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|What did Red Sox do during All-Star break?||07.17.14 at 12:40 am ET|
With Jon Lester and Koji Uehara the lone All-Star representatives in Minnesota for the Red Sox (besides the coaching staff), many members of the team had a chance to relax before the grind of the second half of the season gets underway. Some decided to share their activities on social media.
First baseman Mike Napoli had dinner with some long-time friends in the North End.
‘ Jen Royle (@Jen_Royle) July 16, 2014
|Shane Victorino: Traffic caused rehab schedule adjustment||07.13.14 at 9:29 pm ET|
When Shane Victorino‘s rehab assignment for the Portland Sea Dogs on Saturday was scratched, it seemed reasonable to assume that the outfielder may have suffered another setback, considering how his recent attempts to rehabilitate his injuries have been cut short due to discomfort.
That, however, was not the case. Victorino said that the reason he was scratched on Saturday had to do with the fact that he was stuck in traffic on his car ride from Boston to Portland.
“Yesterday was one of those things where the drive took me almost 2 1/2 hours to get an hour and a half still away,” Victorino said. “It was supposed to be a two-hour drive and it was going to turn into a three-hour-plus drive. They said that being in the car that long and then trying to play in the game was probably not the smartest decision. That was the only thing. I left as early as I could thinking that it wasn’t going to be that bad, but that was my first time ever trying to go down to Portland, Maine, and I understood with all of the beauty of the beaches and the coastline and the beauty of the weekend, it wasn’t the smartest choice.”
According to Victorino, he drove about as far as Salisbury, Massachusetts, before he called Red Sox physical therapist Dan Dyrek regarding his issues with traffic.
Victorino said that the scratch had nothing to do with any physical issues.
“That was the thing that happened yesterday,” Victorino said. “It wasn’t anything due to pulling me back from playing. The thing about at-bats is that’s the part that I’ve still got to get adjusted to. We’ll figure it out. I’m a professional hitter and I should figure it out sooner rather than later so I can’t sit here and worry about trying to get more at-bats. I’ve got to get ready to be physically ready to go and continuously play. Everything is going according to plan.” Read the rest of this entry »
|Closing Time: Clay Buchholz hurls complete-game gem, Red Sox win last game of first half||07.13.14 at 5:30 pm ET|
It looks like Clay Buchholz might have finally figured things out.
Buchholz turned in his best of the start of the season Sunday against the Astros, going nine innings and allowing three hits and no runs with a career-high 12 strikeouts. It led the way in the Red Sox‘ 11-0 win over the host Astros.
It was the first time since Sept. 15, 2013, against the Yankees that Buchholz did not allow an opponent to score. The outing also marked since May 11 against the Blue Jays that Buchholz went more than seven innings.
Buchholz threw his last complete game on Aug. 10 against the Indians, when he allowed two hits and one run (on a home run), with six strikeouts.
Since coming off the disabled list on June 25 and heading into Sunday, Buchholz posted a 3.92 ERA with an opponent batting average of .230, an opponent on-base percentage of .260, 11 strikeouts, one walk and nine earned runs in 20 2/3 innings pitched.
Also highlighting the Red Sox win was Brock Holt‘s five hits.
WHAT WENT RIGHT FOR THE RED SOX
– Holt continues to be the savior of the 2014 Red Sox and adding to his list of conquests. Against Astros starter Brad Peacock, Holt hit a leadoff home run into the upper deck of Minute Maid Park to give the Red Sox a quick 1-0 lead in the first inning. Holt went 5-for-6. Heading into Sunday, Holt was hitting .277/.306/.340 as the first batter of the game.
|Finally: Mike Carp takes advantage of long-awaited opportunity with walkoff||07.10.14 at 11:44 pm ET|
For nearly a month, first baseman Mike Carp sat on the couch of the Red Sox clubhouse in pain. The pain was not so much the result of the broken bone in his right foot that left him in a walking boot, but instead from his inability to help the team in situations that normally called for his skill set. There was nothing Carp could do except sit and cheer on his teammates, despite his desire to help the team through its struggles. As the team struggled through the month of June, winning 12 and dropping 16 games, all Carp could do was wait until his foot healed.
“Some of the nights, you almost have to turn the TV off when those situations come because you can’t be there to help,” Carp said. “It hurts so bad to see your brothers struggling and want to be able to contribute and fill your role.”
On Thursday, Carp finally got that opportunity and made the most of it, delivering a walkoff single in the bottom of the 10th that sent the Red Sox to a 4-3 victory.
After Daniel Nava reached on a pinch-hit walk to lead off the 10th, Mookie Betts advanced Nava to second base with a sacrifice bunt. White Sox manager Robin Ventura decided to intentionally walk Stephen Drew, owner of a .128 batting average, with David Ross due to hit next. Instead of Ross, Red Sox manager John Farrell decided to pinch-hit Carp. With the winning run at second base in the form of Nava and the score tied in the 10th inning, Carp felt that he had a feel for how White Sox reliever Ronald Belisario would attack him.
“I figured that [Belisario] was going to come in,” Carp said. “He attacked me heavily the whole series. I only got three at-bats, but after he went away on the 1-2 pitch, I assumed something would be out over the plate.”
|Closing Time: Red Sox claim second straight walkoff win thanks to Mike Carp||07.10.14 at 7:33 pm ET|
Second straight walkoff. Second straight win. With one out in the 10th inning, Mike Carp singled in Daniel Nava from second base, handing the Red Sox a 4-3 win over the White Sox. The heroics helped make up for an uneasy ninth inning from Koji Uehara.
Conor Gillaspie, who came into the four-game series with one home run, hit his third long ball since arriving at Fenway Park this week. This time the two-run, ninth-inning blast off Uehara took a win away from Sox starter Jon Lester, tying the game at 3-3.
Lester continues to build up more reasons why someone, whether it is the Red Sox or not, will give him a massive contract. The lefty turned in one of his strongest starts of the season, going seven innings and allowing seven hits, no walks and one run and striking out 12 while throwing 76 of his 105 pitches for strikes (72.3 percent).
Throughout the outing, Lester displayed strong command of his entire arsenal, mixing in a terrific cutter, changeup and curveball to keep White Sox hitters off balance. The only blemish on Lester’s day came in the first inning when Jose Abreu knocked in Adam Eaton from first base after left fielder Jonny Gomes slightly misplayed a low fly ball while slamming into the Green Monster.
Lester’s stellar performance on Thursday left him with a 2.65 ERA, a 1.14 WHIP, a .243 opponent batting average, 134 strikeouts and 29 walks in 129 innings pitched over 19 starts. The performance marked the 20th double-digit strikeout game of Lester’s career and the third of the 2014 season. After Thursday’s performance, Lester has the third most games of 10 or more strikeouts, trailing Pedro Martinez (72 games) and Roger Clemens (68 games).
WHAT WENT RIGHT FOR THE RED SOX
– Having not collected a hit through five-plus innings, the Red Sox put two runners on base through walks from White Sox starter Jose Quintana. With the Red Sox‘ first opportunity to score their first run of the game, Jackie Bradley Jr. stepped up to the plate and delivered, breaking up the Quintana’s no-hitter and shutout. Bradley has hit well in July thus far, hitting .353/.421/.471 with two doubles and three runs in five games coming into Thursday.
– David Ortiz knocked in two runs in the sixth inning to push the Red Sox ahead 3-1. Ortiz has started off the month of July hot, hitting .360/.469/.560 with five doubles, four RBIs, six walks, one strikeout and two runs.
WHAT WENT WRONG FOR THE RED SOX
– Mookie Betts turned in an 0-for-3 performance. While Betts has provided a spark for the Red Sox, he has hit .217/.258/.379 in eight games in the majors.
|Red Sox not in talking mood about ‘shared frustration’ of offensive woes||07.08.14 at 12:11 am ET|
The Red Sox very clearly know where they stand in the race for the American League East. They know that they stand in last place at 39-50, 10 games behind the first-place Orioles. The Red Sox know that with every loss, with every lackluster performance against a mediocre pitcher, their chances at reaching the postseason to defend their World Series championship look gloomier.
The growing unlikelihood of a playoff berth gets more real by the day. It stares them right in the face every day in the form of the standings on the Green Monster scoreboard.
“We don’t need to think about [the standings],” said outfielder Jackie Bradley Jr. “We can see it. Every single day we go on the field, we see it out there in left field. I don’t think it’s something that we’re too much focused on. We’re trying to get back to winning, and if you win, it’ll all kind of take care of itself.”
The only problem? The team is grasping for answers as to why it can only muster one hit off a pitcher by like White Sox hurler Scott Carroll, owner of a 4.52 ERA, 1.52 WHIP and .296 opponent batting average.
“I don’t have any answers,” said utility man Brock Holt. “We’ve got guys up and down the lineup that know what to do and have done it before, but we’re just not getting it done right now. It’s not from lack of work. We’re going out and doing what we’re supposed to do. We’re just not getting the results that we want.”
|Closing Time: Red Sox lineup comes up empty against another little-known foe||07.07.14 at 10:44 pm ET|
The Red Sox consistently have made back-of-the-rotation starters look like bona fide aces, going into Monday’s game hitting .245 with a .322 OBP and .369 slugging mark while ranked second to last in the American League with 3.8 runs per game.
Here are some of the pitchers the Red Sox have faced since their seven-game winning streak concluded on June 2:
Edwin Jackson (Cubs): 5.05 ERA, 1.52 WHIP, .281 opponent batting average, 5-8 record in 18 starts
Kyle Gibson (Twins): 4.17 ERA, 1.25 WHIP, .249 opponent batting average, 7-7 record in 17 starts
Vidal Nuno (Yankees): 5.42 ERA, 1.44 WHIP, .282 opponent batting average, 2-5 record in 14 starts
Kevin Correia (Twins): 4.95 ERA, 1.44 WHIP, .298 opponent batting average, 4-10 record in 17 starts
T.J. House (Indians): 4.24 ERA, 1.46 WHIP, .307 opponent batting average, 1-2 in seven starts
Drew Smyly (Tigers): 3.89 ERA, 1.37 WHIP, .267 opponent batting average, 4-8 record in 14 starts
Scott Carroll (White Sox): 4.57 ERA, 1.52 WHIP, .298 opponent batting average, 2-5 record in eight starts
Against the Red Sox, these seven pitchers have a 1.32 ERA and a 0.965 WHIP while allowing seven runs, striking out 30 and walking 12 batters in 47 2/3 innings. Good teams beat good pitchers; bad teams lose to bad pitchers. Right now, it’s not difficult to identify into which camp the Red Sox fall.
WHAT WENT WRONG FOR THE RED SOX
– Clay Buchholz once again showed flashes that his stint on the disabled list did him well. Although he showed glimpses of what made him one of the top pitchers in baseball during the first half of the 2013 season, Buchholz nonetheless struggled with execution, evidenced by the two mammoth home runs he gave up to Adam Dunn and Dayan Viciedo.
Dunn hit his first career home run at Fenway Park in the second inning. The homer was the 453rd of Dunn’s career, moving him past Red Sox legend Carl Yastrzemski for sole possession of 35th place for most home runs all-time. Heading into Monday, Dunn was 0-for-7 in his career against Buchholz.
Viciedo – rumored to be on the trade market — showcased his power at Buchholz’s expense. The at-bat was a prime example of failure to execute pitches when Buchholz needed to. After starting the at-bat 0-2, Viciedo worked the count back to 3-2 and subsequently axed an 89 mph cutter into the deepest part of Fenway Park — the triangle in center field. The three-run, fourth inning home run from the 25-year-old put the White Sox on top 4-0.
– The Red Sox now have been shut out nine times, fourth most in the AL. They were shut out just 11 times in all of 2013.
WHAT WENT RIGHT FOR THE RED SOX
– The Sox did not get no-hit, thanks to a third-inning single by A.J. Pierzynski and an eighth-inning single by Jackie Bradley Jr.
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We’re taking a break from revolvers that I own and looking at some cool wheelguns from SHOT Show. First on the list is the Korth Sky Marshal, a 6 shot, medium frame revolver chambered in 9mm that doesn’t require the use of moonclips.
For a Korth, it’s actually going to be reasonably priced, and should retail for around $1,000 – like I said, reasonable for a Korth. But what’s really important is how the gun shoots, and I’m happy to report that it shoots very well. The factory trigger is excellent, better than a lot of “tuned” actions that you can get, and at least in the limited time I had with the gun it was accurate enough for the task at hand. A further review to really see what it’s capable of would be a valuable investment of my time.
There are some issues with the gun, however. It’s a 2 inch medium frame revolver, but it has full size, finger grooved rubber stocks on it that are just enormous. Even with an alloy frame, 9mm recoil isn’t exactly thunderous, so the over large stocks are an unnecessary feature on a carry gun. That leads us to our second issue: this is 1000 dollar gun that won’t be widely adopted, which means that finding replacement grips, holsters, and other accessories won’t be easy. And that leads us to our final problem, which is the existence of the Ruger LCR. Because if you’re buying a carry gun, the LCR will do nearly everything the Korth does, but costs 350 bucks instead of 1000.
However, what’s really interesting about the Sky Marshal is its moonclip-free ejection system. The rounds headspace off the cylinder, and when it’s time to eject spent cases, pressing the ejector rod pops a small blade out of the star; that blade catches the case rim and extracts the spent shells. It looks more robust than the mechanism on the old 547, but the volume shooter in me wonders how it will hold up to hard use.
But at the end of the day, none of that matters. Because this an affordable Korth revolver, chambered in 9mm, and I need one.


Vets on Frets is a band formed from the non-profit Guitars for Vets, which has been sharing the healing power of music by providing free guitar lessons to veterans since 2007. Vets on Frets consists of 6 guitarists including 2 Guitars for Vets instructors and 3 graduates of the program.
Performing for almost a decade their repertoire includes 60s and 70s rock, folk, as well as country and western, and they’ve recently started writing their own songs.
Member of Vets on Frets, Dan Proud, has been playing and writing music since the 1960s, is an instructor for Guitars for Vets and wrote the music to their recent song, “Swept Away”. Dan joins Friday Buzz host Jonathan Zarov to talk about Guitars for Vets, Vets on Frets, and “Swept Away”.
(Images Courtesy of Vets on Frets)


According to Mr. Kapil Bhati, Managing Director, Robbins India, "We will look towards higher utilization of our equipment's through the advanced technological offerings of our TBMs. Both our EPB, Advanced Double Shield Crossover for mixed ground conditions, and Single Shield TBM's have advanced flexible design, which enables the cutter head to be lowered in pieces through the launching shaft, with provision for full assembly of the unit below the surface."
Added Mr Bhati, "Since gathering of accurate geological data continues to be a constraint in India, we will engage with geological agencies and contractors to gather the right data so that we can orient our products and services accordingly. We have a highly skilled team of geologists, TBM Operators, Technicians, Ring builders and Grouting experts."
"Deployment of TBMs is very cost intensive for contractors, and they have concerns of less optimum utilization of the machines. To make owning and operating our TBMs cost-effective, we are offering options of leasing and buyback of the units. And as part of our services to the contractors, we will look to take up stalled projects and deliver the right product support for timely completion of the jobs."


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Today Ponthieu is a Pays , a kind of voluntary planning region without the quality of an independent regional body within the meaning of the law of February 4, 1995 or in the sense of the subsequent regulation in the Loi Pasqua (LOADDT) of June 25, 1999. The area is pretty much between the Somme and the Authie and is bounded to the west by the Marquenterre . Ponthieu includes the cantons of Crécy-en-Ponthieu , Nouvion-en-Ponthieu and Ailly-le-Haut-Clocher .
Count Arnulf I of Flanders managed to expand his dominion significantly by conquering large parts of Artois , Ponthieu, Amiens and Ostrevant . He took advantage of the internal French disputes between Charles the Simple and Robert I, as well as later those between Ludwig IV and his barons. After his death in 964, these areas were lost again until his successor Arnulf II came of age (976).
The county then remained in the Carolingian count family until 1100. In that year it went by marriage to Robert of Bellême, 3rd Earl of Shrewsbury , Count of Alençon . Abbeville became the capital of Ponthieu around 1130.
In 1221 Ponthieu came back through marriage to Simon von Dammartin , from whom the French King Louis VIII took it for some time in 1228, then to Simon's daughter Johanna (Jeanne), who in 1237 was King Ferdinand III. of Castile married. Their daughter, Eleanor of Castile , married the later English King Edward I in 1254 , who thus came into the possession of Ponthieu. The land also remained in the possession of Edward II and Edward III .
King Philip VI of France seized Ponthieus in 1337 with the beginning of the Hundred Years War and gave it to Jacob of Bourbon , Count of La Marche . Edward III. took the county back into English possession after the Battle of Crécy , which took place in Ponthieu in 1346. 1367 came Ponthieu in the possession of the French king Charles V . In 1417 it was conquered again by the English; Henry VI. gave it to the Duke of Burgundy in 1437 . After the death of Charles the Bold in 1477, Ludwig XI. Ponthieu finally in itself.

domain: history


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Bow Hammer Connection @ November MusicNovember Music has commissioned a new work from Faegre titled Dance Suite in G, with movements based around contemporary dance forms (Dubstep, Drum 'n' Bass, Acid House, etc.). The work will be premiered as part of a new project called "Bow Hammer Connection", featuring Isa Goldschmeding as violinist, Micha de Kanter as sound designer, and Faegre as composer/drummer. For more info watch the November Music site for next season's program.
New Music Jam ClipsShort video excerpts from the rehearsal room are now posted with improvisations around 6 contemporary compositions: Steve Reich's Piano Phase, Hans Abrahamsen's Schnee, Louis Andriessen's De Snelheid, Giacinto Scelsi's String Quartet No. 4, David Lang's killer and Donnacha Dennehy's Glamour Sleeper. Watch the videos here.
New Music Jam TrailerA video trailer is now online for the Edge Ensemble's latest production: the New Music Jam. This project explores the language of contemporary composers through improvisation, with the first edition focusing on the music of Louis Andriessen and Giacinto Scelsi. Watch the trailer here.
Dirt to Gold on WQXR's Q2WQXR's contemporary music program Q2 is broadcasting a live performance of Dirt to Gold by the New Jersey Symphony Orchestra and conductor JoAnn Falletta two times this week. The program also features works by Steve Mackey, Shuying Li, Reinaldo Moya, and Luke Carlson. Tune in October 20th at 8pm (EST), October 25th at 12pm, or stream the audio at this link.
Music for Bars w/ SDHDutch percussion group Slagwerk Den Haag has commissioned Faegre to compose and curate a new project called Music for Bars for 3 percussionists and 3 dancers. This production is a 60-minute amplification of sonic, physical, and social elements of The Bar, exploring and breaking the boundaries of "normal" within these three areas. Music for Bars will do a 10-bar tour around the Netherlands in Autumn 2016. See events for performance dates.
NJSO Cone InstituteFaegre has been chosen to participate in the 2015 New Jersey Symphony Orchestra Edward T. Cone Composition Institute. The program will culminate on July 16th with a concert by the NJSO premiering a new version of Dirt to Gold. For more details see the press release.
Dirt to Gold @ CabrilloThe Cabrillo Festival of Contemporary Music will premiere a new version of Faegre's Dirt to Gold this August through their Conductors/Composers Workshop. Learn more about the concert.
NYYS First Music CommissionFaegre was selected for the New York Youth Symphony's First Music commission for next season. His new work for the orchestra will be premiered at Carnegie Hall on 29 May 2016. Read the full press release here.

domain: entertainment


text:
Also found in: Thesaurus, Wikipedia.
Any of several deciduous or evergreen shrubs of the genera Leucothoe, Lyonia, and Pieris, having clusters of small bell-shaped white or pink flowers.
Switch to new thesaurus
|Noun||1.||fetterbush - ornamental evergreen shrub of southeastern United States having small white bell-shaped flowers|
|2.||fetterbush - showy evergreen shrub of southeastern United States with shiny leaves and angled branches and clusters of pink to reddish flowers that resemble an umbel|
genus Lyonia, Lyonia - evergreen or deciduous shrubs or small trees of United States to Antilles and eastern Asia to the Himalaya

domain: geography


text: Saving for Retirement This calculator can help you estimate how much you may need to save for retirement. You are viewing this website at a small screen resolution which doesn't support calculators. Click here to view this calculator. Share | Have A Question About This Topic? Name Email Address Message Thank you! Oops! Related Content Retirement Plan Detectives A couple become Retirement Plan Detectives, searching records from old employers. Retirement Realities Many pre-retirees can become focused on the “ideal” retirement, but turning that dream into a reality can be tricky. This content piece was written to help clients manage their expectations while maintaining optimism for the future. Social Security: The Elephant in the Room Some people wonder if Social Security will remain financially sound enough to pay the benefits they are owed.

domain: economics


text:
3 edition of The exploited seas found in the catalog.
The exploited seas
2001 by International Maritime Economic History Association in St. John"s, Nfld .
Written in English
Includes bibliographical references.
|Other titles||Marine environmental history|
|Statement||edited by Poul Holm, Tim D. Smith, and David J. Starkey.|
|Series||Research in maritime history,, no. 21|
|Contributions||Holm, Poul., Smith, Tim D., Starkey, David J. 1954-, International Maritime Economic History Association.|
|LC Classifications||SH211 .E86 2001|
|The Physical Object|
|Pagination||xix, 216 p. :|
|Number of Pages||216|
|LC Control Number||2003386301|
stock preservation, and understanding stock–recruitment relationships. The book mainly focuses on wild fish and presents a balanced review of worldwide information on the condition of marine exploited fish with broad geographic/ecological range including dif-ferent life stages of species. Skupinu založil v škótskom Edinburghu bývalý vojak Wattie začiatku skupina The Exploited mala žánrovo bližšie k Oi!, neskôr sa zamerala viac na street až hardcore žne od roku , v období vydania albumu Death Before Dishonour, sa ich hudobný štýl priblížil k žánru crossover thrash.. V marci roku skupina podpísala zmluvu s hudobným.
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The Exploited Seas Book Description: The book combines the approaches of maritime history and The exploited seas book science to explore the evolution of life-forms and eco-systems in the ocean from a historical perspective, in order to establish and develop the sub-discipline of The exploited seas book environmental history.
The book combines the approaches of maritime history and ecological science to explore the evolution of life-forms and eco-systems in the ocean from a historical perspective, in order to establish and develop the sub-discipline of The exploited seas book environmental history.
The Exploited Seas New Directions for Marine Environmental History Edited by Poul. Get this from a library. The exploited seas: new directions for marine environmental history. [Poul Holm; Tim D Smith; David J Starkey; International Maritime Economic History Association.; Census of Marine Life (Program);] -- The book combines the approaches of maritime history and ecological science to explore the evolution of life-forms and eco-systems in the ocean from a historical.
In a way the book reminds me of Jane Urquhart's novel Away, impossible love set in a seafaring location. If you feel - as I do - Wuthering Heights is a romantic novel, you'll probably love The Seas.
So much about these books is similar, enough I have to wonder how much influence Brontë's book had The exploited seas book Hunt's. They feel so alike/5(7). Liverpool University Press is the UK's third oldest university press, with a distinguished history of publishing exceptional research since The book combines the approaches of maritime history and ecological science to explore the evolution of life-forms and eco-systems in the ocean from a historical perspective, in order to establish and develop the sub-discipline of marine.
The narrator of The Seas lives in a tiny, remote, alcoholic, cruel seaside town. An occasional chambermaid, granddaughter to a typesetter, and daughter to a dead man, awkward and brave, wayward The exploited seas book willful, she is in love (unrequited) with an Iraq War veteran thirteen years her senior.4/5.
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Exploited by Emma Jackson is an extremely emotive, heart-wrenching, but also inspirational true story of sex trafficking in the United Kingdom. It tells of Emmas experience of being groomed and sex trafficked by a child sex gang, and her bumpy road to recovery/5.
A story of the wild voyages of the irrepressible Captain Buckingham in Southern seas."Never has the peculiar brand of humor which The exploited seas book America affords been more skillfully exploited than by Arthur Colton in The Belted Seas It is a joyous book, and he were a hardened reader indeed who would not chortle with satisfaction over Kid Saddler's 3/5(1).
The High Seas Are Being Exploited. Exploration Must Keep Pace. Republish The seas are under threat from all sides: while the toxic cocktail of industrialization and global ocean mixing brings contaminants from factories past and present to waters around the world, more acute threats like intensive fishing and seafloor mining wield.
Rarely curious about the waters from which life on earth rose, humans have long exploited the seas for food, transport, mining, recreation, and war.
Until recently, it was assumed that ocean resources were inexhaustible, especially the bounty of fish and marine mammals, and that garbage and chemical waste dumped into oceans would just disappear.
The exploited seas: new directions for marine environmental history / edited by Poul Holm, Tim D. Smith and David J. Starkey ; International Maritime Economic History Association/Census of Marine Life International Maritime Economic History Association St.
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K likes. Community Fan Page to share Exploited Photos, Artwork, Music and Ink. No Haters Please!Nazi Punks Fuck Off. Cheers!/5(21). Book Description. Exploring the themes of the human relationship with the marine environment and the ways in which the peoples of Northern Europe have experienced and exploited their seas, this book reveals how human perception of the northern seas has changed over time.
That book was thrillingly alive with stories of how Europe and Africa evolved through their seafaring history, but his new title is an even grander adventure, beginning with the Pacific Ocean in Author: Alexander Larman.
Symphony of the Seas, exploited by the American company Royal Caribbean International is the biggest cruise ship of the world. Built at the. Human activities have taken place in the world's oceans and seas for most of human history.
With such a vast number of ways in which the oceans can be used for trade, exploited for natural resources and fishing, as well as concerns over maritime security, the legal systems regulating the rights and responsibilities of nations in their use of the world's oceans have long been a crucial part of.
Seas The Complete Guide This is a Wikipedia book, a collection of Wikipedia articles that can be easily saved, imported by an external electronic rendering service, and ordered as a printed book. The End of the Line: How Overfishing Is Changing the World and What We Eat is a book by journalist Charles Clover abouta former environment editor of the Daily Telegraph (London) and now a columnist on the Sunday Times (London), describes how modern fishing is destroying ocean ecosystems.
He concludes that current worldwide fish consumption is : Non-fiction. The labor can be so grueling at Amazon that one worker in Kentucky said she needs four pain meds just to get through the workday. It took just three days of working full time at an Amazon. By Pierre Claude Reynard, Published on 01/01/ Title.
Review of The Exploited Seas: New Directions for Marine Environmental History, edited by Poul Holm, Tim D. Smith, David J. StarkeyAuthor: Pierre Claude Reynard.
Condition and Health Indicators of Exploited Marine Fishes provides a comprehensive introduction to the study of fish condition that will assist advanced undergraduate and postgraduate students, researchers and professionals, working in marine ecology and biology, fisheries biology, environmental sciences and fish pathology.
All universities. Exploring the themes of the human relationship with the marine environment and the ways in which the peoples of Northern Europe have experienced and exploited their seas, this book reveals how human perception of the northern seas has changed over time.4/5(3).
Exploited definition, to utilize, especially for profit; turn to practical account: to exploit a business opportunity. See more. The deep sea as a target for exploitation The deep sea has always been an important area for human exploitation: resources such as fish, oil and gas have been taken from the sea for many decades, and more recently the marine environment has been targeted as a source of renewable energy.
A few things you can do to get started today: Switch to compact fluorescent light bulbs, take the stairs, and bundle up or use a fan to avoid oversetting. “ The Mortal Sea is highly pertinent to urgent matters before us now.
If in the late s the men who worked the sea for their livelihoods could see that creatures were being fished to extinction, while scientists in the employ of business interests argued that the seas were endlessly replenishable, today it is the other way around. Exploring the themes of the human relationship with the marine environment and the ways in which the peoples of Northern Europe have experienced and exploited their seas, this book reveals how human perception of the northern seas has changed over g on a wide variety of sources, from Denmark and Britain to Norway, Finland and Germany, The Baltic and the North Seas is an insightful.
The rich wildlife of the coastal zone is heavily exploited, including endemics, despite piecemeal laws that seek to protect threatened and endangered species.
World Seas: An Environmental Evaluation, Second informed comments on major trends, problems and successes, and recommendations for the future. The book is an invaluable worldwide. Top Scams Top Scams Information about common scams.
their charitable inclinations are more easily exploited by scammers pretending to be persons in need of sympathetic helping hands. Listed. Relations between China and Vietnam have been relatively smooth over the past year, but Beijing's announcement that it would deploy a deep-water oil rig some 20 nautical miles south of the disputed Paracel Islands has rekindled May 3, Beijing issued a notice that China National Offshore Oil Corp.'s oil rig was to carry out drilling operations from May 4 to Aug.
5 and that all. Beat the Bastards is the seventh album by the Scottish band The Exploited, released in through Rough Justice song "They Lie" was covered on End of Disclosure by : Crossover thrash, thrash metal hardcore punk.
Visit to get more information about this book, to buy it in print, or to download it as a free PDF. Exploration of the Seas: existing and new mechanisms for interagency support should be.
The Exploited are a hardcore punk band from Edinburgh, Scotland, formed in by Stevie Ross and Terry Buchan and later joined by his brother Wattie Buchan. They signed to Secret Records in and their debut album Punks Not Dead was released that year. The band maintained a cult following in the s among a working class and skinhead.
Culminating 10 years of photographic prowess, Alex Mustard has joined forced with Callum Roberts to produce the Secrets of the Seas: A Journey Into the Heart of the book features world-class images from Mustard, who is both a renowned photographer and marine biologist.5/5. Life itself arose from pdf oceans.
The ocean is vast and covers million square miles, some 72 per cent of the Earth's surface. The ocean has always been an important source of food for the.World Seas: Download pdf Environmental Evaluation, Second Edition, Volume Two: The Indian Ocean to the Pacific provides a comprehensive review of the environmental condition of the seas from the Indian Ocean to the Pacific.
Each chapter is written by experts in the field who provide historical overviews in environmental terms, current environmental.Shop Official The Exploited Merch, Vinyl Records, Shirts and More.
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domain: literature


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Wine Barrel Ring Bottle Holder - The Rocket - Made from salvaged California wine barrel rings - 100% Recycled!
Handcrafted from retired Napa valley wine barrel rings in the heart of California wine country, our exquisite bottle holder collection will showcase your home or business with a rustic elegance unique to California wine culture. Available in a wide variety of designs and customizable options, our extensive yet singular collection is sure to be the most functional piece of art you own!
"The Rocket" wine bottle tray is a whimsical way to display your favorite bottle of wine. Crafted from recycled wine barrel rings, each piece is hand cut and welded to look like a firing rocket. Modern and chic yet wonderfully rustic. Completely made from recycled wine barrel rings. This is functional art and a delight to have.
The rings are all bent by hand (you should see our forearms) and then carefully welded together. Each one will be slightly different as we never make the same thing twice.
Picture this in your wine cellar or even in your beautiful garden or on the patio. Big enough to make a statement, it's small enough to be in a small entry way as well, bringing the charm of wine country into your home, and is the perfect touch behind a couch.
We do make these slightly smaller and also much larger. If you need a specific size just let us know and we will be happy to create it for you. We love a challenge! Also we have a huge variety of different styles if you need something specific.
100% recycled and reclaimed Napa wine barrel rings!
DIMENSIONS: approx. 12"H x 6"W x 8"D
INCLUDES: One wine bottle holder.
MATERIALS: Retired Napa wine barrel rings.
SHIPPING: We ship internationally! Additional shipping charges are required for orders to Alaska, Hawaii, Puerto Rico and all international destinations. Send us a message with your address for an estimate. Shipping discounts are available for multiple purchases.
CUSTOM DESIGN: Don’t see quite what you’re looking for? We can adapt our designs or create new custom work based on your ideas. Let me know! I love a fun project!
It’s pretty amazing what happens in our shop. Thanks for visiting!
All our products are carefully handmade using 100% recycled materials. They are individually handcrafted, one of a kind creations, and not factory manufactured. It is therefore quite difficult to make identical items. Our attentive artisans make every effort to create only the best from materials with natural variations that should not be misconstrued as flaws. These make each piece of a handmade product charming and unique. The pictures may not be identical to the product you receive. It's probably even more awesome!
We Also Recommend
Grapevine Magnetic Knife Rack - Medietas - Made from retired California grapevines. 100% Recycled!
Wall Mounted Wine Bottle & Cork Display - Kala - Retired Napa Barrels with custom personalized engraving!
Wine Barrel Handrails - Barana - retired California wine barrel oak staves 100% Recycled!
Wine Barrel Ring Pendant Light - Lavaliere - Made from Retired California wine barrel rings 100% Recycled!

domain: design


text:
- Latest available (Revised)
- Original (As enacted)
This is the original version (as it was originally enacted). This item of legislation is currently only available in its original format.
(1)The Board may make regulations—
(a)as respects the conduct of appeals against assessments and decisions on claims under Part III of the Finance Act 1965,
(b)entitling persons, in addition to those who would be so entitled apart from the regulations, to appear on such appeals,
(c)regulating the time within which such appeals or claims may be brought or made,
(d)where the market value of an asset on a particular date, or an apportionment or any other matter, may affect the liability to capital gains tax of two or more persons, enabling any such person to have the matter determined by the tribunal having jurisdiction to determine that matter if arising on an appeal against an assessment, and prescribing a procedure by which the matter is not determined differently on different occasions,
(e)authorising an inspector or other officer of the Board, notwithstanding the obligation as to secrecy imposed by virtue of this or any other Act, to disclose to a person entitled to appear on such an appeal the market value of an asset as determined by an assessment or decision on a claim, or to disclose to a person whose liability to tax may be affected by the determination of the market value of an asset on a particular date, or an apportionment or any other matter, any decision on the matter made by an inspector or other officer of the Board.
(2)In paragraphs (d) and (e) of subsection (1) above references to market value shall, in relation to land in Great Britain, include references to current use value; and the Capital Gains Tax Regulations 1967 shall, except where the context otherwise requires, be construed accordingly. This subsection shall be construed in accordance with Schedule 14 to the Finance Act 1967.
(3)Regulations under this section may contain such supplemental and incidental provisions as appear to the Board to be expedient including in particular—
(a)provisions as to the choice of the Commissioners, whether a body of General Commissioners or the Special Commissioners, to hear the appeal where, in addition to the appellant against an assessment, or the claimant in the case of an appeal against the decision on a claim, and in addition to the inspector or other officer of the Board, some other person is entitled to be a party to the appeal, and
(b)provisions corresponding to section 81 of the Capital Allowances Act 1968 (procedure on apportionments where more than one body of General Commissioners has jurisdiction), and
(c)provisions authorising the giving of conditional decisions where, under section 47 of this Act, or under any provision in the Finance Act 1965, questions on an appeal against an assessment or a decision on a claim may go partly to one tribunal and partly to another.
(4)Regulations under this section—
(a)shall be made by statutory instrument subject to annulment in pursuance of a resolution of the House of Commons, and
(b)shall have effect notwithstanding anything in this Act.
Latest Available (revised):The latest available updated version of the legislation incorporating changes made by subsequent legislation and applied by our editorial team. Changes we have not yet applied to the text, can be found in the ‘Changes to Legislation’ area.
Original (As Enacted or Made):The original version of the legislation as it stood when it was enacted or made. No changes have been applied to the text.
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domain: finance


text:
Kasauli – a small town in Himachal Pradesh that is known for its magnificent views, majestic hills, and amazing food. Kasauli is one of the best places if you want to enjoy your meals with amazing views. From cafes to restaurants, Kasauli is full of places that offer mouth-watering dishes, exquisite bars, and views to go with your food. The restaurants in Kasauli offer both veg and non-veg dishes from a range of cuiyanisines such as Chinese, Indian, Thai, and more.
Kasauli is known for food that is flavorful, rich in heritage, and lip smacking delicious. The food here will keep you on your toes and will make you want to come back. While the place is full of cafes and restaurants, there are a few that cannot and should not be missed. We have listed a few of the most popular restaurants in Kasauli that you should definitely visit.
7 Best Restaurants In Kasauli
1. Cliff Houzz Restaurant and Bar
If you are a hardcore vegeterian and looking for place that serves exquisite veg food, visit Cliff Houzz restaurant and bar when traveling in Kasauli. One of the top restaurants in Kasauli, the restaurant offers an extensive vegetarian menu to their guests. The minimalist decor of the restaurant makes this place quite a favorable place amongst the travelers who are looking for some solace while they dine-in. The ambience of the restaurant reflects a rustic charm owing to the wooden decor and furniture. Visit this place to enjoy a scrumptious meal with majestic views.
2. Hangout, Rooftop Bar and Restaurant
Sparkling lights, decor to attract youngsters, and a bar that serves fine liquor to their customers; Hangout, bar and restaurant is undoubtedly one of the most popular restaurants in Kasauli. Housed in the Hotel Kasauli Regency, this place has comfortable seating, offers a view of the hills, and amazing DJ performances. The service of the staff is impeccable which will make your trip to this restaurant memorable. Along with the delicious food, and amazing cocktail options, the place also offers a great collection of music ranging from Bollywood to classic jazz.
3. Ross Common Restaurant
Ross Common Restaurant is far from being a common restaurant. This is one of the most popular restaurants in Kasauli and is located in the Ross Common hotel which is also very popular amongst tourists and travelers. Owing to its quick service and amazing food, the restaurant has made its name as one of the top restaurants in Kasauli. The restaurant has a nice quaint setting with bright lights and chic decor along with wooden chairs and tables. The casual setting of the restaurant coupled with delicious food makes this restaurant a must-visit.
4. Shack Restaurant
If you like to dine-in in cosy settings and cute decor, then Shack is the best option for you. Do not let the name of the restaurant trip you off; it looks nothing like a shack. The place has a really simple and subtle decor and has a really cosy vibe that makes anyone fall in love with this place. The restaurant offers quick service, delicious meals, and views to go with your food. Come here and enjoy your food within a lovely setting and impeccable service by courteous staff.
Suggested Read: 10 Places To Visit In Kasauli For Nature Lovers
5. Kasauli Regency Restaurant
Who doesn’t like their food with mesmerizing views, live music, and a couple of drinks. Kasauli Regency is one of the most visited and recommended restaurants in Kasauli owing to its amazing ambience, rooftop seating, and delicious food. This is the perfect place to spend some quality time with your near and dear ones while gorgin on scrumptious meals and basking in the glory of nature. This place also offers live music sessions and DJ nights to entertain their guests while they sip on their favorite drinks from the bar.
Suggested Read: Your Guide To Shopping In Kasauli For A Fun Retail Therapy
6. Gyani Dhaba
Gyani Dhaba in Kasauli is one of the most popular restaurants here which is known not only for the food but also the views it offers. The food served here is pure dhaba style food and is cooked freshly. From veg to non-veg, you will get everything that will not only satiate your hunger but also excite your palate. This restaurant is located 200 meters ahead of Kasauli T-Point and is a haven for people who are going to Shimla and other places that lie ahead.
7. NH22 Dhaba
NH22 Dhaba is another home-feel restaurant that is known to provide lip smacking delicious food. The restaurant has a homely feel to it which is not only felt by its ambience but also the taste of the food. The restaurant has a friendly staff which offers amazing hospitality and quick service. The place is a hit amongst people who are travelling through the NH22 highway and you will find travelers filling up their bellies with their delicious food.
Kasauli is one of the most visited tourist destinations. It receives a massive footfall around the year and it is only fitting that it is now home to some of the most amazing restaurants. The restaurants here offer amazing food with amazing views. On your next trip to Kasauli, make sure to visit these amazing restaurants.
Disclaimer: TravelTriangle claims no credit for images featured on our blog site unless otherwise noted. All visual content is copyrighted to its respectful owners. We try to link back to original sources whenever possible. If you own the rights to any of the images, and do not wish them to appear on TravelTriangle, please contact us and they will be promptly removed. We believe in providing proper attribution to the original author, artist or photographer.
Please Note: Any information published by TravelTriangle in any form of content is not intended to be a substitute for any kind of medical advice, and one must not take any action before consulting a professional medical expert of their own choice.
Frequently Asked Questions About Restaurants In Kasauli
What are some of the best restaurants in Kasauli?
Cafe Rudra, Punjabi Rasoi, Hangout – Rooftop Bar and Restaurant, and Shack are some of the best restaurants in Kasauli that should be visited if you are looking to try delicious food.
What are some of the famous food items in Kasauli?
The must try food in Kasauli includes band samosa, Lemon chicken, rice with curries.
What is the average cost of restaurants in Kasauli?
Average cost of restaurants in Kasauli is between INR 400 – INR 1100.
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My Family and I Theme Books for Kids
Shop ParentCircle's "My Family and I" theme books for kids and little learners to encourage them to learn and explore the importance of family relationships. Our collection includes beautifully illustrated books that teach kids the values of love, respect, and kindness towards their family members. The books are designed to spark their curiosity and help them understand different family dynamics, cultures, and traditions. Our books are perfect for parents, grandparents, teachers, and caregivers who want to instill positive values in their little ones. Explore our collection today and choose the perfect book for your child to learn, grow and cherish their family bonds.

domain: library


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On March 8th, we globally celebrate International Women’s Day, a day dedicated to commemorating the achievements of women, advocating for gender equality, and honoring the women who inspire us. The origin of this significant day dates back to the early 20th century when women around the world began to unite and fight for their rights, including the right to vote, better working conditions, and equal opportunities.
You might wonder why peonies on this special day? Well, peonies are not only exceptionally beautiful, but they also carry symbolism of love, happiness, and prosperity. Giving peonies to a woman is like presenting a bouquet filled with warmth, admiration, and appreciation.
And let’s not forget that the peony Sarah Bernhardt is named after the legendary Sarah Bernhardt, a French actress known for her extraordinary talent, charisma, and strength. Sarah Bernhardt was a pioneer in her field and a true inspiration for women around the world. The fact that one of the most beautiful and beloved peonies is named after her only adds to the symbolism and significance of giving these flowers on International Women’s Day.
So let’s celebrate this International Women’s Day by honoring, supporting, and appreciating the women in our lives. And what better way to do that than with the timeless beauty of peonies? Let’s together celebrate the strength of women and make the world a little more beautiful, flower by flower.

domain: sociology


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Salary: $17.58 per hour plus excellent benefits and retirement
Yakima County is now accepting applications to fill the position of Office Specialist (Booking Clerk) with the Yakima County Department of Corrections. The position Performs specialized office support activities associated with the evaluation, interpretation, verification, and correction of information derived from legal documents authorizing the detention, transfer and/or release of inmates into/from the Department of Corrections. Experience and Training: High School Diploma or GED plus three years general clerical experience including experience related to corrections support, accounting, customer service or other duty assignments of the position; or an equivalent combination of education and experience which provides knowledge, skills and abilities sufficient to successfully perform the essential duties of the job.
Position is open until filled. Please apply immediately.
We are an Equal Employment Opportunity (EEO) employer and does not discriminate on the basis of race, color, national origin, religion, gender, age, veteran status, political affiliation, sexual orientation, marital status or disability (in compliance with the Americans with Disabilities Act) with respect to employment opportunities.

domain: law


text:
Square Peg Dilemmas: Undervalued Girls
Teen girls feel most successful when their accomplishments are reflected in the eyes of the people who matter most to them: their parents, teachers, and peers. Those who feel fundamentally different from their families or classmates, however, may find it hard to get that affirmation. While more resilient girls might rejoice in their individuality, vulnerable girls can think of themselves as square pegs in round holes—teens who don’t match up to traditional standards of success, whose particular talents and interests are neither respected nor valued. They are stressed by thinking they will never become the best, much less what others expect them to be. Square pegs perceive themselves as worlds apart from the people around them—in other words, as perpetual misfits.
For example, some live to act, dance, or sing, but aren’t interested in school. Others love to create poetry, sculpture, or cartoons, but shy away from reading books and writing research papers. Undervalued girls are created when tone-deaf teens have musical siblings, when klutzes attend schools that revere athletes, and when artsy girls come from scholarly families or attend academically rigorous schools.
With the cultural frenzy about academic achievement, parents get anxious when our kids don’t look conventional. It is frightening to think their nonconformity will prevent their success later on. It is also harder to support girls who have unfamiliar interests or follow unpredictable adolescent paths. So when parents see daughters struggling, it is easy to pressure them to conform, to do better, or to make more friends. In the process, parents can too easily miss the underlying issue: a daughter who feels terribly misunderstood because her talents lie elsewhere.
To reduce girls’ pressure to measure up, parents: (1) must be mindful of their powerful influence, and (2) must be willing to examine, and possibly to modify, their interactions with their daughters about achievement. In addition, try these strategies:
1. Reduce Pressure
The most potent antidote to your daughter’s stress may be the alleviation of your own. Use whatever strategy usually works for you. Realizing that there are many paths to success may help you to come to terms with your daughter’s struggles. You may also remain calmer if you to attend to what is going on in the moment rather than making anxious projections about her future or harping on her past failures. Then you are in a better position to do everything possible to relieve the pressure she is experiencing.
2. Avoid Comparisons
No matter how tempting, refrain from comparing your daughter unfavorably to siblings, friends, or classmates who look more successful. Not only won’t this help your daughter, but also your judgments may turn out to be wrong. You have no idea if these kids’ talents or achievements will actually pay off later or what struggles they may be hiding beneath their outward accomplishments.
3. Monitor Your Behavior
Be aware of the messages you convey through your behavior. Teens are adept at differentiating between parental efforts that are truly designed to help them and those that are based on other, less beneficial motives.
4. Discover Their Passions
Develop an open mind about the shape of success. When parents are not intent upon seeing specific benchmarks or outcomes, they give daughters an extraordinary gift: freedom from having to choose whether to please others or to follow their own dreams. Know when your daughter wants to be the social director rather than the captain of the ship, the nurse instead of the neurosurgeon, or the ballerina rather than the dance teacher. Then help her pursue those passions in every way possible, whether that means voice lessons, acting classes, art camp, or writing workshops.
5. Relinquish Inappropriate Control
It is difficult for parents to resist the urge to make a B student into an A student, an average athlete into a superstar, or a reserved girl into a popular leader. It is all too easy to think, “If only…” and to offer whatever remedies you see fit. Yet to encourage any daughter’s burgeoning individuality, especially one who feels undervalued, it is necessary to stop trying to control her life. Remind yourself that all kids have a right to focus on their own talents and decide their own futures.
Square pegs are most resilient to stress when their mothers and fathers let go of their own expectations and don’t try to transform them into round pegs. These parents accept that their daughters’ futures are not opportunities to rewrite their own histories or to experience vicarious glory. Being put in charge of their own lives liberates girls like nothing else.
6. Consider Other Options
Square pegs often feel stuck. They certainly can’t change their families, and they often can’t change their schools. But for teens who do have options, parents might consider whether their daughters would be better off in a different environment—whether it is school or camp or jazz class—with which they are better matched.
Whenever parents can reduce stress, maintain broad ideas about success, and give up inappropriate control over the details in their daughters’ lives, girls are best able to cope with being different from their families or classmates. They are less likely to interpret their uniqueness negatively and to feel like misfits. When their parents and teachers honor their individuality, these girls gain the confidence, self-reliance, and genuineness that arise from pursuing their real passions—in their own ways, and in their own time.


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KLUANG, Feb 11 — The Umno and Barisan Nasional (BN) machinery are reminded not to take lightly the current turmoil faced by the opposition pact, especially in Parti Pribumi Bersatu Malaysia (PPBM).
Umno vice-president Datuk Seri Hishammuddin Hussein this was because the weaknesses of the opposition did not mean that Umno and BN were strong, so the machinery must play their respective roles to ensure victory at the 14th General Election.
“We in Umno and BN cannot take it easy. When people don’t like or are not confident with the opposition, that does not mean that they know what we (Umno and BN) are doing. So, we must go down to the ground and tell them about our struggles,” he told reporters after opening the People-Friendly NBOS Fiesta at the Paloh Public Field here today.
He said this in response to crisis in PPBM which had seen many of its members left the party.
Yesterday, 50 PPBM members from the Larut Division declared they were leaving the party and joining Umno as they had lost confidence in the leaders and the struggle of PPBM. — Bernama

domain: news


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Well the apple certainly didn’t fall far from this famous tree!
Allie Colleen, Garth Brooks‘ youngest daughter, is stretching her musical wings and has released her debut single called Work in Progress, a song she co-wrote with Marcus Hummon (Cowboy Take Me Away/Dixie Chicks, Jezebel/Chely Wright) and Greg Beick (Bring It On Home/Little Big Town).
Garth posted a rare picture of himself, Trisha Yearwood, and Allie to social media, praising his daughter and her gift.
“What a beautiful voice on your grandmother’s birthday…perfect. I love you!! Listen to @alliecolleenmusic’s new single #WorkInProgress,” he wrote on social media.
Garth’s lovely wife and Allie’s stepmom, Trisha Yearwood, shared the same picture, proudly writing, “From one work in progress to another, what a beautiful song and your voice sounds amazing! I love you so much, Allie #EveryGirl ? You got this, baby! ”
We’ve known for a long time that Allie was a talented singer and she had made her musical intentions clear in the past, but apparently Allie had promised her famous dad that she’d finish college before moving on to a music career, which she’s now done, and so now here we are.
Check out Allie Colleen’s song Work In Progress below (or on spotify here) and let us know what you think.

domain: artistic


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noun[mass noun] Biology
Natural selection arising through preference by one sex for certain characteristics in individuals of the other sex: long tails in male birds of the species probably evolved through sexual selection
More example sentences
- A large portion of the first volume was devoted to the working of natural and sexual selection as an explanation of the origin of human beings by natural means.
- In fact, Darwin himself postulated that facial hair may have evolved through sexual selection.
- Moreover, he developed a theory of sexual selection in evolution… in which the chief force is the competition among males to be more appealing to discriminating females.
For editors and proofreaders
Line breaks: sex¦ual se¦lec|tion
Definition of sexual selection in:
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domain: biology


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125 Park Avenue, 7th Floor, NYC
Entrance is next to TD Bank on 42nd Street
MSF Corporate Partner, Denis Dufresne and Corporate Associate, Molly Carroll joined client David Mehalick, Chairman of Coeptis Therapeutics Holdings Inc. this morning to ring the Nasdaq bell and open the US Markets in celebration of Coeptis’ listing on Nasdaq.
On October 31st, Coeptis Therapeutics, Inc. announced the closing of the business combination with Bullhorn Holdings Corp. When asked about the combination, David Mehalick stated, “This is a significant step for Coeptis as we seek to become a leader in the development of next generation cell therapy technologies for cancer. This transaction closely follows our recent in-licensing of SNAP-CAR, a multi-antigen CAR T technology platform, providing a springboard into what we envision will be an active period for the company.”
Please join us in congratulating our colleagues Denis Dufresne and Molly Carroll for a phenomenal job!
#business #markets #ipos #nasdaqlisted #nasdaq


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The Vogelwijk Wednesday Morning Group, Vogelwijk Woensdagochten Peutergroep as called in Dutch, is for international families to get together in Leiden every Wednesday morning between 9:30 and 11:30.
Our goal is to connect with other families and give our children a safe place to play under our own supervision.
Parents, grandparents or carers are warmly welcomed with their babies, toddlers and young children.
We speak predominantly English and Dutch, but have families from all over the world including Dutch families.
We meet at the Vogelwijk playground. It has fantastic indoor and outdoor facilities.


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Looking to make a statement in your bedroom? This unusual and colourful distressed bedside table, is painted a strong green, with red sides. Made from a mix of woods, the door has an oval glass insert so you can see inside, and embossed brass detailing adds an authentic Indian flavour to the look. The cupboard has 1 shelf. As a look, it shouldn’t work, but it really does.
OLD OR UNUSUAL FURNITURE
These old or unusual items are mainly from Rajasthan, India. Many items are part new, designed around original old doors to create practical cupboards and sideboards with a traditional Indian feel. Other pieces are true original Indian pieces once used in their homes such as damchiyas (originally used to store the brides dowry) or we’ve even had an old Indian village fridge! Want something different? Then old or unusual is the place to look


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- Jewelry Findings
- Charms for Jewelry Making
- Hammered Silver 1-9/16 inch Cross Charm with Heart - 2 pack
Hammered Silver 1-9/16 inch Cross Charm with Heart - 2 pack
Product ID: 1999-4152
This hammered silver cross charm from Darice® features a hammered silver heart at its center. An opening at the top of this 1-9/16 inch charm allows you to slide a chain or cord through to create a necklace or bracelet easily. 2 pieces per package.
Product Type: Religious
Sale Price: $0.75
2 pieces per package.


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Two thousand three hundred and thirty two nonselected brains from 1- to 100-year-old individuals were examined using immunocytochemistry (AT8) and Gallyas silver staining for abnormal tau; immunocytochemistry (4G8) and Campbell-Switzer staining were used for the detection ofβ-amyloid. A total of 342 cases was negative in the Gallyas stain but when restaged for AT8 only 10 were immunonegative. Fifty-eight cases had subcortical tau predominantly in the locus coeruleus, but there was no abnormal cortical tau (subcortical Stages a-c). Cortical involvement (abnormal tau in neurites) was identified first in the transentorhinal region (Stage 1a, 38 cases). Transentorhinal pyramidal cells displayed pretangle material (Stage 1b, 236 cases). Pretangles gradually became argyrophilic neurofibrillary tangles (NFTs) that progressed in parallel with NFT Stages I to VI. Pretangles restricted to subcortical sites were seen chiefly at younger ages. Of the total cases, 1,031 (44.2%) had β-amyloid plaques. The first plaques occurred in the neocortex after the onset of tauopathy in the brainstem. Plaques generally developed in the 40s in 4% of all cases, culminating in their tenth decade (75%). β-amyloid plaques and NFTs were significantly correlated (p < 0.0001). These data suggest that tauopathy associated with sporadic Alzheimer disease may begin earlier than previously thought and possibly in the lower brainstem rather than in the transentorhinal region.
From beginning to end, the pathologic processes underlying sporadic (versus familial) Alzheimer disease (AD) are confined to the human CNS and chiefly include intraneuronal formation of abnormal tau protein and extracellular deposition of β-amyloid protein (1). Alzheimer disease-related lesions develop at given predilection sites within the brain and progress according to a predictable sequence from there to hitherto uninvolved areas (2-7).
Once initiated, the process progresses for decades without remission until it crosses a threshold to clinically recognizable dysfunction (6). Recently, we found that intraneuronal lesions associated with AD occur before puberty or in early young adulthood and most often affect noradrenergic projection neurons of the locus coeruleus, one of several subcortical nuclei that generate diffuse projections to the cerebral cortex (8). Abnormal tau can be visualized by immunohistochemistry with the antibody AT8, which recognizes a phosphate-dependent epitope at serine 202 and threonine 205 (9). Alzheimer disease may begin with misfolded and abnormally phosphorylated tau protein in the proximal axon of caeruleus projection neurons (8). Thereafter, similar material fills the somatodendritic compartment of involved cells. This soluble and nonargyrophilic “pretangle” material gradually aggregates into insoluble fibrillary and argyrophilic neuropil threads (NTs) in dendritic processes and into neurofibrillary tangles (NFTs) in neuronal somata. These inert neurofibrillary changes of the Alzheimer type are resistant to autophagy and other endogenous cellular removal mechanisms (10-15).
To obtain greater insight into the AD-related pathologic processes in a large cohort, tau lesions were reexamined in 2,332 nonselected autopsy cases ranging in age from 1 to 100 years. Particular attention was paid to a subpopulation consisting of 342 cases, which, when they were studied with only the Gallyas silver technique, lacked argyrophilic intraneuronal lesions (NFTs/NTs) at the typical cortical predilection sites. Subsequently, all 342 cases were assessed by immunohistochemistry for abnormally phosphorylated tau protein (AT8). Sections of 100 μm thickness were made through medial portions of the temporal lobe and through the midbrain and pontine tegmentum to assess brainstem nuclei. The new findings presented here supplement data from an earlier report regarding the frequency of AD-associated argyrophilic lesions in the cerebral cortex in individuals ranging from 26 to 95 years (3).
Materials and Methods
This retrospective autopsy study was performed in compliance with university ethics committee guidelines as well as German federal and state law governing human tissue usage. Consent for autopsy was obtained for all cases. Brains had been obtained at autopsy and included nonselected cases from affiliated university hospitals. One individual (17-year-old adolescent male) had Down syndrome. The only exclusionary criterion was the presence of tauopathy other than AD or argyrophilic grain disease (AGD), such as Niemann-Pick disease type C, subacute sclerosing panencephalitis, progressive supranuclear palsy, Pick disease, or corticobasal degeneration (16). Neuropathologic diagnoses for all cases were made for AD and AGD, as described (2, 4, 17-19). The 2,332 cases were grouped into 10 age categories by decade (Table, Supplemental Digital Content 1, ). The ratio of females to males in each age category is shown in Table 1.
Tissue Fixation, Embedding, and Sectioning
Brainstems and at least a single hemisphere from all individuals were fixed by immersion in 4% buffered aqueous formaldehyde. A set of 2 tissue blocks was excised, embedded in polyethylene glycol (PEG 1000; Merck, Darmstadt, Germany), and sectioned at 100 μm, as previously described (4, 8, 20). This section thickness allows for the superimposition of multiple structures, including nerve cells with their entire dendritic tree. The first block was cut at miduncal level through medial portions of the temporal lobe and encompassed anterior (i.e. uncal) portions of the hippocampal formation and the parahippocampal gyrus (entorhinal region), including the adjoining transentorhinal region as well as portions of the occipitotemporal gyrus and additional gyri of the basal temporal neocortex. The second block was cut through the occipital lobe perpendicular to the calcarine fissure and included high-order visual association areas (peristriate region), a first-order visual association area (parastriate area), and the primary visual field (striate area) (4).
From 342 cases that were negative in the Gallyas stain (i.e. they displayed no argyrophilic NFTs/NTs in the cerebral cortex, particularly in the transentorhinal region), a set of additional blocks was cut perpendicular to the brainstem axis of Meynert. One block was cut through posterior portions of the medulla oblongata at the level of the dorsal motor nucleus of the vagal nerve. A second block showed the pontine tegmentum and contained portions of the locus coeruleus and the dorsal raphe nucleus. The third block was excised at the level of the inferior colliculus and contained posterior portions of the substantia nigra and supratrochlear portions of the dorsal raphe nucleus (8, 21).
Staining and Immunocytochemistry
Collections of free-floating sections from all blocks for each case were processed with the following techniques: Pigment-Nissl staining served to show the presence and extent of lipofuscin deposits (aldehyde fuchsin) and basophilic material (Darrow red) (20) and silver staining with the Campbell-Switzer and Gallyas methods to exploit the physical development of nucleation sites. These advanced silver techniques are reliable and are used to visualize β-amyloid deposition (Campbell-Switzer) and argyrophilic neurofibrillary lesions (Gallyas) (4, 17, 19, 20, 22).
Immunohistochemistry included the use of the following antibodies: monoclonal antibody PHF-Tau (1:2000; Clone AT8; Pierce Biotechnology, Rockford, IL) detected hyperphosphorylated tau protein in pretangle material and Alzheimer-type neurofibrillary changes; monoclonal anti-β-amyloid antibody (1:5000; Clone 4G8; Covance, Dedham, MA) was used for the detection of β-amyloid deposition. β-amyloid plaque phases were assessed as previously published (5). All immunohistochemistry procedures could be performed on the material that had been stored for long periods in formaldehyde (23).
Tissue sections for immunoreactions were treated for 30 minutes in a mixture of 10% methanol plus 10% concentrated (30%) H2O2 and 80% Tris. After pretreatment with 100% formic acid for 3 minutes to facilitate the β-amyloid immunoreactions, blocking with bovine serum albumin was performed to prevent nonspecific binding. Subsequently, each of the various sets of free-floating sections was incubated for 18 hours at 20°C using the primary antibodies. After incubation with secondary biotinylated antibody (anti-mouse IgG, 1:200; Vector Laboratories, Burlingame, CA) for 1.5 hours, immunoreactions were visualized with the avidin-biotin complex (ABC, Vectastain; Vector Laboratories) for 2 hours and the chromogen 3,3′-diaminobenzidine tetrahydrochloride (DAB D5637; Sigma, Taufkirchen, Germany). Omission of the primary antibody resulted in nonstaining. Positive and negative control sections were routinely included. The tissue sections were cleared and mounted in a synthetic resin (Permount; Fisher, Fair Lawn, NJ). All sections were viewed, and AD staging was performed with a Vanox AHB53 Olympus microscope (Olympus Optical Co., Tokyo, Japan). Digital micrographs were obtained using the Soft Imaging System (Münster, Germany).
Statistical analysis was performed using the Student t-test for independent samples to compare normally distributed continuous variables between 2 groups. The Mann-Whitney U test was used to analyze between-group comparisons of ordered variables, and the Spearman ρ statistics was used for measuring rank correlations. Calculations for males and females were performed separately. Partial correlation analysis was performed to examine the relationship among different pathologic variables after adjusting for the effects of age. Computations were performed with the aid of IBM SPSS, release 19, 2010 (SPSS, Inc, Chicago, IL) and GraphPad prism V5.0 (GraphPad Software, San Diego, CA).
Absence of Intraneuronal Lesions
Complete absence of intraneuronal inclusions of AD-related abnormally phosphorylated tau protein within the brain was found in 10 of 2,332 cases; these are designated as “cases devoid of changes” in Figure 1 and “no changes” in Table, Supplemental Digital Content 1, . These “AD-free” cases were encountered in young age categories; 6 persons were younger than 10 years; 2 were younger than 20 years; and the eldest were 22 and 23 years (Fig. 1, Table, Supplemental Digital Content 1, ). These cases did not exhibit β-amyloid plaques.
Intraneuronal AT8-Immunoreactive Abnormal tau Protein (Pretangle Material)
Pretangle Stage a
The first AD-related intraneuronal brain changes were seen in brainstem nuclei with diffuse projections to the cerebral cortex (24-29), most frequently in the locus coeruleus (8, 30-38). Alterations visible by light microscopy developed first in nerve cell processes, possibly the proximal portions of the axon close to the soma but outside the initial segment, where abnormally phosphorylated tau appeared abruptly without precursor or intermediate forms in those areas. The present cohort contained only cases in which immunoreactive neurites were limited to the pontine tegmentum in or close to the locus coeruleus; these are designated “a” in Table, Supplemental Digital Content 1, . Forty of 2,332 cases were classified as pretangle Stage a cases and occurred mainly in young age groups.
Pretangle Stage b
Twelve cases (designated Stage b) showed involvement confined to the locus coeruleus; however, in these cases, involvement included somatodendritic compartments of locus coeruleus noradrenergic projection cells (Table, Supplemental Digital Content 1, ). Normal projection neurons in the locus coeruleus have smoothly contoured cell bodies. By contrast, they often displayed spiked protrusions along their outer somatic rim in the Stage b cases. In addition, the AT8-immunoreactive (ir) pretangle material extended further into the axon and was also observed in more remote portions of the central tegmental tract (i.e. in the superior cerebellar peduncle and in the midbrain tegmentum lateral to the medial longitudinal fascicle). On the other hand, AT8-ir axons at the level of the dorsal motor nucleus of the vagal nerve within fiber bundles descending to the spinal cord were infrequently seen (8, 39).
All pretangle Stage a and Stage b cases exhibited AT8-ir material in the locus coeruleus in the absence of lesions in the anteromedial temporal cortex. Notably, none of these cases had isolated tau-ir neurons in any other subcortical nuclei with diffuse projections to the cerebral cortex (Table, Supplemental Digital Content 1, ).
Pretangle Stage c
Six of 2,332 cases displayed more widely distributed subcortical lesions in the absence of cortical tau pathology. In this group, AT8-ir nerve cells were found not only in the locus coeruleus but also in other nonthalamic nuclei with cortical projections, such as nuclei of the upper raphe system or magnocellular nuclei of the basal forebrain. These cases are designated “c” (Table, Supplemental Digital Content 1, ).
In summary, 58 of 2,332 cases (i.e. pretangle Stages a-c) did not show any cortical AT8-ir projection neurons (or portions thereof) in AD predilection sites of the temporal lobe, including the transentorhinal region (Figs. 1 and 2A, Table, Supplemental Digital Content 1, ) (8). Cases characterized by these 3 lesional distribution patterns usually occurred in young age groups. As anticipated, tissue sections from these pretangle stage cases stained for lipofuscin pigment and basophilic material did not reveal any obvious pathologic alterations, such as loss of basophilic material or displacement of cell nuclei to the periphery.
Pretangle Stages 1a and 1b
In addition to subcortical pathologic findings, 38 of 2,332 cases displayed mild cortical lesions consisting only of AT8-ir pretangle material in nerve cell processes; such lesions originally had escaped recognition in Gallyas silver-stained sections. These subtle lesions occurred in medial portions of the temporal lobe (particularly in the transentorhinal region) in structures that were most probably axons. Such cases are designated pretangle Stage 1a (Table, Supplemental Digital Content 1, ). Remarkably, no cases in this group displayed even slight cortical pathologic findings in the absence of subcortical AT8-ir lesions.
Finally, in addition to the pretangle lesions described previously, 236 of 2,332 cases showed the presence of AT8-ir nonargyrophilic pyramidal cells in the cerebral cortex. Some cases displayed only a single affected pyramidal cell, whereas others exhibited greater numbers of involved neurons. The pretangle material filled the entire somatodendritic domain of the pyramidal cells; no intermediary abnormal forms of the pathologic changes were detectable. Affected neurons occurred preferentially in the transentorhinal region, in which abnormal tau material was confined to cortical projection cells and was not present in local circuit neurons or nonneuronal cells. Such cases are designated in Table 2 as pretangle Stage 1b. All 1a and 1b cases (n = 274) had subcortical lesions similar to those seen in Stages a to c. Nonargyrophilic lesions in the cerebral cortex did not occur in the absence of AT8-ir subcortical pathologic finding. Their prevalence increased during the second and third decades and was maximal in the fourth decade (Fig. 1). From the fourth decade onward, all individuals in the cohort had some degree of AD-associated lesions (Fig. 2A).
Intraneuronal Gallyas-Positive Abnormal tau Protein: Neurofibrillary Stages I to VI
Cases displaying AT8-ir and Gallyas-positive material are indicated by roman numerals in Figure 2A (see also Table, Supplemental Digital Content 1, ). The somatodendritic pretangle material had become insoluble and argyrophilic, forming neurofibrillary lesions, i.e. dendritic NTs and somatic NFTs. The first lesions were usually seen in the transentorhinal region (2). Argyrophilic lesions at subcortical sites were observed only in cases with advanced NFT stages. In NFT Stages I to VI, nerve cells filled with pretangle material were also present. Gallyas-positive neurons alone (i.e. absence of cells with pretangle material) were not observed in this cohort. It is known that nerve cells with NFTs/NTs survive for years (40, 41). However, they die prematurely, and extraneuronal remnants of the argyrophilic material remain as “ghost” tangles in the neuropil thereafter (42). Here, ghost tangles were only present in combination with recently formed intraneuronal NFTs and never in isolation. Moreover, ghost tangles were observed only in cases with advanced NFT stages.
The 589 NFT Stage I cases were characterized by low numbers of Gallyas-positive pyramidal cells that were predominantly in the transentorhinal region. The 497 NFT Stage II cases had additional lesions in both the entorhinal region proper and hippocampal formation. Early (i.e. pretangle Stages a to c and Stages 1a and 1b, NFT Stages I and II) AD-related intraneuronal lesions were observed chiefly in young age categories (Fig. 2A; Table, Supplemental Digital Content 1, ). The intraneuronal pathologic findings during these early stages were not accompanied by insoluble extracellular amyloid deposits with the exception of a 17-year-old adolescent male with Down syndrome (8).
There were 491 NFT Stage III cases that displayed a progression of the intraneuronal lesions into the basal neocortical areas of the temporal lobe; in 191 NFT Stage IV cases, they reached insular and basal frontal areas. The 138 NFT Stage V cases displayed involvement of nearly the entire prefrontal cortex as well as the high-order sensory association neocortex, whereas in the 84 NFT Stage VI cases, the premotor and primary motor areas as well as sensory first-order association areas and primary fields were affected. The prevalence of late NFT Stages (V and VI) increased with age (Fig. 1A; Table, Supplemental Digital Content 1, ). NFT Stages V and VI (222 cases) were frequently combined with late stages of β-amyloid deposition (Table 2 and Fig. 2B) (3).
Extracellular β-Amyloid Protein Aggregation
All 1,031 cases that displayed the presence of β-amyloid plaques also showed abnormal tau protein in specific nerve cell populations. Notably, in this cohort of 2,332 individuals, no β-amyloid deposits were observed in the 10 cases with no AD-related intraneuronal tau protein changes. With the exception of the 17-year-old adolescent male with Down syndrome with advanced β-amyloid pathologic lesions and stage a pretangle lesions, β-amyloid plaque deposition began to appear between ages 30 and 40 years, a point when such cases already exhibited pretangle Stage 1a or 1b (Fig. 2B and Table 2). The prevalence of β-amyloid plaques assessed according to Thal et al (5) increased in higher age groups (Fig. 2B and Table 2; Table, Supplemental Digital Content 2, ) (2, 5, 6).
Males were overrepresented across all age decades ranging from 1 to 80 years (58% males), whereas females were only predominant at ages older than 80 years (54.7% females) (Fig. 2B and Table 1). The cohort contained a greater number of older females than older males (Student t-test, p < 0.0001), and there were more younger males than younger females. The severity of AD-related pathologic findings (AT8 pathologic findings, NFTs, and β-amyloid) was significantly higher in females than in males (all p < 0.0001, Mann-Whitney U tests), possibly attributable to the predominance of females at higher ages. There was a significant correlation between β-amyloid deposits and NFT pathologic findings in both females and males (females, r = 0.69, p < 0.0001; males, r = 0.5, p < 0.0001), between β-amyloid deposition and AT8 pathology (females, r = 0.64, p < 0.0001; males, r = 0.52, p < 0.0001), and between AT8 and AGD pathologic findings (females, r = 0.51, p < 0.0001; males, r = 0.56, p < 0.0001), even after controlling for the effects of age (data not shown). In contrast, the correlation between argyrophilic NFT and AGD pathologic findings was diminished after controlling for age (r = 0.07, p = 0.1).
There was a significant increase of both AT8 and β-amyloid pathologic findings with age (Fig. 3). The slopes of the regression lines between age and AT8 pathologic findings were similar for both sexes (p = 0.23; Fig. 3). However, the slope of the regression line between age and β-amyloid deposition was greater (p < 0.001) in females than in males, indicating that the age-associated increase in β-amyloid burden is greater in females (Fig. 3; Table, Supplemental Digital Content 2, ).
Clinically recognizable AD has long been viewed as a disorder closely associated with old age. In fact, many consider it to be caused by the aging process itself or, at the very least, indirectly attributable to aging (43-45). Age-related factors that can damage postmitotic cells or can exert noxious influences on them are thought to play a central role in the pathogenesis of AD (13, 46-48). Yet it should be emphasized in this context that, in AD, not all of the known types of postmitotic cells inside and outside the CNS become involved in the disease process. Even when the discussion is confined to the brain, it quickly becomes clear that AD does not indiscriminately involve all neuronal types; the pathologic process is a remarkably selective one in that it develops in only a minority of neuronal types while sparing others (49, 50).
It also has been pointed out that the disease process in AD requires an inordinately long prodromal period that lasts for 5 or more decades (51-54). Our current findings indicate that the AD-associated process may manifest itself in young individuals of both sexes as well as in the absence of any harmful influences clearly attributable to “old age” (Table, Supplemental Digital Content 1, ). In addition, pretangle and NFT-bearing nerve cells are capable of surviving into the ninth decade (40, 41). Thus, advanced age per se is not a precondition for the formation of the AD-associated tau lesions; rather, there is now strong evidence that the pathologic process underlying AD is not “age-dependent” but an uncommonly slowly progressive one that frequently extends into old age (55).
We observed 52 cases in younger age groups with abnormal tau only in noradrenergic projection neurons of the locus coeruleus and, initially, only in portions of neuronal processes, probably proximal axons (pretangle Stage “a"; Table, Supplemental Digital Content 1, ). In these cases, the first pretangle material was identified without immunohistochemically detectable precursor or intermediary forms. During formation, neither the axonal initial segment nor the somatodendritic compartment of affected nerve cells showed any traces of pretangle material. In other words, there is no patent evidence for a transfer of pretangle material from the soma of involved cells into the affected neuronal process. As such, our findings are in accord with the assumption that the pretangle material that purportedly occurs in axons originates from normal tau proteins bound to axonal microtubules. Nevertheless, inasmuch as the shape and diameter of the involved nerve cell processes remained unchanged, the present results do not support the tau microtubule hypothesis, which claims that hyperphosphorylated tau becomes detached from microtubules and induces failed microtubule transport owing to the accumulation of improperly transported material (56-59).
Moreover, the soluble pretangle material did not seem to be incompatible with or toxic to cell functions because nerve cell nuclei or somatodendritic compartments of affected neurons did not display signs of acute reactive responses that would have indicated a life-threatening event (i.e. neuronal cell death) (60). Neurons do not undergo cell death during pretangle Phases a to c and 1a and 1b when they are producing large amounts of AT8-ir pretangle material (42, 61). The pretangles underwent modification during the lifetimes of the individuals examined until nonbiodegradable Gallyas-reactive NFTs/NTs became evident and, in the long run, the argyrophilic NFTs/NTs result in dysfunction and death of at least some neuronal types, for example, neurons of nuclei with extensive projections to the cortex and neurons in layer II of the entorhinal cortex and the first sector of the Ammon's horn (2).
The pretangle stages proposed here rest, in part, on the assumption that the AT8-immunoreactive lesions are the earliest (up to now immunohistochemically detectable) ones along a disease continuum. If one views sporadic AD as a dynamic process, it follows that pretangle pathology in individuals without clinically manifest or pathologically confirmed AD may represent neuropathologic markers of a condition that ultimately leads to the manifestations of clinical disease. A further assumption for staging of the pretangle lesions is that the pathologic process associated with NFT Stages I to VI increases in extent with disease duration. A potential methodological drawback to this approach is that the development of the pathology can only be reconstructed with the help of cross-sectional data obtained at autopsy. As such, the inferences drawn from these data permit only (but, arguably, admissible and reasonable) assumptions. Validated biologic markers that can be measured longitudinally could help to confirm, correct, or refute the existence and significance of the proposed pretangle phase (Fig. 4).
In conclusion, the results presented here corroborate those of a very recent study performed on a much smaller cohort, namely, the pathologic process associated with sporadic AD commences with intraneuritic formation of pretangle material in the lower brainstem rather than in the transentorhinal region (Fig. 4; Table, Supplemental Digital Content 1, ) (8). That abnormal tau protein occurred in pretangle stages or early NFT stages without the presence of insoluble β-amyloid plaques (1,291/2,332 cases) means that not only a rethinking of currently existing neuropathologic staging NFT categories for AD is necessary but also a rethinking of the hypothesis that β-amyloid drives AD pathogenesis and secondarily induces the formation of abnormal tau protein (46, 62-68). Sporadic AD may be the result of two separate assaults: first, a tauopathy, possibly beginning in childhood; and second, negative influences of β-amyloid after a given threshold is crossed. β-amyloid might be capable of exacerbating the underlying tauopathy so that it develops into clinical AD (69-71). If the pretangle material is not regressive or transient (72), our findings may indicate that the pathologic process leading to abnormal tau pathology and ultimately capable of inducing NFT formation does not begin in the transentorhinal region but in select subcortical nuclei; it may commence before puberty or in early young adulthood. Currently, too little is known about the pace at which the pathologic process develops. Some individuals were still at NFT Stages I and II at 90 years and older (Fig. 2A). Thus, although all individuals in this study who were 40 years and older exhibited pretangles (owing to a considerable variability in the rate of progression), only a proportion of them would have gone on to develop AD had they lived longer.
If other groups replicate our present findings and confirm that the AD-related tauopathy begins in noradrenergic projection neurons of the locus coeruleus, it might be possible to intervene with therapeutic means earlier than at present, that is, during the first decades of life, by protecting caeruleus projection cells and/or preventing them from developing the pretangle material (73-75).
Autopsy material was supplied by the Braak Collection (Goethe University Frankfurt). The skillful technical assistance of Ms. Simone Feldengut (immunohistochemistry) and Mr. Stephan Mayer (Fig. 4) is gratefully acknowledged.

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