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Apple earns record $13B on sales of 37M iPhones, 15M iPads and 5.2M MacsApple announced Tuesday the best quarter in its corporate history where earnings rose more than 117% to $13.06 billion, or $13.87 per diluted share, on record quarterly revenue of $46.33 billion.
The results compare to revenue of $26.74 billion and net quarterly profit of $6 billion, or $6.43 per diluted share, in the year-ago quarter. Gross margin was 44.7 percent compared to 38.5 percent in the year-ago quarter. International sales accounted for 58 percent of the quarters revenue.
We are very happy to have generated over $17.5 billion in cash flow from operations during the December quarter, said Peter Oppenheimer, Apples CFO. Looking ahead to the second fiscal quarter of 2012, which will span 13 weeks, we expect revenue of about $32.5 billion and we expect diluted earnings per share of about $8.50.
Apple sold an all-time high 37.04 million iPhones in the quarter, representing 128 percent unit growth over the year-ago quarter, in addition to a record 15.43 million iPads — a 111 percent unit increase.
The Cupertino-based company also sold 5.2 million Macs during the quarter, a 26 percent unit increase over the year-ago quarter, and another record benchmark. Meanwhile, iPod sales came in at 15.4 million units, a 21 percent unit decline.
Were thrilled with our outstanding results and record-breaking sales of iPhones, iPads and Macs, said Tim Cook, Apples CEO. Apples momentum is incredibly strong, and we have some amazing new products in the pipeline.
Apple will provide live streaming of its Q1 2012 financial results conference call beginning at 2:00 p.m. PST. AppleInsider will provide full coverage.
On Topic: Investor
- Shares of Apple don't reflect significance of iPhone Upgrade Program, Piper Jaffray says
- Buyers skew towards higher-capacity iPhones, iPhone Upgrade Program shows early popularity
- Pessimistic, questionable iPhone supplier rumor sends shares of Apple further downward
- Apple to reveal fiscal Q4 2015 earnings on Oct. 27
- Apple's record setting iPhone 6s launch weekend impresses Wall Street


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Star Trek: Starfleet Command Volume II - Empires at War (Windows)
Screenshot 6 of 41
A nice touch: each race has its own rank insignia, campaign ribbons and medals. Pictured here is an up-and-coming federation's officer I-love-me board.
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subset: commoncrawl


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Two people have been shot in the Shawnee neighborhood Sunday a little after 7 p.m. [WDRB]
The subject of both praise and controversy, Louisville Metro Police's VIPER Unit is set to fold into a new mobile division that will continue VIPER's data-driven approach to targeting violent crime in the city, officials announced Friday. [C-J/AKN]
Here comes the Louisville media to report on this man's downfall. Locals love blood, gore, suffering and sadness. News directors should be ashamed. Or maybe just straight up kicked to the curb. [WHAS11]
Going to school saved James Mouser's life in early April. Mouser, then a senior at Northpoint Academy in Pike County, cut his hand while at school on a Friday. Unable to see a doctor because he has no car, he lanced his own hand over the weekend after it became infected. [H-L]
WARNING! RIDICULOUS AUTOPLAY VIDEO! Here's a story about those shootings Louisville loves so much. [WLKY]
Kim Davis: dumb as hell. A county clerk in Kentucky who petitioned the Supreme Court to allow her to refuse to wed LGBT couples unknowingly married a trans man and a pansexual woman, the couple says. [HuffPo]
In a closer look at the issue of behavior and discipline in the classroom, the Jefferson County Teachers Association tells us JCPS is not doing enough to deal with the issue. The teacher's union comes to that conclusion after recently conducting a survey this summer. [WAVE3]
President Barack Obama on Saturday defended his decision to allow Royal Dutch Shell to drill for oil in the Arctic Ocean under what he said were rigorous standards, fending off criticism by environmental groups. [Reuters]
Residents are invited to provide comment on a proposed bike lane installation on Sixth Street that would stretch from River Road to Zane Street. [WFPL]
The Kentucky Board of Education has chosen two finalists in its search for a new state education commissioner. It'll be someone the opposite of great and, sadly, you know I'm right. [WKYT]
Why the hell are news directors continually reporting on the downfall of people when they're clearly vulnerable and need assistance instead of hype? It's not just BF. It's every outlet in town. [Business First]
Although Southern Indiana Animal Rescue has operated for 10 years, the Clark County Board of Zoning Appeals decided Wednesday to place restrictions on it. [News & Tribune]
HELP PROTECT OUR SOURCES! Stop the Montgomery County-Joshua Powell-Phil Rison insanity! [CLICK HERE]


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FabFurnish announces The FAB TGIF Contest
FabFurnish.com introduces 'The FAB TGIF Contest' that starts from June 13 and ends on July 3. The contest invites all bloggers to share their creative ideas on how can their home be converted into a rocking party den.
City, State, Country., June 27, 2014 - (PressReleasePoint) - FabFurnish.com launches its FAB TGIF contest on June 13, 2014 to invite all creative minds to pen down their thoughts on how can they transform their home into a rocking party den with the right furniture and furnishings.
The 'FAB TGIF contest' calls all the bloggers with a creative bend for writing on how would they furnish their home with the right party essentials and be the perfect host for a Friday In-house party.
The contest started from June 13 and will end on July 3, 2014. All the contestants are required to submit their entries supported by product pictures that will make their TGIF party all the more rocking. The entries would be accepted in the form of blog via email. Bloggers may send the entries aka blog URL to firstname.lastname@example.com. The selection criteria would be based on creativity and uniqueness of idea.
The top two entries would get gift vouchers worth Rs.5000 each, and the next three would get gift vouchers worth Rs.3000 each. This is not all! Every single remaining valid entry would be entitled to a gift voucher for Rs.500, making it a total win-win deal for every participant.
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text:
3 titles.
|Sort by: MOVIEmeter▲ | A-Z | User Rating | Num Votes | US Box Office | Runtime | Year | US Release Date
Young Frankenstein
Dr. Frankenstein's grandson, after years of living down the family reputation, inherits granddad's castle and repeats the experiments. Dir: Mel Brooks With: Gene Wilder, Madeline Kahn, Marty Feldman Comedy 106 mins.
The Rockford Files
(1974 TV Series)
Episode: Backlash of the Hunter (1974) Jim helps a young girl whose father was murdered and LAPD has closed the case on without finding the killer. Dir: Richard T. Heffron With: James Garner, Lindsay Wagner, William Smith Crime | Drama | Mystery | Thriller 98 mins.
Someone to Love
A Hollywood film director assembles a group of friends and strangers for a social gathering on Valentines Day in a deserted movie theater where he interviews each one on their opinions on love and loneliness. Dir: Henry Jaglom With: Henry Jaglom, Andrea Marcovicci, Michael Emil Comedy | Drama | Romance 111 mins.
3 titles.


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Posted: Thursday, June 13, 2013 8:46 PM
Hey guys! Are u looking for some fun? Will be here for a couple days so dont miss out! 5'5, 150lbs,36-C, long black hair...and sooo exotic. Asian/American Hottie! D/D-free..Very clean at ALL times! 803-336-1985 NO TEXT!! I do NOT have 40 specials..
• Location: 52, Florence
• Post ID: 6033660 southcarolina


text:
Appel: Corporate Inversions Could Mean Big Tax Bills For Shareholders
The California Court of Appeal recently confirmed that employment-related settlements or judgments are wages from which employers must withhold payroll taxes.
In Cifuentes v. Costco Wholesale Corp., Cifuentes...more
October Interest Rates for GRATs, Sales to Defective Grantor Trusts, Intra-Family Loans and Split Interest Charitable Trusts -
The October § 7520 rate for use with estate planning techniques such as CRTs, CLTs, QPRTs...more
State Tax Department Releases Draft Article 9-A Nexus Regulations Under Corporate Tax Reform -
The New York State Department of Taxation and Finance has released draft amendments to the Article 9-A corporate franchise...more
In This Issue:
- The net investment income tax and your estate plan: How one affects the other
- Use a noncharitable purpose trust to achieve a variety of goals
- Addressing adopted children or stepchildren in your...more
Under the Dome: Inside the Maine State House provides a high-level overview of recent activity at the Maine State House.
Double Whammy in Maine's Paper Industry -
This past week, two northern Maine paper mills...more
The U.S. Department of State has announced the opening of the registration period for the DV-2017 Diversity Visa (DV) Lottery Program. The DV Lottery Program enables foreign nationals to apply for permanent residence in the...more
If you live on the East Coast of the United States, you are probably following the weather forecast for Hurricane Joaquin very closely. If you are also filing your U.S. income taxes on extension and are trying to make the...more
Are you at least 62 years of age and have 50% or more equity in your primary residence? Then the reverse mortgage, also referred to as a home equity conversion mortgage, is something you might want to think about. Reverse...more
Tax reform is emerging as a major issue in the 2016 US presidential campaign, and in the growing wave of populist anger at the establishment elite in Washington and Wall Street, the financial industry has become a prime...more
Effective July 1, 2015, Rhode Island now imposes a realty conveyance tax on the transfer of controlling interests in a "real estate company," in addition to any other state taxes. Under prior law, if a person or business...more
HMRC provides guidance on the implications of the recent case Anson v Revenue and Customs Commissioners.
Delaware limited liability companies (LLCs) are regularly seen in many international corporate groups, including in...more
One of the most important factors to consider in any business succession plan is the timing of the transition of ownership. Whether a sale or a gift (or combination of the two), no transition should occur before the next...more
Editor's Overview -
It has been a little more than one year since the U.S. Supreme Court altered the legal landscape for litigating ERISA breach of fiduciary duty claims relating to the investment in employer stock...more
Executive Summary -
Her Majesty's Revenue & Customs (HMRC) has now published its response to the U.K. Supreme Court's recent judgment in Anson v HMRC. The response confirms that HMRC will continue its existing practice...more
North Carolina's General Assembly is continuing the overhaul of the State's tax system that it began in 2013. That year, the General Assembly slashed corporate and individual tax rates, eliminated many income tax deductions...more
The Ministry of Planning and Investment (MPI) is the central administrative body that oversees all investment...more
The IRS recently issued a Private Letter Ruling (PLR) clarifying that an individual investor in a net-metered community solar project may claim the federal residential Investment Tax Credit (ITC) under Section 25D of the...more
The Pennsylvania Department of Revenue has announced that it will soon begin identifying pass-through business entities that have under-reported income, failed to file PA-20S/PA-65 Information Returns, and failed to maintain...more
The Surface Transportation and Veterans Health Care Choice Improvement Act of 2015 (the "Act") was signed into law by President Obama on July 31, 2015. Under the Act, the due dates for certain federal income tax returns were...more
September Interest Rates for GRATs, Sales to Defective Grantor Trusts, Intra-Family Loans and Split Interest Charitable Trusts -
The September § 7520 rate for use with estate planning techniques such as CRTs, CLTs,...more
The Thai government regulates foreign direct investment by requiring foreign investors to obtain approval from the...more
Florida has long been known as a tax friendly state for retirees. The "Sunshine State" has no income tax on individuals and no estate taxes. The state has quite a different reputation for commercial real estate investors who...more
With the top tax bracket at nearly 40 percent, Indian tribes making substantial per capita distributions are asking what they can do to reduce their members' tax liabilities. One option to consider is a deferred per capita...more
On September 9, 2015, the IRS released long-awaited proposed regulations under Internal Revenue Code (Code) section 2801, which imposes a tax on the recipient of a gift or bequest from certain individuals who relinquished...more
This fall, the Arizona Department of Revenue (ADOR) and the City of Tucson (Tucson) are offering tax amnesty programs that can help taxpayers resolve their outstanding tax liabilities from unreported or underreported income....more
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Upcoming Events
Found 52 single-day events and 29 ongoing events
Events for Saturday, October 10, 2015
Michael Morse, the author of "Mr. Wilson Makes It Home," which tells the story of one dog's journey from a shelter to a home, will be at the Friends of Homeless Animals RI Fall Adoption event. The …
Posted 10/7/15 10:59 AM |9 views
Join The North Central Chamber of Commerce at the Grand Opening Ribbon Cutting Ceremony at Sherwin Williams on Saturday, October 10th at 12:00! Check out the new store, the team at Sherwin Williams …
Posted 9/28/15 09:35 AM |1 view
Free family event. Nearly 200 artists of all ages put chalk to concrete to create drawings on the floor of the downtown skating rink. Judges award prizes in a variety of categories. People can …
Posted 9/18/15 02:21 PM |3 views
Lots of dancing, lots of fun! (No jeans please) 7:15pm Quickstep Lesson 8:00 - 11:00pm Ballroom Dancing. Light refreshments served. $15.00 General Admission …
Posted 9/16/15 04:02 PM |3 views
Events for Tuesday, October 13, 2015
Maximizing Your Social Security Benefits: This is an educational and overview session to help married couples learn how to maximize their Social Security Income. Presentation is hosted by Brendan …
Posted 9/17/15 03:35 PM |4 views
This is an educational and overview session to help married couples learn how to maximize their Social Security Income. Presentation is hosted by Brendan Murray, President of Health & Wealth, Inc and …
Posted 10/1/15 02:52 PM |1 view
Events for Wednesday, October 14, 2015
October 14 at 4:30pm Regular genealogy meeting: will be discussing Native American Indian genealogy - the Massasoits October 14 at 5:30pm Learn more about Native American …
Posted 9/26/15 11:10 AM |1 view
Come and learn about the program and the benefits of joining! Such as discount saving, food discounts, and more!
Posted 9/23/15 02:30 PM |4 views
Kevin Connolly @ Norey's, Newport Oct 14 8:30PM FREE with brother Jim Connolly. No reservations on Wednesdays, so come early for dinner and get a great seat. Kitchen open until 10PM. Come …
Posted 10/8/15 01:28 PM
Kevin Connolly @ Norey's, Newport Oct 14 8:30PM FREE with brother Jim Connolly. No reservations on Wednesdays, so come early for dinner and get a great seat. Kitchen open until 10PM. Come …
Posted 10/8/15 01:28 PM |1 view
Ongoing Events
Sunday, Thursday, Friday, and Saturday from Thursday, October 1, 2015 through Sunday, October 11, 2015
A play is performed on the shore of a lake. Its young idealistic author is devastated when his work is mocked by his family and friends. Passions and jealousies rise as his beloved gives her heart to …
Posted 9/23/15 10:08 PM |4 views
Saturday, October 10, 2015 through Monday, October 12, 2015
CHARLESTOWN'S GENERAL STANTON INN FLEA MARKET CELEBRATES THE CLOSE OF ITS 2015, 50TH ANNIVERSARY SEASON WITH 3-DAY FALL FLEA FEST THIS COLUMBUS DAY WEEKEND, OCTOBER 10,11,12 Charlestown's …
Posted 10/9/15 11:15 AM |3 views
Friday, October 16, 2015 through Sunday, October 18, 2015
Family Weekend Dance, produced by Michelle Bach-Coulibaly, presents a weekend of new and established dance performances. This eclectic event runs October 16 – 18 and will be held in the intimate …
Posted 9/23/15 10:17 PM |2 views
Tuesday from Tuesday, September 22, 2015 through Tuesday, October 20, 2015
Tuesdays, Sept. 22 - Oct. 20 at 6:30 pm Families with children ages 4 and older are invited to enjoy books, songs, rhymes and literacy activities. Please register at 231-4980 x5.
Posted 8/24/15 03:25 PM |4 views
Monday, October 19, 2015 through Wednesday, October 21, 2015
The First Party Claims Conference (FPCC) is a nationally recognized provider of education specifically designed for adjusters, public adjusters, attorneys and others in the first party property …
Posted 8/4/15 09:03 AM |33 views |2 comments
Tuesday, Wednesday, and Thursday from Wednesday, September 23, 2015 through Thursday, October 22, 2015
Wednesday Sept. 23 to Thursday Oct. 22 Please note certain ages on certain days. Tuesdays - 0 to 3 years old @ 10:30 am Wednesdays - 3 to 5 years old @ 10:30 am Thursdays- …
Posted 8/24/15 03:04 PM |6 views
Saturday, October 24, 2015 through Sunday, October 25, 2015
Nineteen artists residing in the West Bay of Rhode Island will open their studios to the public for this free two day event. Communities include Warwick, East Greenwich, North Kingstown, Exeter and …
Posted 9/21/15 09:45 AM |3 views
Tuesday from Tuesday, October 6, 2015 through Tuesday, October 27, 2015
PROVIDENCE—EPOCH Assisted Living on Blackstone Boulevard will host Tai Chi classes for seniors at 10 a.m. on Tuesdays in October. Dates include Oct. 6, 13, 20 and 27. These classes will be led by …
Posted 9/25/15 01:47 PM |5 views
Tuesday, Wednesday, and Thursday from Tuesday, October 27, 2015 through Thursday, October 29, 2015
Tues. Oct. 27 at 10:30 am and 6:30 pm; and Wed. Oct. 28 and Thru Oct. 29 at 10:30am Stories, songs, puppets and fun activities. Kids are encouraged to come in costume and parents …
Posted 8/24/15 04:23 PM |9 views
Thursday and Friday from Thursday, October 29, 2015 through Friday, October 30, 2015
Enjoy this enchanting walk through the woods, to view hundreds of hand carved pumpkins. Roast a marshmallow at the start and then take a leisurely stroll down the pumpkin walk. Great for young …
Posted 9/11/15 06:33 AM |58 views
Saturday, August 8, 2015 through Saturday, October 31, 2015
CORPORATE CARES DAYS - HELP BEAUTIFY THE JCS CORRIDOR & ARBORETUM Let's plan ' A Corporate Cares COMMUNITY Day' - with JCS Members from the Kent County Alumni Chapter - would be working …
Posted 8/3/15 04:32 PM |5 views
Monday, Wednesday, Friday, and Saturday from Friday, May 1, 2015 through Saturday, October 31, 2015
Hear stories of entrepreneurship, African American heritage, and religious diversity during Newport's colonial period. reservations recommended. $15 per person
Posted 4/1/15 03:15 PM |12 views
Sunday, Thursday, Friday, and Saturday from Thursday, November 5, 2015 through Sunday, November 15, 2015
The Road Weeps, The Well Runs Dry, a play written by Visiting Lecturer in Playwriting at Brown, Marcus Gardley, presents a story of a spirituality, identity, migration, and growth. Surviving …
Posted 9/23/15 10:12 PM |4 views
Thursday, November 19, 2015 through Sunday, November 22, 2015
Brown University's department of Theatre Arts and Performance Studies present its annual Fall Dance Concert, produced by Julie Adams Strandberg and Body & Sole. Unless otherwise noted, …
Posted 9/23/15 10:20 PM |3 views
Friday from Friday, January 9, 2015 through Friday, November 27, 2015
Bring Your Own Improv (BYOI) is now in its eighth season! This interactive improv show welcomes voluntary audience participation! You can participate in one of three ways: Applaud at a scene you …
Posted 12/30/14 04:50 PM |18 views
Friday from Thursday, January 1, 2015 through Friday, November 27, 2015
Bring Your Own Improv (BYOI) is now in its eighth season! This interactive improv show welcomes voluntary audience participation! You can participate in one of three ways: Applaud at a scene you …
Posted 12/30/14 04:59 PM |15 views
Thursday, December 3, 2015 through Sunday, December 6, 2015
Brown Theatre presents the premiere of The Red Paint, a new play written and directed by Brown University undergraduate, Nikteha Salazar '16. Unless otherwise noted, performances begin at …
Posted 9/23/15 10:23 PM |3 views
Monday from Monday, September 28, 2015 through Monday, December 7, 2015
Social dancing seen in pubs and at festivals in Ireland. Instructors are Barry and Pat Callahan. Beginners welcome. Partner not necessary to participate.
Posted 9/21/15 02:54 PM |2 views
Sunday and Saturday from Saturday, October 10, 2015 through Thursday, December 31, 2015
Take a 90-minute scenic ride down the Pawcatuck River into Little Narragansett Bay for the peaceful views of beautiful fall foliage and a glimpse of some our winter harbor seal visitors as they rest …
Posted 10/7/15 12:29 PM |1 view
Wednesday from Wednesday, April 22, 2015 through Wednesday, December 30, 2015
Ladies of the Rolling Pin, Rhode Island's only Women's Border Morris Dance team, is looking for new dancers and musicians. You no longer have to run away to join the circus to have this much fun and …
Posted 4/18/15 08:18 AM |20 views
Sunday, Thursday, Friday, and Saturday from Thursday, March 3, 2016 through Sunday, March 13, 2016
Mischief meets merriment in this fresh re-imagining of Shakespeare's most popular romantic comedy. Unless otherwise noted, performances begin at 8pm, Thursday to Saturday. Sunday matinees …
Posted 9/23/15 10:28 PM |1 view
Sunday and Saturday from Saturday, March 5, 2016 through Sunday, April 10, 2016
Enjoy a 75-minute scenic boat ride down the Taunton River into Mt. Hope Bay on the lookout for visiting winter harbor seals and early spring wildlife. Expert guides will help your spot our winter …
Posted 10/7/15 12:45 PM |1 view
Sunday, Wednesday, Thursday, Friday, and Saturday from Thursday, April 7, 2016 through Thursday, April 14, 2016
Written by Anne Washburn Directed by Connie Crawford Unless otherwise noted, performances begin at 8pm, Thursday to Saturday. Sunday matinees at 2pm. Tickets: $15 ($12 seniors, $7 …
Posted 9/23/15 10:32 PM |3 views
Sunday, April 17, 2016 through Monday, April 18, 2016
Written by Anne Washburn Directed by Connie Crawford Tickets: $15 ($12 seniors, $7 students). For ticket sales and more information: call (401) 863-2838, or visit the Box Office in the …
Posted 9/23/15 10:37 PM |2 views
Sunday and Saturday from Saturday, November 14, 2015 through Sunday, April 24, 2016
Join us aboard one of our education vessels as we motor through historic Newport Harbor and take in 360º views of seals resting on Citing Rock off of Rose Island and the Newport Bridge. One-hour …
Posted 10/7/15 12:40 PM |1 view
Thursday, May 5, 2016 through Sunday, May 8, 2016
Produced by Julie Adams Strandberg Tickets: $15 ($12 seniors, $7 students). For ticket sales and more information: call (401) 863-2838, or visit the Box Office in the Leeds Theatre Lobby (83 …
Posted 9/23/15 10:39 PM |2 views
Saturday from Saturday, October 10, 2015 through Saturday, May 28, 2016
Family Performance Series September 12th - May 28th Saturdays at 11am-12pm Let us entertain you with Magic, Puppet Shows, Music, Theater, Storytelling, Improv and more! Pay …
Posted 10/8/15 05:46 PM |1 view
Thursday from Thursday, November 14, 2013 through Thursday, December 1, 2016
TOPS (Take Off Pounds Sensibly) Rhode Island Chapter #38 East Greenwich meets every Thursday at the Women & Infants Center, 1050 Main Street, East Greenwich. Weigh-in begins at 9 AM and runs until …
Posted 11/9/13 06:24 AM |126 views |1 comment
Saturday from Saturday, June 13, 2015 through Friday, June 1, 2018
Join us on Saturdays, from 11:00 to 2:00. We have men's, women's, and children's good, clean, used, and new clothes. We also have many other types of items like shoes, toys, dishes, and small …
Posted 6/8/15 01:56 PM |19 views


text:
Reach tens of thousands of people instantly by advertising with Ekklesia. Find out more
Questions have been raised over the UK Government's awareness of the number and identity of British citizens on death row in Pakistan as executions recommence.
Over 230 prison officers are being asked to work in other prisons in the run-up to Christmas as governors in England and Wales face a major staffing crisis.
Many prisoners likely to be executed in Pakistan as executions resume were convicted of crimes that bear no relation to a terrorism threat, says legal charity Reprieve.
UK taxpayers' money has enabled around 2,917 executions in Iran and more than 112 pending death sentences in Pakistan, says a report from legal charity Reprieve.
The final report of Brazil's National Truth Commission has been hailed as an historic step towards justice for victims of the county's military dictatorship.
A US Senate report revealing widespread use of torture by the Central Intelligence Agency has stirred up heated debate. International human rights activists have called for those responsible to be held to account, though CIA director John Brennan has defended the agency's record.
The Obama administration has today appealed against a federal judge's ruling that videotapes showing force-feeding of a Guantanamo prisoner should be released.
A mass trial for almost 500 people is about to resume in Egypt which may see death sentences handed down to the defendants, including an Irish teenager arrested last year.
The Missouri Grand Jury's absolution of a police officer for the fatal shooting of Michael Brown spotlights concerns on institutionalised discrimination in the US, says UN rights chief.
A Tunisian national has been released from Guantánamo Bay after 13 years imprisoned without charge or trial.


text:
|Número de publicación
|Tipo de publicación
|Número de solicitud
|Fecha de publicación
|16 May 2002
|Fecha de presentación
|9 Nov 2001
|Fecha de prioridad
|10 Nov 2000
|También publicado como
|Número de publicación
|Markus Andreasson
|Cesionario original
|Markus Andreasson
|Exportar cita
|BiBTeX, EndNote, RefMan
|Citas de patentes (10), Citada por (23), Clasificaciones (6), Eventos legales (8)
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet
[0001] The present invention relates to methods and devices for automatic application of an address on an item of mail.
[0002] In spite of the fact that modern electronic communication technology makes possible practically instantaneous contact between people, traditional printed publications, such as newspapers, trade publications and magazines, continue to be an important medium for the transmission of information. In addition to being a provider of information from a publisher to readers, many publications can also contain channels for transmission of information in the opposite direction, from the reader to the publisher or advertiser, such as order forms or order coupons.
[0003] Order forms are often used by advertisers to make possible simple ordering of a product or further information, by the reader writing an order on the form, for example ticking an order option, writing his name and address and sending the form in a stamped envelope through the normal postal channels to, for example, the advertiser or some other specified recipient.
[0004] Mail order catalogues and the order forms included in these are another example of an area of application where the present invention can advantageously be used.
[0005] In spite of the obvious disadvantages of this method of communication, for example the fact that the reader/person placing the order must post a physical item of mail in a post box intended for the purpose, there has been no significant simplification of the mail handling procedure for a long time.
[0006] An object of the present invention is therefore to remedy said problems from a number of different aspects. This is achieved by a method according to claim 1, a computer program according to claim 7, a device according to claim 8 a storage medium according to claim 14 and a computer according to claim 15.
[0007] Thus a first aspect of the invention is a method for addressing an item of mail. The method comprises obtaining address information, preferably utilizing one or more suitably programmed computers, where the address information comprises a digitally represented graph of a handwritten address, written by a user. In addition, the method comprises automatically providing the address information to a device adapted to apply the address information on the item of mail.
[0008] A suitable way of obtaining the address information is via a wireless interface from a mobile communication unit, connected to a digitizing pen via, for example, a further wireless interface such as the standardized interface Bluetooth. A digitizing pen suitable for this purpose can generate a data sequence which, by means of suitable coding, represents the pen's instantaneous position in a coordinate system.
[0009] Such a pen is disclosed in the publication WO 01/26032, which comprises a device for position determination is shown. The pen reads a position-coding pattern which has a number of intrinsic advantages. Other examples of digitizing devices comprise those which calculate the movement of a digitizing pen when handwriting is carried out, by means of acceleration sensors or by means of radio-based or ultrasound-based triangulation devices or by means of devices similar to trackballs. The present invention assumes only that a data sequence of position coordinates is obtained, where the data sequence represents a graph of the movement of the pen when writing an address.
[0010] The information obtained is then preferably printed out on an item of mail such as a letter, postcard or address label intended for a parcel. This printout has thereby essentially the same appearance as the originally handwritten address. If required, certain processing can be carried out on the address information obtained, i.e. the sequence of movement coordinates for the pen, for example with the aim of making the handwriting clearer or evening out digitizing effects.
[0011] Other aspects of the invention are devices such as a computer that comprises means for carrying out program instructions in accordance with the method according to the invention, and also storage mediums that contain software comprising program instructions intended to be executed for the implementation of the method according to the invention.
[0012] Other objects, features and advantages of the invention will become apparent from the following detailed description of embodiments of the invention with reference to the drawings.
[0013]FIG. 1 is a schematic view showing a system in which a method according to an embodiment of the invention is implemented.
[0014]FIG. 2 is a schematic view and shows a flow diagram for the implementation of a method according to the invention.
[0015] Below, a detailed description of a method and a device for addressing an item of mail according to the invention will be given.
[0016] The starting point is a user who reads an advertisement in a magazine that gives the opportunity to order, for example, a brochure or other information about the company or advertiser. The advertisement is printed on a surface in the magazine that is at least partly provided with a position-coding pattern according to the above-mentioned publication WO 01/26032. The user puts a tick or a cross in a box to order the brochure and writes the address to which the brochure is to be sent. The writing is carried out using a digitizing pen with a pen point, exemplified, as already mentioned, by the device in the publication WO 01/26032. A digitized and coded information quantity, representing the graph followed by the pen when writing, is sent from the pen via a radio interface, for example Bluetooth, via the user's mobile phone to the company that had the advertisement printed in the magazine and that is allocated the part of the position-coding pattern to be found in the advertisement.
[0017] The digitizing pen thus sends the address information via the mobile phone and the Internet to the company's computer or server. Other modem-connected devices can also be used. Software in the pen sends the coded information quantity to the company using standardized data transmission procedures, in real time or at a later time, via a mobile telephone network operator's server or similar server installation connected to the Internet. The company thereby obtains for its information management system the address information entered by the user.
[0018] The handwritten address is then printed out by the company's information management system on, for example, an item of mail or on an address label that is attached to the item of mail, and the item of mail is then sent to a postal service of traditional type. A postman at the postal service then reads the address on the item of mail in the normal way and delivers it to the recipient, i.e. the user who placed the order.
[0019] A major technical advantage of the invention as discussed above in these different aspects is that the handling of items of mail is simplified, more rapid and more reliable. In particular, the invention involves the simplification that the handwritten text, i.e. the address that is to be attached to the item of mail, does not need to be analyzed at any stage by, for example, processing-intensive optical character recognition (OCR). Even though OCR technology is well-known and frequently used, it is principally intended for the recognition of printed text. The recognition of handwritten text (ICR, intelligent character recognition) is, on the other hand, still very difficult and often generates unreliable results and requires the computers that are carrying out the processing to have a relatively large amount of processing power. Thus, in the present invention, it is a postman who interprets the address information that was written by the user. The requirement for the address information to be legible is the responsibility of the user/person placing the order, instead of the company. The fact that the postman interprets the information is, however, an advantage, as even carelessly written addresses can usually be deciphered.
[0020] A further advantage is that the handling of the address information within the company can be carried out completely automatically and is transparent to the company. That is, manual interference can be avoided and hence the addressing procedure can be seen, from the point-of-view of the user, as a conveniently available remote-control address label printer.
[0021] The advantageous simplification afforded by the invention has in turn the more commercially-oriented advantage that it is easier for an advertiser or publisher of a publication to tempt or persuade a reader/person placing an order to order a product or information, for example.
[0022]FIG. 1 shows schematically the communicating units in the embodiment and, to a certain extent, brief explanations of the signals that are sent between the units.
[0023] A user 100 reads a publication 101 in which an advertisement 102 is printed on one of the pages in the publication 101. The surface on which the advertisement 102 is printed has been provided with a position-coding pattern (not shown in the figure) as described in WO 01/26032. At least the part of the advertisement 102 that contains an order coupon 103 has been provided with the pattern. The position-coding pattern is unique over a very large area, which enables one or more parts of the area to be reserved by and thereby to be allocated to the company or the advertiser that had the advertisement printed.
[0024] The user 100 finds that he is interested in obtaining more information from the advertiser who had the advertisement 102 printed, and so he fills in his name and address on the order coupon 103 in a writing step 201, using a digitizing pen 105 provided with a pen point. If he knows that a friend needs the information, he writes the friend's address.
[0025] After having written the name and address, the user 100 makes a mark with the pen 105 in a send box 104 on the order coupon 103. The digitizing pen 105 has functions for reading off the position-coding pattern along the graph 120 that the point of the pen 105 makes when the user writes his name and address on the order coupon 103. The read-off and digitized graph 120 comprises a data sequence of position coordinates and is sent in coded form, after having been coded in a suitable way in a coding step 202, via a radio interface 106 and onwards via a mobile terminal 107 owned by the user 100, to a server, via the Internet. The mobile terminal thus acts only as a modem for the pen. The user 110 making a mark in the send box 104 initiates the transmission that is carried out in a sending step 203. The server contains information about which company is allocated the pattern in the send box and ensures that the digitized graph 120 is forwarded via a radio interface such as GSM/GPRS, via a mobile communication network 109, to a computer 110, where the graph 120 is received in a receiving step 204.
[0026] The received, digitized and coded graph 120 is decoded in the computer 110 in an identifying step 205 where the allocation to the advertiser has been carried out in the above-mentioned server.
[0027] If required, the graph 120 can be analyzed and improved with regard to legibility and edge definition, after which the graph 120 is printed out in a printing step 206 using a printer 111 connected to the computer 110. The printout 113 can be in the form of an address label intended to be attached to an item of mail or in the form of a direct printout 113 on an item of mail 112. To make the process fully transparent at the server side, in case the address was written on an address label, the label is automatically attached to an item of mail. Thus, no manual intervention is needed at the server side. The only manual step is the writing of the address at the advertisement by the user.
[0028] The printout 113, showing the address written by the user 110, is interpreted in the traditional way by a postman 114 who delivers the item of mail 112 to a mailbox 115 that is located, for example, at the premises of the user 110.
[0029] The method can comprise carrying out all the described steps in real time and an address label can be printed out more or less immediately when the user writes with the pen, so-called remote printout on-line. However, the method preferably comprises delaying the transmission of the address information during one or more of the steps. For example, it can be assumed that a user will use the invention in places where communication with a server via the Internet is impossible, such as when the user's mobile phone is incapable of communicating or is not available. In such cases, the delay can involve a buffering of the information in the pen. In other cases, the information can be buffered on the Internet and, in yet other cases, the server/computer can delay the printing-out of the address information.
[0030] The method as described above is suitably implemented by a person skilled in the art using the programming tools that are available in the known technology and using the information that is to be found in publication WO 01/26032, the technical contents of which is incorporated in the present specification by reference.
[0031] The various steps of the method that are described above can be combined in a different sequence and in a different way to that described. Such combinations that are obvious to a person skilled in the art who reads this description are intended to be included within the scope of the invention. The invention is limited only by the appended claims.
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|Clasificación de EE.UU.
|Clasificación internacional
|Clasificación cooperativa
|Clasificación europea
|8 Ene 2002
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text:
PLAIN2015 conference, Dublin
Congratulations to PLAIN and NALA (the National Adult Literacy Agency in Ireland) on a fantastic conference held in Dublin, Ireland. For more information on the conference visit the PLAIN2015 website.
Clarity is a worldwide network of professionals who are committed to promoting plain legal language. With more than 650 members from 50 countries, Clarity is the largest international plain language organization
Malachy Hargadon discusses the challenges of the plain language campaign within the European Commission. Malachy is an editor and Clear Writing Campaign co-ordinator in the European Commission. He will explain origins and progress of the campaign for clarity within the EU. Time: 8 October 2015, 8.15 – 9:35am Location: Central London […]
Clarity has members all around the world. Contact your country representative to connect with Clarity members in your country. You can find their details on our board page.


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Factor 5 were working on a Superman game for Brash Entertainment, but after Brash went out of business in november 2008, the project was probably cancelled. It was going to be released for the Xbox 360 and Playstation 3.
During development, the game had the project title "Blue Steel", whereas one of their Wii titles was called "Blue Harvest".
Thanks to Fork for the contribution!
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Salesforce Lightning Component Sample SPA
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text: Music from Portugal – The Black Mamba October 8, 2012 "The Black Mamba" is the name of the trio – Pedro Tatanka (vocals and guitar), Ciro Cruz (bass) and Miguel Casais (drummer). "The Black Mamba", the first album of originals, was released on May 7. "It ain't you" is the debut single. Please shareLike this:Like Loading... Related


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Chef'sChoice new
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Chef'sChoice Premium Electric Food Slicer
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Budget-friendly slicer delivers everything from paper-thin slices of turkey breast to thick-cut roast beef in seconds. The powerful, high-torque motor and reliable, smooth gear operation will have you slicing with ease and confidence, while user-friendly features such as precision thickness control, a tilted, high-capacity food carriage, and removable, easy-to-clean components ensure that this handy slicer will have a place in your kitchen for years to come.
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College Men
By The Numbers: Brickyard Collegiate, 5
Wednesday, October 2, 2013
Five is the number heading into the Brickyard Collegiate, which starts Friday at Brickyard Golf Course in Macon, Ga., as five individuals ranked inside Golfweek's top 20 are set to compete.
South Florida's Chase Koepka (No. 5), Georgia's Joey Garber (No. 6), Florida State's Jack Maguire (No. 11), Georgia Tech's Ollie Schniederjans (No. 16) and Virginia Tech's Scott Vincent (No. 18) will all tee it up.
In addition, five teams in the top 25 are in the field: Georgia (No. 3), Georgia Tech (No. 4), Georgia Regents-Augusta (No. 13), Virginia Tech (No. 14) and Florida State (No. 23).
Click here for the updated Golfweek/Sagarin College Rankings.
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The Top 10 In Action Sports
01Kenton Cool And The Legend Of Everest
02The Martyn Ashton Interview: Meet the Man Who Got Back on the Bike
03Legends Behind the Lens: The Dan Milner Interview
04We Asked Surf Star Coco Ho For Her Step-by-Step Guide to the Basics
05The Tony Hawk Interview: How Is The Birdman Still Flying High After All These Years?
06We Toured Britain's Action Sports Hotspots With The New Ford S-MAX
07The Legend Of El Dorado: One Man's Obsession With Finding A City Made Of Gold
08I Am Legend: How Audiences – Real Or GoPro'ed – Can Affect Your Mind And Performance
09Watch A Freerunning King Defy The Laws Of Gravity In This Urban Assault On London
10Living On The Blood and Urine of Dead Sea Turtles: The Shocking Story of A Sailor Stuck in Hell
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A Mountain Biking video by naki_dher - 32,970 views
WynTV heads to Queenstown for the first round of the MTBNZ DH Cup at the Remarkables and then hit up a bit of riding down there too at the Outside Sport Pumptrack jam and a few laps on the Skyline Gondola with the boys.
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NASHVILLE's Chloe Bennet Joins Whedon's S.H.I.E.L.D.
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December 22, 2014
ABC has tapped NASHVILLE's Chloe Bennet for Joss Whedon's upcoming AVENGERS-inspired series S.H.I.E.L.D., The Hollywood Reporter announced.
Bennet is reportedly filling the last 'regular' role in the drama, taking on the role of 'Skye,' a "confident woman who is slightly obsessed with superhero culture and the shadow organizations that exist within it."
She joins the previously announced Ming-Na (ER), Clark Gregg (THE AVENGERS), Brett Dalton (KILLING LINCOLN), Elizabeth Henstridge, and Ian De Caestecker in the ensemble series.
S.H.I.E.L.D. stands for the Strategic Homeland Intervention, Enforcement and Logistics Division, a covert, quasi-military peace-keeping organization which was featured in this summer's Avengers movie, and is a long-time staple of the Marvel universe.
The project was written by Whedon, his bother Jed Whedon and Maurissa Tancharoen and is based on a collection of Marvel comic books. There have been no details as to which Marvel characters will be featured in the TV version. On the big screen, the organization included overseer Nick Fury, Captain America, the Hulk, Black Widow, Tony Stark and Thor.
S.H.I.E.L.D. is expected to premiere in Fall 2013.
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text:
DNA copy number aberration (CNA) is one of the key characteristics of cancer cells. Recent studies demonstrated the feasibility of utilizing high density single nucleotide polymorphism (SNP) genotyping arrays to detect CNA. Compared with the two-color array-based comparative genomic hybridization (array-CGH), the SNP arrays offer much higher probe density and lower signal-to-noise ratio at the single SNP level. To accurately identify small segments of CNA from SNP array data, segmentation methods that are sensitive to CNA while resistant to noise are required.
We have developed a highly sensitive algorithm for the edge detection of copy number data which is especially suitable for the SNP array-based copy number data. The method consists of an over-sensitive edge-detection step and a test-based forward-backward edge selection step.
Using simulations constructed from real experimental data, the method shows high sensitivity and specificity in detecting small copy number changes in focused regions. The method is implemented in an R package FASeg, which includes data processing and visualization utilities, as well as libraries for processing Affymetrix SNP array data.
Most human cancers are characterized by genomic instabilities. In-depth knowledge of genomic aberrations has important clinical values in diagnosis, treatment, and prognostics of cancer [1]. Genomic aberrations can be analyzed using a variety of high-throughput genetic and molecular technologies, such as array-based comparative genomic hybridization (array-CGH) [2] and SNP array-based copy number analysis [3]. A number of methods have been developed to perform smoothing and/or to detect edges of segments containing one consistent copy number [4-23], some of which were compared and summarized by Lai et al. and Willenbrock et al. [24,25].
High-density array platforms, e.g. SNP array, provide the opportunity to identify genomic aberrations that localize to small segments of the chromosome, which we refer to as focused CNA in this paper. To analyze the DNA copy number of a disease sample, the matched normal DNA can be used as a reference for the computation. While this approach yields relatively low noise, such a matched normal DNA sample is often unavailable. By using the existing SNP array data libraries derived from large numbers of normal samples, disease samples can now be analyzed without paired normal samples [14,26]. However, proper handling of the data is necessary to lower the noise and avoid identifying large numbers of false-positive CNA segments. One way to achieve this goal is to reduce noise at the probe level, by selecting probes based on dose response to copy number change [26] or sequence properties [27]. Another approach is to apply data smoothing and segmentation methods with high sensitivity and specificity. While most methods designed for array-CGH data can potentially be applied, their parameters may need to be fine-tuned to adapt to the different characteristics of the SNP array data. Here we present a test-based data segmentation method. In our algorithm, each chromosome is first broken into small segments through an over-sensitive edge detection mechanism. The consecutive segments are then iteratively merged by local testing, using a forward-backward edge selection scheme, until all remaining edges pass a significance threshold. The data sets used in this study were generated with Affymetrix GeneChip® Mapping 50 K Xba arrays on two model cell lines with known genomic alterations and two tumor DNA samples of oral squamous cell carcinoma.
Results and discussions
The SNP array results on two model cell lines were generated as described in the Methods section for the development and testing of our algorithm. The cell lines used here were GM03226 with a known trisomic aberration segment in chromosome 9 [9pter > q11], and GM00870 with a known single copy deletion segment in chromosome 9 [9pter > p21]. The data was first processed with Copy Number Analysis Tool (CNAT 3.0) from Affymetrix Inc, which utilizes Huang et al.'s method to estimate SNP-level copy numbers based on libraries of normal samples [14]. We chose CNAT because of its widespread use for the analysis of SNP array data. Better data pre-processing methods [26,27] may lead to better results than reported here. Following the CNAT process, the SNP-level copy number values were log2 transformed to achieve near-normal distributed copy numbers. The mean and standard deviation (SD) for the signals from one, two and three copies were defined based on knowledge of the cell lines. We found that normal two-copy DNA yielded a mean of 1.03 and SD of 0.77; single-copy DNA yielded a mean of 0.25 and SD of 0.63; and three-copy DNA yielded a mean of 1.45 and SD of 0.91. Compared to single-copy DNA, three-copy DNA has a mean that is closer to two-copy DNA, and a larger standard deviation. Hence three-copy aberrations are harder to detect than single-copy aberrations.
Simulated chromosomes with focused CNA were constructed based on the SNP array results on model cell lines (GM03226 and GM00870) as described in the Methods section. An algorithm which is effective in identifying focused copy number aberrations was developed and tested based on these simulated chromosomes. In the following text, we refer to the algorithm as FASeg (fragment assembling segmentation), which is also the name of the R package. The work flow is illustrated in Figure 1. The optimal parameters for focused CNA detection were determined based on the simulated chromosomes. Preliminary testing was also performed using the simulated chromosomes.
Figure 1. An illustration of the workflow of the forward-backward fragment assembling (FASeg) method.
There are two major parameters that influence the results of edge identification. One is the span of the initial smoothing. The other is the p-value cutoff to define the significance of each edge. In our algorithm, the smoothing span is expressed in terms of number of SNPs. After dividing by the total number of SNPs in a chromosome, it is transformed into the α value in the LOESS smoothing of the data, which controls the degree of smoothing. Six span values, 25, 50, 75, 100, 150, and 200 were tested in simulations using a range of p-value cutoffs (Table 1). We tested 36 different combinations of CNA segment size, CNA copy number and normal segment size using simulation. For each combination, 100 simulated chromosomes were analyzed. Because of the high noise level in the data, we allowed a tolerance distance of 5 SNPs when matching true edges with identified edges. For each simulation setting, the sensitivity was plotted against the false-discovery rate (FDR) to show the performance (Figure 2). We found that the smoothing span values of 25 and 50 performed similarly in most cases. The smoothing span of 25 was chosen as the default value.
Table 1. Parameters tested for the seven R packages
Figure 2. The effect of smoothing span on the sensitivity to detect CNA segments. Every sub-plot is based on 100 simulated chromosomes, each harboring 6 normal segments and 5 CNA segments. Ten alpha levels were examined at each smoothing span.
To evaluate the performance of FASeg in the context of existing methods, we ran the simulation together with six other methods (Table 1), all of which are implemented in R packages. Three of the methods could be easily tuned to change the sensitivity. They include the Hidden-Makov Model-based method in the aCGH package [23], the Circular Binary Segmentation method in the DNAcopy package [10], and the Gain and Loss Analysis of DNA method in the GLAD package [15]. For each of these packages, we identified the most influential parameter and tested 10 values around the default of the parameter in an attempt to improve its performance on noisy data (Table 1). Three other packages do not have obvious tuning parameters. They include two Hidden Markov Model-based methods in the RJaCGH package [21] and the snapCGH package [20] (referred to as BioHMM), and the dynamic programming-based method by Picard et al. [11] (referred to as Picard) which was run through a wrapper function in the snapCGH package. A total of 36 different combinations of CNA segment size, CNA copy number and normal segment size were tested. We compared the performance of the seven packages by plotting the sensitivity against FDR (Figure 3). We noticed that most of the methods tested here did not show the typical monotone ROC type of curve. The results indicated that FASeg was particularly sensitive to CNA segments that were small in size and low in signal-to-noise ratio (three copies, columns 2 and 5 in Figure 3). GLAD showed similar performance when the flanking normal segments were relatively long (200 SNP markers, column 5 in Figure 3). BioHMM and aCGH performed best when the signal-to-noise ratio was low while the CNA segments and the flanking normal segments were long (column 5 in Figure 3). For situations with relatively higher signal-to-noise ratio (single copy, columns 1 and 4 in Figure 3), most of the methods tested here performed reasonably well, with BioHMM and FASeg leading the performance when CNA segments were relatively small (40 SNP markers or less). With chromosomes that contained multiple CNA segments at different copy numbers (columns 3 and 6 in Figure 3), FASeg, DNAcopy, GLAD and Picard achieved the best performance. One observation is that HMM-based methods tend to be less effective when multiple CNA states were present in a single chromosome. Again we allowed a tolerance distance of 5 SNPs when matching true edges with identified edges. Similar results were obtained when other tolerance values (3 and 7) were used [see Additional file 1]. Additional analyses were performed using the default setting of each package [see Additional file 1]. Because some of the methods tested here were tuned to adapt to data with higher signal-to-noise ratio, the results at default settings may not be representative of the performance shown in Figure 3.
Additional File 1. Supplemental tables and figures. The table showing the performance of the seven R packages at default settings, and the figures showing the performance of the seven R packages using the tolerance distance 3 and 7.
Format: DOC Size: 138KB Download file
This file can be viewed with: Microsoft Word Viewer
Figure 3. The comparison of the performance of seven methodsavailable as R packages. Every sub-plot is based on 100 simulated chromosomes, each harboring 6 normal segments and 5 CNA segments. FASeg, aCGH, DNAcopy and GLAD were each run at 10 parameter settings; Picard, RJaCGH and BioHMM were run at default settings. The parameters used are detailed in Table 1.
An R package, named FASeg, was developed to implement the algorithm. In addition to the core algorithm described above, this package also consists of data pre-processing, visualization and gene-level data summarizing functions. The core function accepts simple matrix input and produces simple matrix output, which makes it easily adaptable for data input from various platforms. The package is available at the FASeg website [28]. Plain-text probe level data exported from Affymetrix GTYPE/GDAS can be read into R in batch mode and converted to a single matrix of raw copy numbers, using a simplified version of the method by Huang et al. [14]. For the Mapping 500 K arrays, currently this is the only mechanism for data input. For the Mapping 100 K array data, plain-text output of raw copy numbers from CNAT can be loaded as an alternative. The raw copy number matrix, which can include multiple array data sets, is processed by the core algorithm to produce segment-wise constant estimates. The expected measurement value corresponding to two copies can be input, which will induce the function to perform further re-scaling of the fitted data based on cluster analysis. The fitted data can be displayed in a few modes: single experiment with raw and fitted values side-by-side (Figure 4A); multiple experiments/single chromosome (Figure 4B); multiple experiments/all chromosomes (Figure 4C). Portions of the data can be plotted by simple matrix manipulation. From the fitted data, gene-level copy number and Cytoband information [29] can be summarized in a table. The table can be collapsed by merging nearby genes that show the same copy numbers in all experiments (Figure 4D).
Figure 4. Sample output of the R-package FASeg. The results were obtained using the smoothing span of 50 SNPs and the alpha level of 10-6. (a) Raw copy number (upper panel) and fitted values (lower panel) of chromosome 9 for data from the Mapping 50 K Xba array, generated from an oral squamous cell carcinoma case (CZ T26). (b) Comparison of the copy numbers for chromosome 9 between four samples. Two primary skin fibroblast cell lines: GM03226 (with a known trisomic segment in chromosome 9 [9pter > q11]; red) and GM00870 (with a known single copy deletion segment in chromosome 9 [9pter > p21]; blue). Two previously uncharacterized oral squamous cell carcinoma cases: CZ T26 (green) and CZ T322 (aqua). (c) Color display of the fitted values of the whole genome for all four samples. From top to bottom: GM03226, GM00870, CZ T26 and CZ T322. The gridlines separate chromosomes lined up in numerical order, with the X chromosome being the last. Black: normal; red: higher; green: lower. (d) A section of the condensed table output containing copy number and Cytoband information for samples GM03226, GM00870, CZ T26, and CZ T322.
The computing speed of the FASeg package was tested against the existing packages listed in Table 1 using the complex cancer sample CZ T26. The average computing time over all parameter settings are reported in Table 2. DNAcopy exhibited the fastest computing speed among the packages tested. GLAD, Picard and aCGH showed similar computing speed, at around 1.7 minutes per sample. FASeg used about 3 minutes. From Figure 2, we observed that FASeg showed similar performance when the smoothing span is 50, as compared to the default value of 25. When the smoothing span of 50 was used, FASeg achieved 1.4 minutes in the speed test. BioHMM and RJaCGH were far behind in terms of computing speed. In the simulations, we noticed that RJaCGH could be much faster when the jump parameters were given.
Table 2. Comparison of computing time*
There is a trade-off between sensitivity and specificity in edge detection. We illustrate the behavior of FASeg in Figure 5, where we applied multiple p-value cutoffs to the model cell line GM03226 and the oral cancer sample CZ T26. Results from the other two samples were similar (data not shown). With the cell line GM03226, which only has a trisomic segment in chromosome 9, we saw that larger p-value cutoffs yielded some false CNA segments that were mostly small in size, while the true trisomic segment was consistently identified (Fig. 5a). With the CZ T26 cancer tissue sample, we observed many small segments when less stringent cutoffs were used (Fig. 5b), while we were unable to judge the validity of the segments. The edges identified using a smaller p-value cutoff were mostly in a subset of the edges identified using a larger p-value cutoff (Fig. 5). When tuning the p-value cutoff parameter, the user can visually examine the raw data around the edges that disappear when the cutoff level is lowered, and decide whether the change of cutoff value is reasonable.
Figure 5. Demonstration of the performance of FASeg at different p-value cutoffs. Fitted values at each p-value cutoff were displayed on the left. The gridlines separate chromosomes lined up in numerical order, with the X chromosome being the last. Black: normal; red: higher; green: lower. (a) GM03226 cell line data; (b) CZ T26 cancer tissue data.
When the intent is not finding focused CNA, or there is a strong prior belief that the CNA segments are not focused, more stringent p-value cutoffs should be used. On the other hand, if the intent is to identify focused CNA, less stringent cutoffs have to be used with the risk of identifying false CNA segments. However, the problem of finding false-positive segments is not as severe as it seems in most applications, where multiple samples are analyzed to identify CNAs over-represented in a subgroup of samples. In such applications, after data segmentation, cross-sample testing is performed to find CNA segments consistent across many samples. False segments at random locations will most likely be inconsistent across samples, hence insignificant in the cross-sample testing.
In summary, we presented an algorithm to find break points in copy number data. It consists of an over-sensitive edge detection step and a test-based segment merging step. After the over-sensitive edge detection step, the segmentation task becomes a model-selection task. In the forward-backward model selection, by using the common segment-wise Gaussian assumption, the backward step is reduced to a manageable local search. The model makes no assumption about the number of CNA states in a chromosome. Thus it provides the flexibility to handle multiple CNA states in a single chromosome, which is important in the analysis of complex cancer samples. In the implementation of this algorithm into a user-friendly R package (FASeg), we optimized the parameters for identifying focused CNA in noisy data. In simulation studies based on real data, FASeg was sensitive to CNA segments that were small in size and low in signal-to-noise ratio. It performed well when presented with complex samples with multiple CNA states per chromosome. From the users' stand point, FASeg is intuitive and easy to tune.
The forward-backward fragment-assembling algorithm
The array-based copy number data consists of a series of N observations {(X1, Y1), ..., (XN, YN)} for each chromosome, in which Xi's are positions along the chromosome and Yi's are log2-ratios in the aCGH data or processed copy numbers from SNP array data. Between any twoconsecutive edges, which remain to be identified, we assume a local constant model with Gaussian error. We apply a two step method for the identification of edges. The first step aims to identify most true edges, at the price of identifying possible false-positive edges. This step is a high sensitivity and low specificity step. In the second step, the goal is to remove the false-positive edges, while retaining the true edges through statistical model selection. Figure 1 shows an illustration of the workflow.
Step 1. Over-sensitive edge detection
To identify all possible edges, we apply an ad hoc method, which is based on one-dimensional differential edge detection. At this step, the actual X values are ignored, because the main interest is to find copy number changes between data points. (1) To reduce noise, a locally weighted regression smoother (LOESS) with Gaussian kernel is fitted through the data Y1,....., YN to generate fitted values Y1',....., YN'. (2) An edge is identified in every maximal monotone increasing/decreasing segment in the LOESS fitted curve. The edge position is assigned between the two observations that span the medium height of the segment (Figure 1). If the height of the segment is below a predefined threshold value, the edge is removed. The threshold value should be set such that copy number changes at or below that level is ignorable. The default value in the FASeg package is 0.1.
Step 2. Forward-backward edge reduction
After step 1, the data is overly fragmented into small pieces. The next step is to merge the fragments by statistical testing. The task amounts to a model selection problem with a large number of candidate predictors (edges). The full model is the model that contains all the edges identified in Step 1. We resort to the forward-backward scheme to quickly reduce the full model to a smaller model containing fewer edges. In the segment-wise constant model, the removal of an edge only affects the likelihood of the data points between the previous and the next edge. Thus a local ANOVA test, or unpaired t-test, is equivalent to the likelihood ratio test for model selection. Also, the removal of an edge only changes the significance of the two neighboring edges. Thus in the backward selection step, only previously removed edges within the segment confined by the two neighboring edges need to be re-examined (Figure 1, green dots).
We first define p-values for all the edges. For each edge, we consider the observations between the previous and the next edges. These observations are spatially divided into two groups by the edge of interest. The unpaired Student's t-test is performed to find the significance of the division, and the p-value is associated with the edge. Second, when the p-values for all the edges are defined, we iteratively remove edges from the least significant one. With the removal of each edge, all previously removed edges around this edge are re-examined. For example, if edge i is being removed, with α edges immediately before edge i and b edges immediately after edge i having been previously removed, then for each edge j ∈ [i - a, i) ∪ (i, i + b], we re-compute its p-value after the removal of edge i. If the lowest of the p-values is smaller than that of edge i, the corresponding edge is reinstated. This process is iterated until all remaining p-values are smaller than a cutoff value. This p-value threshold can be user-defined and may be fine-tuned based on each sample to get the best balance between sensitivity and specificity. After the edge identification, for the segment between two consecutive edges, the median value of Y is taken as the estimate.
DNA samples and the SNP array mapping assay
SNP array data was generated on 2 model cell lines (GM03226 and GM00870) with known genomic alterations and 2 previously uncharacterized oral squamous cell carcinoma samples (CZ T26 and CZ T322). Each sample was analyzed using one array. The model cell lines were obtained from Coriell Cell Repositories/NIGMS [30]. GM03226 are fibroblasts with a trisomic segment in chromosome 9 [9pter > q11], and GM00870 are fibroblasts that are known to have a single copy deletion segment in chromosome 9 [9pter > p21]. DNA labeling, hybridization, washing and staining of the Mapping 50 K Xba arrays were performed according to the standard Gene-Chip Mapping 100 K Assay protocol (Affymetrix). The arrays were scanned using a GeneChip Scanner 3000. The scanned array images were processed with GeneChip Operating software (GCOS) 1.3. The genotype calls and intensity of the SNP probes were generated by GeneChip DNA Analysis Software (GDAS) 1.4. The probe-level intensities were further converted to SNP level intensities using CNAT 3.0.
Simulation based on the real data
The simulation data was generated based on the model cell lines GM03226 and GM00870. We obtained pools of SNP-level copy number values for single-, two-, and three-copy DNA. By resampling from these pools, we constructed copy number readings of the simulated chromosome. Each simulated chromosome contained 11 segments. Probesets were evenly spaced. Thus we use the number of probesets to represent the segment size. Starting from the normal segment, the chromosome construction alternated between normal segments and CNA segments. Six normal segments and five CNA segments were simulated for each chromosome. Within each simulated chromosome, a single normal segment size and a single CNA segment size were used. Two normal segment sizes (40 and 200 SNPs) and six CNA segment sizes (15, 20, 30, 40, 60 and 80 SNPs) were tested. Three settings of aberration levels were tested: (1) all five CNA segments in the chromosome represented single-copy DNA, (2) all five CNA segments were three-copy, (3) the five CNA segments were a mixture of single-copy, three-copy and segments of higher-magnitude copy number changes. No real data was available for the higher-magnitude CNA. Because such segments were easier to detect, and some deviation from the truth would not severely affect the results of performance comparison, we simulated them by adding constants to the single-copy and three-copy pools. Three new pools were created. Pool L1 was created by moving the median of the single-copy pool to log2(0.5) to mimic copy numbers lower than one. Pools H1 and H2 were created by moving the median of the three-copy pool to log2(4) and log2(5) respectively, to mimic copy numbers higher than 3. In the simulated chromosome, the five CNA segments were drawn from the three-copy pool, the single-copy pool, H1, L1, and H2 respectively. For each of the 2 × 6 × 3 settings, 100 chromosomes were simulated.
At each simulation parameter setting, to assess the ability of the algorithm to identify CNA segments while limiting the number of false-positive edges, we plotted the sensitivity, which is the proportion of true edges identified, against FDR, which is the proportion of false edges among all identified edges. Because of the high noise level in the data, we allowed a tolerance distance when matching true edges with identified edges. The tolerance distance is defined based on the number of SNPs. If an identified edge is equal to or less than the tolerance distance away from the true edge, we considered the true edge to be correctly detected. The results reported in Figure 2 and 3 were obtained using the tolerance distance of 5 SNPs. The results from using the tolerance distances of 3 and 7 SNPs were reported in the Supplement figures 1 and 2 [see Additional file 1]. In the ideal case, the sensitivity should approach one and the FDR should approach zero.
SNP, single nucleotide polymorphism; CNA, copy number aberration; FASeg, fragment assembling segmentation; CGH, comparative genomic hybridization; aCGH, array comparative genomic hybridization; CNAT, Copy Number Analysis Tool; SD, standard deviation; GCOS, GeneChip Operating System; GDAS, GeneChip DNA Analysis Software.
Authors' contributions
TY conceived the idea for the project, developed the statistical algorithm and the R package, and drafted the manuscript. HY and ZC performed the laboratory analyses and conducted initial statistical analyses. WS and KCL aided in interpretation of the data, and provided general statistical guidance for the study. SJ and DKB assisted the final analyses and development of the package. DW oversaw laboratory, provided general scientific guidance for the study and revised the manuscript. XZ conceived the idea for the project, oversaw the analysis, and drafted the manuscript. All authors read and approved the final manuscript.
This work was supported in part by NIH PHS grants DE015970 (to D. Wong), and DE014847, DE016569, CA114688 (to X. Zhou). We thank Ms. Katherine Long for excellent editorial assistance. The constructive comments from four anonymous referees helped improve the manuscript significantly.
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Edit hours
Expect More, Pay Less.
학교 사거리에 있어 자주 들렀지요. 내 가방을 산 곳도 여기
Look for the Cape. Otherwise you are in normal Target
Not too crowded when I go over lunch. Also not a ton of staff to help at that time. But I always end up with way more stuff than I went in for.
Beware the Dollar section!
Easy returns if u have the receipt
The men's urinals are ergonomically shaped to reduce splash on hands. Enjoy those bad boys!
Sprints 3g doesn't penetrate the metal ceiling. I get one or no bars. It's mostly targets fault because they used a cheap ceiling.
Sprint has horrible cell service in here :(
A lot of the products are damaged. I had to dig around in the back of the shelf to find a box that wasn't open or smashed
go early in the morning less crowd
Great pharmacy staff, always willing to help and take good care of you :)
TSA friendly toiletries
They slice the deli stuff to order, it tastes better, but it takes FOREVER
I can totally leave here without buying something.
Worst pharmacy ever. A bunch of morons with Disney character names.
Panera Soups now available in the deli area buy starbucks!
Electronics cashier cannot ring up alcohol.
This store is the focus and inspiration of "The Target Principle" (page 68).
There is more then one way in and out of this lot. Use the exit on the east by the fbi building, its faster
Can I ever leave Target without buying at least one item?


text:
Before Marten Skrtel was allowed free rein in the Arsenal penalty box to snatch an injury time leveller and deny the Gunners a famous and vital away win at Anfield, there may still have been a few Gooners who were hanging on to the hope that this could be the season when Arsenal win the Premier League title again.
Tag Archives: injuries
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The problems at Arsenal lie deeper than the surface by KM
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Arsenal legend still backs Wenger to succeed!!
Wenger is Arsenal's man according to Gunners legend! by Ash
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Will Arsenal ever get any luck? Other than bad?
They say that luck evens itself out over the course of a season. If that is true, Arsenal are due to win the lottery in the next few weeks, because nothing else has gone the way of the Gunners this year. I know that lots of Gooners will berate me for going on about this subject again, but yet again lady luck was conspicuously absent at the Emirates today.
Should Arsenal fans complain so much about injuries?
Are Arsenal really that unlucky? by Blaz
Why Arsenal need Juan Mata – and why Chelsea are unlikely to let him leave
Juan and Santi… The Differences and similarities! by MH
Juan Mata and Santi Cazorla. Both Spanish. Both midfielders. Both have bags of creative ability and a winning mentality. Both have extremely similar playing styles. So what could the main difference between these two fantastic footballers really be?
Why Arsenal's draw against Everton is NOT a disaster!!
There is little doubt that Arsenal should have won the game against Everton at the Emirates last night, but it seems to me that a lot of fans are taking it too hard. Yes, it was a great chance for the Gunners to fire themselves into a commanding position in the Premier League, but we are still in with a very good chance.
Wigan boss predicts open game against Arsenal
Arsenal are preparing to face yet another team in the relegation zone today as they travel to Wigan Athletic, but the Gunners will not be expecting the Northeners to just roll over after losing to the Latics at the Emirates last season.


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Artwork details
William Hodges 1744–1797
Tomb and Distant View of Rajmahal Hills
Date 1782
Medium Oil paint on canvas
Dimensions Support: 622 x 724 mm
frame: 838 x 965 x 82 mm
frame: 838 x 965 x 82 mm
Acquisition Presented by the Friends of the Tate Gallery 1964
Not on display
Display caption
The alien landscapes and ancient buildings of India were made more familiar to Western eyes by drawing analogies with ancient Greece and Rome. In its form and style, Hodges' picture is very like a conventional view of an Italian landscape with its antique ruins.
Such scenes were the speciality of the painter Richard Wilson, who had been Hodges' teacher. Like a number of painters facing an ever more competitive art market at home, Hodges looked further afield for work. He travelled to India in the early 1780s.
September 2004
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College Completion Gap Between Rich, Poor WidensThe gap in bachelor-degree attainment between the nation's richest and poorest students by age 24 has doubled during the last four decades, according to a report released Tuesday.