 Works On Its Default Theme
New Enlightenment E17 Alpha releases are coming out at a record pace considering that it's taken a decade to get to the first alpha stage. E17 Alpha 4 came just three days ago and there's already a fifth alpha now available.
24 November 2012 - Enlightenment E17 - 7 Comments
Jolla Presents Sailfish OS MeeGo-Fork
Jolla, the Finnish company that was formed by many ex-Nokia employees that were responsible for their MeeGo work and the Nokia N9 smart-phone until Nokia jumped in bed with Microsoft for the Windows Phone, finally showcased its Linux OS today: Sailfish, a fork of MeeGo Linux.
21 November 2012 - Jolla - 26 Comments
Enlightenment E17 Alpha 4 Released
Just a couple days after the release of E17 Alpha 3 there is a fourth alpha version of the forthcoming Enlightenment release.
21 November 2012 - New Release - 6 Comments
Gentoo Developers Unhappy, Fork udev
The udev code-base has been forked by Gentoo Linux developers after they -- and other parties -- have been unhappy with the future direction of udev as set by systemd developers.
16 November 2012 - Udev Forked - 96 Comments
Netflix Comes To Linux Via Silverlight On Patched Wine
Netflix video streaming is now available on Linux through the use of Wine. When running a specially patched version of Wine in conjunction with the Microsoft Windows versions of Firefox and Microsoft Silverlight, Netflix can now do Internet video streaming to the Linux desktop.
15 November 2012 - Netflix - 21 Comments
CGit Maintainer Disappears, Security Hole Found
The maintainer behind the open-source CGit project, the popular web front-end to viewing Git repositories, disappeared some months ago. Since then a new maintainer has taken over work on this widely-used software while also discovering a nasty security hole that allows arbitrary command execution. A new CGit release has now occurred under the new leadership to address this problem.
15 November 2012 - Disappearance - 6 Comments
Canonical Releases Upstart 1.6
While most Linux distributions have moved on to using systemd as their init daemon replacement, Canonical is still investing in their Upstart init daemon for Ubuntu. Upstart 1.6 has now been released and it presents several new features.
15 November 2012 - Ubuntu Job Supervisor - 69 Comments
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GM recently made waves for claiming that its new electric Volt gets 230 mpg, but the magic number seems more like 40. That's because miles per gallon really only matter when a gas engine combusts. The Volt on the other hand will go around 40 miles on its electric battery before switching over to gas. If customers drive less than 40 miles per day, and if GM keeps the price under $40K (plus a $7,500 federal tax credit), many Americans could find themselves getting unlimited mpg for whatever it costs to plug in. So can GM really claim that the vehicle gets 230mpg? That's where public debate heats up.
6 Comments
December 8, 2010 at 6:40 pm
[…] that consumers are finally ready for electric vehicles. Between the Nissan Leaf, Coda Sedan and Chevy Volt (all of which are supposed to be released this month), only the Volt has a hybrid gas-electric […]
August 20, 2009 at 11:25 pm
So my question is, If the batteries are drained and you're just using the gas motor to generate the electricity for the propulsion. What is the gas mileage??? Reason being, if it's better the 40mpg WTF do you need batteries for??
August 13, 2009 at 4:36 pm
Why can't people see the fact that hybrids are more of a danger to the environment by burning coal? The truth is, traditional cars are better than hybrids. Wake up guys.
August 12, 2009 at 4:27 pm
If even half of GM's claims are true, then this car will be a significant step forward. As for the price, sure, 40K is a good chunk of change, but you can be sure it will come down, just like all technology prices do.
Not to get political, but let's get political: all those pundits who were gleefully predicting the death of GM and by extension, the Obama administration, can go suck on a rock. GO USA!!


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Life. Support. Music. Sad. Story. Bad. Movie.
The material covered in the documentary Life. Support. Music. could bring any stoic to convulsive tears. The film's subject, Jason Cringler, was a 34-year-old LES clubrock fixture, sought-after session axeman, and expectant father when, at a gig one night, he had a big ol' brain-bleeding aneurysm, leaving his body curled and clenched like a Pompeii victim. The grinding struggle to regain the simplest motor skills was recorded by Jason's medical personnel. Entrusted with this deeply private, wrenching footage, software-happy filmmaker and family friend Eric Daniel Metzgar (previous credits include James Blunt in Kosovo) has made a not-very-good movie marked by his consistent inability to let the material speak for itself. Photos of a young Jason are accompanied by a slightly creepy telegraphic litany of coming-of-age moments ("Parents' divorce. Guitar lessons. Euphoria.") When Jason goes back onstage for a neighborhood crowd, Metzgar voice-overs a streak of purple prose instead of letting the man's playing speak for itself. ("Something exceptional and quite indescribable occurred"—well, you don't need to describe it if you've got the feed from the sound boards.) Jason, for his part, consistently comes off as a low-key guy who, faced with the worst possible of circumstances, chinned-up and did what he had to do, as ever: "We did the gig."
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Letters to the Editor: 05.27.09
Beatrice Juarez
Not enough trees
I moved here last July from Salinas, Calif. I am a little disappointed with Corpus Christi not having trees at every home. I look down residential streets and at our parks and I hardly see any.
Where I lived in California, our front yard, as well as in our backyard, we were able to plant a tree for every child (7) we had. Our yard was so beautiful.
This is something the City of Corpus Christi should start implementing because of all the refineries around us. Not only would more trees bring beauty to our streets, but they would also clean the air.
I believe that with every new home development, it should be a requirement for the developers to plant a tree in front of the home near the curb of every house they build. And we need to plant more trees in our parks. It's unbelievable that most of our parks do not have shade for children when they are playing.
Perhaps the refineries should start donating trees to be planted every 12 to 24 feet surrounding their properties, as well as promoting tree-planting throughout the community. Something needs to start. We should start making a difference in our city. Plant a tree!
Santiago J. Flores
Value too high
I recently purchased a 1994 Ford Pickup for $1,000. Before I purchased the truck, I did research on its value. I checked three sources through the Internet — Kelly Bluebook.com, Edmonds.com, and CarPrice.com (all three were comparable as far as the value of the truck). The price ranged from $1,300 to $1,500 through third-party sale.
I then went to the Nueces County Courthouse to change the car title to my name and I spoke to a woman at the counter and told her that I paid $1,000 for the vehicle. She informed me that I owed $227.00 for sales taxes. I asked her why the taxes were so high; she said that the State of Texas placed a value of $3,636 on the vehicle. I asked her how the state determined the value of vehicles and she said the state used its own (DPS) software. Apparently this software does not take into consideration the mileage or condition of the vehicle to determine the sales tax.
How could there be a discrepancy of $2,136 between the state's valuation and the price I paid? I wonder if the Nueces County Appraisal District is using the same software to determine property values.
– – – –
Cecil Smith, Rockport
Saving pennies
President Obama has proposed a 2010 budget with a price tag of $3.5 trillion. It will require an additional $1.2 trillion of new debt. In an attempt to placate those of us who think he is putting the country in a debtors' prison from which we may not be able to escape, he says that he has scrubbed this budget "line by line" and identified $16.7 billion of savings.
When critics pointed out that these savings are inconsequential and represent less than a half of a penny for every dollar proposed, Obama says that these savings are not trivial and "is a lot of money." Yet when he recently signed off on the 2009 budget bill with 9,000 earmarks costing taxpayers more than $13 billion, he dismissed critics of the earmarks by saying that the $13 billion was minor in the grand scheme of things. So I guess he expects us to give him a pass on the earmark spending but give him a pat on the back for saving a half a penny.
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text:
A multi-laser flow-cytometry system provides for inter-location emissions crosstalk cancellation, through either pulse subtraction or gating, to avoid false triggering based on shadow (pre- and post-) pulses that occur when red-excited red emissions are detected by a photodetector arranged to detect blue-excited red emissions. This overcomes a problem of undercounting of counting beads that led to misdeterminations of cell counts when blue-excited red fluorescence detections were used as a trigger. The approach also provides for more accurate quantitative data regarding fluorochrome emissions amplitudes.
1. A particle analyzer comprising:
flow means for flowing particles, including a first particle type and a second particle type, through a first location and through a second location;
first illumination means for illuminating said particles at said first location with light having a first spectral distribution;
second illumination means for illuminating said particles at said second location with light having a second spectral distribution different from said first spectral distribution;
first detection means for generating a first indicator when a particle of said first particle type is at said first location;
second detection means for generating a second indicator when a particle of said second particle type is at said second location, said second detection means also providing a third indicator when a particle of said first particle type is at said first detection location; and
cancellation means for at least partially canceling said third indicator in response to generation of said first indicator.
2. An analyzer as recited in claim 1 wherein said first particle type fluoresces when excited by illumination having said first spectral distribution, wherein said second particle type fluoresces when excited by illumination having said second spectral distribution, and wherein said second detection means detects fluorescence from said particle of said second type when it is at said second location, said second detection means also detecting fluorescence from said particle of said first type when it is at said first location.
3. A particle analyzer as recited in claims 1 wherein said second detection means transmits said second and third indicators along a channel, said first indicator having a duration, said cancellation means canceling said third indicator by gating said channel for said duration of said first indicator.
4. A particle analyzer as recited in claim 1 wherein said cancellation means cancels said third indicator by subtracting therefrom a fourth indicator derived from said first indicator.
5. A particle analyzer as recited in claim 1 wherein said particles have a transit time between said first and second locations, said second detection means having an output including said second and third indicators, said canceling means subtracting from said output a concurrent indicator derived from said first indicator and a time-shifted indicator derived from said first indicator and time-shifted relative to said concurrent indicator by said transit time.
6. A method of analyzing particles, including particles of a first type and particles of a second type, said method comprising the steps of:
flowing said particles through a first detection location illuminated by light of a first spectral distribution and through a second detection location illuminated by light of a second spectral distribution different from said first spectral distribution;
generating a first indication when a particle of said first type is at said first detection location, generating a second indication along a second channel when a particle of said second type is at said second detection location, and generating a third indication along said second channel when said particle of said first type is at said first detection location; and
at least partially canceling said third indicator in response to said first indicator.
7. A method as recited in claim 6 wherein particles of said first type fluoresce when excited by illumination of said first spectral distribution and particles of said second type fluoresce when excited by illumination of said second spectral distribution, said generating step including detecting fluorescence from a particle of said first particle type at said second location.
8. A method as recited in claim 6 wherein said second and third indictors are transmitted along a channel, said first indicator having a duration, said canceling step involving gating said channel for said duration.
9. A method as recited in claim 6 wherein said canceling step involves subtracting from said third indicator a fourth indicator derived from said first indicator.
10. A method as recited in claim 9 wherein said particles have a transit time between said first and second locations, said generating step involving generating an output including said second and third indicators, said canceling step involving subtraction from said output a concurrent indicator and a time-shifted indicator, said concurrent indicator being derived from said first indicator, said time-shifted indicator being derived from said first indicator and time-shifted by said transit time relative to said concurrent indicator.
11. A particle analyzer comprising:
flow means for flowing particles, including a first particle, through a first location and through a second location;
first illumination means for illuminating said particles at said first location;
second illumination means for illuminating said particles at said second location;
first detection means for generating a first indicator when said first particle is at said first location;
second detection means for generating a second indicator when said first particle is at said second location; and
cancellation means for at least partially canceling crosstalk in said first indicator and generated when said first particle is at said second location.
12. A particle analyzer comprising:
flow means for flowing particles through a first location and through a second location;
first illumination means for illuminating said first location with light having a first source spectral distribution;
second illumination means for illuminating said second location with light having a second source spectral distribution different from said first source spectral distribution;
first detection means for generating a first indicator when light of a first emissions spectral distribution is emitted from said first location;
second detection means for generating a second indicator when light of a second emissions spectral distribution is emitted from said second location, said second detection means also providing a third indicator when light of a third emissions spectral distribution is emitted from said first location; and
cancellation means for at least partially canceling said third indicator in response to generation of said first indicator.
13. A method of analyzing particles, including a first particle, said method comprising the steps of:
flowing said particles through a first illuminated detection location and through a second illuminated detection location;
generating a first indication when said first particle is at said first detection location, generating a second indication along a second channel when said first particle is at said second detection location; and
at least partially canceling crosstalk generated at said second location when said particle is at said first location.
The present invention relates to analytical instruments and, more particularly, to flow particle analysis such as used in cytometry. A major objective of the present invention is to reduce false triggering in multi-laser flow cytometry systems.
A typical single-laser flow cytometry system includes a flow subsystem for flowing a particle stream along a flow path, a blue laser illumination source for illuminating a location along the flow path, several photodetectors for detecting light modulations (e.g., due to emissions, absorption, and scattering) at the illuminated flow path location, analog pulse-processing circuitry for processing the photodetector outputs, a digitizer, and a digital data processor (computer) for analyzing digitized detector data to characterize the particle stream.
The photodetectors can include a detector for forward-scattered light, a detector for side-scattered light, a green fluorescence detector, a yellow fluorescence detector, and a red fluorescence detector. The scatter detectors can be used to detect the presence and indicate the size of a particle at the illuminated location. The fluorescence detectors can be used to distinguish three fluorochromes: a blue-excited green fluorochrome (e.g., FITC), a blue-excited yellow fluorochrome (e.g., RPE), and a blue-excited red fluorochrome (e.g., PerCP).
Attempts to provide for four-way fluorochrome distinctions using a single-laser system have proved difficult due to ambiguities caused by overlap of emissions spectra. Improved four-way fluorochrome distinction has been achieved using dual-laser systems. A typical dual-laser system adds a red laser illumination source to illuminate a second location along the flow path. The additional laser allows a red-excited (and not blue-excited) red fluorochrome (e.g., APC) to be distinguished from a blue-excited (and not red-excited) red fluorochrome (e.g., PerCP). Each of these red fluorochromes are readily distinguished from the blue-excited green fluorochrome and the blue-excited yellow fluorochrome. Research and development is ongoing on extending the multi-laser approach to provide for greater than four-way fluorochrome distinctions.
The photodetector outputs not only serve as the sources of data to be analyzed, but also determine what portions of the data are to be analyzed. To this end, one or a combination of photodetector outputs can be used to derive a trigger signal that activates processing, including digitization. In the absence of a trigger signal, signals from the photodetector outputs are gated. Peak and hold circuits and subsequent digitizers are examples of analog components that can require recovery time after processing a signal. Therefore, limiting amplification of uninteresting signals can help ensure appropriate processing of interesting data. Furthermore, gating limits the amount of data that must be digitized, processed and stored.
In general, a trigger determines a window of time within which interesting data is expected and, therefore, data processing is activated. Often, a trigger is initiated when a scatter detector output crosses a threshold--indicating with a high level of certainty that a particle is in the flow-path location corresponding to the detector. The fluorescent particle detector outputs can then be amplified, digitized, and processed to identify any fluorochromes in the particle--so that the particle (which may be inherently fluorescent or tagged with one or more fluorescent markers) can be characterized.
Accurate triggering is important. A false negative, i.e., no trigger when a particle (or alternative indicator of interesting data) is present, causes a loss of valuable data. A false positive, a trigger when no particle or alternative indicator of interesting data is present, burdens the analog and digital processing systems. Furthermore, many flow analyzers fail to process new events while processing data relating to the supposed event associated with a trigger. During this "dead time", interesting events can avoid detection, causing a loss of interesting data. Thus, both false positives and false negatives can cause a loss of data required for an accurate analysis. It should be noted that the data loss is often systematic in that certain types of interesting events are more likely to be discarded than others. Thus false triggering can bias the analysis.
In a single-laser system, processing dead time after a trigger can be on the order of the time it takes a particle to traverse the laser beam where it intersects the flow path; this may be a couple of microseconds. In a dual-laser system, the processing dead time can be on the order of the transit time a particle takes in moving from the upstream detection location to the downstream detection location; this may be seven to twenty-five microseconds. More generally, in a multi-laser system, the dead time is on the order of the transit time between the first and last detection locations. Thus, the penalty in lost interesting data for false positive triggers in a dual- or other multi-laser system can be substantial.
Processing dead time in a multi-laser system can be reduced by minimizing the separation of the illumination locations. The cost of this solution is increased interlocation emissions crosstalk between illumination locations. In other words, light emitted or scattered at a first illumination location can leak to a second location so that it is detected by photodetectors arranged to detect light at the second location. In particular, red-excited red fluorescence can be detected by a detector arranged to detect blue-excited red fluorescence. This can lead to a false indication of a blue-excited red fluorochrome when there is no such material at the location illuminated by the blue laser. The converse false indication of a red-excited red fluorochrome at the flow-path location illuminated by the blue laser can also occur.
In the case a particle stimulates fluorescent emission at a location upstream of the location indicated by the detection circuitry, the false indication is referred to as a "pre-pulse". In the case a particle stimulates fluorescent emission at a location downstream of the location indicated by the detection circuitry, the false indication is referred to as a "post-pulse". Herein, the term "shadow pulse" is used to encompass both pre-pulses and post-pulses.
In general, a shadow pulse associated with a trigger signal is outside of the trigger window. For example, in a dual-laser system that triggers on the upstream illumination location, the output of a detector for the downstream illumination location is not processed until the triggering particle has had time to reach the downstream location. The pre-pulse generated concurrently with the trigger is ignored.
However, a trigger particle might fail to trigger if it passes the upstream trigger location during a dead time. If it causes a strong modulation of light when it reaches the downstream illumination location, the resulting post-pulse could result in a trigger. Since the downstream photodetector output would be ignored, there would be no indication that the trigger was false. Hence, a penalty in processing activity and dead time would ensue with no offsetting acquisition of useful data. In fact, there would be a false indication of a non-fluorescent particle; such "selective elimination" would distort the determination of the sample composition.
Evaluating the lymphocyte content of a blood sample is an example of an application in which a shadow pulse could induce a false trigger. The blood sample can be lysed and unwashed, so that sample is filled with uninteresting particles, i.e., debris. The debris particles can be so numerous relative to the white cells of interest that particle presence is not a sufficiently selective criterion for triggering. In fact, the debris can be sufficiently dense that scattering detections are practically continuous, rendering the scatter detectors essentially useless for such a sample.
Accordingly, it is appropriate to tag white cells with a fluorochrome that can be used as a trigger. From a sample preparation standpoint, it can be most convenient to tag white blood cells with blue-excited red fluorochrome, e.g., PerCP, which thus becomes the triggering fluorochrome. Other fluorochrome tags are attached to specific respective lymphocytes.
Fluorochrome detections tend to be much weaker than scatter detections; as a result, trigger thresholds for fluorochrome triggering must be set near the noise floor for the respective fluorochrome detector. A (e.g., blue-excited-red indication) shadow pulse at the trigger location, resulting from a (e.g., red-excited red) fluorochrome at the non-trigger location, can be sufficient to cross the trigger threshold at the location.
The options appear to be to accept the false triggering, to avoid samples where such false triggering is likely to arise, or to develop a scheme to minimize such false triggering where it is otherwise likely to arise. Clearly, the last option is the most attractive.
The present invention provides a multi-laser system with post-detection cancellation of interlocation emissions crosstalk. The multi-laser system includes a flow subsystem for flowing particles along a flow path, at least two lasers with different spectral distributions illuminating different locations along the flow path, and respective detectors for detecting illumination modulations at the two locations. At least one of the detectors is capable of detecting an event at its respective location causing interlocation emissions crosstalk at a detector at a different location. The invention adds means for canceling the indication of crosstalk generated by the detector responding to the optical crosstalk. In the preferred embodiments, the cross-talking detections are of fluorescence--typically red fluorescence.
Interlocation emissions crosstalk cancellation can be performed by subtracting a scaled version of the main indicator of the event causing the crosstalk from the output of the detector detecting the crosstalk. Conveniently, the subtraction can be conducted along with other subtractions designed to cancel other forms of crosstalk, e.g., intralocation emissions crosstalk due to overlap in the emissions spectra of fluorochromes excited by the same laser, and excitation crosstalk due to overlap in excitation spectra. Interestingly, in many cases the subtrahend used for canceling crosstalk in excitation spectra and the subtrahend used for canceling optical crosstalk can be derived from the same event indicator; however, the latter is concurrent with the crosstalk-generating event indicator, while the former is time-shifted by the particle transit time between the illumination locations.
As an alternative to subtraction, the output of the detector responding to interlocation emissions crosstalk can be gated for the duration of the source event indicator, e.g., detection pulse. The gating blocks an interlocation emissions crosstalk detection pulse from a trigger path or from both a trigger and a data path. However, gating also eliminates any coincident indicator. Since the coincident indicator may constitute interesting information, this incidental elimination is considered undesirable. In addition, if gating is employed, it is necessary to determine which is the source indicator and which is the crosstalk indicator so that it is not the source indicator that is canceled. Since this source indicator is likely to be much stronger than the crosstalk indicator, the determination is not hard to make. However, extra circuitry and steps are required.
Where cancellation involves subtraction rather than gating, there is little penalty for mistaking a crosstalk indicator for a source indicator. Subtracting a fraction of a relatively weak crosstalk indication from a relatively strong source indicator would be unlikely to bring the latter below a triggering threshold. Furthermore, if the crosstalk indicator happens to be superimposed on an indication of a real event that is intended to be a trigger, the trigger indicator is likely to remain above threshold after cancellation of the crosstalk indicator.
Empirical data gathered from calibration runs can be used to determine the scaling required to derive the magnitude of a crosstalk indicator from the magnitude of the corresponding source indicator. If the crosstalk corrected output is to be used for particle characterization in addition to (or instead of) triggering, a term corresponding to the predicted crosstalk indicator should be subtracted from the detector output bearing the crosstalk indicator. However, if the crosstalk corrected output is not used for particle characterization, then it can be preferable to overcompensate for crosstalk to bias the system against false triggering.
The present invention provides clear advantages over prior art systems subject to uncompensated interlocation emissions crosstalk. The invention reduces false triggering and provides more accurate particle data. Furthermore, since the adverse affects of optical crosstalk are ameliorated by the invention, optical isolation is less critical. Thus, less separation is required between illumination locations. This, in turn, reduces dead time between event processings. Thus, more useful data can be collected so that a more accurate analysis results. These and other features and advantages of the invention are apparent from the description below with reference to the following drawings.
FIG. 1 is a schematic diagram of a flow cytometry system in accordance with the present invention.
FIG. 2 is a schematic diagram of a crosstalk cancellation circuit of the system of FIG. 1.
FIG. 3 is a method performed using the system of FIG. 1 and incorporating the present invention.
In accordance with the present invention, a multi-laser flow cytometry system AP1 comprises an illumination subsystem 12, a flow subsystem 14, an optics subsystem 16, a detection subsystem 18, a signal processor 20, and a digital data processor 22, as shown in FIG. 1. Illumination subsystem 12 includes a 635 nanometer (nm) wavelength diode red laser LZR for illuminating a upstream location LCR and a 488 nm argon blue laser LZB for illuminating a location LCB 120 microns (μ) downstream. Flow subsystem 14 causes a sample stream including a white cell CEL to flow in the direction of arrow ARW from location LCR to location LCB, traversing the distance in about 20 microseconds (μS).
The sample stream is a lysed and unwashed blood sample for which the lymphocyte distribution is of interest. The sample includes count beads that are used to determine the original sample volume equivalent of sample run through the flow path. White cells are tagged with a blue-excited red fluorochrome PerCP, which is used as a pulse processing trigger. Various lymphocytes are marked with respective red-excited red, blue-excited yellow, and blue-excited green fluorochromes.
In the course of the invention, it was discovered that in a similarly configured system not incorporating the invention, the beads in a test sample were being undercounted; the undercounts led to erroneously high determinations of sample component concentrations. Further investigation indicated the system was triggering on pre-pulses generated by beads at location LCR; when a triggering bead reached the true trigger location LCB, the system aborted the event. The system was programmed to abort events that were too close together to be interpreted reliably. System AP1 applies the invention to solve this problem specifically, as well as minimize acquisition errors due to interlocation emission crosstalk more generally.
Detector subsystem 18 includes six photodetectors: a first photodetector DRR is arranged to detect red-excited red fluorescence, e.g., of APC, from location LCR; a second photodetector DBR is arranged to detect blue-excited red fluorescence, e.g., of PerCP, from location LCB; a third photodetector DBY is arranged to detect blue-excited yellow fluorescence, e.g., of RPE, from location LCB; a fourth photodetector DBG is arrange to detect blue-excited green fluorescence, e.g., of FITC, from location LCB; a fifth photodetector DFS is arranged to detect forward blue scatter at location LCB; and a sixth photodetector DSS is arranged to detect side blue scatter at location LCB. The photodetectors provide output signals RR, BR, BY, BG, FS, and SS, respectively, pulses along which indicate modulations in the light parameter the respective photodetector is designed to receive.
Optics subsystem 16 is designed to guide light of the proper spatial and spectral distribution to the appropriate one of the photodetectors, as indicated by the thicker dotted lines in FIG. 1. However, since optical isolation is not perfect, some crosstalk leaks between locations LCR and LCB as indicated by the thin dotted lines in FIG. 1. Of primary concern is crosstalk from red-excited red fluorescence that reaches blue-excited red photodetector PBR causing pre-pulses. The complementary crosstalk from blue-excited red to red-excited red photodetector DRR is also shown in FIG. 1; this crosstalk causes post-pulses. These two instances of interlocation emissions crosstalk are of concern because the resulting shadow pulses can falsely trigger pulse processing; furthermore they can cause data acquisition errors.
The photodetector output signals are processed by analog signal processor 20. Signal processor 20 includes the following components along the pulse data path: crosstalk cancellation circuit 30, transit delay circuit 32, an amplifier bank 34, pulse processor 36, peak holder 38, and analog-to-digital converter (ADC) 40. ADC 40 provides the output of signal processor 20 to data processor 22, which does the numerical analysis of the sample. In addition to the data path elements, a threshold detector 44 and a controller 46 provide for triggering and control signals for signal processor 20.
Crosstalk cancellation circuit 30 comprising scaling circuitry 50 and eight differential amplifiers serving as subtractors 51-58. All six photodetector outputs are input to crosstalk cancellation circuit 30, but scatter signals FS and SS are passed through unchanged. The four fluorescence signals, RR, BR, BY, and BG are input to scaling circuit 50. In addition, a signal RR2, which is signal RR partially corrected for crosstalk, is fed back to scaling circuitry 50 via transit delay 32.
Scaling circuitry 50 generates eight crosstalk correction terms RRR, RRS, BRS, BRR, BRY, BYR, BYG, and BGY. (In the correction term references, the first letter is the laser color, the second letter is the emissions color, and the third letter is the emissions color of the term to be corrected, with S standing for "shadow".) For each output, scaling circuitry 50 defines an input range and a scaling coefficient and constant used to scale inputs across the range. Inputs below the respective range yield a zero output value, while inputs above the respective range yield a value equivalent to that yielded by the top value of the range when scaled. Electrically, the bottom of the range is defined by a threshold input to a comparator, while the top of range is defined by a Zener diode that clips the input signal; the scaling factor is defined by a voltage divider network, and the offset is defined by a capacitance.
In accordance with the present invention, subtractor 51 subtracts from red-excited red photodetector output RR correction term BRS; signal BRS corresponds to a post-pulse generated by a blue-excited red particle at blue laser location LCB. Correction term BRS is set by scaling circuitry 50 to be about 0.3 BR. The subtraction yields signal RR1 which is an interlocation emissions crosstalk corrected version of signal RR.
Signal RR1 is directed from crosstalk cancellation circuit 30 to transit delay 32, which imposes a delay, about 20 μS, that matches the transit time of a particle flowing from location LCR to location LCB. This delay compensates for the timing misalignment between pulses generated in response to one particle at locations LCR and LCB at two different times. The output RR2 of transit delay 32 is directed to an input of scale circuitry 50 and the plus input of subtractor 52.
Subtractor 52 subtracts from RR2 excitation crosstalk correction term BRR, which is obtained from signal BR by scaling by a factor of about 0.05. All the scaling coefficients are approximate and can be adjusted according to calibration procedures. The difference signal is a crosstalk corrected indication of the APC content of the particle generating pulse RR.
Subtractor 53 subtracts from blue-excited red signal BR intralocation emissions crosstalk term BYR, which is about 0.02, to yield signal BR1. Subtractor 54 subtracts from BR1 inter-location excitation crosstalk term RRR, which is derived by multiplying signal RR2 from transit delay 32 by a factor of about 0.05. This yields signal BR2. In accordance with the present invention, subtractor 55 subtracts signal RRS which is scaled accordingly to the equation 0.33-0.2 RR in the range from 2.0-2.3 Volts. Below RR=2.0 Volts, RRS=0.0 Volts where RR<2.0 Volts; RR=100 mV where RR>2.3 Volts. Note that RRR is time shifted (by transit delay 32) relative to BR, while RRS is not. An RRS pulse thus corresponds to a pre-pulse generated at location LCR and detected at location LCB by an event indicated by a pulse of signal RR.
Subtractor 56 subtracts from blue-excited yellow signal BY intralocation emissions crosstalk term BGY=0.2 BG. The resulting signal BY1 is blue-excited yellow corrected for overlap with the blue-excited green fluorochrome (FITC). Subtractor 57 subtracts from signal BY1 correction term BRY. The contribution of signal BY to BR when RPE is the yellow fluorochrome is negligible, so the scaling factor is 0 and the output indicating PRE is the same as BY1. However, provision for a non-zero coefficient is made to accommodate alternative blue-excited yellow fluorochromes.
Subtractor 58 subtracts from blue-excited green signal BG the intralocation emissions crosstalk term BYG=0.02 BY to provide a crosstalk corrected indication for fluorochrome FITC. Thus, crosstalk cancellation circuitry 30 provides six data signal outputs corresponding to the four fluorochromes and the two scatter signals FS and SS.
These six outputs are input to amplifier bank 34, FIG. 1, which contains six pairs of parallel amplifiers. One amplifier in each pair is linear, the other is logarithmic. A control input determines, for each pair, which amplifier is to be used on the respective throughgoing signal.
The six amplified outputs are directed to pulse processor 36. For each of its six inputs, pulse processor 36 can be set 1) to pass a received pulse, 2) to generate a pulse the peak of which indicates the width of the received pulse, or 3) to generate a pulse the peak of which indicates the area of the received pulse. Pulse processor 36 also imposes a 0.5 μS delay, or about 0.25 pulse durations, on each of pulses. This delay is designed to allow the trigger signal to activate six-channel ADC 40 before the leading ends of the pulses arrive. Before they arrive, they pass through peak holder 38 holds pulse peaks so that ADC 40 need only sample once per pulse. Depending on the setting of pulse processor 36, the output of ADC indicates pulse height, pulse width, or pulse area, for each input pulse.
ADC 40 converts the incoming peak data to digital form for transmission to and processing by data processor 22. In the absence of a triggering event, controller 46 disables ADC 40 to minimize data processing and storage requirements.
The six outputs from amplifier bank 34 are also directed to respective inputs of threshold detector 44. For each input, a threshold is set. For each input, threshold detector 44 transmits a binary signal to controller 46 indicating whether the input is below or above threshold. The thresholds are set by controller 46 in accordance with user and/program instructions. Threshold indications can be disabled by setting a maximum value for an input's threshold.
Controller 46 uses the threshold indications for trigger and other timing determinations. Any of the six amplifier outputs can be selected as a trigger by selecting a suitable threshold below maximum. Any combination of amplifier outputs can be selected as a trigger by setting their respective thresholds below maximum. Controller 46 can also use threshold indications to inhibit triggering.
In accordance with the present invention, controller 46 can raise the threshold of the blue-excited red channel for the duration that a red-excited red pulse is above a 2.0 Volt threshold. This effectively gates a pre-pulse out of the triggering loop. This gating is a severe form of crosstalk cancellation. It ensures against false triggering at the expense of ignoring coincidence of a pre-pulse and real pulse being detected by the blue-excited red detector. This trigger gating approach can still permit triggering along another channel, e.g., the blue-excited yellow channel so that some coincidences are not excluded from triggering. The gating approach makes sense where the interlocation emissions crosstalk cancellation is optimized for quantization and is not biased enough against false triggering; the quantization data is available, but the gating prevents the false triggering.
Of course, as is true for the preferred crosstalk compensation, the gating can be applied to the other detection channels, e.g., the red-excited red channel to prevent triggering on post-pulses. Gating and subtraction are limited to cases where the trigger is to be blue-excited red under logarithmic amplification and where red laser LZR is on. In one embodiment of the invention, gating is not used, but interlocation emissions crosstalk cancellation by subtraction is used when these three conditions are met.
Controller 46 can perform a number of functions in accordance with user/program input. On command, controller 46 can calibrate transit delay 32 by comparing the threshold indications from photodetector DRR the APC and from any of the blue-excited detectors. Controller 46 is coupled to transit delay 32 for adjusting the delay imposed thereby. Controller 46 can adjust the functions applied by scale circuitry 50 of crosstalk cancellation circuitry 30. Alternatively, the crosstalk cancellation or other subtractions can be hardwired and thus not be adjustable. Controller 46 controls selection of logarithmic versus linear amplification according to user/program input. Controller 46 provides control signals to pulse processor 36 to determine for each channel whether peak height, width, or area is to be indicated. Controller 46 provides the timing to enable the conversion of the held peak signals by ADC 40.
Data processor 22 does the final tabulation and analysis of the data received from pulse processor 20. In some cases, crosstalk corrections are optimized to prevent false triggering rather than for data analysis. For data analysis, data processor 22 can correct for non-optimal crosstalk cancellation.
The method M1 implemented by flow cytometry system AP1 is flow charted in FIG. 3. Step S1 involves illuminating the two flow path locations respectively with red and blue laser light. Step S2 involves flowing sample cells, or other particles, past the two locations. Step S3 involves detecting red fluorescence at both locations. Step S4 involves canceling interlocation emission crosstalk from the detection from at least one of the locations. Step S5 involves applying the crosstalk corrected signal for triggering purposes and/or using the corrected signal as data to be used in characterized the sample.
While preferred embodiments of the invention have been described, those skilled in the art can apply the description to enable them to practice the invention a variety of ways. While in the described embodiment, the blue laser is downstream of the red laser, the invention is equally applicable with the red laser downstream; in this case, additional delay lines may be required in the electronic path of the upstream photodetectors. While the described embodiment is a dual-laser system, the invention is more essential in systems with three or more lasers.
In the described embodiment, gating of potential trigger pulses is achieved at the threshold detector. Alternatively, gating can be achieved at the amplifiers or electronically upstream thereof. In these cases, the gating may apply to the data path as well as the trigger path. Alternatively, crosstalk cancellation can be performed separately for trigger bound and data bound pulses; in other words, detection pulses can be duplicated and crosstalk corrected in parallel. This would allow different crosstalk coefficients to be applied to trigger and data pulse streams--allowing independent optimization for both. While in the preferred embodiment, scaling and subtraction are used to compensate for crosstalk cancellation, other embodiments apply non-linear crosstalk cancellation.
If gating is employed, it is important that the real and the shadow detections be distinguished. Otherwise, a shadow pulse could be used as a trigger or data, while a real event is ignored. To this end, a comparator can be used to compare the outputs of the two red fluorescent detectors to determine which has the stronger output. The weaker output is presumed to be the shadow, which is then gated for the duration of the other pulse.
The described embodiments correct for crosstalk in the analog domain. Where ample data processing power is available, the photodetector outputs can be converted to the digital domain without prior crosstalk correction. The present invention provides for crosstalk correction in the digital domain. These and other modifications to and variations up the described embodiments are provided for by the present invention, the scope of which is limited only by the following claims.
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After menopause, estrogen levels decline, which causes the vagina to change — and sex can become painful.
But it's treatable.
Menopause causes vaginal changes.
Menopause — for women, it's a fact of life. As we age, a decline in estrogen changes the vaginal tissues, which can lead to painful sex.
As your estrogen levels start to naturally decline with age, the vagina can become shorter and narrower. And your vaginal tissue thins, becoming quite painful.
- Dr. Tara Allmen
- Board Certified Gynecologist
Center for Menopause, Hormone Disorders & Women's Health, NYC
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Center for Menopause, Hormone Disorders & Women's Health, NYC
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- Board Certified Gynecologist
Center for Menopause, Hormone Disorders & Women's Health, NYC
Indication and Important Safety Information
Important Safety Information and Indication
What is Osphena® (ospemifene) tablets?
Osphena is a prescription oral pill that treats moderate to severe painful intercourse, a symptom of changes in and around your vagina, due to menopause.
Important Safety Information for Osphena
Most Important Information you should know about Osphena®
Osphena works like estrogen in the lining of the uterus, but can work differently in other parts of the body. Taking estrogen alone or Osphena may increase your chance for getting cancer of the lining of the uterus. Vaginal bleeding after menopause may be a warning sign of cancer of the lining of the uterus. Your healthcare provider should check any unusual vaginal bleeding to find out the cause; so tell them right away if this happens while you are using Osphena.
Osphena may increase your chance of getting strokes and blood clots.
You and your healthcare provider should talk regularly about whether you still need treatment with Osphena.
Call your healthcare provider right away if you get changes in vision or speech, sudden new severe headaches, and severe pains in your chest or legs with or without shortness of breath, weakness and fatigue. Osphena should not be used if you have unusual vaginal bleeding; have or have had certain types of cancers (including cancer of the breast or uterus); have or had blood clots; had a stroke or heart attack; have severe liver problems; are allergic to Osphena or any of its ingredients; or think you may be pregnant. Tell your healthcare provider if you are going to have surgery or will be on bed rest.
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What is Osphena® (ospemifene) tablets?
Osphena is a prescription oral pill that treats moderate to severe painful intercourse, a symptom of changes in and around your vagina, due to menopause.
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Golden Earring Artist Bio and Lyrics
Golden Earring was a Dutch Pop group that formed in the early 1960s. They released a lot of albums over the course of their career and achieved considerable success in the 1980s.
The first album from Golden Earring in the 1980s was in 1980 with Prisoner of the Night. This album was released on the label Polydor and produced by George Kooymans who also fronted the band and wrote most of the songs.
In 1981, Golden Earring released a live album, 2nd Live. Their next album was Cut in 1982. The single, "Twilight Zone," was a number one Mainstream Rock single and helped boost the album up to number 24 on the Billboard Pop Albums.
Golden Earring continued releasing albums following-up their success, in 1984 they released N.E.W.S. which slipped in the charts to number 107. Following the album the band released yet another live album, Something Heavy Going Down.
In 1986, Golden Earring tried to hold onto its success with the release of The Hole. The album only went as far as number 196 on the Hot 200 Albums but contained the number 36 single, "Quiet Eyes."
In 1989, Golden Earring released their last album of the 1980s. Keeper of the Flame was released under Batabak Records, but not well-received by the public. The album didn't meet any major success on the charts, and Golden Earring continued on into the 1990s.
Random 80's Artist
Boston -The second set of tapes was recognized by Epic, Boston was signed and the label replaced Jim Masdea with Fran Sheehan. Their debut album Boston would be a decent success. They would tour the album with Black Sabbath in 1976 and would release their follow up two years later in 1978. Don't Look Back, would only be half as successful as their debut an...
80's Music Artists|80's TV Shows|80's Films|80's Games|80's Forum
80's Band Bio biography and videos.


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|By Marketwired .
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|November 28, 2012 11:01 AM EST
SAN FRANCISCO, CA -- (Marketwire) -- 11/28/12 -- The Linux Foundation, the nonprofit organization dedicated to accelerating the growth of Linux, today announced a variety of one-year project milestones for OpenMAMA that include important new code contributions, a fully open source software stack and the first commercial offering to result from the project.
OpenMAMA is a high performance, open source Middleware Agnostic Messaging API (MAMA) that provides a common, consistent interface for passing data between high volume, low latency messaging applications. Demand for high performance messaging in multiple industries has resulted in a variety of products from a wide range of providers, often leading to complex integration scenarios. The OpenMAMA project is a collaborative effort to develop a common, ultra-high-performance middleware API that connects a variety of message passing applications, reducing integration challenges and speeding time to deployment.
OpenMAMA was announced one year ago and is a part of Linux Foundation Labs, which includes other open source software and collaborative development projects that advance Linux or the Linux ecosystem. Participants in OpenMAMA include Bank of America Merrill Lynch, IBM, EMC, Exegy, Fixnetix, J.P. Morgan and NYSE Technologies, among others.
One-year project milestones for OpenMAMA include:
* Eight software bridges have been developed for the project from a variety of organizations. Bridges enable external applications to pass data through OpenMAMA, eliminating complexity and work when integrating multiple data sources with multiple users and decreasing the difficulty of supporting custom and complex environments. Bridges and contributors include:
- AMQP implementation of Qpid, written and contributed by Red Hat
- Avis, written and contributed by NYSE Technologies
- Bloomberg Open API, written, supported and contributed by Tick 42
- Data Fabric Multi Verb, written and supported by NYSE Technologies
- Exegy, written and supported by Exegy
- LBM, written and supported by NYSE Technologies
- Rai, written and supported by Rai
- WebSphere Front Office, under development by IBM
* The OpenMAMA software stack is now completely open source, including a specific API for market data called OpenMAMDA and language support for C, C++, Java, and .Net. This completes the open sourcing process begun by project participants a year ago. From this point forward, all enhancements to the OpenMAMA codebase will come from the open source project, using proven open source development methods.
*The availability of OpenMAMA Enterprise Edition, a commercially supported and certified distribution of OpenMAMA from NYSE Technologies. This new offering is available from NYSE Technologies today as part of its Open Platform. For more information, please visit: http://nysetechnologies.nyx.com/data-technology
"The OpenMAMA project represents how collaborative development can advance technology innovation for an entire industry," said Jim Zemlin, executive director at The Linux Foundation. "In just one year, the project contributors have open sourced and expanded upon a project reduces complexity and cost for financial services companies. OpenMAMA was built for the financial services industry, but the problems it solves are also very applicable to other industries. There's already been interest from companies outside the finance industry, and we look forward to more."
"Red Hat is excited to contribute to The Linux Foundation's OpenMAMA project, which has helped push Apache Qpid's Proton initiative to a working AMQP 1.0 implementation that can be embedded in other applications wishing to support the AMQP protocol," said Brian Stevens, CTO at Red Hat. "AMQP provides an open industry standard protocol for business messaging, allowing for a new type of application development that provides automatic interoperability with other applications at the wire level in both traditional MOM and emerging architectures. We look forward to industry adoption of the OpenMAMA project and anticipate that users of the OpenMAMA AMQP combination will see great cost benefits, as well as the technical benefits provided by AMQP's architecture and design."
To start participating in the OpenMAMA project, please visit: http://www.openmama.org.
About The Linux Foundation
The Linux Foundation is a nonprofit consortium dedicated to fostering the growth of Linux. Founded in 2000, the organization sponsors the work of Linux creator Linus Torvalds and promotes, protects and advances the Linux operating system by marshaling the resources of its members and the open source development community. The Linux Foundation provides a neutral forum for collaboration and education by hosting Linux conferences, including LinuxCon, and generating original Linux research, Linux videos and content that advances the understanding of the Linux platform. Its web properties, including Linux.com, reach approximately two million people per month. The organization also provides extensive Linux training opportunities that feature the Linux kernel community's leading experts as instructors. Follow The Linux Foundation on Twitter.
Trademarks: The Linux Foundation, Linux Standard Base, MeeGo, Tizen and Yocto Project are trademarks of The Linux Foundation. Linux is a trademark of Linus Torvalds.
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Media Contact
Jennifer Cloer
The Linux Foundation
[email protected]
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Comoros - Second Economic Governance Reform Operation
IDA Grant: US $3.0 million equivalentProject ID: P150924Project Description: The objectives of the project are to strengthen economic management, promote transparency, and enhance performance in electricity... Show More +
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Mali - First Recovery and Governance Reform Support Operation
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Union of the Comoros - Economic Governance Reform Operation
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Honest, Fun, Sweet, Caring, Sports Fan, Kcco
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Charger question for France visit
I have a european style 2 prong usb charger that came with my LG hot spot from Verizon designed to let charge a usb device. Input 100-240V-50-60hz 200mA
Output 5.0V 700mA
will that safely charge my iphone 4s and iPad 3?
- Asked by Steve E from Danville
Apple World Travel Adapter Kit
Product No Longer Available
1 Answer from the Community
Best Answer:
The European adapter to USB Cable to iPad will do.
- Answered by Sahal P