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When planning our October 2012 trip to Japan, Jackie and I easily settled on Kanazawa as the destination for our first real exploration beyond Tokyo and Kyoto. The hard part was choosing way-stations as we traveled west-by-northwest from Tokyo: every place sounded interesting. With assistance from the New York office of the Japan National Tourism Organization (JNTO) - and from others, including a friend who used to work for JNTO - we finally constructed a diverse itinerary of towns and villages all easily visited by train and/or bus.
We were especially looking forward to our first stop: Inuyama, a castle town some two and a half hours from Tokyo by rail. Our friend got us all excited about its 15th/16th-century castle, claimed by some to be Japan's oldest surviving example, and about the Meiji-Mura outdoor architecture museum. We were also intrigued by the prospect of seeing cormorant fishing on the Kiso River - and by the fact that a Brooklyn native, Anthony Bianchi, is a member of the city council.
From Tokyo Station we caught the bullet train to Nagoya, then took a short ride on a local rail service (you can look up schedules for all of Japan on this English-language website: http://www.hyperdia.com/en/) to Inuyama, arriving in time for an elegant but not costly lunch at Urashima tofu café, including tofu made with burdock root (which was then in high season) and a most amazing version of miso-glazed grilled tofu served on triple-pronged bamboo skewers. What made it amazing was its fragility: It looked as if it had to have been made with slices of firm or even pressed bean curd, but in fact it was soft and creamy under its flavorful coating.
It was then time to meet the guide who would show us around Inuyama Castle and introduce us to the city. A while ago, I wrote about the English- (and other-language-) speaking volunteer guides that many Japanese towns and cities make available free of charge. This system seems particularly effective in Inuyama, whose goodwill guide association has many members, many of whom have worked in or traveled to the United States. Some indeed have stayed with families in Brooklyn as part of B. Bridges, an educational exchange program developed by Mr. Bianchi in conjunction with his old high school - which will be sponsoring interesting-sounding Inuyama Day events at Brooklyn Borough Hall Plaza on May 3 from 11 a.m. to 3 p.m. (Details toward the bottom of this page on the Japanese consulate's site.)
Inuyama Castle, one of four in Japan classified as National Treasures, is set on high ground overlooking the Kiso River on one side and the town on the other. The cobbled path up to the castle was dotted with well-behaved school children bearing sketchbooks, pencils and water colors, painting the sights (some of them very nicely). In a Westerner's notion, a castle is a vast structure combining residential and military functions; Inuyama castle was not used as a dwelling, except by the soldiers assigned to it; the lord and his family would have lived nearby but not in the building itself. As with any structure made to serve, in part, as a watchtower, you will want to climb all the steep steps to the topmost level; not only do you see the best views in town, but you also get a far better idea of the complexity of the roof, both its form and the way in which it is tiled. Apart from a short period in government hands, the castle was in the Naruse family from 1617 to 2004, when it was transferred to a foundation set up by Aichi Prefecture. It contains a series of portraits of the successive lords, all in medieval pose and costume - until the moment when Japan opened to the West in the mid-nineteenth century: from one portrait to the next, the image changes from that unchanging, stylized depiction to a studio photograph of a man in a Western-style military uniform. That exemplifies the impact of a key moment in Japanese history.
We descended from the castle and spent some time in the Inuyama Artifacts Museum, which, in addition to an interesting collection of objects, contains a model of Inuyama in feudal times, showing who lived where: samurai, merchants, artisans and so forth. The grid of the old city remains to this day, so it is especially interesting to see how the plots were originally allocated; labels are in Japanese, so the presence of our goodwill guide was of great assistance.
Across the street is an annex: the Karakuri Museum, devoted to articulated figures (automatons, almost) some of which are traditionally used as part of the town festival, which takes place in April each year; some of the tall, elaborate floats that form the festival procession are housed in high, narrow "garages" scattered around town - without our guide we would certainly never have guessed what was inside them.
Our hotel, the Meitetsu Inuyama, was on the river bank a short walk from the castle. I can't think why you would want to stay anywhere else: it is pleasant and perfectly situated, with pretty grounds and a hot spring. We opted to stay in a Japanese-style room, but a Western-type double would have been less expensive and, at least for us, more comfortable. From the hotel it was another short stroll to the embarkation point for our cormorant fishing demonstration. We were lucky: we just caught the tail end of the spring-summer season. You can see dates and prices on this website, but you will need to speak Japanese to book, so I recommend asking your hotel or the goodwill guide association for help.
We boarded in the early evening for dinner on the river (you order a bento supper as part of the package and can bring your own beer or other drinks), cruising past the castle and well beyond. Seeing the castle from the water - as a potential invader might have seen it - explains a lot about why such military structures are built overlooking the river and the flat land beyond, just as they are, say, on the Rhine (to which the Kiso has been compared). As the sun disappeared, we returned to the dock and disembarked while the crew removed our dinner debris; we boarded once again and headed out into the dark. Cormorant fishing is quite a sight. In Chinese or Japanese paintings and woodcuts, it seems quite placid, the light (which evidently attracts the fish as well as making it easier for the birds to see into the water) often provided by paper lanterns. In the Kiso River tradition, the light comes from a wood-log fire contained in a metal basket at the end of a boom. The fire is furious, with sparks afly, and the animation is heightened by the cormorants themselves, which noisily roil the water with their diving, and by the fishers, who are able to keep tabs on eight or more birds without tangling the lines that tether them: When a cormorant catches a fish too large to pass down its throat (which is constricted by a collar that will allow only small fish to be swallowed), the fisher will haul it out of the water and retrieve the fish (ayu, or sweetfish - which also appeared in our bento boxes on the boat) before tossing the bird back for more action.
In the telling, this style of fishing sounds cruel. But no one can have any idea of what is like for the cormorants, so I'll say only that it is an exciting treat to view an age-old practice that has been kept alive, if only for tourists.
The next morning our guide took us on visits to a candy shop and a calligrapher's studio. Genkotsu, a hard candy made from soybean flour boiled with sugars and other ingredients, is not unique to Inuyama, but every town has its own traditions: In Inuyama, gentotsu you buy at Fujisawa Seika (confectionary) is made even more appealing with the addition of ground sesame seeds. The firm has been in the same family for 130 years and is currently run by Chizuko Hayashi. We watched Ms. Hayashi and her assistant blend the ingredients, boil the mixture to the proper temperature, then knead it and shape it by hand into ropes before feeding these through a clanking machine of her father's invention to form the candies. Thanks to our guide, we were able to ask questions and learned quite a lot about the process. The sesame seeds and a subtle hint of spice made Ms. Hayashi's genkotsu more tempting to Jackie and me than a lot of other versions we've had. Packages of them are good to take home as easy-to-carry gifts.
We then dropped in on Oson Ito, a exceptionally fine calligrapher and - like Ms. Hayashi - a delightful person to visit. She works in both traditional and more personal styles that convey both grace and power (a combination that, for me, gives Japanese calligraphy its special edge). Beyond the work that is on display in her studio - the Nishi Getsu gallery - she will look you in the eye, discuss your personality (through the indispensable guide) consult some arcane astrological charts and choose a single character that sums you up. In our chat, Ms. Ito pretty much nailed some of our salient traits, and the characters she drew for us seemed apt; in any event, they were both beautiful pieces of art. Typically she charges around $100 for these original works. (She will be giving demonstrations at the Brooklyn event I mentioned above.)
The next, and last, stop was Meiji-Mura, a lush 250-acre privately owned park to which buildings from all over Japan have been transported, mostly complete and mostly well restored. They are all from the late nineteenth and early twentieth centuries, the period when Western design came to dominate public architecture. There are direct buses from town and the rail station; transport details are easily sorted out through the goodwill guide association. I cannot stress too emphatically that there is nothing silly or hokey about this museum. Perhaps the best known of its 60 buildings is the (partial) Imperial Hotel from Tokyo, designed by Frank Lloyd Wright in 1915 to 1923. With its strange, rough stone and concrete sort-of-Mayan decoration, it is rather odd, and well worth seeing. Even more so are buildings such as prisons, theaters, Christian churches, breweries, government offices and large merchants' houses that served day-to-day purposes for a wide range of people. When you see the little tram that runs around the park, you may turn up your nose. Don't: you will certainly want to walk most of the time, but this place is enormous. The restaurant in the park is quite good and offers gorgeous views of the undeveloped parts of the forested grounds: a nice place to stop for a rest - and to treat your guide to something to eat and drink.
Late that afternoon, we were on a train to the next stop: Takayama. There were wonderful things to see (and eat) there and elsewhere on our trip, but somehow Inuyama made a particular impression as a perfect, and diverse, place to spend a couple of days.
Dining and lodging
Tofu Café Urashima. 726-2 Higashi Koken, Inuyama; +81 (0)568 27-5678; lunch around
¥1,575 ($16).
Meitetsu Inuyama Hotel. 107-1 Kitakoken, Inuyama; +81 (0)568 61-2211; http://www.japanican.com/hotels/shisetsudetail.aspx?st=5449005


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WALTHAM, Mass. -- A handful of practice leftovers after the Boston Celtics met with the media on Tuesday before a morning session and afternoon flight to New York in advance of Wednesday's Game 5 of an Eastern Conference first-round series against the Knicks:
* C'S ARE COLORBLIND: Informed that Kenyon Martin told his teammates to wear "funeral colors" to Wednesday's Game 5, Jason Terry brushed off the suggestion that Boston's season will end then. "That's good. I thought they wore that last game, too," said Terry. "I mean, for us, it doesn't change. Whether they wear white, pink, blue, black, green -- it's Game 7 for us. So we know what mindset we have to be in and if you lose you're going home. That's what it is."
* KG NOT THINKING ABOUT HIS FUTURE: Asked if he had considered that Wednesday's Game 5 could be his last NBA game, Kevin Garnett said retirement isn't on his mind at the moment. "I'm thinking about the game Wednesday and pretty much that. I haven't thought about post, after -- I'm focusing on what it's going to take to get to the next game."
* FAITH IN BASS: Celtics coach Doc Rivers said it was Brandon Bass' success guarding LeBron James during the Eastern Conference finals last season that gave him the confidence to put him on Carmelo Anthony in this series. And why has he been so successful, particularly on the perimeter? "[Bass] has a lot of size. Shooting over size, I jokingly said in 2009 or 2010, one of those years we were playing the Lakers, we were getting a lot of wide-open shots, why are we missing them? And then you watch the film, a lot of 7-footers are standing in front of them and you have to shoot over them, and, even though it's not a tight, contested shot, it's still a 7-footer. In Brandon's case, he's not that, but he's bigger than guys that normally guard Melo."
* EYE-OPENING PERFORMANCE? Asked if he thought the league might take notice of his play, particularly given his exploits this round against the Knicks, Jeff Green offered, "I hope so. I've been working hard. The playoffs are where players are made. Hopefully people are starting to take notice of what I can do. I mean, I know what I can do. I don't care what other people think. It doesn't matter to me. I'm just trying to win games and win for my team."


text:
Inky Bits
Karen Fildes
I'm peddling my inky bits- little nothings and little somethings- they are original sketches that were helpful in my process to study for various applications. They are little gems- some of them merely concepts- but nevertheless, I am selling everything I can to raise enough money for my project. Click on these little slug eating guinea hens and poof, you'll be in my inky bits store. I will be able to ship anything to you by September 1st. If you would like your image matted and framed, leave me a note and I'll fix you up. The images that have been posted are snapshots from my phone, so they are not easy to reproduce. But the originals you will receive are a clean white and they dress up real nice in a juicy mat for gifting.
My two recent books, The Secret World of Slugs and Snails, and the Eat A Bug Cookbook, were both reviewed quite nicely with my sketches mentioned. The "Inky Bits" I am posting are being made available as a part of a scheme to raise funds to help me launch my next project. I can't tell you too much about it but it will require my undivided attention and the funds that it will take to pay my bills while I focus.
Many of you know that I double as a nanny, which in my world, is a privilege. Listening and learning from the children is a way to see beyond. My emphasis has been to help the children of loss find their love for life and in that process, they each are met with the challenge to make their mark. We go through extensive sessions as they search and discover the writing instrument that will sing for them. I have made great discoveries about the pen and its play in expression for the healing child. I'd like to pursue my discoveries in an illustrated 26 essay catalog of "Lessons From the Booger Fairy."


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The French man is self-confident because he considers himself individually, both as regards mind and body, irresistibly captivating to either men or women. The Englishman is self-confident through his absolute conviction that he is a citizen of the most fortunately constituted kingdom in the world, and because, as an Englishman, he knows always and in all circumstances what it is requisite for him to do, and also knows that all that he does as an Englishman is correct beyond cavil. The Italian is self-confident because he is excitable, and easily forgets himself and others. The Russian is self-confident for the precise reason that he knows nothing, and wishes to know nothing, because he believes that it is impossible to know anything. But the German is self-confident in a worse way than all the rest above and beyond all the rest, because he imagines that he knows the truth, – the science which he has himself invented, but which for him is absolute truth !
War and Peace by Leo Tolstoy


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How long will SMBC keep in the refrigerator? I made too much and need to know how long it will keep or if I can freeze it?
2 replies
(I've heard) It keeps for about a week in the fridge, about a month in the freezer. I never save it longer than a week, butter (especially unsalted) has a nasty habit of picking up flavors from the fridge, so make sure it is tightly sealed.


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Direct from the Manufacturer
"Develop trimless voltage-controlled oscillators
|Catalog Datasheet
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|Abstract: capacitance CV. EQN8 References 1. 2. 3. 4. 5. 6. 7. Chris O'Connor, Develop Trimless Voltage-Controlled Oscillators, Microwaves and RF, July 1999. Wes Hayward, Radio Frequency Design, Chapter 7 , compliance range is usually fixed by the battery voltage or regulator. Basic Concept for Trimless Design
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text:
This Lucky Reptile Desert Decor Set has been designed to give your desert dwelling pets enclosure a natural look and feel.This Lucky Reptile
The Lucky Reptile Life Experience Desert Décor Set consists of natural dried woods and branches. Ideal to use in nano tanks or simply by placing these around your exotic pet's enclosure will give this a natural feel.
Live Food and Frozen Food orders
Tuesday 04 July 2017
Unfortunately, our wholesale partner has been unable to supply us today with live food and frozen goods to fulfil all our outstanding customer orders.


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Kyle McMillan, GuestAccording to The Business Insider, Steve Jobs only downloaded one book, ever, to his iPad 2: Autobiography of a Yogi, by Paramahansa Yogananda. To those in the know, this should come as no surprise, as it was also his parting gift to all of the attendees at his funeral — the last gesture he made towards everyone closest to him on earth. Jobs' spirituality was not widely well-known during his life, and while many will contest that certain busi [...]
Excerpt from huffingtonpost.com When I was in kindergarten, a boy in my class tossed my favorite book over our elementary school fence. I remember crying profusely, not because I was sad to see it go, but because I was so furious that he was s...
Excerpt from usatoday.comIts fuel tanks empty and its options gone, NASA's Messenger spacecraft smashed into planet Mercury on Thursday afternoon after valiantly fighting off the inevitable.Engineers calculated that the spacecraft, traveling a scorc...
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Frame-shift mutation in TWIST1 is associated with type 2 scurs syndrome.
Interaction with Snail1/2, and Twist function more generally, is regulated by GSK-3-beta-mediated phosphorylation of conserved sites in the WR domain.
These results indicate that Twist1 Ser42 phosphorylation contributes to the pathogenesis of bleomycin-induced pulmonary fibrosis through angiopoietin-Tie2 (show TEK ELISA Kits) signaling.
the epithelial-mesenchymal transition-related transcription factor Twist1 cooperates with Slug (show SNAI2 ELISA Kits) to regulate EMT (show ITK ELISA Kits) upon H2A.X (show H2AFX ELISA Kits) Loss.
Downregulation of CXC chemokine (show CXCL12 ELISA Kits) ligand 11 can inhibit tumor angiogenesis, suggesting that anti-CXC chemokine (show CXCL12 ELISA Kits) ligand 11 therapy may offer an alternative treatment strategy for TWIST1-positive ovarian cancer
The data identify TWIST1 as a central pro-fibrotic factor in systemic sclerosis, which facilitates fibroblast activation by amplifying TGFbeta (show TGFB1 ELISA Kits) signalling.
ETS2 (show ETS2 ELISA Kits) and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2 (show SIAH2 ELISA Kits)
CD44 (show CD44 ELISA Kits), ALDH1 (show ALDH1A1 ELISA Kits) and Twist1 were significantly overexpressed in involved ALN (show TTC21B ELISA Kits). The serum levels of CA153 in those patients were clearly increased and the survival rates decreased, which suggested that a combination of Twist1 in ALN (show TTC21B ELISA Kits) and CA153 may function as an indicator for the prognosis of patients with breast cancer.
TWIST1-E protein heterodimeric complexes may thus constitute the main active forms of TWIST1 with regard to senescence inhibition over the time course of breast tumorigenesis.
nuclear TWIST1 expression was an independent predictor of a poorer prognosis in metastatic melanoma.
HMGA2 regulates the Epithelial-mesenchymal transition of gastric cancer cells and the acquisition of tumor stem cell properties through direct regulation of the downstream target gene TWIST1.
overexpression of miR (show MLXIP ELISA Kits)-10b results from high levels of TWIST-1 and may induce a decrease of E-cadherin (show CDH1 ELISA Kits) membranous protein levels, thus contributing to the acquisition of metastatic phenotypes in colorectal cancer.
the mesenchymal properties of the cranial mesoderm are likely to be regulated by a network of TWIST1 targets that influences the extracellular matrix and cell-matrix interactions, and collectively they are required for the morphogenesis of the craniofacial structures.
TWIST1 expression promotes developmental angiogenesis by inducing endothelial cell proliferation and migration.
There was a possible regulatory link between Twist 1 and PPARgamma (show PPARG ELISA Kits) in 3T3-L1 mature adipocytes. This regulatory link enhanced the regulation of PPARgamma (show PPARG ELISA Kits) and may be a functional mechanism of Twist 1 regulation of adipocyte physiology and pathology
ur study revealed the dynamic Twist localization within the early stage of embryo. The results are discussed in terms of potential roles of Twist1 in the processes of lineage segregation, hatching, and implantation in post-compaction embryos and in blastocysts.
findings demonstrate that Twist-1, which maintains BMSC at an immature state, endows them with an increased capacity for supporting hematopoiesis via direct activation of CXCL12 (show CXCL12 ELISA Kits) gene expression.
Twist1, a target of canonical Wnt (show WNT2 ELISA Kits)/beta-catenin (show CTNNB1 ELISA Kits) signaling, also functions to maintain Wnt (show WNT2 ELISA Kits) responsiveness and is a key effector for cranial bone fate selection and dermal condensation.
Findings indicate that Twist1 has a novel role in epithelial carcinogenesis by regulating proliferation of keratinocytes, including keratinocyte stem cells during tumor promotion.
Data show that administration of MVA (show MYO5A ELISA Kits)-TWIST/TRICOM vaccine induces Twist transcription factor-specific T-cell responses.
TLR4 (show TLR4 ELISA Kits) signaling via NANOG (show NANOG ELISA Kits) cooperates with STAT3 (show STAT3 ELISA Kits) to activate Twist1 and promote formation of tumor-initiating stem-like cells in livers of mice.
the ventral migration of Cranial neural crest cells (CNCCs) away from a source of Bmps in the dorsal ectoderm promotes ectomesenchyme development by relieving Id2a-dependent repression of Twist1 function.
twist1a and twist1b control skeletal development and dorsoventral patterning by regulating runx2b in zebrafish
These observations are consistent with a role for twist1 in craniofacial, vertebral, and early renal development.
Basic helix-loop-helix (bHLH) transcription factors have been implicated in cell lineage determination and differentiation. The protein encoded by this gene is a bHLH transcription factor and shares similarity with another bHLH transcription factor, Dermo1. The strongest expression of this mRNA is in placental tissue\; in adults, mesodermally derived tissues express this mRNA preferentially. Mutations in this gene have been found in patients with Saethre-Chotzen syndrome.
twist homolog 1
, twist transcription factor
, twist homolog 1 (acrocephalosyndactyly 3; Saethre-Chotzen syndrome)
, hypothetical protein
, twist-like protein
, twist-related protein 1
, X-twist
, twist-related protein
, B-HLH DNA binding protein
, H-twist
, TWIST homolog of drosophila
, class A basic helix-loop-helix protein 38
, Pluridigite
, Skam10Jus
, charlie chaplin
, polydactyly EMS
, twist gene homolog 1
, twist 1
, twist homolog 1 (Drosophila)


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Internet trolls use the anonymity of the Internet to inflame emotions, tarnish reputations and possibly damage careers. In Internet slang, troll refers to someone who participates in a range of actions from attacking total strangers and celebrities to bullying. Recently trolls received worldwide attention for their attacks on Nicola Brookes and drew the attention of a court in the United Kingdom, which required Facebook to reveal the identity of an anonymous troll.
Nicola Brookes is a 45 year old who was attacked by trolls after she made a comment on Facebook supporting former X Factor contestant Frankie Cocozza. The trolls set up a fake Facebook account in her name and used it to attract young girls and make inappropriate comments. While Facebook seemed concerned over individuals using its platform to abuse others, Facebook could not disclose the identity or IP address of the trolls without violating data protection laws. Facebook has yet to be served at its headquarters in California, but a representative of the company said the company planned to comply. Brookes is the first person to take a private case to the high court and win an order compelling Facebook to disclose the names, email addresses, and internet protocol addresses of the trolls.
Unfortunately, Brookes is not the first person to be targeted by trolls or other abusive behavior on-line. A survey last month found that just over half of internet users say they have been abused online or via text message. In the United States, Chief Judge Royce Lamberth ruled force Twitter to disclose the identity of a troll who threatened to use a "Vietnam era machete" on then Republican presidential primary candidate Michelle Bachmann.
Extreme cases like these drove some prominent technology executives (Randi Zuckerburg and Eric Schmidt) to speak out against Internet anonymity. New York recently introduced legislation that would require trolls to reveal their identities or remove cruel posts if someone filed a complaint. The legislation has received mixed reviews but indicates a responsiveness to the trolling and Cyberbullying issues.
–Samara C. Pals Cramer
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What is aging? • Aging is the accumulation of changes in an organism or object over time. In humans, aging is a dynamic process with physical, psychological and social dimensions. • The process of aging involves changes shared by all individuals (universal aging) and others which merely become more common with age (probabilistic aging). • Senescence is the technical term for the process of aging. It refers to changes in an organism's biological functioning after maturity is reached and may occur on both a cellular and an organismal level. • Rates of organismal senescence do not always correlate with chronological age, so functional age often varies as much within as it does between age groups.
Two Groups of Theories Regarding Senescence • Stochastic (Damage-Based) Theories of Aging • Accumulated damage as a result of ongoing, imperfect biological processes.
– – – –
Free Radical Theory DNA Damage Theory Telomere Theory Protein Cross-Linking Theory
• Programmed Theories of Aging • Changes in gene expression concerning repair enzymes, hormonal levels, immune system function, etc.
– Evolutionary Theory of Aging
Free-Radical Theory •
When oxygen is used to make energy in human cells, it generates highly reactive compounds known as free radicals or reactive oxygen species (ROS). Free radicals have an odd number of electrons and are therefore highly reactive, making them significant sources of oxidative stress. Antioxidant therapy is promoted by many as a means of combating the effects of free radicals.
DNA Damage Theory •
Proponents of the DNA Damage theory of aging argue that aging results from the accumulated mutations and errors in DNA sequences over the course of an organism's lifespan. The theory explains that errors in the genetic code may lead to cancer, apoptosis, or cellular dysfunction.
Telomere Theory •
Telomeres, sequences of nucleic acids located at the ends of chromosomes, are shortened during each mitotic cell division. The telomere theory of aging suggests that the gradual shortening of our chromosomes is responsible for the cellular damage and dysfunction associated with aging. Telomerase, an enzyme found in germ and cancer cells, acts to restore the telomeres.
Protein Cross-Linking Theory (Glycosylation Theory) •
The glycosylation theory of aging suggests that the aerobic binding of sugars to proteins impairs protein function, leading to the inefficiencies in cellular function associated with aging. Protein Cross-Linking is encouraged by high blood glucose levels, so a diet with moderate to low intake of carbohydrates is recommended to avoid the theoretical aging effects of glycosylation.
Evolutionary Theory •
Evolutionary theories of aging argue that the process of senescence is either not affected by natural selection because it occurs after the peak of reproductive viability or it is selected for because it conserves resources for new generations, avoiding the problem of overpopulation. Hence, aging may actually be an adaptive feature of biological organisms based on a sort of biological clock, rather than an unfortunate and perpetual threat.
Genetics of Senescence • Research suggests a telomerase-based genetic clock may be located on the first or fourth of the 23 homologous chromosome pairs found in humans. • Other genes that appear to affect the aging process include the Sirtuin gene family (which code for Sir2 proteins), RAS genes, and GATA transcription factors. • Twin and adoption studies have suggested that genes account for an estimated 35% of an individual's lifespan.
Maximum Human Lifespan • The maximum human lifespan is currently defined as 122 years and 164 days, as set by a woman named Jeanne Calment. • The oldest man, Christian Mortensen, lived to 115 years and 252 days. • Men consistently have shorter lifespans than women, and this trend is apparent in the life expectancies of nations across the globe. • Japan has the highest average life expectancy of any nation, with 78.0 years for men and 86.1 years for women. • The United States ranks 36th for average life expectancy, with 75.6 years for men and 80.8 years for women.
Historical Human Lifespan Era
Life Expectancy at Birth (years)
Upper Paleolithic
Bronze and Iron Age
Classical Greece
Classical Rome
Pre-Columbian North America
Medieval Islamic Caliphate
Medieval Britain
Early Modern Britain
Early 20th Century
Current World Average
Unfortunately, such measures of average lifespan depend heavily on infant mortality and do not reflect the typical age of death for a fully grown adult. Also, contemporary methods of information collection may have varied enough among periods to produce significant discrepancies.
Blue Zones • Epidemiological research has revealed special regions called blue zones in which people experience healthy, active lives for significantly longer than average. • Examples of these so-called longevity paradises include the island of Okinawa, Japan, the mountain villages of Sardinia, Italy, the island of Icaria in Greece, the Californian city of Loma Linda, and the Nicoya Peninsula in Costa Rica. • Common factors in these blue zone societies include regular yet moderate physical activity, social and familial engagement, a plant-based diet rich in legumes, no smoking, relatively few stressors, a period of the day reserved for decompression, and relatively low caloric consumption. • Not only do these blue zones produce centenarians at a much higher rate than other societies, but they also experience a far lower incidence of disease, so their residents enjoy more healthy years of life.
Non-Human Longevity • The oldest known living organism is a bristlecone pine known as Methuselah. Located in the White Mountains of eastern California, this tree is currently 4,844 years old. • The Methuselah tree is named after the biblical Methuselah (Noah's grandfather), who was the longest living person mentioned in the Hebrew Bible, at 969 years old. • The animal with the longest verified lifespan was a quohog clam found on a seabed off the coast of Iceland, which was determined to be between 400 and 410 years old.
Biological Immortality • • • • • • •
The Gompertz-Makeham law of mortality states that a death rate is a composite of agedependent and age-independent components. The age-dependent components, modeled by the Gompertz function, rise exponentially with age. Defined as the absence of cellular senescence, biological immortality implies a mortality rate that is not a function of chronological age. The Hayflick limit describes the maximum number of times a cell population can divide, which is believed to be related to telomere length. Many scientists believe telomere length acts as an inborn molecular clock for biological organisms. Certain animals, such as Tardigrades and Hydras, are believed to exemplify biological immortality because their cells do not appear to be subject to the Hayflick Limit. Other organisms, such as the bristlecone pine, quahog clam, and sea anemone, are said to exhibit negligible senescence, as they show very few signs of aging. Immortal cells (such as germ and stem cells) have their telomere lengths maintained by the telomerase enzyme, and activation of this enzyme can immortalize mortal cell lines. It is considered significant by many gerontologists that the cells of an organism typically demonstrate near perfect renewal during the peak years of the organism's lifespan, which for humans typically falls between the ages of 20 and 35.
Tardigrade, colloquially known as a water bear
A hydra, a member of the phylum Cnidaria
• • • • • •
It is important to recognize that biological immortality may not be desirable for multicellular organisms because it may predispose an organism to cancer. As somatic cells continue to divide, the probability that they will contain mutated genes increases. Therefore, they would be of increased danger of becoming cancerous. A key factor in cancer cell proliferation is the activation of the telomerase enzyme by mutation, which allows the cell to divide indefinitely. Prevention of genomic instability is an important function for multi-cellular organisms, so aging may have evolved to protect against internal genetic drifts. Whether cellular senescence is directly related to aging on an organismal level is still a matter of scientific debate. In 2010, scientists were able to reverse the effects of aging in mice by activating a gene that stimulated telomerase production. This discovery is highly exciting for the scientific community, but the potential cancer risk and the transferability to humans remains a matter for speculation and experimentation.
Life Extension (Experimental Gerontology) • • • • • • •
Experimental gerontology is the field dedicated to expanding the maximum and average lifespan of human beings. Life extension has fascinated human beings throughout the course of history and is the topic of myths involving the fountain of youth, the holy grail, and the elixir of life. Although terms such as immortality and eternal life are often used to describe the ultimate goals of experimental gerontology, the correct scientific term is indefinite lifespans. The term indefinite lifespans lacks the religious connotations of the former two and does not imply a complete inability to die. An indefinite lifespan eliminates death as a biological inevitability, but does not protect an organism from death as a result of injuries or disease. Theoretically speaking, immortality and eternal life are physical impossibilities because of the second law of thermodynamics, the law of increasing entropy. Some life extensionists believe an indefinite human lifespan to be within the realm of scientific possibility, perhaps even for existing generations. Strategies for life extension may involve nanomedicine, caloric restriction, nutrition and supplementation, or genetic engineering.
Nanomedicine •Refers to the application of nanotechnology to medicine •Advanced drug delivery systems to allow for greater specificity and efficiency in pharmaceutical administration •Nano-electronic sensors to detect concentrations of biomolecules in real time •Nanosensors to communicate and interact with individual biological cells •Medical imaging visualization using luminescent tags known as quantum dots • •
Theoretically, nanoparticles could eventually be used to facilitate or enhance basic physiological mechanisms. Nanomedicine is itself in its initial stages; therefore, the idea of using nanotechnology for physiological enhancement and lifespan extension is completely speculative. The intellectual and cultural movement which advocates the use of technology and science to transform the human condition by eliminating aging and enhancing physiological and psychological capabilities is known as transhumanism.
Caloric Restriction With Adequate Nutrition
• Caloric restriction with proper nutrition is a means of enhancing lifespan by providing the body with only the nutrients which are necessary for its survival. • Caloric restriction usually refers to limiting calories to 30-50% less than what a typical animal would consume ad libitum. • Experimental and theoretical consensus supports the idea that the body, in semistarvation mode activates pathways that reduce cellular damage and improve metabolic efficiency. • Thus, by eating a diet rich in beneficial nutrients but which provides only slightly more than the calories needed to survive, the overall functioning of an organism may be improved. • In experiments comparing caloric restriction to exercise, calorically restricted animals live significantly longer than exercised animals. • Typically, caloric restriction only demonstrates significant effects when begun early in life. Moreover, some scientists believe its effects will be far less significant in long-lived humans as compared to short-lived animals such as rats. • Overall, theories of caloric restriction are closely related to theories of metabolism.
• • • •
• • •
Metabolism and Lifespan Some researchers have also argued that a high basal metabolic rate is inversely correlated with longevity. This idea is based on damage-accumulation theories of aging, since high levels of metabolic activity would produce more opportunities for cellular damage to occur. The suggested connection between metabolism and lifespan is known as the metabolic stability or rate of living hypothesis. The rate of living hypothesis enjoyed great popularity in the scientific community for some time because data appeared to link high metabolisms (as seen in small, active animals) with shorter lifespans when compared to larger, less metabolically active animals (such as humans or whales). However, the rate of living hypothesis has been undermined in more recent times by the observation that bats and birds, despite being small and metabolically active, live several times longer than rats, or other small animals with comparable metabolisms. Modern statistical analysis has also failed to adequately correlate metabolic activity with lifespan when phyletic relationships and more accurate biometric analyses are taken into account. The metabolic stability hypothesis stands on somewhat firmer scientific grounds, as it describes homeostatic metabolism as conducive to healthy aging. Thus, an organism with a stable metabolic rate, such as a human with a healthy BMI, is likely to live longer than a human who is over or underweight. Stress and disease are also regarded as significant metabolic disturbances.
• • • • • • • • • • •
Benefits Reduction of total and LDL cholesterol levels Reduced tryglyceride levels Improved HDL cholesterol levels Reduced inflammation Improved systolic and diastolic blood pressure Reduction of oxidative DNA damage Improved fasting glucose and insulin levels Enhanced memory and neuroprotective effects Protects against diabetes, cancer, and other major diseases Improved body mass index Increased average life span
Concerns • • • • • •
May cause musculoskeletal losses (sarcopenia, osteoporosis, etc)* May weaken the immune system BMI below 18 associated with higher mortality rates May induce gluconeogenesis in individuals with low levels of body fat May not provide sufficient energy for intense physical exercise May hinder natural physical growth in children or young adults (and is therefore contraindicated in individuals under 21) Excessive CR may result in starvation
* = Although reduced caloric consumption should theoretically reduce muscle mass and bone mineral density, experiments on CR animals have actually indicated increased muscle tissue and bone mass. No metabolic explanation for this phenomenon exists; however, some critics have suggested that CR animals enter a foraging state and simply exercise more than their ad libitum fed counterparts.
Nutrition and Supplementation •
A variety of "superfoods" and supplements are marketed at consumers interested in longevity. Some of the most common include: –
• • • •
Resveratrol, Metformin, DHEA (dehydroepiandrosterone), EGCG (epigallocatechin gallate), ALCAR, CoQ-10, DHA, EPA, ALA, and a variety of vitamins and minerals.
As discussed earlier, a plant-based diet high in legumes and low in overall calorie value has been associated with long life spans. A some very recent studies have suggested many of the benefits of caloric restriction to result primarily from the restriction of the amino acid methionine. If this research is upheld, methionine-reduced foods could easily be produced such that the benefits of caloric restriction could be easily be provided to the entire population. It should also be noted that methionine is the first limiting amino acid in legumes.
Details on Longevity Supplements •
• •
Resveratrol - Found in red wine, grape skins, japanese knotweed, and other plants (where it is produced in response to pathogenic infection), resveratrol is the the most heavily researched CR mimetic. In animals as diverse as fruit flies, nematodes, zebrafish, and rats, resveratrol has been seen to mimic many of the beneficial effects of CR. Nevertheless, Resveratrol has yet to be proven beneficial in primates, and some skepticism exists concerning the validity of existing research. DHEA (5-dehydroepiandrosterone) – Produced by the adrenal glands, kidneys, liver, and the brain, DHEA is the most abundant circulating steroid hormone in humans and is a precursor to the major sex hormones. In epidemiological studies, serum DHEA levels are a strong predictor of longevity in men. DHEA has also been found to have antidepressant effects, to lower evening cortisol concentrations. and to rise significantly in serum concentration during caloric restriction. Metformin – an antidiabetic drug used to reduce serum glucose levels, metformin has demonstrated effects similar to caloric restriction in laboratory animals and cell cultures. EGCG (epigallocatechin 3-gallate) – green tea extract, a potent antioxidant and the most abundant catechin in green and white teas. In black teas, EGCG is converted to thearubigins. Note: Consuming tea or tea extracts with milk may block beneficial effects as many tea molecules are rendered inactive when they bond to the casein protein in milk. ALCAR (Acetyl-L-Carnitine) – ALCAR is an acetylated, more bioavailable form of L-Carnitine, a potent antioxidant that plays a major role in fatty acid oxidation. ALCAR is believed to enhance energy metabolism, alleviate male infertility, encourage favorable body composition, improve glucose disposal, increase bone mineralization, and improve the function of neurotransmitters. Coenzyme Q10 (1,4-benzoquinone) – component of the electron transport chain and a potent antioxidant, CoQ-10 functions as an energy carrier in cells and is constantly oxidized and reduced. Its fully oxidized form is ubiquinone, its fully reduced form is ubiquinol, and its intermediate form is ubisemiquinone.
DHA (docosahexaenoic acid) [22:6, n-3]* – an essential omega-3 fatty acid found in cold water fish and microalgae that is metabolized to form a class of signaling molecules known as the docosanoids. DHA is a major fatty acid in the brain, retina, and sperm cells. The increased consumption of DHA by humans is hypothesized by some scientists to have been responsible for the evolution of the modern human brain, which is uniquely large with respect to body size. EPA (eicosapentaenoic acid) [20:5, n-3] – an essential omega-3 polyunsaturated fatty acid which acts as a precursor to the eicosanoids. It is obtained in the human diet by consuming fish oil, and it is also an important component of breast milk. EPA shares many of the anti-inflammatory, anti-cancerous, neuroprotective, cardio-protective, and otherwise beneficial effects also associated with DHA. ALA (alpha linoleic acid) [18:3, n-3] – an essential polyunsaturated omega -3 fatty acid found in Chia, kiwifruit seeds, and flax (linseed). ALA, like DHA and EPA, is necessary to sustain human life because It cannot be biosynthesized de nono and must be attained through diet. ALA can be used as a precursor to DHA and EPA, but the process is extremely inefficient. ALA (alpha lipoic acid) – an antioxidant fatty acid often marketed as a weight loss or energy supplement, ALA appears to demonstrate numerous cytoprotective effects. ALA is a chiral molecule typically taken as a racemic mixture of its two enantiomers, RLA and SLA. ALA is said to act like a B vitamin at low doses but more like resveratrol when higher concentrations are used. * = Fatty-acid nomenclature typically takes the form of [C:D, n-x], where C is the number of carbon atoms in the fatty-acid molecule, D refers to the number of double bonds, and x signifies the location of the first unsaturated carbon-carbon bond from the terminal methyl carbon. This nomenclature is preferred to the IUPAC names when describing fatty-acids because it provides greater denotative information in a more compact form (many of the properties of fatty-acids depend on the location of the first unsaturation relative to the terminal methyl group).
Genetic Engineering • • • •
• • •
Genetic engineering refers to the modification of an organism's genome using DNA technology. A genetically modified organism is one that is created by the introduction of recombinant DNA. This DNA can be either foreign or synthetic. Since the first genetically engineered organisms were genetically engineered in 1973, the field has found applications throughout the realms of research, industry, agriculture, and medicine. In 1982, bacteria were first bioengineered to produce human insulin for diabetics. Since then, genetic engineering has allowed for the mass production of HGH, FSH, albumin, antibodies, blood clotting factors, fuels, vaccines, supplements, and a variety of other substances. In addition to creating organisms that produce human-specific molecules, genetic engineering has allowed for the creation of more appropriate animal models for fundamentally human diseases. Animals can also be genetically engineered to enhance animal-to-human transplantations. Genetically modified food (GMO) is a major health and agricultural topic. Benefits of transgenic organisms include improvements in growth rates, pest and disease resistance, improved crop yield, nutritional value, environmental tolerance, size, and aesthetic appeal. On the other hand, concerns have been raised about the potential health risks of GMO's and about possible gene flow into unmodified organisms. In humans, genetic engineering has the potential to both eliminate genetic disorders and to improve overall physiological function.
These mice have had their genes modified to produce a desired fur monocolor or mosaic. "GloFish� were the first pet to be created through genetic engineering.
Human Genetic Engineering Forms: • Negative genetic engineering (gene therapy) – Cures and treatments for genetic disorders – Non-pathogenic virus or other delivery system is used to insert the "correct" copy of a gene into the genetic code of an individual. The inserted gene is proliferated through normal cell division. – May be used to treat conditions such as CF, PKU, Sickle Cell Anemia, Hemophilia, and other genetic diseases.
• Positive genetic engineering – Enhancement of an organism or species – Questions what defines genetic "disorder" and suggests that curing and enhancement only differ in their extent – Aging and death as medical conditions that may be resolved by genetic engineering. – Might allow "designer babies" and other optimizations of the human genome.
What will perhaps one day be considered a primitive negative genetic engineering technique.
Human Genetic Engineering Techniques: • Somatic Engineering
– Alters genetic information in non-reproductive cells. – Changes will only be expressed by cells altered during the procedure. – Not inheritable; offspring will not display modified traits.
• Germline Engineering
– Alters the genetic code for egg, sperm, or early embryonic cells. – Changes will be present in all cells of the organism. – Inheritable; modified genes will be passed on to subsequent generations.
Gene Therapy: Major Historical Events •
September, 1990: first human gene therapy trials take place at the NIH – –
The trials are performed on a four year old girl named Ashanti DeSilva and a second, a nine year old girl who chose to remain anonymous. Both patients were afflicted with the genetic disease known as Severe Combined Immunodeficiency (SCID). The form of SCID from which the patients suffered was an adenosine deaminase (ADA) deficiency, caused by the inheritance of two ineffective recessive alleles for the gene that codes for the enzyme. A lack of ADA leads to a buildup of adenosene that is toxic to B and T lymphocytes. The impressive positive response seen in DeSilva's immune system after the procedure was a significant victory for the field of gene therapy and led to a flurry of research and funding in the field.
Fall, 1999: University of Pennsylvania's Institute for Human Gene Therapy begins a gene therapy trial for Ornithine Transcarbamylase (OTC) deficiency – – – –
OTC deficiency is a X-linked recessive metabolic disorder involving the urea cycle caused by a mutation in the gene that codes for the OTC enzyme, which is vital to removing ammonia from the body On September 17, 1999, the death of Jesse Gelsinger leads the FDA to terminate all AD vector gene therapy trials while it reviewed the Gelsinger case. A variety of ethical and procedural violations were found in the Gelsinger gene therapy trials, and the FDA and NIH responded by instituting new, more stringent guidelines for future trials. The death of Jesse Gelsinger marked a major setback in gene therapy trials, as it called attention to the often unsuccessful and potentially fatal nature of the therapy.
Dr. James M. Wilson, whose academic misconduct led to the death of Jesse Gelsinger, still teaches as an honored professor at the University of Pennsylvania.
Gene Therapy Procedure: Four Phases of a Clinical Trial 1.
Apply for permission to try the experiment on human subjects. a. b. c.
FDA, NIH, RAC (Recombinant DNA Advisory Committee) 2-20 adult volunteers Informed consent Subjects are given a range of doses, all of which are less than the highest dose given to experimental animals.
Results replicated with a larger number of subjects (100-300)
Drug tested on patients at a variety of research centers a.
Most expensive phase of approval. Can cost millions (even billions) of dollars. 
Typically requires backing from pharmaceutical or biotechnology companies.
If successful in phase III, the procedure is given formal approval for routine treatment. 4.
Treatment is monitored for long term effects (~10-20 years)
Examples of Genetic Engineering Techniques • Plasma Method, commonly used for bacteria, in which a ring of DNA (a plasmid) is placed in a container with the DNA sequence to be inserted. A specific restriction enzyme is then added which splices the DNA to form "sticky ends," allowing the plasmid to combine with the desired gene. Bacteria that have incorporated the new gene can be isolated by comparing molecular weights or by measuring marker genes for antibiotic resistance or pigment production. • Viral Vector Method, similar to the plasma method, uses a viral vector to insert DNA directly into the host chromosome using the enzyme reverse transcriptase. Viral vectors are currently the most effective means for administering human gene therapy. • Biolistic or Gene-Gun Method, often used for engineering plant cells, involves firing pellets of DNA-coated metal (typically tungsten) into the cells of an organism. • Human Artificial Chromosome, or an addition to the original 23 chromosomes, containing large quantities of manufactured DNA to be expressed by a cell.
Theoretical Applications for Positive Genetic Engineering •
Minimizing or reversing the aging process – Higher levels of HGH, telomerase, catalase, and other anti-aging factors – Repairing damaged DNA and proteins – Improving metabolic efficiency and sustainability
Enhancing concentration, learning, and cognitions – Minimize the risk of mental disorder – Optimize potential for long-term potentiating and neural plasticity – Enhance glial cell myelination of axons
Enhancing physiological function (musculoskeletal, cardiorespiratory, gastrointestinal, etc) – Replace iron with a more conductive metal (e.g. silver) in the human respiratory chain – Replace hemoglobin molecules (porphyrin ring with four iron atoms) with hemocyanin (two copper atoms bound as prosthetic groups) seen in arthropods for humans entering cold environments with low oxygen pressure (such as astronauts in space)
• • • • •
En Resumen
Approaches to extending human lifespan may take a stochastic or programmed perspective on aging, and both genetic and environmental factors appear to play a role. Most organisms seem to have a definite lifespan which is theorized to be set by a biological clock, perhaps involving chromosomal telomeres and the Hayflick limit. Common approaches to experimental gerontology include nanotechnology, nutrition and supplementation, and genetic engineering. Longevity evokes ethical questions involving the difference between treating debilitating diseases and enhancing the basic functions of the human body. Although numerous of life extension have shown promise in laboratory studies, no means currently exists by which the human lifespan can be expanded indefinitely.
Things to Come •
• •
In the utopian visions held by the most optimistic and iconoclastic experimental gerontologists, the methods addressed in this presentation, as well as others either not mentioned or not yet developed, will one day allow human beings to eliminate the thusfar perpetual problem of aging and death. Unfortunately, though average life expectancy continues to increase, its rate of increase is on the decline in many developed nations. Considering only current disease treatment methods, humans can expect only modest increases in average life expectancy. Medical specialists currently face an unwinnable battle as the rate of infirmity from any cause increases exponentially with age. Nevertheless, as this presentation should have made clear, confidence is growing among scientists that the ongoing scientific revolution will make humanity's ultimate victory over age a legitimate possibility, perhaps even for existing generations. Whether it is through the elimination of a programmed biological clock, the practice of significant lifestyle modifications, or the mechanical, chemical, or genetic alteration of human physiological function, humankind can remain faithful to its dream that the omnipresent specter of death can perhaps one day be eliminated from its horizons.
Works Cited Allport, Susan. The Queen of Fats: Why Omega-3s Were Removed from the Western Diet and What We Can Do to Replace Them. Berkeley: University of California, 2006. Print. Moore, Thomas J. Lifespan: New Perspectives on Extending Human Longevity. New York: Simon & Schuster, 1994. Print. Panno, Joseph. Gene Therapy: Treating Disease by Repairing Genes. New York, NY: Facts On File, 2005. Print. http://juvenon.com/jhj/vol5no09.htm http://www.newmediaexplorer.org/sepp/2003/07/16/human_genetic_engineering.htm http://www.timesonline.co.uk/tol/news/science/article3908516.ece http://www.dailygalaxy.com/my_weblog/2009/03/the-worlds-fi-1.html http://www.geneticsandsociety.org/article.php?id=3157 http://library.thinkquest.org/C004367/be9.shtml http://www.ijser.org/researchpaper%5CDamage_Based_Theories_of_Aging.pdf http://bioethics.georgetown.edu/publications/scopenotes/sn24.htm http://www.anti-aging-today.org/aging/theory/telomerase.htm http://www.bangor.ac.uk/news/full-ori.php.en?Id=382 http://www.nlm.nih.gov/medlineplus/druginfo/natural/331.html
Published on Jun 15, 2011
2011 AP Chemistry Expo Project by Justin Miller


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Kottayam Thirunakara Temple and Arattupuzha temple are two famous temples in Kerala, each of which plays host to an elephant festival annually. While the 10 day festival at Thirunakara Temple witnesses procession of 22 elephants on each day of the festival, Arattupuzha Pooram festival is marked by a spectacular procession of 61 elephants accompanied by temple percussions. Out two week long 'Elephant Festival in India' will make you witness the pomp, panache and elegance of these two festivals. Also included in the itinerary is the visits to Kovalam beach, Alleppey backwaters, Munnar hill station and Periyar wildlife sanctuary.
Arrive at the Trivandrum airport in the morning followed by assisted transfer to the hotel in Kovalam. The rest of the day is free to relax on the beach. You have an option of indulging in Ayurvedic massage therapies. Stay overnight in Kovalam.
The day 2 is booked for a full day excursion in and around Kovalam beach. There is also an option for a half day guided sightseeing tour of Trivandrum which include visits to the Sree Padmanabhaswamy temple, Art Museum and Sri Chitra Art Gallery. Stay overnight at Kovalam beach.
In the morning, hit the road to Alleppey. Upon arrival, check in at the Coir Village Resort. The rest of the day is free for individual activities. Stay overnight in Alleppey.
In the morning, board the traditional houseboat (Kettuvalam) and cruise through the palm-fringed backwaters, villages and paddy fields. Stay overnight on board the houseboat.
Morning arrival in Kumarakom followed by check out of the houseboat. Thereafter, board the coach and leave by road for Periyar. Upon arrival, check into the jungle resort. Later in the afternoon, enjoy boating on the Lake Periyar and witness the exquisite wildlife. The evening is booked to explore the Kumily Spice Market. Stay overnight in Periyar.
In the morning, leave by road for Munnar. Upon arrival, check into the hotel for overnight stay. The rest of the day is free to rest and relax. Stay overnight in Munnar.
The day 7 is scheduled for the sightseeing tour of Munnar. The places you will visit here include Mattupetty Dam, Dairy Farm, Old Munnar Town and Eravikulam National Park. Stay overnight in Munnar.
In the morning, leave by road for Kumarakom. Upon arrival, check into the Lake Front Resort. The rest of the day is free to relax. Here you have an option to go for fishing (special arrangements will be made), swimming and rejuvenate through Ayurvedic massages. Stay overnight in Kumarakom.
In the morning, go out for a guided sightseeing tour of churches and nearby villages. The afternoon is free to relax and do individual activities. In the evening, go out to explore the famous Kottayam Thirunnakara Temple to see the festival preparations. Dedicated to Lord Shiva, this festival takes place in the month of March-April. Stay overnight in Kumarakom.
In the morning, leave by road for Thrissur. On the way, enjoy a boat cruise at Vaikom and explore the lifestyle of locals in Kerala. You can see and learn the local art such as pottery, khadi weaving and extraction of coconut oil. Later, enjoy a delectable traditional Kerala lunch served on a banana leaf. Post lunch, drive to Thrissur. Upon arrival, check into the hotel for overnight stay.
The day 11 is scheduled for you to witness the Arattupuzha Pooram at Arattupuzha temple. Arattupuzha Pooram is a spectacular procession accompanied by temple percussions. A total of 61 elephants partake in this event. Stay overnight in Thrissur.
In the morning, leave by road for Cochin breeding center. Also visit Palayoor and Kadakallu (umbrella aristocratic households). Stay overnight in Cochin.
For the next two days, you will explore the popular tourist attractions in Cochin which include Jewish Synagogue, St. Francis Church, Mattacherry Palace and Chinese Fishing Nets. Being a seaport, Kochi was an important trade center for Indian spices in medieval times. On the evening of the day 14, you will attend a fair. Stay overnight in Cochin.
Today, check out of the hotel by 12:00 Am and drive to the Cochin airport to board flight back home.


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Maintenance Supervisor
- Recruiter
- Michael Page Engineering & Manufacturing
- Location
- Newton Aycliffe, County Durham
- Salary
- £26,000
- Posted
- 24 Apr 2017
- Closes
- 27 Apr 2017
- Sector
- Manufacturing
My client, an established and progressive Manufacturing organisation based in County Durham are seeking a Maintenance Supervisor to join their senior management team on site. Client Details My client are a global manufacturing organisation going through a period of rapid expansion in the UK. Description The role will include but not be limited to; * Overseeing the Engineering Maintenance department. * Direct supervision of 6 Maintenance Engineers and apprentices. * Ensuring all PPMs carried out on time. * Dealing with breakdowns. * Overseeing machinery relocation and installation. * Machine improvements. Profile The ideal candidate will have / be; * Time served Engineer. * Knowledge of Health and Safety within a maintenance role. * Experience within an Engineering / Manufacturing environment. Job Offer Competitive.


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- Description
Quick Overview
The Olay Total Effects 7 In One Anti-Ageing Night Firming Cream works as a shield to all your aging woes with 7 benefits in one single product and it does all that while you sleep. A power packed dose of moisture, vitamins, antioxidants and wheat protein, the cream works to give you visibly firmer, radiant and youthful.
- Reduces fine lines and wrinkles through skin hydration.
- Fights age spots and uneven color tone.
- Gently exfoliates and smoothens skin texture.
- Fights dullness and leaves your skin supple and radiant.
- Moisturizes and nourishes dry skin with vitamins and antioxidants.
- Minimizes pores for a younger looking skin.
Additional Information : Olay is one of the most recognizable brands and is committed to providing safe products to our consumers. Ensuring the safety of the products is a responsibility that Olay takes very seriously. The Olay Total Effects 7 In One Anti-Ageing Night Firming Cream fights skin aging issues and allows you to experience younger looking radiant skin.
Explore other options for Dull Skin Products here.
Expiry Date : Click Here October 2018
All our products are far from expiry, and procured directly from the brand/authorized resellers of the brand.
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By Anne
Olay total effects night cream
I love the cream for my dry to normal skin. It nourishes and the results can be seen the very next day. It does firm as claimed. I love the ingredients and formulation of the total effects creams. With ingredients like these you don't need high end creams. I don't use this during the summer though as I need extremely light weight lotion only for summer. For all the other seasons I highly recommend this product. I'm not sure as to how it works on oily skin but a quick Google search should satisfy any queries.
Posted on 8/9/2017
By sima
very good moisturizeer.. vry nice product for oily skin.thank you nykaa for first delivery...................................................
Posted on 7/24/2017
By AAYUSHI PRIYADARSHI
in short awesome night cream I have oily skin and it suited eme cream is light and absorb on skin well
Posted on 7/19/2017
By deepa bisht
Healthy and glowing skin in morning!
I have become its fan since the time I stared using this night cream. Only a small amount is sufficient for me as I have oily skin..and the next morning i get a healthy and glowing skin.
Posted on 7/16/2017
By Ankita Chakraborty
currently I am using this product... every morning I wakeup with more healthier skin. very nice product. loved it.. going to repurchase it.
Posted on 7/12/2017
By Devanshi
Works amazing. Skin doesn't feel sticky after application and soaks it in completely. Glowy and dewy effect the next morning.
Posted on 7/10/2017
By yam
I got this cream for my mom.Quantity n price wise its good. Results are fairly visible. One product can last up to 45 days if u are using it only for face. Must try this cream.
Posted on 6/27/2017
By Shefali
Thanks Nykaa for timely delivery and fresh piece. It feels very nice when you open the parcel and found the product in good condition. Though i still have to use the product for its actual review but Nykaa plays its part really well.
Posted on 6/20/2017
By Harsha Chettiar
i have tried several night cream my being oily and sensitive skin. my skin looks like frying pan but this cream is so lightn good gets absorbed in skin and next morning skin feels so fresh n radiant must buy
Posted on 6/18/2017
By Sreepurna Ghosh
The fact that it's available in a travel friendly package adds to the perk . Have used it for almost a week now and though it s supposed to be anti ageing, i find it works well with any age. can appreciate the tightened and soft feel in the morning and also the reduction in pigmentation. it's also non greasy so that you dont feel like a oil machine in the morning. definitely recommended.
Posted on 5/30/2017
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Pay No Attention to the Man Behind the Curtain! Write Your Own C++ AppWizards
AppWizard makes it a lot easier to get projects started with Visual C++®. To make life even simpler, you can create your own code templates and wizard pages, building custom AppWizards that will generate whatever applications you need.
Walter Oney
Visual Basic 5.0 Relieves the Pain and Discomfort of ActiveX Control Creation, Part II
Continuing their look at Visual Basic® and ActiveX components, Guy and Henry Eddon explain events and methods, then show how to develop components that will work properly in both Visual Basic-based applications and Web pages.
Guy Eddon and Henry Eddon
More Fun with MFC: DIBs, Palettes, Subclassing, and a Gamut of Goodies, Part II
This month, Paul DiLascia continues writing his MFC-based Quick View application and shows you all the cool tricks he learned along the way. The reusable MFC classes he creates here will be useful in your own development projects.


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Holliston Youth Basketball: Welcome
K/1 and 2d Grade Clinics
PLACENTINO IS OPEN TODAY and CLINICS WILL BE HELD AS SCHEDULED (as of 11;45 a.m.)
THERE WILL BE NO TOWNBALL on SATURDAY 2/18/17
THERE IS NO 2d GRADE CLINIC ON SUNDAY 2/19
REGULAR TOWNBALL SCHEDULE:BOYS 3/4: SAT. 12p -1:15p OR 1:15p to 2:30p (HHS)
BOYS 5/6: SAT. 2;30p-3:30p or 3:30p - 4:30p (HHS)
BOYS 7/8: SAT. 5p-6p (1 game); 6p-7p (3 games): HHS OR PLACENTINO
GIRLS- Grades 3-6:
SAT. 4:30-6p (HHS) OR Crossover games in Jan. AT Ashland (check your schedule)
PRIMARY PROGRAMS - K/1 CLINIC and 2d GRADE CLINIC:
K/1 Clinics will be on Sundays at Placentino (1/8; 1/15; 1/22; 1/29; 2/5; 2/12)
Week 6 schedule at PLACENTINO
Sunday 12:15 to 1:30pm: K and 1st Grade Boys – Last names "A-L"; 1st Grade Girls – Last names "A-L"
Sunday 1:30 to 2:45pm: K and 1st Grade Boys – Last names "M-Z"; 1st Grade Girls – Last names "M-Z"; ALL K Girls
2d Grade Clinic will be on Sundays at Placentino (1/8; 1/15; 1/22; 1/29; 2/5; 2/12; 2/26; 3/3)
Week 6 schedule at PLACENTINO
Sunday 3:00 to 6:00pm - 2d Graders as per info from coordinators
CONGRATULATIONS to HHS BOYS VARISTY BASKETBALL for QUALIFYING FOR THE STATE TOURNAMENT with their 10th win (10-1, 10-1 TVL) on Tuesday.
Welcome to
Holliston Youth Basketball (HYB)
Town & Travel Basketball Website
Any Questions please contact us at firstname.lastname@example.com
Joe Gentile, Incoming President
Holliston Basketball ONLINE APPAREL store is currently CLOSED, however ...
ONLINE STORE WILL BE OPENING SOON WITH a VARIETY OF "Holliston Basketball" ITEMS, INCLUDING "Shooting Shirts", T-shirts, Sweatpants, and More ...
Holliston Youth Basketball Leagues
|Town Basketball
|Travel Basketball


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Lexmark - Extra High Yield - magenta - original - toner cartridge LRP, government GSAItem#: 7328658 | Model#: C7726MX
- Price:
- $392.99
Free Shipping Today!
- Shipping:
- Temporarily out of stock. Order today and we'll deliver when available. (Details)
Additional Resources
Lexmark - Extra High Yield - magenta - original Product Details
Consumable Type: Toner cartridge
Printing Technology: Laser
Color: Magenta
Included Qty: 1-pack
Cartridge Yield: Extra High Yield
Duty Cycle: Up to 15000 pages at 5% coverage
Pricing Type: Lexmark Return Program (LRP), government GSA
TAA Compliant: Yes
Additional Resources: Product Manuals
Related ItemsPrevious
Manufactured by: Xerox
Warranty provided by: Xerox
UPC No: 0734646009492
Mfg Part No: C7726MX
Shipping Weight: 5.5500 pound(s)
Click here for full warranty and support information
- Xerox logos are registered trademarks of Xerox. All others trademarks and copyrights mentioned herein are the property of their respective owners.


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Devil May Cry – 25 January. Action.
Dead Space 3 – 8 February. For those that are interested by the sequel. A horror third person shooter.
Aliens: Colonial Marines – 12 February. First person shooter. It will be a sequel for the "Aliens" movie, a crew of marines are going to LV-426 in order to investigate the missing crew that was sent before, the
Moba DotA zone in World of Warcraft, rumor07.01.2013
WoWserbia has a post regarding a possible Moba zone that might appear in World of Warcraft at some point. They are saying that the zone will be implemented in patch 5.2 and will be entitled "Defense of the Alehouse".
It is less likely to see this zone in patch 5.2 because Blizzard didn't included any news regarding this content in the ptr notes.
A Moba DotA
Dark Summoner hunter strategy30.12.2012
Spec used: Beastmaster / Pet used: Spirit Beast / Gear level: 480 (mostly PVP).
Must have talents: Exhiliration, A Murder of Crows, Barrage.
Glyphs: Marked for Death, No escape, Endless Wrath.
Start the fight by using Concussive Shot on Dark Summoner. Once the first shadow is up, pop Bestial Wrath and the trinkets (optional) and nuke the shadow. The pet will be on the
Diablo 3 nerfed to the ground25.12.2012
It seems that Diablo 3 was nerfed to the ground in the latest months or the barbarian class was buffed a lot. When I quit the game 3 or 4 months ago, I was stuck at Act 3. And today I beat Diablo with slightly better gear (I bought some small upgrades from the Auction house).
Act 3 and 4 were not very different in terms of difficulty, I've managed to survive huge packs of mobs
GG Engineering hunter strategy08.12.2012
Spec used: BM. Gear: half epic and half rare PVP gear. A few pieces of LFR armor. Pet used: Spirit beast.
The main idea of the fight is to stay very close to the gnome so the rockets that are being throwed by the goblin will hit the gnome too. The gnome will take a lot of damage from rockets. You should avoid getting hit by them as they usually one-shot.
Start the fight by
Brawler's Guild explained, tips04.12.2012
To queue for a fight, talk to the NPCs from the arena's corners. Once you queue, you will have to wait your turn, you can talk to the same NPC again to find out when will be your turn.
There are eight ranks for Brawler's Guild. Each rank has four bosses. The fights are getting harder as you progress. The fights from rank 7 and 8 are insanely difficult, they require the
Gear required for Brawler's Guild04.12.2012
Brawler's Guild requires good gear besides skills.
I have managed to reach the final boss from rank 5 by using only PVP gear, half blue and half epic. Fully upgraded, enchanted and gemed.
Still, there have been some fights where dps was all that mattered. And I can't kill the boss from the last battle from rank 5 because of not having enough dps.
The first
How to get in Brawler's Guild?30.11.2012
To have access to Brawler's Guild, you need to purchase this item: "Blood-Soaked Invitation". The item can be bought from Black Market Auction House in "Tavern in the Mists".
The price starts from 1k gold (BID) and goes up depending on the population of your realm. If you are on a high populated realm, expect to pay more as there will be more players
Level 90 hunters can solo Sunwell Plateau without much effort.
Tips and tricks.
Skip the first boss as it cannot be killed by one player. You can kill all the bosses even if you skip the first boss.
The second boss, Brutallus, is a tank and spank fight. Just try not to stay in front of him. Be prepared with potions, flasks if you think your damage is too low.
I was
How to beat Ai-Li Skymirror as a hunter?13.11.2012
To beat this rare NPC, you will need a gorilla pet. Gorillas have an ability named "Pummel". This ability will interupt the casting of the healing spell. It has a 30 seconds cooldown.
This should be the fourth interrupt. As a hunter, you also have Silencing Shot, Scatter Shot and Intimidation.
I have managed to solo this NPC without much effort, just using Pummel


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fas offers
fas offers a number of financial advantages and has proven to be an excellent alternative to other ship registers.
The Faroe Islands offer highly educated officers and seafarers and well qualified legal representatives and auditors.
- 2. juni 2017
FAS at Nor Shipping> Read more
- 19. maj 2017
Eimskip chooses FAS> Read more


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On Tuesday 27th March 2012, the PASSIVE partners held the general meeting in Waterford Institute of Technology, Ireland. The agenda covered three days of technical workshop and a day plenary session.
Waterford: General MeetingApril 10th, 2012 | Posted in Meetings | | Comments Off
Prague: Alucid WorkshopOctober 11th, 2011 | Posted in Announcements, Events, Meetings | Tags: Authentication, Identity, Workshop
| Comments Off
The PASSIVE project has been working toward integrating new and innovative solutions for user identification and management. In support of this, PASSIVE consortium partner ANECT have contributed intellectual property and knowledge in the form of Alucid (http://www.alucid.eu/).
This electronic identity solution allows users to authenticate with secure tokens. The form of token is based on a the security requirements for the given identity and as such the entire system is designed with integration and flexibility in mind. ANECT held a workshop in its Prague Offices demonstrating Alucid integration techniques and usage scenarios.
London: Advisory Board MeetingNovember 16th, 2010 | Posted in Announcements, Meetings | | Comments Off
On the 11th November 2010, the Project Advisory Board assembled for its first meeting. The board consists of representatives from Bird & Bird, Grant Thornton and Intel.
The Project Advisory Board (PAB) consists of a small number of individuals with special knowledge of the field of e-Government and supporting technologies. These members, while not full members of the consortium, advise the project in a voluntary capacity, particularly in the area of requirements gathering and review of project outcomes.
It was an excellent session covering recently completed deliverables and plans for the coming months of work. The session chair-person, Patrick Phelan of WIT, thanked all in attendance, especially Bird & Bird who hosted the meeting.
Reading: General MeetingSeptember 17th, 2010 | Posted in Announcements, Meetings | | Comments Off
On September 6th and 7th 2010, the participants of PASSIVE met in Reading, UK at the premises of Thales Research and Technology. On the agenda was completion of State of the Art and Use Case documents. The beginning of the Design phase of the project was also kicked off.
Athens: Project Kick-offSeptember 17th, 2010 | Posted in Events, Meetings | | Comments Off
PASSIVE kicked off in Athens on the 10th-11th June 2010. Representatives from all partners attended for what were two days of busy discussions and beginning of work. Project management topics were discussed and all Work Package Leaders presented and discussed the work to be done.


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Once upon a time, there was an idiotic pre-teenager named Ruby. Ruby betrayed her best friend, killing her by stabbing her in the heart with a knife. Ripping out her soul, and feeding on it. Shortly afterwards, she went to visit Dora and lived happily ever after.
The End :)


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Woman saved from River Shannon last night
Heroic fire fighters fought dramatically against gael force winds and lashing rain to rescue a woman from the River Shannon last night.
The crew from the Limerick City Fire and Rescue Service (LCFRS) rescue boat were dispatched to Steamboat Quay, Limerick City at approximately 11.50pm.
The woman entered the river near the Clarion Hotel where the fire fighters located her within minutes after launching their newly purchased rescue boat.
The boat was provided by Limerick City and County Council to allow the fire service perform faster rescues on the river.
The fire service has over thirty members trained as Swift Water Rescue Technicians who are specifically trained to carry out water rescues.
The woman, aged in her 20s, who entered the water last night, was located between the Clarion Hotel and Limerick Docks.
"She was unconscious upon arrival. LCFRS boat crew rescued her from the water and began CPR. They were met at St Michael's slipway by HSE paramedics who treated her on scene before transferring her to University Hospital Limerick," said a fire service source.
"It's believed the woman's injuries are serious, however on leaving the scene she was breathing," the source added.


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We've all heard about cloud computing, but it may still seem like a foreign language to some. Because cloud computing has become a big deal (like, change the face of IT big), we thought we would provide a brief cloud computing introduction. Here are some key points you need to know about cloud computing to help your organization reap its benefits and get you back into the 21st century.
Month: April 2016
Content marketing is not a new concept in the world of digital marketing, but right now, it is more important than ever before. Content is the king and it is increasingly working its way to the forefront of all digital marketing strategies, as it becomes a crucial element that reaps big rewards.
In saying that, a one-size-fits-all approach will not suffice when it comes to content marketing. Instead, a focus on creating unique, high-quality and utterly authentic content that is entertaining, useful and interesting for consumers will get you the crown. From text, video and imagery to infographics, surveys, webinars and podcasts, whatever your preferred content medium is, ensure it is shareable and relevant to your industry.
So, why is content king?
You recognize that in order to succeed in a competitive market you need to have the best brand experience for your customers. With the great waves of marketing change over the past few years the social and mobile web has given the consumer the power to choose on many different platforms. This leaves you with the task of finding the right company to deliver your company's message to your potential customers in the most efficient and effective way possible.
We've compiled a checklist for you to help you make the right decision when choosing a company.
The Communication Authority of Kenya released the Q1 2016 statistics report for the period between July and September 2015 on the mobile telephony sector. The report details among other things mobile money statistics, internet penetration as well as data on market share of all the telecom companies. It also offers insight on courier services and postal services.


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Tuna Frenchee
READY IN: 30mins
Recipe by r_mess
First cousin to the Cheese Frenchee. Served at Kings Food Host in Omaha and Lincoln Nebraska in the 1960's. Now you can get them at Don and Millies in Omana and Lincoln. (Tuna only available during lent)
Top Review by scootersangel
very good you dont need very much tuna on each one they are very very good
See Discussion:1 Review
Ingredients Nutrition
- 1 (6 ounce) can tuna (drained)
- 6 slices white bread
- mayonnaise
- 1 egg
- 1⁄2 cup milk
- 3⁄4 cup flour
- 1 teaspoon salt
- corn flake crumbs, crushed fine
- oil (for deep frying)
Directions See How It's Made
- Mix tuna with just enough mayonnaise to keep it together.
- Lightly spread each piece of bread with mayonnaise. Make 3 sandwiches spreading tuna not quite to the edge of the bread.
- Cut the crusts off the sandwiches.
- Cut each sandwich diagonally both ways, making 4 triangles.
- Combine egg, milk, flour and salt.
- Dip each triangle into egg mixture and then coat with the corn flake crumbs.
- Deep fry at 375 degrees until golden brown.


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This luxury handmade soap is fragranced with top notes of crispy apple, pineapple, and zests of orange; followed by middle notes of neroli and cinnamon; embodied with base notes of sandalwood, fresh musk, bamboo, and patchouli. A very gentle, cleansing and moisturizing bar of soap that is universally pleasing to both men and woman.
We have used our proprietary blend of skin loving ingredients to include Tussah silk to add that luxurious touch of creaminess, our Triple Milk Combination (Buttermilk, Goat's Milk and Coconut Milk) helps to cleanse and nourish the skin and also provides minerals and anti-oxidants. Kaolin Clay has also been added to help detoxify, cleanse and clarify the skin.
Approx. 6 oz.
Distilled Water, Palm Kernel Oil, Coconut Oil, Castor Oil, Olive Oil, Shea Butter, Triple Milk Combination (Coconut, Buttermilk and Goat's Milk), Kaolin Clay, Sodium Hydroxide, Tussah Silk, Sugar, Mica, Titanium Dioxide and Fragrance Oil.
There are no reviews for this item. Be the first to review it!


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Only 1 available
This pin cushion is hand-painted with lead edging like stained glass. It is a china espresso cup pin cushion. The cup and saucer are permanently joined. It has the cushion in the cup to keep all your pins and needles safe and has the added advantage of the saucer area to keep the button/hook/bow or may be bead safe while you thread the needle!It is approx 8cm high and is white china based.
I aim to post any item purchased within 2/3 working days. I will email you to let you know that it has been posted.
PaymentPlease complete payment at time of checkout - this will speed up delivery of your order, as I cannot dispatch your order until payment is cleared. If I haven't received payment within 3 days of the order,the order will be cancelled.I also accept most other standard payment methods including Etsy Gift CardsShippingI aim to dispatch all orders within 2/3 working days; if there is likely to be any delay I will contact you. UK orders are sent via Royal Mail 1st class; US and other overseas Airmail. CUSTOMS DUTY:International buyers may be required to pay customs duty. Please note that you the buyer is responsible for any and all duties and customs charges that may be incurred. If you have any other questions, please don't hesitate contact me direct via Etsy and I'll do my best to help.
I will post all items through the Post office, but if you want insured or signed for postage please email me before you purchase and I will cost this for you.
If the P & P added is more that the actual cost of postage I will refund the difference to you after posting your purchase.


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letloverule Review
Good Flexability
I just finished using this product to clean my window air conditioning unit. It reached into every little nook and cranny. The long tube reached to places my hand never could. The air suction remained great even when I bent the flexible tube at a pretty good angle. It attached to my DC25 perfectly and had strong suction just as all my Dyson attachments do. I have a lot of attachments, but I think this one will become my favorite. I LOVE Dyson products; do not hesitate to buy this one!
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