text:
What can we learn by turning a trail shoe into a bubble machine? See how ASICS never stops innovating, so you can stop at never. Initiate Demo at http://www.StopAtNever.com To demonstrate the technical aspects of ASICS shoes, we created StopAtNever.com, a parallax scrolling site that houses 10 short, fun films, each about a different technical aspect of various ASICS shoes. Click to the right for a more technical look at what's being demonstrated.
Advertising Agency: Vitro, San Diego/New York, USA Creative Chairman: John Vitro Chief Creative Officers: Jonas Hallberg, Liron Reznik Creative Director: KT Thayer Copywriter: Schuyler Vanden Bergh, Simone Nobili Sr. Art Director: Cris Westrell Art Directors: Kevin Lukens, Kevin Cimo, Dominic Al-Samarraie Agency Producer: Mickey Strider Executive Digital Producer: Lina Drott Digital Producer: Christoffer Lorang Dahl Digital Production: Kokokaka Video Production: 13 Keys Video Editing: Dave Friz, 13 Keys Sound Design: 13 Keys Published: April 2012via adsoftheworld.com


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West Chicago, Illinois
September 24, 1898
Dear Mother
I will write a few lines to you. also to May. How do you feel now. do you have those awful paines in you sides. How is your cough is it as bad as before. Is it as bad to take this medicine as the other was?
Is there very many parks out and are you now near one. It is pretty nice out here. Aunt Cora's throat is a little better and Dr. has given her some medicine which is very nice. We have got lots of company-
now in our house. The company is Don and his mother Annie, and we think Rob and his wife will be up to. Annie is very sick and I have to go to the drug store every little while. I think this is all.
To May
I will write a few lines to you. I am getting along alright. Is it warm enough out there to go barefoot. If it is I will go barefoot nearly all of the time.
When Aunt Cora was out I was in the front room with my big double bladed knive ready to spear them if they made a move at me.
Yes I wish I was out there with everyone but I don't want to leave my playmates.
Do you ever see the donkies kick? I did out here.
This is all I can write.
From your Bro Willie
P.S. I will send you 10 cts
Good by. Willie
Interestingly, the dime imprint is still visible on the letter.
There is alot more than meets the eye as to the background and story behind this letter. It's probably the saddest and most tragic story that I have encountered in my family research.
Ellis Judson Ball was born 1855 in Kankakee, Illinois according to sources, which I demonstrated in my posting for Madness Monday regarding his father, Judson Ball as being my brickwall. Ellis lost his father when he was about 12. I supposed that his mother, Caroline struggled to make ends meet so Ellis was living with his married sister, Amelia and her family in the 1870 census where he went to school in Hopkins, Allegan County, Michigan. Somehow he ended up in Manton, Wexford County, Michigan where he met and married Grace Randall in 1879 and they are listed together in the 1880 census with him working in a shingle mill. Apparently Grace contracted tuberculosis and died August of 1880 just after the census was taken. Sadly, Grace was such a distant memory that this was a surprise to family members as I had discovered her existance.
One year later, in 1881, Ellis married Evora A. Hawkins in Grand Rapids. Not sure why they went there to marry as the Hawkins family also resided 1880 in Manton. In 1885, their son, William Edward was born and recorded at Wexford birth records with his sister, Celia May, born in 1887. She was commonly known to the family as "May". Other children followed: Frank born 1889, Mary Frances, Fred and twin boys. These children birth dates are quite sketchy. During this time Evora herself became infected with TB as well.
Ellis and Evora at some point moved on to Chicago with other members of Evora's Hawkins family. Mary Frances was born in 1895 where I recently found her birth certificate. In 1897 Frank, "Frankie" died at about 8 years of age. I have a picture of him with Willie. Around this time frame, Mary Frances, Fred and twin boys where born and died. I assume because of the infectious TB that Evora was suffering from.
My speculation of this letter is that Ellis took Evora and May and they moved to a dryer and warmer climate for her health and maybe to get away from the tragedy of losing so many children in such rapid succession. Aunt Cora would have been Evora's sister and she would have been about 25 years old probably living with another sibling where Willie could be taken care of and continuing with school without disruption. I haven't yet learned who the other people in the letter are as of yet.
Evora died 5 November 1898 supposedly in Las Vegas with her burial place still unknown. Her parents in the meantime moved to El Paso, Texas where they are found in the 1900 census. Cora is with them. Ellis must have retrieved Willie at some point. Ellis was in El Paso by 1901 where his picture was taken. He went on to Oklahoma and secured a homestead with Willie and May. The Hawkins family and Cora moved west to San Diego, California. Cora passed away in July 1904 at the very young age of 30 and is buried in the Mount Hope Cemetery. Was she comsumptive?
Ellis and his two married children ended up in Salem, Oregon and lived good, secure lives.
Posted by Delia Furrer
Sunday, May 30, 2010Labels: Family Stories, My Genealogy Research, Sentimental Sunday
at 3:08 PM
2 comments:
- BBurton said...
What a wonderful thing to have, even with the story behind it so sad. The letter gives so much information as to who to even look for.
With all the moving around, they could of taken Evora back to the family plot and buried her near her children. I have a relative who died in 1910 in Kansas and they buried him in Ohio next to his first wife, while they were buring him in Ohio his second wife died and the family trasported her body back to Kansas.
- June 1, 2010 at 11:09 AM
- Cindy Bergeron Scherwinski said...
What a tragic story but how fortunate you are to have the story behind these letters. Understanding life from the families point of view makes the words much more poignant and takes everyone out of the realm of the two dimensional. Thank you for sharing, Delia.
- June 3, 2010 at 4:54 AM
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journals evaluation
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In Costa Rica the Scielo begins in 2000 with the coordination of BIREME - PAHO and with the support of the Caja Costarricense de Seguro Social through the Biblioteca Nacional de Salud y Seguridad Social -BINASSS- including only magazines Health Sciences, is currently accepting publications in other areas of knowledge.
It has a National Advisory Committee composed of BINASSS, CONICIT, Universidad de Costa Rica Vicerrectoria de Investigacion, Escuela de Historia - UCR, Instituto Clodomiro Picado y el Hospital Nacional de Ninos.
All cases relating with the journals to income Scielo-CR are discussed at meetings of the Advisory Committee, leaving on record the assessments, agreements, conclusions and other aspects to consider.
about this site
Costa Rica aims to develop SciELO purchase commitment with publishers to improve the quality and accessibility of scientific publication. The objective of SciELO is to have an electronic library that can offer full access to a collection of review, whose articles can be retrieved through indexes and search system.
The site will be constantly updated by the coordinating unit in both form and content, with advances in the methodology.
The interface also provides access to the full text of articles via author index or subject index, or by a search form on article elements such as author names, words from title, subject, words from the full text and publication year.
Click an hypertext link at the top to call the corresponding access page.
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THE director of a museum in Bath has been appointed to take charge of Oxford's Ashmolean Museum.
Alexander Sturgis, who is currently director of the Holburne Museum, will replace Prof Christopher Brown when he retires in September.
Dr Sturgis previously held a number of posts at the National Gallery in London including exhibitions and programmes curator for six years.
Dr Sturgis said: "It is a huge honour to be given the chance to lead one of the country's great museums, however hard it will be to leave the Holburne after eight exceptionally happy and eventful years.
"I look forward to working with the Ashmolean team and Oxford University to build on all that has been achieved at the museum in recent years."
Prof Brown is stepping down after 16 years in the role and overseeing the museum's £61m extension to take up a position as a research professor at the university for three years after a sabbatical.
Dr Sturgis read history at University College, Oxford, in the early 1980s before receiving a PhD in art history from the Courtauld Institute in London in 1990.
Dr Sturgis will become the 19th person to take the reins of the Beaumont Street museum in its 331-year history, when he starts work on October 1.


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County offices will be closed next Wednesday due to a scheduled disruption in water service for residents and businesses located within Taylorsville's floodwall.
Spencer County Judge Executive David Jenkins said the decision was made Tuesday afternoon to close all county offices primarily because employees would not have access to functioning restroom facilities.
"I know this may cause some inconvenience but please bear with us as the City of Taylorsville makes necessary repairs to the water system in Taylorsville," said Jenkins.
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Knife Care- Sharpening, honing, and cutting surfaces
Many helpful knife cuts
How to dice an onion like a chef
You will receive a 15% discount on all knife supplies purchased the day of the class


text:
[Note: Dwight is on vacation through this week. Technology Bytes host Peter Hughes will be handling the linkposts while he's out.]
Another Note: Tomorrow night Dwight and I will both be at the Technology Bytes Geek Gathering which happens the first Friday of each month at Khon's in Midtown.
- Sulfur-based tech the answer to burnable lithium-ion batteries? – new type of battery that they say outpaces the ubiquitous lithium-ion batteries in flammability, cost, and ability to hold a charge
- Apple Planning 'Something Really Different' for New Mac Pro – The new Mac Pro model, expected later this year, is "something really different" according to a video professional who says he spoke with the Mac Pro product manager.
- Acer shows 21-inch Android desktop – a 21.5-inch all-in-one desktop PC that is expected on sale in the U.S. later this year
- Study: paperless statements won't take over any time soon – forecasts that paperless document deliveries will increase from 4.2 billion in 2012 to 8.6 billion in 2017, but that paper deliveries will drop from 19.5 billion to 15.9 billion over the same period
- Your Home's Wi-Fi Network Could One Day Replace Your Kinect – the WiSee system instead listens for subtle frequency changes in a modified Wi-Fi signal as it bounces off your moving body
- Warning! Users will have to reinstall all apps if they opt for Windows 8.1 beta – Beginning June 26, users will be able to download the beta or preview version of Windows 8.1 fairly simply, via the Windows Store. But Microsoft officials confirm that upgrading to the final RTM build will include a gotcha
- How a Teenager Rickrolled Vine – You're only supposed to be able to upload a six-second clip to Vine—but somehow yesterday sixteen-year-old Will Smidlein managed to bypass that rule
- Samsung Legal Win Could Halt US iPhone 4 Sales – Samsung has, to some surprise, won a patent battle against Apple that could see the iPhone 4 and 3G iPad 2 banned from sale in the US.
- Developer says Apple artificially limiting iPhone, iPad speeds – Apple and the iPhone's major US carriers are imposing artificial caps on the cellular speeds of the iPhone and iPad, claims Joseph Brown, a developer of hacked carrier updates
- Report: Apple's Got a Brand New MacBook Air or Retina For Next Week – it seems Cupertino's not-quite-so-air-tight seal has leaked a few new model numbers—which point to either a refreshed MacBook Air or Retina Pro waiting in the wings for WWDC.
- Sequel to Thunderbolt is all about 4K video – Intel is hoping that the "widespread adoption of 4K video technologies" will in turn drive more folks to the high-bandwidth bus


text:
Both of the resolutions on the agenda reportedly passed unanimously.
Appalachian State University
NOTE: All Faculty Senate meetings are recorded.
I. Announcements
A. Welcome and Introduction of Visitors.
II. Chair's Reports
A. Discussion of Faculty Senate committee assignments.
III. Committee Report
A. Agenda Committee (Koch, Anderson, Aycock, Botts)
1. Resolution on "Administrative Leave":
Whereas, The Faculty Handbook and the UNC Code are the sources of the rules and procedures that constitute the contracts for faculty at ASU, and
Whereas, The Faculty Handbook and the UNC Code do not mention the use of "administrative leave" as a mechanism for removing a tenured faculty member from his or her duties at the university, and
Whereas, The use of the term "administrative leave" fails to designate whether leave is voluntary or involuntary on the part of the faculty member, and
Noting that involuntary "administrative leaves" are not initiated by the faculty member but by the administration, and
Further noting that the imposition of involuntary "administrative leave" on a faculty member carries a negative connotation regarding the faculty member's performance; therefore, be it
Resolved, That the Faculty Senate at Appalachian State University considers the imposition of involuntary administrative leave on a faculty member to be the equivalent of a faculty suspension and differs only with reference to the term assigned to the act.
2. Resolution on Due Process:
Whereas, Section 22.214.171.124 of the Faculty Handbook states that a faculty suspension is a "serious sanction" that is to be employed only in cases of "incompetence," "neglect of duty," or "misconduct of such a nature as to indicate that the individual is unfit to continue as a member of
the faculty," and
Whereas, The suspension of a faculty member either asserts or infers that a suspension is justified on the grounds that the faculty member may have engaged in activities that warrant such a serious sanction, and
Whereas, A suspension is likely to cause material harm to a faculty member, and
Noting that these harms include, but are not limited to: reputation, fulfillment of obligations to
grants and other contracts, scholarly research, and administrative duties, and
Further noting that faculty suspension causes psychological stress; therefore, it be
Resolved, That the Faculty Senate asserts that when a faculty member is suspended from his or her duties the right to due process outlined in Section 3.8.2 of the Faculty Handbook should be immediately afforded that faculty member.
IV. Unfinished Business
A. None
V. New Business
A. None
VI. Adjournment


text:
The Lincoln-Lancaster County Genealogical Society and the Southeast Community College in Lincoln, NE will be presenting a full day genealogy program on Saturday, 9 October 210. This is in celebration of Family History Month and features noted speaker John Philip Colletta, PhD. He lives in Washington, DC where for twenty years he had conducted workshops for the National Archives and taught courses for Smithsonian Institution. Colletta lectures nationally and is a faculty member of the Institute of Genealogy, Historical Research at Samford University and the Salt Lake Institute of Genealogy.
Colletta's topics include Assembling and Writing a Narrative Family History; Turning Biographical Facts into Real-Life Events: Building Historical Context; Our Spectacular Library of Congress: An overview with Research Examples; Understanding Archives: What They Are and How to Use Them.
In addition to the featured speaker there will a unique music recital and lecture on Woody Guthrie's place in the history of American folk music. This will be presented by Nebraska Humanities Scholars, Mike Adams and Professor Kathryn Benzel.
Make plans now to attend The Lives of Our Ancestors. It will be held at the SCC Continuing Education Center, 301 S. 68th St. Place, Lincoln, NE from 9 a.m. to 4 p.m. on October 9th; cost $50. Check in begins at 8:30 a.m. The tuition includes conference materials and lunch. Deadline for enrollment is October 1st.


text:
Facebook yesterday announced it is jumping into location-based social networking. I know the whole concept sounds absolutely crazy to a lot of people ("Why should let my phone's GPS broadcast my exact location? So I can help robbers and stalkers and perverts find me, of course!). But in the tech world, this is a move everybody saw coming. Smaller networks like Foursquare and Gowalla have been growing like weeds as the ever-expanding hordes of smartphone-lovers use them to tell their friends where they are and what they're doing. Restaurants and retail shops in Charlotte and elsewhere have taken notice of the advertising potential, putting out special discounts for those who most frequently "check-in" on a service like Foursquare -- thus implicitly telegraphing the awesomeness of said restaurant or shop to all their friends.
So, it was just a matter of time before Facebook joined the game. And, perhaps chastened by previous blow-ups over privacy concerns, Facebook has taken pains not to force anybody into sharing their locations. You'll have to opt into it, rather than have it happen automatically. And when you "check-in," by default, only your friends see it, not the general public. The app for iPhone went out last night. Apps for touchscreen Blackberrys and Android-based phones will be available later, though you can access the function now through those phones' Web browsers at http://touch.facebook.com.
I probably won't jump into it right away. I've always been a little squeamish about location-sharing. Seems I'd like it a lot more if I were in my 20s and partying every other night. Plus, I, like many of you, am not sure I trust the motivations of ever-ambitious Facebook. (Read this smart CNET piece raising intriguing macro-analytic questions about what Facebook might be up to). Still, this, as everyone keeps saying, appears to be the future of the Web: mobile, location-based, real-time. Like it or not, we'll all have to deal with it.
What do you think? Are you planning to use Facebook Places? Or does it weird you out?
Wednesday, August 18, 2010
Facebook's new location feature: useful or creepy?
32 comments:
- Anonymous said...
Yes, creepy. I can't see any reason to broadcast my location. I could see where this would be useful for work groups or businesses with people moving around town. Otherwise, no way.
- August 19, 2010 at 10:44 AM
- barkomomma said...
Ha! Like the government doesn't know where everyone is every second of every day!
Wait! I gotta adjust my tin-foil hat.
There! Can't see me now!!!
- August 19, 2010 at 11:01 AM
- Anonymous said...
Creepy. Unless you are Jason Bourne, not needed! These companies are preying on the fact that as a group, most Americans are dummies. File under: invasion of privacy, 1984, etc.
- August 19, 2010 at 11:06 AM
- Linnea said...
Creepy tendencies aside, it also smacks of narcissism. I just don't think it's that interesting to my Facebook friends that I'm at Harris-Teeter, for example. It's kind of like Tweeting one's breakfast.
- August 19, 2010 at 11:10 AM
- Anonymous said...
Creepy, would never have facebook. Unless I'm looking to cheat on my spouse.
- August 19, 2010 at 11:14 AM
- Anonymous said...
This country has gone through the looking glass.
People arrange meetings in private places with strangers they met in a chat room, and publish the most intimate details of their life, including their constantly updated current location on the Internet, but won't get on an airplane or enter a theme park unless everyone is thoroughly searched first.
War is "peace", government tracking of everyone is "protecting out freedom", and the people who ran up the massive national debt are claiming they are the answer to the current administration's massive national debt.
...and morons believe them.
I'm glad I am old. "1984" is coming like a freight train. It's funny; when Orwell wrote that novel we thought it was fiction. It turns out it was prophecy.
- August 19, 2010 at 11:35 AM
- Anonymous said...
facebook/foursquare/etc is making it easier for the sex offenders out there to do their jobs.
- August 19, 2010 at 11:41 AM
- Anonymous said...
Chill people. You have to opt in and then only "friends" can see it so if you don't want it tracking your movements then don't opt in. Personally I don't see the need for it as if I want to find anyone all I have to do is text or call them to see where they are. It is very rare I would happen to run into someone out or even care. This seems much more important for businesses (like bars and restaurants) that could see who is nearby (assuming they are "friends" with the business) and then send them targeted messages.
Overall no big deal. And if you you didn't know the government and others could already track you by just the fact your cell phone is on you are pretty ignorant on technology.
- August 19, 2010 at 11:57 AM
- Anonymous said...
It not about whether or not you "opt in" or if you realize that "the man" can already track you, it is about setting a standard. And who does this feature target? The youth, who think it is normal to have all of their "friends" know their location. 20 years ago this would be considered insane. 18 months from now, this will be considered just as normal as Sunday afternoon apple pie. Keep heading, slow and steady, toward the cliff...nothing to see here.
- August 19, 2010 at 12:32 PM
- Anonymous said...
What I'm doing, where I am, what I'm buying or what I am about to eat at whatever restaurant is my business.
If you care, you need to come up for air from all this facebook/twitter/foursquare and so on crap.
A "mayor" of Harris Teeter? Come on! Or any establishment for that matter.
REALLY? Does that add to your cool factor?
- August 19, 2010 at 12:43 PM
- Anonymous said...
Wrong with regard to opting in. Check your privacy settings. They've opted you in already to allow friends to tag you which then would post your location because a "friend" tagged you there. There are two spots to make sure are disabled to opt out.
- August 19, 2010 at 1:17 PM
- Anonymous said...
To the teenage mind @11:57. No, we damn well will NOT CHILL. This is disturbing as living hell. Most kids on this thing friend everybody, whether they really know them or not. So, there is no defense saying 'only friends see your location'. Many people have been robbed, assaulted, stalked, and harrassed thanks to 'friends' only having access to certain things. Give me a damn break.
- August 19, 2010 at 1:59 PM
- Anonymous said...
These grown men posting their location all over facebook have a real problem. They are the creepy ones that truly lack something in their real lives. There's no way in hell I would have people knowing my location, let alone knowing any personal information over something like facebook in the first place. Truly sad state of affairs with these facebook addicts.
- August 19, 2010 at 2:01 PM
- Anonymous said...
Yeah, I know people using the foursquare tracking thing and it is very CREEPY and scary. They used to act like real grown ups, but now it seems like they are acting like teenie boppers.
- August 19, 2010 at 2:03 PM
- Anonymous said...
This foolish 'defense' that these small minded facebook people are using by saying the government can already 'track' us is ridiculous. Fine, let them track me, if they need to. I don't worry about that half as much as me volunteering my information and every move over something as dangerous as Facebook to everybody you can think of. How stupid can you get?
- August 19, 2010 at 2:07 PM
- Anonymous said...
@anon 1:59, I agree with anon 11:57. You should really chill.
- August 19, 2010 at 2:24 PM
- Anonymous said...
That's because it's you who said it in the first place. Maybe you should get ready for BACK TO SCHOOL time and stay off the internet.
- August 19, 2010 at 2:26 PM
- Anonymous said...
I am going to start posting my every location and whereabouts all over facebook so hopefully someone will stalk me down and beat some living sense into my childish acting self.
- August 19, 2010 at 2:30 PM
- Anonymous said...
sad truth is; it is NOT JUST teenagers doing this foolish stuff. Tracking and posting whereabouts is done by a great deal of so called "ADULTS".
Grow up.
- August 19, 2010 at 2:37 PM
- Eric Frazier said...
Anonymous at 1:17 p.m. brings up an issue people should indeed be aware of when it comes to the new feature. While you're not automatically opted into the location-sharing feature in general, there is this specific wrinkle where Facebook has indeed opted you into allowing your friends to give your location by tagging you. Find a quick overview, along with step-by-step directions on closing that privacy gap, here: http://www.businessinsider.com/facebook-places-privacy-guide-2010-8
- August 19, 2010 at 2:50 PM
- Anonymous said...
Anonymous said...
sad truth is; it is NOT JUST teenagers doing this foolish stuff. Tracking and posting whereabouts is done by a great deal of so called "ADULTS".
Grow up."
Why don't you grow up? That's hilarious. The 'adults' doing the crap are the scariest ones because they should know better.
- August 19, 2010 at 3:01 PM
- Anonymous said...
There are going to be SERIOUS problems that come from this type of insanity. No one should be allowed to track your whereabouts. If you let them or offer it up, then you are asking for it. Just wait and see.
- August 19, 2010 at 3:04 PM
- Anonymous said...
Great for stalkers and peeping toms.
- August 19, 2010 at 3:04 PM
- Anonymous said...
Well, I know a few adults in their 40s, men, who post their every move and location for everyone to see. How pitiful. How sad. How scary!
Only young people who have no responsibility or knowledge of consequences for their actions do such foolish things .........or so we thought!
- August 19, 2010 at 3:08 PM
- Anonymous said...
It sort of paints a sad picture of modern civilization in how easy it is for companies like Facebook and their partners to make a buck off of some people's desperate desire to have others perceive them as cool based on what they do.... and now the next level will be based on where they go.
- August 19, 2010 at 3:10 PM
- Anonymous said...
Mr. Frazier: As with other similar articles, I find your statement "Like it or not, we'll all have to deal with it" to be completely irresponsible. No, we will not ALL have to deal with anything. Especially since there are more people than you think that not only are not on Facebook, but find it dangerous and harmful.
So, please remember to take all people into consideration. We don't have to deal with anything we don't want to. The Facebook addicts who put up their every private piece of information and think it's ok to tell people everything about you and where you are, have no idea of what problems they are inviting on themselves. Then - like it or not - that's something they may have no choice but to 'deal with'.
- August 19, 2010 at 3:14 PM
- Anonymous said...
So, are y'all going to see The Social Network when it comes out?
- August 19, 2010 at 3:32 PM
- Anonymous said...
Why see that? Who cares? Ah yes, the teenagers! Great, but no thanks.
- August 19, 2010 at 3:49 PM
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text:
January, 2009
Clinical studies completed in 2008 caused scientists to raise provocative questions about the "amyloid cascade hypothesis," which has guided a generation of researchers in their quest to cure Alzheimer's. Though most current research still follows the path charted by this theory, efforts toward an effective treatment will require new navigation.
The amyloid hypothesis began to take shape in 1986 when scientists discovered a gene on chromosome 21 that produces amyloid precursor protein (APP), a substance of uncertain function found mostly in the space around neurons and produced abundantly in the healthy brain.1 The APP gene contains the sequence for the peptide amyloid, which is concentrated in the plaques used to diagnose Alzheimer's brain pathology. People who inherit a form of early-onset Alzheimer's have a mutation on chromosome 21 in the APP gene that results in overproduction of the amyloid peptide. People with Down syndrome, who invariably develop Alzheimer's in middle age, have an extra copy of chromosome 21 containing the gene for APP, causing them to produce excess amounts of the protein as well.2
A variety of enzymes in the brain normally clip APP into harmless fragments that float freely between neurons, possibly contributing to the ability of neurons to form new connections with each other—a brain function that is vital to memory. However, specific "beta" and "gamma" enzymes—the presence of which is predicted by the mutations in the APP gene—clip APP so as to yield amyloid peptide. For reasons unknown, amyloid aggregates to form toxic strings known as oligomers, and it is hypothesized that these disrupt the transmission of signals at the synapse—the gap where signals jump from one neuron to another with the help of chemical neurotransmitters.3
According to the amyloid hypothesis, the toxic oligomers eventually accumulate into immobile clumps of protein known as betaamyloid, or "senile plaques." Alois Alzheimer found these in the brain of a profoundly demented woman who died in 1906.
One hypothesis suggests that plaques act like magnets that attract and immobilize toxic oligomers, preventing them at least temporarily from committing mischief. However, the plaques themselves trigger damaging inflammation that contributes to the dysfunction and death of nearby neurons.
A genetic mutation predicts the presence of certain enzymes—shown here as scissors—that clip strands of APP into fragments that clump together in betaamyloid plaques. (NIH National Institute on Aging)
Researchers have devised a variety of ways to clear toxic oligomers from mice, but in human tests such treatments have failed to slow the memory loss, confusion, and other cognitive problems that afflict people with the disease. Though researchers and patients hope for new treatments from this line of study, they may be wrong to assume that significantly slowing down Alzheimer's progression is even possible in patients who already display the symptoms necessary to qualify as a trial patient.
"FDA guidelines generally suggest that one conduct trials first in mild-to-moderate Alzheimer's patients," said Dennis Selkoe of Harvard University, a pioneer in the development of antibodies against toxic oligomers. "But by that time plaques, tangles, gliosis, and neuritic dystrophy are relatively advanced." (Gliosis is the accumulation of glial cells, which clear debris left by neurons when they die. Neuritic dystrophy refers to deformed neurons.)
The free-floating toxic oligomers appear to disrupt synaptic function years if not decades before symptoms of Alzheimer's appear. Selkoe reported in a 2008 paper that toxic oligomers taken from the brains of Alzheimer's patients and injected into rodents profoundly disrupted synapses and impaired memory.4 More distressing, toxic oligomers, though they are certainly part of the problem, may not be the right target for treatment at all—plaques may be forming in response to something else entirely.
Conflicting theories and disappointing results prompted two veteran Alzheimer's researchers, Peter H. St. George-Hyslop of the University of Toronto and John C. Morris of the Washington University School of Medicine in St. Louis, to ask recently in the journal Lancet if the past two decades of anti-amyloid research "were spent barking up the wrong tree."5
Such pessimism is premature, other scientists argue. Some, such as Selkoe, believe that anti-amyloid therapies would be far more effective if started earlier, before the toxic oligomers have had time to damage synapses and kill neurons. Others have been intensifying the search for subtle indicators in blood or cerebrospinal fluid, or perhaps on magnetic resonance imaging scans, that would indicate the earliest signs of pathology and perhaps allow for the prevention of the accumulation of toxic oligomers.
Without such biomarkers, treatment will be limited to people with overt symptoms of Alzheimer's, and judging from clinical trial results reported in 2008, such people do not respond very well to efforts to remove toxic beta-amyloid from their brain. Myriad Genetics, for example, tested an anti-amyloid drug called tarenflurbil (Flurizan) in patients with Alzheimer's. After investing $200 million to develop the drug, the company announced in 2008 that it was suspending all further research because an eighteen-month study involving 1,684 patients—the largest Alzheimer's treatment trial ever—showed that it did not produce significant improvement in memory, cognitive functioning, or the ability to perform activities of daily living such as dressing and bathing.6 The trial did not include tests to detect how much beta-amyloid, if any, was removed from participants.
Elsewhere, follow-up studies have been conducted in patients who participated in clinical trials to test the effectiveness of AN-1792, a vaccine against Alzheimer's developed nearly a decade ago by Elan Pharmaceuticals in cooperation with Wyeth Pharmaceuticals. After conducting one follow-up, Clive Holmes, of the Memory Assessment and Research Centre in England, concluded that "progressive neurodegeneration can occur in Alzheimer's disease despite removal of plaque."7 But the data from a larger follow-up study included tantalizing hints of benefit in those patients who responded to the vaccine by producing antibodies against beta-amyloid. "Patients who still had antibodies in their system at the time of the follow-up did significantly better on activities of daily living, and on a measure of dependency," said Dale Schenk, executive vice president and chief scientific officer for Elan.
Work on AN-1792 was abandoned because it produced serious cerebral inflammation, but Elan and Wyeth have since developed an antibody that attacks beta-amyloid. The eagerly awaited results of a clinical trial of the drug, which bears the unwieldy name of bapineuzumab, were announced at the International Conference on Alzheimer's Disease meeting in July. The antibody reduced brain atrophy and produced some improvement in mental functioning, primarily among patients who did not possess the gene for ApoE4, the strongest genetic risk factor for Alzheimer's disease. (About 25 percent of humans carry one or two copies of the gene for ApoE4, but more than half of those with Alzheimer's carry the gene.) Researchers did not expect the Phase II trial, designed to test for and define safe dose ranges for the antibody, to reveal efficacy in any subgroups. In this respect the study was a success.
However, those in the study who possessed the gene for ApoE4 were barely helped at all. "Perhaps there's a biological difference between carriers and noncarriers (of the gene)," said Sid Gilman, the neurologist who served as the chair of the independent safety monitoring committee for bapineuzumab, as he announced the findings. "Or perhaps carriers have a greater density of beta-amyloid."
Or maybe, according to a growing number of researchers, the amyloid hypothesis needs further refinement. "There are several chinks in the armor of the amyloid hypothesis," said David Morgan, director of the Alzheimer's Research Laboratory at the University of South Florida. "But the question isn't whether the amyloid hypothesis is correct. Every gene mutation we know of that causes Alzheimer's in a dominant fashion modifies the production of amyloid, and there are 100 genes that do this. That seems to provide pretty compelling evidence that amyloid plays a role. The question is whether targeting amyloid will be efficacious."
The original amyloid hypothesis, which emphasized the presence of amyloid plaques, contained one glaring inconsistency: the number of plaques found in elderly brains does not correlate very well with cognitive difficulties. A much stronger indicator is the other hallmark of Alzheimer's, the tangles of tau protein found within neurons.
This has led to debate between "tauists," who believe that tau protein causes Alzheimer's, and "BAPtists," who blame the betaamyloid protein found in brain plaques. The tauists have always had a compelling case. Tau is a crucial brain protein found in the microtubules that act like railroad tracks for transporting neurotransmitters from the cell body to the synapse, where the neurotransmitters are released. Any dysfunction involving tau is catastrophic for the brain, as several "tauopathies," including Alzheimer's, vividly demonstrate.
Today, researchers generally agree that toxic beta-amyloid initiates the dysfunction that leads to tau degeneration, but the most potent trigger by far is age. The aging process plays such a large role in Alzheimer's that Peter Whitehouse, the geriatric neurologist who founded Case Western Reserve University's Memory and Aging Center, published a book in 2008 titled The Myth of Alzheimer's, in which he argues that the disease is nothing but normal brain aging that takes place faster in some people than in others.8 Everyone, he believes, would get Alzheimer's if they lived long enough.
But strong evidence contradicts this assertion. For example, Juan Troncoso, codirector of the Alzheimer's Disease Research Center at Johns Hopkins University, has demonstrated that one region of the hippocampus known as CA1, which is crucial for the formation of short-term memories, remains stable in old age among those who do not have Alzheimer's, but degenerates drastically in people with Alzheimer's.9
In addition, some people live to extreme old age with only minor loss of mental acuity. An article published in 2008 about the autopsy performed on the world's oldest woman, who died at the age of 115, reported that her brain was virtually free of signs of Alzheimer's.10 Clearly Alzheimer's is a disease, not normal aging. Yet the incidence of Alzheimer's disease increases in lockstep with aging, producing at least subtle symptoms in about half of all people by the age of 85. Somehow, the aging process must contribute to Alzheimer's.
One idea gaining ground involves synaptic exhaustion. Neurons communicate with each other by releasing neurotransmitters from the synapse. Receiving fibers known as dendrites, which branch like tree boughs from nearby cells, are stimulated by neurotransmitters and propagate the impulse, which travels to the cell body and then down that cell's axon. Neurons create new synaptic connections among themselves constantly, and this process is energy-intensive.
Few regions of the brain work harder at this than the hippocampus, where short-term memories form—and where Alzheimer's begins. In 2008, Randy Buckner of Harvard and two colleagues published a paper in which they observed an uncanny similarity between hippocampal changes and those in another area affected by early Alzheimer's: the brain's "default network"—regions at the front and rear of the brain connected by long fibers.11 The default network becomes active when the mind wanders and slips into what William James, the founder of modern psychology, dubbed the "stream of consciousness." Since the mind wanders whenever it is not busy, the default network is one of the busiest areas of the brain. In people with Alzheimer's, glucose metabolism in the default network drops significantly, suggesting that synaptic transmissions are becoming sluggish. This drop in the brain's use of glucose continues as the disease progresses, and it correlates with the severity of dementia. In addition, people who possess the gene for ApoE4 show lower glucose metabolism in these areas much earlier in life, suggesting that dysfunction begins years or perhaps decades before the first symptoms appear.
This "metabolism hypothesis," as Buckner calls it, corresponds with a conception of Alzheimer's disease long promoted by Marcel Mesulam, director of the Cognitive Neurology and Alzheimer's Disease Center at Northwestern University Medical School in Chicago. Mesulam, who presented a spirited explanation of his idea at the International Conference on Alzheimer's Disease meeting in July, believes that Alzheimer's evolves from the breakdown of neuroplasticity, the process by which synapses form new connections with other neurons. The rapid breakdown and buildup of connections demands a vigorous repair process, and that, Mesulam believes, is what slows down and eventually produces the "cascade" of degeneration that leads to Alzheimer's disease. Every cause of Alzheimer's disease ever proposed—including head trauma, the ApoE4 gene, cardiovascular disease, inflammation, stroke, and aging itself—interferes in some way with neuroplasticity, he said. Mesulam first proposed his hypothesis nearly a decade ago in an effort to solve what he calls the "central puzzle" of Alzheimer's—the genetics of the disease point to betaamyloid as the cause, but the symptoms coincide more closely with the number of tau protein tangles found within neurons.
Neurons communicate by transmitting chemicals at the synapse, a process that becomes sluggish in brains with Alzheimer's because of a drop in glucose metabolism. (NIH National Institute on Aging)
A revised version of the amyloid cascade hypothesis links these two phenomena by accusing toxic beta-amyloid oligomers of disrupting activity at the synapse, creating stress that leads to the breakdown of the tau protein "tracks" that guide neurotransmitters. In 2006, two researchers at the University of Virginia, Michelle E. King and George S. Bloom, found that beta-amyloid triggers the disassembly of tau microtubules.12 They are preparing to publish more-detailed research on the biochemistry behind this synaptic dysfunction. "We think the breakdown of microtubules in axons caused by the interaction between amyloid and tau simply slows down or halts the replenishment of the proteins involved in making neurotransmitters," Bloom said. "If these proteins are not replaced, the synapse can't function properly. Mesulam's paper was very prophetic. Nobody was thinking at the time he wrote it that amyloid and tau might be conspiring in a way that leads to microtubule disassembly."
Another approach to preserving the vigor of synapses focuses on the cell's ability to break down and dispose of protein debris, a process known as autophagy. Neurons, with their high metabolism, produce a lot of waste and must rely on autophagy to get rid of it. The failure of autophagy results in the accumulation of those toxic protein fragments found in Alzheimer's disease and other neurodegenerative disorders such as Parkinson's and amyotrophic lateral sclerosis (ALS), according to Ralph Nixon of the New York University School of Medicine. "We know that this type of dysfunction develops as part of the normal aging process," he said. "We also have found that genes that promote Alzheimer's disease add another layer of impairment to this age-related impairment."
The accumulation of protein debris within the cell body plays a key role in Alzheimer's, as Nixon and colleagues outlined in a 2008 paper in the journal Autophagy.13 Stimulating autophagy in the elderly presumably would slow or halt the degeneration farther upstream before amyloid plaques, tau protein tangles, and other downstream debris appear, according to Fen Jin-A Lee and Fen-Biao Gao, two researchers at the Gladstone Institute of Neurological Disease in San Francisco.14
Further evidence that autophagy is involved in Alzheimer's comes from Tony Wyss-Coray of Stanford University, who believes that beclin 1, a key regulator of the autophagy pathway, is reduced in certain brain areas of Alzheimer's patients.15 When beclin 1 is reduced, neurons produce more APP, setting the stage for Alzheimer's pathology. "And beclin 1 is reduced by 60–70 percent in Alzheimer's disease," said Wyss-Coray. "Autophagy is involved in neurodegeneration in general."
Despite these tantalizing hints that the most effective treatment for Alzheimer's would involve prevention, most treatments in the pipeline in 2008 involved removing the toxic oligomers. The antihistamine Dimebon, for example, was sold for two decades in Russia before neurologists noticed that it seemed to help people with Alzheimer's. In 2008 the conclusion of an eighteen-month study of Dimebon (dimebolin hydrochloride) showed that the drug improved memory and cognition in Alzheimer's patients somewhat, possibly by stimulating the function of mitochondria, the power source of cells.16
Another drug known as methylene blue, or methylthioninium chloride (MTC), has been found to inhibit the production in the brain of tau protein tangles, according to Claude M. Wischik, chairman of TauRx Therapeutics, which is marketing the compound for Alzheimer's disease under the name rember.17 Before World War II and the widespread availability of antibiotics, MTC was sold as Urolene Blue, a treatment for urinary tract infections. A clinical trial completed in 2008 by TauRx found that the compound slowed the decline of Alzheimer's patients by 81 percent compared with patients taking a placebo.
Elsewhere, Prana Biotechnology is developing a compound known as PBT2, which interrupts the aggregation of beta-amyloid in the brain of Alzheimer's patients by inhibiting the action of zinc and copper. "The drug will keep metals away from beta-amyloid but make them bioavailable to enzymes that need them," said Rudolph Tanzi, the Harvard researcher who founded Prana in his laboratory in 1997. A clinical trial completed in 2008 showed that PBT2 reduced levels of A-beta 42—one fragment of beta-amyloid believed to be toxic to the brain—and produced some improvement in cognition.18
Improved function of mitochondria (the small, pill-shaped structures shown with a healthy neuron, above, and with a neuron affected by Alzheimer's, below), as stimulated by experimental drug dimebolin hydrochloride, may inhibit cell death in brains with Alzheimer's disease. (Rachelle S. Doody, M.D., Ph.D. / Baylor College of Medicine)
Norman R. Relkin of Weill Medical College of Cornell University is leading an effort to develop a new form of immunotherapy known as intravenous immunoglobulin, or IVIg. IVIg contains antibodies from human blood that attack beta-amyloid, but instead of recognizing the protein's chemical makeup, the antibodies recognize its misfolded, aggregated shape, and they leave healthy molecules alone. A clinical trial completed in 2008 showed IVIg capable of reducing beta-amyloid and improving cognition, opening the way for a Phase III trial.19
Such varied approaches underscore the complexity of Alzheimer's—and of the aging process itself. "A greater understanding of the normal aging brain may be necessary before we can fully understand the causes of pathological aging and cognitive decline," said Harvard's Bruce Yankner, who has been studying brain aging for many years.
The current amyloid cascade hypothesis leaves room for hope that the disease might be held at bay, perhaps indefinitely, by preventing the aggregation of beta-amyloid fragments cleaved from APP throughout life. But scientists do not yet understand why the appearance of plaques does not correlate with symptoms of the disease.
Researchers will not find a "magic bullet" that cures Alzheimer's anytime soon. Toxic oligomer research may synthesize the various leading theories. Amyloid toxicity is particularly consequential when it triggers tau formation, a fact that links the amyloid cascade hypothesis to the possible pathogenic role of tau. However, scientists will need to know much more before they can conclude that such a synthesis is possible. Until then, the various hypotheses of Alzheimer's disease are still just that: hypotheses.
1. Tanzi RE and Bertram L. Twenty years of the Alzheimer's disease amyloid hypothesis: A genetic perspective. Cell 2005 120(4):545–555.
2. St. George-Hyslop PJ, Tanzi RE, Polinsky RJ, Haines JL, Nee L, Watkins PC, Myers RH, Feldman RG, Pollen D, Drachman D, Growdon J, Bruni A, Foncin J, Salmon D, Frommelt P, Amaducci L, Sorbi S, Piacentini S, Stewart GD, Hobbs WJ, Conneally PM, Gusella JF. The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science 1987 235(4791):885–890.
3. Hu N, Smith IM, Walsh DM, and Rowan MJ. Soluble amyloid-b peptides potently disrupt hippocampal synaptic plasticity in the absence of cerebrovascular dysfunction in vivo. Brain 2008, 131(9):2414–2424.
4. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, and Selkoe DJ. Amyloid-beta dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nature Medicine 2008 14:837–842.
5. St. George-Hyslop PJ and Morris JC. Will anti-amyloid therapies work for Alzheimer's disease? Lancet 2008 372(9634):180–182.
6. Green RC, Schneider LS, Hendrix SB, Zavitz KH, and Swabb E. Safety and efficacy of tarenflurbil in subjects with mild Alzheimer's disease: Results from an 18-month multi-center phase 3 trial. Presentation at ICAD, July 29, 2008. Also, press briefing by Robert C. Green, Co-Director, Alzheimer's Disease Clinical and Research Program, Professor of Neurology, Genetics, and Epidemiology at Boston University School of Medicine and a lead investigator on the Phase III trial of Flurizan, at ICAD, July 29, 2008.
7. Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal J, Zotova E, and Nicholl JAR. Long-term effects of A-beta42 immunization in Alzheimer's disease: Follow-up of a randomized, placebo-controlled Phase 1 trial. Lancet 2008 372(9634):216–223.
8. Whitehouse, PJ. The Myth of Alzheimer's. St. Martin's Press, 2008.
9. West MJ, Coleman PD, Flood DG, and Troncoso JC. Differences in the pattern of hippocampal neuronal loss in normal aging and Alzheimer's disease. Lancet 1994 344:769–772.
10. den Dunnen WFA, Brouwer WH, Bijlard E, Kamphuis J, van Linschoten K, Eggens-Meijer E, and Holstege G. No disease in the brain of a 115-year-old woman. Neurobiology of Aging 2008 29(8):1127–1132. Also, Del Tredici K. and Braak H. Neurofibrillary changes of the Alzheimer type in very elderly individuals: Neither inevitable nor benign. Neurobiology of Aging 2008 29(8):1133–1136.
11. Buckner RL, Andrews-Hanna JR, and Schacter DL. The brain's default network. Annals of the New York Academy of Sciences 2008 1124:1–38.
12. King ME, Kan HM, Baas PW, Erisir A, Glabe CG, and Bloom GS. Tau-dependent microtubule disassembly initiated by prefibrillar beta-amyloid. Journal of Cell Biology 2006 175(4):541–546.
13. Nixon RA, Yang D, and Lee J. Neurodegenerative lysosomal disorders. Autophagy 2008 4(5):1–10. Also, http://www.landesbioscience.com/journals/autophagy/article/6259.
14. Lee J-A and Gao F-B. Regulaton of A-beta pathology by beclin 1: A protective role for autophagy? Journal of Clinical Investigation 2008 118(6):2015–2018.
15. Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, Small S, Spencer B, Rockenstein E, Levine B, and Wyss-Coray T. The autophagyrelated protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid-beta accumulation in mice. Journal of Clinical Investigation 2008 118(6):2190–2199. Also, Wyss-Coray, T. The autophagy protein beclin 1 is reduced in early Alzheimer's disease and regulates A-beta accumulation in vivo. Presentation at ICAD, July 31, 2008.
16. Doody RS, Gavrilova SI, Sano M, Thomas RG, Aisen PS, Bachurin SO, Seely L, and Hung D. Effect of dimebon on cognition, activities of daily living, behavior, and global function in patients with mild-to-moderate Alzheimer's disease: A randomized, double-blind, placebo-controlled study. Lancet 2008 372(9634):207–215.
17. Wischik CM, Bentham P, Wischik DJ, and Kwang Meng Seng. Tau aggregation inhibitor (TAI) therapy with rember arrests disease progression in mild and moderate Alzheimer's disease over 50 weeks. Presentation at ICAD, July 29, 2008.
18. Masters CL. Rational therapeutic strategies for modifying Alzheimer's disease: A-beta oligomers as the validated target. Presentation at ICAD, July 28, 2008.
19. Relkin NR. Natural human antibodies targeting amyloid aggregates in intravenous immunoglobulin. Presentation at ICAD, July 27, 2008. Also, interview with Relkin.
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text:
So awesome.
Posted by | February 8, 2011, 3:01 pm
So you mean we bake the cookies the girl scouts are selling 😕
Posted by | February 8, 2011, 3:56 pm
Perfect. I love it. Creating and advertising a divide seems like a horrible idea. Telling everybody that Fedora is what they make it is wonderful.
Posted by | February 8, 2011, 3:57 pm
Posted by | February 8, 2011, 4:10 pm
I think this is rather off the mark – there can be only one default environment, only one home page on fedoraproject.org, only one target audience that is used by FESCo as a basis for deciding between conflicting proposals.
What exactly are people supposed to "make" about these things?
Posted by | February 8, 2011, 6:30 pm
What does this mean? I thought the primary bone of contention that started this rift was when a group of people that apparently had a pretty passionate interest in Fedora's artwork was told that they were not needed/wanted for F15 due to a hard restriction that GNOME's default wallpaper be used.
Their graphic never made it easy to determine exactly what they were railing against. Your graphic, though, seems to read as "F You , Make It". That seems … unnecessarily inflammatory without some form of explanatory text, especially as I think they were trying to say "Let Us Make It" in the first place?
Posted by | February 8, 2011, 7:48 pm
I disagree with 'Mo on many things from time to time. But this whole thing just rubs me wrong. "Give our distro back"? While I wish I could agree with the statement for other reasons than the original party.
To "give back" implies they had something to begin with. This is not the case, Fedora belongs to Red Hat, they allow us to participate. I thank them for that opportunity. It's not about "you" or "me" it's about the myth of community ownership. At least that is the way I see it. I am still planning a party for everyone the day the "lie" stops.
Posted by | February 8, 2011, 8:18 pm
I haven't been enjoying Nicu's campaign, since I mostly disagree with him on this issue.
However, yours doesn't feel quite true either: in some areas of Fedora, no matter what your badge says, I don't make it.
One example comes to mind: the default desktop spin. It is treated completely differently, and its team is often referred to (even by themselves) as the "Red Hat desktop team". It makes me really doubt that if I had the inclination, time and skills I could have any say in what happens there. (note: I don't have any of those, and I truely respect the work that this team is putting into Fedora)
A second example is that the Advisory Board is still half-appointed by Red Hat, which makes it more difficult for the wider community to entirely "make it". (not that Red Hat has ever appointed anyone who harmed the community, even non Red-Hat employees have been appointed which is a great proof that Red Hat cares about Doing the Right Thing. The fact that those seats are reserved is still an issue though)
There are a few other examples, but I guess my point is that your badge would be much more accurate if it were saying "You (almost) make it".
Posted by | February 9, 2011, 1:09 am
Speaking as a former _elected_ advisory board member..who has never been employed by Red Hat….
I have _zero_ problem with the current split between appointed and elected positions on the Board. I firmly believe appointed seats are a more appropriate tool than a strict democratic selection based the realities of the economics on how the infrastructure that makes Fedora possible is funded and maintained. Wrapping oneself in the rhetoric of democracy as panacea is at best…naive.
I'm more than happy to talk at length with you about why I am right in my beliefs in another forum if you want to have that discussion. It would be too lengthy to have here, and I don't want to force Máirín to have to act as moderator unnecessarily.
But beyond that, I will also say that every single FPL I have personally interacted with before,during and after my tenure on the Board has _always_ been keenly aware of the need to balance perspectives within the Board when it comes to using the appointment power.
And beyond that, I'll say that the fact that Red Hat employees continue to be _elected_ ahead of externals even though the eligible voter base is mostly made up of non-RedHatters tells me that there isn't a substantiate problem here to be solved by moving to a more democratic process.
I would _love_ to see those who seem to be disenfranchised put a slate of like minded candidates together and _campaign_ with a platform and a plan of action as part of the existing Board elections process and get the silent majority of external contributors excited enough to actually vote for them. I guarantee you any such organized campaign for change via the established election process would have to be much more forward looking than the reactionary campaign for change we are seeing in the "take back" campaign. Based on the negativity of public statements being made right now by the leadership of the "take back" meme…I very much doubt they'd get elected. It's really easy to make noise and to agitate in reactions to decisions you don't agree with. It's much harder to stand-up and raise your hand and ask your peers to raise you up into a position of responsibility for the entire project and have proactive discussions leading to proactive decision-making.
Again…all of that being said as a former _elected_ external community Board member.
Posted by | February 9, 2011, 3:46 pm
In case that wasn't clear enough: I don't enjoy the "give back" campaign, nor do I even agree with it.
My comment was not meant to imply that I personnally find anything unacceptable, I wasn't giving my personal opinion or any judgement.
I was simply pointing facts that tend to show that Mairin's badge is not entirely accurate. (which incidentaly is exactly what some people have an issue with: they feel that there is no way they can "make it" and are demanding there distro back)
Posted by | February 10, 2011, 4:05 am
No slogan is entirely accurate. The reality of the inner workings of any social interaction is never so simple as to be captured entirely accurately in a slogan a few words long. Slogans by their very nature are meant to be emotive, 100% accurate. Do you _really_ think pointing out this fact is going to _help_ move the project forward?
Given that all human language is an approximation for human thought, we won't have 100% fidelity in human communication until we all have Google neural implants. And when we do, we are all going to find out exactly what we all _think_ about each other and it won't be pretty.
In any event, you went well beyond _fact_ in your dissection of the slogan in question and strongly implied there is some sort of substantiate problem with the process by which the Board seats are filled, further implying that in your opinion a more democratic process is necessary to address the problem. I'm more than happy to go into much greater detail in my assessment of these perceived issues (sans any discussion of badge slogans which are just a distraction) in an effort to convince you or anyone else that such opinions concerning the deficiencies about the Board representation are not supported by history or by current project topology. But I'll do so in another forum so Mo' doesn't have to moderate the discussion.
Nickpicking emotive slogans for their inability to express the full depth of the complexity associated with the governance of the Fedora project and the inherent conflicts of interest between individuals and groups inside its boundaries is not going to help _us_ chart a course in defining Fedora as a project with focus and direction versus a project which is entirely diffusive in nature.
Posted by | February 10, 2011, 2:14 pm
except when people don't let you make it
Posted by | February 9, 2011, 2:45 am
Nice one 🙂
It makes me think about this suse poster hanging on a wall at fosdem: http://www.flickr.com/photos/isriya/2289495796
Posted by | February 9, 2011, 3:59 am
@pingou: speaking about suse and fosdem, they really tried there to recruit me into their community… good thing i had handy the Sirko case to disrupt the "recruitment"
Posted by | February 9, 2011, 8:59 am
Marin, I much prefer the tone of this one. Good job.
The earlier one reminds me of someone coming to my door guilting me making a donation. No one likes to be told what to do, especially if it's a hobby.
Posted by | February 9, 2011, 3:24 pm
Too good to be true, unfortunately it is not that easy. Lets see what happens when we try to get shit done(tm). Just a few examples:
In order to get things done, we founded "Fedora EMEA e.V.", a foundation for the promotion of Fedora, but it was closed down by Red Hat Legal. Now we no longer have legal entity to handle money and organizing events has become way more difficult.
Kanarip wants to make extended life cycle happen and has gathered enough contributors, but he first is presented with a long list of questions that he needs to answer. Some of the questions require statistical data that not even the Fedora Project collects. So how can the board demand him to deliver this information?
The EMEA ambassadors want advertise Fedora with a DVD that contains all spins, but the board didn't want to grant the trademark approval without taking a look at it first. So I did a prototype (in fact I already did it before) but the same board members that had concerns before, don't bother to look at it. Instead they ask more questions and raise more concerns, many of them based on false assumption and missing information. I tried to address all concerns and answer all questions but I ended up with fighting people who do not even bother to look at our work. I was asked to do a wiki page to collect all information and have a place for discussions. So I did, but again nothing happened. The talk page is still empty.
Contributors who want to move forward with Fedora are more and more blocked by red tape or stubborn people. Do you really think it is *our* distro and we can *make* *things* *happen*?
Posted by | February 9, 2011, 5:38 pm
ORLY i can make it?
So, i suppose i can make a custom Fedora distro including:
a) freed-ora kernel and not proprietary firmware;
b) real apps like every liveCD is expected to do in the world outside Desktop Team;
c) spanish locales because it would be distributed to people in events in LatinAmerica;
of course, excluding another decisions i didn't take like.
And i'd call it Fedora Freedom². Because i want attribution to Fedora, not to me, because i don't like Blag statements about "overthrowing corporate control" and yet using Fedora repos.
Of course i could request for reimbursemente support as i'd like to distribute in installfests, and another events representing Fedora and how we area big community with freedom to tinker and still being part of the whole ecosystem.
Or, because i wouldn't adhere to trademark control of Fedora by RedHat, i can't do anything of this, and yet call my packaging of Fedora, actually Fedora.
Posted by | February 9, 2011, 6:44 pm
Pingback: February 8, 2011-


text:
I don't know who took this, just some random guy I found on huffpost.
Views: 296
Good stuff! Thanks for putting that up!
And yet MORE from the Reason Rally!
Thank you
Loved looking these! Wish I was there! To be honest, I don't do crowds very well - Im not a crowd kind of guy. But I still wish I could have been there!
I didn't take any side-trips to go check-out the protesters, but this was off to the side of the crowd close to where we were, so I just popped over to get a picture. After I got my pic, I walked up to the guy with the Fail shirt and shook his hand and thanked him. After this, people followed suit, ignoring the Xtian protester and giving the kid his props and shaking his hand, …cool.
I'll post a blog or a thread with more pics when I have time. It was at times both intensely hilarious and profoundly, but never irrelevant.
Love this pic. The ramblings of the believer. The casual silence of the atheist. Their shirts: nuff said.
Tim Minchin is awesome
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I finally got my hands on a wand today... No, not that type of wand... A Neutrino Wand of course!
I got this beauty in the post today Very chuffed with it. I thought a video would be easier to show you what it does than through pictures.
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Cosine Bands: an Exercise for PCPBT
out of 5 stars
21 Aug 2008 | | Contributor(s):: Gerhard Klimeck, Dragica Vasileska
This exercise demonstrates the formation of cosine bands as we increase the number of wells in the n-well structure.
ABACUS - Assembly of Basic Applications for Coordinated Understanding of Semiconductors
16 Jul 2008 | | Contributor(s):: Xufeng Wang, Dragica Vasileska, Gerhard Klimeck
One-stop-shop for teaching semiconductor device education


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Horrifying Tale Of Kidnapped Hitchhiker Held For 7 Years
The harrowing tale of an American woman's kidnapping and seven year-long torture is back in the spotlight thanks to a new TV series.
Colleen Stan was picked up by a couple while hitchhiking in 1977; she thought, as they were travelling with a baby, that she could trust them.
Instead, Cameron and Janice Hooker locked the then-20-year-old in a coffin-like box for SEVEN YEARS, only letting her out to be raped or tortured.
"I learned I could go anywhere in my mind," Ms Stan explained to People. "You just removed yourself from the real situation going on and you go somewhere else.
"You go somewhere pleasant, around people you love. Whatever makes you happy."
The 'Girl in the Box' Speaks: How I survived being held captive for 7 years https://t.co/3xxYjTKW5i pic.twitter.com/ZQfKDdvnP5— People Magazine (@people) September 7, 2016
Just an hour after getting into the Hooker's car, Ms Stan was threatened with a knife, before Cameron gagged and bound her, forcing her into a wooden box under the marital bed when they got her home.
She spent 23 hours a day in the "coffin" and was only allowed out to be beaten and used as a sex slave.
"I thought I was going to die," she admits.
In August 1984, Janice helped Ms Stan escape, later gaining immunity by testifying against her husband.
Cameron Hooker, however, was found guilty and sentenced to 104 years imprisonment.
Ms Stan's horrific story has now been turned into a TV movie called Girl in the Box, set to air in the US this weekend, and the grandmother is happy to be focussing on the future.
"Your life is just kind in limbo when you're in captivity," she said, "and once you get that freedom back and you have that choice again, it's just like the gates open.
"And you just run for it."
Trending now: Truck and car try to merge in Sydney Tunnel


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Samsung's Flexible Smartphone Screens
Samsung is planning to start mass production of smartphone screens using bendable plastic rather than glass. The WSJ's Yun-Hee Kim talks about Samsung's experiment with flexible technology and why this can lower costs.
This transcript has been automatically generated and may not be 100% accurate.
I ... the the ... it stars ... like The Wall ... you can fold joining me here and honk on uni can't ... say any I guess the first question I have is why would anyone want this ... you see this ... on ... he and the ... places that the county that companies investing right now and are aiming to mass produce these place to be used in cellphones ... the aim is to make them kind of bands of all and more flexible and lighter than the current mobile devices and market ... most of the city use of glass so it's a little bit heavier and Dom if you drop your I phone for instance then breaks from scratch as ... PNG is that he is flexible displays ... it's gonna be his year ten to carry and veteran later and I'm certainly want always to light the night that I can see I seem to have the camera and everything like this ... that looks like ... the picture the plastic or we we just let ... um ... it looks like a big band is it is achieving the more compact says it is the best base ... price of this is the theme that this is what Sam something to do guests ... to try to make devices more bands of all and flexible and easier to carry that the U ... K however the displays work when they can hold ... my hand while Samsung and ... Samsung does have the prototype out so ... um it doesn't mean that they're actually manufacturing the Zimbabweans right now so what the companies trying to do is actually ... a mass produce them by the first half of next year ... and they're getting these these displays and some of the devices that there can be launching ... said no one has actually seen the sun gets is just a prototype and still have to wait and see how the actually work ... the August the midst of the commendable but what hearing that it's actually very difficult to manufacture and that's what's taking them a long time to mass produce these displaced again we all know how competitive the smart than the industry is and ... I am a competitor is doing a sign saying I mean could this be the next big thing right I mean the smartphone and tablet markets are ... in competition is intensifying and many factors really really differentiate their products ... one of the reasons why seems unfair to getting into this market is ... he wants to introduce this new display technology that will put them ahead of companies like it's it's Apple ... on ... the Samsung isn't the first one to manufacture these types of displays in fact aam Sony has launched several prototypes ... two years ago they launched a four point one inch prototype display ... but the company spokesman said that they haven't been able to mass produce these displays are commercial I found so Sony hasn't been able to put these products out into the market ... we also met some resulting display to display company based in Mt so ... they are also my defect or trying to mass produce these displaced by the label yet the Tanzania were on our way and then Samsung will release this smart flexible swipe at engine light on the market and how much it will cost my pricing will be the key on the free ... up the aim is to bring this into market in the first half of twenty thirteen is what Samsung is telling us ... what's will have to watch the market and see because of the sea ... um no classes freezer so very popular with ... consumers ... aam and so um we don't know and in terms of I think ... of one of the key things will ... key reasons why Samsung was to use plastic is they can lower than my actual cost ... of the kids are to be cheaper than I've ... of but ... to get to that level of were they able to mass produce clean is a very difficult ... so I don't think they've determined how much to do is sell these devices for ... not given that he wanted different she knew him ... key to profitability and might go for a premium initially when he launched into the market it's always a big new


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Today, Speaker Boehner promoted a statistic concocted by the Weekly Standard claiming that President Obama's Recovery Act (aka "the stimulus") cost $278,000 per job. The stat is simply the overall cost of the Recovery Act, both the government spending and the tax cuts, divided by a low-end estimate of the jobs created or saved by ending the economic free-fall of late 2008 and early 2009.
This first struck me as a rare admission by a Republican that the stimulus created any jobs at all.
But I'm sure the tacit acknowledgment isn't weighing on conservative minds, because the idea behind this "stat" isn't to be intellectually consistent. It's to bolster the claim that government spending is an inherently inefficient way to create jobs.
The White House quickly pushed back with the basic reason why the stat is bogus: the Recovery Act wasn't only about creating jobs, but also to invest in American infrastructure, education and energy and lay a foundation for long-term prosperity. Further, the Recovery Act wasn't only made up of government spending to directly create jobs, but also, as conservatives typically neglect to mention, tax cuts for most Americans to mitigate the drop in demand caused by the recession.
All true, yet easily dismissed by conservatives as mere excuses as they seek to delegitimize the whole concept of active government among a public starving for more jobs.
If the balanced approach of the Recovery Act isn't good enough, what's the conservative response to the lingering jobs crisis? The conservative response to everything: more tax cuts.
We did try that recently. Let's apply the Boehner Math test and see how it worked.
* The estimated cost of the Bush tax cuts through 2008 was $1.5 trillion.
* The number of jobs created during the Bush presidency was 3 million.
* Using Boehner's Math and a trusty handheld calculator, and you end up with
$500,000 per job.
Almost double the cost of Obama's stimulus.
And in the case of the Bush tax cuts, the Boehner Math test is more revelant. There really wasn't any other economic argument to justify the cost of tax cuts heavily skewed to benefit millionaires and billionaires besides the promise of robust job growth.
One can certainly argue that the Recovery Act was not sufficient to bring about a robust recovery, even if it likely prevented a global depression.
But considering that the Bush tax cuts completely flunk the Boehner Math test, perhaps government spending is not what ails the Obama Recovery Act.


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by Tyler Peck, sports information graduate
MILLEDGEVILLE, Ga. - The nine-day layoff proved to be too much for the women's tennis team at No. 22 Georgia College & State University (7-7, 4-5 PBC) as they lost 9-0 to No. 15 Hawaii Pacific University today (April 3).
At first doubles, Gabby Acuna (Peachtree City, Ga.) and Marjorie Ceppo (Sao Paulo, Brazil) fell 8-3 to the team of Ingrid Cseh and Zora Vlckova of the Sea Warriors.
The French duo of Bertille Lion and Diane Danna were shut out 8-0 to the twosome of Anastasia Ageychik and Lauren Shin at second doubles. At third doubles the freshman pair of Adriana Acuna (Peachtree City, Ga.) and Angy Cuellar (Bogota, Colombia) lost 8-1 to Alexsandra Stankovic and Nina Mihova.
No. 22 Ceppo was defeated by No. 12 Vlckova 6-2, 6-1 at the first singles slot. At second singles, No. 40 Mihova of Hawaii Pacific took down Danna of Georiga College 6-2, 6-3. The Bobcats' Lion fell just short of the Sea Warriors' Ageychik by the score of 6-5, 6-3 at third singles.
Gabby Acuna lost 6-4, 6-1 Cseh at the fourth singles postion. The fifth and sixth singles match saw similar results as Cuellar and Adriana Acuna lost 6-1, 6-1 to Stankovic and Shin, respectively.
Georgia College is back in action tomorrow, April 4 against SCAD at 1 p.m at the Centennial Center Tennis Facility.
Visit www.GCSUBobcats.com to nominate your favorite former Bobcats and Colonials to the GCSU Athletics Hall of Fame. The GCSU Department of Athletics sponsors 10 varsity athletic programs at the NCAA Division II level. As a Division II program, GCSU prides itself on balancing the life of the student-athlete, evidenced by the Bobcats' multiple appearances in post-season competition as well as documented academic success and community-service involvement. Sign up at Twitter.com username GCSUSID for up-to-the-minute reports.


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On Wall Street, Consumers Are Key
Polya Lesova takes a look at today's market action, including three stocks to watch. Photo: Getty Images.
This transcript has been automatically generated and may not be 100% accurate.
... the the ... markets Polya Lesova joins us from MarketWatch thank you Brian much for being here Napier said the mining ... age Impact Markets Thai already ... ate into the exotic plant that still yet for U S stock futures are little changed at this point but though with getting some economic data to make their common sense and so will get comb price Tuesday that and also consumer confidence ... is at the after the market opens up the kiddos to a very important people often gloss over those of the consumer does matter because ... happy can seem is ... spent more after today in consumer spending to such a big part of our U S economic well so that's a very very important housing we have had a robust economic recovery since will want to without ... housing is upon us absolutely yes im tellin known as part of what's going on in right ... yet again there is one of the companies that charity pointed to the south this morning Koh Kong go there ... and it felt a vague idea of what the earnings were up about ... twenty percent of the new blue base only about twenty six percent ... when teens to improve ... aam and and I said that while and then maybe some sewing and bonds ... in the housing recovery ... IBB that they don't care how the piece quotes exceedingly bright so aam Diaz seemed to be fairly optimistic about town ... the housing market ... I'm sure I went back to two thousand and seven men and an optimistic to ... however we don't know I don't know that that ... the roots of the other one that's one of the three stocks to looking at today one of the others but materials what's going on now ... yes at some point my Deals announced this morning that it will ... quiet Tokyo Electron ... Ahmed a token it is worth around nine billion dollars the combined company ... will be with twenty nine PM ... NCT sensitive takeover of the few in that town by applying GAO's ... al whites shares were up about six percent in a minute ages at last check ... so I think investors like the news and DC some of the Senate is there ... and the potential for more of don't call me dilutive unimpressed with Red Hat that's the first to start something about him use of lightweight due late yesterday right yet and it has appointed herself after the market closed and that ... brings the end of the new Wealth K but what investors will be disappointed about ... what what they've been inks disobeying Stella's only about eight percent while expectations with a hope of a down fourteen percent ... so that was very disappointing go basically to my kid ... and bindings and in the key to future revenue golf and as a Celtic at Sears and on about ten percent in town ... Alex thinks stings a lot thank you very much Polya Lesova


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I have a 5,5mm neopren wetsuit + gloves/hood/boots.. Now my question how far I can hold out.
I have been kiting on south wind, air-12°c, water 10°c, rainy conditions. I didn't feel any cold, even when I felt in water, i had feelign that i could kite all day. When I was standing outside and rain was pouring on me and I also didn't feel any cold.
Would I be able to hold out this conditions(at least 1 or 2 hours):
-air 8-9°c
-water 10°c
-wind north east - Bora (im little bit scared of NE cold wind chill)
If anybody have expirience with that conditions please let me know!


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|Oracle Workflow Administrator's Guide
Release 2.6.3
Part Number B10283-02
Note: The Oracle Workflow web pages are being converted to the Oracle Applications Framework user interface format. Depending on your version of Oracle Workflow and which patches you have applied, you may see Oracle Workflow web pages in the new format as well as in the previous format. The administrator home page is currently available for the version of Oracle Workflow embedded in Oracle Applications.
Use the Oracle Workflow administrator home page to link to Oracle Workflow's web-based administration features. This page centralizes your access to the features.
Note: The Oracle Applications Personalization Framework provides the ability to customize Oracle self-service web application pages. If you are logged in as a user or with a responsibility for which the Personalize Self-Service Defn profile option is set to Yes, a global Personalize button appears on each self-service web application page, and Personalize Region links appear for every personalizable region on each self-service web application page. You can choose the Personalize button or Personalize Region links to create your personalizations. For more information, please refer to the Oracle Applications Personalization Framework online help.


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Slash Gets Restraining Order Against Alleged Stalker
Guns N' Roses guitarist Slash has obtained a temporary restraining order against a man he says has been trying to get onto his property.
During Slash's Super Bowl party last night, the man in question reportedly tried to convince Slash's girlfriend that he was a party guest, TMZ reports.
When he was denied entry, he reportedly became very angry and smashed a security camera at the musician's gate.
The man returned a few weeks later, Slash says, and tried to get into another party he was having. When he was turned away he sat nearby on his motorcycle, loudly revving the engine.
It's not clear what the man wanted with the famous guitarist, but a judge granted a restraining order Monday.
Slash rejoined Guns N' Roses in 2016 along with co-founding bassist Duff McKagan. The pair's reunion with frontman Axl Rose and the ensuing tours made GNR once again one of the top-grossing acts in music for both 2016 and 2017.
GNR will tour Europe again this summer.
In the meantime, Slash is apparently finishing up another a new studio album with Myles Kennedy & The Conspirators.
Photo: Getty Images


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March 23, 2005, Amarillo, Texas. Fr. Frank Pavone, National Director of
Priests for Life, officially announced today that he is founding a pro-life
community dedicated to the formation and training of priests, deacons, brothers
and seminarians who will devote themselves fully to the proclamation of the
Gospel of Life. This initiative will be based in the diocese of Amarillo, Texas,
under the authority and stewardship of Bishop John W. Yanta.
"It has been a dream of mine for over a decade to form a community that can
accept seminarians who want to devote their entire ministry to the defense of
the unborn," said Fr. Pavone. "While there are religious communities that give
special emphasis to the right to life, the Church has no 'institutional' society
of men whose exclusive focus is to protect innocent human life from the tragedy
of abortion and euthanasia. It is time for such a community. I am grateful to
Bishop Yanta for allowing me the opportunity to make this dream a reality."
Bishop Yanta, who has served on the Priests for Life Episcopal Board of
Advisors since 1998, and who has been particularly devoted to the pro-life cause
throughout his priesthood, has already offered several buildings in his diocese
that will serve as the center for the new apostolate. "I am excited about
supporting Fr. Pavone in venturing forth, with and through the Holy Spirit, in
the establishment of a Society of Apostolic Life for priests and seminarians
dedicated to pro-life ministry - an immense need at this time in history," said
Bishop Yanta today. "The Lord has provided several vacant buildings that once
served as a Christian Brothers High School with boarding facilities, a chapel,
gym, and spacious grounds. The Diocese of Amarillo is happy to make these
available (at no cost) to Priests for Life and the proposed Society of Apostolic
This society of apostolic life, while drawing on the spirit and mission of
the Priests for Life organization, will be a completely separate entity, known
as Missionaries of the Gospel of Life. Priests for Life will continue to
exist as an association of the Christian faithful under Canon Law, and Fr.
Pavone will continue to serve as its National Director. In order to initiate the
historic formation of this pro-life community of priests, deacons, brothers and
seminarians, Fr. Pavone has officially become a priest of the Diocese of
Amarillo, and will begin assembling a formation team for the community. Priests
for Life is also in the process of establishing a headquarters in the diocese,
but will continue to maintain its current offices and staff in New York,
Washington D.C., Virginia, California, and Rome, Italy.
"This is a pivotal moment in time," said Fr. Pavone. "Throughout the history
of the Church, God has intervened in times of great moral crisis and has raised
up within His Church the charisms necessary to address those crises. I have long
been convinced that God is raising up numerous disciples ready to devote their
entire lives to ending the tragedy of abortion, which the bishops have
identified as the 'fundamental human rights issue of our day.' I have no doubt
that we will see a tremendous and immediate response to this initiative."
Fr. Pavone announced that men considering joining this community can attend a
discernment retreat he will conduct on June 24-26 in Amarillo. There will also
be a seminarians' pro-life conference in Newark, NJ from August 16-21, during
which Fr. Pavone will also discuss the new community. Those interested in the
community may contact
Bishops from around the world praised the historic effort.
From Denver, Colorado, Archbishop Charles J. Chaput said: "Under
Father Frank Pavone's leadership, Priests for Life has been a tireless and
important national voice defending the sanctity of human life. In supporting Fr.
Pavone's new initiative, Bishop Yanta and the people of the Diocese of Amarillo
are offering a vital service to Catholics throughout the United States."
From St. Louis, Missouri, Archbishop Raymond L. Burke said: "I have
received with great joy the news of the foundation of a priestly society of
apostolic life dedicated to the apostolate of the respect for human life. In
every time period, the Holy Spirit has inspired founders of institutes of the
consecrated life and societies of apostolic life, so that the spiritual needs of
the Church and world might be more fully addressed. Surely, there is a great
need in our time for a priestly society dedicated to the conversion of our
culture of death and the promotion of a civilization of life. The work of the
Priests for Life and its National Director, Father Frank Pavone, has surely
prepared the way for the timely foundation of the priestly society of apostolic
life. I commend Bishop John W. Yanta for his pastoral vision and generosity in
inviting Father Pavone to make the new foundation in the Diocese of Amarillo. I
pray that God will bless abundantly Bishop Yanta, Father Pavone and the new
From Phoenix, Arizona, Bishop Thomas J. Olmsted praised Priests for
Life: "[This organization] has offered a courageous and articulate proclamation
of the Gospel of Life for a number of years. While standing strong in the
defense of every human life, it has offered persuasive reasons for respecting
the dignity of each person, especially the most vulnerable and innocent among
From Rome, Cardinal Renato Martino, president of the Pontifical
Council for Justice and Peace, said: " In today's world, the idea of a new
religious community founded for the purpose of working to protect human life may
seem like a sign of contradiction—but it may just be what the world of today
needs! The call to protect life is not only a foundation of our faith as
Catholics, but it is the very basis of our recognition of human rights and the
right to life. The human dignity with which we have been endowed by God binds us
together as members of the one family."