text:
Era-defining local legend DJ Qbert scratches out his first album in 16 years, Extraterrestria
That's a long time between official releases, but it wasn't like Qbert had been kidnapped by aliens. Although his live performance schedule was less-than-usual bonkers, he still made regular appearances, by himself or as part of his extended Bay Area scratch crew family. He popularized turntable techniques in a series of instructional videos and launched online educational community Qbert Skratch University, in 2009. He also went all in on the equipment tip, putting out his own brand of turntable cartridges and needles, an Invisibl Skratch Piklz-branded mixer, "and of course our own vinyl to scratch with — which is really vinyl on one side and a digital interface on the other, for use with DJ software like Traktor."
Fifteen years has also seen the rise of social media and a more user-friendly Internet. Has that changed the way he produces beats or performs at all? "Of course it's been great for finding new sounds to use," Qbert said. "If I want to hear, say, a tarantula farting, I can look it up instantly and hear that. On the other hand, most of my old sets are up there now, with all their mistakes, and a lot of times I'm cringing and say in a small voice, 'Please, please let them delete that.' It keeps me on my toes now, knowing everything can be recorded in all its glory. But because I've actually been working on this album for seven years, all that's been incorporated — it's not like a shock. I use what I can use.
"But I try not to be trapped in the present. I often think back to the past, to cats like Sun Ra, Miles Davis, Louis Armstrong. That timeless, improvisational jazz feeling where you practice and practice, but when the time comes you're just an instrument connecting with the god-force, channeling the sound through you, swinging through that ocean of feeling. When you're in that zone, that's the most wonderful thing. It's a meditation, a spiritual thing. We're all spirits, so we have to connect to other spirits and the most high, whatever you want to call it — God, Allah — connect to that creator source and use it because it's yours to use. Like how some writers just flow and do that automatic writing, they're just instruments. We're just instruments you know, it all flows through us."
When Qbert, raised in SF's Excelsior neighborhood, astonished the DJ world by winning its spun-out version of the Olympics, the DMC World Championships, not once (solo, 1991) but three more times in a row after that (as part of Rocksteady DJs with Mixmaster Mike and Apollo) it was an unparalleled triumph not just for local scratch and hip-hop community, but for Bay Area Filipino American culture as well.
As music critic and Guardian contributor Oliver Wang details meticulously in his forthcoming book Legions of Boom: Mobility, Identity and Filipino American Disc Jockeys in the San Francisco Bay Area (Duke University Press), a vibrant scene of Filipino mobile DJ crews — independent groups of teenage sound and lighting specialists hired to provide entertainment for weddings, graduations, and parties — thrived here since the 1970s. When hip-hop eclipsed disco on the request lists in the 1980s, the mobile crews defined streetwise Bay Area Filipino youth culture and provided a fertile training ground (and sometimes needed cash) for young DJ up-and-comers.
I really couldn't ask for more from this article.
That insight's just what I've been looking for. Thanks!
That's more than sensible! That's a great post!
That's really thinking at a high level
You're the one with the brains here. I'm watching for your posts.
Apparently this is what the esteemed Willis was talkin' 'bout.
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Find a synagogue near your campus or your home.
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The letter of recommendation from your Hillel (or other Jewish campus) professional is required in order to consider your application. This letter demonstrates the campus' willingness to participate in the KOACH Internship Program and its endorsement of you as a candidate. Campus professionals can endorse multiple candidates for KOACH's review, though only one will be selected.
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text:
30. Charlotte Bobcats | Future Power Rating: 382
PLAYERSMANAGEMENTMONEYMARKETDRAFT78 (30th)45 (26th)142 (9th)18 (28th)99 (1st)
We had the Bobcats ranked last for two years before they bottomed out last season. Now that they've cratered well, we still have them in last. But encouraging signs are on the horizon, and they may not be in this position for too much longer.
The biggest reason the 'Cats stayed at No. 30 is a lack of talent -- rookie Michael Kidd-Gilchrist seems like the only potential star here -- and so they still rank last in the players category. But that will change in coming years -- between their own picks and future first-rounders from Portland and Detroit, we have them rated first in the draft category. The only drag is a protected pick owed to the Bulls, one that could blow up on them if they don't become good in a few years.
Financially, Charlotte's position has improved considerably. The Bobcats essentially bought a likely lottery pick from Detroit when they agreed to take on Ben Gordon's leaden contract, yet still have plenty of cap room going forward. Finding somebody who will take it may prove more challenging, as we rated this market 28th because of its lack of fan support and losing history. That can change, however; this city has supported better Charlotte teams in the past, and while it's a small market it's at least not a cold one.
The Bobcats also have some professional management in the well-regarded Rich Cho, who has steered them away from some of the disastrous short-term gambles that were commonplace in the Larry Brown era. Baby steps, but they won't be 30th for much longer.


text:
Almost all teens get acne. It happens when an oily substance called sebum clogs pores.
Pimples usually pop up on the face, neck, back, chest, and shoulders. Acne isn't a serious health risk, though severe acne can cause permanent scars. Acne can also damage self-esteem.
What Does Acne Look Like?
Acne can appear as one of the following:
Whiteheads: White dots that are pores impacted with oil and skin covered by skin layers.
Blackheads: Black bumps that are impacted pores in which material pushes out through the follicles. The black color is not from dirt. It may be from bacteria, dead skin cells, and matter that react with oxygen.
Papules, pustules or nodules: More serious lesions appearing red and swollen due to inflammation or infection of the tissue around the clogged follicles, which are often painful and feel hard.
Cysts: Deep, pus-filled pimples.
Why Do Some People Get Acne and Others Don't?
It is not clear why some people are more prone to acne than others.
The exact cause of acne is not known, but hormones called androgens can play a role. Androgens increase in both boys and girls during puberty. Androgens make the skin's oil glands get larger and make more sebum. Androgens also can increase because of hormonal changes related to pregnancy or starting or stopping birth control pills.
Genetics may also matter. If your parents had acne, you may have inherited that tendency.
Some medications (for example, epilepsy medication, prednisone, androgens taken as medicine, and lithium) can cause acne.
Cosmetics that have a greasy consistency may also clog pores. Water-based products are less likely to cause acne than oil-based makeup.
Other things that can make acne worse include:
- Friction caused by leaning on or rubbing the skin; harsh scrubbing
- Picking or squeezing blemishes
- Pressure from bike helmets, backpacks, or tight collars
- Changing hormone levels in adolescent girls and adult women two to seven days before the start of the menstrual period
- Stress
How Is Acne Treated?
Dermatologists (doctors who specialize in skin problems) often treat acne, particularly in severe cases. Family or general practitioners, pediatricians, or internists can treat milder forms of acne.
Treatments may include:
Nonprescription ("over the counter") topical treatments: "Topical" means that you put these products on your skin. They're not pills. These include salicylic acid, benzoyl peroxide, and sulfur. These treatments are available in many forms including gels, lotions, creams, soaps, and pads. When these products are used regularly, they are moderately effective in treating acne. It may take 4-8 weeks for skin to improve.
Prescription topical treatments: These include benzoyl peroxide, antibiotics, tretinoin, tazarotene, adapalene, dapsone, and azelaic acid.
Prescription oral drug treatments: For people with moderate to severe acne, doctors often prescribe oral antibiotics (pills) in addition to topical medication. Oral antibiotics are thought to help control acne by curbing the growth of bacteria, thereby decreasing inflammation. They are usually taken daily for four to six months and then tapered and discontinued as acne improves. The most potent oral drug, isotretinoin, is usually taken once or twice a day for 16 to 20 weeks. It is believed to reduce the size of the oil glands so that much less oil is produced and to help prevent clogged pores. That curbs the growth of acne-causing bacteria. Because of the risk of birth defects, women of childbearing age must not be pregnant and must not become pregnant while taking isotretinoin.


text:
Monday September 3, 2012
Guests can laugh it up at Catch A Rising Star every night except Mondays and starting September 28 every Friday and Saturday night, the fun and excitement continues when Dueling Pianos take the stage at 10 p.m. till 2 a.m. Its two great entertainment options for the price of one!
The famous club that helped launch the careers of today's hottest comedians such as Robin Williams, Jerry Seinfeld, Billy Crystal, Ray Romano, Rosie O'Donnell and many more can be found right here in Reno at Silver Legacy Resort Casino. The legendary Catch A Rising Star Comedy Club showcases stand-up comedy from the country's hottest up-and-coming comedians six nights a week. Beginning September 28, Friday and Saturday evening shows begin at 6:30 p.m. and 8:30 p.m. followed by outrageous Dueling Pianos at 10 p.m.! After the comedy, keep your seat, order a cocktail and continue the fun as the piano players keep the party going till 2 a.m...AND admission is free! Tuesday through Thursday, comedy show times remain at 7:30 and 9:30 p.m.
Make it a complete night out with Dinner & A Laugh packages. Starting at just $20.50 a person, the package includes dinner at one of four fabulous Silver Legacy restaurants and tickets to a show at our Reno comedy club. The Dinner & A Laugh package is not available on Saturdays or Holidays.For more information visit us online atwww.silverlegacy.comof call 1-800-MUST-SEE (687-8733)or find us on Facebook, Twitter, YouTube or Silver Legacy's iPhone, iPad and Android Apps.
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text:
My drawing is set to state plane and feet. when I import GE the elevations are different that thos reproted on the GE screen. For example at a given location GE reports 538 but the c3d surface report 164 a factor of 3.28. sounds like a meter thing going on. is this normal? can It be adjusted?
Solved! Go to Solution.
I've gotten around this by typing UNITS at the command line and setting the "Insertion Units" to Feet.
Thanbks Ken
You're welcome! Trying to start to give back to the boards when I can!
Got get em!
Hey you got 1 kudo for 3 post. You'd be heading for Cooperstown with numbers like that
Yes Joe, this is a Feet to Meter thing. There are 3.28 Feet per Meter, just to clarify a tiny bit here!
Hi Sindarin,
That much I got. But if GE is saying feet and my c3d says feet other than acad units were unitless why would it come in in meters?
Hey Joe, not much work to do today I see... Instant replies!!! *forget I said that*
I have had that problem in Civil 3D 2011 as well. If I imported something into my drawing, it would show up in inches, and put itself out way in outer space, but if I copy and pasted it, it would show up properly.
Both my drawings and units were set up to be the exact same, so I have no clue what happened.
Under your Toolspace drawing settings, what is your drawing units set up too? That may have something to do with it. Also make sure the "Scale objects inserted from other drawings" is selected.
Give that a try I guess.
(I waited a few minutes this time)
Thankes I see the check boxes that apply. Thats a big help.
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This apartment is currently off the market. Go to the building page to see availabilities.
Home › 326 East 81st Street › 1FW
326 East 81st Street › 1FW
Apartment Features
This one-bedroom features a full size refrigerator and a recently renovated kitchen. It is situated on a great block in Manhattan's Upper East Side, close to restaurants, movie theaters, boutique shopping, and public transportation.
Building Features & Amenities
- Walk-up
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Shares Allowed. No Walls. Income Required: 40x Rent. Guarantors Allowed, Income Required: 80x Rent.
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text:
Jujube Age Control Serum 1 floz (30 ml)
Offers & Perks
Infused with 9 herbs, this all-in-one anti-aging serum instantly calms and improves the appearance of redness. It helps restore the appearance of elasticity and diminish the appearance of wrinkles.
© 2012 Wei East |
Aqua\Water, Butylene Glycol, Glycerin, PEG-12 Dimethicone, PEG/PPG 8/3 Diisostearate, Phenoxyethanol, Zizyphus Jujuba Fruit Extract, Camellia Sinensis Leaf Extract, Thuja Orientalis Seed Extract, Bambusa Vulgaris Leaf Extract, Panax Quinquefolium Root Extract, Citrus Reticulata Peel Extract, Cucumis Sativus Fruit Extract, Momordica Charantia Fruit Extract, Carbomer, Tromethamine, Xanthan Gum, Caprylyl Glycol |
Daily in the morning and evening, apply 3 to 4 drops on clean face and neck. Gently massage into skin. Follow with moisturizer. |


text:
Provo Proves - Steelers Out to Show Everyone |
Clubs - Men's DI Clubs |
Club rugby in Utah has had a confused history of late. With various DI or Super League clubs coming and going, it's easy to assume that all clubs from that state are unreliable. "Every competition we've been in, whether we've had to travel to Northern California, or play in Utah, or play in Colorado, we've shown up and played," said captain and lock forward Timote Halasima. That chapter started with a tie against Glendale and a win over the Denver Barbarians in the fall. New coach Suliasi LeFai expects even more from them in the spring. An old Steelers player originally from Tonga, LeFai is bringing in new ideas and a new energy. "We're excited," said Halasima. "We like it a lot. The coach is bringing in some new things. Jason Garcia is training our team and we've been working really hard with him. It's been really nice having him around. Playing in Colorado – we like that. The competition level is higher for us. We always met these guys in the Round of 16 and it's always nice to play some good teams like that." Halasima said while his club might be characterized as one that doesn't travel well, he says travel has not been a problem. "This club has been around since 1979," he said. "We sit down with the players and say this is where we are going this year. This is what we need. And we do it. The community helps us out big-time." "We're really glad to have a proper schedule," Halasima said. "We've always traveled and always played wherever we've been asked to play. With this dependable league, we're excited about it." Things are looking up for Provo also in their recruiting. Known for a long time as a somewhat older group of players who rattle teeth and pummel defenses, they have gone somewhat younger and faster this year. Provo sits 1-0-1 so far in the league, and will re-awaken their league season March 9 when they host the Kansas City Blues and then play at Denver Highlanders and Boulder. They will also play a friendly against the Utah Islanders, a new Salt Lake City club put into DII but with DI aspirations. Provo has a favorable schedule, playing their three toughest opponents in Utah and being on the road for the other two. While the Highlanders are another club on the rise, it's quite possible Provo could finish the season 4-0-1. That is no surprise to the Steelers. They know they have a talented team. And with the hard work they have been doing during the winter break, they are eager to prove it. |


text:
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Sripat Guesthouse16 Soi7 Moon Muang Road, T.Sriphoom, A.Muang, Old City, 50200 Chiang Mai (Show map)
Score from 133 reviews
Location great - clean hotel with friendly staff.
location location
Den Haag
Friendly staff. Good tour can be booked at the reception (by Panda Tours)
Excellent value for money, the pool looked nice although I didn't use it. I would definitely stay there again, good location.
North Point
The room was large and clean, providing excellent value for the money. The staff was pleasant and accommodating, although you do have to provide a deposit to the use the in-room safe.
Sacramento, CA
We especially liked the older lady owning Sripat Guesthouse. Friendly staff also and a great doorman at nighttime who was blowing up balloons One night when we returned.....we sang him Happy Birthday ;))
Big room, comfortable staying
exellent, great family business, very friendly staff, we felt at home. great massage salon just beside the guesthouse (further up the street). great place / choice to start our trip here.
This a lovely and comfortable guest house with ultra-friendly staff. I highly recommend it.
Good location and friendly staff. Excellent value for money.
Sripat Guesthouse is only a 20-minute walk from Chiang Mai International Airport. It offers an outdoor pool and a tour desk.
Night Market and Sunday Walking Street are within a 20-minute drive from Sripat Guesthouse. Chiang Mai Old City Area is also a 20-minute ride away. All rooms have air conditioning, a cable flat-screen TV and a fridge. Free toiletries are offered in en suite bathrooms. The guest house has a tour desk to help guests with travel arrangements. Guests can relax at the garden with leisure activities. Bicycle and car rental services are available. A range of both Thai and international restaurants are only a 5-minute walk from the residence. Hotel Rooms: 24 Why use Booking.com?Why use Booking.com?Low ratesNo booking fees • Save money! • Best Price Guaranteed 435,605 properties worldwide
Including 117,323 vacation rentals Unbiased reviews26,360,000 reviews from real guests We speak your languageWebsite and customer service in English (US) and 41 other languages Booking is safeWhen you book with us your details are protected by a secure connection. OutdoorsOutdoor Pool, Grounds, Terrace ActivitiesBicycle Rental Food & DrinkRestaurant, Breakfast in the Room InternetFree! Wi-Fi is available in all areas and is free of charge. ParkingNo parking available. ServicesCar Rental, Tour Desk, Ticket Service, Baggage Storage, Laundry, Fax/Photocopying GeneralNewspapers, Safe, Non-smoking Rooms, All Spaces Non-Smoking (Public and Private), Air Conditioning Check-inFrom 2:00 PM Check-outUntil 11:00 AM Cancellation/
Roseate Chiang MaiRoseate Chiang Mai features modern rooms with air conditioning, a 5-minute walk from Sunday Walking Street. It has a 24-hour front desk and an on-site restaurant.Most recent booking for this hotel was today at 01:33
Score from 934 reviews
Very good
- 8/10
BB Mantra Boutique and BudgetBB Mantra Boutique and Budget is 1 km from Thapae Gate. It offers air-conditioned rooms with free Wi-Fi. The hotel has a pool, tour desk and 24-hour front desk. The hotel is 1.5 km to Wat Chedi Luang....Most recent booking for this hotel was today at 00:32
Score from 51 reviews
Very good
- 8.5/10
Yindee Stylish GuesthouseYindee Stylish Guesthouse is in Chiang Mai's historic quarter, a 10-minute drive from Chiang Mai Airport. It offers free Wi-Fi and serves free drinks at the lobby.Most recent booking for this hotel was yesterday at 23:09
Score from 436 reviews
Very good
- 8/10
The Sila Boutique Bed & BreakfastThe Sila Boutique Bed & Breakfast is located opposite from Wat Phra Singh Temple. It offers modern air-conditioned rooms with a balcony and free Wi-Fi.Most recent booking for this hotel was yesterday at 22:46
Score from 178 reviews
- 9/10


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How to read literature like a professor : a lively and entertaining guide to rea
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Adult Nonfiction 809 F 2003
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Copyright © 2012 The Authors All rights reserved.
Cell Reports, Volume 2, Issue 4, 732-737, 27 September 2012
The Rate of Increase of Short Telomeres Predicts Longevity in Mammals
Elsa Vera1, 3, Bruno Bernardes de Jesus1, 3, Miguel Foronda1, Juana M. Flores2 and Maria A. Blasco1, ,
1 Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Center, Melchor Fernández Almagro 3, E-28029 Madrid, Spain
2 Department of Animal Surgery and Medicine, Facultad de Veterinaria, Universidad Complutense de Madrid, 28029 Madrid, Spain
3 These authors contributed equally to this work
Graphical Abstract
► Mouse telomeres shorten ∼100 times faster than human telomeres ► The increase in the percentage of short telomeres predicts individual mouse longevity ► Longitudinal telomere length studies are necessary to predict mammalian longevity
- Aberrantly short telomeres result in decreased longevity in both humans and mice with defective telomere maintenance. Normal populations of humans and mice present high interindividual variation in telomere length, but it is unknown whether this is associated with their lifespan potential. To address this issue, we performed a longitudinal telomere length study along the lifespan of wild-type and transgenic telomerase reverse transcriptase mice. We found that mouse telomeres shorten ∼100 times faster than human telomeres. Importantly, the rate of increase in the percentage of short telomeres, rather than the rate of telomere shortening per month, was a significant predictor of lifespan in both mouse cohorts, and those individuals who showed a higher rate of increase in the percentage of short telomeres were also the ones with a shorter lifespan. These findings demonstrate that short telomeres have a direct impact on longevity in mammals, and they highlight the importance of performing longitudinal telomere studies to predict longevity.
Telomeres are repeated DNA nucleoprotein structures at the ends of eukaryotic chromosomes (Blackburn, 1991; de Lange, 2005) that protect them from degradation and DNA repair activities, and are essential for chromosomal stability (Chan and Blackburn, 2002). Telomere repeats can be added de novo by telomerase, a reverse transcriptase that elongates telomeres in cells in which it is expressed (Blackburn, 2005; Flores et al., 2006; Greider, 1998; Greider and Blackburn, 1985; Marion et al., 2009). In telomerase-negative cells, telomeres shorten with each round of cell division as a result of end replication and DNA-degrading activities. Short telomeres are passed onto daughter cells, and thus telomere shortening is exacerbated by cell division and increasing age in both humans and mice (Flores et al., 2008; Harley et al., 1990). Critically short telomeres can trigger a persistent DNA damage response that leads to cellular senescence and/or apoptosis (Collado et al., 2007; Deng et al., 2008), eventually compromising the regenerative capacity and function of tissues (Blasco, 2007). Short telomeres are proposed to be sufficient to cause the degenerative pathologies associated with aging even in the presence of telomerase activity (Armanios et al., 2009; Hao et al., 2005).
In further support of this notion, both telomerase-deficient mice and human diseases due to mutations in telomerase components result in accelerated-aging phenotypes and decreased longevity due to premature depletion of stem cells and subsequent organ/tissue failure (Armanios et al., 2007; Blasco et al., 1997; García-Cao et al., 2006; Herrera et al., 1999; Mitchell et al., 1999; Tsakiri et al., 2007; Vulliamy et al., 2001; Yamaguchi et al., 2005). Telomere shortening associated with normal aging can be influenced by known risk factors for disease and premature death, such as psychological stress, smoking, cognitive impairment, and obesity (Canela et al., 2007; Cawthon et al., 2003; Cherkas et al., 2006; Epel et al., 2004; Valdes et al., 2005). However, whether the rate of telomere shortening in individual mammals has an influence on their longevity remains unexplored. In this regard, although serial telomere length measurements were previously obtained in baboons, a correlation with longevity was not sought (Baerlocher et al., 2003). Of interest, it was recently reported that telomere length measured at 25 days of age is a predictor of lifespan in birds (Heidinger et al., 2012).
Evidence from telomerase loss-of-expression and gain-of-expression transgenic mouse models suggests that telomere length may be rate limiting for mouse longevity (García-Cao et al., 2006; Tomás-Loba et al., 2008). Nonetheless, a role for telomere length in normal mouse aging is brought into question by the fact that although mice have very long telomeres compared with humans (∼50 kb in young C57BL/6 mice, compared with ∼15 kb in young humans) (Gomes et al., 2011; Wright and Shay, 2000), mice have a much shorter maximal lifespan (∼5 years in mice of mixed background homozygous [−/−] for the GHR/BP gene) (Brown-Borg and Bartke, 2012) than humans (122 years). Although numerous studies have measured the average rate of telomere shortening per year in human population studies, which ranges from 31 base pairs (bp)/year to 72 bp/year in peripheral blood cells (Canela et al., 2007; Hastie et al., 1990; Slagboom et al., 1994; Vaziri et al., 1993), this rate has not been obtained in mice. Moreover, only one study has linked the increase in the percentage of short telomeres with age in humans, which was calculated as a 0.6% increase per year (Canela et al., 2007).
Here, we reasoned that the rate of increase in the percentage of short telomeres and the rate of telomere shortening throughout the lifespan of individuals might explain the different longevities of wild-type (WT) mice and humans, as well as the interindividual variations in longevity in mammals.
Results and Discussion
With the aim of determining the rate of telomere shortening and the rate of increase in the percentage of short telomeres with aging in mice, we performed longitudinal telomere length determinations in the blood of individual mice by using an automated high-throughput quantitative fluorescence in situ hybridization (HT-QFISH) platform (Canela et al., 2007).
To correct for gender and genetic background, as well as to circumvent possible effects of reproduction on telomere length, we used only male mice of a 100% C57BL/6 background. In addition, the mice were individually housed at 3 months of age and fed a defined diet of 92.5 kcal per week (see Experimental Procedures ). This caloric intake represents ∼10% fewer calories than the average daily intake of C57BL/6 mice, and was used to avoid a possible impact of obesity on longevity. In parallel, we determined the same parameters in a transgenic mouse line overexpressing the mouse catalytic subunit of telomerase reverse transcriptase (TERT) in various epithelial tissues (hereafter termed transgenic TERT [TgTERT]; González-Suárez et al., 2001, González-Suárez et al., 2002). This mouse line has a comparable 100% C57BL/6 background; however, it presents delayed signs of aging compared with WT mice (González-Suárez et al., 2005; this work), as well as a 40% increase in median longevity when combined with overexpression of tumor suppressor genes (Tomás-Loba et al., 2008). As shown in Figure 1A, the TgTERT mice used here show a delayed onset of the first deaths in the colony compared with the WT cohorts (see Figure 1A), in agreement with their increased healthspan. Thus, we set out to study whether any telomere-related parameter could predict longevity in these two independent mouse cohorts (TgTERT and WT) with slightly different longevities.
For cell analyses, we used peripheral blood leukocytes (PBLs), which are widely used for human telomere length studies because hematopoietic stems cells proliferate throughout life and thus reflect on cellular turnover associated with the aging process. Telomere length measurements in the blood have been shown to be representative of the general health status in humans (Canela et al., 2007; Cawthon et al., 2003; Collerton et al., 2007; Mainous et al., 2010; Valdes et al., 2005) and mice (Bernardes de Jesus et al., 2012), and provide an indicator of the general healthspan. In this regard, although the TERT transgenic mice used here do not target telomerase to blood cells, TERT expression in these mice has systemic beneficial effects that delay aging (Tomás-Loba et al., 2008), as also observed recently when a gene therapy strategy was used to overexpress TERT late in life (Bernardes de Jesus et al., 2012). We extracted 300 μl of blood from the facial vein of each mouse at 4, 8, 12, and 25 months of age (see Experimental Procedures ) and the mice were left to age until the end of their lifespan, to obtain their complete longevity curve (Figure 1A). To avoid morbidity associated with this procedure in old mice, blood extractions were not performed after 25 months of age. Of note, we observed a delay in the age at onset of first death in the TgTERT cohort: the first mouse died at >100 weeks of age, compared with <50 weeks of age in the case of the WT cohort (Figure 1A). We determined both the average telomere length and the percentage of short telomeres at the indicated time points per individual mouse by using HT-QFISH (Canela et al., 2007). HT-QFISH is able to measure individual telomere signals at a single-cell level in interphasic nuclei. In this setting, each telomere signal corresponds to a clustering of few individual telomeres. The percentage used to represent short telomeres by HT-QFISH usually corresponds to the 10%–20% percentile in the reference population (in this case, we used 4-month-old WT mice as reference), which is 15 kb. We previously determined that telomere signals <15 kb are a good indicator of the presence of short telomeres in mouse blood cells and reflect differences in telomere length between different cohorts and treatments (Bernardes de Jesus et al., 2012). Therefore, here we set a cutoff of 15 kb to quantify the presence of short telomeres. In addition, we performed correlations with other cutoffs (<2, <5, and <10 kb), but we observed the strongest correlations at the 15 kb cutoff (not shown).
First, it is apparent that even though mouse telomeres are very long at young ages (>50 kb at 4 months of age), they shorten with age, as reflected by both a significant decrease in the mean telomere length and a significant increase in the percentage of short telomeres, detectable at 4 month intervals (Figures 1B and 1C). By adjusting the data to a linear regression model, we determined a rate of telomere shortening (as estimated by the slope of the regression line) of 7,000 bp per year (Figure 1D), which was comparable in both mouse cohorts and is 100 times faster than that obtained for human PBLs using the same technology (Canela et al., 2007). These results indicate that even though mouse telomeres are much longer than human telomeres at younger ages, they exhibit a much faster rate of shortening with age, highlighting the relevance of performing longitudinal telomere length studies rather than measuring telomeres at a single time point. The rate of increase in the percentage of short telomeres per year was 6.6% in WT mice and 4.9% in the TgTERT cohort (as estimated by the slope of the regression line; Figure 1E).
Next, we investigated whether the telomere length or the percentage of short telomeres at any of the studied timepoints is predictive of mouse longevity, as was recently reported for zebra finches (Heidinger et al., 2012). In the case of mice, however, we did not find a significant correlation between either the average telomere length or the percentage of short telomeres with longevity in any of the two mouse cohorts, with the exception of an inverse correlation between average telomere length and longevity at 12 months of age in the TgTERT mice (Figure S1).
Longitudinal studies allow one to examine telomere dynamics in a given individual over time. A given rate of telomere shortening or a rate of increase in the percentage of short telomeres is the result of a longitudinal trend in individual mice that may reflect very complex genetic traits associated with longevity, which cannot be inferred from a single time-point measurement. Therefore, we determined the rate of increase in the percentage of short telomeres per month and the rate of telomere shortening per month for every mouse under study. Strikingly, we found a significant correlation between the rate of increase in the percentage of short telomeres per month and longevity (Figure 2A), which could be observed in both mouse cohorts, and between the rate of telomere shortening per month and longevity (Figure 2B), which was only observed in WT mice. We also observed a significant correlation between the rates of increase in the percentage of short telomeres and mean telomere shortening (Figure 2C). Together, these results indicate that the rate of increase in the percentage of short telomeres is a reliable and robust predictor of mouse longevity in two different mouse strains with different TERT expression levels and different longevities. The mice with the higher rates of increase in the percentage of short telomeres were the ones that had shorter lives, while those with lower rates of increase in the percentage of short telomeres were the ones that enjoyed longer lives.
The fact that the TgTERT cohorts did not show a correlation between the rate of telomere shortening per month and longevity prompted us to address whether this was the consequence of TgTERT mice showing a delayed time of onset of the first death in the colony. In particular, to assess whether lifespan can influence the rate of telomere shortening or the rate of increase in the percentage of short telomeres, we plotted these two parameters at different time intervals of measurement (Figure S2). Indeed, age influenced the rate of mean telomere shortening per month in a discontinuous manner, so that we found higher rates of telomere shortening per month in young mice compared with older mice (Figure S2B). Of interest, this was not the case for the rate of increase in the percentage of short telomeres per month, which was quite constant at different age intervals in both mouse cohorts, with the exception of lower rates of increase in the percentage of short telomeres in old TgTERT mice (Figure S2A). The fact that the rate of telomere shortening per month was not constant with age in both mouse cohorts could account for the significant correlation between the rate of mean telomere shortening per month and longevity in the WT mice but not in the TgTERT mice (Figure 2B), because a significant fraction of WT mice (versus only one TgTERT mouse) died before measurement of the four time points. Indeed, even if we exclude the single TgTERT mouse that died before the fourth measurement, we observe a strong correlation between the rate of increase in the percentage of short telomeres and longevity (Figure S3). These findings indicate that the rate of increase in the percentage of short telomeres is a robust and reliable telomere marker for longevity studies.
It is of interest to note that differences in telomere length and longevity could not be attributed to differences in gender, reproduction, genetic background, or environmental factors, as only male mice of the C57BL/6 genetic background housed at our specific pathogen-free (SPF) facility were studied. In this regard, we did not find a correlation between the rate of increase in the percentage of short telomeres or rates of telomere shortening and weight gain with age (Figure S4), which together with the fact that the mice were fed a defined diet rules out a possible dietary contribution. These results suggest that differences in the rate of increase in the percentage of short telomeres or in the rate of telomere shortening, which have been shown to vary among individuals of the same age in different species (Canela et al., 2007; Heidinger et al., 2012; Monaghan, 2010), may be the result of small differences in modifier genes, or environmental factors, and offer an experimental platform to uncover new factors for modulation of aging and longevity.
Finally, we sought to determine whether variations in the rate of increase in the percentage of short telomeres had an impact on pathologies found at the time of death. To that end, we performed a full histopathological analysis of mice under study at their endpoint. The more prevalent pathologies found in C57BL/6 mice at their time of death are cancer (in ∼50%–80% of mice) and age-associated pathologies (∼50%–20%) (González-Suárez et al., 2002; Herranz et al., 2010; Tomás-Loba et al., 2008). We first determined whether the incidence of malignant cancers (lymphoma, sarcoma, and adenocarcinoma) showed any differential prevalence in mice belonging to either the higher or lower quartile of rate of increase in the percentage of short telomeres. We found a similar incidence of cancer or degenerative diseases in both cases, in spite of the fact that mice belonging to the higher quartile of rate of increase in the percentage of short telomeres showed a median age at death of 105 weeks, compared with 140 weeks in the case of mice belonging to the lower quartile (Figure S5). We observed the same tendency in the TgTERT cohort, and mice belonging to the higher quartile of rate of increase in the percentage of short telomeres showed a median age at death of 116 weeks, compared with 149 weeks in the case of mice belonging to the lower quartile.
Collectively, these findings demonstrate that the rate of increase in the percentage of short telomeres during an individual's lifetime, rather than the rate of telomere shortening over time, determines longevity in mice. These results bring into question the prevailing viewpoint that telomere shortening does not influence replicative aging in WT mice (Gomes et al., 2011; Wright and Shay, 2000), and highlight the importance of performing longitudinal telomere studies to predict traits as complex as longevity.
Experimental Procedures
Male mice of a 100% C57BL/6 background were produced and stored at the SPF barrier area of the Spanish National Cancer Center, in accordance with the recommendations of the Federation of European Laboratory Animal Science Associations.
In this study we used a total of 38 mice (20 WT and 18 TgTERT; Figure 1B). Two mice from each cohort were sacrificed after the last telomere length measurement point for experimentation, and were excluded from the survival curves and other correlations involving final lifespan.
Experimental Setup
After weaning, five mice were housed per cage and fed a nonpurified diet (No. 2018; Harlan) ad libitum. For the aging study, 3-month-old mice were individually housed and were fed 92.5 kcal per week of chemically defined control diet (AIN-93M, diet No. F05312; Bio-Serv). This caloric intake was ∼10% fewer calories than the average daily intake of C57BL/6 mice, to ensure that all food was consumed. Defined diets were cold-packed into 1 g pellets. The mice were fed two-sevenths of the weekly allotment of food on Monday and Wednesday, and three-sevenths of that amount of Friday (Dhahbi et al., 2004; Pugh et al., 1999).
Mice were inspected on a daily basis and sacrificed when they presented signs of illness or tumors, in accordance with the Guidelines for Humane Endpoints for Animals Used in Biomedical Research (Harrison et al., 2009). The date of euthanasia was considered as an estimation of the natural lifespan. The mice were subjected to necropsy and histopathological analysis.
Histological Analysis
Histopathology was performed as previously described (González-Suárez et al., 2001). Briefly, tissues and organs were fixed for 24 hr in a 10% neutral buffered formalin solution at room temperature, dehydrated through graded alcohols and xylene, and embedded in paraffin. Histological analysis was achieved on 4–5 μm sections according to standard procedures. Cancer-related pathologies and senile lesions were grouped as described previously (Tomás-Loba et al., 2008).
HT-QFISH on PBLs
Blood was extracted from the facial vein at the indicated time points. Upon erythrocyte lysis (buffer EL; Qiagen), PBLs were plated on a clear-bottom, black-walled, 96-well plate, and HT-QFISH was performed as previously described (Canela et al., 2007). The accuracy and sensitivity of HT-QFISH are similar to those of telomere QFISH on metaphasic chromosomes (Canela et al., 2007). We analyzed telomere length values using individual telomere spots (>5,000 per sample) corresponding to the specific binding of a Cy3-labeled telomeric probe. Fluorescence intensities were converted into kilobases as described previously (Canela et al., 2007; McIlrath et al., 2001).
Statistical Analysis
A log-rank test was used to calculate statistical differences in the survival curves. Student's t-test was used to calculate the statistical significance of the mean telomere and short telomere variation over time. To calculate the rate of increase in the percentage of short telomeres and the rate of mean telomere shortening, linear regression lines were calculated for each mouse with GraphPad Prism, representing the best-fit values of the four values calculated at the different time points (either percentage of short telomeres or mean telomere length). For mice that died before the acquisition of all time points, linear regression lines were determined from the available measurements. The p value was calculated by dividing the slope by its standard error, and represents the correlation between the axes (slope significantly different from zero). Pathological analysis was calculated with the χ2 test.
We are indebted to Rosa Serrano for mouse colony management. The Blasco laboratory is funded by the Spanish Ministry of Science and Innovation, European Union (GENICA and TELOMARKER), European Research Council (Advanced Grant), Fundación Botín, and Fundación Lilly. E.V. performed most of the experimental work. B.B.J. and M.F. analyzed data and wrote the paper. J.M.F. did the pathological analysis. M.A.B. directed the project and wrote the paper.
Armanios et al., 2009 (2009). Short telomeres are sufficient to cause the degenerative defects associated with aging. Am. J. Hum. Genet. 85, 823–832. Abstract | Full Text | PDF (566 kb) | CrossRef | PubMed
Armanios et al., 2007 (2007). Telomerase mutations in families with idiopathic pulmonary fibrosis. N. Engl. J. Med. 356, 1317–1326. CrossRef | PubMed
Baerlocher et al., 2003 (2003). Telomere shortening in leukocyte subpopulations from baboons. J. Leukoc. Biol. 73, 289–296. CrossRef | PubMed
Bernardes de Jesus et al., 2012 (2012). Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol. Med. 4, 691–704. PubMed
Blackburn, 1991 (1991). Structure and function of telomeres. Nature 350, 569–573. CrossRef | PubMed
Blackburn, 2005 (2005). Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. FEBS Lett. 579, 859–862. CrossRef | PubMed
Blasco, 2007 (2007). Telomere length, stem cells and aging. Nat. Chem. Biol. 3, 640–649. CrossRef | PubMed
Blasco et al., 1997 (1997). Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25–34. Abstract | Full Text | PDF (281 kb) | CrossRef | PubMed
Brown-Borg and Bartke, 2012 (2012). GH and IGF1: roles in energy metabolism of long-living GH mutant mice. J. Gerontol. A Biol. Sci. Med. Sci. 67, 652–660. PubMed
Canela et al., 2007 (2007). High-throughput telomere length quantification by FISH and its application to human population studies. Proc. Natl. Acad. Sci. USA 104, 5300–5305. CrossRef | PubMed
Cawthon et al., 2003 (2003). Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361, 393–395. CrossRef | PubMed
Collado et al., 2007 (2007). Cellular senescence in cancer and aging. Cell 130, 223–233. Abstract | Full Text | PDF (710 kb) | CrossRef | PubMed
Collerton et al., 2007 (2007). Telomere length is associated with left ventricular function in the oldest old: the Newcastle 85+ study. Eur. Heart J. 28, 172–176. CrossRef | PubMed
Chan and Blackburn, 2002 (2002). New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin. Oncogene 21, 553–563. CrossRef | PubMed
Cherkas et al., 2006 (2006). The effects of social status on biological aging as measured by white-blood-cell telomere length. Aging Cell 5, 361–365. CrossRef | PubMed
de Lange, 2005 (2005). Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 19, 2100–2110. CrossRef | PubMed
Deng et al., 2008 (2008). Telomere dysfunction and tumour suppression: the senescence connection. Nat. Rev. Cancer 8, 450–458. PubMed
Dhahbi et al., 2004 (2004). Temporal linkage between the phenotypic and genomic responses to caloric restriction. Proc. Natl. Acad. Sci. USA 101, 5524–5529. CrossRef | PubMed
Epel et al., 2004 (2004). Accelerated telomere shortening in response to life stress. Proc. Natl. Acad. Sci. USA 101, 17312–17315. CrossRef | PubMed
Flores et al., 2006 (2006). Telomerase regulation and stem cell behaviour. Curr. Opin. Cell Biol. 18, 254–260. CrossRef | PubMed
Flores et al., 2008 (2008). The longest telomeres: a general signature of adult stem cell compartments. Genes Dev. 22, 654–667. CrossRef | PubMed
García-Cao et al., 2006 (2006). Increased p53 activity does not accelerate telomere-driven ageing. EMBO Rep. 7, 546–552. PubMed
Gomes et al., 2011 (2011). Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination. Aging Cell 10, 761–768. CrossRef | PubMed
González-Suárez et al., 2001 (2001). Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes. EMBO J. 20, 2619–2630. CrossRef | PubMed
González-Suárez et al., 2002 (2002). Cooperation between p53 mutation and high telomerase transgenic expression in spontaneous cancer development. Mol. Cell. Biol. 22, 7291–7301. CrossRef | PubMed
González-Suárez et al., 2005 (2005). Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice. Oncogene 24, 2256–2270. CrossRef | PubMed
Greider, 1998 (1998). Telomerase activity, cell proliferation, and cancer. Proc. Natl. Acad. Sci. USA 95, 90–92. CrossRef | PubMed
Greider and Blackburn, 1985 (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405–413. Abstract | | CrossRef | PubMed
Hao et al., 2005 (2005). Short telomeres, even in the presence of telomerase, limit tissue renewal capacity. Cell 123, 1121–1131. Abstract | Full Text | PDF (616 kb) | CrossRef | PubMed
Harley et al., 1990 (1990). Telomeres shorten during ageing of human fibroblasts. Nature 345, 458–460. CrossRef | PubMed
Harrison et al., 2009 (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395. PubMed
Hastie et al., 1990 (1990). Telomere reduction in human colorectal carcinoma and with ageing. Nature 346, 866–868. CrossRef | PubMed
Heidinger et al., 2012 (2012). Telomere length in early life predicts lifespan. Proc. Natl. Acad. Sci. USA 109, 1743–1748. CrossRef | PubMed
Herranz et al., 2010 (2010). Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat. Commun. 1, 3. PubMed
Herrera et al., 1999 (1999). Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J. 18, 2950–2960. CrossRef | PubMed
Mainous et al., 2010 (2010). Leukocyte telomere length and coronary artery calcification. Atherosclerosis 210, 262–267. CrossRef | PubMed
Marion et al., 2009 (2009). Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell 4, 141–154. PubMed
McIlrath et al., 2001 (2001). Telomere length abnormalities in mammalian radiosensitive cells. Cancer Res. 61, 912–915. PubMed
Mitchell et al., 1999 (1999). A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402, 551–555. CrossRef | PubMed
Monaghan, 2010 (2010). Telomeres and life histories: the long and the short of it. Ann. N Y Acad. Sci. 1206, 130–142. CrossRef | PubMed
Pugh et al., 1999 (1999). Controlling caloric consumption: protocols for rodents and rhesus monkeys. Neurobiol. Aging 20, 157–165. CrossRef | PubMed
Slagboom et al., 1994 (1994). Genetic determination of telomere size in humans: a twin study of three age groups. Am. J. Hum. Genet. 55, 876–882. PubMed
Tomás-Loba et al., 2008 (2008). Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135, 609–622. Abstract | Full Text | PDF (1371 kb) | CrossRef | PubMed
Tsakiri et al., 2007 (2007). Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc. Natl. Acad. Sci. USA 104, 7552–7557. CrossRef | PubMed
Valdes et al., 2005 (2005). Obesity, cigarette smoking, and telomere length in women. Lancet 366, 662–664. CrossRef | PubMed
Vaziri et al., 1993 (1993). Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am. J. Hum. Genet. 52, 661–667. PubMed
Vulliamy et al., 2001 (2001). The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413, 432–435. CrossRef | PubMed
Wright and Shay, 2000 (2000). Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology. Nat. Med. 6, 849–851. CrossRef | PubMed
Yamaguchi et al., 2005 (2005). Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N. Engl. J. Med. 352, 1413–1424. CrossRef | PubMed
Publication Information
Received: May 3, 2012
Revised: July 11, 2012
Accepted: August 21, 2012
Published online: September 27, 2012


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Now we've got a horse race.
Tim Urban's
Teflon coating finally wore off, and he got stuck with the American Idol pink slip. He caught a break when he didn't have to sing himself off the show because of how long Idol Gives Back ran over. It was about 9:20 when the announcement was made, which meant that all the Gleeks missed the last half hour of the ensuing GLEE episode when they DVR'd it. (FOX got so much invective in the social media that they decided to re-run GLEE on Friday night.) Ryan Seacrest had said Tuesday night that the show would run long, so I allowed an extra half-hour for my recording and was able to catch all of Idol Gives Back. The highlight was the performance of "Stairway To Heaven" by an all-star band of Steve Vai and Orianthi on guitars, Travis Barker from Blink 182 on drums, A.I.'s Randy Jackson on bass, and the incomparable Mary J. Blige on the lead vocal. Mary J. is quite possibly the coolest person on the planet. She's one of the few artists who can step between genres and perform each with authenticity and integrity. If you've never heard her version of U2's "One", do yourself a favor and Google it right now. Carrie Underwood once again proved why she is the superstar that she is when she sang "Change". That's how you take ownership of a song. Carrie wrings every bit of emotion out of every song she sings. Can't wait to see her here in October. (BTW—Tickets for Carrie's concert at INTRUST Bank Arena go on sale Saturday.) Joss Stone and Jeff Beck blazed through "I Put A Spell On You". Stone is today's preeminent Blues singer. Talk about an old soul; she's only 23 and she sings like she's lived decades of hard times and pain. Incredible. As far as the other performances go--Black Eyed Peas were terrible, Elton John was so-so, and Alicia Keys was solid. George Lopez' roasting of the judges was funny and on the money; and Wanda Sykes' skewering of the whole Idol process was really good, too. Overall, I thought the show was excellent, but I do have an admission to make: I fast-forwarded through all the charity vignettes. Come on—you did it too! Admit it! I was pretty much dead wrong in my predictions yesterday. It's like the only time I didn't have Tim Urban getting the boot, and the one time I don't list him, he gets hosed. "Bout time. Wasn't that surprised to see
Aaron Kelly
in the Bottom 3, but was pretty stunned when
Casey James
joined the bunch. Teflon Tim's finally gone. Look for him in a Brady Bunch revival coming to your town soon! How I rank the remainder:
Crystal Bowersox
Lee Dewyze
Casey James
Siobhan Magnus
Michael Lynche
Aaron Kelly
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I was upset for two reasons! First of all I missed last nights performances due to work (I am working on that!) and second of all that one of the most talented singers up there went home. I think that Casey is being kept there for sex appeal. Don't get me wrong I don't have anything against him personally. He just sounds the same week after week. I just don't think he is as talented as Sibhan.
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31 Oct 2007 1:47 PM #1
[2.x][discontinued] Ext.ux.Andrie.Select (ComboBox with multiSelect)
[2.x][discontinued] Ext.ux.Andrie.Select (ComboBox with multiSelect)
March 26, 2008
This extension has been discontinued! A new extension with the same capabilities, but with cleaner and smarter code will be uploaded within the future days.
* This extension is merely the new-comer after Ext.ux.form.Select for Ext 1.x
Same features are available. To summarize: a ComboBox with multiple selection support.
Nothing much changed on the surface, other than switching the config property singleSelect to it's counter-property: multiSelect. The reason behind the change is to make it more logical when using Ext.DataView.
Since 0.3.6 - it also features history capabilities (the former HistoryComboBox)
Live DEMO is available here. Testcase is included in the attached ZIP file.
As always - looking forward to reactions on this!
TO DO (not in the very near future)
- add key search (Ext 1.x - SelectBox)
- add grouping capability (Ext 1.x - GroupComboBox)
Post Scriptum- I sincerely apologize, but you won't be seeing "Mine is better because..." regarding this post. People can choose and make up their own mind. This is one reason why I switched to Ext.ux.Andrie namespace. I want to govern over Ext.ux.Select (sounds like community-work, consensus toward official release) no more than I want somebody else to use Ext.ux.Andrie namespace (personal work).
- I apologize for a second time because there was a "nice" delay since I promised to support Ext 2.x and the current time - release time. To be honest, this switch has only taken one day - today -, so it could have been released a long time ago.
- All in all, I'd like to thanks the Ext2 team - it was fairly easier to implement this on the new framework, than it was on Ext1.
[GMT 14:33 Nov. 5] - Update to v0.3.4 (fixed clearValue, improved reset, new clear button/trigger)
[GMT 23:14 Nov. 5] - Update to v0.3.5 (improved clear trigger and transform capabilities)
[GMT 10:04 Nov. 6] - Update to v0.3.6 (added history capabilities) [GMT 13:40 Nov. 7] - Update to v0.3.7 (removed a faulty JS hack - It's important to go ahead with this update!!!)
[GMT 17:02 Nov. 12] - Update to v0.3.8 (improved setValue function)
[GMT 10:35 Nov. 17] - Update to v0.4 (improvements and fixes + cleaner code; full changelog on the demo page)
[GMT 14:19 Nov 20] - Update to v0.4.1 - LIVE DEMO IS NOT YET UPDATED TO USE THE LATEST VERSION! (Having problems with accessing the webhost)
31 Oct 2007 3:21 PM #2
IE6. Error in line 51 "Console is not defined".
Thanks in advance.
1 Nov 2007 12:49 AM #3
Nice job, Andrei!
Nice job, Andrei!
This extension is very useful for the application I'm working on it right now.
P.S.: o treaba buna...
1 Nov 2007 2:08 AM #4
@galdaka - Pfff.. Ok, I will switch to another way of showing the values of the fields. Right now it is using console.log which supposedly it was available on IE in the debug version of ExtJS. It will get fixed today
@lucian - mersi
1 Nov 2007 8:11 AM #5
The component has now been updated and has some fixes, but most importantly some enhancements (e.g. deleting the value by keyboard - the feature was available in 0.2 but wasn't included in 0.3).
The testcase uses form textfields to show components' values.
The testcase also now features a comparison between Select and the formal ComboBox.
[PS: I'm not able to reach my hosting server for the moment, so the Live Demo is not yet updated]
PS: Live Demo now Online
2 Nov 2007 10:37 AM #6
I like the extention but whats up with the name lol :p
2 Nov 2007 2:52 PM #7
@TommyMaintz - what's wrong with the name? If you are talking about Andrie - it's not a mispelling from Andrei.. and if you are talking about why it is not Ext.ux.Select, you find the explanation in the starting post of this thread.
2 Nov 2007 5:17 PM #8
Ah yes you are right. I didnt read the small characters. Lucky me its not a contract And indeed i thought it was based on your name. Andrie is a name sometimes used in the netherlands so i thought it would maybe be your real name.
Again really nice work, i think its worth getting the actual Ext.ux.Select namespace!
2 Nov 2007 7:29 PM #9
Great widget, but the items aren't deselected if you remove items from the list even though the field's text updates. I added a deselect method that also removes it from the dataview because I needed to be able to clear any selected values if the first item was clicked.
Code:deselect:function(index){ this.removeValue(this.store.getAt(index).data[this.valueField || this.displayField]); this.view.deselect(index, this.multiSelect); },
3 Nov 2007 5:18 AM #10
@shade - you mean you would like to have this situation:you remove items from the store and you would like them to be removed automatically from the combobox/select ? is this what you are talking about?


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Milner, E., 2008. Exploring the social use of space using principles of relativity. Masters Thesis (Masters). Bournemouth University.
Morris, J. T., 2008. Re-examining associated bone groups from southern England and Yorkshire, c4000BC to AD1550. PhD Thesis (PhD). Bournemouth University.
Waller, R., 2008. Archaeological evaluation, land use and development: an application of decision analysis to current practices within local government development control processes. PhD Thesis (PhD). Bournemouth University.
Backhouse, P. N., 2008. Campfires in context hunter-gatherer fire technology and the archaeological record of the South High Plains, USA. PhD Thesis (PhD). Bournemouth University.
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text: When you come to the junction of Highways 99 & 198, exit east to Visalia. Follow 198 east through Visalia, past the Exeter exit, flashing lights, past the Woodlake exit, flashing lights, through Lemon Cove. After leaving Lemon Cove, you will see a Prince Mart on the left. Turn left (west); you are now on State Highway 216, which will eventually be the same as Avenue 344. Proceed 3.2 miles. You will find our blacktop driveway on the right within a city block's distance after turning left (west) at the 20 mph corner.


text:
Mutations can be defined as any change in the sequence of DNA, the complex molecule which codes for life. Many teach that such changes are accidents or errors. While this is certainly possible, it is not something scientists can observe directly. So to say that mutations are errors is really an opinion or educated guess.
Many mutations have been identified that cause disease, and it is certainly easy to believe that these are probably the result of errors. Mutations causing disease are often the easiest to find because there is a considerable amount of money spent on disease research. However, more information is becoming available on mutations that can be valuable in some way. A closer look at how different mutations affect livestock can give a better understanding of the role mutations play in our world.
Spider lambs
There are thousands of different genes1 involved in normal growth and development. When bones develop in a lamb, some genes signal for the bone to grow, and other genes signal for bone growth to stop. It is amazing how these genes are turned on or off at the proper time so that a little lamb can develop into a healthy adult sheep.
Some lambs have a mutation in a gene that signals for bone growth to stop.2 This mutation results in a defective protein, so the bones continue to grow longer. As with all genes, a lamb will carry two copies of this gene, one inherited from each parent. Lambs carrying only one copy of this mutation are healthy but tend to grow a bit larger than normal. Lambs with the mutation in both copies of this gene have a disease known as spider lamb syndrome. These lambs have severe abnormalities in their skeleton and generally die, resulting in serious loss to the owner.3
Litters of lambs
Sheep are seasonal breeders. This means that there is only one part of a year that a ewe can get pregnant. Since the ewe can only give birth once a year, a farmer can get more lambs if the ewe has more than one lamb at a time. Most sheep give birth to a single lamb or sometimes twins. However, there are some sheep that can have 3 or 4 lambs at a time: a nice sized litter!
The Booroola Merino sheep of Australia often produce large litters. A mutation was identified in a gene which causes this.4 If a ewe has only one copy with this mutation, she will have an average of one extra lamb per litter. If she carries the mutation in both copies of this gene, she will average between one and two extra lambs.5 It is believed that this mutation was introduced from certain sheep in India. The same mutation is also in a breed of sheep in Indonesia.6
Mutations in a second gene can also affect litter size.7 There are several different mutations that have been identified in this gene. In most cases, one copy of the mutant gene will result in the ewe averaging more lambs per litter, but two copies result in ewes that are infertile.8
Pretty pigs
There are hundreds of genes that can affect the color of animals, but one is particularly interesting that codes for a protein "switch."9 When the switch is off, a lighter yellow to red pigment is made.10 When the switch is on, a darker brown to black pigment is made.11 There are several other genes that can "tell" the switch to turn on or off.12 Often the switch cycles between on and off and produces a pretty brownish color found in many wild animals.
This gene appears designed to be able to change. Many mutations have been found in this gene, but none cause disease.13 They do add to the variety of colors we see in animals. For example, some mutations will cause the switch to remain on, regardless of any signal from other genes. This is the reason why certain pigs, such as the Hampshire, are black. Different mutations can make it so the switch is always off. This is the case in the red Duroc. There are other interesting patterns found in this gene. Based on these patterns, it has been suggested that God may have designed ways to make this gene change.14 This would mean that some of these mutations are not accidents, but the result of intelligently designed programming in the DNA.
More butter and cheese
Sometimes it is better for a farmer if the milk from their dairy cattle has a high percentage of fat, because milk fat is important in making butter and certain types of cheese. There are many genes that influence milk production. Mutation in one of these has a very strong effect on milk fat.15 This gene controls the last step of making milk fat, and the mutation makes it so the milk is higher in fat. There are other genes which can also affect milk fat, but differences in those genes are not as dramatic.16
More meat
Farmers raising beef cattle are interested in producing more meat. Similar to how bone growth is controlled, there are genes which signal muscle to grow and others that signal for it to stop growing. Mutations have been found in a gene that signals for muscle growth to stop.17 These mutations damage the signaling protein and muscle growth continues causing a condition known as double muscling.18 Cattle with two mutant genes are more strongly affected than those carrying only one affected gene. Double muscling is usually considered a disease because these cattle often have serious problems, such as difficulty giving birth. During natural birth, the mother is often injured by the muscular calf she is trying to deliver; there is also a much higher chance of injury or death to the calf. Some cattlemen have been successful raising double muscled cattle, but it requires extra work and many calves have to be delivered by c-section.19
Patterns in Mutations
The examples above can help us understand what mutations can do: they introduce a change in a gene. Genes are organized in complex networks which are necessary for proper development and the continuation of life. Changes in these genes can have different effects on the animal depending on where they occur.
There are three examples where one mutant gene may be helpful, but two mutant genes are harmful. Larger sheep, ewes that deliver more lambs, and more muscular cattle can be beneficial to a farmer. However, "spider lambs," infertile ewes, and cattle so muscular they have serious trouble giving birth are obvious disease problems. So any benefit from these mutations involves a serious cost when the mutation is inherited from both parents.
Two examples appear to be beneficial with no obvious problems: the mutation in Booroola Merinos that increases litter size and the mutation increasing milk fat percentage in dairy cattle. While the extra lambs or milk fat may not be helpful in the wild, they are certainly beneficial in an agricultural setting for a farmer who adequately feeds and cares for his animals.
The one example involving coat color in pigs does not appear to be particularly beneficial to a farmer, but it does add interesting variety. In wild animals, some mutations in this gene do appear to contribute to adaptive coloration. Surprising repeating patterns of mutation found in different mammals suggest designed mechanisms are involved in at least some mutations in this gene.
There is one thing all these mutations have in common. They change the existing balance found in the complex networks of genes, but do not add to the complexity of the networks. To change the number of lambs a ewe has requires starting with a ewe that is capable of reproducing. Similarly, to change the relative amount of bone, muscle, fat, or pigment requires an animal with the complex network of genes capable of producing these in a well-regulated fashion. So these mutations can explain changes, but they do not explain the origin of the complex gene networks.
Mutation in a biblical worldview
The patterns observed above fit very well within a biblical worldview. The Bible tells us of an awesome, wise God who created the world as well as the animals that inhabit it (Genesis 1). This explains the origin of the complex networks of genes that enable life to exist.
While originally the world was very good (Genesis 1:31), things did not stay that way. Soon mankind sinned and brought disease, suffering, and death into the world (Genesis 3). Mutations that result in disease are a reminder that the world was cursed as a result of sin and that we are in need of God to save us.
Even in the midst of a fallen world, God is still the provider and sustainer of life (Psalm 147:8, 9; Matthew 6:25-34; Colossians 1:17). Evidence of this is seen in providential mutations that allow for increased productivity for agriculture, enable adaptation to different environments, and add beauty and variety to what we see in the world. The observations that some genes can handle mutations well and that some mutations appear to result from designed mechanisms are both evidence of God's providence in our fallen world.
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- Sections of DNA that code for specific proteins. Back
- The gene codes for a protein called fibroblast growth factor receptor 3 (FGFR3). This gene is found in other mammals, although in other species different mutations in this gene keep it turned on all the time causing dwarfism. Back
- Smith, L.B., Dally, M.R., Sainz, R.D., Rodrigue, K.L., and Oberbauer, A.M., Enhanced skeletal growth of sheep heterozygous for an inactivated fibroblast growth factor receptor 3, J Anim Sci 84:2942–2949, 2006. Back
- The bone morphogenetic protein receptor IB (BMPR-IB) gene located on sheep chromosome 6. It is a missense mutation that causes an amino acid change in the protein receptor (Q249R). Chu, M.X., Liu, Z.H., Jiao, C.L., He, Y.Q., Fang, L., Ye, S.C., Chen, G.H., and Wang, J.Y., Mutations in BMPR-IB and BMP-15 genes are associated with litter size in Small Tailed Han sheep (Ovis aries), J Anim Sci 85:598–603, 2006. Back
- Davis, G.H., Major genes affecting ovulation rate in sheep, Genet Sel Evol 37(suppl. 1):S11–S23, 2005. Back
- Davis, G.H., Galloway, S.M., Ross, I.K., Gregan, S.M., Ward, J., Nimbkar, B.V., Ghalsasi, P.M., Nimbkar, C., Gray, G.D., Subandriyo, Inounu, I., Tiesnamurti, B., Martyniuk, E., Eythorsdottir, E., Mulsant, P., Lecerf, F., Hanrahan, J.P., Bradford, G.E., and Wilson, T., DNA tests on prolific sheep from eight countries provide new evidence on origin of the Booroola (FecB) mutation, Biol Reprod. 66:1869–1874, 2002. Back
- The bone morphogenetic protein 15 (BMP-15) gene on the X chromosome. Back
- Davis, ref 5. Back
- Melanocortin 1 receptor (MC1R) Back
- Pheomelanin Back
- Eumelanin Back
- α-melanocyte stimulating hormone (MSH) signals the production of eumelanin; Agouti (or agouti signaling protein, ASIP) competes with MSH in binding the MC1R and inhibits this response, thus signaling a switch back to pheomelanin production. Back
- In humans, mutations in MC1R are associated with red hair and light skin. It shows up in people whose ancestors lived far from the equator. It is believed to help by allowing more absorption of UV radiation so the body can produce sufficient vitamin D. If these people are exposed to too much UV radiation, they burn easily and may be at higher risk of developing certain skin cancers. So, while the mutations do not directly cause disease, they can come at a cost (i.e. be risk factors for disease under certain conditions). Back
- Lightner, J.K., Genetics of coat color I: the melanocortin 1 receptor (MC1R), ARJ 1:109–116, 2008. Back
- A lysine to alanine substitution (K232A) in the diacylglycerol acyl transferase 1 (DGAT1) gene. It is possible that this could be a created variant of the gene, but because it is relatively uncommon and not found in other ruminant species it is more likely to be a mutation. Back
- Grisart, B., Farnir, F., Karim, L., Cambisano, N., Kim, J.J., Kvasz, A., Mni, M., Simon, P., Frere, J.M., Coppieters, W., and Georges, M., Genetic and functional confirmation of the causality of the DGAT1 K232A quantitative trait nucleotide in affecting milk yield and composition, PNAS 101(8):2398–2403, 2004. Back
- The myostatin gene (MSTN) which has previously gone by the name growth and differentiation factor 8 (GDF8). Back
- There at least 6 different mutations associated with double muscling in various cattle breeds. Many other mutations/polymorphisms have been identified in this gene which may have milder effects on muscle growth. Grisolia, A.B., D'Angelo, G.T., Porto Neto, L.R., Siqueira, F., and Garcia, J.F., Myostatin (GDF8) single nucleotide polymorphisms in Nellore cattle, Genet Mol Res 8(3):822–830, 2009. Back
- Lightner, J.K., Mutations, selection and the quest for meatier livestock, TJ 19(2):18–20, 2005. Back


text:
European Journal of Lipid Science and Technology
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Maria Luisa of Savoy
Princess Maria Luisa | |
Tenure | 2 November 1701 – 14 February 1714 |
Spouse | Philip V of Spain |
Issue | |
Louis I of Spain Ferdinand VI of Spain |
Full name | |
Maria Luisa Gabriella di Savoia | |
House | House of Savoy (by birth) House of Bourbon (by marriage) |
Father | Victor Amadeus II, Duke of Savoy |
Mother | Anne Marie d'Orléans |
Born | Royal Palace of Turin, Savoy |
17 August 1688
Died | 14 February 1714 Royal Alcazar of Madrid, Spain |
(aged 25)
Burial | El Escorial |
Religion | Roman Catholicism |
Maria Luisa of Savoy (Maria Luisa Gabriella; 17 September 1688 – 14 February 1714) was a Savoyard princess and the first wife of Philip V of Spain.[1] She acted as Regent of Spain and had great influence over her husband. She is closely associated with Princesse des Ursins.
Infancy and background[edit]
She was the third daughter and second surviving child of Victor Amadeus II, Duke of Savoy and his French-born wife Anne Marie d'Orléans, the youngest daughter of Philippe of France and Henrietta of England. Throughout her life, Maria Luisa remained close to her older sister Maria Adelaide who later married Louis, Duke of Burgundy, the eldest grandson of Louis XIV. In her youth, Maria Luisa was described as playful and fun loving and had received a good education.[2]
Philip V of Spain, a French prince, was recently crowned King of Spain upon the death of childless Charles II. In order to enforce his shaky authority over Spain due to his French birth, Philip V decided to maintain ties with Victor Amadeus II, Duke of Savoy. Philip V's brother, Louis, Duke of Burgundy, had married the elder sister of Maria Luisa several years earlier, and in mid-1701, Philip V asked for Maria Luisa's hand with the permission of his grandfather Louis XIV.[3]
Maria Luisa was wed by proxy to Philip V on 12 September 1701 at the age of barely thirteen and was escorted to Nice, arriving there on 18 September. While in Nice, she was greeted by Pope Clement XI who gave her the Golden Rose on 20 September as a ritualistic gift for the young princess.[2] Within a week, she sailed from Nice for Antibes and was taken to Barcelona. The official marriage took place on 2 November 1701.[2] The princesse des Ursins was a member of the household of the Queen. She would maintain great influence over Maria Luisa as her Camarera mayor de Palacio, chief of the household to the young queen, who was still a child.
The couple were deeply in love. In 1702, Philip V was obliged to leave Spain to fight in Naples as part of the ongoing War of Spanish Succession.[4] During her husband's absence, Maria Luisa acted as Regent from Madrid. She was praised as an effective ruler, having successfully implemented various changes in government and insisted upon all complaints being investigated and reports made direct to her. Her leadership encouraged the reorganization in the junta and, in doing this, inspiring people and their cities to make donations towards the war effort.[1] Despite her young age, Maria Luisa's effective regency made her admired in Madrid and throughout Spain. After her husband's return in 1703, she resumed her role as queen consort. In 1704, the Princess of Ursins was exiled at the order of Louis XIV, devastating Maria Luisa. However, in 1705, the Princesse des Ursins returned to Madrid, much to the joy of the young queen.[5]
Maria Luisa gave birth to the couple's first child, Infante Luis Felipe in 1707. Maria Luisa gave birth to three more children, two of whom would survive infancy. Towards the end of her life, the Queen became ill with tuberculosis. She eventually died from the effects of tuberculosis on 14 February 1714. She was buried at San Lorenzo de El Escorial. Maria Luisa died in her 25th year.
In December 1714, just months after Maria Luisa's death, her widower Philip V remarried, to Elisabeth Farnese, the only child and heiress of the Duke of Parma. All of Maria Luisa's children were to die without issue, thus there are no descendants of Maria Luisa of Savoy.
She was nicknamed La Savoyana by her adoring subjects and was well loved in Spain. After her death, two of her sons, her youngest and oldest, were to become Kings of Spain. Her niece, Princess Maria Luisa was named after her.
- Louis I of Spain (25 August 1707 – 31 August 1724) married Louise Élisabeth d'Orléans, no issue.
- Infante Felipe of Spain (2 July 1709 – 18 July 1709)
- Infant Felipe Pedro Gabriel of Spain (7 June 1712 – 29 December 1719) died in childhood.
- Ferdinand VI of Spain (23 September 1713 – 10 August 1759) married Infanta Maria Barbara of Portugal, no issue.
Titles, styles, honours, and arms[edit]
Titles and styles[edit]
- 17 September 1688 – 2 November 1701 Her Highness Princess Maria Luisa of Savoy
- 2 November 1701 – 14 February 1714 Her Majesty The Queen of Spain
- ^ a b Sharp. Martin Andrew: Queens of old Spain, New York, McClure, Phillips & company, 1906, p 532
- ^ a b c The Gentleman's magazine, Volumes 302-303, F. Jefferies, 1789, p 284
- ^ The Gentleman's magazine, Volumes 302-303, F. Jefferies, 1789, p 286
- ^ Sharp. Martin Andrew: Queens of old Spain, New York, McClure, Phillips & company, 1906, p 531
- ^ Sharp. Martin Andrew: Queens of old Spain, New York, McClure, Phillips & company, 1906, p 535
External links[edit]
Media related to Maria Luisa of Savoy at Wikimedia Commons
See also[edit]
Maria Luisa of Savoy
Born: 17 November 1688 Died: 14 February 1714 |
Spanish royalty | ||
Preceded by Mariana of Neuburg |
Queen consort of Spain 2 November 1701 – 14 February 1714 |
Succeeded by Elisabeth Farnese |
Queen consort of Naples and Sardinia 1700–1713 |
Succeeded by Elisabeth Christine of Brunswick-Wolfenbüttel |
Queen consort of Sicily 1700–1713 |
Succeeded by Anne Marie d'Orléans |
- Royal consorts of Naples
- Royal consorts of Sicily
- Deaths from tuberculosis
- Spanish royal consorts
- Duchesses of Brabant
- Duchesses of Limburg
- Duchesses of Luxembourg
- Countesses of Flanders
- Countesses of Hainaut
- Duchesses of Milan
- Regents of Spain
- 17th-century Italian people
- 18th-century Italian people
- 1688 births
- 1714 deaths
- People from Turin
- Princesses of Savoy
- Recipients of the Golden Rose
- Burials in the Pantheon of Kings at El Escorial
- Female regents
- House of Savoy
- House of Bourbon (Spain)


text:
John Auerbach Distinguished Professor of Practice and Director of the Institute on Urban Health Research Department: Institute on Urban Health Research Department 2: Department of Health Sciences Office: 324 INV Résumé/CV Phone: 617.373.5668 Fax: 617.373.7309 Email: firstname.lastname@example.com |
John Auerbach's area of expertise is public health policy and practice. He served as the Commissioner of Public Health in Massachusetts from 2007 to 2012, as the Executive Director of the Boston Public Health Commission from 1998 to 2007 and as the state's leading AIDS governmental official during the early years of the epidemic. He has worked at local, state and national levels to develop policies and programs to address racial and ethnic disparities, to promote wellness, to combat infectious and chronic disease and to support the successful implementation of health care reform. Auerbach was the President of the Association of State and Territories Health Officials (ASTHO) and a Board member of the National Association of County and City Health Officials.