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Emerigo Hotel
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TripAdvisor Reviews Emerigo Hotel Angeles
Travel Blogs from Angeles
Caves of Past
... Just a brief history once that it was the headquarters of the Katipuneros. Everybody is familiar with Andres Bonifacio. Isa sya sa matatapang bayani nagtanggol sa ating pinakamamahal na PIlipinas. Sa mga kwebang ito matatagpuan ang isa sa mga historic relics.
- Balaong Bridge
Pres. Estrada inaugurated this bridge that serves an easy way for the farmers to transport their goods and crops to Balintawak market in Manila. A 50 ...
"Palaging Mayo'ng Dahilan Upang Tayo ay Maging Masaya"
"There is always a reason to be happy"
By Romeo Bobby Dela Rosa
(Filmed on Day 77 of the Milman adventure, Plaridel. 13.11.14)
Day 78. Pagsanjan Falls
... children ahead of us. They were getting quite excited as we were approaching and Jane commented that they were plotting something. She was right. Several of them sheepishly came forward to Jane and gave her flowers as the rest of the kids ran of giggling. It was so sweet :)
We headed back home for a few beers and a fairly early night. Rodel would be collecting us tomorrow at 4am for our two night trip away to Puerto Galera.
Magandang gabi (goodnight).
Day 77. Market and haircut
... things to say about it. They do well with so little management (1x fresh graduate engineer only) to build so fast, even the steel window frames are fabricated on site. Safety wise, no edge protection, flips flops, untidy, throwing material of the roof with no bottom man and anybody can go anywhere. Quality wise, tie-wire sticking out, no cover, poor formwork, missed conduits. At the end of the day it stands up and is built very cheaply, which essential to help ...
Party time
... Kokomo's restaurant and sit in one of the seats overlooking the street and watch the show. Watch the parade of old, fat white guys walking arm in arm down the street with their young Filipina lovers, followed by an occasional lady boy and then comes the pack of Indian guys traveling together with their eyes and mouths wide open.
After that head to one of the larger clubs and enjoy the dancing and San Miguel Light(try the apple flavor) the rest of night is up to ...
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He isn't taking flying lessons or anything is he?
I honestly don't have a clue.
Let it not be said that no one cared, that no one objected once its realized that our liberties and wealth are in jeopardy.
---Ron Paul
"He who passively accepts evil is as much involved in it as he who helps to perpetuate it."
---Dr. Martin Luther King
"If you think we are free today, you know nothing about tyranny and even less about freedom."
---Tom Braun
with him being only 20? i really think he is feeding you a line of crap. he may have a handgun, but i doubt it's legal to carry as he says. and his dad got him the carry permit because he works as a federal corrections officer? that i also find hard to believe. again i think he's feeding you a line of crap. sounds like a line of BS!
Why not just call campus security and ask. Tell the story anyway you like. For the record, Im callin 100%, USDA approved BS but I feel like I need closure on this.
You don't have to ask about a drug bust. Just tell them you know a guy who claims that he carries a gun and has a permit that allows for it and you think he's full of crap, but you thought they might like to know for security purposes.


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More Trouble for Darwinism
Regis NicollRegis Nicoll is a Centurion of The Chuck Colson Center for Christian Worldview. He spent 30 years as a nuclear specialist, and is now a freelance writer who writes on current issues from a Christian perspective. His work regularly appears on BreakPoint online and SALVO magazine among other places. Regis also teaches and speaks on a variety of worldview topics, covering everything from Sharing the Gospel in a Postmodern Generation to String Theory. He currently serves as lay pastor of Hamilton Anglican Fellowship (www.hamiltonaf.org) in Chattanooga, Tennessee.
- 2008 Apr 25
Now this is something that should trouble the Darwinian establishment. In a study published in the New England Journal of Medicine (NEJM), researchers found "that a deficiency in an enzyme called pyruvate kinase, which is required for energy production in the body, provides protection against malaria infection."
Here's the trouble: Darwinian evolution depends on the ability of unguided, naturalistic processes to build genomes over geological time scales. Note that the information content of the smallest genome would fill a 500-page book. (The instructions in the human genome would fill a 50,000 page book!)
The astute person will wonder how an unconscious process could lead to the creation of what amounts to a mini-library from scratch. The catechistic answer is that genetic words, sentences, and whole books are written through the creative power of genetic mutation. Mutations that have "cash value" in evolutionary "fitness" are accumulated over time, leading to an increasingly complex code of life.
It's like believing that, given two hundred million years, a double-wide trailer could become the Taj Mahal from the combined influences of cosmic rays, wind erosion, tectonic movement and quantum effects. As any homeowner knows, it's precisely such unconscious effects that lead to home deterioration, not home improvement. But, on occasion, even deterioration can have a beneficial effect.
Consider that double-wide in the tropics without air conditioning. A wind that wasn't strong enough to destroy it, but sufficiently strong to blow out all the windows, could enhance creature comfort without any structural additions.
And that was what the researchers in the NEJM found. The enzyme deficiency needed for malaria protection, results from the suppression of genetic instructions rather than from their creation.
Increased "fitness" by the shuffling or suppression of existing genes, rather than by the accumulation of new ones, is a direct affront to gradualism. While that should rattle the ranks of the Darwinian faithful, their resiliency against such evidence never ceases to amaze.
Consider the "crystals" and "aliens" offered, in Expelled, as the best answers to the question of life's origin by their most celebrated evangelists. They may be still on the playing field, but the game is long over.


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Slice of SciFi contributor Alan Kistler of Stay Geeky shares some brilliant historical insight on the origins of the big 'ol "S" on Superman's chest. See how it evolved, what it meant over the years, who had a say in the designs and how we perceived it, and why it all makes sense now… thanks to Alan's concise report. Join Sam, Michael, Meghan and Tim as they dig deeper into this "S-capade"!
"That's How I Was Raised And I Turned Out TV!"
Slice of SciFi takes on Television and unravels the mystery behind your viewing habits by asking the one simple question the Lame Stream Media is AFRAID to ask!!!
What are you watching?
Debate: Agents of S.H.I.E.L.D.
Slice takes on it's next great debate… Is Marvel's "Agents of SHIELD" TV series living up to it's comic book roots? Or has Joss Whedon lost his midas touch when it comes to TV screen programming. Mike and Sam have kept up with the series while Meghan and Tim have had limited exposure thus far to AoS… which really keeps the conversation grounded and on-track ~ or does it??
Feedbackapalooza: Theater Survival
Slicer Tim Adamec is in the house and dumps $100 into the Swear Jar. Spoiler Alerts pale in comparison to Heart Break Alerts. Rocket launches are life changing experiences. CON Report from Joe. Hey! What about all these little ma-pa movie theaters that can't afford the change to digital. Support your local theater! Gravity scares the crap out of Sam – here's why! Mike thinks size doesn't matter… wake up and smell the aspect ratio!
The Future of Space Exploration
Slice welcomes Geoff Notkin to the studio to geek out on Private Space Exploration companies and the amazing opportunities they might seize. Geoff, Meghan and Michael share boundless enthusiasm for the future of space flight, working and living in space.
Halloween Cosplay
Slice plays dress up in time for Halloween with a report from Toni Darling, Professional Cosplayer, and Geoff Notkin of Meteorite Men who shows off a pair of the actual monster hands prop used in a movie ~ Can you guess what film?? Plus Meghan gets dolled up with a flattering hat, but comes down with a case of head lice in the process! EEWWWW SPOOKY!
Alan Kistler wants a Wonder Woman Movie!
Slice welcomes Alan Sizzler Kistler as a contributor, who asks one o f the most obvious and under considered questions in geekdom… Where's Our Wonder Woman Movie?? Alan does a brilliant job of laying out all the facts, traces Wonder Woman's history, raises concerns and rebuts the nay sayers before they speak.
Radio Free Albemuth
Slice rolls out another episode with guest-host Geoff Notkin who gets all Philip K. Dick in our faces as he pimps his latest project involvement with the new Radio Free Albemuth movie. Geoff and Sam debate the merits of Agents of SHIELD based on the pilot episode. Plus, Meghan steps way over the TMI line when she grills Geoff about his personal anatomy. After all, it's Notkin's love of Dick we're talkin' 'bout!
STEM Journals with Geoff Notkin
Slice welcomes Geoff Notkin, host of Meteorite Men on Science Channel back to the studio to tell us about his new series: STEM Journals. Geoff seduces us with his Euro-Arizona accent as he describes the wicked-cool subjects he covers on STEM Journals and shows off a brilliant prop from the show.
GRAVITY: A Spoiler Free Preview
Sam got to see a sneak preview of "Gravity" and shares her experience – OMG! What a ride it is… a beautifully done film that scares the crap out of you. Mike thinks it will be like "Open Water", and worries that Sandy Bullock can't be credible. Will it be like "Moon"? NO SPOILERS ARE IN THIS REPORT!
UK Programmes on US TeeVee
Hulu Plus connects US audience to UK genre programming from BBC, including Doctor Who, Black Adder and a crap-ton of great series! Oh and Luther is insanely good too! Mass Whovian Weddings are a great bargain – if you're a hyper hard core Doctor Whovian. Zombies comic The Other Dead has quite a collaboration of talent whipped together in a hurricane, Flight Test Land has a bitchin aircraft museum on the way! Con Report: Star Base Indy, Dead Tribbles rise from the grave, Sci-Fi Hall of Fame in Seattle is a must see, cable tv is a pain in the ass…
Please Pass The Plutonium?
NASA's Voyager has wandered for so long it's running our of juice and needs to borrow some of your plutonium; Bagcast tells us about the Ladee project to the moon; Mars is the new Moon; Self healing technology comes from the Terminator movies; Microscopic App for your smart phone; how much poo is around you?; Multiverse; Flight Test Land; Sociology experts support Meghan's Feminism Nerd;
Slice shows you the seedy underbelly of… most things.
Announcing Ichabod Crane v3.0
Sleepy Hollow's hype hooked millions and has Noble, but is it really that cool? How much makeup is too much? One example of how to spend your money on sci-fi stuff in the UK; George RR Martin is a huge Breaking Bad fan; Trivia: Comic Books; Con Report: Brown Coat Ball on 10/04; AMC does more UnDead, Agent Carter needs help, Syfy goes small town; Continuum ends with a "Holy Crap" moment; Spoiling Dexter??
Genre TV is Blowing Up!
Genre TV is blowing up so here's a network by network preview: CW's The 100,The Originals, Star Crossed, Tomorrow People; on FOX it's Almost Human, Sleepy Hollow, Wayward Pines; plus on NBC there's Believe, Crossbones, Dracula; oh but on CBS it's Intelligence; and ABC has Marvel's Agents of Shield, Once Upon A Time in Wonderland, and Resurrection. More awesome geeky programming is coming this fall that you'll hear about first… on Slice!
Where No One Has Gone Before
Slice of SciFi's "Star Trek Geek Week" continues: merchandise and collectibles emerged over the decades and set a standard for all other genre shows. Emotions run high when a Trek fan comes close trekdom, What happened to the Star Trek Experience in Vegas?? Cell Phones are a direct result of Trek Tech, ST is a sense of adventure and exploration, and with a mission statement to Go Where No One has Gone Before… thats what we love about Trek!
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|Property type
|Minimum Stay
|3 - 14 nights
LA SCUOLA DI FURIO Holiday Home is a small holiday complex in a very quiet countryside (within the Parco delle Cerbaie) overlooking a green valley. You stay in a relaxing location and you can reach in less than 1 hour almost every tourist destination in Tuscany (Lucca, Pisa, Vinci, San Gimignano, Florence, the beach). So, in the morning you can have a massage by the pool, take a walk to the little country shops or go to the supermarkets in Fucecchio (5 kms) with your car, then visit one or more tourist attraction in Tuscany, come back to enjoy a swim our fantastic pool (12x6), relax in the large equipped garden sipping an aperitivo while the tomato sauce boils in the kitchen, then have a relaxing dinner in the garden alfresco with your loved ones. The 6 apartments (all equipped with AC) in the former school building have 1, 2 or even 4 bedrooms while Villa Maura (equipped with AC) offers some more comforts and sleeps up to 6. Parking inside the property. Nice country pizzeria / restaurant at walking distance. Free Wi-Fi.
*Everyday Life*
A big plus for all our guests is that we live nearby. We will welcome you, show you around, provide maps of the area and give you a list of restaurants - based on our personal experience - and enjoyable excursions. We are always on hand if you need us but we will leave you to your well deserved holiday!
We sometimes see that families arrive here with the car full of groceries and food (after maybe a long journey under the hot Italian summer sun). Please note that most of the food you buy at home is available also here. Local supermarket Coop is open from 8AM to 9PM every day except Sunday; and 9AM to 8 PM on every other Sunday. Another supermarket, CONAD, is open from 8AM to 8PM and also every Sunday morning from 9AM to 12.30AM. And another smaller grocery shop, Gelsastore, is open any day of the year from 4 in the morning to 1 at night (fresh bread on Sundays, too)!
At 1,1 kms there is Il RitroVino di Caino, that sells good quality local food, cheese, extra virgin olive oil and wine and has fresh bread also on Sundays!
* Market *
A medley of colors and scents awaits you every Wednesday morning in Fucecchio in Piazza XX Settembre.
One of the reasons to rent a holiday accommodation is that you can cook your own food and avoid eating out. You can shop at farmers' markets, try local recipes, keep your children entertained while cooking... But sometimes you just want to relax and unwind with a nice glass of wine and let others cook! Among other local area information, we will give you a list of nearby restaurants (one of them is at walking distance!) we usually go to! And we will be happy to call and reserve a table for you, if you like!
*Farmers' Market Agripolis*
Local organic and quality food in Piazza Montanelli every third Saturday of the month, 4pm - 7pm
*Palio di Fucecchio (horse race)*
Every year since 1981, there is this horse race in Fucecchio. The town is divided into contrade (just like Siena!). You will spend your holidays at La Scuola Holiday Home, so in contrada Torre, whose colours are white and blue. It is a brilliant experience. Before THE day, there are lots of dining occasions in each contrada, sometimes al fresco, in order to spend nice time together, get to know each other and have a home style meal with some good wine. The date of the event is usually the third Sunday of May. In the morning you can attend the historical parade with its lively display of 1200 persons in rich locally made costumes along the streets of Fucecchio. The 3 afternoon races take place at la Buca del Palio (Via Fratelli Rosselli in Fucecchio). Palio might last until sunset! The races only last a minute or two, so you have to spend some time in Fucecchio beforehand, soaking up the atmosphere and the rivalry between the different districts, each of which is represented in the first two races. For a fucecchiese, Palio is like Football World Cup for Italians! The date for 2015 is the 24th of May!
*Infiorata di Corpus Domini (flower carpets)*:
On the Sunday of Corpus Domini the streets of historic Fucecchio are covered by beautiful floral carpets. In Fucecchio the custom of sprinkling the streets with flowers and forest sprigs compose sacred figures, dates back to the 30es but it was only in 1990 that the Flower Festival has become a tradition.
The carpet of flowers are displayed in the old city centre, starting from and coming back to the Collegiate Church. The materials used are many varieties of seasonal flowers (poppies, brooms, carnations, roses ...) and many other type of natural material (grapes, coffee, wood chips ...).
*Padule di Fucecchio, a bird watchers' paradise*
The Padule di Fucecchio is the largest non-coastal marshland area in Italy (around 1,800 hectares!).
The Padule is one of the last refuges for many plant species (the yellow floating heart or water fringe, now very rare in Tuscany, or white and yellow pondlilies, etc.), and is a big attraction for birdwatching enthusiasts, especially during the spring migration. Over 150 species can be observed throughout the year, at least fifty of which are nesting birds. Of particular interest are the herons, which nest in colonies, and migratory birds like the stilt bird, crane and black stork. There are 9 nature trails in the marshes, most on foot, some by car.
*Events Calendar 2015*
Corse di Primavera - Horse Race 6 April 2015 in Fucecchio
ObiHall Florence - James Taylor 21 April 2015 in Florence
Fiera del Gusto - Food Festival in Fucecchio 25 April 2015
Corse di Primavera - Horse Race 26 April 2015 in Fucecchio
Palio dei Bambini - Children Festival in Fucecchio 17th May 2015
Palio dei Cavalli - Medieval Parade and Horse Race 24 May 2015 in Fucecchio
Toscana - Arcobaleno d Estate 20th of June 2015 all over Tuscany
Lucca Summer Festival - Bob Dylan + Francesco De Gregori 1st July 2015 in Lucca
Pistoia Blues Festival - Counting Crows 3th July 2015 in Pistoia
Lucca Summer Festival - John Legend 5th July 2015 in Lucca
Lucca Summer Festival - Los Lobos 7th July 2015 in Lucca
Pistoia Blues Festival - Hozier 7th July 2015 in Pistoia
Lucca Summer Festival - Paolo Nutini 8th July 2015 in Lucca
Lucca Summer Festival - The Script 9th July 2015 in Lucca
Lucca Summer Festival - Billy Idol Kings and Queens of the Underground Tour 2015 10th July 2015 in Lucca
Lucca Summer Festival - Elton John And His Band 11th July 2015 in Lucca
Pistoia Blues Festival - Passenger 15th July 2015 in Pistoia
Mercantia: a medieval international festival of street theater in Certaldo from the 15th to the 19th July 2015
Pistoia Blues Festival - The Darkness and Black Label Society 18th July 2015 in Pistoia
Pistoia Blues Festival - Dream Theater 19th July 2015 in Pistoia
Pistoia Blues Festival - Santana 21st July 2015 in Pistoia
Lucca Summer Festival - Mark Knopfler An evening With Mark Knopfler and Band 22nd July 2015 in Lucca
Lucca Summer Festival - Robbie Williams Let Me Entertain You Tour 23rd July 2015 in Lucca
Pistoia Blues Festival - Sting 24th July 2015 in Pistoia
Lucca Summer Festival - Fedez and J-Ax 24th July 2015 in Lucca
Lucca Summer Festival - Lenny Kravitz Strut Tour 26th July 2015 in Lucca
Lucca Summer Festival - Snoop Dog + Marcus Miller, 28th July 2015 in Lucca
Salamarzana - Medieval Festival the second weekend of September 2015 in Fucecchio! The city will be animated by fiery warhorses, fearless knights, noblemen, ladies, artisans and merchants, common people and peasants, flag wavers and crossbowmen, musicians and jesters....if by magic they will bring back the mysterious and magic Middle Ages in Fucecchio.
Teatro Le Mulina in Florence - David Gilmour 15th of September 2015
On arrival you will receive information regarding pool rules when you collect the keys. The pool rules are also stated on posters in the holiday home, and for your own health and safety it is important that you follow these rules. Otherwise, La Scuola srl cannot be held responsible for any inconveniences.
I was born in Fucecchio and I have been living here all of my life. Even if I have been working in the fashion industry for more than 20 years now, I am more and more interested in the holiday rental world. I also attended a course to become a professional manager in hospitality and tourism management; it was fun to come back to school. I even started a blog about everyday life in Tuscany. You learn something new every day!
Ms. Tiziana Fierli purchased this apartment in 1998
My father bought this property in the late '90. It was in such a state! No heating, no electricity, no running water! He started to restore it (with Italian burocracy, this process can take a lot of time and even more patience!), then came with this idea: 'Why don't we rent to tourists?'. At that time (pre-internet era for me) I thought it was a terrible idea. 'Tourists in Fucecchio? This is not going to happen!'. How wrong I was!
It is easy to fall in love with this location! Splendid views over a tranquil valley, fantastic pool. Real possibility of reaching from nearby Empoli train station: Florence in 24 minutes, Pisa in 28 minutes and Siena in 45 minutes (stress free solution), or Lucca in under 30 minutes by car.
We are back and missing our Home in Tuscany. Our stay was wonderful, we are planing to go back in a future. So many places to see that in our four days stay we miss few places that we want to visit.
It was great to meet you at the restaurant, it was a pleasant surprise to see you there!!!
We enjoy the villa very much and took wonderful pictures!
Elsie, Pepe, Lydia y Cesar from San Juan, Puerto Rico
Wij hadden een geweldig verblijf tijdens onze huwelijksreis in LA SCUOLA Holiday Home. Tiziana was erg vriendelijk en verwelkomde ons met een taart met onze initialen voor ons huwelijk en fles rode wijn. De kamers zijn erg ruim en de omgeving is erg mooi. Het ligt erg centraal. Helaas was het zwembad defect toen wij er waren, maar we kregen als goedmaker 100 euro terug voor het verblijf en een gratis maaltijd aangeboden in het plaatstelijke restaurant. Ik zou er zo weer naar toe gaan! Bedankt voor het geweldige verblijf!
Our stay in La Scuola was marvelous, quiet, picturesque, serene, and totallying peaceful. The grounds are beautiful, the apartment well furnished and spotless, and the pool a welcome sight after a day of touring and walking. The layout encourages renters to socialize with other tenants in the early evening, with tables and benches out on the lawn. La Scuola is well situated for day trips to Florence, Lucca, Sienna, Pisa, and many other small tuscan towns. Our second floor apartment allowed us to open all the windows at night and be woken by the morning breezes and birds. Would recommend to anyone looking to spend a few days in one place. It felt like home.
Wir hatten mit unseren beiden Kindern (7 und 1,5 Jahre) eine wunderschöne Zeit in der Toskana und in Tizianas "La Schola"!
Tolle Lage des Objekts für Ausflüge nach Florenz, Pisa etc. und kleinere Orte in der Toskana, super Objekt ansich (Appartmentausstattung top, Pool top, wunderschöner Garten mit Spielplatz für die Kinder, Grillmöglichkeit!), super nette Betreuung durch Tiziana und ihren Bruder - ein rundum perfekter Urlaub! Vielen Dank nochmal dafür!
Wir werden definitiv wiederkommen!
Wir haben zwei sehr schöne Wochen in La Scuola verbracht. Die Anlage ist außerordentlich gepflegt und die Wohnungen geschmackvoll eingerichtet. Wir haben oft im Pool gebadet, weil es sehr heiß war. Tiziana hat uns umfassend mit Informationen über Einkaufsmöglichkeiten, örtlicher Gastronomie und Ausflüge versorgt und uns sogar ins Krankenhaus begleitet, als unsere Tochter sich den Fuß verstauchte. In der nahe gelegenen Pizzeria in Torre haben wir häufig gegessen, aber auch in Massarella war eine gute und preisgünstige Osteria.
Fucecchio ist ein toller Ausgangspunkt für Ausflüge, da man von dort aus die toskanischen mittelalterlichen Städte besuchen, aber auch zum Meer fahren kann. Wir empfehlen La Scuola unbedingt weiter!
We went to Italy the last week of June and was very happy to find La Scuola Holiday Home. The owners are very serviceminded and generous and provided us with good information on what to see and explore in the area. We particularly enoyed the city of Lucca and our visit to Cinque Terre. The pool at La Scuola Holiday Home was very much appreciated by our children since it was very hot this week but they also enjoyed the beaches around Pisa and particularly snorkling and looking for squids.Toscana offers so many beautiful places to visit and we did not have time to see it all and will most certainly come back.
To sum up - we had a lovely week and would really recommend a stay at La Scuola Holiday Home.
Famiglia Skoog
La Scuola ist ein Ort zum Wohlfühlen. Die Wohnung ist sehr gemütlich und komplett ausgestattet. Herrlich ist der Blick abends bei einem Glas Chianti. Das Haus und der Pool liegen in einem wunderbaren, gepflegten Garten - ideal für Familien mit Kindern. Die Lage ist sehr gut für Ausflüge. Man ist schnell in Lucca, Pisa oder Florenz. Vielen Dank Tiziana für die Gastfreundschaft und nette Betreuung.
Wir kommen gerne wieder!
Fucecchio is not yet well known, but its location is ideal for those wanting to combine relax, getting lost in the countryside and visit all the beautiful reasons why Tuscany is famous in the world. In less than an hour you can reach the beautiful walled town of Lucca; the world famous leaning tower of Pisa; Leonardo's birthplace Vinci; Florence - the jewel of Renaissance, home of Michelangelo's David and Ponte Vecchio -; the nice hill town of San Miniato; taste the wines of Montecarlo, walk on the golden beaches in Versilia or visit the Vespa museum in Pontedera. Driving to medieval gems Siena, Monteriggioni, San Gimignano and Volterra takes a little more than one hour. La Scuola Holiday Home is set inside the Cerbaie Natural Park, with trekking trails and picnic areas.
*Salvia e Ramerino is a nice country cafè / restaurant /pizzeria (also take-away) at walking distance
*Il Cacciatore and
*Osteria Numero Uno are a couple of good country restaurants within a very short drive.
*I' RitroVino di Caino has bakery products, ice creams, extra virgin olive oil, wine, cheese and other yummy local products. Fresh bread on Sunday morning!
*Gelsastore is a cafè, pizzeria and grocery shop offering a comprehensive range of goods, including groceries, fresh bread (also on Sundays), fresh fruit and vegetables, food to go and alcohol open from 4AM to 1AM!
*Free unlimited Wi-Fi.
*Spa services available on site.
Other Activities:
*Prada and various shoes/bags/clothes outlet shops in Fucecchio.
* NEW * Possibility to attend the local gym club.
* NEW * Special discounted price at a private beach in Versilia!!!
*Pistoia Zoo
Home of over 600 animals including about 65 species of mammals, 40 species of birds and 30 of reptiles.
*Botanical Gardens of Parco delle Mura - Lucca
Open from April to the end of October from 10 AM
*Whale and dolphin watching trips in Viareggio
Day long whale and dolphin watching trips in the Pelagos sanctuary with the only Tuscan licensed guide. From 6 to 20 persons per boat with lunch provided.
*Kayak Trips on Massaciuccoli Lake, near Viareggio
Courses and excursions in kayaks on Lake Massaciuccoli with Circolo Kayak Airone. 10 single kayaks and 1 Canadian kayak available for use.
*Migliarino San Rossore Massaciuccoli Park
One of the two regional parks in Tuscany. The park extends along the coast of Pisa and Lucca. Activities include horse riding, guided nature walks, bicycle tours and bird watching on lake Massaciuccoli.
*Museo Piaggio 'Giovanni Alberto Agnelli'
Vespas, automobile and locomotive museum. Open Tuesday to Saturday from 10 AM to 6 PM.
*Pinocchio Park and Villa Garzoni Gardens
Pinocchio based theme park in the medieval village of Collodi, birthplace of the author Carlo Lorenzini of the adventures of Pinocchio.
Beautiful Villa Garzoni Gardens
Learn and get to know butterflies at Collodi Butterfly House
*Inspiring Ideas for a Rainy Day: Caverns and Caves
Antro del Corchia: Corchia's cavern
Marble caves on the southern slope of the Corchia Mountain (1678 ms). Guided tours available in July, August and first half of September.
Grotta del Vento
Situated in the centre of the Apuan Alps' Natural Park, this is one of the most complete European caves, presenting an extraordinary variety of phenomena which are outlined with competence and precision by expert speleological guides. One, two or three hour tours to discover stalactites and stalagmites, polychrome flowstone, alabaster curtains and crystal-brimmed lakes at Grotta del Vento.
* Golf. There are various clubs in Tuscany. Choose from:
- A.S. Montecatini Golf Club in Monsummano Terme
- Club de Golf Fontevivo San Miniato in San Miniato
- Montelupo Golf Club in Montelupo Fiorentino
- Le Pavoniere Golf Country Club in Prato
- Castelfalfi Golf Country Club in Montaione
- Golf Club Poggio Vittorio in Lastra a Signa
You will need a car to reach La Scuola and to benefit from your stay here. We'll send you detailed driving directions.
If you have questions, need anything at the facility or if you need help, just ask! Please inform us immediately. This is the only way we can correct any shortcomings quickly.
|Rate Period
|Weekend Night
Mar 19 2015 - Mar 31 2015
13 night minimum stay
Springtime in Tuscany
Apr 1 2015 - May 8 2015
3 night minimum stay
Summer Start at La Scuola
May 9 2015 - Jun 26 2015
3 night minimum stay
Summer Sun at La Scuola
Jun 27 2015 - Aug 28 2015
Changeover Day: Saturday
14 night minimum stay
Wine Grape Harvest Time
Aug 29 2015 - Oct 30 2015
3 night minimum stay
My Standard Rate
7 night minimum stay
|Cleaning Fee
|Refundable damage deposit
|Stay tax
|€1 per night, per person. This amount will be due to the owner upon arrival. Does not apply to children under 14 years.
The Tourist Tax is not included (1,00 euro per person/per night, maximum of 6 nights, children under 14 free). The Tourist Tax is levied on behalf of the municipality of Fucecchio separately.
We at La Scuola Holiday Home advise all our guests to purchase travel insurance to indemnify them against any costs that they may incur as a result of unavoidable changes in their travel plans.
A 25% non-refundable deposit is due when booking. Balance to be paid 2 months prior arrival.
Please note that full payment will be required for any bookings made within 70 days of the start of the rental date. Payments accepted also through credit card (plus 3% credit card charge). Any charges incurred for bank transfer payments must be met by you.
Payment is usually accepted in the quoted currency (EUR) unless the currency and the amount is specifically agreed in advance with the owner / advertiser.


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Ninfeo Mio Cologne
By Annick Goutal for Men
Ninfeo Mio Cologne by Annick Goutal, Ninfeo mio is an exciting fragrance introduced by annick goutal in 2010 . This versatile unisex fragrance works well for the boardroom or a night out on the town with your friends. With alluring notes of italian lemon, petitgrain, bitter orange, and fig leaf, this well-balanced fragrance will leave you with a clean and light scent throughout the day. Subtle notes of lemon tree wood add a pleasant citric appeal to this classic scent. All products are original, authentic name brands. We do not sell knockoffs or imitations. ... Read More
- Daddy Yankee
- Daffy Duck
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- Dakar
- Dali
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- Dana
- Dark Blue
- Dark Obsession
- Darwin
- Datura Noir
- David Beckham
- David Beckham Essence
- David Beckham Homme
- David Beckham Instinct
- David Beckham Instinct Sport
- David Beckham Intense Instinct
- David Beckham Signature Story
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- Davidoff Champion
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- Day Off
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- Daytona 500
- Db Decibel
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- Deauville
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- Desir De Rochas
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- Dina Cosmetics
- Dior Homme
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- Disney
- Disney 102 Dalmations (unisex)
- Disney Babies (unisex)
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- Dk Men
- Dkny
- Dkny Energy
- Dkny Men
- Dkny Summer
- Dkny Unleaded
- Dna
- Dog Generation
- Dolce & Gabbana
- Don Ballare
- Donald Duck
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- Douce Amere
- Douro
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- Ducati
- Ducati Fight For Me
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- Due
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- Dunhill Black
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- Dzing
3.4 oz Eau De Toilette Spray (unboxed)
Item #500055
Unboxed items are a great way to save! They are the same as the boxed version, always original, fresh and authentic... Read more Why are they unboxed? Sometimes boxes can be damaged in transit, torn, or in less than perfect condition. We can buy these items cheaper than the boxed versions and we pass the savings on to you. Be sure to take advantage of great unboxed deals!
In Stock & Ready to Ship!
$ 62.99Add To Cart
3.4 oz Eau De Toilette Spray
Item #500054
In Stock & Ready to Ship!
$ 74.25Add To Cart
Customers Who Bought This Item Also Bought
About Annick Goutal
History and background of Annick Goutal. Goutal blossomed late, coming to perfume making after a career as a prizewinning pianist and model. She then met a man, separated from him, found herself alone with a baby (her daughter Camille), was diagnosed with breast cancer and married her childhood sweetheart. She went into the skin cream business with a friend and instinctively felt they were missing two things, fragrance and packaging. Read more about Annick Goutal
More Annick Goutal fragrancesfor Women: Eau Du Sud , Un Matin D'orage , Grand Amour , Le Jasmin , Mandragore , more
for Men: Sables , Eau D'hadrien , Mandragore , Les Nuits D'hadrien , Annick Goutal Vetiver , more
See all Annick Goutal products
Customer Comments
FragranceX.com did provide prompt service and the products were in good condition. Will do business again with them. Thank you
K. Noorani (Northbend, WA)


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PROBABLY THE MOST ABSORBENT SINGLE UNIT IN-CAR HUMIDIFIER BAG ON THE MARKET INTRODUCING:DAMP EATER!! Sick of having to set off 10 mins earlier for work JUST TO CLEAR THE WINDSCREEN? BUY ME AND GIVE ME A CHANCE then spend your ten mins sipping on your morning cuppa. I AM DAMP EATER I love the damp moisture in your car,caravan and home. Just place me on your dashboard or rear parcel shelf, leave overnight then remove in the morning and marvel at your clear condensation free windscreen! I come in an extremely strong virtually indestructible bag that will not go soggy when moisture has been absorbed. Very easy to regenerate just place on radiator for approx 3 hrs then re-use. or a microwave for 5-mins I Will last for many years 3-4 recommended. I have a unique carrying handle that makes it easy to hang anywhere eg, in cupboards to dry out shoes and camping/walking gear. Can Also use me around the house especially on the window sills of that condensation covered window.I am Damp eater and I have been designed and assembled in The United Kingdom where we have one of the most unpredictable climates for damp in the world. I am filled with 1.5kg of the best silica holding upto 800g/l of moisture, or 80% of my own weight.We do not fit any Velcro or sticking fasteners to mess up your dashboard.as this also could restrict your view Get into the habit of leaving me on your dashboard overnight then removing in the morning.Ideally one on the dashboard and one on the rear parcel shelf should keep your car condensation free. Try using me in the caravan You will know when I needs charging as My gauge will change color Do not worry that the bag will break,they are the same bags used to carry shot lead by deep sea divers around the world,so are virtually indestructible. My dimensions are a substantial yet not overly to much 380 mm long x 140 mm wide x 50 mm deep. I AM THE FIRST TO BE FITTED WITH A GAUGE SO YOU CAN SEE ME AT WORK A to let you know when I need charging
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Bat for Lashes Announces Tour
By Lindsay Zoladz on January 16, 2013 at 12:11 p.m. EST
Bat for Lashes has announced a string of tour dates that will take her around Australia and the West Coast -- marking American audiences' first chance to catch live performances of the songs from her gorgeous record The Haunted Man (which landed at #17 on Pitchfork's Top 50 Albums of 2012). No word yet on more U.S. dates, but note the suspiciously Coachella-shaped hole at the end of April...
Watch the Video for Bat for Lashes' "A Wall"
By Carrie Battan on December 21, 2012 at 9:45 a.m. EST
Here's the latest video to go along with Bat for Lashes excellent 2012 album The Haunted Man. This one, for "A Wall", tells a Labryith-like modern fairy-tale love story in a house party setting.
Watch Bat For Lashes on "Jools Holland"
By Evan Minsker and Laura Snapes on November 7, 2012 at 5:54 a.m. EST
On the latest episode of "Later... With Jools Holland", Bat for Lashes delivered a pretty flooring performance of The Haunted Man highlight "Laura".
Bat for Lashes Cover Rihanna's "We Found Love"
By Carrie Battan on October 11, 2012 at 10:18 a.m. EDT
A lot of the recent comments on the YouTube video for Rihanna's 2011 hit "We Found Love" are in the vein of, "Still listening to this song constantly." We agree, and so does Bat for Lashes' Natasha Khan. Last night, she and Bat for Lashes appeared on Zane Lowe's show on BBC Radio 1, where she performed a stripped-down cover of "We Found Love" live in the Maida Vale studios. Sadly, the song is not as affecting without Calvin Harris' blown-out whirl of a house beat, but it'll do.
Listen to Three New Bat for Lashes Songs
By Jenn Pelly on October 9, 2012 at 3:50 p.m. EDT
Photo by Anna Weber
On October 23 in the U.S., and October 15 in the UK, Natasha Khan a.k.a. Bat for Lashes will release The Haunted Man, her followup to 2009's Two Suns. Following the previously shared cuts "Marilyn", "Laura", and "All Your Gold", an additional three tracks are now available to stream: "A Wall", "Oh Yeah", and "Winter Fields". Check them out below, via SPIN, and watch a recent interview with Khan regarding the record for Pitchfork Weekly.
Watch: Bat for Lashes' Seven Song Set on the BBC
By Jenn Pelly on October 3, 2012 at 11:53 a.m. EDT
Today at BBC 6 Music's Maida Vale Studios in London, Bat for Lashes performed seven songs, including material from her upcoming record The Haunted Man, as well as tracks from previous albums Two Suns and Fur and Gold. From the new album, out October 23 in the U.S. via Capitol and October 15 in the UK via Parlophone/EMI, she performed "Laura", "Marilyn", and "All Your Gold".
Watch Bat For Lashes Dance on the Beach in "All Your Gold" Video
By Evan Minsker on September 30, 2012 at 8:25 p.m. EDT
On October 23, Capitol will release the new Bat for Lashes album, The Haunted Man in the U.S.; Parlophone/EMI will release it on October 15 in the UK. Now, there's a music video for "All Your Gold", wherein Natasha Khan dances on the beach. Watch it below, via Listen Before You Buy.
Listen: Bat for Lashes: "All Your Gold"
By Carrie Battan on September 18, 2012 at 2:31 p.m. EDT
Bat for Lashes: "All Your Gold" (via SoundCloud)
On October 23, Capitol will release the new Bat for Lashes album, The Haunted Man in the U.S. (Parlophone/EMI will release it on October 15 in the UK). Following "Laura" and "Marilyn", here's "All Your Gold".
New Bat for Lashes: "Marilyn"
By Jenn Pelly on September 13, 2012 at 10:21 a.m. EDT
Natasha Khan a.k.a. Bat for Lashes has a new album, The Haunted Man, out October 15 in the UK via Parlophone/EMI and October 23 in the U.S. via Capitol. Following "Laura", another cut from the record has surfaced, titled "Marilyn".
Watch Bat for Lashes talk about the new record with Pitchfork.tv below.
Watch: Bat for Lashes Discusses Her New Album, Cover Art, New Single "Laura", The Term "NSFW"
By Pitchfork on August 28, 2012 at 12:52 p.m. EDT
Pitchfork.tv recently sat down for some bangers, mash, and beans with Bat for Lashes' Natasha Khan. She talked about her upcoming album The Haunted Man, out October 23 via Capitol in the U.S. and October 15 in the UK via Parlophone/EMI. Khan also discussed her evolution as an artist, the meaning behind the album's cover, her feelings about the term "NSFW", and her recent collaborations with Beck and Dave Sitek.
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The Top 10 In Action Sports
01This is What It Looks Like To Break The World Record For The Fastest Time on a Bike
02This All-Action Edit Encapsulates Every Single Reason We Should All Love Motocross
03A Glacier The Size Of Manhattan Has Disappeared, And These Guys Got It On Film
04Cork 720s and Flipping Madness: The World's Best Slopestyle Stars Just Opened the MTB Season in Style
05Welcome to Qasr Al-Farid: The Rock With A Door That Will Rock Your World
06Already Got MTB Withdrawal Symptoms? Here Are The Crazy Downhill and Enduro Highlights From Crankworx New Zealand
0724 Reasons Why Snowboarding Was Better In The Early Noughties
08Win a Holiday for 2 in Chamonix with Three #holidayspam
0918 Things That Will Give Anyone Who Did Duke Of Edinburgh A Serious Flashback
1016 Things That Will Give 90s Skater Kids A Serious Flashback
Atlantic Winter Retrospective
A look back at some memorable moments of chasing beasts around the Atlantic from the perspective of Andrew Cotton. Building on a history of quietly and humbly charging these European big wave spots, to suddenly being touted by the media as one of the key players in this new to be famous arena, Andrew just gets on with the job and continues to put himself in to the most critical situations the Atlantic can throw at him and his crew. Once again, footage kindly donated by various people who are credited on the end, and the track is by Bastie Latham.
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Check out the new, mobile-friendly WineSpectator.com!
The 21st Masters of Food & Wine, held Feb. 22-25 at the Park Hyatt (formerly the Highlands Inn) in Carmel, Calif., was the last one. And this time they really mean it (since last year's event had been rumored to be the final one).
For the full article, check out the new issue of Wine Spectator, on newsstands April 12, 2007.
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Item in stock
Colour Wonder
Item No.1710103880
Color Wonder is a magical way of coloring in as the special markers only show up on the special Colour Wonder paper. Colour in your favourite Disney Princess characters with Color Wonder, where the colour only appears within the lines! For ages 3years up.
This item is available for
UK Home Delivery Free (UK orders over £30) or £3.99
Delivered within 4 working days
Next or Named Day Delivery
7 days a week between 8am - 6pm
Monday to Friday - order by 7pm - £4.99
Saturday & Sunday - order by 6pm - £4.99
Next or Named Evening Delivery
7 days a week between 6pm - 10pm
Monday to Sunday - order by 10pm - £6.99
Collect from store the next day - FREE
Order before 7pm for next day collection after 12pm midday
Show participating stores
Full Delivery details
- Age: 3+
- HWD: 32 x 23 x 2.2 cm
- Exclusively available online


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Rams figure to negotiate buyout of Martz's contract
|• Mike Tice was fired less than an hour after the Vikings' 34-10 win over the Bears in Sunday's regular season finale. The team announced that owner Zygi Wilf would not renew Tice's contract. Tice had already addressed the media before the move was made public.
|• St. Louis Rams coach Mike Martz, away from the job since early October as he received treatment for a bacterial infection of a heart valve, had his contract terminated Monday. Still to be determined is whether Martz's termination will take the form of a contract settlement or an outright firing, the St. Louis Post-Dispatch reported.
|• Texans coach Dom Capers will be fired on Monday, league and team sources told Mortensen. Capers is the only coach the expansion Texans have had during their four-year existence. Houston was 17-45 record under Capers, the 45th loss being a 20-17 overtime defeat in San Francisco that guaranteed the Texans the top pick in the 2006 draft.
|• Dick Vermeil went out with a win Sunday, retiring as coach of the Chiefs following a 37-3 dismantling of the Bengals. Kansas City became only the fourth team to go 10-6 and miss the postseason since the NFL expanded the field to 12 teams after the 1990 season. The Steelers' win over the Lions preventing the Chiefs from qualifying.
|• The Raiders fired Norv Turner Tuesday following consecutive losing seasons. The 53-year-old Turner, who had a year remaining on his contract worth about $1.75 million, had known his job was in jeopardy for the last two months after struggling to get the most out of a stacked offense. The Raiders went 4-12 -- one fewer win than they had in Turner's first season a year ago -- losing their final six games and eight of nine.
|• Coach Mike Sherman is uncertain of his future after the Packers finished an injury-riddled season at 4-12 Sunday. Packers GM Ted Thompson gave Sherman a two-year contract extension in August. But as injuries and losses have mounted this season, Thompson has sidestepped questions about Sherman's status.
St. Louis Rams coach Mike Martz, away from the job since early October as he received treatment for a bacterial infection of a heart valve, has been cleared by doctors to return to coaching on Jan. 1.
But no one should expect that Martz will be back on the sideline for the team's New Year's Day season finale against the Dallas Cowboys -- or, for that matter, that he will ever coach the Rams again.
Dr. Victoria Fraser of Barnes-Jewish Hospital in St. Louis apprised Rams officials this week that Martz is medically cleared to return to his job in two weeks. And team president John Shaw also confirmed to the St. Louis Post-Dispatch that Martz's agent, Bob LaMonte, phoned him this week to tell him the veteran coach was permitted back on the job on Jan. 1.
On the surface, the medical clearance would technically indicate that Martz could resume the duties he left following an Oct. 9 game against the Seattle Seahawks. From a practical standpoint, however, the news that Martz has all but recovered following more than two months of treatment for a condition known as endocarditis actually figures to hasten his exit from the organization.
Shaw reiterated several times in the past two months that he would not address Martz's future until the coach's medical status was resolved. With that hurdle out of the way, it is expected that the Rams and Martz's representatives will commence negotiations aimed at settling the head coach's contract.
Martz, 54, is under contract through the 2006 season with a salary of $3.25 million. The conventional wisdom is that the Rams will attempt to settle for less than that, essentially ending Martz's six-year tenure as head coach. An expeditious resolution of the contract would permit Martz -- who led the Rams to four playoff berths, two division titles and a Super Bowl XXXVI appearance in his first five seasons as head coach -- to pursue a new position from among the several anticipated openings in the league.
Sources close to both parties have told ESPN.com several times in recent weeks that a negotiated settlement would be the best approach for Martz and the team.
Through the October loss to Seattle, Martz compiled a record of 56-36, including a 2-3 mark this season. The Rams are 3-5 under interim coach Joe Vitt.
When he was originally stricken with endocarditis, Martz felt he would miss only a few weeks. But he then announced on Oct. 24 that, because he needed time to recuperate, he would sit out the balance of the season and return in 2006. Late last month, however, Martz angered Rams officials by suggesting that he hoped to come back to the team for the final few weeks of the 2005 campaign.
At the time, Shaw, who seemed intent on having Martz not return, said: "After speaking to Mike and his doctor several weeks ago, we were led to believe there is no way that he could come back full-time before the end of the season. I would be surprised if he is medically cleared. I'm not going to speculate as to what we would do at that point. But we're all concerned about him getting the sufficient amount of rest he needs to fully recover from this illness."
Len Pasquarelli is a senior NFL writer for ESPN.com.
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Wanted: Astrid Lindgren
tkopari(Z4 MN)April 17, 2013
I really want some cuttings of Astrid Lindgren, preferably rooted (or not). I have rooted cuttings of Abraham Darby and Music Maker available now. I will have un-rooted cuttings available from all of the roses on my Have List sometime in early June (I hope).
This post was edited by tkopari on Wed, Apr 17, 13 at 14:21


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We created Pandora to put the Music Genome Project directly in your hands
It's a new kind of radio –
stations that play only music you like
Thunder Kiss '65
Features of This Trackgrunge recording qualities
a subtle use of vocal harmony
repetitive melodic phrasing
extensive vamping
a vocal-centric aesthetic
an electric guitar solo
a gravelly male vocalist
a partially spoken vocal delivery
an unintelligible vocal delivery
prominent percussion
These are just a few of the hundreds of attributes cataloged for this track by the Music Genome Project.show more
Similar Tracks
This man speaketh with the tongue of the devil!
But I never try something I just do it! Brb g2g to 1965
If you don't like this song, then just skip it. Take your rude comments elsewhere.


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This was our first visit to Paramount. Me and my girlfriend visited during our work holidays. We had a great time, what was very impressive was the friendliness of the staff, they were very polite and always helpful. The food was tasty, although they could include some more deserts on the buffet.
The rooms seemed renovated, and provided all necessities, even microwaves. The beach was about 100 meters and there is a great diving center for those who are interested in diving.
Overall, we were satisfied and would visit Paramount again if we would choose Protaras area in the future
- Reservation Options:
- TripAdvisor is proud to partner with TripOnline SA and Otel so you can book your Paramount Aparthotel reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.
- Also Known As:
- Paramount Aparthotel Hotel Protaras
- Paramount Hotel Protaras
- Paramount Protaras
- Paramount Hotel Aparthotel
- Protaras Paramount


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Bathroom Vanities
1-24 of 43
Stufurhome 30-1/2 Inch Single Laundry Bowl$699Item #: GM-Y01WFree Shipping
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In October 2013, a program entitled "Health Care from the Pulpit" was introduced by Enroll America, a non-profit organization whose purpose is to increase enrollment in services provided by the Affordable Care Act among the previously uninsured. They intend to bring churches of different faiths together to "be engaged in the education and outreach efforts around the Affordable Care Act open enrollment period."
Programs like "Health Care from the Pulpit" have existed for centuries and in a number of national contexts. The greatest example occurred during the spread of the smallpox vaccine in France in the early 19th century.
Remember in the fall, when Obamacare's insurance exchanges got off to a shamefully bad start, and people who never liked the health-care law in the first place started cheering its impending doom?
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Instapundit's op-ed on the problems at Veterans Affairs hospitals reads like a plug-and-play template for libertarian commentary: "The cleanup will be, basically, impossible. That's because the VA is government health care." He goes on to argue that the unacceptably long wait times, deceptive record keeping, and undeserved executive bonuses at VA facilities are due to a lack of free-market competition: there's no bottom-line issue, so managers mismanage with impunity.
This would be a more compelling argument if the free-market alternative—the real-world one, not the theoretical one used so often to bash (real-world) government work—actually performed consistently better, and actually had a better system for accountability.
Life and Death in a Storm-Ravaged Hospital
There are few heroes in Sheri Fink's harrowing narrative of overwhelmed health-care workers during and after Hurricane Katrina.
Several GOP governors have made plans to go along with Obamacare's expansion of Medicaid. This is very good news.
When a hospital charges you $1.50 for a Tylenol pill—which a consumer can buy for 1.5 cents— you may shrug and figure you just don't understand the system.
But Steven Brill's cover story in Time magazine shows that the 10,000 percent markup on Tylenol is just a hint of the vast price-gouging that goes on in hospital billing.
There's a rough consensus that Steven Brill's massive story on health-care prices is an impressive piece of reporting with some less compelling analysis.
Last week, Christian social justice activist Ron Sider declared that he is quitting AARP because it's opposing changes to Social Security and Medicare that he finds reasonable: proposals that would ask more from wealthier seniors.
There are a lot of ideas out there for shoring up Medicare and Social Security, ideas that should be given serious consideration. And I agree with Sider on several points.
In case you missed it last Friday, the Obama administration quietly issued a proposed update to regulations coming out of the Affordable Care Act, popularly known as "Obamacare."
The verbiage is a bit dense, but here's the upshot: the ACA requires health plans to provide contraceptive coverage to all insured members. Some religious organizations and even a few for-profit companies objected to this requirement, citing religious beliefs.
Sick people long to be touched—the very thing loved ones tend to avoid. In today's mechanized medicine, doctors keep their distance as well.
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Part III- the action potential הודעות from neuron to :• ספרים מומלצים: להולכה פסיבית )4-5 (פרקיםbrain/Nicholls (פרקprincipal of neural science/Kandel :• לפוטנציאל פעולה nicholls9) או פרק 6 ב Rehearsal As we said • Membrane potential is the adjusted sum of equilibrium potential of it's ions )mostly K, also Na and Cl(. These are all concentration dependent channels. Which other type of channels are possible? • The flow for each Ion is determined by it's conductance and driving force. The flow in each channel can be described by V=IR. In which cases is the curve non linear? • The entire flow can be described as parallel RC circuit. time constant is τ =RC, (exponential increase) • The membrane also serve as a cable: Input is transmitted till trigger zone where action potential is created and it is transmitted from there to axon. rm Space constant is l= and resistance can be retrieved. ra Axonal size effect R's )preserves voltage better(-safety factor, myelin… Conductance velocity is determined by l & t. the paradigmatic view • Input arrive to dendrites in the form on Voltage change. • Voltage flow passively to axon hillock • In axon hillock starts the active process of Action Potential. • Action potential travels (regenerated) along the axon to cause Transmitter release in the synapse (gap) between neurons. This is the output • Transmitter attaches to receptors in dendrites of following neuron, causing voltage change… (starting point sensing receptor-skin, eyes… end- muscle. All that is in the middle between sensation and action, is in the input- output relationship, somehow…( The action potential- phenomenology Shortly: It's an electrical signal – high amplitude (up to 100mV) lasting ~0.5-1ms non-attenuated The ending first: positive feedback through depolariztion dependent Na channel, followeed by a negative feedback through depolarization dependent K channel Action potential phenomenology - different time periods • A-resting potential • B-threshold (sufficient depolarization), followed by rapid depolarization until a certain peak • C-re-polarization • D-after hyper- polarization The action potential phenomenology- what would you check for? • You have intra- and extra-cellular recordings • You can change the stimulus • You can try dissociating ions (how) • You can influence Vm (how?) =>What would you do to DECRIBE the phenomena? The action potential- phenomenology (what Hodgkin did) I all Threshold- "all or none" either full action potential, or nothing (note- "big enough stimulus" can indicate bigger amplitude of stimulus or longer duration) (first intuition- what does it tell us about the mechanism? can it be dependent solely on driving forces changes?) None The action potential mechanism- 1. it's the conductance • If it was the driving force it would be linear (no threshold) • Also, Curtis found it (Cole and Curtis, 1938) : How would we call such I-V curve? What it is assumed to be influenced by? (note: this dependence start at about half of the voltage of the AP threshold- the process starts before) The action potential mechanism • How can g be calculated? Ii=gi(Vm-Veq) =>gi= Ii/ (Vm- Veq). In voltage clamp we manipulated Vm and measure I- we can extract g. • But not in intra-cellular recordings since g & Vm are now interdependent g(Vm) Vm(g) Vm is controlled(Vm=Vc) in voltage clamp dV =0 dt IC = 0 I total = I R The action potential- phenomenology (what Hodgkin did) II Refractory period • Absolute: No amount of current will produce a second action potential • Relative: Second action potential will be achieved with only with larger currents (threshold increased) The action potential- phenomenology (what Hodgkin did) III Accommodation - extension of the refractory period concept- • If a cell is held (by voltage clamp!) at long sub- threshold depolarization, threshold increased (analogous to relative refractory period) Also taken to the extreme-a big/long enough depolarization will increase threshold to ∞ (analogous to absolute refractory period)- Depolarization block • Also opposite- if held at hyper- polarization, threshold decreases. With enough hyper-polarization- Vm is above threshold (anodic break response) The action potential mechanism- what did Hodgkin & Huxley check? • Is it all ions or part? Separating ion currents • Understanding the mechanism causing ion changes The action potential mechanism 2. it's not all ions • Overshoot- if permeability would have been increase for all ion the maximal peak of the action potential would have been 0mV. It's bigger )Hodgkin and Huxley, 1939( What is it closer to? (1909-K is in repolarization. 1945-K is sufficient) So far we know that there are: depolarization dependent Na channels->positive feedback Later depolarization dependent K channels->Negative feedback What can this alone explain? How can we prove it is Na and K indeed? The action potential mechanism 3.Separating ions- several methods • Changing concentration of extra-cellular ions. Or better- exchange (putting choline extra-cellularly instead of Na (why is it better to put something instead?) .problem-changes more then we wished. • Changing Vm (by voltage clamp)(note- NO AP!) • Specific toxins, if you have ones, of course. TTX is one The action potential Separating ions-results from mechanism concentration change • The amplitude of the action potential increase as extra-cellular concentration of Na are increased. =>:the amplitude of the action potential is due to Na current! If Na was replaced by choline What would have happened? The action Separating ions-results from potential Voltage clamp mechanism • A fuller explanation: When voltage is held constant above threshold there is inward current (which ion would move inward passively?), followed by outward current (which ion would move outward passively?) • The inward current is Na, K is probably outward (no proof yet) • Notice I-K is slower. Why? • Notice II- Na stops while stimulus continue- why? The action potential Separating ions-results from toxins mechanism • TTX - High affinity voltage dependent Na+ channel blocker (also Saxitoxin and cocaine to a lesser extend) ), proves that early current is Na- a specific voltage dependent channel! • TEA - Low affinity voltage dependent K+ channel blocker (also apamin), proves that later current is K- a specific voltage dependent channel! How did they find the right ions? Changing concentrations, voltage clamp, specific toxins (with voltage clamp) Rehearsal • Each ion current's direction is determine by Nernst, Vm by all ions that have channels (dependent on their Z) • Ion pass passively according to V=IR, with an exponential charge (rate dependent on t=RC), and decay (rate dependent on l = rm ) ra • In parallel, depolarization dependent Na and K channels exist in the cell (highest distribution- on the axon hillock, the paradigmatic "spike initiation zone"(. H & H found that action potential is due to conductance change )"depolarization dependent"(, leading to first a flow of Na, then K. Re-constructing the currents: • Na faster and Stubbed, • K slower and longer Open questions- • Why is Na faster then K? • Why is NA current terminated while K continues? How did they find the right ions? Changing concentrations, voltage clamp, specific toxins (with voltage clamp) The action potential The basic mechanism mechanism • Conductance increase and is voltage dependent • The ions flowing are first Na (inward) until peak, followed by K (outward) Conclusion about mechanism- positive feedback for Na causes rapid depolarization. Negative feedback for K causes later re-polarization (maybe also after-hyper polarization?) Re-constructing the currents: • Na faster and Stubbed, • K slower and longer Open questions- • Why is Na faster then K? • Why is NA current terminated while K continues? Explaining phenomenology Explaining phenomenology- threshold Two possibilities- 1. Enough voltage is needed to open the voltage dependent channels? 2. Enough Na current (in voltage dependent channel) is need to overcome K hyper polarization to create positive feedback -what do you think? -How would you test it? Explaining phenomenology Explaining phenomenology- the action potential • Resting potential Σcurrent=0 -> K=Na+Cl -> K>Na With depolarization Na voltage dependent channels open (K not yet), increasing Na threshold: Na=K. Then Na increase to create depolarization to increase… this is the rapid depolarization. Maximal peak= ENa (55mV) Maximal peak isn't always reached: K voltage dependent current opens, Causing hyper-polarization and the re-polarization and after-hyperpolarization phases. The action Evidences from single channel potential recording mechanism • From a much later times, when there were single channels recording and Na voltage dependent channel was known (and traceable) The action more issues : potential 1. what do we see in voltage clamp mechanism Voltage dependency: what do we see? Reversal potential Explaining phenomenology 2. The currents • currents dependency on voltage- as extracted from voltage clamp: K I-V curve K current is outward above -60mV inward below outward Na Na current is inward, decreasing when bigger then 0mV and outward intward above 55mV. Why the decrease? G and driving force interplay 3. conductance • Conductance time dependency as extracted from voltage clamp gion=Iion Vm-Eion =>Well someone will have to explain this Na inactivation Someday… Explaining phenomenology- what is missing here? • We are yet unable to explain refractory period and accommodation, so lets do discuss this inactivation.. Activation: Increased probability of channel opening with depolarization (in case on voltage sensitivity). Deactivation: the natural closing of the channel. Inactivation- active blocking of a channel (a type of control mechanism over opening type) De-inactivation- the natural ceasing of the inactivation process… =>The Na Channel goes through inactivation Explaining phenomenology The PEAK conductance • Conductance (peak conductance!) voltage dependency as extracted from voltage clamp: gion=Iion Vm-Eion 1. Conductance is monotonically increasing 2. It isn't an exponent, it's a Sigmoid (several exponents, Indicating reaction of higher degree) HH model A second look at conductance We have two channel (for K and for Na) that are: • Voltage dependent • Sigmoid (few exponents) Shaped • Similar, but not identical (K is more sigmoid then Na) • Na have inactivation (why not visible in the voltage dependency graph?) Introduction to action potential- first order reactions b open close a 1-n α(V) n closed β(V) open Probability to open a channel is a Probability to close a channel is b (P(close) ≠1-P(open) ) Voltage dependent=>a,b changes with voltage 1 t= An exponential process with (a b ) t = a 1 n bn dn n = n (V )1 e t n (V ) dt At a given V, n will approach n∞ in an exponential rate with time constant t bigger a,b, faster reaching n ∞( For specific V At equilibrium = a 1 n b n dn dN dt =0 1 dn a dt = n a a b dt a b N (t = ) = (a b ) dn t n (V ) = n n(V ) HH model The Hodgkin Huxley model for channel conductance )"gating model"( Assumptions: • membrane can be describe by RC circuit analogy • Membrane channels are separated and independent of each other • Membrane channel are ion selective • Membrane channel transit between two states- "open" and "close" a nclose First order reaction nopen a is the probability to open. b to close. b a & b are independent of each other (as if there are infinite ions). How many gates will be open at equilibrium? HH model For a first order reaction (Hodgkin Huxley): If a is P(open), b=P(close) 1-n α(V) n n opened, 1-n closed closed β(V) open n ∞ =a/a+b = a 1 n bn Then a change is dn t=1/a+b dt exponential increase and decrease = a 1 n b n dn t dt n = n (V )1 e t n (V ) 1 dn a = n a b dt a b dn t n (V ) = n n dt HH model K+ conduction is sigmoid= 4 first order reactions=4 n gates n∞ n g K (V , t ) = g K n 4 n4 0 n 1 With a pencil, H& H found that 4 mounted exponents fit the K sigmoid =>The K channel have 4 gates, opens only when all have opened HH model Na+ conduction is sigmoid= 3 first order reactions=3 m gates g Na (V , t ) = g Na m 3 0 n 1 With a pencil, H& H found that 3 mounted exponents fit the K sigmoid =>The Na channel have 3 gates (m) and an inactivation gate (h) opens only when all have opened HH model Implications I- the voltage dependent element is a & b • For gates N and M-a increase β α with depolarization, b decrease V • For gate h- M-a decrease α β with depolarization and b increase Gates time constants Dependence of time constants on voltage: m only in depolarization, n& h are slower at it (but available also in hyper -polarization m Time constants at h threshold depolarization: M>n~>h n Gates voltage sensitivity • Dependence of channels on depolarization>m>h HH model The final Hodgkin Huxley equations = I ext g l Vm Vl g K n 4 Vm VK g Na m 3 hVm VNa dV C dt dn t n (V ) = n n (V ) dt dn t m (V ) = m m (V ) dt dh t h (V ) = h h (V ) dt M=α (u) (1 - m) - β (u) m N=α (u) (1 - n) - β (u) n H=α (u) (1 - h) - β (u) h The Hodkgin-Huxley model of action potentials - currents I C = I R I ext L-leak (passive channels) dV C = I l I K I Na I ext dt dV C = gl (Vm El ) g K n 4 (Vm EK ) g Na m3h(VNa EK ) I ext dt dV C = g l (Vm El ) g K (Vm EK ) g Na (Vm ENa ) I ext dt Real numbers 25 v a m v = 0.1 exp 25 v /10 1 bm v = 4 expv /18 10 v a n v = 0.01 exp 10 v /10 1 bn v = 0.125expv /80 a h v = 0.07expv /20 1 b h v = exp 30 v /10 1 g Na = 120 g K = 36 g L = 0.3 HH model Evidences- a biochemical model for the gates and inactivation Basic structure Armstrong and Benzilla, 1977 The ball and chain And the K channel as 4 model for voltage sensitive domains inactivation 3-D Na+ (and Ca+) channel specificity • (Na is smaller then K) outer mouth:2 p loops with glutamic acid (-), select cations • inner mouth: 0.3x0.5nm pore )enough for Na+•H20 or smaller-not K) HH model More elaborated structure (Na and K) Shaker A type K+ pore channel voltage sensor Inactivation segment Voltage activated Na+ channel Selectivity filter (both Na and K) For K: Ion flow Voltage sensor -S4 helix • Present in all voltage sensing channels • Every 3rd residue is a charged lysine or arginine • Depolarization causes movement of their C termini from cytosolic to exoplasmic surface → gate opening • Activation involves movement of 12-14 charges Inactivation segment- • Na+ channel: Cytoplasmatic plug connecting S3 and S4(Evidence:Pronase is a proteolytic enzyme specific for blocking inactivation For K calculation show the ion transfer Selectivity to K by size Energy states for more/less ions Berneche S & Roux B 2001 Explaining phenomenology- the action potential • Resting potential Σcurrent=0 -> K=Na+Cl -> K>Na With depolarization Na voltage dependent channels open (K not yet), increasing Na threshold: Na=K. Then Na increase to create depolarization to increase… this is the rapid depolarization. Maximal peak= ENa (55mV) Maximal peak isn't always reached: K voltage dependent current opens, Causing hyper-polarization and the re-polarization and after-hyperpolarization phases. Explaining phenomenology- the action potential-conductance • Resting potential G(Na)>G(k) (but I(k) is bigger). • With depolarization g(na) increases (m gates), if enough for I(Na)>I(K) the depolarization will increase G(Na) (m gates) - rapid depolarization. • Then G(k) increase (n gates) and G(Na) decrease(h gate)- re- polarization and after-hyperpolarization (because G(k) decreases with delay)-refractory period • Returning to Vm G(Na) react faster then G(K)- Supra normal period) Explaining phenomenology- refractory potential again • Refractory period depend upon the time constant of gate h- at the re polarization period of the action potential gate h is closed. Re-polarization and after hyper-polarization will open it, but with delay. All closed- absolute refractory some opened- relative refractory. Accommodation, Depolarization block and anodic break • True on longer time scale- long depolarization will close h gates, elevating threshold. If elevated so that no threshold is feasible- Depolarization block • also the opposite-long hyper-polarization will open h gates, lowering threshold. If lowered so the Vm is above threshold- anodic break response. What does it means that hyper-polarization can open more h gates? Not all h gate are opened at Vm- Inactivation function • Accomodutions Effects = fraction of h gates opened. What else is this line Similar to? In Vm-60% .Why? pronase • Blocks Na channel inactivation how will it effect- the Action Potential? refractory period? accommodation? general information transmit? Method to see only Na activation: pronase conditioning hyper-polarization very brief stimulus Side note pronase allows viewing Na+ deactivation 1. Pronase Vm INa Oddities • A second look at the Na current voltage current Now do you understand better the time constant for h and m? Oddities II-current window Behavior of H and M gates is opposing. The depolarization required for the transition in interleaved. Result- depolarization window where there's constant current Improvement( few examples) • Azouz 2000- since the h gate in depolarization dependent, a slow increase in depolarization will close more h gate then a fast increase-> Action potential threshold will be smaller for lager depolarization pulse then a slow one. When do we see large depolarization pulse- when the input is synchronized. Meaning- threshold prefer coincidences • Naundorf 2006- the m gates are not independent (at least in the cortex where they measured, but cooperative- opening one increase the likelihood of the other gates to open, making the rapid depolarization steeper (as indeed they find) and making synchronous input more preferable. Action potential conductance • Saltatory conductance- only in nodes of renviar. • Formally- depolarization should be carried from dendrite to axon hillock, and then action potential should be carried across (myelin coated) axon. Actually- from all places to all place. Speed is depend upon myelin and size and (locally) upon t & l Action potential conductance is unidirectional Depolarization spread passively to both sizes, but depolarization is unidirectional- in the place last AP occur there is still refractory. Hyper-polarization will spread passively-how will it effect future activation? Notice- depolarization will spread passively back to dendrites- Back propagation The H&H variations-in space Variations in excitability along the neuron Axon hillock: lowest threshold:High density of Na+ channels,Voltage gated channels sensitive to near Vr Nodes of ranvier: many Na+ and leak channels (1000-2000 chnls/μm2) And also: Presynaptic terminals: Voltage sensitive Ca2+ channels Dendrites: voltage gated Ca2+, K+ and Na+ channels capable of producing APs Action potential propagation Depolarizatin fades in time and space, action potential regenerates. In the Axon-Salutatory conductance jumping between nodes of renviar. Formally- depolarization should be carried dendrite-> axon hillock(action potential) ->axon(ranier)->pre synaptic terminal Actually- from all places to all place. Speed is depend upon myelin and size and (locally) upon t &l Action potential conductance is unidirectional Depolarization spread passively to both sizes, but depolarization is unidirectional- in the place last AP occur there is still refractory. Notice- depolarization will spread passively back to dendrites- Back propagation Part IV- Single neuron computation Models of action potential H&H is a good "conductance model", but most models are simpler: They use "integrate and fire neurons"- • point neurons (no spatial considerations) • every input give small depolarization / hyper-polarization - excitatory or inhibitory but of costant size(+1 or -1). • The inputs are summed. The only determining factor is above/below threshold(and the threshold is constant) 1.linearly summing all inputs (conductance is passive) 2.threshold impose non linearity t is a low pass filter)= AND & OR functions =>McCullough and Pitts(1943)- This is sufficient to allow any computation Integrate and fire models Simple common model- leak integrate and fire: Summing input across time: V(t)=Vm+Rm*Ie(1-exp(-t/t Time difference (isi) between spike is linear to input amplitude 1 1 Rm I e EL Vreset risi = = t m ln R I E V tisi m e L th I&F : What will input integration be dependent upon? integration in time Two stimuli arrive with a time difference. Will they be united to a bigger stimulation or be separated? Dependent on t As t increase, stimuli are less separable Very brief: low firing rate, coincident detection Prolonged: higher rate, lower sensitivity Problems with I&F I & F models are DETERMINISTIC- Same input will necessarily lead to same firing rate, and all the cell can do is add up inputs )not only the AP is "all or none", the neuron is "all or none"(. Theoretically, this played a big part in the bottom up approach to visual processes- basic features are added up to more complex features… In reality input and threshold ARE NEVER CONSTANT Inadequacy of I&F models • Problems: 1. No inactivation (or other conductance references)-can be imposed on the models 2. Regular firing- if input is same on average , I&F model will produce very regular periodic firing rate with constant Inter Spike Interval (ISI) 1 1 Rm I e EL Vreset risi = = t m ln R I E V tisi m e L th Tal & Schwartz 1999 Tal & Schwartz 1999 3.Nonlinear I-V curve In reality, neurons have near Gaussian firing rate. Rate/Noise: for Gaussian =1, for integrate and fire ∞, for neuron ~1.2). Realistic ISI distribution I&F inadequacy solutions TYPE I-assume that the neurons ARE DETERMINISTIC therefore their only source of variance is the input. Therefore claiming that input is naturally Poisson-like (true). Especially true for high threshold and small t Cannot explain why experiment controlling input give variable results Variable input Increasing input variance make variable will broder ISI distribution, firing rate Stevens & zador 1997 TYPE II- assuming non deterministic response and implementing it by any of the various non linear component of the neuron-voltage gated ion channels, channel is difference kinetics, differential distribution of channels, morphological changes… Strong VS weaker negative feedback, softky & koch 1993 Sometimes give good predictions Conductance models Adding to H&H specific channels known to be found in various cells, or known geometry… Multitude of voltage activated channels: • 4 subtypes of voltage activated Ca2+ channels • Voltage activated Cl- channels • Voltage activated non-selective cation channels • Activation in hyperpolarization (h type) • Ca2+ activated voltage dependent K+ channel • Rapid, inactivating K+ channel (A type) "Allows complex information processing" Example: Epilepsy in mutant mice lacking Ka channels Example of other channels' importance- Action potential is not the only spiking mechanism Burst firing due to Ca firing: • Exist cells with 2 additional type of channels: 1. T type voltage activated Ca channels (T for transient)- open at very low threshold, inactivate fast. 2. L type voltage activated Ca channels (L for long)- open only at higher threshold, very very slow de-activation (not inactivation-what is the difference?) =>T open at low threshold (Vm)->inward current->depolarization-> action potential (T close)->higher depolarization->L open for long period- chain of action potential (what stops it?) Burst firing due to Ca firing: =>T open at low threshold (Vm)->inward current- >depolarization-> action potential (T close)->higher depolarization->L open for long period- chain of action potential what stops it? When will it start again? How are the action potential effected? • Burst firing due to Ca firing: what will happen at these cells if held depolarized? Conclusion- Action potential isn't everything! Action potential conductance • Saltatory conductance- only in nodes of renviar. • Formally- depolarization should be carried from dendrite to axon hillock, and then action potential should be carried across (myelin coated) axon. Actually- from all places to all place. Action potential conductance is unidirectional Depolarization spread passively to both sizes, but depolarization is unidirectional- in the place last AP occur there is still refractory. Hyper-polarization will spread passively-how will it effect future activation? The H&H variations-in space Variations in excitability along the neuron Axon hillock: lowest threshold:High density of Na+ channels,Voltage gated channels sensitive to near Vr Nodes of ranvier: many Na+ and leak channels (1000-2000 chnls/μm2) And also: Presynaptic terminals: Voltage sensitive Ca2+ channels Dendrites: voltage gated Ca2+, K+ and Na+ channels capable of producing APs
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December 09, 2014
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