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In 2007 my beloved son Andrew died from vJCD aged just 24. Since then I have created a campaign to find out how and why he died and who is to blame for this terrible disease. This is my blog containing much of the material I have collated and the history of the campaign.
Friday 19th June 2015
Confirmed case of BSE in Ireland June 2015, how many cases of BSE are still entering the food chain and not being reported? As the UK no longer tests its cattle for BSE!
Ireland Department of Agriculture, Food and the Marine Identifies Suspected BSE Case
Department of Agriculture, Food and the Marine Identifies Suspected BSE Case
The Department today announced the identification of a suspected BSE case in county Louth. The case was identified through the Department's on-going surveillance system on fallen animals (that is animals which die on farm). The animal was not presented for slaughter and did not enter the food chain.
Confirmatory tests are being undertaken and results will be available in approximately one week. If confirmed, this will be the first BSE case found in Ireland since 2013.
DAFM is now undertaking a full investigation into all relevant factors in this case – including a full epidemiological examination.
DAFM is informing the relevant national and international reference organisations and the European Commission, and will be liaising with trading partners.
If, as expected, the tests confirm this to be a classical case of BSE, this may impact on Ireland's recently awarded "negligible risk status" from the World Organisation for Animal Health (OIE). In this case Ireland will revert to "controlled risk status" which applied up to last week and which facilitated trade to a wide range of international markets. It will also result in the continuation of the existing range of controls for a further number of years.
The full range of risk mitigating measures continue in place at slaughter plants, including the following:
All animals presented for slaughter are systematically subjected to ante-mortem examination by veterinary inspectors to ensure that only healthy animals are allowed into the food chain.
A range of tissues – identified as 'specified risk material' – where the BSE infectivity resides in potentially infected animals are systematically removed from all slaughtered bovines of differing ages as follows:
All ages: tonsils, intestines and mesentery
Over 12 months: skull (including eyes and brain) and spinal cord
Over 30 months: the vertebral column and associated tissues
The animal involved is a five year old cow on a dairy farm in county Louth. The investigation will include an examination of the birth cohort and progeny of the cow involved.
Monday 18th May 2015
http://www.express.co.uk/news/uk/577667/Cordelia-Gummer-Mad-Cow-disease-BSE-scandal-25-years The Express this Saturday had a one page feature for the 25th anniversary when John Gummer tried to feed a burger to his
4 year old daughter Cordelia in May 1990.
The Express journalist interviewed me at length, I was shocked to hear that Gummer's son Ben is now junior health minister and John Gummer continues to re-invent himself as some sort of environmentalist, when he was responsible for killing my son, disabling and killing hundreds of innocent people and putting 'one in 2,000 of the UK at 'risk' of developing the human form of mad cow disease. The bitter irony is not lost on this grieving mother. I remain steadfast, determined to see John Gummer and his co-horts behind bars for the man-slaughter of my son and so many other destroyed lives and futures.
Friday May 8th 2015 Sadly another Tory government will be back in Number 10 Downing Street for another term, but the campaign for justice has grown stronger and in the near future www.justice4andy.com will put those Tory officials and cronies responsible for infecting and killing thousands of people with vCJD, in the dock..
Tuesday 17th February 2015
Sarah Cheverton freelance journalist who also writes for the Huffington Post, has composed this brilliant feature about the campaign and my fight for justice. Anyone who cares about the food they eat, scientists they place trust in and the politicians they vote for should read this and be informed! THIS MUM WILL NEVER BE SILENCED! http://www.starandcrescent.org.uk/mad-cows-disease-still-a-threat-to-all-of-us/
Friday 13th February 2015
Roger Hirons the artist who has put together a shocking exhibition revealing disturbing truth behind BSE/vcjd cover-up was interviewed with me by the BBC. Below is the link to that interview which was broadcast on BBC Breakfast Radio Solent. Also photo of me getting a much needed hug from Roger during the press preview of the show at the Southbank Centre, London. Thank you Roger so much for being another voice for my son Andrew.
Tuesday 10th February 2015
Southbank Centre, Hayward Gallery, London My Andrew's voice is being heard loud and clear at the Hayward Gallery, The Southbank Centre, London from today. The art exhibition, History is Now! will be running for three months and Turner nominated artist Roger Hirons, was inspired by this website and my Andrews story. Roger Hirons has used pages of this website, images of Andrew and placards from my many demonstrations to illustrate the thousands who have been affected by human BSE and also the millions of us exposed to the deadly human from of mad cow disease. An extensive part of the exhibition is dedicated to BSE/vCJD and the cover-ups that created the lethal man-made pathogen. My book 'Who killed my son?' is also part of the exhibition and art. I was at the private viewing and unveiling of the show yesterday. Roger Hirons inspiring artist and innovative work, reveals the cover-ups, scandals and political and scientific manipulation behind BSE and the human form of mad cow disease. With shocking images of cattle and people dying of BSE it is clear evidence once again of the corruptions within Westminster. (above is photo Christine with Roger Hirons at the show) Roger said ' I was at school during the mad cow epidemic and was terrified the food I was eating was going to give me human BSE. Reading Andrews story was integral and Andrew's voice and voices of all the victims needed to be heard.' History is Now, also includes works by DavId Hockney, Damien Hirst, Andy Warhol, and many other artists. The vcjd/BSE exhibition by Roger Hirons is shocking, poignant and at timely reminder that BSE poses a ticking health time-bomb. Essential viewing as we move towards a general election in the UK. HISTORY IS NOW is 7 artists take on Britain and highlights the political, health and historical changes that affect us in 2015, as a consequence of past decisions by government and ministers. Here is a link to the website http://www.southbankcentre.co.uk/whatson/history-is-now-7-artists-take-88866 http://www.theguardian.com/artanddesign/2015/feb/09/history-is-now-7-artists-take-on-britain-hayward-gallery-review
Monday February 3rd 2015
CATTLE IN NORWAY DIAGNOSED WITH BSE Bovine spongiform encephalopathy, Norway Information received on 29/01/2015 from Dre Kristina Landsverk, Chief Veterinary Officer, Norwegian Food Safety Authority, Ministry of Agriculture and Food, Brumunddal, Norway This event pertains to the whole country Epidemiology Source of the outbreak(s) or origin of infection Unknown or inconclusive Epidemiological comments Based on status on 29 January 2015: On 20 January 2015, the Norwegian Veterinary Institute reported suspicion of BSE on a cow in Norway, based on initial test done on CNS material. Part of this material was sent to European Union Reference Laboratory in Weybridge (21 January 2015) for verification of diagnosis. The affected cow was a 15-year-old and born in Norway. The dam was imported from Sweden. The cow did not show clinical signs of neurological disease before she was killed (12 January 2015) due to old age and injuries. The BSE test was taken as part of the BSE surveillance program. The Norwegian Food Safety Authority (NFSA) has put restrictions on movement on the farm, and performed epidemiological investigations. The NFSA has identified four risk animals, according to relevant legislation. These animals are also placed under official movement restrictions. The four identified risk animals will be killed and disposed by incineration according to European Union legislation. The epidemiological investigation including tracing of risk animals from the holding of origin as well as the present holding has identified 2 offspring borne within two years prior to the incident in addition to 2 cattle belonging either to (1) the cohort of animals born in the same herd as the affected animal within 12 months preceding or following the date of birth of the affected cow or (2) the cohort of animals which at any time during the first year of their lives were reared together with the affected cow during her first year of life. Progeny borne within two years prior to the incident and the cohort of risk animals are put under movement restrictions and the killing and destruction of these animals will be carried into effect as soon as possible. The affected cow's carcass has been completely destroyed. The NFSA ensures that the cow's carcass has been processed by pressure sterilisation in a Category 1 processing plant and that the resulting material has been sent for incineration/co-incineration in accordance with the By-Products Regulatio
Wednesday 7th January 2015
As, this New Year begins the campaign for justice and my investigations into my son Andrews's criminal death speeds into action. Despite cyber attacks on this website, personal threats to my well being and intimidation towards families affected by government officials, we remain determined and upbeat. The current Chief Medical Officer Sally Davies crafted rhetoric regarding Human BSE, is false and does not inform or disclose the true numbers of people who have died are dying and will die of vCJD. Whitehall and Westminster continue to spin their web of lies and the corruption that has seen serious child abuse thrive in the corridors of the UK establishment was hand in hand with the BSE cover-up. Today at the beginning of this New Year, I remember my beloved Andrew and all those loved family members who have died, been disabled and continue to be affected by the human form of mad cow disease/vCJD. You will never be forgotten and your cause will soon be centre stage. 'Justice is truth in action' Benjamin Disrael
Thursday 18th December 2014
I was recently asked to appear on Green Radio a station based in London. Below is the link to the podcast of the two hour show, which included my choice of five songs which had particular significance to me and my family. Anna Watson the presenter was sensitive, professional and very well informed about the issues surrounding BSE and its human victims. Listening to my favourite songs such as Abba's Mama Mia and the Circle of Life from the Lion King, brought back many happy memories of family life before it was shattered by my Andrew developing vCJD. Thank you Anna and producer Sam for making this experience so touching and warm, it was at times hard to talk about my heart break but the songs and show helped me to access the many happy family memories I shared with Andrew and my daughter Emma. I will continue to fight and podcasts such as these are a reminder of the wonderful young man my son was and how a bereaved mother has the strength to take on the world when defending her child and loved ones. Because that's what mums do…… http://www.mixcloud.com/kingstongreenradio/the-natural-health-show-justice-for-andy/
Tuesday 16th December 2014
At 9:25pm on 16th December 2007 my only son Andrew died of vCJD aged just 24. Time doesn't heal especially when those responsible for Andrews unlawful death, have never been punished but, outwardly seem to have flourished due to their corruption and lies. However whatever means, patronage, and influence those responsible for Andrews's death continue to use, they are running out of places to hide and people willing to conceal their criminal acts. Within Westminster and Whitehall there are sweeping changes, knives are being sharpened and loyalties abandoned as rats jump a sinking ship of shame. Justice will be done! Below is a poem which reminds me of Andrews big, caring heart, my handsome, once healthy, strong young son, a true gentleman with an honest heart who would have done so much for society the world is a much sadder place without my Andrew. If I should go tomorrow If I should go tomorrow It would never be goodbye, For I have left my heart with you, So don't you ever cry. The love that's deep within me, Shall reach you from the stars, You'll feel it from the heavens, And it will heal the scars. Anon
Wednesday December 10th 2014
There was a summit at the House of Lords regarding early onset dementia, read the story below from Victoria McDonald Health Correspondent Channel 4 News Yet not one family affected who is affected by human BSE and is challenging of the government was invited or informed about this event. Loosing a child/ young person to the human form of mad cow disease and watching a teenager or twenty year old son or daughter suffering from dementia due to Human BSE is devastating. Families and current victims of vCJD should have been included and informed. Once again vcjd victims and their families are side lined and seen as a group that can be ignored and dismissed, well these attempts to silence our voice just makes it stronger. http://blogs.channel4.com/victoria-macdonald-on-health-and-social-care/early-onset-dementia-devastate-family/2685
Friday November 21st 2014
Read why this bereaved mother and investigative journalist has been repeatedly threatened by the establishment, and why Prime Minister David Cameron and his government continue to ignore human mad cow disease a UK deadly disease, which one in 2,000 of the population silently carry or incubate. http://www.portsmouth.co.uk/news/health/local-health/portsmouth-mum-s-anger-as-government-says-no-to-vcjd-probe-1-6428090
Monday 17th November 2014 PORTSMOUTH BOOKFEST Many families previously unknown to me who have been affected by human BSE came forward during my recent book signing. The list of victims of human mad cow disease grows daily and yet the UK government continues to deny the true numbers of people who have died, are dying ,disabled or are 'at risk' of developing vCJD. The biggest health and political cover-up of modern times continues to weave its sinister web perpetrated by the establishment and condoned by the Westminster cronies of those I name and shame on this website. http://www.portsmouth.co.uk/news/health/local-health/who-killed-my-son-1-6414276
Thursday 6th November 2014
There was a wonderful response from members of the public during my meet the author, talk, book signing as part of Portsmouth BookFest. People were appalled at the lack of cohesion and dis-regard Prime Minister David Cameron and his government have for victims of Vcjd and blood safety. I have several more leads too, invites to give talks to various organizations and of course book sales went very well too! Below is link to Andrew's Facebook page and also some photographs taken at the event by my PR supporter and the media. https://www.facebook.com/WhoKilledmySon?fref=ts GOVERNMENT REJECTS WARNINGS MAD COW DISEASE FROM TOP EXPERTS MPS https://www.youtube.com/watch?v=NVSm9Mr7TFk The Government has rejected calls for further research and safeguards into vCJD the human form of mad cow disease. It has dismissed the significant and essential recommendations that an Inquiry by influential MPs from the Science and Technology Committee made in their report. (Published 24th July 2014.) The MPs took a detailed look at Britain's blood supply and the very real risk that human BSE is being passed on by blood donors who are unaware they are carrying the infection. Two essential recommendations the Inquiry members made was a large scale vCJD blood prevalence study in the UK within 12 months, to find out how many in the population have been exposed to BSE. The second recommendation was research into dementia, amid concerns that CJD is being mis-diagnosed particularly in the elderly. The government has rejected both of these stating there is no test for vcjd and the second that funding is not available to explore just how many people with dementia are really dying of vcjd.
I challenged this very strongly, there are and have been tests but these have been vetoed by the Department of Health. Myself, and other families affected by vCJD tried to send our late family members blood samples to foreign independent scientists developing screening tests for vcjd. We were intimidated and blocked from doing this, the Department of Health control all blood and tissue samples. I appeared on BBC Radio just thirty minutes after the report was published, late on Friday evening. (see link above) It the usual tactic by Whitehall spin doctors a good time to bury bad news.
The UK population face a deadly potential epidemic on our doorstep which was highlighted repeatedly within the Inquiry's published report. Every time this campaign and experts present facts about the ticking health time bomb that is human BSE and demand action, it is dismissed and pushed aside by the authorities. This is not about lack of funding this is all about protecting those responsible for BSE and its deadly on-going consequences. Hospital patients are not screened for vcjd, blood donors are not screened for human BSE, and with upwards of 60,000 of us carrying or incubating the disease, Human BSE is being re-cycled again and again within the wider population. I remain determined and upbeat, my evidence is now in the archives of Hansard my book selling well on Amazon, my investigations on track and gaining more momentum.
When Andrew was dying he asked me to find out who was responsible for his illness and also to protect other families, I continue to honour those promises as a mother, campaigner and journalist. These are the recommendations which were rejected by the Government.
1. A recommendation that the Government begin a large scale vCJD blood prevalence study in the UK within 12 months ( Conclusion paragraphs 14/15)
2. A recommendation that the Government conduct immediate audit on those 'at risk' of vCJD. ( see Conclusion Report paragraph 18)
3. Calls for the Government to back research into atypical dementia- amid concerns that CJD is being mis diagnosed in the elderly (Report Conclusion paragraph 21)
4. Criticism of SABTO ( the advisory committee on the Safety of Blood, Tissues and Organs) for its 'relaxed' approach to vCJD in the light of recent evidence as one in every 2,000 people could be infected with vCJD without showing any symptoms. (Conclusion Report paragraph 22)
5. Criticism of the Government for its current attitude ' our fear is that the Government current attitude is driven less by the available scientific evidence than by its optimism that vCJD is no longer a threat to public health that it once was. In the current economic environment this attitude is not surprising. However its is not justified for all we know the storm may well be on-going.' (Report Conclusion paragraph 23)


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Keyboard/synth player wanted for indie rock type band heavy influence of joy division, simple minds
Metronomy, house, wire, joy division, simple minds, We have had one single out. Check iTunes for Ghosts by The Reward. about to release our second single. Looking for keyboard played to join the fun. We have our own recording studio and all avail

subset: commoncrawl


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While human-caused global climate change has long been a concern for environmental scientists and is a well-known public policy issue, the problem of excessive reactive nitrogen in the environment is little-known beyond a growing circle of environmental scientists who study how the element cycles through the environment and negatively alters local and global ecosystems and potentially harms human health.
Two new papers by leading environmental scientists bring the problem to the forefront in the May 16 issue of the journal Science. The researchers discuss how food and energy production are causing reactive nitrogen to accumulate in soil, water, the atmosphere and coastal oceanic waters, contributing to the greenhouse effect, smog, haze, acid rain, coastal "dead zones" and stratospheric ozone depletion.
"The public does not yet know much about nitrogen, but in many ways it is as big an issue as carbon, and due to the interactions of nitrogen and carbon, makes the challenge of providing food and energy to the world's peoples without harming the global environment a tremendous challenge," said University of Virginia environmental sciences professor James Galloway, the lead author of one of the Science papers and a co-author on the other. "We are accumulating reactive nitrogen in the environment at alarming rates, and this may prove to be as serious as putting carbon dioxide in the atmosphere."
Galloway, the founding chair of the International Nitrogen Initiative, and a co-winner of the 2008 Tyler Prize for environmental science, is a longtime contributor to the growing understanding of how nitrogen cycles endlessly through the environment. In numerous studies over the years he has come to the realization of the "nitrogen cascade," and has created with his colleagues a flow chart demonstrating the pervasive and persistent effects of reactive nitrogen on Earth's environment (www.initrogen.org).
|Contact: James Galloway
University of Virginia


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Mississippi State University's Music Maker Productions (MMP) announced Monday that The Neighbourhood, an alternative rock band known for its Billboard Hot 100 hit "Sweater Weather," will headline the Old Main Music Festival.
The festival is tentatively scheduled for 7 p.m. April 12 at the MSU Amphitheater, with plans to coordinate with MSU's baseball series against the University of Mississippi as part of Super Bulldog Weekend. Opening for The Neighbourhood will be The Red Thangs, a high-energy pop band that placed second at MSU's 2013 Plazapalooza Battle of the Bands.
To subscribe to the E-edition, please click here [3].
[1] mailto:email@example.com
[2] http://www.starkvilledailynews.com/sites/default/files/04_The_Neighbourhood_Group_121-1.jpg
[3] http://www.starkvilledailynews.com/eedition


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"The Doomsday Show" with Jason Jägel @ Rappcats, Los AngelesMusic // Thursday, June 18, 2015
Not sure if you remember dear reader, but back in August 2014, we did a very special issue that we dubbed the "Alter Ego" issue, featuring a cover story on musician Madlib with cover illustration by SF's own Jason Jägel. So, we highly endorse you going to check out the special one-day only day show of paintings and prints by Jason Jagel at the Rappcats space about Madlib's collaborator, DOOM. There will be prints for sale, 40 "Extra Doom" hand-embellished Hoecakes prints, and back stock of MF DOOM Operation Doomsday lunch boxes (out of print), and two new tees.
THE DUCK SHOW: Curated by Ryan Travis Christian @ Minotaur Projects, LAJuxtapoz // Friday, March 27, 2015
In late 2014, there was a Duck show curated by the great Chircago artist Ryan Travis Christian. Now, that Duck show has evolved into DUCKS! and is opening tonight (March 27) at our friend Louis Schmidt's new LA space, Minotaur Projects. There will be ducks painted by Jason Jagel, Richard Colman, Nat Russell, Mel Kadel, Paul Wackers, Ryan Travis Christian, Brian Willmont, Allison Schulnik, and so many more we can't even name them.
Best of 2014: Madlib, Art and the Alter EgoVault // Monday, December 22, 2014
In our August cover story Madlib, "Egon" Alapatt, Freddie Gibbs, and Jason Jägel sit down to discuss sampling, being born into music, and the art of the Fringe.
In the Magazine: Madlib with Freddie Gibbs, Jason Jägel, and EgonJuxtapoz // Monday, July 14, 2014
For 20 years, Otis Jackson Jr., aka Madlib, has been crafting underground hip hop classics under the guise of countless monikers. Raised in a large family by parents who instilled an insatiable appetite for composing, experimenting and absorbing influences through their own musical careers, he has simultaneously progressed, fashioned and expanded the genres of hip hop and rap music, while developing his own styles in the process.
On Sale Now: August 2014 w/ Madlib and the Art of the Alter EgoJuxtapoz // Monday, July 07, 2014
Juxtapoz is proud to announce a very special August 2014 issue, featuring one of our all-time favorite musicians, creatives, and all around artistic personas, Madlib. For years, we have followed Madlib's eclectic career, from Quasimoto, Madvillain, Jaylib, Yesterday's New Quintet, the Beat Konducta series, and everything in between. One common thread has always been the unique and artistically-driven alter egos that Madlib has given to the world, and in this issue, we talk to the musician about his world of music and art.
Waves For Water Benefit Auction is LIVE!Juxtapoz // Tuesday, March 18, 2014
Juxtapoz Magazine, Encinitas, California-based shop UNIV and San Francisco-based Chandran Gallery have teamed for a special auction and exhibition benefit for Waves For Water, an organization on the ground in the Philippines, mobilizing an urgent clean water disaster relief initiative in the aftermath of Super Typhoon Haiyan. From March 18—31st, a special curated selection of hand-painted surfboards will be available at auction on Paddle8. Artists who participated include Geoff McFetridge, CR Stecyk III, Tim Biskup, Lucy McLauchlan, Andrew Schoultz and more.
UNIV x Chandran Gallery x Juxtapoz Benefit & Auction for Waves For WaterJuxtapoz // Monday, March 03, 2014
Perhaps you followed our Instagram feed during the week of Art Basel 2013, but you may have saw our collaborative surfboard project with Encinitas, California-based shop UNIV and San Francisco-based Chandran Gallery. In Miami, we kickstarted the project that will soon be fully announced as a full auction and exhibition benefit for Waves For Water, an organization on the ground in the Philippines, mobilizing an urgent clean water disaster relief initiative in the aftermath of Super Typhoon Haiyan.
JASON JÄGEL "From the Sky, Rivers Look Like Snakes" @ Gallery 16, SFJuxtapoz // Tuesday, February 11, 2014
Jason Jägel, a SF-based artist who we have championed for years on this site and in our print edition, just opened "From the Sky, Rivers Look Like Snakes" at Gallery 16 in San Francisco.The exhibition contains three bodies of work; large oil paintings, works on paper and smaller mixed media peices. This marks the first time Jason has exhibited oil paintings since Bay Area Now 1 at the Yerba Buena Center in 1997.
"Everyone's Time Is Their Own" Curated by Gabe Scott @ Alter Space, SFJuxtapoz // Monday, February 10, 2014
This is a fantastic group show, and don't mind our biasbecause one of our contributors Gabe Scott did a fantastic job curating it, just opened in San Francisco that you should go check out. "Everyone's Time Is Their Own," features the works of Alejandro Diaz-Ayala (Dallas), Carlos Donjuan (Dallas), Clynton Lowry (New York), Derek Albeck, (Los Angeles), Derrick Velasquez (Denver, CO), Grady Gordon (Oakland, CA), Jacob Magraw-Mickelson (Seattle), Jason Jagel (San Francisco), JR Doty (San Francisco), Rachell Sumpter (Seattle), Roya Falahi (Los Angeles), Xi Zhang (Denver, CO).
Chandran Gallery & Juxtapoz @ Beach House, Shore CLub South BeachJuxtapoz // Thursday, December 05, 2013
Last night, Juxtapoz and Chandran Gallery opened a special exhibition, installation, and performance art piece at the Beach House in the Shore CLub South Beach, featuring works amazing installation and performace from Monica Canilao and Sorne, paintings by Jason Jagel, special beach robes and towels by Geoff McFetridge, poolside decor by Richard Colman, lobby installation by Andrew Schoultz, and pool floating canoe by all the artists.


text: "The Planned Parenthood of Nebraska & Council Bluffs mission is: Medical Services: To provide comprehensive reproductive and complementary health care services in settings which preserve and protect the essential privacy and rights of each individual. Education: To provide educational programs which enhance understanding of individual and societal implications of human sexuality. Advocacy: To advocate public policies which guarantee these rights and ensure access to such rights."


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World War Z
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My son is reading it right now so I've been taking it with me on the occasional trip to the throne, lol. Haven't made it far enough to develop an opinion yet.
Kinda off topic but I just finished book three in a series called
The Remaining
. It centers around a somewhat zombie apocalypse. The US government had established a program that placed a "Coordinator" and a very large cache of supplies in each state. The Coordinators are placed into bunkers in the event of a possible end of times situation and instructed not to come out until 30 days after having lost contact with the outside world. Their mission then is to reunite and rebuild on behalf of the US government. The series follows the Coordinator for North Carolina. I thoroughly enjoyed it and am looking forward to book 4.
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From Wikipedia, the free encyclopedia
|Look up circumpolar in Wiktionary, the free dictionary.
Circumpolar may refer to:
- Antarctic region
- Arctic region
- Circumpolar star, stars that never rise or set from the perspective of a given latitude on Earth.
- Polar front in meteorology.
- circumpolar navigation, a global circumnavigation which traverses both poles
See also[edit]
|This disambiguation page lists articles associated with the title Circumpolar.
If an internal link led you here, you may wish to change the link to point directly to the intended article.


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- 125Promote
Phone Skins
Minions (Patterns Please Series #1)by Lalaine Lim
Skins are thin, easy-to-remove, vinyl decals for customizing your device. Skins are made from a patented material that eliminates air bubbles and wrinkles for easy application.
Patterns Please Series #1 - Minions
Sharing my love of minions! Here's a bunch of adorable minions to keep you company throughout the day.
minions, green, yellow, digital illustration, pattern
awesome illustration! :D
haha great style!
thank you so much :D
we stole the statue of liberrrty! well from las vegas
ahahaha soooooooooo cute
It's too bad this isn't available as a duvet cover, it would work perfectly... :D
@Amanda It's available as a duvet cover now, just updated the shop :DD
Loving this piece :)
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|ISSN 1088-6826(online) ISSN 0002-9939(print)
The dominated ergodic estimate for mean bounded, invertible, positive operators
Abstract | References | Similar Articles | Additional Information
Abstract: We characterize those positive linear operators with positive inverse for which the dominated ergodic estimate holds. We also prove that for such operators one has mean and a.e. convergence.
Retrieve articles in Proceedings of the American Mathematical Society with MSC: 47A35, 28D05, 46E30, 47B38
Retrieve articles in all journals with MSC: 47A35, 28D05, 46E30, 47B38
Additional Information


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English, , 858kb
This document contains an analysis of data on 205 polymers to identify correlations between polymer characteristics and the potential for health or ecotoxicological concern.
English, , 872kb
The Nanoscale Materials Stewardship Program (NMSP) was developed to help provide a firmer scientific foundation for regulatory decisions by encouraging submission and development of information for nanoscale materials. The NMSP comprised two sub-programs, the Basic Program and the In-Depth Program. When the NMSP was initiated, EPA committed to issue this interim report after one year. The Agency welcomes comments on this interim
English, , 471kb
The Pesticides Programme has undertaken work to: (i) identify and overcome obstacles to work-sharing; (ii) harmonise data requirements and test guidelines; and (iii) harmonise hazard/risk assessment approaches.
English, , 282kb
This guidance document focuses on microbiological efficacy testing. It covers efficacy testing of articles treated with antimicrobials in the manufacturing process with the intention of the achieving an external effect.
English, , 32kb
The world is rapidly transforming and a number of dynamic emerging economies,including South Africa, have become major players and trading partners with the members of the Organisation for Economic Co-operation and Development(OECD). In this context, the OECD Members have recognised the need for theOrganisation to become more open and relevant in order to realise its strategicgoal of becoming an important hub for dialogue on globally
English, , 1,637kb
This report presents the results of an OECD seminar on ways to achieve risk reduction while addressing issues associated with the use of chemical pesticides or non-chemical means of crop protection on a small scale.
English, , 567kb
The report is a collation of various aspects such as responsible regulatory authorities/agencies, data requirements, activities being pursued and regulatory mechanisms for approving minor uses in member countries.
This page lists, in chronological order, the Pesticides Publication Series that relate to Minor Uses.
This document intends to provide a "snapshot" of how OECD countries have developed and run their PRTR programmes. It shows the similarities and differences across countries in their requirements to collect and display high quality data, which is required for an effective PRTR system. It also presents compliance and regulatory requirements, the development of guidance material, and emerging issues and challenges for the future.
OECD's Working Party on Manufactured Nanomaterials launched a "sponsorship programme" at its 3rd meeting (November 2007). Countries will share the testing of specific nanomaterials (MNs) under this programme.


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Simeon Rice's assessment of his first four games with the Broncos isn't pretty.
"A farce. It was a faulty me," Rice said. "You haven't seen the real Simeon Rice. That hasn't been me out there."
In his typical, passionate approach, Rice talked at length Wednesday about dealing with his ongoing shoulder pain, the frustration of not being able to be his usual disrupting self and having to watch the Broncos' 41-3 loss to visiting San Diego.
Rice was among Denver's eight inactive players Sunday. Broncos coach Mike Shanahan said Rice was deactivated because the team wants him to strengthen his shoulder, which was operated on in the offseason. Rice said the deactivation was a product of the coach's belief that Rice was not healthy enough to produce.
Denver Broncos
- Find analysis and notes from the gridiron and locker room on the All Things Broncos blog.
- Ask Mike Klis about the team or NFL in the Broncos Mailbag.
- Evaluate the latest team numbers on the Broncos Stats Page.
- Post photos of your team spirit.
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Rice, who has 121 career sacks, has not had one this season.
"It was humbling for me not to be out there Sunday, but that was the right thing to do," Rice said. "Look at the tape: I wasn't getting it done. I was hardly playing with two arms. A lot of the time, I wasn't able to play with my left arm. The coaches looked at the film and told me I wasn't right. I didn't want to believe it, but it was the best thing for me."
Rice said he has started to feel better in the past week and showed an improved range of motion with his left arm. He expects to be able to play Oct. 21 against Pittsburgh. On one of his first plays with the Broncos, Rice batted down a ball against Buffalo.
"I thought my left arm was going to explode on that play," Rice said. "It was terrible."
Rice said in retrospect he may have rushed himself onto the field because he was so eager to show the Broncos and their fans what he can do. Six days before the season, Rice signed a $3 million deal, with a chance of $1 million more on incentives.
"It was like when I was 13 and I had a 101 temperature and I wanted to play," Rice said. "But my mom wouldn't let me play. It destroyed my whole weekend, but that was the right thing to do. I rushed myself out here because I wanted to show everyone that I am a dominant player. But I just wasn't right. ... But I will get there and be my old self. Everyone will see that."
Bill Williamson: 303-954-1262 or email@example.com


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CLEARANCE SALE: Check Our SALE Items link for up to 50% DISCOUNTS on selected items. Many very nice gifts can be found there!
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Item #
Antique Toy Cast Iron Sky Scraper Coin Bank Piggy Money
Antique Toy Cast Iron Sky Scraper Coin Bank Piggy Money. Very nice old castiron bank which has retained most of the original paint. Building is silver, while roof and spires are gold. Knob of one spire appears to have never been present, as it is quite smooth across top. This building is actually two pieces held together by a nail like piece which fits through hole in one side, through the center and out the other side. When turned, it is held closed. Portions of un-painted interior show smooth cast iron, which tells it is old. Bank measures 2 inches X 2 inches X 4 1/2 inches. This is a very nice old Victorian bank from circa 1900 - 1920s. Great addition to any vintage castiron or bank collection.Inv # 47100
Condition: Used
Manufacturer: Unknown
Royal Doulton Classic Disney Pooh Bear Book Money Bank
White Bone China Disneyana Child's Coin Bank.Made in Indonesia.Has Plastic Plug. Measures 4 1/8 X 3 3/4 X 2 1/2 inches.Gently used. No chips, cracks. There is some very light crazing on top, and some possible light rubs along the top edge. It would make a great Nursery display piece.
Condition: Used
Country of Origin: ID
Manufacturer: Royal Douton
Bakelite Clock Money Coin Bank Pig Piggy Vintage Toy
My Own Bank. Marked: An Ardee Product Made in U.S.A.Plastic alarm clock with numbers, marks for each minute, two hands, and a smaller clock for setting the alarm time. Lettering, numbers, and hands are all indented in the plastic and painted white. Stands on two raised feet and has the dinging alarm bell on top.The back 3 knobs for setting the time, alarm, and winding, plus the little lever for setting sound level. None work, but looks so authentic for a toy! Also has a coin slot, turn stopper for removal of coins. It is made of early plastic called bakelite (gives off a odor similar to burnt matches, when rubbed). The original brick red plastic has faded to a Caramel or Butterscotch color now.Measures 4 inches high X 3 1/8 X 1 3/4 inches.No breaks, Does have a 5/8 inch long hairline crack on the dome top, and some minor surface scratches. Excellent condition for probable 1930s childs toy.NOTE: This product is a collectible item not intended for use by children under age 12.
Condition: used
Manufacturer: Ardee
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Talk about taking your country back.
Young people are in their third week of operation "Occupy Wall Street." They're protesting the rich getting richer and the poor getting punk'd.
The white collar criminals on Wall Street aren't the only targets of the protesters —- the big corporation greed mongers are also a big part of the demonstrations.
Not surprisingly, it took a while for cable news networks to start providing coverage of the protests. Not surprisingly because cable news networks are big corporations. Maybe that's why they're still asking what it is the protesters are protesting. They want to know their goal, so they can pigeon-hole them.
Try social injustice —- a topic that people in positions of authority now believe died with the 1960s.
"Oh, ya, social injustice. That was mentioned in a song from that hippie musical 'Hair,' wasn't it?"
It won't be long, if it hasn't happened yet, before Fox News fascists start discrediting the young people and start blaming the Marxist in the White House for igniting anti-American sentiment by making class warfare a major part of trying to sell his jobs bill, and his re-election campaign.
The socialist president is now a Marxist, according to Fox News-controlled Republican lawmakers.
One could imagine Princess Photo-0p Palin before she's edited saying that Groucho was always her favorite Marxist.
Some 700 protesters were arrested over the weekend. The protests are being joined in eight major cities this week, including Boston, Chicago and L.A. Of course in L.A., the protest site will need to be near a Starbucks, so the protesters can have easy access to their lattes.
Imagine what the fat cat CEOs on Wall Street are saying as they look down on the protesters:
* "Hey, hippies —- get a job! Oh, that's right, there are no jobs, losers!"
* "If it's class warfare they want, let's institute a draft. Then you'll see them scamper with their tails between their legs back to mommy and daddy like the little spoiled brats that they are."
* "You won't see these little SOBs protest the big corporations that are making millions of dollars off of them buying their cell phones and iPads."
The anarchy needs a song. So sung to the tune made famous by the Drifters and later by George Benson, "On Broadway," here's "On Wall Street":
"The young are taking their country back
On Wall Street.
They say the stakes couldn't be higher.
We bailed you out when times were dire
there's no one among us you would hire
it's a crowded theater and we're yelling 'fire!'
On Wall Street.
"They say presidential candidates are bought and sold
On Wall Street.
Then they tell us taxing the rich is wrong.
They say you won't hold out for long.
Keep going at least until Bruce writes a song.
The days of telling the Great Lie are long gone
On Wall Street.
"The media wants to know what you want
On Wall Street.
But they're so easily led astray.
They report what they want to say
like civil disobedience never pays
but there's not enough pepper spray
On Wall Street."


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This is the book lover's community that has been waiting for you. Join us for fun and meet people who share the same love of books that you do. Java Junction is filled with publisher and author groups. Special Interests is filled with hobbies, fun things, cooking tips, recipes, and great things to do. Author's Coffee Corner - Stop by our Author group area and find hundreds of authors who have their Author area with us.
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Radio GTO
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Playing great music from the Sixties , Seventies and Eighties .
Good time oldies 60s 70s 80s


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First, second- and third-year students and alumni up to one year after graduation are eligible to participate in Spring On-Campus Interviews per employer requests. Online bidding takes place January 28-February 4, 2013 via UT Law Symplicity.
727 East Dean Keeton Street
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Posted by Marian on 7th Jan 2014
I first tried this product years ago when my hairdresser was using it. She switched to something else but I prefered this. I first found it at Target, but they quit carrying Lusk products. Then I checked drugstore.com and found it there. I tried to buy it from them again and they didn't have it listed. I found it at goodlookingdiscounts.com and would have bought 2 but they only had 1. I love it. I really hope Lusk has not quit manufacturing it. I LOVE it. It keeps my 81 year old hair looking healthy and beautiful.


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How to Build a Greenhouse on a Budget
This describes how to build an inexpensive greenhouse. It offers plans on how to construct a small greenhouse for under $35.
If you are wanting to build another edition of the Biosphere line, it cannot be done on a budget. However, if you want a compact greenhouse for starting plants and other garden projects, there are some inexpensive ways to produce a greenhouse. The main thing to remember if you want to build a greenhouse without taking out a second mortgage is to use items that you already have or that can be acquired cheaply.
Decide on what size greenhouse you need.
Many gardeners who just want a place to give their tomatoes a boost or start some other types of plants do not need a huge space. By using shelves, you can turn even a small greenhouse into a much large growing area. A greenhouse that measures about 3 feet by 4 feet and is 3 feet high can give enough space for many plants. This size greenhouse can be constructed in a couple of hours for under $35. If you have some of the materials already, it can drive the price down a lot.
Sketch out how you want the frame work of the greenhouse to be made.
Keep this part as simple as possible. If you make the greenhouse box shaped, you do not even have to worry about getting the peak of the roof to come out right. For box shaped units, you should make one of the long sides slightly taller than the other. This will give you a sloped roof that will shed water better when it rains. If the water pools up, it can tear through the plastic covering.
Use light weight lumber for the frame.
If you purchase 1×2 pine lumber, it will be extremely cheap. To build a greenhouse of the previously listed dimensions, you will need 9 boards that are 8 feet long. These cost about $2 each. Larger lumber can be used, but it will make your greenhouse bulky and heavy. Use drywall screws to assemble the pieces to make the project go faster.
Buy a clear plastic drop cloth for the fabric to cover the greenhouse.
Using a heavy weight plastic drop cloth like you would use for painting will give enough strength to the exterior of your green house. These cost about $5 to $10 at most discount stores. You will use tacks or staple to attach the plastic to the frame. Do not cover the floor. It will just stay open.
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Ek Main Aur Ekk Tu
Release Date
10 Feb 2012
Ek Main Aur Ekk Tu movie a witty, feel-good, slice-of-life comedy. The movie starts with the story of Rahul Kapoor (Imran Khan) who is on his way to become a ...
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love thhis movie
at least show justice after blindly copying
dherai bakwass lagyo mali ta tunga ta pungo ko . i promise i willn't watch any of the movies played jointly by these two actor n actress
ek dum dabba movie hai maha bakwas kareena kapoor ki acting ko chodkar kuch bhi dekhne laayak nahi hai is movie me
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InsideOut Poetry Group @ HYPE
Improve your written word and performance skills with this talented Detroit poetry organization. All skill levels welcome to attend.
Age:Teens, ages 13-18. HYPE card required
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text: facebook [ Our Gang Players Present Legally Blonde [AUDIO] By Shawn Michaels October 3, 2012 The Our Gang Players Community Theatre Group Presents "Legally Blonde" Read More|Comment Category: Articles, Audio, Community, Hometown Happenings, Lifestyle, Ocean County Breakfast Show, Pretty in Pink Tags: Breast cancer awareness, Health, Legally Blonde, Our Gang Players, Pink, radio, shawn michaels, Theatre, wobm Send to a friend! Share on Facebook Share on Twitter Pin it! Reddit This! Share on Tumblr!


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Towels & Robes
You can't go to the spa every day. But you can always get a little pampering with Brookstone bath towels and bathrobes. Deliciously soft and plush, they're a modest luxury even tough guys will love. Be nice to your skin and check them out.
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Uptown Bath Towel


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This was on one of my favourite records of last year. Just found a youtube transfer of it. And it's the time of day for relaxing and dreaming for five minutes. Therefore, from INCAPULCO, I give you the tropical hypnagogia of High Wolf's "Bizarre Moonlight."
4 thoughts on "Bizarre Moonlight"
While not the same kind of music, I have four tracks available for free off an ambient album I'm working on:
They contain no DRM and you are free to distribute them however you wish. I highly recommend you use headphones, as they were all mixed for headphone users. Enjoy!
PS: I did a review of Scars a couple of weeks ago, in case you are interested in reading it: http://livingwithanerd.com/scars-mini-review/
I had a hard time listening to this at first. I couldn't find the beat. It seems like this is in 3/4 time maybe?
What nice nose to eat to, cheers Warren.
Pingback: Warren Ellis : Not Quiet
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1796 $2 1/2 No Stars MS63 NGC. BD-2, R.4....
2012 August 2-5 US Coins Signature Auction- Philadelphia #1173
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|Printable auction results for all items in the 2012 August 2-5 US Coins Signature Auction- Philadelphia.
1796 No Stars Quarter Eagle, MS631796 $2 1/2 No Stars MS63 NGC. BD-2, R.4. The 1796 No Stars quarter eagle shares a reputation with its later sibling, the 1808 quarter eagle, as among the most significant and rarest gold type coins of any denomination. Both are single-year types, with low mintages (an estimated 963 pieces for the 1796 No Stars, and 2,710 coins for the 1808).
BD-2, Bright Yellow-Gold Example
Among the Finest Known of This One-Year Type
BD-2, Bright Yellow-Gold Example
Among the Finest Known of This One-Year Type
The 1796 No Stars quarter eagles are now known to appear in two varieties, with the Normal Arrows (BD-2) and Extended Arrows (BD-1) reverses sharing a single obverse. Although the BD-1 pairing is considerably rarer in terms of numbers known, the incredible demand for the 1796 No Stars overall, as a first-year type, lessens the price differences between the two varieties. An appearance of either variant at auction is bound to be the occasion for intense bidding on the part of multiple collectors. (This is a similar phenomenon to the 1796 Draped Bust quarter dollars, also one-year types known in two varieties.)
The companion piece to the 1796 No Stars is the 1796 With Stars quarter eagle, which is also technically a one-year type with an even lower mintage (put at 432 coins, based on delivery warrants). Even though the 1796 With Stars is the only obverse in the series with 16 stars, it is an underrated variety due to its association with the other With Stars quarter eagles (showing 13 or 14 stars), which extend through the 1807 issue.
The celebrated B. Max Mehl 1941 auction of the William Forester Dunham Collection provides an interesting comparison between the 1796 No Stars and With Stars quarter eagles during an earlier era. Lot 1904 was a 1796 No Stars, "just a shade from uncirculated, with considerable semi-proof surface, especially on reverse. The upper right part of reverse is not as bold as the rest of the coin. A beautiful specimen of this rare and valuable coin. Listed at $150.00 in very fine condition." The lot nonetheless brought only $81.50.
Lot 1905 in the Dunham Collection was a 1796 With Stars quarter eagle, which Mehl cataloged as "extremely fine, with considerable semi-proof surface. Extremely rare. Listed at $250.00." The lot brought $185.
Two Gem examples of the 1796 No Stars and With Stars from our FUN 2008 Signature provide much more recent comparisons. The finest certified 1796 No Stars MS65 PCGS (Heritage, 1/2008), lot 3058, a coin pedigreed to the legendary collection of Lorin G. Parmelee, realized $1,725,000. The 1796 With Stars MS65 NGC, also the only certified Gem, brought $1,006,250 in the same auction. Clearly, the marketplace today values the 1796 No Stars more highly, given the increased emphasis and popularity of type collecting.
This high-grade example has uniformly bright yellow-gold surfaces. The centers on each side show the usual softness, and the reverse displays light, diagonal die adjustment marks. Both obverse and reverse display the small, scattered abrasions one would expect from an MS63. The only marks that might be used for pedigree purposes is a curved abrasion in the upper-right obverse field, and a shallow scrape on the reverse between STATES and OF.(Registry values: P10) (NGC ID# 25F2, PCGS# 7645)
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text:
The concept behind Thumbs and Ammo is fairly simple: Users remove guns from classic movie stills and replace them with a big thumbs up. Or, as the site explains it, "Real tough guys don't need guns, they just need a positive, can-do attitude."
Got it?
Check out this meme: "Mila Kunis and Words" (it's exactly what you think)
Sure, there's a timely gun-policy statement in there somewhere. But mostly it's just hilarious:
Thumbs up, indeed! Check out tons more over at Thumbs and Ammo's site.
Check out some of our other favorite things in pop culture this week!


text:
Monthly newsletter: Read the latest issue
Learn more about our degree programs and admission requirements
Find the information you need to conduct your research and academic studies
See KCU's beautiful campus
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KCU-COM alumni enjoy free CME in conjunction with Homecoming
Promote excellence in post-doctoral osteopathic medical education
Provide post-doctoral instruction and education in the art, science, principles and practice of osteopathic medicine, socio-cultural diversity, and to contribute to the advancement of knowledge, including osteopathic contributions to medicine through scientific research. Members of Kansas City University of Medicine and Biosciences-College of Osteopathic Medicine Educational Consortium (KCU-COMEC) have mutual goals to promote the highest possible quality in the continuum of osteopathic pre-doctoral and post-doctoral medical education, thereby enhancing both.
Board members of the KCU-COM Educational Consortium:
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1750 Independence AvenueKansas City, Mo. 64106-14531-800-234-4847 | 816-654-7000


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2006 Jeep Liberty Sport equipped with the 3.7L V6 and Automatic Transmission. Bright Silver Metallic Exterior with Gray Interior. Features include 4X4, Keyless... More
In a class by itself! Isn't it time for a Jeep?! This Wrangler may look a little tough but runs and drives good. It... More
Local Trade.This vehicle comes with a 12 month/12000 mile powertrain warranty included in the price. Where can you buy an older vehicle with warranty?... More


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Tauro V8 Spider - A Spanish Supercar
Tauro V8 Spider - A Spanish Supercar
Tauro V8 Spider - A Spanish Supercar
2010 HURST/Pontiac H.O.
Pontiac has announced that it is ringing in the new year with a fresh look for its best-selling line of G6 mid-size vehicles. Additional fuel-saving powertrain options, more aggressive exterior styling, and a sleek new instrument panel highlight the 2009.5 model G6, which will begin arriving in Pontiac dealerships in January. "The G6 has alway
GMC and Pontiac today announced pricing for two new models arriving in dealerships in early 2009, further reinforcing the channel's reputation for value combined with efficiency
The Australian-made Pontiac G8 has been shortlisted for the prestigious North American Car of the Year (COTY) award in 2009. Pontiac G8 is one of 14 semi-finalists for the esteeme
Expanding its portfolio in the rapidly growing small car segment, Pontiac announced plans to bring the sporty, five-door hatchback G3 to U.S. showrooms early next year. When it arr
After sifting through more than 18,000 possibilities, Pontiac has chosen to keep it simple, naming the recently revealed G8 sport truck the " G8 ST." Thousands of fans submitted suggestions during a "Tame the Name" promotion, which delayed a final announcement until each possibility was considered and cleared for possible trademark use. "Frankl
Four months after the Pontiac G8 went on sale in the United States, GM Holden has expanded its G8 exports to Canada, the first time that the company has undertaken a major export program to the country. On sale now through dealers nationwide, the rear wheel drive performance sedan is available as either a V6-powered G8 model or V8-equipped G8 G
From nicely equipped entry subcompacts to award-winning midsize sedans and a capable, compact SUV, General Motors offers plenty of choices for consumers who want to wring more mile
Confirming its commitment to style and performance, Pontiac introduced a show car version of an all-new, rear-wheel-drive performance sedan at the Chicago Auto Show. The 2008 Pontiac G8 will be available in dealerships early next year. "With the balance of rear-wheel drive and the availability of V-8 power, the G8 represents another step in Po


text:
Are you Gary E. Gibson?Claim your profile
Publications (237)1077.89 Total impact
Article: Abnormal Glucose Metabolism in Alzheimer's Disease: Relation to Autophagy/Mitophagy and Therapeutic Approaches[Show abstract] [Hide abstract]
ABSTRACT: Diminished glucose metabolism accompanies many neurodegenerative diseases including Alzheimer's disease. An understanding of the relation of these metabolic changes to the disease will enable development of novel therapeutic strategies. Following a metabolic challenge, cells generally conserve energy to preserve viability. This requires activation of many cellular repair/regenerative processes such as mitophagy/autophagy and fusion/fission. These responses may diminish cell function in the long term. Prolonged fission induces mitophagy/autophagy which promotes repair but if prolonged progresses to mitochondrial degradation. Abnormal glucose metabolism alters protein signaling including the release of proteins from the mitochondria or migration of proteins from the cytosol to the mitochondria or nucleus. This overview provides an insight into the different mechanisms of autophagy/mitophagy and mitochondrial dynamics in response to the diminished metabolism that occurs with diseases, especially neurodegenerative diseases such as Alzheimer's disease. The review discusses multiple aspects of mitochondrial responses including different signaling proteins and pathways of mitophagy and mitochondrial biogenesis. Improving cellular bioenergetics and mitochondrial dynamics will alter protein signaling and improve cellular/mitochondrial repair and regeneration. An understanding of these changes will suggest new therapeutic strategies.Neurochemical Research 06/2015; DOI:10.1007/s11064-015-1631-0 · 2.55 Impact Factor
Article: Alpha-ketoglutarate dehydrogenase complex-dependent succinylation of proteins in neurons and neuronal cell lines[Show abstract] [Hide abstract]
ABSTRACT: Reversible post-translation modifications of proteins are common in all cells and appear to regulate many processes. Nevertheless, the enzyme(s) responsible for the alterations and the significance of the modification are largely unknown. Succinylation of proteins occurs and causes large changes in the structure of proteins; however, the source of the succinyl groups, the targets, and the consequences of these modifications on other proteins are unknown. These studies focused on succinylation of mitochondrial proteins. The results demonstrate that the α-ketoglutarate dehydrogenase complex (KGDHC) can serve as a trans-succinylase that mediates succinylation in an α-ketoglutarate-dependent manner. Inhibition of KGDHC reduced succinylation of both cytosolic and mitochondrial proteins in cultured neurons and in a neuronal cell line. Purified KGDHC can succinylate multiple proteins including other enzymes of the tricarboxylic acid (TCA) cycle leading to modification of their activity. Inhibition of KGDHC also modifies acetylation by modifying the pyruvate dehydrogenase complex. The much greater effectiveness of KGDHC than succinyl CoA suggests that the catalysis due to the E2k succinyltransferase is important. Succinylation appears to be a major signaling system and it can be mediated by KGDHC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Journal of Neurochemistry 03/2015; DOI:10.1111/jnc.13096 · 4.24 Impact Factor
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ABSTRACT: Post-transcriptional regulation of mRNA by the RNA-binding protein HuR (encoded by Elavl1) is required in B cells for the germinal center reaction and for the production of class-switched antibodies in response to thymus-independent antigens. Transcriptome-wide examination of RNA isoforms and their abundance and translation in HuR-deficient B cells, together with direct measurements of HuR-RNA interactions, revealed that HuR-dependent splicing of mRNA affected hundreds of transcripts, including that encoding dihydrolipoamide S-succinyltransferase (Dlst), a subunit of the 2-oxoglutarate dehydrogenase (α-KGDH) complex. In the absence of HuR, defective mitochondrial metabolism resulted in large amounts of reactive oxygen species and B cell death. Our study shows how post-transcriptional processes control the balance of energy metabolism required for the proliferation and differentiation of B cells.Nature Immunology 02/2015; 16(4). DOI:10.1038/ni.3115 · 24.97 Impact Factor
Article: Interactions of endoplasmic reticulum and mitochondria Ca(2+) stores with capacitative calcium entry.[Show abstract] [Hide abstract]
ABSTRACT: Thiamine dependent enzymes are diminished in Alzheimer's disease (AD). Thiamine deficiency in vitro and in rodents is a useful model of this reduction. Thiamine interacts with cellular calcium stores. To directly test the relevance of the thiamine dependent changes to dynamic processes in AD, the interactions must be studied in cells from patients with AD. These studies employed fibroblasts. Mitochondrial dysfunction including reductions in thiamine dependent enzymes and abnormalities in calcium homeostasis and oxidative processes occur in fibroblasts from Alzheimer's Disease (AD) patients. Bombesin-releasable calcium stores (BRCS) from the endoplasmic reticulum (ER) are exaggerated in fibroblasts from patients with AD bearing a presenilin-1 (PS-1) mutation and in control fibroblasts treated with oxidants. ER calcium regulates calcium entry into the cell through capacitative calcium entry (CCE), which is reduced in fibroblasts and neurons from mice bearing PS-1 mutations. Under physiological conditions, mitochondria and ER play important and interactive roles in the regulation of Ca(2+) homeostasis. Thus, the interactions of mitochondria and oxidants with CCE were tested. Inhibition of ER Ca(2+)-ATPase by cyclopiazonic acid (CPA) stimulates CCE. CPA-induced CCE was diminished by inhibition of mitochondrial Ca(2+) export (-60 %) or import (-40 %). Different aspects of mitochondrial Ca(2+) coupled to CPA-induced-CCE were sensitive to select oxidants. The effects were very different when CCE was examined in the presence of InsP3, a physiological regulator of ER calcium release, and subsequent CCE. CCE under these conditions was only mildly reduced (20-25 %) by inhibition of mitochondrial Ca(2+) export, and inhibition of mitochondrial Ca(2+) uptake exaggerated CCE (+53 %). However, t-BHP reversed both abnormalities. The results suggest that in the presence of InsP3, mitochondria buffer the local Ca(2+) released from ER following rapid activation of InsP3R and serve as a negative feedback to the CCE. The results suggest that mitochondrial Ca(2+) modifies the depletion and refilling mechanism of ER Ca(2+) stores.Metabolic Brain Disease 04/2014; 29(4). DOI:10.1007/s11011-014-9541-4 · 2.40 Impact Factor
Article: The negative impact of α-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation.[Show abstract] [Hide abstract]
ABSTRACT: A decline in α-ketoglutarate dehydrogenase complex (KGDHC) activity has been associated with neurodegeneration. Provision of succinyl-CoA by KGDHC is essential for generation of matrix ATP (or GTP) by substrate-level phosphorylation catalyzed by succinyl-CoA ligase. Here, we demonstrate ATP consumption in respiration-impaired isolated and in situ neuronal somal mitochondria from transgenic mice with a deficiency of either dihydrolipoyl succinyltransferase (DLST) or dihydrolipoyl dehydrogenase (DLD) that exhibit a 20-48% decrease in KGDHC activity. Import of ATP into the mitochondrial matrix of transgenic mice was attributed to a shift in the reversal potential of the adenine nucleotide translocase toward more negative values due to diminished matrix substrate-level phosphorylation, which causes the translocase to reverse prematurely. Immunoreactivity of all three subunits of succinyl-CoA ligase and maximal enzymatic activity were unaffected in transgenic mice as compared to wild-type littermates. Therefore, decreased matrix substrate-level phosphorylation was due to diminished provision of succinyl-CoA. These results were corroborated further by the finding that mitochondria from wild-type mice respiring on substrates supporting substrate-level phosphorylation exhibited ∼30% higher ADP-ATP exchange rates compared to those obtained from DLST+/- or DLD+/- littermates. We propose that KGDHC-associated pathologies are a consequence of the inability of respiration-impaired mitochondria to rely on "in-house" mitochondrial ATP reserves.-Kiss, G., Konrad, C., Doczi, J., Starkov, A. A., Kawamata, H., Manfredi, G., Zhang, S. F., Gibson, G. E., Beal, M. F., Adam-Vizi, V., Chinopoulos, C. The negative impact of α-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation.The FASEB Journal 03/2013; 27(6). DOI:10.1096/fj.12-220202 · 5.48 Impact Factor
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ABSTRACT: Reduced glucose metabolism is an invariant feature of Alzheimer's Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression. This article is part of a Special Issue entitled 'Mitochondrial function'.Molecular and Cellular Neuroscience 09/2012; 55. DOI:10.1016/j.mcn.2012.09.001 · 3.73 Impact Factor
Article: Inactivation of a key mitochondrial protein may lead to reduced brain glucose utilization in Alzheimer's diseaseAlzheimer's and Dementia 07/2012; 8(4):P304. DOI:10.1016/j.jalz.2012.05.831 · 17.47 Impact Factor
Article: Deficits in the mitochondrial enzyme α-ketoglutarate dehydrogenase lead to Alzheimer's disease-like calcium dysregulation.[Show abstract] [Hide abstract]
ABSTRACT: Understanding the molecular sequence of events that culminate in multiple abnormalities in brains from patients that died with Alzheimer's disease (AD) will help to reveal the mechanisms of the disease and identify upstream events as therapeutic targets. The activity of the mitochondrial α-ketoglutarate dehydrogenase complex (KGDHC) in homogenates from autopsy brain declines with AD. Experimental reductions in KGDHC in mouse models of AD promote plaque and tangle formation, the hallmark pathologies of AD. We hypothesize that deficits in KGDHC also lead to the abnormalities in endoplasmic reticulum (ER) calcium stores and cytosolic calcium following K(+) depolarization that occurs in cells from AD patients and transgenic models of AD. The activity of the mitochondrial enzyme KGDHC was diminished acutely (minutes), long-term (days), or chronically (weeks). Acute inhibition of KGDHC produced effects on calcium opposite to those in AD, while the chronic or long-term inhibition of KGDHC mimicked the AD-related changes in calcium. Divergent changes in proteins released from the mitochondria that affect endoplasmic reticulum calcium channels may underlie the selective cellular consequences of acute versus longer term inhibition of KGDHC. The results suggest that the mitochondrial abnormalities in AD can be upstream of those in calcium.Neurobiology of aging 12/2011; 33(6):1121.e13-24. DOI:10.1016/j.neurobiolaging.2011.11.003 · 4.85 Impact Factor
Article: Brain [U-13C]glucose metabolism in mice with decreased α-ketoglutarate dehydrogenase complex activity[Show abstract] [Hide abstract]
ABSTRACT: The activity of the α-ketoglutarate dehydrogenase complex (KGDHC), a mitochondrial enzyme complex that mediates the oxidative decarboxylation of α-ketoglutarate in the TCA cycle, is reduced in Alzheimer's disease. We investigated the metabolic effects of a partial KGDHC activity reduction on brain glucose metabolism using mice with disrupted expression of dihydrolipoyl succinyltransferase (DLST; gene encoding the E2k subunit of KGDHC). Brain tissue extracts from cortex and cerebellum of 6-week-old heterozygote DLST knockout mice (DLST+/-) and corresponding wild-type mice injected with [U-(13) C]glucose and decapitated 15 min later were analyzed. An increase in the concentration of glucose in cortex suggested a decrease in the cortical utilization of glucose in DLST+/- mice. Furthermore, the concentration and (13) C labelling of aspartate in cortex were reduced in DLST+/- mice. This decline was likely caused by a decrease in the pool of oxaloacetate. In contrast to results from cell culture studies, no indications of altered glycolysis or GABA shunt activity were found. Glucose metabolism in the cerebellum was unaffected by the decrease in KGDHC activity. Among metabolites not related to glucose metabolism, the concentration of taurine was decreased in the cortex, and that of tyrosine was increased in the cerebellum. These results imply that diminished KGDHC activity has the potential to induce the reduction in glucose utilization that is seen in several neurodegenerative diseases.Journal of Neuroscience Research 12/2011; 89(12):1997-2007. DOI:10.1002/jnr.22606 · 2.73 Impact Factor
Article: Up-regulation of the mitochondrial malate dehydrogenase by oxidative stress is mediated by miR-743a[Show abstract] [Hide abstract]
ABSTRACT: These experiments reveal for the first time that microRNAs (miRNAs) mediate oxidant regulated expression of a mitochondrial tricarboxylic acid cycle gene (mdh2). mdh2 encoded malate dehydrogenase (MDH) is elevated by an unknown mechanism in brains of patients that died with Alzheimer's disease. Oxidative stress, an early and pervasive event in Alzheimer's disease, increased MDH activity and mRNA level of mdh2 by 19% and 22%, respectively, in a mouse hippocampal cell line (HT22). Post-transcriptional events underlie the change in mRNA because actinomycin D did not block the elevated mdh2 mRNA. Since miRNAs regulate gene expression post-transcriptionally, the expression of miR-743a, a miRNA predicted to target mdh2, was determined and showed a 52% reduction after oxidant treatment. Direct interaction of miR-743a with mdh2 was demonstrated with a luciferase based assay. Over-expression or inhibition of miR-743a led to a respective reduction or increase in endogenous mRNA and MDH activity. The results demonstrate that miR-743a negatively regulates mdh2 at post-transcriptional level by directly targeting the mdh2 3'UTR. The findings are consistent with the suggestion that oxidative stress can elevate the activity of MDH through miR-743a, and provide new insights into possible roles of miRNA in oxidative stress and neurodegeneration.Journal of Neurochemistry 05/2011; 118(3):440-8. DOI:10.1111/j.1471-4159.2011.07333.x · 4.24 Impact Factor
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ABSTRACT: Reduced brain metabolism is an invariant feature of Alzheimer Disease (AD) that is highly correlated to the decline in brain functions. Decreased activities of key tricarboxylic acid cycle (TCA) cycle enzymes may underlie this abnormality and are highly correlated to the clinical state of the patient. The activity of the α-ketoglutarate dehydrogenase complex (KGDHC), an arguably rate-limiting enzyme of the TCA cycle, declines with AD, but the mechanism of inactivation and whether it can be reversed remains unknown. KGDHC consists of multiple copies of three subunits. KGDHC is sensitive to oxidative stress, which is pervasive in AD brain. The present studies tested the mechanism for the peroxynitrite-induced inactivation and subsequent reactivation of purified and cellular KGDHC. Peroxynitrite inhibited purified KGDHC activity in a dose-dependent manner and reduced subunit immunoreactivity and increased nitrotyrosine immunoreactivity. Nano-LC-MS/MS showed that the inactivation was related to nitration of specific tyrosine residues in the three subunits. GSH diminished the nitrotyrosine immunoreactivity of peroxynitrite-treated KGDHC, restored the activity and the immunoreactivity for KGDHC. Nano-LC-MS/MS showed this was related to de-nitration of specific tyrosine residues, suggesting KGDHC may have a denitrase activity. Treatment of N2a cells with peroxynitrite for 5 min followed by recovery of cells for 24 h reduced KGDHC activity and increased nitrotyrosine immunoreactivity. Increasing cellular GSH in peroxynitrite-treated cells rescued KGDHC activity to the control level. The results suggest that restoring KGDHC activity is possible and may be a useful therapeutic approach in neurodegenerative diseases.Journal of Biological Chemistry 05/2011; 286(20):17640-17648. · 4.60 Impact Factor
Article: Abnormalities in the tricarboxylic acid (TCA) cycle in the brains of schizophrenia patients[Show abstract] [Hide abstract]
ABSTRACT: Images of brain metabolism and measurements of activities of components of the electron transport chain support earlier studies that suggest that brain glucose oxidation is inherently abnormal in a significant proportion of persons with schizophrenia. Therefore, we measured the activities of enzymes of the tricarboxylic (TCA) cycle in dorsolateral-prefrontal-cortex from schizophrenia patients (N=13) and non-psychiatric disease controls (N=13): the pyruvate dehydrogenase complex (PDHC), citrate synthase (CS), aconitase, isocitrate dehydrogenase (ICDH), the alpha-ketoglutarate dehydrogenase complex (KGDHC), succinate thiokinase (STH), succinate dehydrogenase (SDH), fumarase and malate dehydrogenase (MDH). Activities of aconitase (18.4%, p<0.05), KGDHC (26%) and STH (28.2%, p<0.05), enzymes in the first half of the TCA cycle, were lower, but SDH (18.3%, p<0.05) and MDH (34%, p<0.005), enzymes in the second half, were higher than controls. PDHC, CS, ICDH and fumarase activities were unchanged. There were no significant correlations between enzymes of TCA cycle and cognitive function, age or choline acetyl transferase activity, except for aconitase activity which decreased slightly with age (r=0.55, p=003). The increased activities of dehydrogenases in the second half of the TCA cycle may reflect a compensatory response to reduced activities of enzymes in the first half. Such alterations in the components of TCA cycle are adequate to alter the rate of brain metabolism. These results are consistent with the imaging studies of hypometabolism in schizophrenia. They suggest that deficiencies in mitochondrial enzymes can be associated with mental disease that takes the form of schizophrenia.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 03/2011; 21(3):254-60. DOI:10.1016/j.euroneuro.2010.10.007 · 5.40 Impact Factor
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ABSTRACT: Reduced brain metabolism is an invariant feature of Alzheimer Disease (AD) that is highly correlated to the decline in brain functions. Decreased activities of key tricarboxylic acid cycle (TCA) cycle enzymes may underlie this abnormality and are highly correlated to the clinical state of the patient. The activity of the α-ketoglutarate dehydrogenase complex (KGDHC), an arguably rate-limiting enzyme of the TCA cycle, declines with AD, but the mechanism of inactivation and whether it can be reversed remains unknown. KGDHC consists of multiple copies of three subunits. KGDHC is sensitive to oxidative stress, which is pervasive in AD brain. The present studies tested the mechanism for the peroxynitrite-induced inactivation and subsequent reactivation of purified and cellular KGDHC. Peroxynitrite inhibited purified KGDHC activity in a dose-dependent manner and reduced subunit immunoreactivity and increased nitrotyrosine immunoreactivity. Nano-LC-MS/MS showed that the inactivation was related to nitration of specific tyrosine residues in the three subunits. GSH diminished the nitrotyrosine immunoreactivity of peroxynitrite-treated KGDHC, restored the activity and the immunoreactivity for KGDHC. Nano-LC-MS/MS showed this was related to de-nitration of specific tyrosine residues, suggesting KGDHC may have a denitrase activity. Treatment of N2a cells with peroxynitrite for 5 min followed by recovery of cells for 24 h reduced KGDHC activity and increased nitrotyrosine immunoreactivity. Increasing cellular GSH in peroxynitrite-treated cells rescued KGDHC activity to the control level. The results suggest that restoring KGDHC activity is possible and may be a useful therapeutic approach in neurodegenerative diseases.Journal of Biological Chemistry 03/2011; 286(20):17640-8. DOI:10.1074/jbc.M110.203018 · 4.60 Impact Factor
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ABSTRACT: Diminished thiamine (vitamin B1) dependent processes and oxidative stress accompany Alzheimer's disease (AD). Thiamine deficiency in animals leads to oxidative stress. These observations suggest that thiamin may act as an antioxidant. The current experiments first tested directly whether thiamin could act as an antioxidant, and then examined the physiological relevance of the antioxidant properties on oxidant sensitive, calcium dependent processes that are altered in AD. The first group of experiments examined whether thiamin could diminish reactive oxygen species (ROS) or reactive nitrogen species (RNS) produced by two very divergent paradigms. Dose response curves determined the concentrations of t-butyl-hydroperoxide (t-BHP) (ROS production) or 3-morpholinosydnonimine ((SIN-1) (RNS production) to induce oxidative stress within cells. Concentrations of thiamine that reduced the RNS in cells did not diminish the ROS. The second group of experiments tested whether thiamine alters oxidant sensitive aspects of calcium regulation including endoplasmic reticulum (ER) calcium stores and capacitative calcium entry (CCE). Thiamin diminished ER calcium considerably, but did not alter CCE. Thiamine did not alter the actions of ROS on ER calcium or CCE. On the other hand, thiamine diminished the effect of RNS on CCE. These data are consistent with thiamine diminishing the actions of the RNS, but not ROS, on physiological targets. Thus, both experimental approaches suggest that thiamine selectively alters RNS. Additional experiments are required to determine whether diminished thiamine availability promotes oxidative stress in AD or whether the oxidative stress in AD brain diminishes thiamine availability to thiamine dependent processes.Neurochemical Research 12/2010; 35(12):2107-16. DOI:10.1007/s11064-010-0242-z · 2.55 Impact Factor
- Alzheimer's and Dementia 07/2010; 6(4). DOI:10.1016/j.jalz.2010.05.665 · 17.47 Impact Factor
- Alzheimer's and Dementia 07/2010; 6(4). DOI:10.1016/j.jalz.2010.05.1307 · 17.47 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) is defined by senile plaques made of amyloid-beta peptide (Abeta), neurofibrillary tangles made of hyperphosphorylated tau proteins, and memory deficits. Thus, the events initiating the cascade leading to these end points may be more effective therapeutic targets than treating each facet individually. In the small percentage of cases of AD that are genetic (or animal models that reflect this form of AD), the factor initiating AD is clear (e.g., genetic mutations lead to high Abeta1-42 or hyperphosphorylated tau proteins). In the vast majority of AD cases, the cause is unknown. Substantial evidence now suggests that abnormalities in glucose metabolism/mitochondrial function/oxidative stress (GMO) are an invariant feature of AD and occur at an early stage of the disease process in both genetic and non-genetic forms of AD. Indeed, decreases in brain glucose utilization are diagnostic for AD. Changes in calcium homeostasis also precede clinical manifestations of AD. Abnormal GMO can lead to plaques, tangles, and the calcium abnormalities that accompany AD. Abnormalities in GMO diminish the ability of the brain to adapt. Therapies targeting mitochondria may ameliorate abnormalities in plaques, tangles, calcium homeostasis, and cognition that comprise AD.Journal of Alzheimer's disease: JAD 01/2010; 20 Suppl 2:S591-607. DOI:10.3233/JAD-2010-100336 · 3.61 Impact Factor
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ABSTRACT: Presenilin-1 (PS1) and -2 (PS2), which when mutated cause familial Alzheimer disease, have been localized to numerous compartments of the cell, including the endoplasmic reticulum, Golgi, nuclear envelope, endosomes, lysosomes, the plasma membrane, and mitochondria. Using three complementary approaches, subcellular fractionation, gamma-secretase activity assays, and immunocytochemistry, we show that presenilins are highly enriched in a subcompartment of the endoplasmic reticulum that is associated with mitochondria and that forms a physical bridge between the two organelles, called endoplasmic reticulum-mitochondria-associated membranes. A localization of PS1 and PS2 in mitochondria-associated membranes may help reconcile the disparate hypotheses regarding the pathogenesis of Alzheimer disease and may explain many seemingly unrelated features of this devastating neurodegenerative disorder.American Journal Of Pathology 11/2009; 175(5):1810-6. DOI:10.2353/ajpath.2009.090219 · 4.60 Impact Factor
Article: Mitochondrial dihydrolipoyl succinyltransferase deficiency accelerates amyloid pathology and memory deficit in a transgenic mouse model of amyloid deposition[Show abstract] [Hide abstract]
ABSTRACT: Mitochondrial dysfunction and oxidative stress are involved in Alzheimer disease (AD) pathogenesis. In human AD brains, the activity of the α-ketoglutarate dehydrogenase enzyme complex (α-KGDHC) is reduced. KGDHC is mostly involved in NADH production. It can also participate in oxidative stress and reactive oxygen species (ROS) production. The mitochondrial dihydrolipoyl succinyltransferase enzyme (DLST) is a key subunit specific to the α-KGDHC. In cultured cells, reduction of DLST increased H2O2-induced ROS generation and cell death. Thus, we asked whether partial genetic deletion of DLST could accelerate the onset of AD pathogenesis, using a transgenic mouse model of amyloid deposition crossed with DLST+/− mice. Tg19959 mice, which carry the human amyloid precursor protein with two mutations, develop amyloid deposits and progressive behavioral abnormalities. We compared Tg19959 mice to Tg19959-DLST+/− littermates at 2–3 months of age and studied the effects of DLST deficiency on amyloid deposition, spatial learning and memory, and oxidative stress. We found that α-KGDHC activity was reduced in DLST+/− mice. We also found that DLST deficiency increased amyloid plaque burden, Aβ oligomers, and nitrotyrosine levels and accelerated the occurrence of spatial learning and memory deficits in female Tg19959 mice. Our data suggest that α-KGDHC may be involved in AD pathogenesis through increased mitochondrial oxidative stress.Free Radical Biology and Medicine 10/2009; DOI:10.1016/j.freeradbiomed.2009.07.008 · 5.71 Impact Factor
Article: Cause and consequence: Mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases[Show abstract] [Hide abstract]
ABSTRACT: Age-related neurodegenerative diseases are associated with mild impairment of oxidative metabolism and accumulation of abnormal proteins. Within the cell, the mitochondria appears to be a dominant site for initiation and propagation of disease processes. Shifts in metabolism in response to mild metabolic perturbations may decrease the threshold for irreversible injury in response to ordinarily sublethal metabolic insults. Mild impairment of metabolism accrue from and lead to increased reactive oxygen species (ROS). Increased ROS change cell signaling via post-transcriptional and transcriptional changes. The cause and consequences of mild impairment of mitochondrial metabolism is one focus of this review. Many experiments in tissues from humans support the notion that oxidative modification of the alpha-ketoglutarate dehydrogenase complex (KGDHC) compromises neuronal energy metabolism and enhances ROS production in Alzheimer's Disease (AD). These data suggest that cognitive decline in AD derives from the selective tricarboxylic acid (TCA) cycle abnormalities. By contrast in Huntington's Disease (HD), a movement disorder with cognitive features distinct form AD, complex II+III abnormalities may dominate. These distinct mitochondrial abnormalities culminate in oxidative stress, energy dysfunction, and aberrant homeostasis of cytosolic calcium. Cytosolic calcium, elevations even only transiently, leads to hyperactivity of a number of enzymes. One calcium-activated enzyme with demonstrated pathophysiological import in HD and AD is transglutaminase (TGase). TGase is a crosslinking enzymes that can modulate transcription, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TGase can silence expression of genes involved in compensating for metabolic stress. Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic approaches in age-associated neurodegenerative diseases.Biochimica et Biophysica Acta 09/2009; 1802(1):122-34. DOI:10.1016/j.bbadis.2009.08.010 · 4.66 Impact Factor
Top Journals
Weill Cornell Medical College
New York, New York, United States
- Department of Neurology and Neuroscience
Cornell University
Итак, New York, United States
- Department of Neurology and Neuroscience
Burke Medical Research Institute New YorkNew York City, New York, United States
Salk Instituteلا هویا, California, United States
White Plains HospitalWhite Plains, New York, United States
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical CenterTorrance, California, United States
New York Presbyterian Hospital
New York City, New York, United States
- Department of Neurology and Neuroscience
University of Western AustraliaPerth City, Western Australia, Australia
Harvard Medical SchoolBoston, Massachusetts, United States
National Institute of Mental Health (NIMH)Maryland, United States
CUNY Graduate CenterNew York City, New York, United States
Johns Hopkins UniversityBaltimore, Maryland, United States
University of California, Los Angeles
Los Ángeles, California, United States
- Center for Culture and Health


text:
"This tool is extremely valuable as CBP seeks to identify and detect changing smuggling patterns," she said.
Seizing on documentary filmmaking as a tool to build impact is "not just the responsibility of the mainstream," she says.
What is it about music that makes it a tool for activism and change?
Old English tol "instrument, implement," from Proto-Germanic *tolan (cf. Old Norse tol), from a verb stem represented by Old English tawian "prepare." The ending is the instrumental suffix -l (e.g. shovel). Figurative sense of "person used by another for his own ends" is recorded from 1660s. Slang meaning "penis" first recorded 1550s.
"to drive a vehicle," 1812, probably from tool (n.). The meaning "to work or shape with a tool" is recorded from 1815; that of "equip (a factory) with machine tools" is from 1927. Related: Tooled; tooling.
adjective phrase
Very delicate or explosive; very controversial: The March was rejected by PBS as ''not suitable to their programming'' (nobody actually said it was too hot to handle)
[1940s+; found in baseball by 1932, designating a very hard-hit ball]
2. A Unix application program with a simple, "transparent" (typically text-stream) interface designed specifically to be used in programmed combination with other tools (see filter, plumbing).
[Jargon File]


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Two Campbellsville residents have been charged with drug crimes in indictments recently unsealed by a Taylor Circuit Court judge.
A grand jury may seal an indictment if there is a possibility that the accused will try to evade police.
Glenn Burchett, 60, of 736 Buckner St. was charged with second- and third-degree selling a controlled substance.
Bond was set at $15,000 cash. If convicted, Burchett could be sentenced to as much as five years in prison.
The Jacob Hiestand House Foundation spent last week preparing for the past.
Workers dug holes and poured concrete, laying the foundation for a log cabin that will be placed in that location next month. The cabin, which will be rebuilt by Springfield-based American Antique Cabin Co., will represent an 1820s-era plantation slave quarters.
The cabin will be a dogtrot-style structure. Popular in the south, a dogtrot is essentially two cabins joined by a shared roof.
Campbellsville has gained 25 jobs and a trip to Mars.
Gov. Steve Beshear's office last week announced that Fluortubing USA will open a manufacturing facility in Campbellsville. The announcement coincided with news that the company will manufacture tubes to be used on NASA's Mars probe to be launched in 2010.
Fluortubing USA, a manufacturer of Polytetrafluoraethylene (Teflon(r)) plastic tubing, will move part of its manufacturing operations to Campbellsville from its subsidiary company - Fluortubing B.V. of Utrecht, The Netherlands.
A local woman is among the several committee appointments made by Gov. Steve Beshear last week.
LaWanda K. Hazard was appointed to serve on the Kentucky African-American Heritage Commission. Hazard is a social worker for the Jefferson County School District.
She represents the public at large. The appointment replaces Earl Junior Jackson, whose term has expired. Hazard will serve for a term expiring Feb. 1, 2012.
A Campbellsville man has violated the terms of his probation and will spend seven years in prison on theft and other charges.
Kyle Alan Mardis, 28, of 101 Grandview Drive appeared before Taylor Circuit Court Judge Doughlas M. George on Tuesday, Aug. 5.
In July 2007, Mardis pleaded guilty to theft by unlawful taking more than $300. A charge of being a first-degree persistent felony offender was dismissed.
Two months later, Mardis was sentenced to four years' probation and ordered to pay $1,325 in restitution.
A Russell Springs man has been arrested and charged with theft by unlawful taking more than $300 after he was seen stealing construction materials.
According to a Taylor County Sheriff's report, deputies received a complaint on Monday, July 28 that three people were loading I-beams onto a trailer at a lot on Heather Drive. The three left before deputies arrived, however.
After an investigation, sheriff's deputies discovered that I-beams had been also been loaded on Thursday, July 24.
Citing a battle with cancer, Democrat Doug Mullins has dropped out of the 51st District State Representative's race.
Mullins, who currently serves on the Campbellsville City Council, ran unopposed in the May primary. He would have faced Republican John "Bam" Carney in the race to fill the position that incumbent Russ Mobley, R-Campbellsville, will vacate when his term ends this year.
Mobley will not seek re-election. In a press release issued earlier this year, Mobley cited health issues as his reason for stepping down after eight years in office.
First week school enrollment numbers have provided few surprises for administrators this year.
Attendance is up at both districts. Taylor County Schools' attendance rose 69 students from last year to 2,688. Campbellsville Independent gained 35 students for a total of 1,093.
At Taylor County, the only school to increase individual enrollment so far is the elementary, which added 80 students, according to Angela Wheat, Taylor County director of pupil personnel. After the first week of classes, the school has 1,190 students.
A Campbellsville man has been arrested and charged with selling cocaine and other charges after a traffic stop.
Christopher R. Tungate, 26, of 807 N. Hoskins Ave. was arrested at 2:44 a.m. Sunday, Aug. 3.
According to Tungate's arrest citation, he was stopped by Taylor County Constable Jamie Gaddis for failing to signal and having an expired license plate.
After Campbellsville Police Officer Brian Morgan arrived at the scene, he observed that Tungate had glassy eyes and smelled of alcohol.
Seeking to stem the tide of home foreclosures, Kentucky Gov. Steve Beshear this week announced at a press conference in Owensboro the creation of the Kentucky Homeownership Protection Center.
The Protection Center, created by the passage of HB 552 during the 2008 General Assembly, will help Kentuckians in financial trouble become more proactive in keeping their homes.
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