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5 Min Read
* FTSEurofirst down 0.2 percent * Political instability knocks Italy, Spain indexes * Autos fall with banks cautious after recent run * Telecoms dip on div worries, Vodafone down after downgrade * Utilities rise, Centrica up on 500 mln stg buyback By David Brett LONDON, Feb 4 (Reuters) - European shares dipped by midday on Monday as a near-term risk of a technical sell-off and political uncertainty in the euro zone prompted a bout of profit taking with indexes hovering near multi-year highs. By 1124 GMT, the FTSEurofirst 300 was down 2.58 points, or 0.2 percent, at 1,165.50, lingering near mid-February 2011 closing highs of 1,187 but off early morning highs. It has gained 9 percent since November. "Markets have been very strong since last November and technically we are ready for a correction in the short term," Nicola Marinelli, fund manager at Glendevon King asset management said. European shares are likely to deliver an average return of minus 11 percent over the next six months, BNP Paribas's Love-Panic sentiment indicator showed, with six indicators signalling a 'strong sell' for an overall 'sell' rating. Spain's benchmark Ibex index was down 1.5 percent, and Italy's FTSEMIB fell 2 percent. They were the region's major laggards as a corruption scandal in Spain and uncertainty ahead of an election this month in Italy posed a threat to the growth outlook for the euro zone region and also prompted a rise in debt yields. Marinelli said a sell-off would be justified given the political uncertainty. While he retained long positions in his portfolio established late last year, he was waiting for a pullback across all asset classes before putting fresh money to work. "Not putting new money to work has not been a huge pain because at these levels we are not losing much. A bit of pullback can only be a healthy thing for portfolio returns," he said. Deutsche Bank said investors were looking for a recovery in corporate earnings to support further gains with European shares trading at 12 times price-to-earnings. Over the last six months I/B/E/S 12-month forward earnings per share forecasts on Stoxx 600 companies have been downgraded by 5.7 percent. European auto stocks dropped 1 percent after decent gains left investors such as Citi and HSBC sifting through the sector for companies that still offer some value. The auto sector was the best performer in Europe in 2012, surging 38 percent, and since September it has rallied 20 percent, despite continued earnings per share downgrades. Over the last six months I/B/E/S 12-month forward earnings per share forecasts have been downgraded by 12 percent as European car market fundamentals have deteriorated further. HSBC said French car makers face major challenges and downgraded Renault to "neutral" from "overweight" after its recent strong share price run, which saw it rise 32 percent since mid-November. Renault fell 1.9 percent. HUNG UP Telecoms shed 0.8 percent with the sector dragged down by concerns over dividend cuts and with heavyweight mobile communications firm Vodafone falling 1.8 percent after Citi downgraded the stock to "neutral" after its recent rally. With investors in a cautious mood defensive sectors such as healthcare and utilities were the main gainers. Germany's largest energy group E.ON rose 1.2 percent after traders pointed to the delay of a strike that was originally planned for Monday, Feb. 4. Suez Environment climbed 2.7 percent after HSBC upgraded the French water and waste group to "overweight" ahead of results due on Feb. 14. Utility group Centrica rose 0.7 percent after announcing plans to launch a 500 million pound ($787 million) share buyback scheme. While investors were in risk-off mode on Monday, data showed euro zone sentiment improved for a sixth consecutive month in February with expectations rising to their highest level since June 2007. Signs of improving sentiment in the euro zone have helped boost inflows into global equity funds, which attracted another $18.7 billion during the final week of January, according to EPFR Global. That has fuelled talk of a long-awaited 'great rotation' out of fixed income and into stocks. "Several factors still favour equities and the performance relative to fixed income should continue to be positive," Dan Morris, global strategist at JP Morgan Asset Management, said in a note. "The most important consideration for longer-term returns is valuations ... Equity valuations have increased over the last year but remain "good value" compared to the average PE since 1985," he said.


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Just a reminder summer is around the corner and summer camp is starting to fill up fast./
We have added more weeks on this year and are looking forward to a great summer.Also welcoming back alot of horse favorites such as Binn Movin and Samson who are coming home for the summer from college.
Another reminder for the Tom Poulin Dressage clinic thursday the 26th. Rider slots are full but
welcome auditors.

subset: commoncrawl


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WALLINGFORD-L ArchivesArchiver > WALLINGFORD > 2000-08 > 0966894413
Subject: [WALLINGFORD] Pension of William R Wallingford (KY)
Date: Mon, 21 Aug 2000 17:46:53 EDT
William R Wallingford
Pvt Co K 16 KY Vols
Mother's Pension Application
Mother: Sarah B Wallingford of Fleming Co, KY
Application #: 144319 Certificate # 109181
William R Wallingford drowned in the Big Sandy River 7 June 1862
She received $8 a month.
Statement from Adjutant General's Office
Enrolled 10 Oct 1861 at Camp Lee in Company K 16th Regiment of KY Vols for 3
years service.
Mustered in to service on 28 January, 1862. Drowned 7 June 1862.
Affidavit of Sarah B Wallingford, filed in Mason Co, KY 15 March 1867. Her
residence was
given as Mt. Carmel, Fleming Co, KY. Her age was given as 54. She stated she
was the widow
of Samuel B Wallingford and the mother of William R Wallingford. William R
served in a
company commanded by James A Lee and Col Charles A Marshall. William R
drowned when a boat
he was on capsized in the Big Sandy River in the state of Kentucky on the
7th day of June
1862. She stated that she was "wholly dependent upon" William R and that "he
left no widow
or minor child under 16 years of age, he having never married."
Affidavit of Santford C Becket and M L Middleton, dated 15 March 1867 in
Mason Co, KY. They
both swore that Sarah B Wallingford was the widow of Samuel B Wallingford and
the mother of
William R Wallingford. That William R was never married and left no minor
children under 16.
They said he lived with his mother and supported her. M L Middleton further
stated that
William R sent Sarah money ($43) while he was in the service of the United
In a letter dated 10 June 1869, Sarah B returned her Pension certificate to
the Commissioner
of Pensions and requested arrears from the time of William's death. She gave
her address as
Tollesboro, Lewis County, Kentucky.
Affidavit of Stephen Applegate and Martin M Wallingford, residents of Lewis
County, KY. Dated
15 February 1868. They both stated they were acquainted with Samuel B
Wallingford, father of
William R Wallingford and husband of Sarah B Wallingford. Samuel B
Wallingford died "the 7th
day of August 1847, or thereabout". They stated that Sarah B possessed "no
property or other
means of support, except a small amount of household property and that of
little value".
They also stated that William R supported Sarah as a laborer up until the
time he entered the
service. After he enlisted, he sent her part of his pay--$20 at one time and
$43 at another.
This thread:


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Explore the Rosario Islands, made up of 43 idyllic tropical islands, covering 20 hectares of coral islands and reefs. The climate is tropical, humid, and averages 27 degrees Celsius. The Parks mangroves, coral reefs, and sea flora constitute one of the most diverse and productive ecosystems on the planet. Stay in the quaint fisherman's cove of Taganga, and watch the sun set over the sandy bay dotted with old fishermen's boats that bobble in the seas tranquil waters.
Tayrona National Park has long been known to connoisseurs as one of the wildest and most beautiful corners of South America. Its swimming beaches are reached by a trail that dips and climbs through the rain forest and over mounds of giant white boulders. Santa Marta boasts a fine natural harbor and splendid views, but that's not the only reason the Spaniards conquers chose it for their first settlement. They also came hypnotized by the legends of gold as the local Tayrona indigenous communities were known for their incredible goldsmith work.
Destinations visited:
- Cartagena
- Rosario Islands
- Santa Marta
- Taganga
- Parque Tayrona
- Pueblito Chairama.
Tour Itinerary:
Day 1: Cartagena. Transfer Airport – Hotel in a private car. Once here you can rest in the romantic and tropical atmosphere of the historic city. Meals – Breakfast Accommodation – Hotel 3 Banderas.
Day 2: Cartagena.
Morning city tour (approximately 4 hours)- Includes visits to the modern El Laguito and Bocagrande districts before returning to the old city. Complete tour of the old city, with extensive visits to the most important historical sites and buildings, and a visit to the magnificent San Felipe Fort and Castle, and La Popa monastery. Meals – Breakfast, Accommodation – Hotel 3 Banderas.
Day 3: Cartagena.
Tour to the beautiful Rosario Islands – (8 hours). Visit the Rosario Islands at the San Pedro de Majagua resort includes lunch, welcome cocktail, and transportation in a private boat. Meals – Breakfast, Accommodation – Hotel 3 Banderas.
Day 4: Taganga.
Transfer from Cartagena – Taganga, in a semi- private car (this is a shuttle that will pick you up at the hotel in Cartagena and drop you off at the hotel in Taganga). Free Afternoon in Taganga to walk around the quaint fisherman town. Meals – Breakfast, Accommodation – Hotel La Ballena Azul.
Day 5: Taganga.
Private guided Visit to the Tayrona National Park (entry fee is included). A guided trek through the Park, going along the different beaches and through beautiful trails as far as the Pueblito Chairama - indigenous village (8 hours). Meals – Breakfast, Accommodation – Hotel La Ballena Azul.
Day 6: Taganga.
Private guided visit to the Tayrona National Park (entry fee is included). This time you will have the opportunity to visit Neguanje and Playa Cristal; some of the most beautiful beaches you can find in the Caribbean. Meals – Breakfast, Accommodation – Hotel La Ballena Azul.
Day 7: Santa Marta. Fully guided city tour of Santa Marta (4 hours approximately). Meals – Breakfast. Accommodation – Hotel La Casa.
Day 8: Cartagena.
Transfer from Santa Marta – Cartagena in a semi- private car, (this is a shuttle that will pick you up at the hotel in Santa Marta and drop you off at the hotel in Cartagena). You will have a free afternoon to enjoy the city. Meals – Breakfast. Accommodation – Hotel 3 Banderas.
Day 9: Cartagena. Transfer Hotel – Airport in a private car, to take your flight back home.
- Starting from $1,827 US
- Type of trip: Classic
- Length of trip: 9 days/8 nights
- Start location: Cartagena International airport
- End location: Cartagena International airport.
- Prices per person for the complete package
- International flights not included.
Price Includes:
About This Supplier
Also see tour packages in:
South America Colombia Local Culture Cultural Journey
Email it to a friend:
Click here to email this vacation to a friend


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Your donations keep RPGWatch running!
DS2: Broken World - Product Page Launched
by Dhruin, 2006-07-01 23:24:002K Games has kicked up a product page for DS2: Broken World. There doesn't appear to be much there but it might be worth a look for those following this expansion.
Source: Blue's
Newsbit options: Add / View Comments (0) | Forward this newsbit | Link to this Newsbit
Information aboutDS2: Broken World
SP/MP: Single-player
Setting: Fantasy
Genre: Hack & Slash
Platform: PC
Release: Released


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Former Saints K Garrett Hartley Signed by Pittsburgh
Garrett Hartley, who kicked the field goal that sent the New Orleans Saints to the Super Bowl, has been signed by the Pittsburgh Steelers...
Garrett Hartley, who kicked the field goal that sent the New Orleans Saints to the Super Bowl, has been signed by the Pittsburgh Steelers...
Following another bad performance on Sunday, kicker Garrett Hartley has been released by the New Orleans Saints.
New Orleans Saints kicker Garrett Hartley was put on injured reserve yesterday. Hartley suffered an unspecified hip injury while kicking an extra point during the preseason. Hartley's agent claims that Hartley recently suffered a set back while rehabbing the injury, leading the Saints place him on IR. New Orleans also released defensive tackle Mitch King and signed linebacker Ramon Humber and offensive tackle Pat McQuinston.
Saints get it done against their hated rivals.
Garrett Hartley has had his struggles this season. Fans and media began to speculate that Hartley would be cut. While many lost faith in Hartley, the Saints were not in that number.
New Orleans Saints place-kicker Garrett Hartley came up big, in the 30-27 win over the Cowboys, on Sunday, booting home three field goals, including a 50-yarder. James Varney, of the Times-Picayune, has the story, below.
Who are the top 5 placekickers in the history of the New Orleans Saints?
If you're a Saints fan this will give you chills.
All summer long, we're going to list the best players in New Orleans Saints history to wear every number, 00-99.
The New Orleans Saints released veteran kicker Shayne Graham today, leaving two unproven kickers on the current roster.


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Game design is nothing short of popular, which makes sense given the popularity of gaming in this day and age. Anyone can get involved in the act of playing video games, regardless of how much they know about technology in general. Many young men and women get involved in this major, and the fact that art colleges offer it cannot … Read More
Game Design & 3 Tips for Creating Characters
Game design hinges on numerous factors, chief among them the characters we see and relate to. Some will be more empathetic than others, depending on how they're created. For example, an average, everyday person will be more relatable than a being with unimaginable power. Of course, this is just one of the many facets of character design, which can be … Read More
Questions to Ask When Developing Game Art
For game design to be carried out most effectively, art must be created. This can be related to anything, ranging from the most diverse character models to the simplest of textures. Without art, no video game will be created to the level of quality that it deserves. Much like the work that an online marketing company is involved in, game … Read More
3 Potential Jobs for Game Design Graduates
There's no denying the sheer popularity associated with the video game industry. In fact, one can make the argument that it's just as big as – if not bigger than – the movie industry itself. People have taken to the aforementioned type of media, like fish take to water, and continuous advancements have resulted in more engrossing experiences as well. … Read More
Game Design & How to Approach Additional Content
One of the biggest points of contention in game design – and it's one that developers and consumers alike can observe – is the idea of content. Specifically, people want to be certain that they are getting as much out of their investment as possible. It's for this reason that many people look at downloadable, or additional, content with skepticism … Read More
The Do's & Don'ts of Game Art
Game design is composed of many unique points, some of which stand out more than others. Nonetheless, if you're someone who is looking to get involved in this field, nothing should take your attention away from art. To say that this factor matters would be an understatement, but there are those who may be curious about how much weight it … Read More
The Lessons You'll Learn in Game Design
Sometimes, the knowledge you'll obtain from college isn't always academic. Yes, you'll retain specific details, which is great for the sake of personal growth. However, I would argue that it's the life lessons that help to round out your character, allowing it to become far stronger than it had ever been before. Those who have taken part in game design, … Read More
3 Ways To Implement Difficulty in Game Design
Game design hinges on various factors, though there are few which hit you the hardest as the element of challenge. Of course, this component can vary from one project to the next, depending on what audience it's being built for and what developers have had in mind beforehand. Those who have learned from art schools in New York, like ITT … Read More
The Top 3 Subjects for Game Design Students
There's more to be learned, in the realm of game design, than simply how games are created. Yes, this is viewed as the goal of any student in this major, since he or she would like to reach as many players as possible with their projects. With that said, it's not like people can jump into the process. Education matters, … Read More
A Game Design Student's Dos and Don'ts
As you can imagine, there are right and wrong ways to go about game design. There's no doubt that this type of media can capture the imaginations of many people, regardless of their experience with gaming as a whole. If you want to talk about the best work to come into the industries, you have to look at graduates from … Read More


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Project Description2012 RADA
Restoration/Preservation / Merit
Architects Tryggvi Thorsteinsson, Assoc. AIA, and Erla Dögg Ingjaldsdóttir, Assoc. AIA, Separated this master bath from its adjacent bedroom with a multipurpose cube of Walnut millwork that serves as Headboard, Closet, and Lavatory Base. Two other freestanding elements—a vessel tub and a floating partition that shelters the shower and a separate toilet area—round out the bathroom space, which opens onto a private courtyard. The jury praised the room's integration of separate functions, noting in particular the inset panel of ipe decking that drains the shower and bath areas. One judge called the net result "beautifully done, but not precious."


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Collective Procurement
What we do
Does your municipality need new emergency vehicles or personal gear, smarter parking equipment, or other equipment or services? We can help! MAPC coordinates the decision-making, performs the procurements, and lifts the administrative burden from municipalities. Our procurement expertise ensures complete compliance, and our intense customer focus means the savings in time and money are substantial.
We can help your municipality procure - and save on - a full range of apparatus, equipment, and services.
FCAM Collective Purchasing Program
Acquiring fire apparatus doesn't have to be so complex, expensive, and time-consuming. As purchasing agent for the Fire Chiefs Association of Massachusetts, MAPC handles the procurement and negotiates the pricing with vendors, so FCAM members just choose the apparatus and manufacturer - at incredible discounts. Click here to learn more about the FCAM Collective Purchasing Program.
GBPC Collective Purchasing Program
MAPC also acts as the purchasing agent for the Greater Boston Police Council. Members of GBPC nationwide can use our easy "shop and buy" program to purchase discounted police vehicles, personal gear, and more easily. Find out more about the GBPC Collective Purchasing Program here.
Public Works Collective Purchasing Program
MAPC works with several groups of public works departments to procure a variety of highway maintenance services. This simplifies the process, lowers prices, and makes for more manageable outcomes and beter scheduling within the group. MAPC coordinates the decision-making process, performs the procurements compliant with M.G.L. c.30, s.39M, and M.G.L. c. 30B, and serves as an advocate for the users whenever problems arise with contractors. With MAPC managing the procurement, DPW users are relieved of the administrative burdens and left to focus on the work.
We offer a multitude of contracted services, listed below. For more information, please contact Lorraine See.
- Roadway management
- Surface sealing treatments
- Crack filling (e.g. microsurfacing)
- Street sweeping
- Traffic markings
- Guardrail
- Earth materials
- Catch basin cleaning
- Tree services
- Debris disposal
- Street name signs and posts (furnish and install)
- Trench patch repairs
Additional Contracting Opportunities
Automatic Vehicle Location (AVL) Systems
MAPC, in partnership with the Cities of Boston, Cambridge, Newton, and Somerville, and the Town of Brookline, Lexington, Natick, Wakefield, and Westwood, has conducted a collective procurement for AVL technology to support municipal snow and ice removal operations, on behalf of the MAPC Region municipalities. Any MAPC municipality is elegible to use these contracts. Click here for information about AVL.
Bicycle Parking Program
MAPC is pleased to continue the Regional Bicycle Parking Program for 2017 - 2019! Find out how to use this Program to purchase bike parking here.
Parking Payment Systems
MAPC, in partnership with the Massachusetts Association of Regional Planning Agencies (MARPA), has conducted a joint procurement for parking payment systems, on behalf of municipalities across the Commonwealth. Any municipality in Massachusetts is now able to contract directly with any approved vendor for a variety of parking meters at deep discounts. Click here to learn more.
EMS Supplies & Medications
MAPC, in partnership with the Central Massachusetts Regional Planning Commission (CMRPC), Hampshire Council of Governments (HCOG), and the Southeastern Regional Planning and Economic Development District (SRPEDD), participated in a cooperative group bid for EMS supplies commonly used by municipal ambulance departments, school nurses, and athletic departments.
Find out more about using this bid to purchase EMS Supplies & Medications here.
For additional information on any of MAPC's Collective Purchasing Programs or to discuss ideas for other regional procurements, please contact Mark Fine, MAPC's Director of Municipal Collaboration at (617) 933-0789 or email@example.com.


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We'd love to hear from you! To earn points and badges for participating in the conversation, join Cisco Social Rewards. Your comment(s) will appear instantly on the live site. Spam, promotional and derogatory comments will be removed.
3 Comments
However, living here means more to Jersey residents than any list of characteristics can explain. A Jersey childhood means being exposed to an incredibly diverse group of people you may never get a chance to meet in other states. It means learning more in a year of public school than many kids from other states learn throughout high school. Being from this state means developing the fast-paced, aggressive spirit we are known for combined with a passionate desire to better the situation around us. Growing up in New Jersey is a feeling you get when you think about the incredible friends you've made, the unforgettable experiences you've had, and the vast possibilities of a future yet to come.
It has been suggested that the crown could skip a generation, and William could be the next king. Technically, I guess that would happen through Charles abdicating before being crowned (as Edward VIII did for another reason). William is probably more popular, in part thanks to his recent marriage, and is young enough to expect another long reign. But perhaps selecting a monarch for their popularity would put us on a slow course towards an elected head of state.
Getting the reproduction timepieces can allow you to affect the timepieces on wrist typically. It is possible to select the ideal part to pair along with your correct dress. Certainly, reproduction Hermes totes may provide you with the benefit to experience a huge variety of them. The action with the todays lifestyles is evolving constantly and speedily, so vary your reproduction Hermes timepieces to satisfy the new challenge in every single new morning you will end up the founder with the tendencies with the occasions


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Michael Barone |Washington Examiner
Gallup has released President Obama's approval numbers for 2013 for the 50 states and the District of Columbia. I thought it would be interesting to compare those percentages with Obama's percentage of the 2012 popular vote in each state and D.C. His approval ratings seem to track closely with his percentage of the vote: His job approval nationally was 50 percent in the first week of November 2012, and he received 51 percent of the popular vote. Gallup conducts many interviews over the course of a year, and so its figures for each state are statistically meaningful, although I think that the error margin in small states is probably pretty large.
With that caveat in mind, let's look at where Obama's job approval fell significantly from 2012 to 2013 and where it remained relatively steady — or remained identical (in one state) or improved (in three). Nationally, Obama's Gallup job approval in 2013 (46.5 percent) was down 4.5 percentage points from his 2012 popular vote percentage of 51.[…]
Click Here To Read The Rest of: Gallup poll: Obama approval numbers suggest shifting Electoral College map


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Phoenix Symphony Association Archives
APS invested $10M in Arizona nonprofits in 2015
APS announced, Monday, its 2015 community investment in Arizona, which totaled more than $10 million. This amount includes grants, sponsorships and in-kind donations from APS and the APS Foundation to nonprofit organizations and educators throughout the state. In addition, APS employees donated more than 123,000 hours in volunteer time to Arizona nonprofits, an economic impact… Read More →
Phoenix Symphony Names 2 to Board
The Phoenix Symphony Association named Jaime Daddona Brennan and Tim K. Schultz to its Board of Directors. "Jaime and Tim bring invaluable experience to our Board of Directors," said C.A. Howlett, Chairman of the Board for The Phoenix Symphony. "We are truly fortunate to welcome such high-caliber individuals to our team" he added. Jaime Daddona… Read More →


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Zoe Saldana: Pretty Parker in L.A.
Looking cute in the California sunshine, Zoe Saldana headed to a meeting in Los Angeles on Thursday (March 21).
The "Avatar" star sported a black and white patterned top, black pants, and black buckled boots as she dutifully fed her parking meter before heading inside.
Recently, the 34-year-old actress spoke to People about her personal style, sharing, "The trend of trying to dress like everybody else is the tackiest and most dishonest thing you can do to yourself. You suffer so much because you don't ever really find your own true voice."
As for what is hot for her right now, Zoe says, "I'm into jeans on jeans. There's a Johnny Depp thing to it that I'm digging and I feel really sexy wearing it."
For more entertainment news, click here!


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"Love others as you love yourself"
It is only upon the basis of this Divine Command that the Ambassador network of the Jesus Calls Ministries was founded. Anointed people who have experienced great freedom, healing and power of God volunteered their services to help others get this power too by spreading the love and compassion of Christ.
Today Ambassadors represent the Ministry all over India and abroad. The main role of a Ambassador is three-fold as enlisted below.
1) As a Prayer Warrior/ Counsellor/ Evangelist, to meet and pray for all the needy and tell about the love and compassion of Christ- the founding principal of the Ministry.
2) As an Ambassador of Christ/ Promoter of Ministry- to liaise between the people, partners and Jesus Calls Headquarters, Chennai. And to introduce our magazines, books, cassettes etc. and other facets of the Ministry so that many more can taste the Saviour's Love.
3) As a faithful stewardship - to be upright and honest for Christ's sake.
They are indeed the ambassadors of 'Jesus Calls' Ministry, set as witnesses to Christ, and have been drawing so many to experience His love, compassion and power.
You can get in touch in with one of them near your area anywhere in the world to get our materials and information.
If you desire to represent this ministry of love and compassion, please write to us.
Jesus Calls


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In the shops of Baghdad, Iraq's capital, American cigarettes and Turkish beer are once again on sale. To Iraqi citizens, who watched the fifth anniversary of the war with Iran pass this week, the availability of products from abroad provided an unaccustomed sense of well-being. Another good omen is the imminent opening of a linkup with a Saudi pipeline to the Red Sea, which will permit Iraq to step up its vital oil exports by as much as 50%. The Iraqi government is even upbeat about the military situation. Says Information Minister Latif Nasif Jasim: "Our morale is excellent. Our supply...
The Gulf: Anniversary of a Stalemate
Anniversary of a Stalemate
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Next up on our growing stable of ways to trade the CBOE Volatility Index (VIX), we have weekly VIX options. On Sept. 28, the CBOE Futures Exchange (CFE) will introduce its first options on a futures contract, VIX Weeklys (ticker: VOW).
Yes, Weeklys. If you like them in the SPDR S&P 500 (NYSE: SPY) and PowerShares QQQ Trust (NASDAQ: QQQQ), you will love them in VIX!
There is, however, one major difference when it comes to VIX Weeklys. SPY, QQQQ and every other weekly option that trades now are exactly like "regular" monthly options except with different expiration dates. But VIX Weeklys are very different from the VIX options that currently trade.
Regular VIX options with a monthly expiration get cashed out when they expire. You get delivery of nothing; you simply get a cash debit or credit based on the VIX settlement price (VRO) and the options you are long or short. What's more, they are European-style options, which mean you cannot exercise them.
With the new VIX Weeklys, you get delivery of a VIX future. In other words, let's say you buy VIX weekly calls this week and they close in the money. You get delivery of VIX futures. Now, if you hold those VIX futures until expiration, you then cash settle based on the VIX settlement price at the future expiration.
My head spins thinking about these options. The longer a future has until expiry, the less it responds to each blip in the VIX itself. So even though weekly VIX options will always expire a week and a day from the onset of trading, they will behave very differently depending on where we sit in the expiration cycle. Let me explain.
Weekly VIX options will presumably list on Oct. 19 for delivery on Oct. 27 of November VIX futures. They will also presumably list again two weeks later, on Nov. 2, and will also result in delivery of November futures. November futures will bounce around much more on the latter batch of Weeklys, as they are much closer to cash out time. Translated back to the options themselves, the Oct. 19 VIX Weeklys should carry a significantly lower volatility than the Nov. 2 Weeklys (all other things being equal).
Of course, these two sets of Weeklys will not trade concurrently. The first batch will expire before the second batch starts trading. But it's not a distinction without merit, rather something to keep in mind if you plan to trade VIX Weeklys.
Confused? You should be. Remember this all refers to the volatility of a VIX option, Yes, the volatility of volatility. Earlier cycle weekly VIX options will carry lower volatility than later cycle weekly VIX options.
So, if you plan to try you're hand at these VIX Weeklys, make sure you're ready for odd quirks like this and the many others that will surely crop up.
Follow Adam Warner on Twitter @agwarner.
The Secret to Banking Giant Options Gains — If you're ready to make serious money, we're talking about 100%-5,300% profits, read our just-released trading guide online now. In it we reveal the money-doubling secret we were banned from sharing, plus two free trades to get you started. Get your FREE copy here!


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It all started with an onion article:
Shirtless Biden Washes Trans-Am in the White House Driveway
But after last night's stunning debate performance, where Biden was finally able to nail down a number of Paul Ryan's outright lies, the internet decided this should be a case of life imitating the Onion. A post went up over at fark.com with the headline I think we should get the internet to buy Biden a Trans-Am. Following in the footsteps of The Oatmeal's successful campaign to start a Tesla museum, a donation page was set up, a suitable Trans-Am was located (fire engine red, presumably for the pants-on-fire emergency response monster Biden has become) and, within hours, had gathered over a thousand dollars.
Meanwhile, discussions continued. Biden, as a public official, cannot accept such a gift. So the idea has shifted to purchasing a Trans-Am and aucting it off with the proceeds going to charity The current recipient list is the Biden Breast Health Initiative, Doctors Without Borders, the Wounded Warrior Project and GLAAD. It is the internet's fervent hope that before the Trans-Am is auctioned, Biden will himself wash it in front of the White House.
Since then, the link has spread to reddit, twitter and other social media. So if you enjoyed last night's debate, if you found it refreshing, even exhilarating to finally see the Romney/Ryan campaigned called on it's continual stream of malarkey, or if you just love a good internet meme, why not toss Uncle Joe a fiver?
The donation page is here.


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« Back to Schedule |
Print Camp Details
| Download Camp Waiver Form
H.S & J.C Players
Location: Baseball Stadium-SSU Campus-Savannah, Ga
Sunday, June 22, 2014
Starts: 10:00am / Ends: 4:00pm
Camp Cost: $100.00
The Savannah State University Baseball Prospect Showcase Camp will give players the opportunity to be instructed by the SSU Coaching Staff and provide an opportunity to be seen by our staff and other college coaches and scouts.
The 4th Annual Summer Savannah State University Baseball Prospect Showcase Camp will give players the opportunity to be instructed by the SSU Coaching Staff and provide an opportunity to be seen by our staff and other college coaches and scouts.
This camp is open to all potential campers in high school and junior college players ages and is designed to allow these athletes an opportunity to participate in a college-style workout, complete with position drills, scrimmages, and game situations. The Savannah State Baseball staff will conduct this camp and evaluate players on their potential to play college baseball.
Campers and Check In
Check-in will be from 9:15- 9:45am Sunday. Open to all High School and Junior College Players.
What to bring:
Each Player must bring his own baseball equipment. Players should bring a glove, bat, cleats, running shoes/turf shoes, hat, and any other equipment they feel necessary to compete. Catchers must bring their own gear. Helmets will be provided.
To reserve a camp spot: E-mail head coach Carlton Hardy at firstname.lastname@example.com or call 912-358-3082.
Please check your email regularly as this is our primary way we communicate. Any additional information that we need to convey as the camp draws closer will be passed on to you via the e-mail address that you supplied when you signed up for camp. Please make it a habit to check your e-mail daily, this will eliminate any confusion and or miscommunication.
Liability form will be attached to your e-mailed receipt and is available on-line. Please print, fill out and bring to camp.
Download Waiver Form
Lunch will be provided at this event.
What if I have to cancel a camp?
We do not offer refunds on cancelled campers, just a future camp credit if you decide to cancel, but we do have what is called "Cancellation Protection".
We offer basic Cancellation Protection to allow participants some peace of mind in case plans change. This allows us to keep our prices low and provide the best service possible. Due at the time of registration, Cancellation Protection entitles you to a full refund of camp fees should you cancel your registration more than 14 days prior to the start of an overnight camp, and 7 days prior to the start of a day camp. If you cancel within 14 or 7 days of the start of your session, we will give you a camp credit for all money paid.
The credit is valid for three years from camp date at any of our camps. Credit with insurance is transferable to family members or friends, and good toward a future camp.
For questions regarding Savannah State University Baseball Camps contact 912-358-3082 or e-mail email@example.com
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Job Reference #: 40-72119-14AC
Duties will include:
Processes AP/AR including: coding invoices, getting approvals, preparing check runs and distributing checks.
Processing the monthly and annual A/R functions: billings, coupons, maintain the receivables ledger by applying pre-paid balances and working with the PM's on any outstanding balances, lease renewals, obtaining W-9 forms, inputting P/R journal entries, and credit applications,assisting with budgets and more!
Salary will DOE with phenomenal benefits, retirement, bonus and company perks!
Qualifications include:
Bachelor's degree preferred, and 2-4 years of AP/AR, Strong MS Office skills, experience using MRI or Yardi software is a plus!
Pay - DOE
If you have questions concerning this position, please contact Angela Carroll by email email@example.com.
Please be sure to tell us where you saw this job posting. Thank you for the opportunity to consider you for this position. EOE


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Christopher And Albie Manzo Get The Millionaire Matchmaker Treatment
Holy Bravo Crossover! It turns out that Patti Stanger is "old friends" with Caroline Manzo of "The Real Housewives of New Jersey," so on the upcoming season of "Millionaire Matchmaker," Manzo's sons Christopher and Albie will be set up. I can't imagine the boys are millionaires, but maybe with their burgeoning reality TV careers, they'll get there soon enough? Apparently, the boys are looking for "brunette, Italian-Catholic girls" and since this season is filming in New York, there should be no shortage of those. Since Patti is from New Jersey, I already suspected this season will be all about tricking New York ladies into dating guys from the Garden State, and now Patti's confirmed this theory. "There are five women to one guy, so what do you do if the city is metrosexual, gay, with not enough men? Carpe diem! You go to Jersey!" Maybe we could combine three shows at once and throw the ladies of "Jersey Shore" in as bait for the Manzo man-boys? [NY Mag]


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I have worked in UAE -Dubai for 5 yrs and i have bank debts (Credit cards and personal loans and car loans) in that country and i came back to India without paying them back.My UAE residence visa also not cancelled.Its been a year now.
Basically i am from India and What can i do other than this if i don't have a job.
I got a job again in a GCC Country. I got a entry visa to other GCC Country
I heard if there is one bank security cheque bounce case UAE police issue the arrest warrant
2.will i get arrested if i go to any other GCC?
3.If the UAE issues arrest warrant thats applicable only in UAE right? They can issue GCC arrest warrant to arrest in any GCC country?
4.If the immigration systems are not shared by the GCC countries how UAE will come to know if i am in other GCC country
5.UAE can extradit me from other GCC? The UAE warrant info shared among all the GCC countries?
Please let me know so that i can decide and get it into another job and then will pay off my debts


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Thats very bad and very sad
Printable View
Thats very bad and very sad
"The newspaper also stated that the couple were unaware that they were breaking any laws, and said that "we don't want to raise them, we just want to sell them for some money.""
Wow. On another note, can you have three children in China now?
well they sold them so they only ever had one at a time?
sidenote: who would want to buy children from parents dumb enough to sell them?
OOh I was under the impression that something happened and they needed money so they sold all their kids. As to the side note, probably gold farming sweat-shops.
Does that still count as micropayment?
Yeah watching a documentry recently, apprantly if you go into the country of china you see more families with a bit more children. I think they are fined for it though, but apprantly some of them don't get caught that much since its in the country.
This is just so messed up, you really have to be sick in the head to do this.
On the positive side they can hardly be fit parents to consider gaming more important than the welfare of their children.
Call me Mr Cynical-pants but this is a second-hand report of a story in a foreign language newspaper. If a similar story was told about a couple in Little Sheepbotheringford, Aberdeenshire or Bumfuck, MO then we'd be up in arms about the paper linking games to a story about people doing something so awful, as if games are the cause and not a symptom of the problem. But it seems like it's all "oh, it's China, you know what they're like with their MMOs and their weird family planning issues". No-one's even slightly sceptical about this?
Selling children is - or was - not uncommon in China, although usually it's daughters. Can't speak as to present day, as I don't live there, but they just recently busted a sizeable human trafficking ring.
You're right, though, who knows how authentic the piece was. Maybe more sensationalist tripe aimed at gaming - the source was a chinese newspaper, after all.
Might I remind you that forced marriage is still pretty much a thing of now. Its just that completely fucked up notion that "the children you bare, you own"
(also, any kind of marriage is actually a business deal. it just got romanticised by the church)


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Carnival Fantasy Review: Carnival Fantasy Cruise Review by Johnshan
Overall Member Rating
Carnival Fantasy Review
Destination: Bahamas
Embarkation: Charleston
The main reason we chose this cruise was because of the close proximity to home (about four hours from our home in Georgia). The Charleston port was easy to navigate. Parking at the terminal was $85 for the week. The whole process was quick and smooth.
We boarded the ship and immediately went to check out our rooms. Our room had a king and a trundle and our friends had a king and two bunks. If you've been on Carnival, you know what the room looks like... small but plenty of room to sleep, shower, and change. I took the advice of several on this site and brought an over the door plastic shoe holder. Best idea EVER!!!! It was a wonderful organizer and an amazing More space saver!!! Our luggage had not arrived, so of course we went to find something to eat. We ended up getting lunch from the grill by the pool (burgers, hot dogs, chicken fingers, fries, etc.). It was yummy!
After eating, we checked our room again and our luggage had arrived so we unpacked. I unpack everything! I do not enjoy living out of suitcases. We then explored the ship and got our bearings including where the teen clubs were. We also went to the meeting about the teen clubs and made sure the kids were signed up (we had previously signed them up online). We went back to our rooms to get ready for dinner.
This is the first time we have chosen anytime dining. The first night we had to get a pager and wait about 10 minutes for a table. We got a horrible table and a very mediocre waiter (which has never happened to us on a cruise before). All of the other nights we were seated right away, at better tables, and with better waiters. We will probably not do anytime dining again. The flexibility was great but the dining experience was NOT at all the same as assigned. The personalization was missing as well as the wait staff entertainment. As for food, we loved just about everything...especially the flatiron steak, lobster, shrimp, beef stroganoff, and of course the warm chocolate melting cake!
We saw the new show with a Detroit theme (can't remember the name). Good music but just an okay performance. The kids went to there clubs and had a blast and we went to the casino to play the slots.
The first day at sea we slept in and spent most of our day laying out on the deck and watching the kids (and adults) go down the slides. Even though carnival says that saving lounge chairs isn't allowed....everyone apparently does it because it was very difficult to find chairs. We had to stalk people for awhile but we were able to get two and then two more opened up after a bit.
Our first stop was Nassau. It took about 30 min to get off the ship, big pile up in the hallways and stairwells going down. We decided to try to go get day passes at Atlantis. The excursion through Carnival was $189.00 per person so we thought we would take our chances on our own. We took a water taxi for $4 pp. not the best idea. It was a 10 minute ride but we had to wait until they filled the boat and it took us about an hour all together. I would take a van taxi next time. The aquaventure passes to Atlantis were $129.00 pp ($80 for kids 12 and under). We got them no problem and enjoyed our day. It was lots of fun but VERY spread out. I'm glad we did it but we probably won't do it again. We took a van taxi back for $4pp and it was very quick and easy. So all told, it ended up being $137.00pp for the passes and transportation.
Our second stop was Freeport. We made arrangements ahead of time with a private company, Pat and Diane's, to go on a snorkeling excursion. It was AWESOME!!!!!! Someone from the company met us right off the boat and bussed us to the boat. We paid ($42.50 pp) and got right on and fitted for our gear. The boat was fantastic...it had a grill area waterslide into the ocean and a rock wall. They took us out to a reef and off we went. The water was perfect and the reef and fish were plentiful and beautiful! Laura, our guide, was very knowledgable and super friendly. It was a wonderful excursion. We spent the rest of the day eating and straw market shopping. The same bus took us back to the ship.
On our next day at sea, we slept in again and then went back to the deck to enjoy the weather. We also did some shopping, gambling, eating, and card playing. We chose to do self disembarkation so we packed late. Disembarkation in Charleston is silent so you watch the tv to see when to get off. We were in our cars by 9:15.
Highlights: teen clubs, family comedy show, 24 hour frozen yogurt, food, great picture opportunities, snorkeling, sun, and friendly staff! We loved Carnival Fantasy! Less
Published 07/02/13
Cabin review: 4CM108 InteriorInterior (4C) Reviews >>
Port and Shore Excursions
We thoroughly enjoyed our day of snorkeling with Pat and Diane's! Our guide Laura was fantastic! The boat was great, especially for the kids (teens). It had a water slide and a rock wall. The reef we snorkeled on was gorgeous! Tons of fish and coral! The whole trip was about 3 hours. We paid $42 pp. I highly recommend this company and excursion!
Atlantis was fun but did not meet my expectations. We got day passes for aqua adventure. This included the pools, beach, aquarium, and slides. All were great but Atlantis is so spread out and very hard to navigate.
Read Cruise Critic's Carnival Fantasy Review >>
OLD OLD OLD Boat
Carnival actually wins (?!)
Positive Cruising Experience!
Don't have overly high expecta...
Lots of Shenanigans
Never Disappoints
Lots of winners and few losers...
Cruise to Cuba
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One chilly spring morning, a view on top of the Preston Center illuminates a rarely seen perspective of WKU. Eighty-eight solar panels on Preston's roof transfer heat from the sun to the pool. The sustainability tour of WKU's facilities is just beginning.
This insider access to the mechanics of our University's sustainability efforts are part of HON 380: Trends Shaping our Future: Local and Global Perspectives. The class addresses the trends shaping our local and global communities over the next 30-50 years and our part in creating the best possible future.
Each day in the class is different. Discussion drives the course, allowing students to take the talks in the direction they want to explore. It makes class exciting. Innovative ideas open up and students engage with the content more than in any lecture.
It's mind opening to say the least. After taking the class, I became conscious of the impact of even seemingly inconsequential choices and how they affect our future. Noticing the key trends unfolding inspires action. We all impact the future, for better or worse. HON 380 questions how you will impact it.
HON 380 provides multiple outlets for observing real world instances and applications for the trends discussed in class. Taking a tour of WKU's sustainability highlights brought course material into the real world. This type of class is as much about application as class discussion and content.
Last year, motivated by a desire to bring attention to hunger disparities, the two sections of the class teamed up to engage with the community through hosting an international banquet.
The banquet's guests assumed the roles of people in different parts of the world and received a meal according to actual data from that area. Plates ranged from a full steak dinner to a petite bowl of plain rice to demonstrate disparities in the world's food systems. Local eateries donated all the food.
Applying information is a critical part of the learning experience, making HON 380: Trends Shaping our Future: Local and Global Perspectives a perfect opportunity to enhance your education at WKU.


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Make any room fabulous with this beautiful ClaireaBella Angel Cushion. The angel design has been beautifully created by ClaireaBella founder Claire Barratt, and would look perfect in any aBella home. The design features an angel ClaireaBella character and the simple but beautiful quote 'Live Like Heaven Is On Earth.'
ClaireaBella cushions are the perfect size for a decorative scatter cushion on your bed, sofa or chair and will add instant glamour to any room.
Every ClaireaBella cushion is hand-made with love in the UK.
Technical Details
Please note: ClaireaBella cushions can take up to 10 working days to produce as they are hand-made with love.
The Angel Cushion features the ClaireaBella design beautifully printed on to the front, and the reverse of the cushion features black polycotton fabric.
Every ClaireaBella cushion features the ClaireaBella signature to show its authenticity.
Measurements: 36cm (W) x 25cm (H)
Please note: The cushion cover is sewn closed and is not removable


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CES 2014: 'Mother' device keeps tabs on the home
Looking slightly like a little Russian doll, "Mother" promises to keep tabs on any number of activities around the home.
Using small sensors referred to as "cookies", Mother can handle up to 24 tasks at once.
According to the company those tasks could include monitoring how much coffee is left in the jar, whether the kids have got home from school in time, and even whether they have brushed their teeth before bed.
Follow Dave Lee on Twitter @DaveLeeBBC
06 Jan 2014
- From the section Technology


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Church history is a vital subject for any serious student of theology. Without church history, we don't have a historical framework for the development of liturgical styles, church music, culture, and doctrine. Church history is not confined to pews and hymnals, though; because of the seeping nature of Christianity, Church history interacts with and affects everything around it. When the dots are connected, sacred and secular prove to be moot terms in the scope of history. Culture and s … [Read more...]
God and Country: Echoes of the Church in American Music
September 24, 2013 by Leave a Comment


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Canvas Print
No158 My SCARFACE minimal movie posterby Chungkong
Fine art print on bright white, fine poly-cotton blend, matte canvas using latest generation Epson archival inks. Individually trimmed and hand stretched museum wrap over 1-1/2" deep wood stretcher bars. Includes wall hanging hardware.
No158 My SCARFACE minimal movie poster
In 1980 Miami, a determined Cuban immigrant takes over a drug cartel while succumbing to greed.
Director: Brian De Palma
Stars: Al Pacino, Michelle Pfeiffer, Steven Bauer
Tony Montana manages to leave Cuba during the Mariel exodus of 1980. He finds himself in a Florida refugee camp but his friend Manny has a way out for them: undertake a contract killing and arrangements will be made to get a green card. He's soon working for drug dealer Frank Lopez and shows his mettle when a deal with Columbian drug dealers goes bad. He also brings a new level of violence to Miami. Tony is protective of his younger sister but his mother knows what he does for a living and disowns him. Tony is impatient and wants it all however, including Frank's empire and his mistress Elvira Hancock. Once at the top however, Tony's outrageous actions make him a target and everything comes crumbling down.
SCARFACE, Brian, De, Palma, Al, Pacino, Michelle, Pfeiffer, Tony, Montana, Cuban, Refugee, Friend, Cocaine, Drugs, Colombian, coke, guns, gangster, Miami, Florida,
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EL SEGUNDO, Calif., Nov. 5, 2012 /PRNewswire-iReach/ -- IQ BackOffice, a leading accounting solutions provider, announced today that Everest Group has recognized the company as an "Emerging Player" in the Finance & Accounting Outsourcing ("FAO") market. IQ BackOffice applies automation and best practices to client financial processes, delivering 99.97% quality and up to 68% cost savings. The company has more 60 clients worldwide, for whom it processed more than US$10 billion in transactions in 2011.
Everest Group's 75-page Finance and Accounting Outsourcing (FAO) – Service Provider Profile Compendium http://research.everestgrp.com/Product/11754, published in July, provides comprehensive coverage of the global FAO service provider landscape, including detailed analyses of leading service providers' market success, capability assessments and emerging trends. In the report, Everest Group utilizes their Performance | Experience | Ability | Knowledge ("PEAK") Matrix, a framework for assessing leading FAO service providers based on their market success and delivery capability from 2010 to 2011. Market success was measured by the annual value of active customers, while delivery capability was evaluated based on each company's scale of operations, scope, enabling capabilities, such as technology, and the company's delivery footprint.
IQ BackOffice has experienced rapid growth since an early 2011 strategic investment by LiveIt Investments, Ltd., a part of the Ayala Corporation. This investment helped the company capitalize on its high quality, software-enabled, real-time, SSAE16 Type II-certified services and the strong talent pool in their shared service centers in the US, the Philippines and India.
Recent contract awards, and investments in technology and delivery capability in general accounting, accounts payable, accounts receivable, payroll and human resources, have also enhanced the company's market standing. In addition, IQ BackOffice clients have benefited from a number of recent enhancements to Archimedes®, the company's Enterprise Process Management solution.
"We are honored that Everest Group has designated IQ BackOffice as an Emerging Player in Finance & Accounting Outsourcing," said David Schnitt, IQ BackOffice's President and CEO. "IQ BackOffice leverages clients' existing systems to deliver significant process improvements and faster access to information. Our clients achieve improved process quality and receive real-time access to information, giving them better control over their operations. We drive costs lower, help our clients make informed decisions, and help them implement stronger financial controls."
For example, IQ BackOffice's accounts payable service reengineers client processes to SSAE 16 standards, and automates them via Archimedes® to make invoices ready for web-based approval within 24 hours. IQ BackOffice offers a comprehensive procure-to-payment solution that allows clients to pay via check, ACH, wire and a credit card payment solution with monthly rebates.
About IQ BackOffice
IQ BackOffice is a leading accounting outsourcer, processing more than US$10 billion in transactions for clients around the globe in 2011. With more than 60 clients and a large staff with deep expertise in all facets of back office operations, IQ BackOffice delivers high quality, software-enabled, real-time, SSAE16/SAS70 Type II-certified finance and accounting BPO services that provide 99.97% quality and up to 68% savings. IQ BackOffice is majority-owned by LiveIt Investments Limited, the holding company for Ayala Corporation's investments in the business process outsourcing sector. Ayala was established in 1834 and is one of the leading conglomerates in the Philippines. For more information, visit IQ BackOffice at www.IQBackOffice.com or call (310) 322-2311.
News distributed by PR Newswire iReach: https://ireach.prnewswire.com
SOURCE IQ BackOffice


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Docket Management
Docket: 02N-0204 - Bar Code Label Requirements for Human Drug Products
Comment Number: EC -46
Accepted - Volume 13
Comment Record
Mr. James Carpenter
2003-05-02 10:44:46
Legacy Health System
Health Professional
Comments for FDA General
1. General Comments
Legacy Health System is fully in favor of the placement of bar codes on immediate containers for pharmaceutical product. There is concern that industry pushback will diminish the number of medications that are packaged in unit-dose packaging, a proven error-reducing method of drug product packaging and institutional drug delivery. For this reason, the FDA is encouraged to consider examining the effect of this new legislation on the rate of unit dose packaging of medications by manufacturers. Concern is, of course, that if the number of unit-dose packaged drugs decreases significantly, the burden of repackaging into bar-code compliant packaging will rest on the institution, possibly potentiating repackaging medication errors and a significant step away from industry GMP's. Jim Carpenter, RPh, MS Legacy Health System Portland, OR


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Palmer's coconut oil formula conditioning shampoo is a blend of the finest natural coconut oil and vitamin E. Its gentle cleansing, neutralizing base helps to soften dry, brittle hair. May be used on permed, pressed or bleached hair.
Water (aqua), sodium lauryl sulfate, sodium laureth sulfate, cocamide DEA, glycol stearate, sodium chloride, cocos nucifera (coconut ) oil, tocopheryl acetate (vitamin e), polyquternium-10, fragrance (parfum), quaternium-15, methylparaben, propylparaben, tetrasodium EDTA, hydroxypropyl methylcellulose, phosphoric acid.
Wet hair. Take shampoo and massage gently and then rinse it. Repeat.
Avoid contact with eyes.
Palmers Instant Coconut Oil Formula Repairing Hair Conditioner, 8.5 Oz
Our Price:$4.16
Palmer's Coconut Oil Formula Hair Milk Smoothie , 8.5 oz
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Palmers Coconut Oil Formula Hair Conditioner Jar - 5.25 Oz
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Palmers Hair Success Gro Treatment With Vitamin E - 3.5 Oz
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Palmers Hair Food Formula - 5.25 Oz
Our Price:$2.73
Palmers Olive Hairdress With Vitamin-E Jar, 8.8 Oz
Our Price:$4.76


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Psychosocial Issues Require Close Attention
By Sherry Guralnick Cohen, NP
Hemangiomas occur in 2.6% of all neonates and 10% of infants by 2 months of age.1 Although these benign tumors usually regress after a period of growth in early infancy, they are a major source of concern for parents.
Hemangiomas are distinguishable from vascular malformations using established classifications for vascular birthmarks. Hemangiomas have a growth phase involving endothelial cell proliferation, followed by an involutional phase.2 The involutional phase is characterized by apoptosis, a process of preprogrammed cell death.
Although the pathogenesis of hemangiomas is not known, investigators have implicated vascular dysgenesis and hormonal, immune-mediated, iatrogenic, infectious and genetic factors. Increased levels of heparin and mast cells may also play a role.1 High serum estradiol has been the subject of study as well, since 17B levels have been found in hemangiomas.3 Researchers have also noted an association between vessels in the placenta and hemangiomas involving a shared immunoreactivity.4 An increased risk has been reported in women who undergo chorionic villus sampling and in some women with human papillomavirus infection.5,6
Cellular markers of angiogenesis (development of new vessels from existing vasculature) have been identified by immunochemical analysis. These include proliferating-cell nuclear antigen, type IV collagenase, basic fibroblastic growth factor, vascular endothelial growth factor, urokinase, and E-selectin. Basic fibroblastic growth factor is elevated in infants with hemangiomas.7 In rare cases, hemangiomas may occur as an autosomal dominant trait instead of sporadically.8
Early clinical findings of superficial hemangiomas include a small pale or blanched macule, a telangiectasias surrounded by a blanched halo, or a red macule.9 Deeper hemangiomas have a bluish cast, since they are within the dermis and the telangiectasias or erythema may not be as visible. During the rapid growth stage, a bright plaque forms. It may range from 5 mm to 2 cm in diameter or larger.
During the involutional phase, lesions soften and the colors shift from red to purple to gray. Eventually, they lighten to skin color. Between 20% and 40% of children have some residual changes in the skin, such as telangiectasias, hypopigmentation or epidermal atrophy. Subcutaneous hemangiomas may leave fibrofatty residuum. Areas that take longer to recede are the tip of the nose, lip and parotid.10
Vascular Malformations
A brief discussion of vascular malformations assists in clinically distinguishing hemangiomas. Vascular malformations have normal endothelial cell turnover. They derive mainly from the capillary system, although they can develop from venous, arterial or lymphatic vessels.1 Most vascular malformations are present at birth and clinically stable. The most common vascular malformations include the salmon patch (also known as stork bite, angel's kiss, nevus simplex and erythema nuchae) and the port wine stain.11 A salmon patch is present at birth in more than 75% of infants. It appears as a pink to red macule on the nape of the neck, glabella, forehead, upper eyelids, nasolabial region or lower back. Facial salmon patches tend to be located on the central portion of the face and do not follow dermatomal distribution. These fade by age 1 or 2 years, but lesions on the back of the neck often persist into adulthood. Another form of the salmon patch, which disappears more slowly, occurs on the sacral region and is known as the butterfly mark.12
A port wine stain, also called nevus flammeus, is a congenital reddish purple patch. In childhood, port wine stains tend to be stable and increase proportionately in size. They are present at birth and are usually unilateral and segmental. Although 50% of port wine stains occur on the head and neck, any body part can be affected. The port wine stain initially is pink but darkens and becomes more irregular, thickened and nodular with advancing age. Although most port wine stains are isolated findings, they can sometimes be associated with malformation syndromes. Pyogenic granulomas and basal cell carcinomas can occur within a port wine stain.12
Klippel-Trenaunay Weber syndrome is characterized by a large port wine stain. It is associated with venous varicosities and progressive hypertrophy of underlying soft tissues or bone. It usually involves an arm or leg, but multiple extremities or the trunk can be involved. Lesions can be extensive.13
In Cobb syndrome, a port wine stain occurs in a dermatonal pattern on the posterior trunk. This syndrome is associated with an underlying vascular malformation of the spine. The severity of neurological problems depends on the amount of underlying spinal cord involvement.14
Epidemiology of Hemangiomas
Hemangiomas occur in 10% to 12% of children younger than 1 year. Hemangiomas can progress rapidly within a few weeks, with coloring ranging from subtle to pronounced.15,16 Fewer than 30% of hemangiomas are evident at birth, but 90% are visible within the first 4 weeks of life.17 They are three times more common in girls than boys and are also more common in preterm infants. Some investigators believe that black and Japanese infants have a decreased incidence of hemangiomas compared with white infants.13
Although the majority of affected infants have a single lesion, in rare cases a baby can have hundreds of hemangiomas. They can appear at any site, including internal organs, but they most commonly occur on the head and neck. Hemangiomas can be located in the superficial dermis and extend into the deep soft tissue. Maximum size is typically reached by age 4 months to 6 months, but some may continue to grow for up to 12 months.18 In a case review of 510 patients with hemangiomas, less than 80% to 90% doubled in size, less than 5% tripled in size, and only about 2% quadrupled in size or grew dramatically.19 A hospital-based study showed that 50% of hemangiomas resolved by age 5 years, 75% by age 7 years, and 90% by age 10 to 12 years.20
Proper diagnosis of hemangioma can usually be made with a thorough history and physical alone. But when the presentation is atypical an increase in size or number, or systemic symptoms studies such as ultrasound, magnetic resonance imaging and angiography may be warranted.
Since most hemangiomas resolve completely on their own, treatment consists of observation and education of families about the usual course. Regular follow-up, more frequent during the growth phase, is important to reassure parents and manage complications. Images of children with hemangiomas demonstrating the usual course of spontaneous regression can also be reassuring, particularly during the early period of rapid growth. Many references and Web sites are available for parents, including http://www.dermatlas.org, http://www.birthmarks.com and http://www.novanews.org.
Take photographs semiannually or annually to monitor the course of the hemangioma. Parents may benefit from support groups and, when necessary, mental health counseling. The cosmetic concern or disfiguring nature of especially large facial hemangiomas can create significant stress for families.
Primary care nurse practitioners are in an ideal position to incorporate careful follow-up, teaching and reassurance to patients with hemangiomas and their families. Because these lesions can last 5 to 10 years or more, families require ongoing monitoring and support.
Complications of Hemangiomas
Hemangiomas are occasionally complicated by high-output cardiac failure, necrosis and ulceration (Figure 4), compression of vital structures, or associated malformation syndromes. These problems may require special monitoring, imaging studies, laboratory evaluation, and specific medical or surgical intervention.
High-output cardiac failure is a complication of visceral hemangiomas typically associated with involvement of the liver. Multiple hepatic hemangiomas may be difficult to manage and carry a high mortality rate. Be aware that infants with or without cutaneous hemangiomas can present with heart failure from occult hepatic hemangiomas. Hepatomegaly and a bruit over the liver suggest this diagnosis.7
In diffuse neonatal hemangiomatosis, multiple cutaneous hemangiomas may be associated with visceral involvement of one or more organs, usually the liver, lung, gastrointestinal system or central nervous system. Hepatic involvement with heart failure is a common complication of diffuse neonatal hemangiomatosis.16 Affected infants develop multiple rapidly growing 1- to 3-mm hemangiomas shortly after birth. The physical examination should include palpation for cranial and abdominal bruits. Further studies (magnetic resonance imaging, cardiac or abdominal ultrasound and laboratory evaluation) should be directed by individual clinical findings and symptoms. Healthy infants with normal growth and development and no evidence of complications are diagnosed with benign cutaneous hemangiomatosis.12
During the rapid growth period, hemangiomas in certain locations are prone to complications. In areas that receive friction, such as the diaper area, neck crease, flexural creases of arms and legs, or occipital scalp, hemangiomas may develop painful ulcerations. This is also true of massive lesions at any site. Bleeding and secondary infection can occur. Anogenital hemangiomas are particularly prone to ulceration and can interfere with urination or defecation. Infected hemangiomas (a rare occurrence) can lead to cellulitis, arthritis, osteomyelitis or septicemia.7
Close proximity to vital organs can result in occlusion or obstruction. The most common sites of concern are the eye, airway and auditory canal. Periocular hemangiomas require close evaluation and early evaluation by an ophthalmologist to prevent permanent visual impairment. Amblyopia, significant refractive errors and strabismus have been noted in 80% of patients with untreated periocular hemangiomas.1 Hemangiomas involving the nose or mouth can cause partial or complete airway obstruction and eating difficulties. Complete airway obstruction can also result from circumferential laryngeal hemangiomas. Hemangiomas involving the ear and external auditory canal can cause scarring and conduction hearing deficits. Oral steroids may be used to treat these complications.1,7,12
Large facial hemangiomas may be associated with PHACES syndrome. This is a malformation syndrome with posterior fossa brain abnormalities, hemangiomas, arterial anomalies or intracranial hemangioma, cardiac anomalies (coarctation of the aorta), eye anomalies, and sternal or other midline deformities. PHACES syndrome should be considered a possible diagnosis in children with large, segmental, plaque-like facial hemangiomas including one or more dermatomes. These patients require eye examination, imaging studies of the brain with contrast, careful cardiac examination, and ultrasound of the heart and major vessels.1,21
When a cutaneous hemangioma involves the anogenital area or the lower back, rule out midline malformations of the spinal cord (tethered spinal cord) and anorectal or urogenital defects by ultrasound examination of the lumbosacral spine. This should be performed before 6 months of age.22,23 In older infants, magnetic resonance imaging is necessary.22,23
Kasabach-Merritt syndrome, which occurs rarely in newborns and infants, presents as a large, rapidly growing, deep-seated vascular lesion. The three components of this syndrome are severe thrombocytopenia, hemolytic anemia and a consumption coagulopathy. Although the vascular lesions associated with this disorder may demonstrate clinical features of a hemangioma, biopsies usually reveal kaposiform hemangioendothelioma or tufted angioma. Screening tests should include a complete blood count, blood smear, prothrombin time, partial thromboplastin time, platelet count and fibrinogen level. It is also necessary to determine soluble fibrin, platelet and fibrinogen survival. Systemic corticosteroids and alpha-interferon have been used to stop the progression of rapidly growing tumors and correct the potentially life-threatening thrombocytopenia and consumptive coagulopathy.12
Treatment of Complications
Ulcerated hemangiomas can be treated conservatively with topical antibiotics (mupirocin [Bactroban], bacitracin), gentle daily cleansing and nonstick dressings. Recalcitrant lesions may improve with pulsed dye laser therapy, and when all else fails, oral corticosteroids.7,18
Systemic or intralesional corticosteroids are used when the hemangiomas impinge on vital organs and act to shrink them or stop the rapid growth phase. Oral steroids may be safer and more effective. Most prescribers choose oral corticosteroids for complicated hemangiomas at a dose of 3 mg/kg/day to 5 mg/kg/day until the lesions respond, and then taper the dose over 2 to 6 months. Interferon is usually reserved for life-threatening or eye-threatening complications that do not respond to systemic steroids.1 Risks of oral steroids include colic, hypertension, decreased growth, fluid retention and predisposition to viral and bacterial infection. These children need to be monitored closely and the corticosteroid tapered as soon as possible.
The pulsed-dye laser (PDL) causes selective thermal destruction of the abnormally dilated blood vessels but has little effect on normal surrounding cutaneous structures. For this reason, some experts advocated early treatment of hemangiomas with PDL to stop the development of hemangiomas and trigger early regression. However, a prospective, randomized controlled study demonstrated no value to laser treatment for hemangiomas during the first year of life.18 In this study, 121 patients were randomized to an observation or a treatment group. The clearing of hemangiomas occurred similarly in the observation and treatment groups, but PDL significantly increased the risk of skin atrophy and hypopigmentation. Other studies have shown that PDL is an effective treatment for residual telangiectasias after the hemangiomas have involuted without therapy.24
Recent reports of spastic paresis have discouraged the use of interferon for hemangiomas except in life-threatening circumstances when other measures fail.1
In select cases, there may be a role for surgical excision or interventional radiologic sclerotherapy.1
Psychosocial Issues
Fifty percent of hemangiomas occur on the head and neck, often in a highly visible location. Understandably, the period of rapid growth is a concern for parents and families.
Upon entering school, residual lesions become a social concern for the child. Research shows that parents' emotional reactions include feelings of loss, grief, guilt, self-blame and aloneness.24 Reaction from the general public is a major stress and prevents some parents from taking their children on outings. A common concern is how the child's self-image and development will be affected over time. Parents recognize their child's awareness of the lesion by age 12 to 24 months, and social sensitivity starting after age 4 years.
Children with craniofacial anomalies receive less attention and are provided with less social involvements than unaffected children, shortfalls that lead to signs of aggression and antisocial behaviors.25 Research has documented few psychological differences between 3- to 5-year-old children with and without facial hemangiomas.26 The differences begin to surface as the children enter school.
To improve the psychological outlook for families, provide ongoing support to parents. Discuss the natural history of hemangiomas, and give families the opportunity to ask questions and express concerns. Explain that you are following the progression of the lesion, and that you will be available to discuss treatment options and follow their child's social and behavioral development.
Parents can help their children by modeling how to react appropriately to the lesion. Parents have found it helpful to teach a simple response to the inevitable questions about the hemangioma. "It's my birthmark and will go away" is an appropriate response. Regular playgroups or preschool environments provide support for the child, as well as a "rehearsal" for the school years.24
In most cases, sequential photographs demonstrate regression of the lesion and are a source of comfort to parents. Direct all parents to educational Web sites where they can see images of how other children's hemangiomas have regressed. These, too, can be a source of comfort.
Finally, counsel parents that residual hemangiomas, scarring, persistent vessels and loose skin can usually be repaired before children enter school. Intervention at that time may be safer and more effective than aggressive treatment in early infancy.18
1. Ceisler EJ, Santos L, Blei F. Periocular hemangiomas: what every physician should know. Pediatric Dermatology. 2004;21:1-9.
2. Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg. 1982;69:412-420.
3. Sasaki GH, Pang CY, Wittliff JL. Pathogenesis and treatment of infant skin strawberry hemangiomas: clinical and in vitro studies of hormonal effects. Plast Reconstr Surg. 1984;73:359-370.
4. North P, et al. A unique microvascular phenotype shared by juvenile hemangiomas and human placenta. Arch Dermatol. 2001;137:559-570.
5. Burton BK, Schulz CJ, Angle B, Burd LI. An increased incidence of hemangioma in infants born following chorionic villus sampling (CVS). Prenatal Diagnosis. 1995;15:209-214.
6. Cannistra C, Standoli L. Viral implication in immature angiomas. Etiopathogenic hypothesis and immunohistopathologic study of eleven cases. Pathol Biol. (Paris) 1994;42:150-155.
7. Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in children. NEJM. 1999;341:173-181.
8. Blei F, Walter J, Orlow SJ, Marchuk DA. Familial segregation of hemangiomas and vascular malformations as an autosomal dominant trait. Arch Dermatol. 1998;134:718-772.
9. Hidano A, Nakajima S. Earliest features of the strawberry mark in the newborn. Br J Dermatol. 1972;87:138-144.
10. Nakayama H. Clinical and histological studies of the classification and the natural course of the strawberry mark. J Dermatol. 1981;2:277-291.
11. Jacobs AH, Walton RG. The incidence of birthmarks in the neonate. Pediatrics. 1976;58:218-222.
12. Rabinowitz LG, Esterly NB. Vascular birthmarks and other abnormalities of blood vessels and lymphatics. In: Schachner LA, Hansen RC, eds. Pediatric Dermatology. 2nd ed. New York, N.Y.: Churchill Livingstone; 1996: 953-989.
13. Young A, Cohen BA, Siegfried E. Cutaneous congenital defects. In: Taeusch HW, Ballard RA, Gleason CA, eds. Avery's Diseases of the Newborn. Philadelphia, Pa.: Elsevier Saunders; 2004:1521-1538.
14. Enjolras O, Garzon MC. Vascular stains, malformations, and tumors. In: Eichenfield LF, Friedman IJ, Esterly NB, eds. Textbook of Neonatal Dermatology. Philadelphia, Pa.: W.B. Saunders Co.; 2001: 324-352.
15. Jacobs AH. Strawberry hemangiomas: the natural history of the untreated lesion. Calif Med. 1957;86:8-10.
16. Holmdahl K. Cutaneous haemangiomas in premature and mature infants. Acta Paediatr. 1955;44:370-79.
17. Finn MC, Glowacki J, Mulliken JB. Congenital vascular lesions: clinical application of a new classification. J Pediatr Surg. 1983;18:894-900.
18. Betta K, et al. Randomized controlled study of early pulsed dye laser treatment of uncomplicated childhood haemangiomas: results of a 1-year analysis. Lancet. 2002;360:521-27.
19. Bowers RE, Graham EA, Tomlinson KM. The natural history of the strawberry naevus. Arch Dermatol. 1960;82:667-680.
20. Ezekowitz RA, et al. Interferon alfa-2a therapy for life threatening hemangiomas of infancy. New England Journal of Medicine. 1992;326(22):1456-1463.
21. Poetke M, Frommeld T, Berlien HP. PHACE syndrome: new views on diagnostic criteria. Eur J Pediatr Surg. 2002;12:366-374.
22. Albright AL, Gartneer JC, Wiener ES. Lumbar cutaneous hemangiomas as indicators of tethered spinal cords. Pediatrics. 1998;83:977-80.
23. Goldberg NS, Herbert AA, Esterly NB. Sacral hemangiomas and multiple congenital anomalies. Arch Dermatol. 1986;122:684-687.
24. Tanner JL, Dechert MP, Frieden IJ. Growing up with a facial hemangioma: parent and child coping and adaptation. Pediatrics. 1998;101:3:446-451.
25. Dieterich-Miller CA, Safford PL. Psychosocial development of children with hemangiomas: home, school, health care collaboration. Children's Health Care. 1992;21:84-89.
26. Dieterich-Miller C, et al. Behavioral adjustment and self concept of young children with hemangiomas. Pediatric Dermatology. 1992;9(3):241-245.
Sherry Guralnick Cohen is a family nurse practitioner and psychiatric clinical nurse specialist who practices dermatology at Johns Hopkins University Medical Center in Baltimore.
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This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
All the therapeutic strategies for treating cancers aim at killing the cancer cells via apoptosis (programmed cell death type I). Defective apoptosis endow tumor cells with survival. The cell can respond to such defects with autophagy. Autophagy is a cellular process by which cytoplasmic material is either degraded to maintain homeostasis or recycled for energy and nutrients in starvation. A plethora of evidence has shown that the role of autophagy in tumors is complex. A lot of effort is needed to underline the functional status of autophagy in tumor progression and treatment, and elucidate how to tweak autophagy to treat cancer. Furthermore, during the treatment of cancer, the limitation for the cure rate and survival is the phenomenon of multi drug resistance (MDR). The development of MDR is an intricate process that could be regulated by drug transporters, enzymes, anti-apoptotic genes or DNA repair mechanisms. Reports have shown that autophagy has a dual role in MDR. Furthermore, it has been reported that activation of a death pathway may overcome MDR, thus pointing the importance of other death pathways to regulate tumor cell progression and growth. Therefore, in this review we will discuss the role of autophagy in MDR tumors and a possible link amongst these phenomena.
Biosynthesis and degradation are two processes that regulate the maintenance of internal homeostasis of an organism. Intracellular degradation is governed by two distinct systems: the ubiquitin-proteasome and the lysosome-autophagy system. The ubiquitin-proteasome system targets short-lived and misfolded proteins, while the lysosome-autophagy system additionally can target long‑lived macromolecular complexes and organelles [
Microautophagy participates in the continuous basal turnover by forming random invaginations in the lysosomal or vacuolar membrane that differentiate into the autophagic tube to enclose the portions of cytosol. In 1981, chaperone-mediated autophagy (CMA) was discovered [
Autophagy is a distinct form of membrane trafficking [
One of the most unnerving clinical issues is the recurrent tumor progression after treatment, due to resistance to structurally and mechanistically unrelated compounds [
On the basis of mechanisms of resistance, MDR is broadly classified as non-cellular and cellular mechanisms as discussed below (
The phenomenon of non-cellular drug mechanisms is associated with some types of solid tumors. Poor tumor vascularization and ischemic regions in solid tumors can induce resistance to chemotherapeutic agents. The acidic pH in ischemic regions of the tumor microenvironment is due to lactic acid generation, which may also contribute to the resistance to weak bases [
Cellular-based resistant mechanisms are further classified into non-classical MDR phenotypes and transport-based classical MDR phenotype. Non-classical MDR is acquired by the tumors because of the activity of some specific enzymes, such as glutathione S-transferase and topoisomerase [
Classification of MDR. A flowchart illustrating the classification of MDR.
Although autophagy occurs as a continuum, it is conceptually helpful to dissect the core autophagic pathway into several key stages. These stages include initiation and formation of the phagophore, autophagosome formation and lysosomal fusion. This core pathway has been the focus of several review articles that thoroughly discuss the roles of many proteins, as well as several lipids [
Cellular survival during metabolic stress depends on the proper implementation of autophagy. The formation of an autophagic vacuole from intracellular membranes that surround the proper cytosolic constituents is complex and requires the interplay of many molecular machines. Although we are starting to understand the mechanism of this process, great progress has been achieved identifying many of the proteins involved in autophagy. A central regulator for the initiation of autophagy is Beclin1 (Bcl-2 interacting coiled-coil protein 1; also known as ATG6) [
An early observation that linked the regulation of autophagy and apoptosis is in non-stressed cells, where Beclin1 forms a complex with, and is inhibited by, Bcl2, a central anti-apoptosis regulator [
Formation of the autophagosome from the phagophore requires recruitment of Atg 12, Atg5, Atg 7, Atg10, Atg16, and the subsequent post-translational lipidation of LC3 (microtubule associated protein 1 light chain3/Atg8). Lipidation of LC3-I requires post-translational conjugation of Atg12 with Atg5 (this process is analogous to ubiquitin conjugation) [
Interestingly, LC3 undergoes a series of post-translation modifications prior to joining the phagophore. First, the c-terminal arginine of nascent LC3 is cleaved off by the cysteine protease Atg4 to form LC3-1. The c-terminal amino acid of cytosolic LC3-1 is a glycine. Now, LC3-1 can be lipidated by the Atg7, Atg3, and the Atg12-5 conjugate to form LC3-II [
Although it has long been known that autophagosomes with cytosolic contents fuse with lysosomes for degradation, the molecular mechanism underlying the process is largely unknown. Recently it has been reported that TECPR1 (Tectonin domain-containing protein 1) binds to the Atg12-Atg5 conjugate and phosphatidylinositol 3-phosphate (PtdIns(3)P), and this interaction promotes autophagosome-lysosome fusion [
Beclin1 has multiple binding partners and it seems the binding partner determines Beclin1-mediated alterations in cellular physiology. As described above, Beclin1 associates with PI3Kinase class III to promote autophagy, while Beclin1-mediated autophagy is inhibited by complex formation with Bcl2. Cellular physiology is under the influence of another recently identified heterodimer combination, Beclin1/HMGB1 (
The chromatin binding protein high mobility group box 1 (HMGB1) has a well-characterized damage-associated molecular pattern. It is found in the nucleus, bound to chromatin, in undamaged cells. HMGB1 is released from the nucleus and has a cytosolic localization in damaged but living cells while it is released from necrotic cells into an extracellular environment [
Autophagy cannot escape control by p53. p53, the prototypical tumor suppressor, regulates autophagy-mediated homeostasis, by monitoring the rate of autophagy to the varying nutrient availability [
Summary of regulatory mechanisms of autophagy. (
Activation of receptor tyrosine kinases (RTK) inhibits autophagy. RTK activation promotes activation of Ras (rat sarcoma) signaling, including activation of PI3Kinase class I. PI3Kinase class I phosphorylates ptdIns(4,5)P2 to form PtdIns(3,4,5)P3 at the plasma membrane. This molecule signals recruitment of AKT (also known as protein kinase B) and phosphoinositide-dependent protein kinase1. Co-recruitment of these two kinases leads to activation of AKT. Active AKT promotes accumulation of RHEB GTP by phosphorylating and inhibiting TSC1/TSC2, RHEB GTPase activating proteins. RHEB GTP activates mTOR (mammalian target of rapamycin). Activation of this serine/threonine kinase is a potent inhibitor of autophagy (
AKT activation and inhibition of autophagy is predicated on the accumulation of PtdIns(3,4,5)P3. PTEN, a potent tumor suppressor that is deleted in many cancers, is a phosphatase that converts PtdIns(3,4,5)P3 to PtdIns(4,5)P2. This prevents activation of AKT, mTOR, and the subsequent inhibition of autophagy [
Negative regulation of autophagy by PI3Kinase/AKT/mTOR pathways followed by DEPTOR-mediated positive feedback loop for mTOR.
DEPTOR, a DEP domain containing mTOR-interacting protein, is an endogenous inhibitor of mTOR. DEPTOR is degraded by the 26S proteasome in response to phosphorylation by mTOR leading to SCF (TrCP)-mediated degradation. Thus activation of mTOR leads to reduced inhibition of DEPTOR and a positive feedback loop controlling autophagy [
Extensive studies indicate that autophagy plays a controversial role in the survival and death of cancer cells [
In contrast to the well-documented cancer-promoting effect of autophagy, a function of autophagy in an anticancer role has been proposed. Accordingly, some oncogenic proteins (Bcl-2, PI3K, Akt1,
Taken together, the double face of autophagy in tumor cell survival and suppression is complex and context-dependent. A better understanding of molecular mechanisms of autophagy, as well as the role of autophagy, in different stages of carcinogenesis will help develop new approaches for the prevention and therapy of tumors.
The overexpression of ABC transporters is predominantly correlated with drug resistance. Hence, compounds that can inhibit ABC transporter-mediated efflux are developed as potential chemotherapeutic agents against MDR. However, modulators of MDR are not as effective as expected because, besides ABC transporters, various other mechanisms contribute to drug resistance. Recent studies have suggested approaches to exploit autophagy to overcome MDR during anticancer therapy [
There is a large body of evidence demonstrating that autophagy is required to kill the MDR tumor cells. However, a recent study showed that the inhibition of autophagy is required to sensitize NIH 3T3/MDR cells to a Src tyrosine kinase inhibitor, PP2 [
Cancer progression is governed by numerous genetic factors; MDR is also regulated by a combination of several drug resistant factors. MDR is an intricate, dynamic and intangible phenomenon. Although, conventional anticancer drugs have multiple targets, MDR seems to be highly unavoidable because anticancer drugs may be substrates and inducers of ABC transporters. Thus, it has been followed as a rule in clinical trials that a modulator of the activity of the ABC transporter in combination with standard anticancer drug is administered, to make resistant cancers responsive to the therapy. However, even this combination treatment does not completely abolish resistance. This makes it important to further elucidate the role of other pathways that may be communicating with MDR. As known, autophagy in healthy cells acts as a janitor by removing the damaged organelles and proteins, reducing the reactive oxygen species, and suppressing necrosis-induced inflammation that can induce cancer when chronic. However, it behaves as a cytoprotectant in established tumors and hence, its inhibition could enhance apoptosis [
Role of autophagy in MDR tumors. Autophagy has a dual role in MDR tumors. Autophagy may lead to survival of MDR tumors or its activation may lead to tumor cell death.
The authors declare no conflict of interest.
This work was supported by funds from NIH R15 No. 1R15CA143701 (ZS Chen), and St. John's University Seed grant No. 579-1110 (ZS Chen).


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nice job sickness, i'm guessing the metsploiting is good out in romania!
Printable View
nice job sickness, i'm guessing the metsploiting is good out in romania!
Free File Hosting Made Simple - MediaFire like g0tmi1k's video.
i can download from Free File Hosting Made Simple - MediaFire and fast!!!
Actually pentesting is rare in Romania :))
Please could u how to solve this issue. I tried already during a few days but it doesn't work: When I try to load the nessus plugins, it gave me the following message
Whatever, problem solved. It was solved by updating the framework (I did before but it didn't work) and asking some help on #offsec (Nice guys actually).Code:
Failed to load plugin from /opt/metasploit3/msf3/plugins/nessus: no such file to load -- nessus/nessus-xmlrpc
Will the nessus bridge work with nessus 4.4?
Great Vid :cool:
@podjackel it should work fine, I did not try it yet but I'm certain it will work flawless.
Ok I will test it tomorrow with Nessus 4.4 and see if it works.
Excellent work sicness, thank you.
4.4 works fine here as well


text:
Superintendents (subordinated to the governor
of Jamaica)
First minister
¹Full style:
Territorial Disputes: Guatemala persists in its territorial claim to half of Belize, but agrees to the Line of Adjacency to keep Guatemalan squatters out of Belize's forested interior; both countries agreed in Apr 2012 to hold simultaneous referenda, scheduled for 6 Oct 2013, to decide whether to refer the dispute to the ICJ for binding resolution; Belize and Mexico are working to solve minor border demarcation discrepancies arising from inaccuracies in the 1898 border treaty. Honduras claims the Belizean-administered Sapodilla Cays off the coast of Belize in its constitution, but Guatemala claims that the Belize–Guatemala maritime boundary is northwest of Sapodilla.
Party abbreviations: PUP
= People's United Party (social-democratic, to 1954
named People's Committee, est.1950); UDP =
United Democratic Party (conservative, merger of Liberal
Party, National Independence Party, and People's
Development Movement, est.1974)
© Ben Cahoon


text:
Log Candelabra
So, I have a fireplace but have never lit it. Just don't know how, but I'd love to use it. I mean, it's one of the selling points of my home. Here's the perfect solution, pretty birch logs that can be lit to give that glow of the fireplace (with the heater on to keep me warm).


text:
victoria martinez
My Eden - Poem by victoria martinez
I came here to understand this sin
I walk around to see the beauty that faded in the end
I came here to unite with him
I walked along breathing it all in
And I realized that it was right for Eden to end
There was evil planted that caused gods light to dim
These green trees withered and died
These pieces of fruit were consumed by vines
The golden earth turned pitch black
Sin dripped like morning dew on trees
The air was thick with Eve's pleas
I could feel the love that was once so strong
And I felt it fade as I walked alone
I came to a spot
The darkest spot of all
I shivered and tears streamed down my checks
I didn't feel sad but some how I knew
This is where Eve did…
She did what well all regret from time to time
She simply gave in
Temptations were beckoning and she was weak
I know what's right but still I seek
I look for those answers even though I know they are wrong
I ask these questions to find out if heaven will allow my mistakes
And I beg god to help me each and every day
I look to find out where I want to be
But my mind doesn't let me see
I block out all light because the unknown darkness makes me feel free
And I lost it all when I realized I'm what I've always avoided being
I look down and see my mistakes laid before me
I sit here and feel everything falling
I gave up when I looked for this sin
I gave up when I found out why Eden came to its end
I understand why temptation is it
I understand why Eve needed it
I understand it
I know it
I am it
And then Eden fades out as I let go once again
Eden was my life I let it become this tattered place
Eden was heaven and I let it become destroyed with my lost faith
Eden is gone and I let you fall
Eden I'm now lost
I'm out here all alone
And my hate grew my blame is new my heart has to be glued from time to time
People hurt me, I hurt me, God hurt me?
Confusion makes all of it blurry…
Eden I wish you were once again new
I came here with all my sin and it grew as I entered into the forsaken garden
Eden you are the distorted part of my mind
I came to Eden to forget the happiness I once knew
I came to Eden to break the glue
If my heart is broke let it shatter
If my hate is thick let it grow
I lied and that's when Eden died
The evil planted from deep with in was my mistrust that I knew would become my end
Eden I'm here now to burry you
Eden I'm here now to let go of all those memories you brought
God take me away and please help me make Eden just fade
I came here to understand my sin
I walk alone and my mind is breaking from deep with in
And then I realized it was right for Eden to end
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