শনিবার, ৩০ জুন, ২০১২

San Francisco Bay Area Internet Book Company Seeking Non-Profit ?

SellUsedBooks.com, an online book buying company, continues philanthropic endeavors to promote literacy for the underprivileged, with offer to donate 1,000 children?s books to a local non-profit cause.

San Leandro, CA (PRWEB) June 29, 2012 (PRWEB) June 29, 2012

SellUsedBooks.com, where people can sell books back online, is an internet book business located in the San Francisco Bay Area. SellUsedBooks are looking to expand upon their altruistic works by seeking out a local non-profit organization to donate 1,000 children?s book. The goal is to reach out to find a locally based charitable cause, whose mission is to help provide disadvantaged children with reading resources they may otherwise lack. Since its inception in 2002, SellUsedBooks has believed that there is a direct link between using reading as a meaningful activity to help shape young people?s identity, so that they may be more focused on their future with a more positive outlook.

With successful partnerships in the past with Goodwill Industries International, The Salvation Army, Danny Foundation, The Hope Foundation, Susan G. Komen for the Cure and others, the goal with this particular outreach is more localized, with an intent to give back to the community. Marketing Specialist, Andrew Ha, has always felt that if you are fortunate enough to be able to share some of your success, you should do so by finding the appropriate worthy causes. ?Ever since I can remember, supporting literacy has always held a special place in my heart. Growing up as a youngster in Honolulu, Hawaii, I had witnessed first hand how learning to read better prepares children to achieve their potential by developing stronger language skills. With this campaign, we are once again looking to give back, and seeking a locally based non?profit community program in need of children?s books.?

In order to promote literacy and encourage children to learn to love reading, the donation offer will include a wide assortment of 1,000 children?s books with varying reading levels and topical interests. The classification of children?s books contained within this library will range from Scholastic Readers and Picture books, generally intended for early readers ages 4 and older, up to Reading Level (RL) 5 chapter books for ages 9 to 12. RL1 to RL4 chapter books for ages 6-9 will also be well represented, with many popular series titles, and while there is a

Source: http://uk.ab2w.net/san-francisco-bay-area-internet-book-company-seeking-non-profit/

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Adele Is Expecting Her First Child!

The Grammy winner is pregnant with her first baby! Plus, see more stars who are expecting

Source: http://www.ivillage.com/pregnant-celebrity-photos-look-whos-popping/1-b-18178?dst=iv%3AiVillage%3Apregnant-celebrity-photos-look-whos-popping-18178

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শুক্রবার, ২৯ জুন, ২০১২

HTC teases something incredible for next week, it's the Droid Incredible 4G LTE

Droid Incredible 4G LTE

We've gone hands-on with it; we've compared it to the HTC EVO 4G LTE plus, Verizon and HTC have made it official. Now  it looks as though we may actually see the Droid Incredible 4G LTE finally land into some consumers hands according to a tweet sent out by HTC.

Next week, we've got some special fun headed your way. We hear it's going to be INCREDIBLE. 

We don't think we're reading into it too much here, so if you had your eyes and heart set on the Droid Incredible 4G LTE you only have a few more days to wait and then you can give one a home. Any takers? Specs can be found here if you're looking for them.

Source: @HTCUSA



Source: http://feedproxy.google.com/~r/androidcentral/~3/gmYp4BNjUBc/story01.htm

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Sheen's 'Anger' premiere gets warm ratings welcome

FILE - This file publicity image provided by FX shows Charlie Sheen as Charlie Goodson and Selma Blair as Kate Wales in a scene from the new comedy "Anger Management." FX network says Thursday's debut of his sitcom, "Anger Management," was the most-watched series premiere in that network's history, drawing 5.5 million viewers. Then the audience for the evening's second episode grew to more than 5.7 million viewers, FX said Friday, June 29, 2012. (AP Photo/FX, Adam Rose)

FILE - This file publicity image provided by FX shows Charlie Sheen as Charlie Goodson and Selma Blair as Kate Wales in a scene from the new comedy "Anger Management." FX network says Thursday's debut of his sitcom, "Anger Management," was the most-watched series premiere in that network's history, drawing 5.5 million viewers. Then the audience for the evening's second episode grew to more than 5.7 million viewers, FX said Friday, June 29, 2012. (AP Photo/FX, Adam Rose)

(AP) ? Charlie Sheen can claim a winning reception back on weekly TV.

FX network says Thursday's debut of his sitcom, "Anger Management," was the most-watched series premiere in that network's history, drawing 5.5 million viewers. FX said Friday that the audience for the evening's second episode grew to more than 5.7 million viewers.

"Anger Management" marks Sheen's return to sitcoms after his tumultuous exit from his long-running CBS hit "Two and a Half Men" last season.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/4e67281c3f754d0696fbfdee0f3f1469/Article_2012-06-29-TV-Anger%20Management%20Ratings/id-2a6a18a71a0e42e388ec5cf52e3fe250

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Supreme Court Upholds Right to Lie About Military Honors

Is it accurate?

Can you confirm that it is true?

Have you yourself verified some of the facts and observations in this story? If so, did you find that information to be correct? If not, are you confident that the information has been verified? To answer this question, you may want to do some of your own research, and look at how other publications covered this story. If you do not know anything about this topic and do not have time to research it, please do not answer this question.

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বৃহস্পতিবার, ২৮ জুন, ২০১২

Boosting Positive Energy Using Crystal - Home and Garden ...

Some of my favorite treatment of feng shui, including the placement of the crystals. Good Feng Shui crystal energy home improvements. In your inner space of the outside world to help bring around your house yin and yang, has the advantage of the energy balance was created from the ground. Placing the decision in the house room calm and help energy flow more easily where there is discord and conflict and to bring harmony and peace.

Here to use the crystal can be used to maximum benefit and how are some of the favorite tips. Home as part of an array of crystal-mail in addition to improvements in the energy, you can create beautiful images.

Decisions about the property

Amount of blowing frequency energy, and decrease in income or financial lucky you are suffering from decline, then you smaller the area of ??your life ?on the energy transfer should be promoted. Red high gloss crystal volume, or the beautiful golden Citrine Carnelian or in your home?s southeast should be installed inside your front door. They are rectangular or square crystals both he, and metal or glass by placing them these leads, all the energy which represents vessel benefits to minimize the unwanted citrine and carnelian of the best effects, wooden bowl should be placed in the well. You do not want to vanish as the energy they do not place in direct sunlight.

Decisions for your career

The area that represents a career in the north facing rooms of the house, and if you work from home, your home office. Your job, career change, or if you are trying for a promotion if you run a business in the area of ??Sui and amazing work putting a high negative decision I would like to improve your business success. Negative for regional career high of my favorite crystal bowl of lapis lazuli, and Jet, round or irregularly-shaped glass, when placed in a beautiful all. Moving the crystal in front of a small water feature integrated water if the location of the energy can be improved by experience. When you move a job or stagnation of water sports can bring to the business.

Decisions about love

Treatment of people who want to find love in their lives because of people?s decisions about treatment, it is often asked. Strengthen the determination of such love, such as feng shui crystals probably all of the treatments of the most popular. The most well-known love of crystals and amethyst purple rose pink to modify their home in the bedroom or in the southwestern part of the decorations can be beautiful.

Love in your life if you are looking for a part of treatment is important to love as a couple. Place on both sides of the bed, two quartz crystal or amethyst rose bowl or two of them decorated in a different way the two sides to put the crystal. We rose quartz crystal in his hands at home, sitting side by side, each holding two children in the no

You in a relationship and we want to enhance the treatment of a beautiful crystal crystal to buy a pair of partner to each other so that you can take down the state will provide. Crystal Hand remember every time you touch the love between you two.

Decisions about family

The family room of the house can not stay home rather than conflict or inconsistency of the relationship, if any treatment or enhancements should be focused on here. They help to bring balance and stability, such as fluorite, jade green or green crystals of sedatives should be placed here. Large green plants such as bamboo and ferns in the room to help lift energy plants scattered around the base of the family and the crystal can have a sense of peace and tranquility in the area will help. Or your family pictures around the green or green fluorite, jade, you can enter the decision.

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Drexler denies he gave quotes about Magic in book

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বুধবার, ২৭ জুন, ২০১২

Happy 28th Birthday, Khloe Kardashian!


Khloe Kardashian turns 28 years old today, and the reality star has reportedly started the process of getting herself the most beautiful birthday present possible: a baby!

Yes, folks, Khloe has started fertility treatments, according to multiple reports.

Khloe Image

Aside from that major step, Khloe's life is relatively calm when compared to her sisters. She isn't dating the world's most famous rapper or battling with ex in court.

She isn't pregnant, nor is she dating Scott Disick, a man who constantly makes John Mayer look UN-douchebag-like.

Instead, Khloe just appears on her family's scripted reality show, poses on many red carpets and appears genuinely happy in her marriage to Lamar Odom. Those two certainly showed us!

So on a day where Ed Westwick turns 25 and Tobey Maguire 37, we choose to single out Khloe Kardashian for being the least irritating of all Kardashians. And we honor her with the following photo montage:

Kardashians in UnderwearKhloe Kardashian Promo PictureKhloe Kardashian Cosmo CoverKhloe Kardashian, Yo!Kardashian Kollection Lingerie Ad

Shot of Khloe KardashianKim, Kourtney and Khloe ToplessNot a Kardashian?!?A Kiss from KhloeLamar Odom and Khloe Kardashian Together

Khloe Kardashian Us Weekly CoverKhloe and Lamar on the Red CarpetKardashians in LingerieKardashian Kollection Premiere PicKhloe Kardashian Lucky Cover

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Facebook email switch prompts outcry

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Some MacBook Pro Retina screens may have ghosting issue

4 hrs.

Some of?Apple's new MacBook Pros with the?Retina display may be seeing?ghosting images?appearing on the screen.

The issue has been noticed and commented on by those on Apple's community forums, on?YouTube?(see below),?as well as by long-time Mac pros. Among them is Lloyd Chambers, whose Mac Performance Guide website for pro photographers and "performance addicts," showed a photo of the ghosting problem.

"A latent image 'burns in'?to the deskop when a window is left on screen," wrote Chambers on his website. "This has now happened repeatedly.

"The problem occurs in as little as 20 minutes; close the window and the desktop is left with a latent image; a ghost image of whatever text or graphic was in the window left on screen."

Msnbc.com has contacted Apple for comment; we will update this post if we hear back. Individual users, sharing their stories on the company's support site, have said that when they've notified Apple, or taken their laptops into Apple stores, new laptops have been ordered for them as replacements. The reason for the problem has not yet been explained.

But the issue is frustrating, especially as the new laptop's starting price is $2,199. The Retina display, which has an?unprecedented 2880-by-1800 pixels, has received generally rave reviews.

Different users are seeing the problem in different areas of the display. "Aut0maticdan" wrote on Apple's support site:

Hey, those of you having this issue, I'd love to know what part of the screen your burn-in occurs.

I was messing with it last night and the mark goes from the bottom to about an inch above the bottom of the screen.? Its about two inches wide above the F8, F9, F10 keys. ...?I didn't notice it until I changed my desktop background to be a solid color, but its also noticeable in apps like Aperture.

Below is the YouTube video, posted by?Wilson Chan, of what he saw.

Check out Technolog, Gadgetbox, Digital Life and In-Game on?Facebook,?and on Twitter, follow Suzanne Choney.

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মঙ্গলবার, ২৬ জুন, ২০১২

Local Governments Can Assist Businesses By Improving Customer ...

By Paul Wolf, Esq, on June 25th, 2012


Businesses understand the importance of making interactions with customers as easy as possible. Most local governments have a long way to go as far as improving their approach to customer service. Recognizing that government is complicated, New York City Mayor Michael Bloomberg has launched a Business Customer Service Initiative to make it easier for businesses to deal with government offices.

Bloomberg?s Customer Service Initiative for businesses involves the following:

- Appointing the City?s first Chief Business Operations Officer, a new, dedicated position that will oversee the initiative and serve as the lead official ensuring that business-friendly practices are made permanent where possible.
- Enabling businesses to pay license, permit and other fees, including taxes, online.
- Making it possible for businesses to apply online for the necessary licenses, permits and other credentials they need to open their doors.
- Reducing the number of agencies involved in issuing permits.
- Reporting on the progress of these initiatives every 90 days.

Some interesting facts that show how important it is to improve the bureaucracy of government for businesses:

- New York City issues 300 business-related licenses and permits ? but less than a quarter of them can be applied for online. Bloomberg believes that in 2012, a business owner shouldn?t have to leave his or her business in the middle of the day to visit an office and fill out a paper application.
- While some items are able to be paid online, businesses are often forced to come to city offices during certain hours, or to pay someone to come on their behalf, and to bring cashiers or other checks.

In addition to this Customer Service initiative, a previously established Regulatory Review Panel, a joint initiative of the Bloomberg Administration and the City Council, has identified ways to make New York City more supportive of small businesses. The Regulatory Review Panel:

- Is working to improve the permit process for ?Place of Assembly? ? businesses in which 75 or more people gather indoors by reducing the number of steps in this process by more than 20 percent, eliminating unnecessary steps and an unnecessary handoff between city agencies.

- Continuing improvements to the sidewalk caf? approval process. Since 2003 the number of agencies involved in this process has been reduced from six to three, and the approval processing time has been cut roughly in half. The number of sidewalk cafes has grown from 700 to 1100. Efforts are continuing to reduce the number agencies involved to one and to further shorten the approval process.

Forming a Regulatory Review Panel and implementing a Business Customer Service initiative is a great way to help local businesses in your community.

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Technology | Joomla Development- Highly Customizable CMS ...

?Joomla Web Development A New Trend In Web Development
Many companies are using Joomla Web Development Framework to build their website. This is the most advanced and easy technique to control and manage your website. You must have heard about Joomla, the free CMS (Content Management Software). Have you tried working on it? Yes, it is that uncomplicated to get started with Joomla. With least per-requisites, Joomla web development solutions provide a vast prospective to work in. It works on the foundation of PHP, and is qualified enough to meet...

?Why to Hire An Offshore Joomla Development
Joomla development is a popular Content Management System (CMS) and a free open source widely used by the developers to create highly advanced and feature-rich web applications or websites. This is a popular CMS mainly used to create flexible business or blogs websites so that even a non-technical person can handle properly his or her website. This is the biggest advantage of this open source technology as well as the reason for the popularity of this CMS. Joomla is prominent because of its...

?Essentials To Consider A Joomla Web Development Company
Website designing and development is becoming a popular trend in all types of businesses. Various industries such as retail, marketing, finance & insurance, agricultural, real estate, IT and many others are now creating their websites to have a unique online identity. Therefore, they hire some or the other website development company that can offer them best services. These companies own skilled team of developers who are expert in developing customized web solutions as per the client?s needs...

?Joomla Website Development Escalating Your Business
Joomla website development is an application which is used for the development of the websites. It helps in creating the interactive and well designed website with ease. Online business or internet marketing has become a craze due to its flexibility to reach customers worldwide. People nowadays are depended on internet for the expansion of their business and making their presence throughout. When a user wants to buy something he wants to research about that particular product. If he can...

?Joomla Development The Most Potent Web Development Tool
The internet marketing sector is booming with a faster pace giving web development or web designing a new path to prosper. There are many content management systems which handles this process easily. It provides a potential growth to various corporate bodies helping them to showcase their products and services worldwide. Open source web development has become one of the popular choices due to its simplicity and versatility. Joomla web development is one of the widely used open source...

?Create Your Unique Website with Joomla Web Development
Online marketing is a new way to promote business in the most affordable manner. It can help in gaining customers with ease. For making a presence in the web world, creating an interactive website is necessary. Different web development applications are there to make your website successful, but Joomla web development is the most popular web designing platform. Joomla development has a tremendous range and it is very much convenient to use. It is simple to use for the consumer which helps...

?Customize Your Website Through Drupal Web Development
Internet and Online businesses have revolutionized the world and brought a new scenario of business. Now-a-days, businesses are moving forward in the way of online trading to reach a wider market. Thus, they create their websites to get unique online identity and open source web development has enabled the companies to build their online stores. There are various CMS (Content Management System) tools are used by the developers to create high quality ecommerce websites or other websites. These...

?Open Source Development Creating A Niche In The Web World
Website development industry is booming since the demand for online marketing has increased. From a teenager to a high class professional, everyone is now depended upon internet for various tasks. It has made the communication process simpler and has connected people around the world. Now every person can reach anywhere virtually through the magic of web. Nowadays, many software has been introduced to design the webpage in the most spectacular manner. Open source development tools such as...

?WordPress Development Create Your Blogs With Great Ease
In this modern era, WordPress development plays a major role in maintaining and creating your own website or blog site. It offers various advanced features that enables you to manage your site properly. WordPress development is one of the best techniques of open source development that enables the owners to manage and handle their business websites, blog websites, forums, corporate websites and many more. This CMS (Content Management System) is written in MySQL and PHP language that includes...

?Drupal Development The Most Influential CMS Software
Drupal was developed by Dries Buytaert as a bulletin board in 1999 and back then, there accept been innumerable changes to its software. Immediately the software got its own association in the year 2001 and has acquired force anytime since. Also, it has already gained the interest of masses because of its open source technology and is broadcast beneath the GNU authorization that lets anybody to download it and deliver it to others. Drupal development enables the companies to create their...

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সোমবার, ২৫ জুন, ২০১২

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New Paraguay leaders mount international defense

Paraguay's former President Fernando Lugo smiles after talking to his followers gathered outside the Public Television building in downtown Asuncion, Paraguay, in the early hours of Sunday, June 24, 2012. Lugo spoke in a pre-dawn special televised "open microphone" program hosted by the state-funded Public Television channel that was created by his government, to denounce his ouster as a "parliamentary coup". (AP Photo)

Paraguay's former President Fernando Lugo smiles after talking to his followers gathered outside the Public Television building in downtown Asuncion, Paraguay, in the early hours of Sunday, June 24, 2012. Lugo spoke in a pre-dawn special televised "open microphone" program hosted by the state-funded Public Television channel that was created by his government, to denounce his ouster as a "parliamentary coup". (AP Photo)

Paraguay's new President Federico Franco, sitting center, gives a news conference at the presidential palace in Asuncion, Paraguay, Saturday, June 23, 2012. Paraguay's newly sworn in president is promising to honor foreign commitments and reach out to Latin American leaders after the Senate removed President Fernando Lugo from office in a rapid impeachment trial on Friday. (AP Photo/Jorge Saenz)

Paraguay's former President Fernando Lugo talks through the ?open microphone? of the Public Television, surrounded by reporters and followers in downtown Asuncion, Paraguay, in the early hours of Sunday, June 24, 2012. Lugo spoke in a pre-dawn special televised "open microphone" program hosted by the state-funded Public Television channel that was created by his government, to denounce his ouster as a "parliamentary coup". (AP Photo)

Paraguay's new President Federico Franco gives a news conference at the presidential palace in Asuncion, Paraguay, Saturday, June 23, 2012. Paraguay's newly sworn in president is promising to honor foreign commitments and reach out to Latin American leaders after the Senate removed President Fernando Lugo from office in a rapid impeachment trial on Friday. (AP Photo/Jorge Saenz)

Paraguay's new President Federico Franco gives a thumbs up as he arrive to give a news conference at the presidential palace in Asuncion, Paraguay, Saturday, June 23, 2012. Paraguay's newly sworn in president is promising to honor foreign commitments and reach out to Latin American leaders after the Senate removed President Fernando Lugo from office in a rapid impeachment trial on Friday. (AP Photo/Jorge Saenz)

(AP) ? Paraguay's new government battled a wave of criticism on Sunday as several of the nation's closest allies condemned the dismissal of President Fernando Lugo by lawmakers, some calling it a congressional coup.

Venezuelan President Hugo Chavez said his government will cut off fuel sales to the poor South American country. Venezuela had become a key supplier to Paraguay as Chavez built close ties with Lugo, a moderate leftist.

Argentina's Foreign Ministry announced Sunday that Paraguay had been suspended from the Mercosur trade bloc, issuing a joint resolution by member nations expressing "their most energetic condemnation of the rupture of democratic order" in Paraguay.

The statement also said Paraguay would be suspended from a Mercosur summit to start Monday in Mendoza, Argentina.

Earlier Sunday, former Vice President Federico Franco, who was sworn in as Paraguay's president following Lugo's ouster Friday, had said newly appointed Foreign Minister Jose Felix Fernandez would represent Paraguay at the Mendoza summit, with heads of state gathering there on Thursday.

"He will take charge of seeking to solve the discrepancies with countries that are our neighbors and friends," Franco said after attending Sunday Mass.

Lugo had also said earlier Sunday that he planned to attend the summit and would even hand over the rotating presidency of Mercosur to Peru next week, months before it is due to switch in November.

"I will not collaborate with Franco's government because it is bogus. It has no legitimacy," Lugo said. Earlier he denounced his ouster as a "parliamentary coup."

Two of his Cabinet ministers also announced the establishment of an alternative continuation government to attend to matters of state Monday.

"President Lugo will be with his ministers to take decisions and then inform what those determinations were," said Augusto Dos Santos, Lugo's minister of social communication.

It was an apparent reversal from days earlier when Lugo said he would respect the outcome of his Senate trial.

Lugo, a former Catholic bishop, said early Sunday that Roman Catholic bishops visited him before Friday's Senate trial, and he told them he agreed to accept the outcome of a process he considered illegitimate only to avoid bloodshed.

All three other full Mercosur members reacted with alarm to Lugo's removal, denouncing the fact that the Senate's impeachment trial lasted just five hours, giving the president little time to mount a defense. Brazil and Argentina announced they were calling their ambassadors home and Uruguay also expressed concern.

Chavez announced Venezuela also was pulling its envoy. "We do not recognize this government," he said, calling Lugo's ouster a "coup."

Chavez's decision to cut oil shipments could hurt Paraguay, which has received increasing quantities of Venezuelan oil since 2004. Paraguay currently owes Venezuela's state oil company Petroleos de Venezuela SA nearly $300 million, out of about $400 million in total debts to oil suppliers. Paraguay's new government downplayed the Argentine announcement, noting that the last ambassador, Rafael Roma, had already left three months ago after finishing his diplomatic assignment.

Lugo was elected four years ago, ending 61 years of rule by the conservative Colorado Party, on promises of agrarian reform to help the country's many poor and landless people, but his allies increasingly turned against him in recent years.

Ultimately, a deadly clash between police and landless protesters cost Lugo all but a handful of votes in both legislative houses.

Police were attempting to evict about 150 farmers from a remote forest reserve that is part of a large estate. Six police officers, including the brother of Lugo's chief of security, and 11 farmers died in this month's clash.

Lugo's opponents blamed the president. Advocates for the farmers say the landowner, a politician, had used his influence to get the land from the state decades ago, and say it should have been put to use for land reform.

The president also was tried on four other accusations, including that he improperly allowed leftist parties to hold a political meeting in an army base in 2009; that he let about 3,000 squatters illegally invade a large Brazilian-owned soybean farm; that his government failed to capture members of a guerrilla group, and that he signed an international protocol without properly submitting it to Congress for approval.

Lugo said his truncated presidency was targeted because he tried to help the South American nation's poor majority. Asked whether he had any hope of retaking office, Lugo exhorted his followers to remain peaceful but suggested that national and international clamor could lead Paraguayan lawmakers to reverse his impeachment.

"In politics, anything is possible," Lugo said.

Franco is set to serve out the rest of Lugo's term, which ends in August 2013. His government has been recognized by Germany, Canada and Spain.

Late Saturday, a crowd of protesters waved flags in the capital and chanted: "We will not recognize any other president!"

In calling its ambassador home for consultations, Brazil's Foreign Ministry said in a statement that the "Brazilian government condemns the summary removal of the Paraguayan president ... during which the right to a full defense was not assured."

It said the process "compromises a fundamental pillar of democracy, an essential condition for regional integration," and that Brazil was evaluating what actions to take with its partners in Mercosur and Unasur.

It added that Brazil would do nothing to "harm the people of Paraguay," suggesting that it may not intend to cut off economic partnerships with its much poorer neighbor.

Franco said Fernandez, the foreign minister, would try to win back the support of Argentina, Brazil and Uruguay.

"There was no break with democracy here. The transition of power through political trial is established in the national constitution," Franco said.

The U.S. State Department has urged "all Paraguayans to act peacefully, with calm and responsibility, in the spirit of Paraguay's democratic principles." It has not said whether the U.S. will recognize the new government.

___

Associated Press writers Belen Bogado in Asuncion and Christopher Toothaker and Ian James in Caracas, Venezuela, contributed to this report.

___

Follow Peter Orsi on Twitter at www.twitter.com/Peter_Orsi

Associated Press

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রবিবার, ২৪ জুন, ২০১২

4 NATO service members killed in Afghanistan

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Rain on the Queen's parade

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শনিবার, ২৩ জুন, ২০১২

Stopping and starting cancer cell cycle weakens and defeats multiple myeloma

Friday, June 22, 2012

Weill Cornell Medical College researchers have devised an innovative boxer-like strategy, based on the serial use of two anti-cancer drugs, to deliver a one-two punch to first weaken the defenses of multiple myeloma and then deliver the final knock-out punch to win the fight.

The study, published online by the journal Blood, is the first to show that precise timing of therapies that target a cancer cell's cycle ? the life phases leading to its division and replication ? disables key survival genes, resulting in cell death. The drug that delivers the weakening jab at the cell cycle is the experimental agent PD 0332991, which allows bortezomib, a proteasome inhibitor already approved for use in myeloma and lymphoma, to land the final defeating blow at lower than normal doses.

While this is potentially good news for patients with multiple myeloma, a cancer of blood plasma cells that is currently incurable, the study suggests that using this therapeutic strategy could also work for other tumor types, says the study's senior investigator, Dr. Selina Chen-Kiang, professor of Pathology and Laboratory Medicine and of Microbiology and Immunology at Weill Cornell Medical College.

"Because robust functioning of the cell cycle is crucial to cancer growth and survival, this mechanism-based strategy could theoretically be used against many kinds of cancers," she says.

"Based on the genetics of a patient's tumor, we could pair PD 0332991 with the right cytotoxic partner drug to both inhibit cancer cell division and sensitize the cells for that knock-out punch," says Dr. Chen-Kiang. "We are very excited about the promise of this approach."

In fact, physicians at Weill Cornell have opened two new human clinical trials, one in multiple myeloma and one in mantle cell lymphoma, based on the findings of this study in a mouse model as well as on a previous phase I clinical trial led by Weill Cornell investigators that tested PD 0332991 in patients with mantle cell lymphoma.

Playing Havoc with the Cancer Cell Cycle

Dr. Chen-Kiang and her laboratory colleagues have long studied genes and proteins that control the cell cycle and cell suicide (apoptosis) in cancer. Cancer is fundamentally a disease of uncontrolled cell proliferation, where cells are able to continuously divide. In contrast, cell division in a healthy individual is regulated by the cell cycle, an orderly sequence of programmed gene expression in which the cell is driven through various checkpoints by a highly regulated network of proteins.

Cyclin-dependent kinases (CDKs) are molecules that power the progression of the cell cycle through its four phases. For example, CDK4 and CDK6 help move cells through the first G1 "gap" phase to later phases where the cell splits in two. In many cancers, these two enzymes are over-expressed, ensuring continual growth. Therefore, targeting CDK4 and CDK6 to shut them down has long been a goal of cancer drug discovery, but clinical success, so far, has been disappointing because of lack of effectiveness as well as drug toxicity, says Dr. Chen-Kiang.

PD 0332991, a small molecule synthesized by Pfizer, is different because it is exceptionally selective for CDK4 and CDK6, she says. The drug initially did not receive much attention because it is also reversible, meaning that it needs to be used continuously to inhibit CDK4 and CDK6; withdrawing it would reactivate these enzymes, stimulating growth.

But Dr. Chen-Kiang had been searching for a drug that she could use for her selective cell cycle-based therapy ? the idea being that playing havoc with a cancer cell's cycle would fatally weaken it when more traditional anti-cancer drugs are used sequentially.

"Given that the gene expression program is coupled to the cell cycle, we hypothesize that inhibition of CDK4/CDK6 maintains gene expression programmed for early G1, while preventing the expression of genes scheduled for other cell cycle phases," she explains. "And because metabolic needs in tumor cells differ from normal cells, this prolonged arrest in G1 would create an imbalance in gene expression that preferentially sensitizes tumor cells to cytotoxic drugs, allowing for low-dosage treatments."

"Because PD 0332991 is also reversible, we further hypothesize that release from G1 by removal of the inhibitor would synchronize the cell cycles, but may not synchronize gene expression schedules," Dr. Chen-Kiang adds. "This tension between cell cycle synchronization and differential gene expression synchronization further weakens the tumor cells during their progression, as does the heightened metabolic load and demand for energy to replicate DNA."

Loss of Survival Protein

This is exactly what the researchers found. By using PD 0332991 several times to induce a prolonged arrest of G1, and then a release from that arrest, the cells were sensitized to killing by bortezomib. They found this to be the case in laboratory studies of primary myeloma tumor cells and in mice, which were left with healthy bone marrow cells.

"We found bortezomib, even when used in a low dose, was significantly more effective when the cancer cells were sensitized by our strategy," says the study's first author, Dr. Xiangao Huang, assistant research professor of Pathology and Laboratory Medicine at Weill Cornell Medical College.

In exploring the underpinning mechanism, the researchers discovered that prolonged arrest in G1 markedly enhances cell suicide, induced by bortezomib. They discovered that during this phase, the cell loses a protein called IRF4, an essential survival factor for myeloma cells, and gains several pro-apoptotic proteins.

"These findings demonstrate for the first time that key survival and apoptotic genes are regulated by the cell cycle in cancer cells, and suggest new molecular targets for intervention," Dr. Chen-Kiang says.

"This work represents the seamless integration of basic biological research on the cell cycle and direct medical application in clinical trials," she adds. "Both the tools available to us, and our unique location at NewYork-Presbyterian/Weill Cornell Medical Center, allow us to move biological research forward while rapidly translating our findings to therapy."

###

New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College: http://www.med.cornell.edu

Thanks to New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College for this article.

This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.

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Personal Injury Claims Legal professional ? Gov Products

Article by Dick Zinia

Personal Injury Claims Lawyer ? Legislation ? Civil Regulation

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Individual Injuries Instances Can Be Challenging
Seeking for an injury promises attorney can be a challenging task. There are tens of 1000?s of legal professionals in the nation, and finding a law professional is challenging just because of the quantities. Few this with the fact that your predicament as an hurt individual struggling from accidents and damages tends to make your psychological situation fragile. Beginning the method of turning out to be involved in a healthcare negligence lawsuit can be emotionally draining.

Specifics &amp Circumstances
Even even though you may possibly consider the details of your harm claim are clear and past dispute, you will shortly discover that in the planet of private injury litigation things are almost never witnessed as that easy. Locating the proper attorney to argue your situation is vital to the final results and to the financial award you receive.

Retain the services of an Legal professional Knowledgeable in Personal Damage Case Law
It is important to hire a damage promises attorney with experience in the subject. The area of injuries regulation is intricate and tough to navigate without having an expert injuries professional. The moment you have picked a number of experts in harm legislation you really should interview them to decide which personal injury claims lawyer is the finest fit for you and your private damage scenario.

No-Get No-Charge Personalized Injury Contingency
A single aspect affecting the determination about who to hire to signify your authorized interests is the fee billed by the attorney. Your resources may possibly be constrained, so it may be worthwhile to consider selecting only attorneys who work on a no-gain no-fee individual injuries contingency. Doing so will limit the out of pocket expenditures you will have to incur as attorney compensation will arrive out of any income settlement acquired in your damage case. Utilizing a law company who operates on a no win no charge representation can be your most cost effective way to commence with your damage lawsuit.

Personalized Injury Instances Can Be Hard
Searching for an attorney can be a daunting job. There are tens of 1000?s of legal professionals in the country, personal injury claims and obtaining an damage law expert is tough just because of the quantities. Couple this with the simple fact that your scenario as an injured particular person suffering from accidents and damages tends to make your psychological predicament fragile. Starting up the approach of turning into included in a health care negligence lawsuit can be emotionally draining.

Damage Case Specifics &amp Situations
Even though you might think the specifics of your damage claim are very clear and past dispute, you will before long uncover that in the planet of injuries litigation factors are almost never seen as that straightforward. Discovering the right attorney to argue your injuries situation is vital to the supreme success and to the financial award you get.

Employ an Legal professional Knowledgeable in Personal Injuries Situation Legislation
It is critical to hire a harm promises lawyer with encounter in the field. The place of personal harm regulation is sophisticated and tough to navigate without having an skilled personal damage expert. Once you have selected numerous experts in harm legislation you really should interview them to decide which damage statements lawyer is the best fit for you and your individual harm situation.

No-Get No-Price Damage Contingency
1 aspect affecting the determination about who to hire to symbolize your legal passions is the payment charged by the lawyer. Your methods could be constrained, so it may possibly be worthwhile to contemplate selecting only attorneys who function on a no-win no-fe injury contingency. Carrying out so will restrict the out of pocket bills you will have to incur as attorney compensation will occur out of any money settlement obtained in your injuries case. Employing a regulation agency who performs on a no gain no charge contingency promises representation can be your most price efficient way to continue with your injuries lawsuit.

This report was originally printed at No Gain No Fee Attorney.

About the Writer

Mr. Zinia is a frequent contributor to GoArticles. He writes content articles for Rotary Telephone, Bosch Blades, Rotary Telephones, Geranium Cuttings and Repel Squirrels.

Use and distribution of this report is topic to our Publisher Suggestions

whereby the original author?s data and copyright ought to be incorporated.

Dick Zinia

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