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Altmetrics and societal impact analysis
The shift towards open access, the rise of web based and networked research and acknowledgment of the importance of societal impact of research have in recent years led to the development of alternative metrics. By capturing mentions in social media, blogs, news, policy documents, as well as the number of downloads, online readers and bookmarks, alternative metrics look beyond journal citations to give us more speedy and multifaceted feedback and a glimpse into how these impact broader audiences.
When used together with bibliometrics, altmetrics can provide a more holistic and broad picture of research and societal impact. This is not to say that it should be used without care – metrics in general, and in particular alternative metrics, should be transparent and reproducible in order to be used in evaluations. The University of Groningen Research Impact Services also adheres to these principles – if in doubt, please contact us.
|Last modified:||20 November 2018 2.10 p.m.|

domain: sociology


text:
Flynn Pleads Guilty to Lying to the FBI
Continue Reading Below
Mike Flynn, President Trump's former national security adviser, pleaded guilty Friday to lying to the FBI about communications with the Russian ambassador late last year, becoming the senior-most Trump aide to face criminal charges in the sprawling special counsel probe.
U.S. Stocks End Lower but Recover From Sharp Drop
The Dow Jones Industrial Average fell 350 points before sharply paring declines Friday in its most turbulent session of the year.
GOP Says It Has Enough Votes to Pass Senate Tax Bill
Senate Republicans, pushing to notch a major legislative victory, locked in enough votes to pass a sweeping tax overhaul later Friday after winning over wavering GOP senators in a flurry of last-minute dealmaking.
Continue Reading Below
CFPB Interim Chief Mulvaney Taps Hensarling Aide for Senior Role
The Consumer Financial Protection Bureau's new interim chief, Mick Mulvaney, tapped Republican congressional lawyer Brian Johnson to assist him as he takes charge of the agency.
Fed's Bullard Warns More Rate Increases Would Raise Risk of Recession
St. Louis Fed chief warns of a possible inversion of the flattening bond-market yield curve, which often is an indication of impending economic troubles.
Bitcoin Futures Set to Start Trading as Regulator Gives Thumbs Up
The U.S. Commodity Futures Trading Commission said it will allow two major Chicago exchanges, CME Group and Cboe Global Markets, to launch bitcoin futures.
Dudley Suggests Tax Cuts Could Lead Fed to Raise Rates
New York Fed President William Dudley said that he sees a "reasonable case" to raise short-term interest rates this month and that any new fiscal stimulus approved by lawmakers in Washington could shape the central bank's expectations for additional rate increases next year.
Bitcoin Is the World's Hottest Currency, but No One's Using It
As businesses accepting bitcoin payments find few takers, the virtual currency is a long way from its traditional counterparts.
Brazil Growth Slowed Amid Political Upheaval
Brazil's economy slowed to 0.1% growth in the third quarter amid heightened political turmoil, though increases in private consumption and investment suggested that a recovery from the country's longest recession on record is strengthening.
Oil Jumps After OPEC Output Extension
Oil prices rose after the Organization of the Petroleum Exporting Countries and other big producers agreed to continue limiting their output for an additional nine months.
(END) Dow Jones Newswires
December 01, 2017 19:15 ET (00:15 GMT)

domain: finance


power window issue
I had issues rolling down my windows on my 2000 jeep GC. I checked the boot (drivers side) and found a broken wire that had been previously repaired but did not hold. Some other wires were also broken. The main wire that goes into the connector was too short to repair and that connector that goes into the door is loose. I think I need a new connector. It is a oblong shaped connector that goes to a black regulator(?) within the door. The boot actually snaps onto that connector I need. Any ideas of what I am looking for in a part?


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Italian cinema's leading lady Sophia Loren will be bringing her Hollywood glamour to Tel Aviv’s Mann Auditorium on November 25 at 9 p.m.
As part of her one-woman show, An Evening with Sophia Loren, the 81-year-old icon will share memories of her fabled career in Hollywood, her native Italy, play clips of some of her favorite scenes from her movies, and engage the audience in a Q&A session. Bill Harris of Entertainment Tonight will moderate the Q&A session.
Loren, once a major sex symbol on a par with Marilyn Monroe and Brigitte Bardot, has frequently been voted in public polls as the most beautiful woman in the world.
Born in 1934 in Rome, Italy, Loren is a veteran of over 100 movies spanning over five decades. In 1962 she gained worldwide fame for her role in Two Women for which she won the Academy Award for Best Actress in a Leading Role and made her the first artist to win an Oscar for a foreign- language performance. Other notable performances include Yesterday, Today, and Tomorrow (1963), which won the Oscar for Best Foreign Film, Marriage, Italian Style (1964), for which she earned another Oscar nomination for Best Actress, and A Countess from Hong Kong (1967), co-starring Marlon Brando.
To purchase tickets (starting from NIS 300) visit www.leaan.co.il or call *8780.
All rights reserved © The Jerusalem Post 1995 - 2022

domain: artistic


text:
70-liter capacity backpack for long journeys and trips, so that you can carry everything you need regardless of the amount or type of material you have to carry in order to carry out your adventures.
It has a new suspension system with two integrated structures that provides efficient load distribution and great stability. The suspension system, the position of the load straps and the shoulder straps are fully adjustable.
The belt is perfectly padded to comfortably carry heavy loads. It includes a total opening system to have access to all the equipment in a comfortable way. Several handles facilitate its transport in any way.
- Made of 79% polyamide and 21% polyester. Polyurethane reinforcements.
- Adjustable backrest.
- Padded belt with pocket.
- Detachable mushroom that can be used independently.
- Removable separation of the lower compartment.
- Fully adjustable suspension system, position of the load straps and shoulder straps.
- Full front opening.
- Pocket in the mushroom.
- Pole holder.
- Compatible with hydration system.
- Volume 60 liters + 10 of extension.
- Dimensions 80 x 33 x 29 cm.
- Approximate weight of 1985 g.

domain: design


text:
Traseul crosului Apuseni
Real length: 7 km
Altitude gain: + 440 m
Hydration Post (PH), only one: at ”Sesu Cald”, 4,7 km from the Start/Arrival
Control Post (PC): 2 (two), on Buscat peak and at the base of the skiing slope
Start/Arrival: Skiland boarding house, altitude 1390 m
Track gpx kmz
Legend: PH – Hydration Post, PC – Control Post
Until Sesu Cald (4,7km) the course follows the marathon and half marathon course. After the start, competitors run for 1 km uphill on the main road leading to Muntele Mare until La Plopis saddle, where they leave the main road, being directed forward-right by a volunteer and marked ribbons. For the next 2,2 km Buscat peak is passed by to the right side, on narrow forrest roads, passing by Izvorul Gabrienii, where thirsty runners will be able to quench their thirst. Next, after the first glade (Buhuia), the narrow road is abandonned by suddenly turning left, 200 m through the grass, without a trail (it`s a mountain running marathon!), then we take a road that climbs right on the Buscat peak 1676 m, next to the terminus point of the cable car. Here is PC 1 Buscat. Runners descend from this point, on the opposite side, on the slope, until they reach the parking lots in the Sesu Cald glade, used during winter times by tourists. Here cross runners leave the course used by marathon and half marathon runners, and turn left on the ski slope. Soon you will be able to quench you thirst at a PH. At the base of the slope, where the the cable car “starts” you will find another PC. Another 50 m follow uphill towards left, and then, the course continues on a forrest road, on a gentle descent. Towards the end, the road gently goes uphill, and touches a curve of the main road to the left. The cross course doens`t follow the road, but descends for about 100 m forward-right, meeting the marathon and half marathon course, then, it turns left towards the soon to be reached Arrival!
If you found the course easy and you enjoyed the run, you will train during the next editions of the Apuseni Marathon msg systems, and you will maybe compete in the future half marathon and marathon races! Good luck! Looking forward to meet you!

domain: geography


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Discover our amazingly on-trend two-piece swimsuits, ultra fashionable and the best way to laze in the sun! Printed or plain, choose your favourite amongst the bandeau, triangle and Brazilian styles we have selected for you. A wide range of trendy brazilian two-piece swimsuits in various forms: bandeau, triangle, balconette, scrunch, high pants, with jewellery... Original and colorful printed materials. Inspired and manufactured in Brazil.
|Brazilian bikini||Thong bikini||Bikini Tops||Bikini Bottoms|
|Push up bikini||Black Bikini||White Bikini|


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Sodexo Dining Services at Huntington University offers a variety of options to meet the culinary needs of the campus community. We provide multiple daily dining options for students, faculty, and staff as well as catering services for special events.
The Habecker Dining Commons offers daily meals, with a variety of freshly prepared food selections made with quality and care to satisfy all tastes.
Norm's Place, featuring SubConnection and Pandini's, provides additional dining options and extended hours to serve varying schedules and appetites.
The Loew-Brenn Cafe, located on the 2nd floor of Loew-Brenn Hall, offers another convenient option for busy students.

domain: food


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On World TB Day, March 16, Dr. Margaret Chan, director-general of the World Health Organization, addressed public health professionals at the Centers for Disease Control and Prevention in Atlanta at the eighth annual Jeffrey P. Koplan Global Leadership in Public Health Lecture. In introducing Chan, Koplan noted their long-term friendship, which grew from their work together in China.
While in Atlanta, Chan also visited Emory to meet with President James Wagner and Emory Global Health Institute Director Koplan. She heard presentations about global health field projects by students in public health, medicine, and theology.
Chan recalled the â€œlost decade for development,â€ the 1980s, a dismal time for public health. The 1979 energy crisis followed by a recession made for tighter public health resources and few health care improvements worldwide, she explained. Some developing countries have still not recovered.
In contrast, public health has faired better in the new millennium, when the world has benefited from financial commitments backed by substantial resources, often from innovative sources, says Chan.


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Rimbaud the Son, widely celebrated upon its publication in France, investigates the life of a writer, the writing life, and the art of life-writing. Pierre Michon in his groundbreaking work examines the storied life of the French poet Arthur Rimbaud by means of a new literary genre: a meditation on the life of a legend as witnessed by his contemporaries, those who knew him before the legends took hold. Michon introduces us to Rimbaud the son, friend, schoolboy, renegade, drunk, sexual libertine, visionary, and ultimately poet. Michon focuses no less on the creative act: What presses a person to write? To pursue excellence?
The author dramatizes the life of a genius whose sufferings are enormous while his ambitions are transcendent, whose life is lived with utter intensity and purpose but also disorder and dissolution-as if the very substance of life is its undoing. Rimbaud the Son is now masterfully translated into English, enabling a wide new audience to discover for themselves the author Publishers Weekly called "one of the best-kept secrets of modern French prose."
Pierre Michon is an author of high acclaim in France and Europe. He was winner of the Prix France Culture in 1984 for his first book, Small Lives, and of the 1996 Prix de la Ville de Paris for his body of work. He lives in France. Jody Gladding, a poet and translator, has translated over twenty books from the French. Elizabeth Deshays is a teacher, translator, and specialized horticulturalist. In 2009 Gladding and Deshays won the Florence Gould French-American Foundation Translation Prize for Pierre Michon's Small Lives.


Tool 2: a decision grid:
All of these promotions and loyalty clubs can be done inexpensively using digital media, including Web, search and mobile with a variety of tools included in the media (online video, SMS and more).
Next page- A Benchmark and conclusion
Geico is probably one of the most prolific examples. They had running, at the same time, regular campaigns:
Fifteen minutes could save you 15 percent or more, the cavemen, the eyes, the living under a rock and the hyperbolic guy (Can Geico save you 15 percent in your car insurance? followed by some outlandish example).
Capital One (Whats in your pocket?) also has several campaigns running at the same time: the Vikings, the guy with the baby who doesnt want money back and Alec Baldwin.
In both cases, not only do the different creatives not cause any noise, you might notice sales points in one campaign but not in the other (cash back, no black-out dates, etc.).
The era of simple solutions died a decade ago. Consumers have always been complex. Today, however, we have much better (and affordable) tools to understand them and a broader media environment with which to reach them with highly segmented messages.
In addition to thinking about consumers along smaller segments (e.g., by lifestyle in addition to age, gender and geography), we should also consider their state of consumption, because it is now feasible to create and deliver multiple campaigns to address these differences.


1936 BSA Y13 Motorcycle
The BSA Y13 was derived from an overhead-valve, 499cc, V-twin originally developed for military use.
However, the British War Office rejected the motorcycle model in favour of side-valve singles and so, the V-twin appeared on the civilian market in 1934 as the J34-11. In 1935, it became the J34-12 and was subsequently joined by a 750cc model, the Y13. With its stylish, sporting lines and high-quality build, it was considered by some as a competitor to even the Brough Superior.
Production of the 499cc machine drew to a close at the end of 1936, but the Y13 was produced until 1938. About 1600 examples of the BSA Y13 model were manufactured in total, but it’s believed that about a dozen of BSA’s last V-twin models survive today.
Our BSA Y13 was once part of the Sinless Cycles collection hailing from Woodworth, Louisiana.
- Nothing’s as good as seeing the real deal: to admire this beauty up close and to find out more technical details, make sure you come on into Classic Motorcycle Mecca – the leading classic motorcycle collection in the Southern Hemisphere.
- We’ve done our utmost to ensure details about each bike in our extensive collection are accurate: but if you spot something that’s not quite right, we’d love to hear from you.


When Jocelyn Lehrer founded The Men’s Story Project, she wanted to create spaces where male-identifying people can explore their identities without the social standards of masculinity. On May 26 and 27, students at the University of Oregon and members of the Eugene community will take part in actualizing Lehrer’s vision.
“There’s a lot of preventable pain and suffering in the world that’s connected with social issues about masculinity,” Lehrer said. “The big secret is that most men are not comfortable with the social expectations about masculinity that are placed upon them, and yet, we continue as if there’s nothing to talk about.”
The purpose of The Men’s Story Project is to provide a platform where men can speak about their experiences concerning societal expectations of them, and challenge social norms.
Lehrer added that these social norms often contribute to transphobia, homophobia, violence toward women and violence between men, fraternity hazing, and anything concerning a man’s desire to prove himself as manly. She also said that some men don’t want to ask for support for fear of being labeled as weak.
“Every problem that I just mentioned to you has underlying roots in social ideas about masculinity and gender relations,” Lehrer said. “And so the more that we can challenge those underlying ideas about masculinity that contribute to those kind of problems, the better.”
Eleven people who identify as male from all ages and backgrounds will be speaking about their personal experiences during The Men’s Story Project. Some of these experiences will concern the challenges associated with being a man of color or identifying as transgender, among others.
These stories will be presented through song, prose, monologue, dance, poetry and so on.
In 2009, Clover Mathis participated in The Men’s Story Project event at UC Berkley. He performed a dance with a younger dancer that represented an older man serving as a guide to a younger man.
He said he wanted to get involved with The Men’s Story Project when he was studying the way society defines masculinity.
After participating, he found that the project encourages people to discover themselves in separation from societal expectations of men.
“We must ask ourselves: ‘who are we?’” Mathis said. “And maybe get a different definition of manhood.”
Aaron Porter, president of the Men’s Center, said that part of accomplishing this is by listening to less-heard stories of others and their experiences, while also educating oneself on how to build healthy relationships and live healthy lives.
He said that currently, society places men in a box that limits their character to the social definitions of manhood.
“Let’s throw away the box all together, and let’s be healthy human beings. Let’s talk openly about the crap that’s going on around us that men are perpetuating that’s really unhealthy. And let’s celebrate the beautiful things that men around us are doing,” Porter said. “The men that are not just a part of the problem. But let’s talk about the ways that men we know are part of the solution.”


The first commercially available portable computer, the Osborne 1, hit the market in 1981. This pioneering invention weighed a whopping 24 pounds, sported a tiny 5-inch screen, and cost over $5,200 adjusted for inflation. Even though you’d now consider the Osborne 1 to be an overpriced hunk of junk, taking your computer on the go was a groundbreaking concept at the time.
Today, powerful laptop computers and music production software software make producing music accessible to anyone. Music producers can compose, record, edit, and publish tracks from anywhere in the world, eliminating the need to book an expensive recording studio. Modern laptops are especially a game changer for musicians on tour, as they can continue working on new songs while they’re on the road.
Below we break down five important considerations for shopping for a music production laptop. If you’d rather just get straight to our picks, here they are.
The 5 best laptops for music production
When looking for the best laptops for music production, we aimed for a mix of options that cover the needs of all types of music makers. Whether you have a low or high budget, or need an entry-level or professional machine, the list below should have at least one laptop for you.
Price: From $1,299
Apple’s flagship laptop for media professionals comes with a hefty price tag, but it's powerful, reliable, fast, and worth every penny. Their new 5th Generation MacBook addressed several criticisms of the previous generation by giving the laptop a higher base memory, eliminating the Touch Bar, and restoring MagSafe charging and HDMI ports. It's our top pick for the best music production laptop thanks to its powerful Apple M1 Pro or M1 Max processor, up to 64GB RAM, up to 8TB of storage, 17-21 hours of battery life, a gorgeous liquid retina XDR display, and three Thunderbolt 4/USB-C ports. Plus, if Logic Pro is your DAW software of choice, the software is only available on the Mac operating system.
The cheapest version is the 13-inch model, but working with DAW software on such a small screen size may leave you squinting at your monitor and wishing you’d sprung for the 14- or 16-inch.
Price: From $1,449
If you’re not in the market for a Mac, the Dell XPS 15 is a strong pick for on-the-go music production in terms of performance and value. Dell even lets you customize your XPS 15 laptop to your specific requirements. For your processor, you could choose 12-core Intel Core i5 on the low end, or you could splurge for a higher-end 14-core Intel Core i9. You can also select up to 64GB RAM, up to 2TB of SSD storage space, and either a non-touch or touch screen display.
On the downside, the Dell XPS 15’s battery life, with a maximum capacity of approximately 10 hours, pales in comparison to the MacBook Pro . If you choose a lower-end processor, you might also find its noisy fan frequently kicks in to prevent overheating.
Price: From $999
Professional music producers should likely stick to Apple’s superior MacBook Pro line. But the latest MacBook Air with the impressive 8 core M1 processor is more than sufficient for music makers who don’t require top-of-the-line performance. It's the slimmest MacBook Air yet at 0.63 inches think, meaning it’s ideal if you’re constantly on the go. Apple also improved the Air’s battery life from its previous incarnation, boosting its capacity from 12 hours all the way up to 18 hours.
Unlike previous models, the newest MacBook Air is designed without an internal fan, which is great for eliminating excess noise but could sacrifice performance. If you don’t mind the smaller screen and the fact that it only has two ports (both Thunderbolt 3/USB-C ports), the MacBook Air is one of the best second-tier music production laptops you can buy.
Price: From $800
The Microsoft Surface Laptop 4 is a great laptop for music producers who like the Windows operating system and want more bang for their buck. While the Surface Laptop 4 comes in a smaller and cheaper 13.5-inch model, the 15-inch model will give you more computing power and a beautiful PixelSense display that’s conducive to audio editing. It features either an AMD Ryzen 7 or Intel Quad Core i7 processor, up to 32GB of memory, and up to 17.5 hours of battery life.
The Surface Laptop 4’s biggest flaw is that it has just two ports — one USB-C port and one USB-A port. That means many users will need to carry around a USB adapter, but that’s probably a fine trade-off for those who value the thin and sleek design. The Surface Laptop 4 is comparable in price and performance to Apple’s MacBook Air — so if you’re on the fence between the two, go with whichever operating system floats your boat.
Price: From $3,000
If price isn’t an issue and your number one laptop priority is power, look no further than the Razer Blade 15 Studio Edition. This expensive top-tier gaming laptop boasts an exceptional Nvidia Quadro RTX 5000 graphics card, which isn’t necessary for music production, but is an added bonus if you also use your laptop for video editing or gaming. The Razer Blade 15 Studio Edition also has a stunning 15.6-inch 4K OLED Touch display and all the ports you could ask for: three USB-A ports, two USB-C ports, an HDMI output, and an SD Card Reader. The inside of the machine packs a major punch as well, with an 8-core Intel Core i7 processor, 32GB RAM, and a 1TB solid-state drive.
Besides being by far the priciest laptop on this list, the one major downside of the Razer Blade 15 Studio Edition is that you won’t get more than six or seven hours of battery life on one charge. While it’s likely excessive for those who focus only on music production, this powerhouse laptop fits the bill for anyone with both audio and video production needs.
5 things to consider before buying your laptop
If you’re a songwriter primarily recording music in your home studio, your needs will differ quite a bit from a DJ who travels constantly with their laptop and uses it to play live gigs. So in addition to the following considerations, when you’re shopping for a music production laptop, remember to take your specific situation into account.
- RAM. RAM, or random-access memory, is your computer’s short-term memory capacity. To run most music production software efficiently you’ll want at least 8gb of RAM, but 16gb of RAM will give you the optimal performance. On the bright side, if you purchase a laptop and realize you’d benefit from a memory boost, it’s relatively easy to upgrade your RAM later.
- Processor. Also called a CPU, the processor is the brain of your computer. If you’re mixing lots of tracks using DAW (digital audio workstation) software, you’re going to want a high-performing processor. For serious music production, look for a quad-core processor or higher (hecta-core, octo-core, etc.). It’s difficult to upgrade your processor after the fact, so when in doubt, go for the most powerful option within your budget.
- Hard drive space. Raw audio files tend to take up a ton of storage space on your computer’s hard drive. To avoid getting into a situation where you have to delete files to make room for new tracks, try to get at least 1TB of SSD storage space. SSD stands for “solid-state drive” and will read/write much faster than a traditional HDD (hard disk drive).
- USB ports. When producing music, your laptop most likely isn’t your sole piece of equipment — you’ll need external components like an audio interface, microphone, and MIDI keyboard controller. This means you want to look for laptops with several USB ports so you can plug those components in. You can always buy inexpensive USB port adapters though, so don’t sweat it too much if your ideal laptop is low on ports.
- Battery Life. If you expect to work outdoors, while traveling, or anywhere without a power outlet, look for laptop models with a higher battery capacity. There’s nothing worse than seeing the dreaded red “low battery” icon pop up in the middle of a productive work session.
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text: Exceedingly Rare German Document Signed (Autographed) By Hitler, And Blomberg Certified By The Gettysburg Museum Of History And 3rd Party Certification. This RARE document appoints German Army Officer Karl Heinrich Georg Ferdinand Kreipe who was abducted by British and Greek agents during WWII. You wanted the best, we give you the best! Mega Rare! Investment quality. Original signatures of Adolf Hitler, and Werner von Blomberg on a certificate of appointment with very nice ink signatures by “Adolf Hitler” and “v.Blomberg” as countersigner. The sheet is unfolded, in very good condition. As commander of Infantry Regiment 909 of the 58th Infantry Division, Kreipe participated in the Battle of France and the drive towards Leningrad and fighting in Kuban during Operation Barbarossa. He was awarded the Knight’s Cross of the Iron Cross on 13 October 1941. Kreipe remained on the Leningrad front until May 1942, when he was transferred back to Germany, where he took up administrative and teaching positions. In June–October 1943, he was returned to the Eastern Front, where he led the 79th Infantry Division. On 1 March 1944, Kreipe was appointed Commander of the 22nd Air Landing Infantry Division, operating on Crete, replacing General Friedrich-Wilhelm Müller, who had been made the German commander of Crete in Chania. In the spring of 1944 the Allies hatched a plan to kidnap General Müller, whose harsh repressive measures had earned him the nickname “the Butcher of Crete”. Major Patrick Leigh Fermor led the planned operation, assisted by Captain Bill Stanley Moss, Greek SOE agents and Cretan resistance fighters. However General Müller left the island before the plan could be executed. Major Leigh Fermor decided to abduct Kreipe instead. On the night of 26 April 1944 General Kreipe left headquarters in Archanes. The car headed without escort to a well-guarded residence, “Villa Ariadni”, about 5 km outside Heraklion. Major Leigh Fermor and Captain Moss, dressed as German military policemen, waited for him 1 km before his residence. When he arrived, they asked the driver to stop and asked for their papers. As soon as the car stopped, Leigh Fermor opened Kreipe’s door, jumped in, and threatened him with his pistol, while Moss took the driver’s seat. (The abduction is now commemorated near Archanes.) Moss drove the kidnappers and the General for an hour and a half through 22 controlled road-blocks in Heraklion, before leaving Leigh Fermor to drive on and abandon the car, with material being planted that suggested their escape from the island had been made by submarine. Moss set off with the General on a cross-country march, supported by the Greek resistance, soon rejoined by Leigh Fermor. Hunted by German patrols, the kidnappers crossed the mountains to reach the southern side of the island, where a British Motor Launch (ML 842 commanded by Brian Coleman) was waiting to rendez-vous. Eventually, on 14 May 1944, they were picked up from Peristeres beach near Rhodakino and ferried to Egypt.Kreipe was interrogated, then sent to a POW camp in Canada. Later transferred to a special camp in Wales,Kreipe was finally released from British captivity in 1947. General Kreipe met his kidnappers one more time in 1972 on a Greek television programme.He died at Northeim on 14 June 1976. A document from a very famous German officer. 100% Guaranteed to be authentic. Original period double signed documents are rare, most were destroyed at the end of WWII. in excellent condition. Complete museum documentation (COA) Provided. Certified by The Gettysburg Museum of History. Also includes a third party COA. The Gettysburg Museum of History does not support or condone Adolf Hitler or the Nazi Party and is only offering this as a historic relic. Please see our other items. Also note when browsing our web site there are several pages of items, at the bottom of the list look for other page numbers. RARE! Don’t miss this one! EXCELLENT HITLER BOLD DARK SIGNATURE! .

domain: history


text:
Art Silk Lehenga in Dusty pink.This attire with Poly Shantoon Lining is Prettified with Resham, Zari, Sequins, Dori and Patch Border Work.Available with a dusty pink Semi-stitched Art Silk Choli Crafted in Boat Neck and Elbow Sleeve and a Dusty pink woven silk Dupatta. Choli Length- 14 to 15 and Sleeve Length- 1 to 12 inches respectively.The Semi-stitched Lehenga Waist and Hips are Customizable from 30 to 38 and 38 to 42 inches respectively and Lehenga Length is 42 inches.Do note: Accessories shown in the image are for presentation purposes only.Slight variation in actual color vs. image is possible.it can be wear in wedding occasion.It will add glam beauty to you and will make you center of attraction.
Fabric Art Silk
Type A Line Lehenga
Work Contemporary, Dori Work, Resham, Sequins


text:
"A recent investigation into potential mold at the Horace Mann Middle School came up negative for any mold spore.
AcuHealth Inc. conducted the inspection and testing on Nov. 9. They conducted visual, air, and wall cavity tests all of which indicated there was no mold in the building.
The report, released earlier this week, also says there’s no water damage, visible mold growth, or discernable odor. Air quality numbers were normal, and no action was recommended from AcuHealth.
The concerns arose from members of the Horace Mann Middle School community that became suspicious of mold development. The suspicions partially stem from a period of time where the structure was openly exposed to the elements."
Continue reading the article online (subscription may be required)
|Horace Mann-Oak St Complex entrance|

domain: news


text:
If 5e is to 4e what 4e is to 3e and 3e is to AD&D, then maybe it will be a game I'll actually like instead of just finding passable!
Siela Tempo by the talented Kasanip. Tengu by myself.
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domain: hobby


text:
African American Studies
Emigration and Immigration
Prostitution and Sex Trade
Race and Ethnicity
Slavery and Slave Trade
Social Science Essays
Social Science, Methodology
Violence in Society
Native American societies, often viewed as unchanging, in fact experienced a rich process of cultural innovation in the millennia prior to recorded history. Societies of the Hocking River Valley in southeastern Ohio, part of the Ohio River Valley, created a tribal organization beginning about 2000 bc.
The award-winning Stolen Life is a remarkable collaborative work between a distinguished novelist and a Cree woman who broke a lifetime of silence to share her story. Imprisoned for murder at the age of twenty-seven, Yvonne Johnson sought out Rudy Wiebe, the chronicler of her ancestor Big Bear, as a means of coming to terms with her self, her past, and the crime that defines her future.
“Mysticism is peculiar to the mountainbred,” Frank Waters once told an interviewer for Psychology Today. And in Mountain Dialogues, available for the first time in paperback, the mountainbred Waters proves it true. Ranging over such diverse subjects as silence, spirits, time, change, and the sacred mountains of the world, Waters sounds again and again the radiant, mystic theme of man’s inherent wholeness and his oneness with the cosmos.
Pontiac, Sequoyah, Geronimo, Sitting Bull, Chief Joseph, and Chief Seattle. These legendary names are familiar even to the uninitiated in Native American history, yet the life stories of these great spiritual leaders have been largely unknown. In this, his last book, internationally celebrated author Frank Waters makes vivid the poignant, humorous, and tragic stories of these neglected and heroic Native Americans.
Traditionally, the legends, myth-cycles, tales, rituals, songs and poems of Native Americans (both North and South) have been treated as ethnological data or as curious objects. William Brandon believes that the songs and poems in this volume will, in time, be accepted as representatives of one of the world’s great literatures.
In Mexico Mystique Frank Waters draws us deeply into the ancient but still-living myths of Mexico. To reveal their hidden meanings and their powerful symbolism, he brings to bear his gift for intuitive imagination as well as a broad knowledge of anthropology, Jungian psychology, astrology, and Eastern and esoteric religions. He offers a startling interpretation of the Mayan Great Cycle — our present Fifth World — whose beginning has been projected to 3113 B.C.,
The Mound Builders traces the speculation surrounding the thousands of earthen mounds built across the Midwest some time between 1000 B.C. and 1000 A.D. and the scientific excavations which uncovered the history and culture of the ancient Americans who built them.
Though study of American Indian cultures had been fostered for several centuries by missionaries and explorers, it was not until he nineteenth century that a disciplined and systematic approach to the study of New World cultures began to emerge.
While earthworks, or “mounds,” are the most widely known fixed monuments of Native American history in Ohio, the state shares with the rest of the upper Ohio Valley a widely dispersed collection of smaller monuments. The animal, mythical, and human designs scratched into soft rock faces throughout the region constitute a fascinating, enigmatic, and fragile record of the world of the late prehistoric peoples of the American Midwest.
W. Y. Evans–Wentz, great Buddhist scholar and translator of such now familiar works as the Tibetan Book of the Dead and the Tibetan Book of the Great Liberation, spent his final years in California. There, in the shadow of Cuchama, one of the Earth’s holiest mountains, he began to explore the astonishing parallels between the spiritual teaching of America’s native peoples and that of the deeply mystical Hindus and Tibetans.
Frank Waters lived for 3 years among the strange, secretive Hopi Indians of Arizona and was quickly drawn into their mythic, timeless reality. Pumpkin Seed Point is a beautifully written personal account of Waters' inner and outer experiences in the subterranean world.
I Have Spoken is a collection of American Indian oratory from the 17th to the 20th century, concentrating on speeches focusing around Indian-white relationships, especially treaty-making negotiations. A few letters and other writings are also included.

domain: literature


text:
Woeful lack of diversity in fire services, says minister Brandon Lewis
A Government minister has criticised fire services over a "woeful" lack of diversity.
Brandon Lewis cited figures showing firefighters in England are 96% white and 95% male.
He said: "Any workforce should represent the community that it serves, but in fire this simply at the moment is not the case.
"I've been to fire stations where, I have to say, I noticed more diversity in the fire hoses used than I have in the workforce."
The minister for policing and the fire service said the proportion of black and minority ethnic and female firefighters must increase.
He dismissed any attempt to blame the lack of diversity on a reduction in recruitment, saying: "That isn't good enough."
Mr Lewis called for a "culture shift" and said there is a "golden opportunity" for services to make sure their workforces reflect the communities they serve as almost a third of personnel are due to retire in the next few years.
In a speech in central London, the Home Office minister set out his vision for a "year of change" for the fire and rescue sector.
He announced the creation of a new inspectorate to probe service's performances and outlined plans to introduce a professional standards body.
Mr Lewis also highlighted large differences in the amounts of money spent on the same pieces of equipment in different parts of the country.
Figures last year showed that some services were paying as much as five times more than others for similar items.
One spends £85 per fire helmet, compared with another which pays £252. Prices paid for breathing kit range from £328 to more than £1,500.
Mr Lewis called for services to work together and get a better deal from suppliers to save themselves and the taxpayer money.
He also said the practice of senior fire officers retiring from their posts then being re-employed in the same or similar roles "needs to stop".


- The trademark feature on Samsung’sGalaxy Fold is its foldable display, which enables it to function as both a smartphone and a tablet.
- But it was the device’s long battery life that impressed me most.
- I was able to use the Galaxy Fold for two full days without plugging it in.
There’s nothing typical about the way Samsung’s Galaxy Fold looks or how it works.
The Fold, which starts at $US1,980 and hits stores on April 26, is the company’s first foldable phone. It opens like a book to reveal a large, flexible screen on the inside that enables it to serve as both a smartphone and a tablet, with its front and back panels connected by a custom-designed hinge.
But after spending nearly one week with the device, it’s not the Fold’s unconventional design that stood out to me the most. Rather, it’s the Galaxy Fold’s extensive battery life – which lasted for two full days on a single charge – that left me impressed.
I charged the device overnight on a Tuesday and unplugged it around 7:45 a.m. on Wednesday when I left home to commute to work. It lasted all day Wednesday and the following day before it finally died overnight on Thursday going into Friday morning.
The Galaxy Fold has a 4,380 mAh dual battery, which means the phone actually has two batteries – one on each side of the device. But Samsung says it’s built custom technology to combine the energy from two batteries into one power source.
Many large-screened smartphones offer lengthy battery life, but they don’t seem to last quite as long as the Galaxy Fold. Reviews of the Galaxy S10+, for instance, indicated that the phone persisted for an entire day with some battery life to spare, while iPhone XS Max reviews suggested the phone lasts for about a whole day.
That’s about on par with my usual experience with modern phones like the S10+ and iPhone XS Max. I can typically get through an entire day with some power left over at night. If I choose not to plug in my phone before going to sleep, I could probably get through about half of my work day the following day. But certainly not an entire additional day.
Of course, battery life will always vary depending on how you use your smartphone. During my time with the Fold, I typically used it for sending messages, perusing Facebook and Instagram, watching Netflix, playing games like “Asphalt 9,” and browsing the web. But you’ll likely experience slightly different results, and could see a dip in battery life if you do things like crank up the brightness to the highest setting and often run power-hungry apps.
Have you preordered the Galaxy Fold? We want to hear from you. Contact this reporter at [email protected]
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MIAMI — In a coverage dispute between a contractor’s insurer and a subcontractor’s insurer over the duty to defend a construction defects lawsuit on a primary and noncontributory basis, a Florida federal judge on Feb. 5 ruled that the subcontractor insurer’s policy precludes additional insured coverage under the completed-operations hazard exclusion (Scottsdale Insurance Co. v. Granada Insurance Co., No. 18-21207, S.D. Fla., 2019 U.S. Dist. LEXIS 19240).
PHILADELPHIA — A commercial general liability insurer alleges in a Jan. 24 complaint filed in a Pennsylvania federal court that it has no duty to defend or indemnify a contractor and subcontractor in an underlying construction defects case (Seneca Specialty Insurance Co. v. Top Class Construction Inc., et al., No. 19-363, E.D. Pa.).
ST. LOUIS — A Missouri federal judge on Feb. 1 denied an insured subcontractor’s motion to dismiss its insurer’s dispute regarding coverage for an underlying breach of contract and breach of express warranty case brought by homeowners (Great Lakes Insurance SE v. AMCO Insurance Co., et al., No. 18-631, E.D. Mo., 2019 U.S. Dist. LEXIS 16040).
SAN DIEGO — A commercial general liability insurer showed that its insured must reimburse it $50,000 in deductibles for payments it made in settlement of two construction defects actions, a California appeals panel held Jan. 31 (Lexington Insurance Co. v. Timber Ridge Framing Inc., No. D073412, Calif. App., 4th Dist. Div. 1, 2019 Cal. App. Unpub. LEXIS 802).
NEWARK, N.J. — A commercial general liability insurer is responsible for paying damages for defective concrete delivered to two New Jersey projects, a concrete producer claims in its Jan. 30 complaint filed in New Jersey federal court (County Concrete Corp. v. Greenwich Insurance Co., No. 19-03449, D. N.J.).
PHILADELPHIA — An insurer has a duty to defend two construction defect actions because there are sufficient allegations of products-related tort claims such that there may have been an “occurrence,” a Pennsylvania federal judge ruled Jan. 30 (Nautilus Insurance Co. v. 200 Christian Street Partners LLC, et al., Nos. 18-1364 & 18-1545, E.D. Pa., 2019 U.S. Dist. LEXIS 15060).
OKLAHOMA CITY — An insurance policy covers damage to a school caused by the rupture of a water pipe beneath the school, a majority of the Oklahoma Supreme Court held Jan. 29, reversing the entry of summary judgment to an insurer (Oklahoma Schools Risk Management Trust v. McAlester Public Schools, No. 114553, Okla. Sup., 2019 Okla. LEXIS 2).
DALLAS — A subrogated insurer sued another insurer on Jan. 7 in a Texas federal court asserting breach of contract and declaratory judgment claims and seeking recovery of costs in the defense of a mutual insured in an underlying construction defects lawsuit (Employers Mutual Casualty Co. v. Philadelphia Indemnity Insurance Co., No. 19-32, N.D. Texas).
AUSTIN, Texas — According to its Jan. 25 orders pronounced, the Texas Supreme Court denied an insurer’s petition for writ of mandamus seeking to clarify a party's right to object to an assigned judge when the party first learns of the assignment the day of the first hearing or trial, also lifting the stay of the coverage lawsuit over the installation of defective heating ventilation and air conditioning units (In re Union Insurance Co., No. 18-0353, Texas Sup.).
ST. LOUIS — An insurer has no duty to defend or indemnify allegations that defective construction caused water infiltration in condominium units, the Eighth Circuit U.S. Court of Appeals held Jan. 28, because the property damage occurred outside the policy period (Clarke Company Ltd. v. American Family Mutual Insurance Co., No. 17-2418, 8th Cir., 2019 U.S. App. LEXIS 2760).
TAMPA, Fla. — An insurer on Jan. 7 sued a home builder and the owners of the property in a Florida federal court, seeking a declaration that it has no duty to defend or indemnify them in relation to an underlying lawsuit in which the owners allege the property contains defects (Southern-Owners Insurance Co. v. Russ Building Concepts, et al., No. 19-00042, M.D. Fla.).
MADISON, Wis. — The Wisconsin Supreme Court majority on Jan. 25 determined that a pollution liability insurer breached its duty to defend an additional insured for underlying property damage claims arising out of a sewage backup and said that the additional insured’s defense costs, which were paid by another insurer, must be allocated on a pro rata basis between the two insurers (Steadfast Insurance Co. v. Greenwich Insurance Co., No. 2016AP1631, Wis. Sup., 2019 Wisc. LEXIS 9).
SAN FRANCISCO — A California federal judge on Jan. 22 addressed the change in a cited case as it pertains to four orders issued in an insurance coverage lawsuit concerning underlying construction defects lawsuits and denied the insurer’s motion for leave to file motions for reconsideration (Travelers Property Casualty Company of America, et al. v. Centex Homes, No. 11-03638, Related Case Nos. 12-00371 & 13-00088, N.D. Calif., 2019 U.S. Dist. LEXIS 10261).
ROCKVILLE, Conn. — Insureds seeking coverage for the cracking of their home’s foundation walls filed a notice of appeal on Jan. 3 to the Connecticut Appellate Court following a Connecticut state judge’s finding that no coverage is afforded for the cracking foundation walls because there was no abrupt collapse of the home’s walls, as required by two of the applicable policies, and because the loss was caused by cracking, an excluded cause of loss under another of the policies (Michael Willenborg, et al. v. Unitrin Preferred Ins. Co., et al., No. 166010936S, Conn. Super.).
SAVANNAH, Ga. — Claims that work on a pool resulted in a faulty and unusable pool are not claims for covered “property damage,” a Georgia federal judge ruled Jan. 17, granting summary judgment to an insurer on declaratory judgment, breach of contract and bad faith claims (Delma Cowart v. Nautilus Insurance Co., NO. 17-142, S.D. Ga., 2019 U.S. Dist. LEXIS 8531).
ALBUQUERQUE, N.M. — In a dispute over coverage for water damage, a New Mexico federal judge on Jan. 8 denied summary judgment to a homeowners insurer on statutory claims and negligence asserted under the New Mexico Unfair Practices Act and the New Mexico Unfair Insurance Practices Act but granted summary judgment on a negligence claim (Hector Fava, et al. v. Liberty Mutual Insurance Corp., No. 17-456, D. N.M., 2019 U.S. Dist. LEXIS 4158).
DENVER — “Pop-outs” in a concrete floor “did not physically injure or damage any tangible property other than the floor” and, thus, did not constitute “property damage” under a commercial general liability insurance policy, a Colorado federal judge held Jan. 8 (Kalman Floor Co. v. Old Republic General Insurance Corp., No. 17- 01703, D. Colo., 2019 U.S. Dist. LEXIS 3319).
BOSTON — Leaks in a condominium unit were not “property damage” that occurred during a policy period, a Massachusetts federal judge held Jan. 8, granting summary judgment to an insurer on another insurer’s breach of contract claim (Clarendon National Insurance Co. v. Philadelphia Indemnity Insurance Co., No. 17-12541, D. Mass., 2019 U.S. Dist. LEXIS 3322).
ALBUQUERQUE, N.M. — An insurer is not entitled to summary judgment on a bad faith claim alleged by insureds who maintain that they are entitled to coverage for water damage because the insureds presented sufficient facts from which a jury could find that the insurer’s coverage denial was made in bad faith, a New Mexico federal judge said Dec. 20 (Hector Fava, et al. v. Liberty Mutual Insurance Corp., No. 17-456, D. N.M., 2018 U.S. Dist. LEXIS 215009).
BOSTON — A contract liability exclusion precludes coverage for any work assumed by a general contractor to repair a subcontractor’s defective work in a gymnasium floor, a Massachusetts federal judge ruled Jan. 4, granting summary judgment to an insurer on breach of contract and declaratory judgment claims (Lee Kennedy Co. Inc. v. Arch Insurance Co., No. 17-10698, D. Mass., 2019 U.S. Dist. LEXIS 1448).


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Domino's Pizza NUNGAMBAKAM, Chennai
152 & 153,DR. MGR SALAIKODAMBAKKAM HIGH ROADBIG FM BUILDINGNUNGUMBAKKAM,CHENNAI - 600034 PH.NO. 044-28221111/2011/2012/2013/2014/2015
Pizza, Fast Food
₹400 for two people (approx.)
Exclusive of applicable taxes and charges, if any
Cards and Meal Coupons accepted
Opening hours Open now
Today 11 AM to 11 PM
152 & 153,DR. MGR SALAIKODAMBAKKAM HIGH ROADBIG FM BUILDINGNUNGUMBAKKAM,CHENNAI - 600034 PH.NO. 044-28221111/2011/2012/2013/2014/2015See more locations in Chennai
No Alcohol Available
Domino's Pizza Photos
Store Ratings & Reviews
22 Oct, 2021 02:08
Ashwin Jaipaul Singh
This was a great place to hangout with friends.
19 Oct, 2021 11:26
Good taste and the best if you can compromise with your health I'm giving 4star because of it's health issues Firing pizza entice you..... ???
18 Oct, 2021 07:12
This place has really lost it. The pizzas are terrible including their new four cheese pizza. I really loved this place in the beginning but now they have no taste at all. I hope they do something about this. Maybe concentrate on the thin crust pizzas and improve their dough. Pizza hut is comparatively better considering their competition. But then again there are lot more pizza apart from these corporates that really know how to make a pie.
16 Oct, 2021 04:58
syed nasir ahmed
Good and Excellent
14 Oct, 2021 03:00


|Grade||Genuine Rolex||AAAAA Clone||AAA Replica||A Replica|
|Movement||Rolex Calibre 4130||Genuine Swiss Clone 4130 movement||Swiss 7750 Movement||Asian MingZhu Movement|
|Time Accuracy||-3/+5 sec per day COSC certified||-5/+6 sec per day COSC certified||-10/+10 sec per day COSC certified||-1/+2 min per day COSC certified|
|Stainless Steel Type||904L Stainless Steel||904L Stainless Steel||316L Stainless Steel||316L Stainless Steel|
|Crystal||Sapphire crystal||Sapphire crystal correct date magnification||Sapphire crystal||Mineral Glass|
|Logo & Markings||laser etchings||Exact on entire watch||90% Exact on entire watch||70% Exact on entire watch|
|Dial||Genuine Rolex||Exact detail and font||90% exact detail and font||70% Exact detail and font|
|Luminous Markers||Rolex Lumen||SuperLuminova Swiss Lumen||Swiss Lumen||Normal Lumen|
|Waterproof||100m on standard models||Tested up to 300m||Tested up to 30m||Life waterproof|
|Life expectancy||Lifetime||Lifetime||3-5 years||1-2 years|
|Warranty||2 Years||Up to 5 Years||Up to 3 Years||Up to 1 Years|
|Engine||Rolex Calibre 7750/Mingzhu Engine|
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Hand: Silver-tone. About the hand design of the watch is silver-tone, which is delicated and cool.
Second Markers: Minute Markers around the outer rim. The other mark in the watch is designed to be a small round dial placed on the outside of the watch to indicate the time.
Dial Markers: Luminous Index. When you are not in light, the luminous stickscan of the watch will light up.
Luminiscence: Hands and Markers. About the watch, the luminiscence is hands and markers. It makes your watch look more high-end.
Bezel Material: Stainless Steel. A stainless steel bezel a unique structure that makes it an excellent choice for watches. The material can resist scratches, abrasions and indentation. This bezel material is the most resistant to heat and cold of all materials used in watchmaking.
Clasp: Deployment. This watch case has a designed lock to make it easier and faster for the user to open and fold the watch case to keep it secure.
Water Resistance: 30 meters. As for the waterproof depth of the watch, it is 30 meters, which is similar as real watch. Tips: The A Replica is just daily waterproof, need to purchase additional waterproof service which is up to 30 meters.
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text:
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domain: medical


text:
Arteriors Geordi Cherry Sculpture - White
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text:
© 2017, SyfyWire. All rights reserved.
Comic legend Mark Waid is already keeping busy with two flagship comic runs spun out of Marvel’s Secret Wars event (not to mention an Archie reboot), but he’s also found room for a passion project he’s been kicking around for years: Captain Kid.
Marvel has released a preview for its upcoming All-New, All-Different Avengers #9 hinting at the All-New Wasp's identity.
Here comes Janet Van Dyne's replacement as the All-New Wasp.
The roster for the Avengers is taking some interesting turns in the wake of Secret Wars, and now we have a fresh look at the new additions.
We already knew Marvel’s flagship team would be retooled in the wake of Secret Wars, but now we have some intriguing new details on the All New, All Different Avengers
The entire Marvel comic catalog is getting a shakeup thanks to the upcoming Secret Wars event, and here’s our first peek at how it’ll affect one of the flagship teams.


text:
Canada Post to stop door-to-door mail
Canada Post has announced it will stop delivering regular mail door-to-door to homes in urban centres, as part of sweeping cost-cutting measures.
The Crown corporation announced Wednesday that door-to-door delivery will be phased out over the next five years.
Those areas – which account for about one-third of Canadian households -- will transition to community mail boxes. Implementation of the changes will begin in the second half of 2014.
The first neighbourhoods that will stop receiving door-to-door mail delivery have yet to be announced.
The postal service also announced Wednesday that the cost of stamps will be increasing from $0.63 each to $0.85 beginning March 31, 2014.
The changes are part of a five-point action plan aimed at returning Canada Post to “financial sustainability” by 2019.
A think-tank commissioned by Canada Post warned earlier this year that the postal service will be losing $1 billion a year by the end of this decade.
Conference Board of Canada said, in this age of digital communication, the postal service is being hit by a dramatic reduction in the volume of it mail it handles.
It estimated $576 million a year could be saved by eliminating of door-to-door delivery for urban homes.
Read more Canada News
- No leads on latest homicidesCentral Okanagan - 4:00 pm
- Teachers' stalemateBC - 7:26 pm
- Foreign workers' scandalCanada - 7:20 pm
- Evacuation orderBC - 12:43 pm
Government of Canada
Canada Revenue Agency


text:
Deranged Calcium Signaling in Purkinje Cells and Pathogenesis in Spinocerebellar Ataxia 2 (SCA2) and Other Ataxias
Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of more than 30 autosomal-dominant genetic and neurodegenerative disorders. SCAs are generally characterized by progressive ataxia and cerebellar atrophy. Although all SCA patients present with the phenotypic overlap of cerebellar atrophy and ataxia, 17 different gene loci have so far been implicated as culprits in these SCAs. It is not currently understood how mutations in these 17 proteins lead to the cerebellar atrophy and ataxia. Several pathogenic mechanisms have been studied in SCAs but there is yet to be a promising target for successful treatment of SCAs. Emerging research suggests that a fundamental cellular signaling pathway is disrupted by a majority of these mutated genes, which could explain the characteristic death of Purkinje cells, cerebellar atrophy, and ataxia that occur in many SCAs. We propose that mutations in SCA genes cause disruptions in multiple cellular pathways but the characteristic SCA pathogenesis does not begin until calcium signaling pathways are disrupted in cerebellar Purkinje cells either as a result of an excitotoxic increase or a compensatory suppression of calcium signaling. We argue that disruptions in Purkinje cell calcium signaling lead to initial cerebellar dysfunction and ataxic sympoms and eventually proceed to Purkinje cell death. Here, we discuss a calcium hypothesis of Purkinje cell neurodegeneration in SCAs by primarily focusing on an example of spinocerebellar ataxia 2 (SCA2). We will also present evidence linking deranged calcium signaling to the pathogenesis of other SCAs (SCA1, 3, 5, 6, 14, 15/16) that lead to significant Purkinje cell dysfunction and loss in patients.
KeywordsPurkinje cell Calcium Ataxia Polyglutamine Excitotoxicity Neurodegeneration SCA2
Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of autosomal-dominant genetic and neurodegenerative disorders. SCAs are generally characterized by cerebellar atrophy and a progressive incoordination of movement known as ataxia [1, 2, 3]. Over 30 SCAs have been identified and named in the chronological order of their discovery from SCA1 to SCA30 . Although all SCA patients present with the phenotypic overlap of cerebellar atrophy and ataxia, other brain regions are differentially affected in each SCA. Seventeen genes have been associated with these SCAs and it is not understood how mutations in those SCA-associated genes lead to the SCA pathogenesis . The pathogenesis of SCAs is not fully understood, however, several different pathogenic mechanisms have been studied in SCAs such as dysregulation of transcription and gene expression, alterations in calcium homeostasis and synaptic neurotransmission, mitochondrial stress and apoptosis (reviewed in [4, 6, 7]). Currently, therapy for SCA patients is mainly supportive and directed at treating individual symptoms in each [7, 8]. No disease modifying therapy exists for any of the SCAs. In order to develop a successful treatment of SCAs, it will be important that a valid therapeutic target and the pathogenic pathways are identified.
Emerging research suggest that a fundamental cellular pathway is disrupted by some of the mutated SCA genes, which could explain the characteristic death of Purkinje cells, cerebellar atrophy and the resulting ataxia [9, 10, 11, 12, 13, 14, 15, 16, 17]. We propose that mutations in SCA genes disrupt multiple cellular pathways but SCA pathogenesis does not begin and progress until calcium homeostasis is disrupted in cerebellar Purkinje cells. This can occur either as a result of an excitotoxic increase or a compensatory suppression of calcium signaling, which eventually leads to cellular dysfunction and cell death. Similar hypothesis has been recently proposed based on the comparison of genes involved in cerebellar plasticity and human ataxias . Calcium signaling in Purkinje cells is important for normal cellular function as these neurons express a variety of calcium channels, calcium-sensitive kinases and phosphatases, calcium sensors, and calcium buffers to tightly maintain calcium homeostasis. Glutamate, an excitatory neurotransmitter, induces a transient increase in the cytoplasmic calcium levels of PCs via activating ionotropic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors and metabotropic glutamate receptors (mGluR). Activation of AMPA receptors causes membane depolarization, activation of voltage-gated calcium channels and calcium Ca2+ influx into the cytoplasm. Activation of mGluR causes Ca2+ release from endoplasmic reticulum stores via activating inositol 1,4,5-triphosphate receptors (ITPR) to allow a transient increase in cytoplasmic Ca2+ levels. Initial Ca2+ signals further amplified by Ca2+-induced Ca2+ release mechanism (CICR) which involves activation of ryanodine receptors (RyanR), an intracellular Ca2+ release channels. When tightly controlled, a transient change in calcium levels functions as an intracellular messenger important for gene transcription  and synaptic neurotransmission . Aberrant calcium levels can uncouple neuronal plasticity and activate toxic cascades leading to cell death. Several studies have implicated deranged calcium signaling in neurodegenerative disorders culminating in the “calcium hypothesis of neurodegeneration”. This hypothesis posits that as fundamental as calcium levels are to cellular functions, dysregulation of calcium homeostasis is detrimental to neuronal survival .
Features of spinocerebellar ataxias linked with abnormal Ca2+ signaling
SCA patient repeats
Effect on calcium signaling
>75% PC loss
>75% PC loss
<25% PC loss
Non-repeat mutations & deletions
>75% PC loss
Non-repeat deletions or mutations
Deranged Calcium Signaling in SCA2
SCA2 patients suffer from a progressive cerebellar syndrome with ataxia of gait and stance, ataxia of limb movements, and dysarthria [1, 2, 3]. The SCA2 is caused by an expansion and translation of unstable CAG repeats in the gene encoding ataxin-2 from the normal 22 to more than 31 extra glutamine repeats [24, 25, 26]. The pathogenesis of SCA2 is currently not understood. Polyglutamine-expanded ataxin-2 (ATXN2exp) protein, similar to wildtype ataxin-2 (ATXNwt), has a wide spread expression. No severe aggregation of ATXN2exp or formation of inclusion bodies was observed in studies of brain samples from SCA2 patients . The cerebellar PCs are preferentially lost in SCA2 patients (Table 1) . Genetic knockouts of ATXN2 orthologs in fly and worm resulted in embryonic lethality [28, 29]. ATXN2 knockout mice were viable but displayed a late-onset obesity phenotype . Mice deficient in ATXN2 did not show Purkinje cell loss or marked changes in the Purkinje cell dendritic tree . Non-essential role of ATXN2 in rodents is most likely related to the presence of orthologs and redundancy in its function . Thus, the polyglutamine expansion in ataxin-2 likely does not cause a loss of function nor a dominant negative effect but a gain of toxic function . The role of calcium signaling in the pathogenesis of SCA2 is supported by the genetic association between polymorphisms in the CACNA1A gene and the age of disease onset in patients diagnosed with SCA2. The CACNA1A gene encodes the pore-forming α1A subunit of CaV2.1, a P/Q-type voltage-gated calcium channel. Patients with a prematurely early age of onset of SCA2 tended to have a longer CAG-repeat length in the CACNA1A gene . Longer CAG-repeat lengths in this gene have been genetically linked to SCA6.
The role of aberrant neuronal calcium signaling in SCA2 pathogenesis was strengthened further by a finding in our laboratory that ATXN2exp but not ATXN2wt specifically binds type 1 inositol (1,4,5) triphosphate receptors (ITPR1s) . This suggested that its association would result in either a sensitization or desensitization of ITPR1s to activation by inositol 1,4,5-triphosphate (InsP3) during glutamate signaling in PCs. PCs express extremely high levels of intracellular ITPR1 [32, 33], which are present on endoplasmic reticulum (ER) membranes. ATXN2exp and ATXN2wt were found to localize and associate with ER membranes . In a lipid bilayer reconstitution experiments, we examined the effect of ATXN2exp expression on ITPR1 activation in single channel recordings of ITPR1s co-expressed with ATXN2exp. We found that the presence of ATXN2exp but not ATXN2wt substantially sensitized ITPR1s to activation by InsP3 in bilayers .
To test the importance of Ca2+ signaling in SCA2 pathogenesis we performed a series of experiments in a SCA2 transgenic mouse model (SCA2-58Q, generated by ) expressing 58 glutamine repeats (ATXN2exp) in the ataxin-2 gene under the control of the L7/Pcp2 PC-specific promoter. These mice exhibit behavioral deficits, loss of Purkinje cell dendritic arborization and Purkinje cell death, which is progressive and akin to SCA2 patient pathology . We found that there was a significant increase in calcium release from ER stores via ITPR1s in calcium imaging experiments in primary PCs cultured from SCA2-58Q transgenic mice, which was not observed in PCs cultured from wildtype littermates . When ryanodine or dantrolene were added to block ryanodine receptors and ER calcium release in PC cultures, the effect of ATXN2exp expression was reversed as ER calcium release returned to the wildtype levels . In a TUNEL assay of PC death, we found that the addition of dantrolene to block the excessive ER calcium release caused by ATXN2exp expression attenuated exogenous glutamate-induced PC death . Furthermore, long-term feeding of SCA2-58Q mice with a calcium stabilizer dantrolene alleviated the age-dependent motor coordination deficits in these mice quantified by rotarod and beam-walk behavioral assays . Stereological counting of PCs showed a rescue of PC death in 12-month-old SCA2-58Q mice fed with dantrolene . The above lines of evidence supported the hypothesis that deranged calcium signaling plays an important role in SCA2 pathogenesis.
Supranormal Calcium Signaling and Purkinje Cell Dysfunction in SCA2
Some of the excess released calcium is also taken up by mitochondria , which can become overloaded as well, eventually creating free radicals and inducing oxidative stress, activating apoptotic cascades and necrotic cell death [21, 40] (Fig. 1). Excessive cytoplasmic calcium also leads to excitotoxic glutamate release which can cause reactive oxygen species production and damage DNA . Intracellular calcium levels higher than physiological concentrations can also cause an increase in activation of multiple calcium-sensitive enzymes. These include calcium-sensitive phosphatases and kinases that alter gene transcription upon activation , as well as proteases such as calpains, which upon activation cause degradation of cellular substrates . Excessive activation of nitric oxide synthase also abnormally increases intracellular nitric oxide levels and causes DNA and mitochondrial damage . In the absence of sufficient intracellular calcium buffering, calcium-induced excitotoxicity is detrimental to cell survival.
We argue that the uncontrolled calcium burden could then fall on cerebellar plasticity mechanisms to attempt to control. Indeed, it has been suggested that cerebellar LTD could instead or in addition to playing a role in motor learning also play a role in neuroprotection in PCs . Cerebellar LTD is triggered in response to an increase in intracellular calcium following stimulation at both parallel and climber fiber synapses [44, 45, 46, 47]. This coincident and transient rise in calcium could function in coding information, supporting the idea that LTD is involved in motor learning [48, 49]. However, in instances of supranormal calcium signaling, LTD could also function to suppress synaptic transmission and to prevent overexcitation. Accordingly, it has been reported that blocking glutamate uptake and increasing synaptic glutamate levels increases the induction of LTD in cerebellar slices , suggesting that LTD could protect PCs from detrimental effects of excitotoxic synaptic transmission. This idea that cerebellar LTD could play a separate role from motor learning in the cerebellum is supported also by evidence showing that LTD can be disrupted without affecting motor learning in two types of motor tasks [51, 52]. Therefore, we propose that LTD could be a mechanism that PC cells use to relieve themselves from excitotoxicity by suppressing glutamatergic synaptic transmission when intracellular calcium exceeds a safe threshold. Although meant to be protective, this “super LTD” may also be linked with early manifestation of ataxic phenotype (Fig. 1). This is because increase in LTD supresses activity of PC cells and removes inhibition of postsynaptic DCN neurons. As a result, hyper-excitability and ataxia symptoms can occur .
The proposed hypothesis predicts that LTD is abnormal in PCs of SCA2 mice. ITPR1s, which are required for calcium release from intracellular stores in the induction of cerebellar LTD [45, 46, 53], are excessively sensitized to activation by InsP sub(3) in PCs of SCA2 mice . Consequently, in PCs of SCA2 mice, when there is a calcium overload resulting from the sensitization of ITPR1s to activation by InsP3, it is possible that this overwhelms and uncouples synaptic plasticity mechanisms that require specific and transient changes in intracellular calcium levels. This can be tested by comparing LTD induction in cerebellar slices from SCA2 and wild type mice. These studies, currently in progress in our laboratory, may also provide novel insights into cerebellar plasticity in normal and pathophysiological situations.
Purkinje Cells in SCA2-58Q Mice Die by Dark Cell Degeneration
Although a dysfunction in cerebellar LTD may be responsible for initial symptoms of SCA2, it is likely that the degeneration and eventual death of PCs are responsible for the symptoms of the disease in the late stages. What is a mode of PC cell death in SCA2? In our previous studies, we demonstrated that application of glutamate induces apoptotic cell death of SCA2-58Q PC neurons in in vitro culture which can be detected by TUNEL staining . What is a mode of cell death of PC cells in vivo? A number of previous studies described a characteristic mode of excitotoxic cell death of PC neurons which has been termed dark cell degeneration (DCD). DCD has been reported in PCs resulting from excitotoxicity in the form of excessive presynaptic glutamate stimulation or sensitivity to glutamate in the synapse [54, 55, 56]. It is suggested to lie in a spectrum between classical apoptotic and passive necrotic cell death because it shares characteristics with both forms of death . DCD mode of PC cell death has been previously identified in mouse models of SCA7 and SCA28 suggesting that excitotoxicity could be central for pathogenesis of these disorders [56, 57]. DCD in SCA7 PCs is induced by the absence of Bergmann glia, which ensheath PCs and re-uptake glutamate from synapses . In SCA28, DCD appears to be mitochondria-mediated .
Typically DCD is evaluated by the analysis of transmission electron microscopy (TEM) images of cerebellar sections. The rationale behind this method is that unlike healthy PCs, as unhealthy PCs degenerate as a result of excitotoxity-induced cell death cascades, the cytoplasm fills with cellular aggregates and debris. The compounds used for TEM processing form an extensive complex that bind to cellular protein structures. Once processed for TEM, the DCD PCs appear to have higher intracellular electron density and appear darker than healthy PCs. In our experiments ten-month-old SCA2-58Q mice and age-matched nontransgenic mice were euthanized and transcardially perfused (according to ) with PBS followed by 2% paraformaldehyde/2% glutaraldehyde in 0.1M cacodylate buffer. The cerebellum was left in fixative overnight, subsequently cut into 1 mm3 coronal sections and post-fixed in 1% Osmium Tetroxide. The specimens were then stained en bloc with aqueous 1% uranyl acetate and lead citrate, dehydrated through a graded ethanol series, and embedded in EMbed 812 resin. Thinner sections (70–90 nm in thickness) were cut, placed on copper grids and stained with aqueous 2% uranyl acetate and lead citrate. Sections from each animal were examined on a FEI Tecnai G2 Spirit Biotwin transmission electron microscope, operated at 120 kV and digital images were captured with a SIS Morada 11 megapixel side mount CCD camera.
Deranged Calcium Signaling in Other Polyglutamine SCAs
The Ca2+ hypothesis is not only relevant for SCA2 but can be expanded to other SCAs [7, 18, 21]. Deranged calcium signaling likely plays a role in the pathogenesis of SCA1. Similar to SCA2, SCA1 is caused by the translation of polyglutamine expansions in the gene encoding ataxin-1 from the normal 30 (ATXN1wt) to over 40 CAG repeats (ATXN1exp) (Table 1). ATXN1exp is widely expressed and selectively toxic in Purkinje cells . Though its aggregation is not required to cause SCA1 pathology, ATXN1exp has to translocate to PC nuclei to cause cell death and ataxia . In the nucleus, ATXN1exp alters transcription by destabilizing the RORα and SP-1 transcription factors [11, 60]. Microarray analyses of transgenic mouse models have shown that SCA1 mice may have altered calcium signaling. Early in SCA1 pathogenesis, SCA1 mice express significantly reduced levels of the calcium buffers calbindin and parvalbumin, ITPR1, type 1 inositol phosphate 5-phosphatase, ER calcium transporter SERCA, glutamate transporter EAAT4, EAAT4-stabilizer β-spectrin III, T-type volage gated calcium channels and transient receptor potential type 3 (TRPC3) calcium channels [9, 10, 11, 61]. Since ITPR1 and SERCA2 have contradictory roles on ER calcium storage, it is possible that ATXN1exp downregulates the expression of only one of the two. One mechanism may be that by blocking ER loading, SERCA2 downregulation causes higher cytoplasmic calcium levels and the PC counteracts this effect by downregulating ITPR1 expression, which decreases ER calcium release and reduce cytoplasmic calcium levels . We suggest that decreased expression of glutamate transporters in SCA1 could result in excitotoxic glutamate signaling that is upstream of calcium signaling leading to cytosolic calcium overload. Similar hypothesis has been previously proposed to explain SCA1 phenotype . Reduced expression of calcium buffers could also decrease the ability of PCs to handle high calcium levels in the cytoplasm. Furthermore, SCA1 mice crossed with calbindin-knockout mice presented with an accelerated SCA1 phenotype , which supports the role of calcium buffers in working to relieve SCA1 PCs from excitotoxic calcium levels and the role of deranged calcium homeostasis in the progression of SCA pathogenesis. We have also found that mutant ATXN1exp specifically interacts with ITPR1 (X.Chen and I. Bezprozvanny, unpublished observations). As we have seen in SCA2, this suggests that excessive calcium release from ER stores via ITPR1s may also contribute to pathogenesis of SCA1. Therefore it would be necessary to study SCA1 mouse models further for any other change in calcium signaling besides the already reported differences in gene expression of calcium signaling proteins [9, 10, 11].
Although we have outlined SCAs that display significant PC loss, aberrant calcium signaling may also play a role in the pathogenesis of other SCAs, such as for example SCA3 (Table 1). Although less than 25% of PCs are lost in SCA3 patients, we have found that deranged calcium signaling may also play a role in pathogenesis of SCA3. SCA3 is similar to SCA1 and SCA2 in that it is caused by a translation of polyglutamine expansions in the ataxin-3 (ATXN3) protein. But unlike SCA1 and SCA2, substantia nigra and pontine nuclei neurons are mainly affected with some PC death . We have shown that polyglutamine expanded ATXN3exp specifically interacts with ITPR1, sensitizing it to activation by InsP3 . Similar to SCA2, we found that feeding SCA3 transgenic mice with dantrolene results in alleviation of the age-dependent motor deficits, as well as the prevention of neuronal loss in both the substantia nigra and pontine nuclei .
SCA6 is caused by a polyglutamine expansion in the C terminus of a P/Q-type calcium channel, CaV2.1 (Table 1). It has been reported that this mutation enhances P/Q-type Ca2+ channels activity . However, recent analysis of SCA6 knock-in mouse model indicated that pathology may be related to aggregation of mutant CaV2.1 subunits and reduction in the density of dendritic P/Q-type Ca2+ currents . Animals expressing polyQ expanded CaV2.1 subunit exhibit age-dependent motor deficits and lower expression of the CaV2.1 channels but no difference in calbindin staining of slices when compared to WT . This further supports our hypothesis of ataxia preceding cell death as these animals are ataxic in the absence of significant cell death. Future functional studies will be needed to understand alterations in Ca2+ signaling in PC cells from SCA6 mice.
Deranged Calcium Signaling in Non-Polyglutamine SCAs
Abnormal neuronal calcium signaling is not restricted to polyQ-expansion ataxias . In SCA5, mutant β-III spectrin (SPTBN2) is unable to stabilize the glutamate transporter, excitatory amino acid transporter (EAAT4) on the PC membrane (Table 1). This would allow extended glutamate activation in the parallel fiber-PC synapse and lead to excitotoxicity in SCA5 . Recent genetic evidence indicated that SCA14 is caused by mutations in protein kinase Cγ (PKCγ). PKCγ is highly expressed in PCs  (Table 1). Eighteen of the 22 identified mutations in PKCγ decrease the ability of PKCγ to phosphorylate and inactivate TRPC3 channels, which allow sustained calcium influx into the cell and results in elevated cytosolic calcium levels . These calcium elevations, if left uncontrolled, could become toxic and result in PC loss via excitotoxic cascades described above. The rest of the mutations suppress calcium influx likely by hyperphosphorylating and over-inactivating TRPC3 channels . Suppression of calcium signaling has been shown to be a cause of apoptotic cell death . Therefore, even though we have described excitotoxicity as one possible effect of SCA-associated gene mutations on calcium signaling and cell survival, suppression of calcium signaling could be equally as detrimental as increasing it.
Unlike most of the SCAs we have discussed above, SCA15 and SCA16 are a result not of excitotoxity but of suppressed cytosolic calcium signaling (Table 1). SCA15 is genetically linked to 5′ deletions, total deletions or missense mutation (P1059L) in the gene encoding ITPR1 and located in 3p26.1–p25.3 chromosomal region [14, 67]. Although initial studies of a SCA16 family suggested linkage to chromosome 8q22.1–24.1 , additional studies of the same family showed linkage to chromosome 3pter-p26.2 . Initially point mutation in the 3′ untranslated region of the contactin 4 gene (CNTN4) located in the same region was implicated [69, 70], but more recent analysis demonstrated that the real cause of SCA16 is haploinsufficiency of ITPR1 expression due to heterozygous deletion of exons 1 to 48 of the ITPR1 gene . Thus, SCA15 and SCA16 are the same disorder (SCA15/16), due to haploinsufficiency of ITPR1 (Table 1). Although, SCA15/16 is not polyQ disorder, aberrant calcium signaling is likely to play a role in pathogenesis given the high expression of ITPR1 in PCs , and their importance for stimulating BDNF production for PC dendritic morphology , and cerebellar plasticity . There are at least two possible physiological roles of these alterations on ITPR1 function and calcium homeostasis in PC. A gain of function of ITPR1s could occur if the mutation or deletion causes constitutive activity or increased sensitivity to activation of the mutated protein. A loss of function could also occur if the mutation or deletion suppresses ITPR1 activation and signaling. Affected patients of SCA15/16 and mice with spontaneous mutations in ITPR1 express less ITPR1 protein . As we await studies on the functional roles of the reported ITPR1 mutation and deletions in the pathogenesis of SCA15/16, we can only speculate that suppressed activity of ITPR1s in SCA15/16 may uncouple plasticity mechanisms in PCs. Indeed, ITPR1 knockout mice do not survive past postnatal day 20–23 and completely lack cerebellar LTD, although hippocampal LTD is unaffected and hippocampal LTP is partially intact [53, 71, 72, 73]. Thus, disruption of ITPR1 expression or function may result in cerebellar-specific phenotypes, as observed in SCA15/16 patients.
Deranged PC Calcium Signaling in Mouse Ataxic Mutants
The premise that abnormalities in PC calcium signaling cause PC death and cerebellar ataxia is supported by a study of moonwalker mice, which are mutant mice expressing a point mutation (T635A) in a conserved residue of the TRPC3 cation channel that is highly expressed in PCs and important for mGluR signaling [74, 75]. In this study, the moonwalker mice were found to exhibit a progressive loss of PCs and severe ataxia. The point mutation did not affect the expression pattern of the channel but did alter its mGluR-mediated gating by causing an abnormal occurrence of glutamate-induced channel opening and spiking at low mGluR-agonist concentrations. This effect was not seen in wildtype mice. Interestingly, the mutation is located at a site phosphorylated by PKCγ. An in vitro kinase assay showed that the mutated channel is unable to be phosphorylated , as reported in SCA14, which leads to hyperactivity of TRPC3 channels and sustained calcium influx into the cytoplasm . This is likely the cause of pathogenesis in moonwalker mice.
Concluding Remarks and the Prospects for Therapeutic Development
We propose that abnormal Purkinje cells Ca2+ signaling plays an important role in pathogenesis of SCA2 and many other SCAs. We argue that disruptions in Purkinje cell calcium signaling lead to initial cerebellar dysfunction and ataxic symptoms and eventually proceed to Purkinje cell death. Many brain areas affected in SCAs have afferent and efferent connections to the cerebellum, hence cerebellar dysfunction could result in dysfunction in these brain areas as well. We speculate that the earlier clinical symptoms in these ataxias result from enhanced cerebellar LTD and uncoupling of synaptic plasticity mechanisms in PC cells from intracellular Ca2+ signaling. These responses may be compensatory and aimed at reducing excitotoxic load on PCs, but the same synaptic plasticity changes may lead to initial ataxic phenotypes and onset of the disease. Ion channel modulators may have therapeutic value at this early symptomatic stage of disease, as has been recently demonstrated in mouse model of episodic ataxia type 2 . Eventually PCs succumb to excitotoxic cell death, leading to progression of the symptoms and eventual death. In the specific case of SCA2, deranged PC Ca2+ signaling results from pathological interactions between ATXN2exp and ITPR1 (Fig. 1). In other SCAs, different mechanims may be responsible for disruption of PC Ca2+ signaling (Table 1). The experimental test of the proposed hypothesis will require analysis of Ca2+ signaling in SCA mouse models.
Based on these ideas, we would like to propose that calcium blockers and stabilizers have potential utility for treatment of SCAs. Consistent with this idea, we previously demonstrated that long-term feeding with intracellular Ca2+ stabilizer dantrolene resulted in neuroprotective effect in mouse models of SCA2 and SCA3 [7, 13, 17]. Similarly, neuroprotective and LTD-inhibitory effects were demonstrated for a novel ITPR1 inhibitor T-558 . If deranged calcium signaling can be identified as a common underlying mechanism in all or most of the SCAs irrespective of the genes they are genetically linked to, then therapy directed at stabilizing calcium levels could be used for patients who have been diagnosed with SCAs with identified associated genes and also help others who have been diagnosed with SCAs yet to be linked to a particular gene. Controlled clinical evaluation of Ca2+ blockers and stabilizers in SCA patients is necessary to test clinical importance of these ideas. Although dantrolene and T-558 may not be optimal candidates for clinical testing, we hope that more specific and potent “Ca2+ stabilizers” will be developed in the future and evaluated in clinical trials with ataxia patients.
A.K. is a Howard Hughes Medical Institute Med into Grad Scholar. I.B. is a holder of Carla Cocke Francis Professorship in Alzheimer's Research and supported by the McKnight Neuroscience of Brain Disorders Award. The work on SCA2 and SCA3 was supported by the National Organization for Rare Disorders, National Ataxia Foundation, Ataxia MJD Research Project, and the National Institutes of Health grants R01NS38082 and R01NS056224.
Conflicts of interest
Authors declare no conflicts of interest related to this article.
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text:
Carrie “Mindy” Duncan, PhD
Mindy Duncan is the Director of the Center for Psychosocial Organization Studies in Columbia, Missouri. She has an MA in anthropology and a PhD in Public Affairs, both from the University of Missouri. Her research interests include the psychodynamics of organizational culture and change, nonprofit management, behavioral health organizations, aesthetics in organizations and entrepreneurship, and psychosocial research methods. Mindy has published in Organisational and Social Dynamics, Organization Studies, and Organization.

domain: psychology


Former Queens of the Stone Age bassist Nick Oliveri has unearthed his collaboration with Slash, “Chains and Shackles.”
The track was originally recorded for the Guns N’ Roses shredder’s self-titled debut solo album, which was released in 2010. It was included on various deluxe versions of the album but is now getting its own official release.
“I feel the Song is Hard Driving and it has the right amount of uncensored Dirt, filth, Sex, Drugs and Rock n Roll to be called a SLASH song!” Oliveri says. “Until Now, this track has only been available for those who happen to stumble upon it online streaming. But 13 Years later It is available through the Good People at [Heavy Psych Sounds] Records!”
You can listen to “Chains and Shackles” streaming now on YouTube. The song will also be included on Oliveri’s upcoming compilation N.O. Hits at All Vol. 8, due out January 19.
(Video contains uncensored profanity.)
Copyright © 2023, ABC Audio. All rights reserved.


Social network service (SNS) – the web-based interaction tool introduced in late 20th century – has become increasingly popular in modern life. The SNS providers’ capability of launching a ‘killer application’, i.e., an attractive interface that motivates user engagement and stickiness, plays a crucial role in surviving the keen competition in the SNS market, and the development of such a service requires rapid and continuous innovation practice. This study proposes an IDEA Diamond model that aims to help SNS providers effectively develop (through a well-defined process and systemized methods/tools) new services that can meet user needs and deliver exceptional user experience.
Chu, I-Chieh and Chou, Seng-cho T., "Idea Diamond: a Systematic Innovation Model for Social Network Services" (2009). ICEB 2009 Proceedings (Macau, SAR China). 125.


text:
Wolfe Research Starts American Woodmark (AMWD) at Peerperform
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Wolfe Research analyst Truman Patterson initiates coverage on American Woodmark (NASDAQ: AMWD) with a Peerperform rating.
Shares of American Woodmark closed at $101.82 yesterday.
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domain: economics


text:
"In honor of the Donald’s “Mother of All Bomb” (MOAB) attack on the Hindu Kush mountains Thursday, let me introduce MOAD. I’m referring to the “Mother of All Debt” crises, of course... The opening round is coming when Washington goes into shutdown mode on April 28, which happens to be Day 100 of the Donald’s reign."
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Senate Democrats are set to unveil a $1 trillion infrastructure plan and offer President Donald Trump their support if he backs it. The plan includes $180 billion to rail and bus systems, $65 billion to ports, airports and waterways, $110 billion for water and sewer systems, $100 billion for energy infrastructure, and $20 billion for public and tribal lands.
As the world's elite gather in Davos to decide for the minions what the world should look like, The IMF has taken a far dimmer view of global (and by that we mean Trumpian) economic growth than markets appear to be. In addition to slashing Brazilian, Mexican, and Saudi Arabian economic growth forecasts, Lagarde's lackeys are taking a cautious stance toward the policies of U.S. President-electDonald Trump, who takes office this week, assuming only a modest boost to the U.S. economy from his promise of fiscal stimulus.