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Arts and entertainment reports from The Times
Nurse Rimes: The mother cartier bracelet with lock replica of a 7 year old car accident victim is crediting country singer LeAnn Rimes with bringing her daughter out of a coma. On Aug. 6, Rimes visited Tamra Diehl, who was injured July 17 when she was thrown from her mother's pickup truck in Reno. The girl reportedly stirred and her eyelids fluttered as Rimes sang a lullaby version of her hit cartier bracelet lock copy "Blue." The girl, still hospitalized, now "laughs and everything," said mother Debra Diehl, who has pleaded innocent to drunken driving charges from the accident. "She started coming out of the coma ever since . . . Rimes came here."Dietrich Auction: In an ongoing parade of celebrity auctions, Sotheby's in Beverly Hills will offer the contents of the late German cartier lock bracelet fake actress and singer Marlene Dietrich's New York apartment on Nov. 1. Marshall. She becomes the third woman elected to the TV academy's top post, following actresses Gail Patrick Jackson replica cartier mens jewelry (1960 62) and Diana Muldaur (1983 85). Marshall succeeds Richard H. Frank, who had served the maximum two successive terms.QUICK TAKES"The X Files" brought otherworldly success to cable's FX Tuesday night when the original series premiere attracted about 1.2 million viewers ages 18 49, beating out all other cable networks in that coveted age group, even though only about half of homes with cable actually receive FX. showing was the highest rated premiere of a network series ever on cable, according to Nielsen, attracting a higher percentage of available viewers than the previous record holder, "Murder, She Wrote," which began on USA in 1988. . . . About 100 people were evacuated from the nearly completed Getty Center in the Sepulveda Pass Tuesday after a sulfur dioxide leak, fire officials said. The leak came from a hose attached to a tank of sulfur dioxide, which is used in restoring and preserving artwork. The Getty Center opens on Dec. 16. . . . A United Airlines flight attendant said an ailing Gary Busey struck her after she accidentally bumped his head Monday en route from Los Angeles to Las Vegas. Busey, who is battling cancer, said she startled him and he pushed her in reaction to pain. The woman wasn't injured, and no charges were filed.in concern of cartier ring plating silver nail replica up to the minute vogue Information present dynamic
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Nurse Rimes: The mother cartier bracelet with lock replica of a 7 year old car accident victim is crediting country singer LeAnn Rimes with bringing her daughter out of a coma. On Aug. 6, Rimes visited Tamra Diehl, who was injured July 17 when she was thrown from her mother's pickup truck in Reno. The girl reportedly stirred and her eyelids fluttered as Rimes sang a lullaby version of her hit cartier bracelet lock copy "Blue." The girl, still hospitalized, now "laughs and everything," said mother Debra Diehl, who has pleaded innocent to drunken driving charges from the accident. "She started coming out of the coma ever since . . . Rimes came here."Dietrich Auction: In an ongoing parade of celebrity auctions, Sotheby's in Beverly Hills will offer the contents of the late German cartier lock bracelet fake actress and singer Marlene Dietrich's New York apartment on Nov. 1. Marshall. She becomes the third woman elected to the TV academy's top post, following actresses Gail Patrick Jackson replica cartier mens jewelry (1960 62) and Diana Muldaur (1983 85). Marshall succeeds Richard H. Frank, who had served the maximum two successive terms.QUICK TAKES"The X Files" brought otherworldly success to cable's FX Tuesday night when the original series premiere attracted about 1.2 million viewers ages 18 49, beating out all other cable networks in that coveted age group, even though only about half of homes with cable actually receive FX. showing was the highest rated premiere of a network series ever on cable, according to Nielsen, attracting a higher percentage of available viewers than the previous record holder, "Murder, She Wrote," which began on USA in 1988. . . . About 100 people were evacuated from the nearly completed Getty Center in the Sepulveda Pass Tuesday after a sulfur dioxide leak, fire officials said. The leak came from a hose attached to a tank of sulfur dioxide, which is used in restoring and preserving artwork. The Getty Center opens on Dec. 16. . . . A United Airlines flight attendant said an ailing Gary Busey struck her after she accidentally bumped his head Monday en route from Los Angeles to Las Vegas. Busey, who is battling cancer, said she startled him and he pushed her in reaction to pain. The woman wasn't injured, and no charges were filed.
What Am I Missing
Pandora A/S is a category killer jewelry business that has built significant competitive advantages right down the middle of secular growth trends that will continue indefinitely. Despite a 65% ROIC, 20% top line growth rate (25% adjusted for currency) and mid 30s% earnings growth,rolex daytona ladies watch replica, the company trades at slightly less than 20x trailing earnings and 16x forward earnings for reasons I find hard to understand. This is the very essence of GARP.
"I don't try to jump over 7 foot hurdles: I look for 1 foot hurdles that I can step over." Warren Buffett
It is difficult to find one foot hurdles in general, especially these days, with markets at all time highs, but if one takes a look over to DenmarkWhile it appears that Pandora A/S has burst onto the scene in just the past 5 10 years, the company is 34 years old, having started by Per Enevoldsen and his wife Winnie in Copenhagen, Denmark at a single jewelry shop, in 1982. They often took trips to Thailand, and, inspired by the rich history of jewelry and craftsmanship in the country, began to import jewelry from Thailand. In the late 80's, they hired a new designer, and built a production factory in Thailand, and moved there. The company then switched to selling wholesale to other shops in successful expansion.
In the 90's, the company's designers came up with its signature product, the silver charm bracelet, which was first launched in 2000. This is the hit product that launched Pandora onto the global stage. Charms currently make up 62% of revenue and Bracelets make up 17% of revenue. This percentage was even higher, before the recent ramping of rings and earrings and necklaces. and Canada, before moving on to Continental Europe and then globally to where the company sells to over 100 countries over six continents, as it built out large, industrial scale production facilities in Gemopolis, Thailand. In 2015, Pandora launched the Pandora EStore. Online sales have already grown from 2.5% of revenues in 2015 to 4% of revenues in 2016.
In 2008, the private equity firm Axcel bought a 60% stake in the company, and the company IPO'd in 2010 at 250 DKK/ share. The company currently trades at 830 DKK/ share. The company has 1) re defined the value proposition of jewelry 2) has a product that reduces customer pain points, and inspires repeat buying and 3) has been able to scale incredibly quickly to the point where other jewelry brands would find it hard to compete with a similar quality product (Pandora has in fact even partnered with rival brands to have shops in shops in rival stores more on this later). rival Tiffany and most other jewelry companies, and benefits from large scale production in Thailand, a country with very low labor costs, which buttresses sustainably high margins (mid 30's operating margin).
A different type of value proposition: Pandora's charms, like many other high growth consumer companies of recent years, is built on "affordable luxury." Think , Ulta Salon, Chipotle, Netflix, and other great growth stocks of the past decade. Some of the common attributes among these companies is that their offerings are desirable and accessible to a wide swath of the population on a very global scale. For instance, a Netlfix subscription is just another add on to the regular bundle for well off families, but also may be used as a substitute for the cable bundle for more economically challenged consumers. Similarly, Pandora charms are very well crafted in a variety of interesting designs, with charms ranging anywhere from about $25 to higher end pieces for as much as $450. In this way, Pandora appeals to everyone, and as a new brand with great design, customizability, and 7 annual product collections (or drops), is also trendy even for the wealthy.
Indeed, the company has in many ways re defined the value proposition, or "willingness to pay" of jewelry, as shown in this graph:Pandora has substituted the usual drivers of jewelry value: rarity, type, quality, high price point (a value in itself), with other value propositions Interesting designs, customizability,daytona rolex replica, personalization, variety, and, most importantly, "meaning." Pandora's goal is to become the "most loved jewelry brand in the world." Indeed, each charm is meant to signify something meaningful in someone's life this also makes the charms especially interesting for gift giving. Delivering this value proposition is much less costly one doesn't need to source very rare stones, or invest in high priced real estate and owned retail operations. Thus, Pandora can still achieve a meaningful WTP Cost gap that leads to its outsized ROIC.
Interestingly, the charm bracelet has many added benefits. Once you buy a charm bracelet, it leads to incremental charm buying. Moreover, all your relatives and friends know you have a bracelet, and this makes them even more likely to purchase a charm when the inevitable "What do I get Lucy for her birthday/holiday/anniversary/etc." question comes up.
In many ways, the charm bracelet acts as an ecosystem, not just a piece of jewelry! Much like Apple talks about its "installed base" of devices and is now emphasizing services, so does Pandora have a large "installed base" that primes the customer for further charm purchases. With seven annual "drops" or collections, there is constantly something new at Pandora. One can see how this is not just a jewelry company, but an ecosystem, or "universe of jewelry" as the company likes to put it.
This is also powerful for the customer, who can add charms when they have available funds, on their own schedule. If you buy a $500 Tiffany necklace, even if you have a payment plan,rolex daytona oyster fake, you are locked into regular payments and interest. Pandora is a less anxiety producing purchase.
: Pandora also has a competitive advantage in being an "unpretentious" brand. Whereas Tiffany, Cartier, and Swarovski must source rare stones and control their retail stores to preserve their "high end" image, Pandora operates mostly as a franchised model to jewelry franchisees all over the world. By selling wholesale, the company can expand very quickly with very little risk into new markets. Once a market has been proved to be receptive to the charms, the company then goes in and upgrades its points of sale to either branded "concept stores," or "shop in shops" (a branded store within a larger jewelry or department store, with dedicated Pandora staff), and can close down 3rd party or multi branded stores, which are not as effective.
The charm bracelet, combined with a "middle class" brand, allows the company to focus on cementing its competitive advantage through economies of scale. Production of bracelets combines elements of both mass production (casting of charm shapes) along with hand crafted finishing, as you can see in this video
In this way, one is reminded of other successful companies that mass produce high quality "bricks," and then lets the customer assemble to their liking, or self customize. Other companies that come to mind that use this very successfully are Chipotle (limited high quality menu, let customers customize their burritos), LEGO (limited bricks, can be arranged in infinite amount of designs), and Ulta Salon (bring prestige brands, discount brands, and hair salon care under one roof, let the customers decide). Judging from the results of all these companies, it seems to be a recipe for success and generating high ROIC. It allows the company to deliver high quality "ingredients," at affordable price points that the customer is happy to play with and assemble on their own.
Thus, a competitive advantage is established if the company scales to a significant degree, which Pandora has, while the competition has slept. The company has huge scale in Thailand, a country that is advantaged by its a) close proximity to silver resources b) a verylong history with jewelry craftsmanship and design, and bc very low wages compared with the US or Europe (1/8 1/10 as much).
With this low labor cost and economies of scale built over 20 years, it would be a formidable task for another jewelry manufacturer to source, scale, and produce charm bracelets, and be able to earn the returns that Pandora does at a similar price point.
In fact, Pandora is actually increasing the complexity of its designs as it achieves other economies of scale, putting it even further ahead of competitors and knock offs. For instance, a new charm bracelet with intricate cubic zirconia designs woven in now requires 72 casks to make, as opposed to a "simpler" bracelet model from just 2013,imitation daytona rolex watch, which required 8 casks. A very detailed new lace silver ring design (below) requires 4x the manpower to produce than the simpler mother of pearl ring from 2007.
(Source: Capital Markets Day Presentation)
Why would the company deliberately eat into their margins to do this? To put even more distance between their design capabilities and those of other large jewelers or upstart brands. And it seems to be working.
This can be seen in the recent partnership with jeweler Jared, which is owned by Signet. retail stores during 2016 (now 168 as of Q2 2016). This is another advantage of being an unpretentious brand, and selling wholesale it's you can turn rivals into allies, and get them to market your products for you for a cut of the profits.
Pandora A/S is a category killer jewelry business that has built significant competitive advantages right down the middle of secular growth trends that will continue indefinitely. Despite a 65% ROIC, 20% top line growth rate (25% adjusted for currency) and mid 30s% earnings growth,rolex daytona ladies watch replica, the company trades at slightly less than 20x trailing earnings and 16x forward earnings for reasons I find hard to understand. This is the very essence of GARP.
"I don't try to jump over 7 foot hurdles: I look for 1 foot hurdles that I can step over." Warren Buffett
It is difficult to find one foot hurdles in general, especially these days, with markets at all time highs, but if one takes a look over to DenmarkWhile it appears that Pandora A/S has burst onto the scene in just the past 5 10 years, the company is 34 years old, having started by Per Enevoldsen and his wife Winnie in Copenhagen, Denmark at a single jewelry shop, in 1982. They often took trips to Thailand, and, inspired by the rich history of jewelry and craftsmanship in the country, began to import jewelry from Thailand. In the late 80's, they hired a new designer, and built a production factory in Thailand, and moved there. The company then switched to selling wholesale to other shops in successful expansion.
In the 90's, the company's designers came up with its signature product, the silver charm bracelet, which was first launched in 2000. This is the hit product that launched Pandora onto the global stage. Charms currently make up 62% of revenue and Bracelets make up 17% of revenue. This percentage was even higher, before the recent ramping of rings and earrings and necklaces. and Canada, before moving on to Continental Europe and then globally to where the company sells to over 100 countries over six continents, as it built out large, industrial scale production facilities in Gemopolis, Thailand. In 2015, Pandora launched the Pandora EStore. Online sales have already grown from 2.5% of revenues in 2015 to 4% of revenues in 2016.
In 2008, the private equity firm Axcel bought a 60% stake in the company, and the company IPO'd in 2010 at 250 DKK/ share. The company currently trades at 830 DKK/ share. The company has 1) re defined the value proposition of jewelry 2) has a product that reduces customer pain points, and inspires repeat buying and 3) has been able to scale incredibly quickly to the point where other jewelry brands would find it hard to compete with a similar quality product (Pandora has in fact even partnered with rival brands to have shops in shops in rival stores more on this later). rival Tiffany and most other jewelry companies, and benefits from large scale production in Thailand, a country with very low labor costs, which buttresses sustainably high margins (mid 30's operating margin).
A different type of value proposition: Pandora's charms, like many other high growth consumer companies of recent years, is built on "affordable luxury." Think , Ulta Salon, Chipotle, Netflix, and other great growth stocks of the past decade. Some of the common attributes among these companies is that their offerings are desirable and accessible to a wide swath of the population on a very global scale. For instance, a Netlfix subscription is just another add on to the regular bundle for well off families, but also may be used as a substitute for the cable bundle for more economically challenged consumers. Similarly, Pandora charms are very well crafted in a variety of interesting designs, with charms ranging anywhere from about $25 to higher end pieces for as much as $450. In this way, Pandora appeals to everyone, and as a new brand with great design, customizability, and 7 annual product collections (or drops), is also trendy even for the wealthy.
Indeed, the company has in many ways re defined the value proposition, or "willingness to pay" of jewelry, as shown in this graph:Pandora has substituted the usual drivers of jewelry value: rarity, type, quality, high price point (a value in itself), with other value propositions Interesting designs, customizability,daytona rolex replica, personalization, variety, and, most importantly, "meaning." Pandora's goal is to become the "most loved jewelry brand in the world." Indeed, each charm is meant to signify something meaningful in someone's life this also makes the charms especially interesting for gift giving. Delivering this value proposition is much less costly one doesn't need to source very rare stones, or invest in high priced real estate and owned retail operations. Thus, Pandora can still achieve a meaningful WTP Cost gap that leads to its outsized ROIC.
Interestingly, the charm bracelet has many added benefits. Once you buy a charm bracelet, it leads to incremental charm buying. Moreover, all your relatives and friends know you have a bracelet, and this makes them even more likely to purchase a charm when the inevitable "What do I get Lucy for her birthday/holiday/anniversary/etc." question comes up.
In many ways, the charm bracelet acts as an ecosystem, not just a piece of jewelry! Much like Apple talks about its "installed base" of devices and is now emphasizing services, so does Pandora have a large "installed base" that primes the customer for further charm purchases. With seven annual "drops" or collections, there is constantly something new at Pandora. One can see how this is not just a jewelry company, but an ecosystem, or "universe of jewelry" as the company likes to put it.
This is also powerful for the customer, who can add charms when they have available funds, on their own schedule. If you buy a $500 Tiffany necklace, even if you have a payment plan,rolex daytona oyster fake, you are locked into regular payments and interest. Pandora is a less anxiety producing purchase.
: Pandora also has a competitive advantage in being an "unpretentious" brand. Whereas Tiffany, Cartier, and Swarovski must source rare stones and control their retail stores to preserve their "high end" image, Pandora operates mostly as a franchised model to jewelry franchisees all over the world. By selling wholesale, the company can expand very quickly with very little risk into new markets. Once a market has been proved to be receptive to the charms, the company then goes in and upgrades its points of sale to either branded "concept stores," or "shop in shops" (a branded store within a larger jewelry or department store, with dedicated Pandora staff), and can close down 3rd party or multi branded stores, which are not as effective.
The charm bracelet, combined with a "middle class" brand, allows the company to focus on cementing its competitive advantage through economies of scale. Production of bracelets combines elements of both mass production (casting of charm shapes) along with hand crafted finishing, as you can see in this video
In this way, one is reminded of other successful companies that mass produce high quality "bricks," and then lets the customer assemble to their liking, or self customize. Other companies that come to mind that use this very successfully are Chipotle (limited high quality menu, let customers customize their burritos), LEGO (limited bricks, can be arranged in infinite amount of designs), and Ulta Salon (bring prestige brands, discount brands, and hair salon care under one roof, let the customers decide). Judging from the results of all these companies, it seems to be a recipe for success and generating high ROIC. It allows the company to deliver high quality "ingredients," at affordable price points that the customer is happy to play with and assemble on their own.
Thus, a competitive advantage is established if the company scales to a significant degree, which Pandora has, while the competition has slept. The company has huge scale in Thailand, a country that is advantaged by its a) close proximity to silver resources b) a verylong history with jewelry craftsmanship and design, and bc very low wages compared with the US or Europe (1/8 1/10 as much).
With this low labor cost and economies of scale built over 20 years, it would be a formidable task for another jewelry manufacturer to source, scale, and produce charm bracelets, and be able to earn the returns that Pandora does at a similar price point.
In fact, Pandora is actually increasing the complexity of its designs as it achieves other economies of scale, putting it even further ahead of competitors and knock offs. For instance, a new charm bracelet with intricate cubic zirconia designs woven in now requires 72 casks to make, as opposed to a "simpler" bracelet model from just 2013,imitation daytona rolex watch, which required 8 casks. A very detailed new lace silver ring design (below) requires 4x the manpower to produce than the simpler mother of pearl ring from 2007.
(Source: Capital Markets Day Presentation)
Why would the company deliberately eat into their margins to do this? To put even more distance between their design capabilities and those of other large jewelers or upstart brands. And it seems to be working.
This can be seen in the recent partnership with jeweler Jared, which is owned by Signet. retail stores during 2016 (now 168 as of Q2 2016). This is another advantage of being an unpretentious brand, and selling wholesale it's you can turn rivals into allies, and get them to market your products for you for a cut of the profits.
commercial real estate sees continued short supply
Metro Vancouver rental housing and industrial markets remain highly active, with demand outstripping supply on both fronts, leading to sales and price surges in some areas and low vacancy rates in others, according to recent reports.
CBRE Q4 market review of Metro Vancouver industrial real estate sector showed that the region saw industrial leasing space vacancy rates drop to 2.4 per cent at the end of last year, the lowest level since 2007. Sales, meanwhile, reached a record $1.2 billion in 2016, up nine per cent from the previous year.
The average property price was up 13 per cent, hitting $195 per square foot in Metro Vancouver, and industrial land prices saw their largest increases in a single year. All this despite apparent lack of properties available for sale, the report said, with only 312 acres of industrial land trading hands in where to buy cartier bracelet copy 2016.
definitely been the trend in the last three years that demand has outpaced supply almost two to one, said Chris MacCauley, CBRE senior vice cartier bracelet screw president (industrial and logistics). something that has copy chain love no easy fix; it will take some long term planning throughout Metro Vancouver to find out what are the right places for industrial land of various uses. CBRE report called the depletion of Metro Vancouver industrial land noting Vancouver, Burnaby and Richmond all have less than 10 years of supply left.
50 per cent of the supply coming on this year (in Metro Vancouver) is already spoken for, and it January, MacCauley said, adding that clients looking at Vancouver have been driven out to Surrey and Delta because of lack of availability. Surrey has 30 per cent of Metro Vancouver future land supply, MacCauley noted.
On the rental side, the Goodman Report on Metro Vancouver apartment sector showed the average price per suite in 2016 jumped 52 per cent to $377,000.
anticipated that the regional population will increase by an average of 35,000 per year until 2040, the report said. Goodman Report expects local landlords to remain insulated from any apparent decline in tenant demand or softening of rents. short supply of rental housing and the resulting rising rents are serious concerns for David Goodman, who said Vancouver municipal officials have relied too heavily on federal aid, which takes time and often doesn fulfil the community needs. The result, Goodman said, is serious damage of the city social and economic fabric.
can just have condos and have a viable society, he said. need rentals. And if you are not building enough rentals, people are going to throw their hands up in disgust and they are going to leave our city. These are often people who are educated and have lost all hope of even renting, so they go to Alberta or back east where they won have such a stressful time finding a roof over their heads. urged city officials to reduce red tape for developers looking to build rentals in Vancouver, an application process right now that can take up to three years.
One of the only things, for both Goodman and MacCauley, that can derail demand in Metro Vancouver in the short term may be the new Trump administration in the United States. Both analysts said people should keep a close eye on the policy changes in Washington toward tariffs and other trade mechanisms. some of our clients are saying that, if there are additional tariffs coming, they may balance their expansion plans and look at south of the border. agreed.
could very well experience potential disruptions to trade and commerce, quite possibly triggering higher deficits and interest rate increases here at home, he said in the report. in for a bumpy ride bet on it. epaper, Digital Access, Subscriber Rewards), please input your Print Newspaper subscription phone number and postal code.
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Metro Vancouver rental housing and industrial markets remain highly active, with demand outstripping supply on both fronts, leading to sales and price surges in some areas and low vacancy rates in others, according to recent reports.
CBRE Q4 market review of Metro Vancouver industrial real estate sector showed that the region saw industrial leasing space vacancy rates drop to 2.4 per cent at the end of last year, the lowest level since 2007. Sales, meanwhile, reached a record $1.2 billion in 2016, up nine per cent from the previous year.
The average property price was up 13 per cent, hitting $195 per square foot in Metro Vancouver, and industrial land prices saw their largest increases in a single year. All this despite apparent lack of properties available for sale, the report said, with only 312 acres of industrial land trading hands in where to buy cartier bracelet copy 2016.
definitely been the trend in the last three years that demand has outpaced supply almost two to one, said Chris MacCauley, CBRE senior vice cartier bracelet screw president (industrial and logistics). something that has copy chain love no easy fix; it will take some long term planning throughout Metro Vancouver to find out what are the right places for industrial land of various uses. CBRE report called the depletion of Metro Vancouver industrial land noting Vancouver, Burnaby and Richmond all have less than 10 years of supply left.
50 per cent of the supply coming on this year (in Metro Vancouver) is already spoken for, and it January, MacCauley said, adding that clients looking at Vancouver have been driven out to Surrey and Delta because of lack of availability. Surrey has 30 per cent of Metro Vancouver future land supply, MacCauley noted.
On the rental side, the Goodman Report on Metro Vancouver apartment sector showed the average price per suite in 2016 jumped 52 per cent to $377,000.
anticipated that the regional population will increase by an average of 35,000 per year until 2040, the report said. Goodman Report expects local landlords to remain insulated from any apparent decline in tenant demand or softening of rents. short supply of rental housing and the resulting rising rents are serious concerns for David Goodman, who said Vancouver municipal officials have relied too heavily on federal aid, which takes time and often doesn fulfil the community needs. The result, Goodman said, is serious damage of the city social and economic fabric.
can just have condos and have a viable society, he said. need rentals. And if you are not building enough rentals, people are going to throw their hands up in disgust and they are going to leave our city. These are often people who are educated and have lost all hope of even renting, so they go to Alberta or back east where they won have such a stressful time finding a roof over their heads. urged city officials to reduce red tape for developers looking to build rentals in Vancouver, an application process right now that can take up to three years.
One of the only things, for both Goodman and MacCauley, that can derail demand in Metro Vancouver in the short term may be the new Trump administration in the United States. Both analysts said people should keep a close eye on the policy changes in Washington toward tariffs and other trade mechanisms. some of our clients are saying that, if there are additional tariffs coming, they may balance their expansion plans and look at south of the border. agreed.
could very well experience potential disruptions to trade and commerce, quite possibly triggering higher deficits and interest rate increases here at home, he said in the report. in for a bumpy ride bet on it. epaper, Digital Access, Subscriber Rewards), please input your Print Newspaper subscription phone number and postal code.
{ phone }
{ addressPostalCode }
By clicking "Create Account", I hearby grant permission to Market to use my account information to create my account.
I also accept and agree to be bound by Postmedia's Terms and Conditions with respect to my use of the Site and I have read and understand Postmedia's Privacy Statement. epaper, Digital Access, Subscriber Rewards), please input your Print Newspaper subscription phone number and postal code.
{ phone }
{ addressPostalCode }
By clicking "Create Account", I hearby grant permission to Postmedia to use my account information to create my buy cartier bracelet copy account.
I also accept and agree to be bound by Postmedia's Terms and Conditions with respect to my use of the Site and I have read and understand Postmedia's Privacy Statement. I consent to the collection, use, maintenance, and disclosure of my information in accordance with the Postmedia's Privacy Policy.
Competentiemanagement en opleidingsplannen in het leren van managementsystemen LMS
In onze serie over de bedrijfseconomische aspecten van de training management, het eerste artikel gekeken naar dingen om te overwegen bij het maken van een learning management system (LMS) hirarchie voor uw bedrijf of organisatie. Hiermee kunt u om te certificeren dat werknemers vereiste vaardigheden of bevoegdheden bezitten, en dat zij in aanmerking komen where to buy cartier bracelet replica voor hun functies. Het geeft gebruikers ook duidelijke, specifieke, gemakkelijk gevolgd paden aan vooruitgang. Op elk gewenst moment zien gebruikers wat ze nog steeds nodig hebben aan de vooruitgang, verzoek of toegang opleiding die hun vaardigheden verbetert, en op een duidelijk opleiding spoor gecentreerd op de behoeften van het bedrijf blijven. Het bedrijf ook ten goede komt in verbeterde werknemer retentie.
Werknemers weergeven gedefinieerde opleidingsplannen ook hoe ze kunnen verbeteren en nieuwe baanvaardigheden opdoen. Op deze manier wordt de opleiding belangrijk aan de werknemer, gemakkelijk toegankelijk en noodzakelijk. Deze certificering is ook een pad naar promotie. Als alle nodige opleiding is voltooid voor een functie, kunt de werknemer afdrukken van een certificaat, en bieden fysieke bewijs dat zij alle eisen voor de rol hebben voltooid.
Vele industrien moeten ook voldoen aan de federale of andere vereisten (zoals overheidsvoorschriften) die hen dwingen om te vereisen overeenkomstige werknemer certificeringen. Werknemers moeten voldoen aan verwante bevoegdheden, en uitvoeren van taken en verantwoordelijkheden op manieren die ondersteuning bieden voor de verplichte prestaties. Welke baan rollen beschikken mensen? Hoe worden deze rollen gedefinieerd? Wat is gemeenschappelijk onder de rollen? Welke vaardigheden of bevoegdheden ondersteuning voor elke rol? Wat educatieve evenementen (cursussen, vergaderingen, demonstraties, on the job training, enz.) ondersteunen en deze competenties te bouwen? Hoe begint een nieuwe wagens hun opleiding? Dit kan ontmoedigend lijken, maar bestaande baan rollen definiren is de moeite waard, en brengt veel inzicht in de behoeften van het bedrijf voor bevoegde prestaties. De gegevens van dergelijke onderzoeken ook helpt bij het opbouwen van meetbare manieren om te bepalen wanneer werknemers benodigde vaardigheden bereiken, en omgekeerd, vaststellen opleidingsbehoeften die nog niet voldaan aan.
Gebeurtenissen leren dat medewerkers bevoegdheden krijgen, en moeten worden gedefinieerd, samen met verwante hercertificering datums. Het zou nutteloos om te hebben functies die niet regelmatig bijwerken verplicht, als de bedrijfsbehoeften voor deze rollen veranderen. U kunt niet opgeven hercertificering datums op het eerste, maar u zal later wilt identificeren en informeren van de werknemers, die het bezit van bepaalde functies, die zij moeten voldoen aan nieuwe behoeften en vereisten. Denken door deze taken vereist bepaling van bedrijfsbehoeften, zodat de trainingsafdeling met alle andere afdelingen waarvoor bekwaam personeel werken moet, inzichten te krijgen in hun belangrijke taak rollen, bevoegdheden en educatieve evenementen.
Het is niet verwonderlijk dat sommige organisaties geen idee wat "maakt het werk" in hun bedrijf hebben. Landmeetkunde succesvolle, competente medewerkers is meestal de beste manier om dergelijke situaties te analyseren. Communiceren die resultaten en vergelijken met de ideen van de hoofd eigen departement kunnen geven u een goede uitvalsbasis. Succes!
Mensen die genteresseerd zijn in het bovenstaande artikel zijn ook genteresseerd in de aanverwante artikelen hieronder:
Wat maakt een goede keuze Web to Print oplossing voor uw zakelijke afdrukken?
Als het gaat om de vaststelling van nieuwe oplossingen voor iemands bedrijf, zijn sommige bedrijfseigenaars een beetje terughoudend. Ze zijn niet zeker of ze zullen omgaan met de where to buy cartier bracelet copy nieuwe technologie en haal het meeste uit het. Bent u cartier screw on bracelet in de drukkerij, zou u niet hebben geprobeerd te weten in detail over wat web to print industrie is en waarom is het een goede keuze voor uw bedrijf. Dus is hier een beetje perspectief op dezelfde.
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Heeft de populariteit van mobiele benvloed ook de web to print industrie? In dit artikel zullen we praten over de overgang van het print bedrijf en proberen te begrijpen wat zullen in de toekomst meer populair: Web to print of mobile to print?
Uitstekend, Larry. Dank u voor het nemen van het nieuwe artikel directory technologien en waardoor het werk aan de max. Ik moedig iedereen om bij te dragen en regelmatig bij te dragen. Ik kan getuigen van het feit dat deze site al een sterke directory in een veld van vele is. Kudos to Larry!
Matthew C. Keegan
De schrijver van het artikel
Ik vind het een genot om te gebruiken als een auteur en een uitgever. Het staat vol met leuke kleine verrassingen, waardoor het hele proces van het schrijven, lezen en publiceren van artikelen een volledige genot. Dit is een die komt uit tops, en slaat de rest handen naar beneden.
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In onze serie over de bedrijfseconomische aspecten van de training management, het eerste artikel gekeken naar dingen om te overwegen bij het maken van een learning management system (LMS) hirarchie voor uw bedrijf of organisatie. Hiermee kunt u om te certificeren dat werknemers vereiste vaardigheden of bevoegdheden bezitten, en dat zij in aanmerking komen where to buy cartier bracelet replica voor hun functies. Het geeft gebruikers ook duidelijke, specifieke, gemakkelijk gevolgd paden aan vooruitgang. Op elk gewenst moment zien gebruikers wat ze nog steeds nodig hebben aan de vooruitgang, verzoek of toegang opleiding die hun vaardigheden verbetert, en op een duidelijk opleiding spoor gecentreerd op de behoeften van het bedrijf blijven. Het bedrijf ook ten goede komt in verbeterde werknemer retentie.
Werknemers weergeven gedefinieerde opleidingsplannen ook hoe ze kunnen verbeteren en nieuwe baanvaardigheden opdoen. Op deze manier wordt de opleiding belangrijk aan de werknemer, gemakkelijk toegankelijk en noodzakelijk. Deze certificering is ook een pad naar promotie. Als alle nodige opleiding is voltooid voor een functie, kunt de werknemer afdrukken van een certificaat, en bieden fysieke bewijs dat zij alle eisen voor de rol hebben voltooid.
Vele industrien moeten ook voldoen aan de federale of andere vereisten (zoals overheidsvoorschriften) die hen dwingen om te vereisen overeenkomstige werknemer certificeringen. Werknemers moeten voldoen aan verwante bevoegdheden, en uitvoeren van taken en verantwoordelijkheden op manieren die ondersteuning bieden voor de verplichte prestaties. Welke baan rollen beschikken mensen? Hoe worden deze rollen gedefinieerd? Wat is gemeenschappelijk onder de rollen? Welke vaardigheden of bevoegdheden ondersteuning voor elke rol? Wat educatieve evenementen (cursussen, vergaderingen, demonstraties, on the job training, enz.) ondersteunen en deze competenties te bouwen? Hoe begint een nieuwe wagens hun opleiding? Dit kan ontmoedigend lijken, maar bestaande baan rollen definiren is de moeite waard, en brengt veel inzicht in de behoeften van het bedrijf voor bevoegde prestaties. De gegevens van dergelijke onderzoeken ook helpt bij het opbouwen van meetbare manieren om te bepalen wanneer werknemers benodigde vaardigheden bereiken, en omgekeerd, vaststellen opleidingsbehoeften die nog niet voldaan aan.
Gebeurtenissen leren dat medewerkers bevoegdheden krijgen, en moeten worden gedefinieerd, samen met verwante hercertificering datums. Het zou nutteloos om te hebben functies die niet regelmatig bijwerken verplicht, als de bedrijfsbehoeften voor deze rollen veranderen. U kunt niet opgeven hercertificering datums op het eerste, maar u zal later wilt identificeren en informeren van de werknemers, die het bezit van bepaalde functies, die zij moeten voldoen aan nieuwe behoeften en vereisten. Denken door deze taken vereist bepaling van bedrijfsbehoeften, zodat de trainingsafdeling met alle andere afdelingen waarvoor bekwaam personeel werken moet, inzichten te krijgen in hun belangrijke taak rollen, bevoegdheden en educatieve evenementen.
Het is niet verwonderlijk dat sommige organisaties geen idee wat "maakt het werk" in hun bedrijf hebben. Landmeetkunde succesvolle, competente medewerkers is meestal de beste manier om dergelijke situaties te analyseren. Communiceren die resultaten en vergelijken met de ideen van de hoofd eigen departement kunnen geven u een goede uitvalsbasis. Succes!
Mensen die genteresseerd zijn in het bovenstaande artikel zijn ook genteresseerd in de aanverwante artikelen hieronder:
Wat maakt een goede keuze Web to Print oplossing voor uw zakelijke afdrukken?
Als het gaat om de vaststelling van nieuwe oplossingen voor iemands bedrijf, zijn sommige bedrijfseigenaars een beetje terughoudend. Ze zijn niet zeker of ze zullen omgaan met de where to buy cartier bracelet copy nieuwe technologie en haal het meeste uit het. Bent u cartier screw on bracelet in de drukkerij, zou u niet hebben geprobeerd te weten in detail over wat web to print industrie is en waarom is het een goede keuze voor uw bedrijf. Dus is hier een beetje perspectief op dezelfde.
Een universele Raster en Vector Editor voor Mac
Als u op zoek bent voor afbeeldingen tekenprogramma's voor Mac, zoek dan niet verder dan het Canvas tekent. Canvas Draw is een echt universele grafische tekening oplossing die eenvoudig te gebruiken. Canvas Draw is een krachtige oplossing ontworpen met professionele ontwerpers en illustratoren in gedachten, evenals degenen die een hulpmiddel nodig om te bewerken van zowel vector en raster.
Web to print of Mobile to print: cartier love necklace price knock off die heeft een betere toekomst?
Heeft de populariteit van mobiele benvloed ook de web to print industrie? In dit artikel zullen we praten over de overgang van het print bedrijf en proberen te begrijpen wat zullen in de toekomst meer populair: Web to print of mobile to print?
Uitstekend, Larry. Dank u voor het nemen van het nieuwe artikel directory technologien en waardoor het werk aan de max. Ik moedig iedereen om bij te dragen en regelmatig bij te dragen. Ik kan getuigen van het feit dat deze site al een sterke directory in een veld van vele is. Kudos to Larry!
Matthew C. Keegan
De schrijver van het artikel
Ik vind het een genot om te gebruiken als een auteur en een uitgever. Het staat vol met leuke kleine verrassingen, waardoor het hele proces van het schrijven, lezen en publiceren van artikelen een volledige genot. Dit is een die komt uit tops, en slaat de rest handen naar beneden.
Eric Garner
Ik deed een googleonderzoek en kwam over uw site. Het was precies wat ik zocht en was opgetogen te vinden die een breed scala aan artikelen. Zoals ik ben de lancering van een gratis magazine in een klein stadje in Florida, wilde ik zo vindingrijk mogelijk terwijl nog steeds in staat om sommige inhoud die is interessant en goed geschreven. Uw site heeft alle variabelen in de mix. Uitstekende Site raken van alle notities in de schaal soort spreken.
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Richemont, the Swiss luxury goods giant whose stable includes the Montblanc, Purdey and Cartier brands, saw sales rise by 13pc to in the three months to June.
Although the figure was boosted by strong growth in Asia, the company's overall robust performance provides evidence that that the luxury end of the retail market copy cartier love mens ring is proving resilient to the credit crisis. Earlier this week Burberry, the UK clothing and accessories brand, reported sales growth of 22pc.
The company said that the Asia Pacific region "continued to report very strong growth", particularly in China and Hong Kong. Sales in Asia Pacific now account for one quarter of all Richemont's overall turnover.
Sales were also strong in Europe and the Middle East, where they rose by 17pc. However sales suffered from the weak US dollar in the Americas.
Richemont said that Japan continued to suffer from "challenging market conditions" with sales down eight percent over the quarter.
Sales of jewellery from the Cartier, Van Cleef Arpels brands were strong across cartier copy love ring for men all geographical regions. Richemont's watch cartier love ring engraving knock off makers (such as Jaeger LeCoutre) were strong in all regions bar Japan, and sales of its cartier love ring engraving replica fountain pen brands grew by 5pc at constant exchange rates.
Fashion brand Chloe saw a "mid single digit" sales decrease at constant exchange rates.
Richemont is the world's second biggest luxury goods maker after France's LVMH.
In May Richemont announced details of a restructuring that would see the group split into two entities; a luxury business based in Switzerland and a separate investment vehicle.
Under the proposals Richemont investors will receive shares in both businesses as well as benefiting from Richemont's 19.4pc stake in British American Tobacco. Over the quarter, Richemont received a final dividend of 186m from its BAT stake.
Bedrijfsplannen vandaag nog steeds Relevant zijn
Een recente studie van de Universiteit voorgesteld dat een businessplan geen statistische effect op de resultaten of de financile rentabiliteit van een bedrijf cartier love ring box copy heeft. Maar op een algemeen niveau, een businessplan is nog steeds noodzakelijk. Het is noodzakelijk voor analyse, planning en communicatieve doeleinden maar mag niet worden verwacht dat drastische invloeden op de uitkomst of het financile succes van een bedrijf maken.Een businessplan biedt een directe en grondige uitleg van het bedrijf, een stapsgewijze handleiding waarin alle fasen van de bouw van het bedrijf. Het plan kan helpen uw team en doorsturen van berichten naar uw potentile investeerders stollen de informatie die ze nodig hebben om beslissingen te kunnen.Echter het wijden van tijd en energie aan een businessplan kan worden niet alleen vervelend, dat het kan ook mens imitation cartier love ring blijken te zijn een ware uitdaging. 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Het zal ook helpen u fouten gemaakt door concurrenten.Veranderingen zich zullen voordoen en plannen zullen worden aangepast wees voorbereid op deze kromme ballen.Als een Business coaching strategie ik suggereren met behulp van het bedrijf plannen als een marketing tool en nemen uw bedoelingen en doelstellingen die op zijn beurt uit uw financile opties en strategien zal liggen. Het woord 'blauwdruk' wordt veel gebruikt in verband met wat een goede businessplan maakt. Dit soort strategische analyse geeft de meest objectieve blik en zal beide bieden u en uw team met richtsnoeren en betere communicatie, evenals aantrekkelijk aan potentile investeerders met zijn helderheid en gedefinieerde bedoelingen. Op deze manier, het schrijven van een businessplan een voordeel in een zoektocht naar een succesvolle onderneming kan worden.Mensen die genteresseerd zijn in het bovenstaande artikel zijn ook genteresseerd in de aanverwante artikelen hieronder:Effecten gebaseerde denkend: Deel 3In deel 1 van deze serie, is het concept dat alles binnen een systeem vanuit het perspectief van complexiteit bestaat gentroduceerd. In deel 2, werd een kader voor het drieledige van effecten gebaseerde denken (EBT) en planning kritieke tot begrip verandering in organisaties, markten en cartier love ring engraving replica gemeenschappen besproken. 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Met EBT zijn we in staat om te bouwen, uitlijnen en aan te passen onze metingen om succes binnen de organisatie te verzekeren.Strategische Planning en effecten gebaseerde denken: deel 1In de strategische planning en besluitvorming is effecten gebaseerde denken (EBT) een belangrijke tactiek om te beoordelen van de effecten van specifieke acties, niet in een strikt gedefinieerde cartier love ring box knock off en tijd beperkte manier, maar door een perspectief dat gevoelig is voor breed opgezette en duurzame effecten. In onze snelle persoonlijke en werk leven, hebben we de neiging te denken meer over hedendaagse kwesties dan morgen maar effecten gebaseerde denken is het tegenovergestelde van kortzichtigheid.Uitstekend, Larry. Dank u voor het nemen van het nieuwe artikel directory technologien en waardoor het werk aan de max. Ik moedig iedereen om bij te dragen en regelmatig bij te dragen. Ik kan getuigen van het feit dat deze site al een sterke directory in een veld van vele is. Kudos to Larry!Matthew C. KeeganDe schrijver van het artikelIk vind het een genot om te gebruiken als een auteur en een uitgever. Het staat vol met leuke kleine verrassingen, waardoor het hele proces van het schrijven, lezen en publiceren van artikelen een volledige genot. Dit is een die komt uit tops, en slaat de rest handen naar beneden.Eric GarnerIk deed een googleonderzoek en kwam over uw site. Het was precies wat ik zocht en was opgetogen te vinden die een breed scala aan artikelen. Zoals ik ben de lancering van een gratis magazine in een klein stadje in Florida, wilde ik zo vindingrijk mogelijk terwijl nog steeds in staat om sommige inhoud die is interessant en goed geschreven. Uw site heeft alle variabelen in de mix. Uitstekende Site raken van alle notities in de schaal soort spreken.in relation to cartier necklace plating copper leve copy up
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Een recente studie van de Universiteit voorgesteld dat een businessplan geen statistische effect op de resultaten of de financile rentabiliteit van een bedrijf cartier love ring box copy heeft. Maar op een algemeen niveau, een businessplan is nog steeds noodzakelijk. Het is noodzakelijk voor analyse, planning en communicatieve doeleinden maar mag niet worden verwacht dat drastische invloeden op de uitkomst of het financile succes van een bedrijf maken.Een businessplan biedt een directe en grondige uitleg van het bedrijf, een stapsgewijze handleiding waarin alle fasen van de bouw van het bedrijf. Het plan kan helpen uw team en doorsturen van berichten naar uw potentile investeerders stollen de informatie die ze nodig hebben om beslissingen te kunnen.Echter het wijden van tijd en energie aan een businessplan kan worden niet alleen vervelend, dat het kan ook mens imitation cartier love ring blijken te zijn een ware uitdaging. Een goed businessplan moet worden gedetailleerde nog beknopte en veel genvesteerd ondernemers vinden het moeilijk te breken hun meest waardevolle concepten tot een minimum te beperken. Als u kan niet uw businessplan als een skelet of een schema voor wat je hoopt schrijven te bereiken en hoe u van plan te doen, bent u kostbare tijd verspilt.Het schrijven van uw plan zal geven u een meer gerichte en objectieve kijk op wat u van plan bent te voeren uit en hoe. Dit diepgaande analyse zal helpen u voorzien van potentile lacunes of hik, en helpen om verrassing horden en hinderpalen te elimineren. Het zal ook dwingen je om uw broodnodige markt onderzoek te doen en om echt hebben een diepgaande kennis van uw industrie, middelen en markten. Het zal ook helpen u fouten gemaakt door concurrenten.Veranderingen zich zullen voordoen en plannen zullen worden aangepast wees voorbereid op deze kromme ballen.Als een Business coaching strategie ik suggereren met behulp van het bedrijf plannen als een marketing tool en nemen uw bedoelingen en doelstellingen die op zijn beurt uit uw financile opties en strategien zal liggen. Het woord 'blauwdruk' wordt veel gebruikt in verband met wat een goede businessplan maakt. Dit soort strategische analyse geeft de meest objectieve blik en zal beide bieden u en uw team met richtsnoeren en betere communicatie, evenals aantrekkelijk aan potentile investeerders met zijn helderheid en gedefinieerde bedoelingen. Op deze manier, het schrijven van een businessplan een voordeel in een zoektocht naar een succesvolle onderneming kan worden.Mensen die genteresseerd zijn in het bovenstaande artikel zijn ook genteresseerd in de aanverwante artikelen hieronder:Effecten gebaseerde denkend: Deel 3In deel 1 van deze serie, is het concept dat alles binnen een systeem vanuit het perspectief van complexiteit bestaat gentroduceerd. In deel 2, werd een kader voor het drieledige van effecten gebaseerde denken (EBT) en planning kritieke tot begrip verandering in organisaties, markten en cartier love ring engraving replica gemeenschappen besproken. In deze laatste aflevering, ontdekken hoe effecten worden geplande binnen complexe systemen en hoe adaptieve leiderschap stuwt die effecten.Effecten gebaseerde denken: Deel 2In ' effecten gebaseerde denken deel I ", de definitie van effecten gebaseerde denken, of EBT, werd opgericht als een benadering van strategische planning, die aan duurzame organisatie effecten bijdraagt. Uitbreiding op dit concept, kunnen wij de verschillen tussen strategische planning met EBT en gewoon voortgang met statistieken bekijken. Met EBT zijn we in staat om te bouwen, uitlijnen en aan te passen onze metingen om succes binnen de organisatie te verzekeren.Strategische Planning en effecten gebaseerde denken: deel 1In de strategische planning en besluitvorming is effecten gebaseerde denken (EBT) een belangrijke tactiek om te beoordelen van de effecten van specifieke acties, niet in een strikt gedefinieerde cartier love ring box knock off en tijd beperkte manier, maar door een perspectief dat gevoelig is voor breed opgezette en duurzame effecten. In onze snelle persoonlijke en werk leven, hebben we de neiging te denken meer over hedendaagse kwesties dan morgen maar effecten gebaseerde denken is het tegenovergestelde van kortzichtigheid.Uitstekend, Larry. Dank u voor het nemen van het nieuwe artikel directory technologien en waardoor het werk aan de max. Ik moedig iedereen om bij te dragen en regelmatig bij te dragen. Ik kan getuigen van het feit dat deze site al een sterke directory in een veld van vele is. Kudos to Larry!Matthew C. KeeganDe schrijver van het artikelIk vind het een genot om te gebruiken als een auteur en een uitgever. Het staat vol met leuke kleine verrassingen, waardoor het hele proces van het schrijven, lezen en publiceren van artikelen een volledige genot. Dit is een die komt uit tops, en slaat de rest handen naar beneden.Eric GarnerIk deed een googleonderzoek en kwam over uw site. Het was precies wat ik zocht en was opgetogen te vinden die een breed scala aan artikelen. Zoals ik ben de lancering van een gratis magazine in een klein stadje in Florida, wilde ik zo vindingrijk mogelijk terwijl nog steeds in staat om sommige inhoud die is interessant en goed geschreven. Uw site heeft alle variabelen in de mix. Uitstekende Site raken van alle notities in de schaal soort spreken.
W Montreal Hotel Review
The hotel is conveniently located in historic Old Montreal and faces Victoria Square,rolex daytona black imitation, one of Montreal's prettiest squares. The green cast iron Art Nouveau metro entrance across the street was a gift from the city of Paris. The W is also connected to the metro, the Palais des Congrs (Montreal's main conference hall) and the downtown core and shopping centres via a series of underground passageways. Old Montreal's main attractions, including Notre Dame Cathedral,imitation rolex oysterdate, the Lachine Canal, the Old Port and Place Jacques Cartier, are all within walking distance, as are many of the city's best restaurants such as Toqu! and Le Club Chasse et Pche.
Clusters of hanging globe lighting fixtures accentuate the impressive double height lobby. Plush seating and low lighting in the lobby's living room create a comfortable and welcoming space. The hotel's design is bold, contemporary and full of winks to its historic past as a bank for example, the reception and concierge desks at opposite sides of the lobby area are located in the exact spots where the bank teller desks used to sit, while recurrent French Neoclassic wall motifs and gold accents are also a reminder of the building's previous incarnation.
From the beaming welcome at reception to the insightful staff at the restaurant, the service was flawless in every department. The hotel's signature Whatever/Whenever service is available 24/7 for any request, from a fresh toothbrush to a helicopter ride. The FIT gym is open 24 hours a day and the AWAY Spa offers a full range of treatments. Furry companions are welcome at the W and are provided with beds and many dining options on the room service menu (25 Canadian Dollars/15 per day per pet and a one time 100 Canadian Dollars/61 fee for cleaning). A small office as well as five meeting rooms are located on the mezzanine level.
All 152 rooms and suites include an iPod docking station,rolex daytona ladies watch imitation, bathrobes, bath amenities, 24 hour room service, 350 thread count cotton linens and a glass encased rain shower with a view of the room. Plush black and gold carpets, a desk with an ergonomic gold chair and a TV are also standards across rooms, as is the W MixBar, a testament to W's predilection for cocktail hour, allowing guests to mix their own in room cocktail. Each room has a wall decorated in a French rococo motif wallpaper inspired by the building's history. Standard rooms have views of the hotel's atrium while others have views of Victoria Square. The menu features seafood platters as well as dishes such as house paella and calamari carbonara (the pasta is replaced by the squid). Service is done on a guridon, an old school cart that gets wheeled tableside.
Of the three bars in the hotel,rolex day date ladies fake, the Bartini and its six seats is the cosiest, while wunderbar and its lively ambiance is where the hotel guests mingle with Montrealers. Note that the upstairs bar located right above the reception area is only open on weekends.
The hotel is conveniently located in historic Old Montreal and faces Victoria Square,rolex daytona black imitation, one of Montreal's prettiest squares. The green cast iron Art Nouveau metro entrance across the street was a gift from the city of Paris. The W is also connected to the metro, the Palais des Congrs (Montreal's main conference hall) and the downtown core and shopping centres via a series of underground passageways. Old Montreal's main attractions, including Notre Dame Cathedral,imitation rolex oysterdate, the Lachine Canal, the Old Port and Place Jacques Cartier, are all within walking distance, as are many of the city's best restaurants such as Toqu! and Le Club Chasse et Pche.
Clusters of hanging globe lighting fixtures accentuate the impressive double height lobby. Plush seating and low lighting in the lobby's living room create a comfortable and welcoming space. The hotel's design is bold, contemporary and full of winks to its historic past as a bank for example, the reception and concierge desks at opposite sides of the lobby area are located in the exact spots where the bank teller desks used to sit, while recurrent French Neoclassic wall motifs and gold accents are also a reminder of the building's previous incarnation.
From the beaming welcome at reception to the insightful staff at the restaurant, the service was flawless in every department. The hotel's signature Whatever/Whenever service is available 24/7 for any request, from a fresh toothbrush to a helicopter ride. The FIT gym is open 24 hours a day and the AWAY Spa offers a full range of treatments. Furry companions are welcome at the W and are provided with beds and many dining options on the room service menu (25 Canadian Dollars/15 per day per pet and a one time 100 Canadian Dollars/61 fee for cleaning). A small office as well as five meeting rooms are located on the mezzanine level.
All 152 rooms and suites include an iPod docking station,rolex daytona ladies watch imitation, bathrobes, bath amenities, 24 hour room service, 350 thread count cotton linens and a glass encased rain shower with a view of the room. Plush black and gold carpets, a desk with an ergonomic gold chair and a TV are also standards across rooms, as is the W MixBar, a testament to W's predilection for cocktail hour, allowing guests to mix their own in room cocktail. Each room has a wall decorated in a French rococo motif wallpaper inspired by the building's history. Standard rooms have views of the hotel's atrium while others have views of Victoria Square. The menu features seafood platters as well as dishes such as house paella and calamari carbonara (the pasta is replaced by the squid). Service is done on a guridon, an old school cart that gets wheeled tableside.
Of the three bars in the hotel,rolex day date ladies fake, the Bartini and its six seats is the cosiest, while wunderbar and its lively ambiance is where the hotel guests mingle with Montrealers. Note that the upstairs bar located right above the reception area is only open on weekends.
Opening is opportunity to give back
COURTESY MARC BRODSKY OF COOPER JEWELERSFrom left, former Gov. Donald DiFrancesco,rolex lady day date imitation, Joanne Kaiser of Resource Center for Women Their Families, Cooper Jeweler owners Elayne Pei and Jack Kung and Mae Belin of Women's Health Counseling Center during a recent open house held at Cooper Jewelers of Warren.
WARREN Cooper Jewelers of Warren held a ribbon cutting ceremony on Saturday,imitation rolex daytona white gold, Sept. 29 to celebrate the grand opening of its new flagship store on Mountain Boulevard.
"The open house was standing room only," exclaimed Cooper Jewelers President and Proprietor, Jack Kung. "We had nearly 500 residents from throughout the Central new Jersey area attend our grand opening."
As part of its grand opening, Cooper Jewelers was raising funds for two of Somerset County's leading women's organizations Women's Health Counseling Center of Somerville and The Resource Center for Women Their Families of Hillsborough. Representing the organizations at the event were and Mae Belin, Women's Health Counseling Center program director, and Joanne Kaiser, the Resource Center for Women Their Families' development director.
"Cooper Jewelers rolled out the red carpet in support of the many different programs and projects that our centers provide to women and their families throughout Somerset County," said Kaiser. "The customers who attended were not only shopping for diamonds and watches, they were also given the opportunity to find out that our women's centers are real jewels themselves."
Joining Cooper Jeweler owners Jack Kung and Elayne Pei for the ribbon cutting ceremony were former Gov. Donald DiFranceso and his wife Diane, new residents of Warren, Warren Mayor Victor Sordillo, Warren Township Committeeman Gary DiNardo, Assemblyman Kip Bateman, R 16th, Watchung Borough Councilwoman Debra Joren and Watchung Borough Councilman Thomas Franklin. Entertainment was provided by harpist and violinist Joanne Hansen and Svetoslav Slavov of Mountainside.
Cooper Jewelers has been providing superior personal jewelry services at reasonable prices in the Bridgewater Commons since 1988, and is now bringing a free standing store to another part of Somerset County.
The store specializes in custom design and the creation of one of a kind pieces through in house designer Elayne Pei, the wife of Kung. It has also added designer lines such as Cartier, Yvel,imitation rolex lady day date, Ulysses Nardin, Chimento, Baume Mercier,rolex day date imitation, Corum and IWC/Schaffhausen.
COURTESY MARC BRODSKY OF COOPER JEWELERSFrom left, former Gov. Donald DiFrancesco,rolex lady day date imitation, Joanne Kaiser of Resource Center for Women Their Families, Cooper Jeweler owners Elayne Pei and Jack Kung and Mae Belin of Women's Health Counseling Center during a recent open house held at Cooper Jewelers of Warren.
WARREN Cooper Jewelers of Warren held a ribbon cutting ceremony on Saturday,imitation rolex daytona white gold, Sept. 29 to celebrate the grand opening of its new flagship store on Mountain Boulevard.
"The open house was standing room only," exclaimed Cooper Jewelers President and Proprietor, Jack Kung. "We had nearly 500 residents from throughout the Central new Jersey area attend our grand opening."
As part of its grand opening, Cooper Jewelers was raising funds for two of Somerset County's leading women's organizations Women's Health Counseling Center of Somerville and The Resource Center for Women Their Families of Hillsborough. Representing the organizations at the event were and Mae Belin, Women's Health Counseling Center program director, and Joanne Kaiser, the Resource Center for Women Their Families' development director.
"Cooper Jewelers rolled out the red carpet in support of the many different programs and projects that our centers provide to women and their families throughout Somerset County," said Kaiser. "The customers who attended were not only shopping for diamonds and watches, they were also given the opportunity to find out that our women's centers are real jewels themselves."
Joining Cooper Jeweler owners Jack Kung and Elayne Pei for the ribbon cutting ceremony were former Gov. Donald DiFranceso and his wife Diane, new residents of Warren, Warren Mayor Victor Sordillo, Warren Township Committeeman Gary DiNardo, Assemblyman Kip Bateman, R 16th, Watchung Borough Councilwoman Debra Joren and Watchung Borough Councilman Thomas Franklin. Entertainment was provided by harpist and violinist Joanne Hansen and Svetoslav Slavov of Mountainside.
Cooper Jewelers has been providing superior personal jewelry services at reasonable prices in the Bridgewater Commons since 1988, and is now bringing a free standing store to another part of Somerset County.
The store specializes in custom design and the creation of one of a kind pieces through in house designer Elayne Pei, the wife of Kung. It has also added designer lines such as Cartier, Yvel,imitation rolex lady day date, Ulysses Nardin, Chimento, Baume Mercier,rolex day date imitation, Corum and IWC/Schaffhausen.
Based Comparative Genome Hybridization in Clinical Genetics
Humanitarian Fund.
Top of pageAbstractAbnormalities in DNA copy number are frequently found in patients with multiple anomaly syndromes and mental retardation. Array based comparative genomic hybridization (array CGH) is a high resolution, whole genome technology that improves detection of submicroscopic aberrations underlying these syndromes. Eight patients with mental disability, multiple congenital anomalies, and dysmorphic features were screened for submicroscopic chromosomal imbalances using the GenoSensor Array 300 Chip. Subtelomeric aberrations previously detected by fluorescence in situ hybridization (FISH) analysis were confirmed in two patients, and accurate diagnosis was provided in two previously undiagnosed complex cases. Microdeletions at 15q11.2 q13 in a newborn with hypotonia, cryptorchidism, and hypopigmentation were detected with few discrepancies between the array results and FISH analysis. Contiguous microdeletion of GSCL, HIRA and TBX1 genes at 22q11.2 was identified in a previously undiagnosed boy with an unusual presentation of the VCF/DiGeorge spectrum. In a newborn with aniridia, a borderline false negative WT1 deletion was observed, most probably because of differences between the size of the genomic deletion and the microarray probe. A false positive rate of 0.2% was calculated for clone by clone analysis, whereas the per patient false positive rate was 20%. Standard cytogenetic techniques, such as G banding fake cartier gold diamond ring and SKY cartier fake men wedding ring (spectral karyotyping), can identify large aberrations including deletions, duplications, amplifications and unbalanced translocations, although their limited resolution makes these tools unreliable for the detection of copy number changes of less than 5 Mb (2). FISH has the advantage of high resolution, but is best suited for the confirmation of known microdeletion and microduplication syndromes in patients presenting with a suggestive phenotype due to the limited number of chromosomal loci that can be simultaneously analyzed.
Array CGH is an innovative high resolution technology that detects and maps submicroscopic DNA copy number alterations (3,4), improving the diagnostic detection rate of subtle copy number changes. Array CGH detects quantitative aberrations spanning small regions of the genome, with resolution determined by both the size and the spacing of the clones on the array. CGH arrays have successfully identified submicroscopic unbalanced chromosomal rearrangements in multiple clinical samples. In three previous studies of patients with mental retardation and dysmorphisms that had normal karyotypes in standard cytogenetic analyses, genomewide arrays have reported rearrangement detection rates of 15%, 24%, and 10%, respectively (1,2,5). Thus, an even higher frequency of rearrangements is expected in the entire population of patients with mental retardation and dysmorphisms.
Top of pageMETHODSPatients and chromosomal analysis. All cases were referred for consultation to The Genetic Institute, Tel Aviv Sourasky Medical Center and are presented in Table 1. Patients' informed consents were obtained. Cytogenetic analysis was made according to a standard technique. Karyotypes were established according to the 1995 International System for Human Cytogenetic Nomenclature (17).
FISH analysis. Commercially available probes were used for FISH analyses of the telomeric regions at chromosomes 1q, 2q, and 12q (TelVysion, Abbot Vysis, Chicago, IL), 10q (QBiogene, Illkirch Cedex, France) and 14q (Cytocell, Windsor, CT). Commercially available probes (LSID15S11, SNRPN, GABRB3 and LSID15S10/UBE3A) for the PWS region at 15q11.2 q13, TUPLE1 and N25 for the VCF/DiGeorge region at 22q11.2 (Cytocell and Abbot Vysis, respectively), and LSILIS1 for the Miller Dieker/Lissencephaly region (Abbot Vysis) were also used for FISH analyses. The following BAC (bacterial artifical chromosome) clones that contain specific gene sequences were used as templates for FISH probes synthesis (Table 2): RPCI11 894C9 for RASSF1 (3q21.3) (M. Rocchi, University of Bari, Bari, Italy), RPCI1 74J1 for WT1 and RPCI11 307I15 for PAX6 (both at 11p13) (CHORI BACPAC Resources, Oakland, California). Cosmid 1p3 for the FLI1 gene at 11q24 (18) was provided by Dr. Shai Izraeli, and the FISH analysis for the WT1 and PAX6 genes (19) was performed using cosmids B2.1 and AN2, respectively (Dr. Karen Gronskov, personal communication). DNA probes cartier gold diamond ring imitation were directly labeled by nick translation with Spectrum Orange fluorescent nucleotide (Abbot Vysis) and coprecipitated in the presence of Cot 1 (Abbot Vysis) and salmon sperm DNA (Sigma Chemical Co. Aldrich, Rehovot, Israel). The chromosome preparation and the fluorescent probes were denatured separately at 73 and probes were allowed to preanneal at 37 before overnight hybridization. Following posthybridization washes, the chromosomes were counterstained with 4 (DAPI Vectashield, Vector Laboratories, Burlingame, CA). Hybridization signals were detected using rhodamine and DAPI filters on an Olympus B52 microscope, and the images were captured using a CCD camera and Cytovision Software (Applied Imaging, Santa Clara, CA). For the RASSF1 gene (3q21.3), in addition to FISH hybridization with the entire BAC as a probe, three specific genomic fragments of about 6 Kb each, representing the 5 the middle, and the 3 regions of the gene, were prepared by polymerase chain reaction (PCR), pooled together and labeled for FISH as described. The primers for the specific RASSF1 FISH probes and the PCR conditions are available upon request.
Array CGH. High molecular weight genomic DNA was extracted from patient's peripheral blood leukocytes using the PureGene DNA Isolation Kit (Gentra Systems, Minneapolis, MN) according to the manufacturer's instructions. Detection of gene copy number was performed by array CGH using Abbot Vysis GenoSensor system (Abbot Vysis) according to the manufacturer's instructions (Abbot Vysis). Briefly, 100 ng of each test DNA and normal reference DNA (from an individual of the opposite sex of the test sample) was labeled by Random Priming Kit (Abbot Vysis) to incorporate Cy3 or Cy5 fluorophores (Perkin Elmer, Boston, MA). DNA was denatured at 100 for 10 min and was cooled to 4 before the addition of Klenow fragments and nucleotide mix. After incubation at 37 for 2 h, the samples were digested using a 1:20 DNAse dilution for 1 h at 15 Unincorporated nucleotides were then removed using Sephadex G 50 spin columns (Amersham Biosciences, Piscataway, NJ). Probes were precipitated with ethanol and resuspended in 10 mmol/L Tris, pH 8.0. Equal aliquots of labeled test and reference DNA were combined in a tube with hybridization buffer, denatured at 80 for 10 min, and incubated for 1 h at 37 to allow blocking of repetitive sequences. The solutions were then hybridized for 72 h at 37 with a GenoSensor Array 300. This array contains 287 genomic clones, including those for each human telomere, as well as all the known microdeletion syndromes and additional selected loci representing each chromosome arm. After hybridization, the arrays were washed in 50% formamide/2 SSC at 40 and 1 SSC at 25 and were counterstained with 4 (DAPI). Hybridization signal images in three colors (Cy3, Cy5, and DAPI blue) were then analyzed by the GenoSensor reader system based on DAPI staining that identified target spots and their location on the grid. By analyzing the set of Cy3/Cy5 ratios (test to reference ratios) on all targets, the GenoSensor Array 300 Reader Software (version 1) calculates the ratio most representative of the modal DNA copy number of the sample DNA. For each target the normalized ratio, relative to the modal DNA copy number is calculated. This normalized ratio of the target indicates the degree of gain or loss of copy number, and for each clone the copy number changes are presented. For each target, a p value is calculated automatically by the GenoSensor Array 300 Reader Software (Abbot Vysis), and a p value of was considered significant.
Top of pageRESULTSWe screened eight patients with mental deficiency, multiple congenital anomalies, and dysmorphic features for submicroscopic chromosomal imbalances using array CGH. All cases were analyzed previously by routine cytogenetic techniques, and chromosomal aberrations were identified in three. CGH results were compared with previous G banding and FISH analyses to ascertain whether CGH arrays could verify previously detected abnormalities. In the remaining five cases, array CGH was implemented in an attempt to identify potential submicroscopic rearrangements in complex undiagnosed patients. Each analysis was performed once by an operator with no knowledge of the previous diagnosis. We also performed four versus normal control experiments and confirmed these threshold values. Our analysis of the normal control samples resulted in a standard deviation (SD) of 0.05, suggesting that 4 SDs determine the threshold of either gains or losses. Power analysis, assuming an SD of 0.05 among samples and a mean difference of 0.2 between the normal controls and the patients was 0.996 when n 4 in each group (Power and Precision Software, Biostat, Englewood, NJ). Gains and/or loss of chromosomal material were detected in six of the eight patients tested (Table 2).
Validation experiments. In two of the three previously diagnosed patients (cases 1 and 2), array CGH validated the results of FISH and G banding. In case 1, we verified unbalanced t(2;12)(q37;q24) with trisomy 12q37 and monosomy of 2q24 In case 2, we validated the trisomy of 1qtel and the adjacent AKT gene (at 1q44), and the deletion of 11qtel. The latter is compatible with the balanced translocation t (1;11)(q42;q23) detected in this family.
FISH analysis of case 3 using cosmid probes detected the deletion of one copy of the PAX6 and WT1 genes located at chromosome 11p13 (22). PAX6 gene is not present on the Array 300, but a T/R ratio of 0.81 and a significant p value of 0.002 were observed for WT1 in the Array 300 analysis of this case (Fig. 1A). Although a few other probes came close to a T/R ratio of 0.8 (0.81 none of them, except the WT1 probe in case 3, had a significant p value. Therefore, this target was designated as a borderline false negative. Repeated FISH analysis of case 3 with BAC probes for PAX6 and WT1 genes validated the deletion of one copy of the PAX6 gene, but detected two copies of the WT1 gene (Fig. 1B and C, respectively), suggesting that the differences in probes' sizes (BAC versus cosmid) determine whether the deletion could unequivocally be detected. (A) The array CGH profile. The WT1 targets are marked in a yellow frame. Because the T/R ratio is 0.81, the signal is gray and does not appear as a deletion. Male test DNA was hybridized against female reference DNA, resulting in deletion signals of X chromosome targets (red) and amplification signals of Y chromosome targets (green). (B) FISH analysis using PAX6 RPCI11 307I15 BAC clone as probe. The red arrow indicates the deletion. (C) FISH analysis using WT1 RPCI1 74J1 BAC clone as probe.
Full figure and legend (363K)
Detection of novel chromosomal aberrations in complex undiagnosed patients. CGH microarray results provided diagnoses in two of the five previously undiagnosed cases. In case 4, array CGH analysis showed losses of one copy of two probes in the 15q11.2 q13 region: SNRPN and GABRB3. Four target probes were tested at the Prader Willi/Angelman region, D15S11 SNRPN, UBE3A and GABRB3, from the centromere to the telomere, using FISH probes and the Array 300. The probes located at both ends of this region, GABRB3 and D15S11, demonstrated one and two copies of these genes, respectively, using both methods. With the two other probes, there was a discrepancy between the FISH and Array 300 results. Deletion of one UBE3A copy was seen in FISH analysis, but not in the array CGH. In contrast, deletion of one SNRPN copy was detected in the Array 300 analysis, whereas FISH analysis demonstrated two copies, although one signal was weak, suggesting that one of the breakpoints might have occurred within the SNRPN gene region. Because hypopigmentation was found in this patient, we further suggest that the second deletion breakpoint located distal to the P locus. Additional microdeletion of one of the subtelomeric clones at the 14qtel was not validated by the FISH analysis.
Case 5 demonstrated contiguous microdeletion of three genes at the 22q11.2 region: GSCL, HIRA, and TBX1. Additional microdeletion of one of the subtelomeric clones at the 10qtel was not detected by FISH analysis.
In case 6, FISH hybridizations using probes of both the entire BAC and specific sequences of this gene did not confirm the deletion of RASSF1 at 3q21.3 detected by the Array 300, and it was therefore regarded as false positive.
Finally, no abnormalities were detected in the array CGH analyses of cases 7 and 8.
Top of pageDISCUSSIONWe used array CGH as an additional tool to resolve undiagnosed complex cases of children with mental deficiency, multiple malformations, and dysmorphic features. The GenoSensor Array 300 chip, containing 287 different probes representing regions significant in cytogenetics or oncology, successfully identified gains and/or losses of DNA copies in cartier diamond replica rings five of the eight cases examined.
Results from our array CGH analyses of cases 1 and 2 correlated well with the rearrangements previously detected by FISH. The array CGH analysis also detected chromosomal alterations in two previously undiagnosed cases (cases 4 and 5). Microdeletion at the chromosome 15q11 q12 region was detected in case 4, confirming the suspected clinical diagnosis of Prader Willi syndrome in the newborn boy. The discrepancies between the Array 300 results and the commercial FISH probe analysis emphasize the importance of specific FISH probes for the validation of microarray data.in concern of cartier bracelet pink gold screw imitation Latest mode magazine present tell you
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Humanitarian Fund.
Top of pageAbstractAbnormalities in DNA copy number are frequently found in patients with multiple anomaly syndromes and mental retardation. Array based comparative genomic hybridization (array CGH) is a high resolution, whole genome technology that improves detection of submicroscopic aberrations underlying these syndromes. Eight patients with mental disability, multiple congenital anomalies, and dysmorphic features were screened for submicroscopic chromosomal imbalances using the GenoSensor Array 300 Chip. Subtelomeric aberrations previously detected by fluorescence in situ hybridization (FISH) analysis were confirmed in two patients, and accurate diagnosis was provided in two previously undiagnosed complex cases. Microdeletions at 15q11.2 q13 in a newborn with hypotonia, cryptorchidism, and hypopigmentation were detected with few discrepancies between the array results and FISH analysis. Contiguous microdeletion of GSCL, HIRA and TBX1 genes at 22q11.2 was identified in a previously undiagnosed boy with an unusual presentation of the VCF/DiGeorge spectrum. In a newborn with aniridia, a borderline false negative WT1 deletion was observed, most probably because of differences between the size of the genomic deletion and the microarray probe. A false positive rate of 0.2% was calculated for clone by clone analysis, whereas the per patient false positive rate was 20%. Standard cytogenetic techniques, such as G banding fake cartier gold diamond ring and SKY cartier fake men wedding ring (spectral karyotyping), can identify large aberrations including deletions, duplications, amplifications and unbalanced translocations, although their limited resolution makes these tools unreliable for the detection of copy number changes of less than 5 Mb (2). FISH has the advantage of high resolution, but is best suited for the confirmation of known microdeletion and microduplication syndromes in patients presenting with a suggestive phenotype due to the limited number of chromosomal loci that can be simultaneously analyzed.
Array CGH is an innovative high resolution technology that detects and maps submicroscopic DNA copy number alterations (3,4), improving the diagnostic detection rate of subtle copy number changes. Array CGH detects quantitative aberrations spanning small regions of the genome, with resolution determined by both the size and the spacing of the clones on the array. CGH arrays have successfully identified submicroscopic unbalanced chromosomal rearrangements in multiple clinical samples. In three previous studies of patients with mental retardation and dysmorphisms that had normal karyotypes in standard cytogenetic analyses, genomewide arrays have reported rearrangement detection rates of 15%, 24%, and 10%, respectively (1,2,5). Thus, an even higher frequency of rearrangements is expected in the entire population of patients with mental retardation and dysmorphisms.
Top of pageMETHODSPatients and chromosomal analysis. All cases were referred for consultation to The Genetic Institute, Tel Aviv Sourasky Medical Center and are presented in Table 1. Patients' informed consents were obtained. Cytogenetic analysis was made according to a standard technique. Karyotypes were established according to the 1995 International System for Human Cytogenetic Nomenclature (17).
FISH analysis. Commercially available probes were used for FISH analyses of the telomeric regions at chromosomes 1q, 2q, and 12q (TelVysion, Abbot Vysis, Chicago, IL), 10q (QBiogene, Illkirch Cedex, France) and 14q (Cytocell, Windsor, CT). Commercially available probes (LSID15S11, SNRPN, GABRB3 and LSID15S10/UBE3A) for the PWS region at 15q11.2 q13, TUPLE1 and N25 for the VCF/DiGeorge region at 22q11.2 (Cytocell and Abbot Vysis, respectively), and LSILIS1 for the Miller Dieker/Lissencephaly region (Abbot Vysis) were also used for FISH analyses. The following BAC (bacterial artifical chromosome) clones that contain specific gene sequences were used as templates for FISH probes synthesis (Table 2): RPCI11 894C9 for RASSF1 (3q21.3) (M. Rocchi, University of Bari, Bari, Italy), RPCI1 74J1 for WT1 and RPCI11 307I15 for PAX6 (both at 11p13) (CHORI BACPAC Resources, Oakland, California). Cosmid 1p3 for the FLI1 gene at 11q24 (18) was provided by Dr. Shai Izraeli, and the FISH analysis for the WT1 and PAX6 genes (19) was performed using cosmids B2.1 and AN2, respectively (Dr. Karen Gronskov, personal communication). DNA probes cartier gold diamond ring imitation were directly labeled by nick translation with Spectrum Orange fluorescent nucleotide (Abbot Vysis) and coprecipitated in the presence of Cot 1 (Abbot Vysis) and salmon sperm DNA (Sigma Chemical Co. Aldrich, Rehovot, Israel). The chromosome preparation and the fluorescent probes were denatured separately at 73 and probes were allowed to preanneal at 37 before overnight hybridization. Following posthybridization washes, the chromosomes were counterstained with 4 (DAPI Vectashield, Vector Laboratories, Burlingame, CA). Hybridization signals were detected using rhodamine and DAPI filters on an Olympus B52 microscope, and the images were captured using a CCD camera and Cytovision Software (Applied Imaging, Santa Clara, CA). For the RASSF1 gene (3q21.3), in addition to FISH hybridization with the entire BAC as a probe, three specific genomic fragments of about 6 Kb each, representing the 5 the middle, and the 3 regions of the gene, were prepared by polymerase chain reaction (PCR), pooled together and labeled for FISH as described. The primers for the specific RASSF1 FISH probes and the PCR conditions are available upon request.
Array CGH. High molecular weight genomic DNA was extracted from patient's peripheral blood leukocytes using the PureGene DNA Isolation Kit (Gentra Systems, Minneapolis, MN) according to the manufacturer's instructions. Detection of gene copy number was performed by array CGH using Abbot Vysis GenoSensor system (Abbot Vysis) according to the manufacturer's instructions (Abbot Vysis). Briefly, 100 ng of each test DNA and normal reference DNA (from an individual of the opposite sex of the test sample) was labeled by Random Priming Kit (Abbot Vysis) to incorporate Cy3 or Cy5 fluorophores (Perkin Elmer, Boston, MA). DNA was denatured at 100 for 10 min and was cooled to 4 before the addition of Klenow fragments and nucleotide mix. After incubation at 37 for 2 h, the samples were digested using a 1:20 DNAse dilution for 1 h at 15 Unincorporated nucleotides were then removed using Sephadex G 50 spin columns (Amersham Biosciences, Piscataway, NJ). Probes were precipitated with ethanol and resuspended in 10 mmol/L Tris, pH 8.0. Equal aliquots of labeled test and reference DNA were combined in a tube with hybridization buffer, denatured at 80 for 10 min, and incubated for 1 h at 37 to allow blocking of repetitive sequences. The solutions were then hybridized for 72 h at 37 with a GenoSensor Array 300. This array contains 287 genomic clones, including those for each human telomere, as well as all the known microdeletion syndromes and additional selected loci representing each chromosome arm. After hybridization, the arrays were washed in 50% formamide/2 SSC at 40 and 1 SSC at 25 and were counterstained with 4 (DAPI). Hybridization signal images in three colors (Cy3, Cy5, and DAPI blue) were then analyzed by the GenoSensor reader system based on DAPI staining that identified target spots and their location on the grid. By analyzing the set of Cy3/Cy5 ratios (test to reference ratios) on all targets, the GenoSensor Array 300 Reader Software (version 1) calculates the ratio most representative of the modal DNA copy number of the sample DNA. For each target the normalized ratio, relative to the modal DNA copy number is calculated. This normalized ratio of the target indicates the degree of gain or loss of copy number, and for each clone the copy number changes are presented. For each target, a p value is calculated automatically by the GenoSensor Array 300 Reader Software (Abbot Vysis), and a p value of was considered significant.
Top of pageRESULTSWe screened eight patients with mental deficiency, multiple congenital anomalies, and dysmorphic features for submicroscopic chromosomal imbalances using array CGH. All cases were analyzed previously by routine cytogenetic techniques, and chromosomal aberrations were identified in three. CGH results were compared with previous G banding and FISH analyses to ascertain whether CGH arrays could verify previously detected abnormalities. In the remaining five cases, array CGH was implemented in an attempt to identify potential submicroscopic rearrangements in complex undiagnosed patients. Each analysis was performed once by an operator with no knowledge of the previous diagnosis. We also performed four versus normal control experiments and confirmed these threshold values. Our analysis of the normal control samples resulted in a standard deviation (SD) of 0.05, suggesting that 4 SDs determine the threshold of either gains or losses. Power analysis, assuming an SD of 0.05 among samples and a mean difference of 0.2 between the normal controls and the patients was 0.996 when n 4 in each group (Power and Precision Software, Biostat, Englewood, NJ). Gains and/or loss of chromosomal material were detected in six of the eight patients tested (Table 2).
Validation experiments. In two of the three previously diagnosed patients (cases 1 and 2), array CGH validated the results of FISH and G banding. In case 1, we verified unbalanced t(2;12)(q37;q24) with trisomy 12q37 and monosomy of 2q24 In case 2, we validated the trisomy of 1qtel and the adjacent AKT gene (at 1q44), and the deletion of 11qtel. The latter is compatible with the balanced translocation t (1;11)(q42;q23) detected in this family.
FISH analysis of case 3 using cosmid probes detected the deletion of one copy of the PAX6 and WT1 genes located at chromosome 11p13 (22). PAX6 gene is not present on the Array 300, but a T/R ratio of 0.81 and a significant p value of 0.002 were observed for WT1 in the Array 300 analysis of this case (Fig. 1A). Although a few other probes came close to a T/R ratio of 0.8 (0.81 none of them, except the WT1 probe in case 3, had a significant p value. Therefore, this target was designated as a borderline false negative. Repeated FISH analysis of case 3 with BAC probes for PAX6 and WT1 genes validated the deletion of one copy of the PAX6 gene, but detected two copies of the WT1 gene (Fig. 1B and C, respectively), suggesting that the differences in probes' sizes (BAC versus cosmid) determine whether the deletion could unequivocally be detected. (A) The array CGH profile. The WT1 targets are marked in a yellow frame. Because the T/R ratio is 0.81, the signal is gray and does not appear as a deletion. Male test DNA was hybridized against female reference DNA, resulting in deletion signals of X chromosome targets (red) and amplification signals of Y chromosome targets (green). (B) FISH analysis using PAX6 RPCI11 307I15 BAC clone as probe. The red arrow indicates the deletion. (C) FISH analysis using WT1 RPCI1 74J1 BAC clone as probe.
Full figure and legend (363K)
Detection of novel chromosomal aberrations in complex undiagnosed patients. CGH microarray results provided diagnoses in two of the five previously undiagnosed cases. In case 4, array CGH analysis showed losses of one copy of two probes in the 15q11.2 q13 region: SNRPN and GABRB3. Four target probes were tested at the Prader Willi/Angelman region, D15S11 SNRPN, UBE3A and GABRB3, from the centromere to the telomere, using FISH probes and the Array 300. The probes located at both ends of this region, GABRB3 and D15S11, demonstrated one and two copies of these genes, respectively, using both methods. With the two other probes, there was a discrepancy between the FISH and Array 300 results. Deletion of one UBE3A copy was seen in FISH analysis, but not in the array CGH. In contrast, deletion of one SNRPN copy was detected in the Array 300 analysis, whereas FISH analysis demonstrated two copies, although one signal was weak, suggesting that one of the breakpoints might have occurred within the SNRPN gene region. Because hypopigmentation was found in this patient, we further suggest that the second deletion breakpoint located distal to the P locus. Additional microdeletion of one of the subtelomeric clones at the 14qtel was not validated by the FISH analysis.
Case 5 demonstrated contiguous microdeletion of three genes at the 22q11.2 region: GSCL, HIRA, and TBX1. Additional microdeletion of one of the subtelomeric clones at the 10qtel was not detected by FISH analysis.
In case 6, FISH hybridizations using probes of both the entire BAC and specific sequences of this gene did not confirm the deletion of RASSF1 at 3q21.3 detected by the Array 300, and it was therefore regarded as false positive.
Finally, no abnormalities were detected in the array CGH analyses of cases 7 and 8.
Top of pageDISCUSSIONWe used array CGH as an additional tool to resolve undiagnosed complex cases of children with mental deficiency, multiple malformations, and dysmorphic features. The GenoSensor Array 300 chip, containing 287 different probes representing regions significant in cytogenetics or oncology, successfully identified gains and/or losses of DNA copies in cartier diamond replica rings five of the eight cases examined.
Results from our array CGH analyses of cases 1 and 2 correlated well with the rearrangements previously detected by FISH. The array CGH analysis also detected chromosomal alterations in two previously undiagnosed cases (cases 4 and 5). Microdeletion at the chromosome 15q11 q12 region was detected in case 4, confirming the suspected clinical diagnosis of Prader Willi syndrome in the newborn boy. The discrepancies between the Array 300 results and the commercial FISH probe analysis emphasize the importance of specific FISH probes for the validation of microarray data.
The Light of Day
A lean man in a trench coat stands in a darkened lobby gazing out onto the street. Light from an open doorway beckons, but the man appears frozen in an attitude of perpetual watchfulness. Outside,imitation rolex date just, people walk by seemingly unaware of the lonely figure in the shadows.
Jack Eisenberg, who photographed this scene at Baltimore's Rochambeau Apartments, Franklin and Charles streets, back in the 1980s, is a portly, white haired man who looks more like Santa Claus than the shadowy silhouette in the trench coat. Yet in a way that figure is his alter ego the solitary observer of the passing parade, just outside the circle of light, who sees without being seen.
Eisenberg has devoted his life to photography, capturing images that haunt the imagination and touch the heart with their subtle, multiple meanings. But it is a career that has brought him little recognition or material reward. Instead,imitation rolex daytona steel, he ekes out a frugal existence, constantly scrimping and saving and worrying whether he'll have to choose between buying food or film.
At 61, Eisenberg remains one of Baltimore's virtually unknown treasures, a local genius with a battered Leica camera whose pictures of Israel and America are full of incident and detail, pathos and drama. And yet,imitation daytona rolex, as with the man in the trench coat, most people don't even know he's there.
Street photography is one of the most difficult forms of the craft because it requires split second decisions and a quicksilver coordination between hand and eye to capture what photojournalist Henri Cartier Bresson called "the decisive moment."
Eisenberg has captured hundreds of such moments during his career. There's whimsy in his pictures, and a deep humanism. His photographs are marvelously poised, insightful, compassionate and informed by wry humor whether the subject is a barbershop on Greenmount Avenue or a tense political standoff in Jerusalem. In his best pictures, there is an uncanny coincidence of composition and subject matter, so that the photographic form perfectly embodies its content.
But it's not just their formal qualities the play of light and shadow, the complex, layered juxtapositions of near and far that make Eisenberg's pictures compelling. They are also informed by a genuine historical erudition, both about Baltimore and Israel (before taking up the camera, Eisenberg earned a bachelor of arts degree in history at Columbia University in New York and later taught high school history in Baltimore County public schools). His photographs of African Americans in Baltimore and Palestinians in the West Bank show a genuine empathy with the underdog. His Jerusalem pictures, in particular, evoke the feel of people living with adversity and terror and still enjoying life, be they Arab or Jew. His pictures are life affirming in the deepest sense.
"I need to relate what I know intellectually to what I see in the world around me," he says. "Photography for me has been to go out and find something that is like an epiphany, a moment when everything becomes clear."
Over the years, he has shown his work in the occasional local show and published photographs in the Jewish Times, which for a while paid him as a stringer for stories from Israel. But the Times stopped publishing his photographs several years ago after a new editor took over, and Eisenberg hasn't found another outlet for his work.
Nor have the city's museums and galleries shown much interest, despite the fact that he has produced what amounts to a documentary treasure trove of Baltimore images in the last 25 years. Part of the problem is Eisenberg himself. He is fanatical about doing things his own way so much so that he can seem argumentative or eccentric to people who don't know him.
So last month, Eisenberg decided to put on his own show in the modest Mount Washington home where he grew up and where he returned to live several years ago after his parents died. He mounted a couple of photo floodlights in the center of his living room to better display his art; the bright lights also emphasized the lifelong bachelor's domestic jumble.
The show focused on some two dozen mounted but unframed pictures Eisenberg shot in Israel during the country's most recent election campaign. Eisenberg, who is Jewish, has been photographing the Middle East since 1967, and he has seen hatred on both sides. But as a photographer his concern is always with the individuals who represent the human aspect of the conflict, not their politics.
There are shots of the second Palestinian intifada, which began in the fall of 2000, and the daily street demonstrations by Labor and Likud supporters, pictures of funerals of Israelis killed by Palestinians and of Palestinians killed by Israelis.
Eisenberg hoped to sell a few pictures, but mostly he did the show to keep his spirits up. He wants to return to Israel to photograph,rolex daytona black imitation, but right now he's struggling just to make ends meet at home.
A lean man in a trench coat stands in a darkened lobby gazing out onto the street. Light from an open doorway beckons, but the man appears frozen in an attitude of perpetual watchfulness. Outside,imitation rolex date just, people walk by seemingly unaware of the lonely figure in the shadows.
Jack Eisenberg, who photographed this scene at Baltimore's Rochambeau Apartments, Franklin and Charles streets, back in the 1980s, is a portly, white haired man who looks more like Santa Claus than the shadowy silhouette in the trench coat. Yet in a way that figure is his alter ego the solitary observer of the passing parade, just outside the circle of light, who sees without being seen.
Eisenberg has devoted his life to photography, capturing images that haunt the imagination and touch the heart with their subtle, multiple meanings. But it is a career that has brought him little recognition or material reward. Instead,imitation rolex daytona steel, he ekes out a frugal existence, constantly scrimping and saving and worrying whether he'll have to choose between buying food or film.
At 61, Eisenberg remains one of Baltimore's virtually unknown treasures, a local genius with a battered Leica camera whose pictures of Israel and America are full of incident and detail, pathos and drama. And yet,imitation daytona rolex, as with the man in the trench coat, most people don't even know he's there.
Street photography is one of the most difficult forms of the craft because it requires split second decisions and a quicksilver coordination between hand and eye to capture what photojournalist Henri Cartier Bresson called "the decisive moment."
Eisenberg has captured hundreds of such moments during his career. There's whimsy in his pictures, and a deep humanism. His photographs are marvelously poised, insightful, compassionate and informed by wry humor whether the subject is a barbershop on Greenmount Avenue or a tense political standoff in Jerusalem. In his best pictures, there is an uncanny coincidence of composition and subject matter, so that the photographic form perfectly embodies its content.
But it's not just their formal qualities the play of light and shadow, the complex, layered juxtapositions of near and far that make Eisenberg's pictures compelling. They are also informed by a genuine historical erudition, both about Baltimore and Israel (before taking up the camera, Eisenberg earned a bachelor of arts degree in history at Columbia University in New York and later taught high school history in Baltimore County public schools). His photographs of African Americans in Baltimore and Palestinians in the West Bank show a genuine empathy with the underdog. His Jerusalem pictures, in particular, evoke the feel of people living with adversity and terror and still enjoying life, be they Arab or Jew. His pictures are life affirming in the deepest sense.
"I need to relate what I know intellectually to what I see in the world around me," he says. "Photography for me has been to go out and find something that is like an epiphany, a moment when everything becomes clear."
Over the years, he has shown his work in the occasional local show and published photographs in the Jewish Times, which for a while paid him as a stringer for stories from Israel. But the Times stopped publishing his photographs several years ago after a new editor took over, and Eisenberg hasn't found another outlet for his work.
Nor have the city's museums and galleries shown much interest, despite the fact that he has produced what amounts to a documentary treasure trove of Baltimore images in the last 25 years. Part of the problem is Eisenberg himself. He is fanatical about doing things his own way so much so that he can seem argumentative or eccentric to people who don't know him.
So last month, Eisenberg decided to put on his own show in the modest Mount Washington home where he grew up and where he returned to live several years ago after his parents died. He mounted a couple of photo floodlights in the center of his living room to better display his art; the bright lights also emphasized the lifelong bachelor's domestic jumble.
The show focused on some two dozen mounted but unframed pictures Eisenberg shot in Israel during the country's most recent election campaign. Eisenberg, who is Jewish, has been photographing the Middle East since 1967, and he has seen hatred on both sides. But as a photographer his concern is always with the individuals who represent the human aspect of the conflict, not their politics.
There are shots of the second Palestinian intifada, which began in the fall of 2000, and the daily street demonstrations by Labor and Likud supporters, pictures of funerals of Israelis killed by Palestinians and of Palestinians killed by Israelis.
Eisenberg hoped to sell a few pictures, but mostly he did the show to keep his spirits up. He wants to return to Israel to photograph,rolex daytona black imitation, but right now he's struggling just to make ends meet at home.