text:
Berlin attack: Police say lorry crash 'probably terror attack'
German police are investigating a "probable terrorist attack" after a man ploughed a lorry into a Christmas market in the heart of Berlin, killing 12 people and injuring 48.
They have detained the driver, who security sources reportedly say is an Afghan or Pakistani asylum seeker.
He arrived in Germany in February as a refugee, the DPA news agency said.
The daily Tagesspiegel said the man was known to the police for minor crimes, but not terror links.
"All police measures related to the suspected terrorist attack at Breitscheidplatz are progressing at full steam and with the necessary diligence," Berlin Police said on Twitter.
Berlin witnesses describe devastation
German politicians had avoided branding the bloodshed a terror attack in the hours immediately following, but Interior Minister Thomas de Maiziere told ARD television, "there are many things pointing to one".
What happened?
The market is at Breitscheidplatz, close to the Kurfuerstendamm, the main shopping street in Berlin's west.
The crash happened in the shadow of the Kaiser Wilhelm Memorial Church, which was damaged in a World War Two bombing raid and preserved as a symbol of peace.
The truck, which was loaded with steel beams, veered into the market at 20:14 local time (19:14 GMT),one of its busiest times. It crashed through wooden huts and stands packed with tourists and locals.
According to the DPA news agency, police believe the lorry drove 50-80 metres (160-260 ft) through the market area.
What do we know about the suspect?
The lorry driver was reportedly seized after leaving his truck and fleeing on foot.
Berlin police spokesman Winfried Wenzel told the German newspaper die Welt that the man ran down the street towards the Tiergarten, a large public park.
A witness followed him at a distance for more than a mile (2 km), and called the police, who quickly detained him near the Victory Column monument.
The police spokesman speculated that the driver may have wanted to "find shelter in the darkness of the park".
German media say the suspect was from Afghanistan or Pakistan and had entered the country as a refugee in the past year.
Where did the lorry come from?
Police confirmed that a passenger was found dead in the lorry, and said he was a Polish national. There are fears he may have been the original driver of the vehicle, and that he was subject to a hijacking.
Ariel Zurawski, the Polish owner of the lorry, confirmed that his driver was missing and had been unreachable since 16:00 (15:00 GMT) on Monday.
"We don't know what happened to him," he told the AFP news agency. "He's my cousin, I've known him since I was a kid. I can vouch for him."
The truck was registered in Poland and police said it was believed to have been stolen from a building site there, the Associated Press news agency reports.
How has Germany reacted?
Chancellor Angela Merkel has been briefed by the interior minister and the mayor of Berlin, her spokesman Steffen Seibert tweeted.
"We are in mourning for the dead and hope that the many injured can get help," he added.
Reacting to the news from Berlin, Nice Mayor Christian Estrosi tweeted: "Horror in Berlin. Support for the mayor of Berlin and the German people. never again."
What do eyewitnesses say happened?
A British eyewitness, Mike Fox, told Associated Press at the scene that the 25-tonne lorry had missed him by only about three metres as it smashed through stands and knocked down a large Christmas tree.
"It was definitely deliberate," said the tourist, visiting from Birmingham.
He said he had helped people who appeared to have broken limbs, and that others were trapped under Christmas stands.
Australian Trisha O'Neill told the Australian Broadcasting Corporation she witnessed "blood and bodies everywhere".
"I just saw this huge black truck speeding through the markets crushing so many people and then all the lights went out and everything was destroyed.
"I could hear screaming and then we all froze. Then suddenly people started to move and lift all the wreckage off people, trying to help whoever was there."
Is this the first such attack?
A series of small-scale attacks by Islamist militants alarmed Germany earlier this year.
Monday's incident evoked memories of the lorry attack on Bastille Day crowds in the French city of Nice on 14 July, when 86 people were killed. That attack was claimed by so-called Islamic State (IS).
Both IS and al-Qaeda have urged their followers to use trucks as a means to attack crowds.
The United States labelled the tragedy an apparent "terrorist attack" and pledged its support.
President-elect Donald Trump blamed "Islamist terrorists" for a "slaughter" of Christians in the German capital.
"Today there were terror attacks in Turkey, Switzerland and Germany – and it is only getting worse. The civilized world must change thinking!" he tweeted.
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Welcome to Librarium Online!
Join our community of 80,000+ members and take part in the number one resource for Warhammer and Warhammer 40K discussion!
Registering gives you full access to take part in discussions, upload pictures, contact other members and search everything!
Hey this is the first time I have posted here. Since I only just descovered this vantastic sight. I have been playing warhammer fantasy for about 6 years all of which I have been playing competitively. I have just recently purchased ogres and am very exited about this army. I have been number crunching lists:wacko: . Ok, I have come up with a list that can take care of many types of of armys including heavy hitting ones and magic centered, which are very common at big tournaments. I will explain my choices and explain my strategys.
Tyrant - Gut maw and 3 Gnoblar Thief stones. As well as a great wepon, heavy armor and 2 sword gnoblars. (305)
The point of this character is to be able to let the unit take on calvary and win, He has no ward save, but makes up with it by the maw. So he is a challege aholic. He goes in the Bull unit.

Butcher - Dispell scroll. As well as two tooth gnoblars. (165)
The point of this character is to be able to mabey get off a spell mabey... but to have the one dispell scroll to get rid of that one game swinging spell that must not go off. Goes in the Iron guts unit.

Hunter - 2 cats and beast killer and grayback belt. (235)
The point of this character is to take out all those big monsters, as terror can still affect my army. With one lucky wound roll, I can do 6 wounds, plus I can hid in a forst and help out the gnoblar trappers.
7 Bulls(general goes here) - Armed with light armor and iron fists.
I like this because an ogre with aa 4+ save in combat cant be beat on a charge being taken. plus on a charge on with me charging an extra attack. Its all about versitility. I gave them a standard and a musician. (331)

7 Iron Guts (butcher goes here) - I gave the magical standard rune maw banner. This way if a spell is cast on them it is most licly deflected upon my ogres which is at a maggic resistace 3. They have a standard and a musician. They must be placed within 6 inches of the general, may seem constricting but really isnt. 2 huge units of ogres together is good. (376).

20 Gnoblars - These are given nothing. Like they could. They are for the points of a table quarter. I dislike them as screeners since they hamper the movment of the ogres but if agains a super shooter I have too. (40)

8 gnoblar scouts - These are for the usual reasons, preventing marching, war macs. and to kill those other scouts or at least let them kill this crappy unit instead of hurting my my good units. I dont like the champion I like point crunching and this was a nessesary to kill him for what he does.(4.

Special

3 Leadbelchers - These are my flanking units still have bull charge with the unit of 3 and thats why i have them at 3 and not at two. I like the fact that they can fire every turn if they make no movment in the movment phase. I know this fact may be challenged but until it is changes in the rule book it, they can fire stand still and fire the next shooting phase. (175)

3 leadbelchers - Same as above.

1 Gorger - This is for the shooting that is devastating if unchecked against my ogres. (75)
1 Gorger - This second is to make sure that the shooting is keeped in check. Some may not agree, but with a second one, the probablility of one comming on at turn 2 is 75 percent and that is great. Even if one is blown to pieces by there shooting, then there not shooting at my other ogres, or my hunter wich can take care of shooting too. You may think I am paranoid about shooting, but if you have ever been on a competative tournament you know how powerful well constructed shooting magic armies can be. SO I stand by in my decision.(75)

I make sure that the two major units are put together, and the leadbelchers are on the flanks, the gnoblars are as described above, The spells will most likly be dispelled, the ones that target units. and on turn two their shooting should be concered with the beasts that are immanent. Other than that the terain is a major factor, ad depends on set up for what will occure.

I have gone against high elves and khorn with great sucess. As khorn is suseptable to lures of the gnoblar hunters and the high elves only hope was a great commet since i dispelled all magic and as described on turn two both came out and caused them to shoot at the gorgers and not my unit of bulls. all in all I am pleased with this roster and just wanted some minor critiques if you can explain your decision I will do my best to answer it with my reasons thx.
Last edited by Wolf_Pack; February 16th, 2006 at 02:10.
I have edited your test to include spaces.
A second scroll for your butcher, or a bang stick.
Ironfists and light armour makes your bulls very expensive, naked with clubs will let you feild more, and keep your units cheap.
Musicians for your leadbelchers.
Best Regards,
i appoligise my lead belcher have musicians. Just forgot to post them, but thx for the spacing. The second scroll was unneccesary so far. I have been able to get by with one since i usually can go wizard hunting at turn 3,4. Offencive magic is also counter intuative, since those 25 points are very strained. I like the 4 up save on the bulls, they are only 2 heavy units in the game and for the points thay are effective enough since there is my general in the unit. I have tried naked but with that even streanth 3 attacts can kill a bull. but thx for some opinions.
Last edited by laughingman; February 16th, 2006 at 02:35.
yeh as Wolf pack said the Bangstick is a very good idea :yes:


text:
Dpmt 7 is constantly researching and exploring new materials, connections, technologies, and ways of executing design, art, and architecture at all scales.
Our work is centered on process and collaboration in making. Through making we get to know space and material, structure, and craft more fully. Our 10,000 square foot warehouse space in lower price hill allows us to build and work at full scale. It is in the explorations, curiosities, and overlaps that we find our inspiration.
We offer a range of design services here at dpmt 7 and within our collective we possess individual expertise in many areas. If you are curious about anything you see on the website or have a project in mind that you would like to see made real, please send us an email at email@example.com or come on down and see us.


text:
by Robert Hughes
(Weidenfeld, £25)
This history of Rome is as much about the glory that is Robert Hughes as the wonders of the Colosseum, St Peter's or the Piazza Navona.
Hughes, with Barry Humphries, is the most significant of the fêted group of media-ravenous Australians who colonised Sixties England; and as the art critic with the fiercest stare in the business it is Hughes and not Sir Les Paterson who is Australia's pre-eminent cultural attaché. It has taken this national monument, the façade a little weatherbeaten now, more than 50 years but he has turned at last to the city that made him what he is.
Hughes arrived in Rome in 1959 aged 20, "nuts" about the idea of it: he had never seen classical architecture, public statuary or, outside the pages of a book, many paintings. For him, as for all first-time visitors, the city was a daunting entity - a dense accretion of history, art and symbolism - but it was also a chance to see "the real thing in the real place". It is this pared-down definition that underlies his approach to Rome's past.
Hughes is what the milordi of the 18th century on their Grand Tour would call a bear leader; a guide and chaperone who shows his wide-eyed charges not just the expected sights but also the hidden and quirky spots, with a bit of moral guidance added too. A great city, he notes, "is not mere raw size but the amount of care, detail, observation and love precipitated in its contents" and, in one long, smooth chronological sweep, he sets about describing each element and the men and forces that brought them about.
Hughes begins his informative and entertainingly opinionated tour with Rome's mythical founders Romulus and Remus and he works his way briskly through the Roman kings and the republic before himself following Suetonius for his punchy account of the deeds and misdeeds of the emperors.
Augustus, who famously "found Rome a city of brick, and left it a city of marble", is something of a hero figure. Like all good historians Hughes is not afraid to let his admiration show: the Pantheon, built around AD125 by Hadrian, which still has the largest unreinforced dome in the world, is a thing of wonder; the Roman road system which spread 120,000 kilometres is another.
With Christian Rome, at least after the papacy's economically disastrous sojourn in Avignon from 1305 to 1376 - the effect of which he likens to Los Angeles losing the entertainment business - he is even more spoilt for choice. There are, of course, Michelangelo's Sistine ceiling, Borromini's churches, Caravaggio's transformative paintings (an artist who "thrashed about in Seicento Rome like a shark in a net"), Canova's sculptures and, above all, Bernini, "the marble megaphone of papal orthodoxy".
If there is one object that sums up the whole city and its distinctive genius it is the baldacchino, that extraordinary bronze fantasy wrought by Bernini from 1623-34 to stand over the tomb of St Peter at the heart of the greatest church in Christendom. Neither fully architecture nor sculpture, this towering metal canopy, commissioned by Urban VIII, is quintessential Rome: it reuses the past (its bronze was stripped from the roof of the Pantheon); it is a monument to ambition; it inspires awe; it is overwhelmingly theatrical; it is a physical statement of the power of the Catholic Church and even more so a statement of the power of art. It sets Hughes buzzing.
He is witheringly frank about the artistic sterility that struck the once virile city in the 19th and 20th centuries and which shows no sign of ending. Silvio Berlusconi's TV stations with their "cushion-lipped, big-breasted" presenters are the bread and circuses of modern Italy. Indeed, there is something of the toga-clad republican about Hughes as he fires out bracing polemics on everything from why there will never be another Rubens to the horror of visiting the Sistine Chapel ("the most trying conditions under which I have ever looked at art"). An honorary citizen he may be but Hughes has a claim to be the noblest (modern) Roman of them all.
- More about:
- Australasia
- Australia
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text:
You're the Target
"Social Engineering is the act of deceiving people into giving away access to confidential information such as passwords or member information"
"A skilled social engineer can circumvent all of our technical controls in a matter minutes if we allow it"
"Awareness of social engineering by all of us is one of our greatest security controls"
Social Engineering
Email Security
"85% of malware comes from the web with drive by downloads"
"30,000 sites are infected daily"
"80% of infected sites are legitimate"
-Sophos Labs
Internet Security
"Passwords are one of the weakest forms of security"
"123456 is the #1 most common password"
"password is the #1 most common base word"
Workspace Security
Incident Response
Security Awareness
Secures data between your PC and another PC
Plain Text - "The account number is xxxxxx"
Cipher Text - "JGKDASOIREMVPSOKEIMISFF"
The Key - password, token, biometric
Anything digital can be encrypted
How Social Engineering Works
How to Detect Social Engineering
How to Respond to Social Engineering
They will contact you:
Phone call
In person
Establish a connection
Develop trust through a relationship
Requests for valid information
Request for confidential information
An uninitiated contact by a stranger
Quick talker who quickly becomes friends
Asks a lot questions
Stresses urgency
Asks for confidential information
Passwords, member info, company info, employee info, IT info, personal info, operations info, building info
Ask for their name and number
Ask for the name of a company contact
Verify their information
Verify with their contact if applicable
Verify with their company if applicable
Technology - Verify with IT
Operations, etc - Verify with supervisor
Sending Emails Securely
Don't use member info such as account numbers and social security numbers
Only use last 4 of account # to reference
Don't use personal information
Types of Malicious Emails
Email Spoofing
Spear Phishing
Bad grammar and spelling
How to Respond to Malicious Emails
Did you initiate the email conversation?
Yes - Most likely legitimate but use caution
No - Most likely fake
Verify the sender with another communication means
Beware of links, attachments, and pictures
If in doubt call or email myself or anyone else in IT
"74% of email messages are spam"
"92% of malicious emails contain a web link"
"9% of data stealing attacks occur over email"
HTTP vs HTTPS
Domain - www.cinfed.com
Understanding the URL
Never install add-ons unless it is a secure site required for work purposes
Never download files unless it is a secure site required for work purposes
Never download email attachments unless you were expecting an attachment
Downloading Files
At least 8 characters
Uppercase letters
Lowercase letters
No personal references
Example - "%28PluTo13%"
How to Create Your Password
A complete phrase
20-30 characters
Uppercase letters
Lowercase letters
No personal references
Example - "CaptainJack$parrowAndTheBlackPear1"
Convert a phrase into an acronym
At least 8 characters
Uppercase Letters
Lowercase letters
"My son's birthday is January 22 2007"
Store in an encrypted file
Why It Works On Us
Strong Affect
Induce panic
Create an emergency situation
Too much information too fast
Deceptive Relationships
Build a relationship and exploit it
Portray authority figure
Key logging
Brute force
Wire tapping
Over the shoulder
Public PC
How They Get Your Password
Lock your drawers
Lock your door if applicable
Clean desk
Shred documents with account numbers and other confidential information
Examine your workspace as a whole
Securing Your Workspace
Securing Your PC - Windows + L
Escort your visitor
Unknown Visitors
In person social engineering
Notify your supervisor
Ask for purpose, name, company, Cinfed contact
Verify with their Cinfed contact
Verify with their company if necessary
Social engineering attempt
Malicious email
Internet security issue
Password compromise
Confidential data theft
What if you suspect:
Don't ignore or hide your suspicion
Notify your supervisor and contact anyone in IT quickly to mitigate any possible damage
"90% People & Processes"
"10% Technology"
IT User Policy
External and Remote Access
Must be approved
No one else can use your connection
No pictures of your screen are allowed
Internet Access
During business hours for business use only
Limited personal use allowed during lunch, breaks, etc
All internet usage is monitored and logged
Don't transmit sensitive data over unencrypted connection
Only download files required for job duties
Only access appropriate sites
Phone System Usage
No sensitive information allowed over the phone unless the recipient has been verified
Reasonable and limited personal use is allowed
Acceptable Use
Don't put any files you consider personal on the system
Files on the system are owned by the company
Reasonable and limited personal use is allowed during lunch, breaks, etc
Approved Hardware and Software
All hardware connected to the network must be approved
All software downloaded and installed must be approved
Digital Camera Usage
Don't take pictures of members, IT equipment, private branch areas, security systems, computer screens
Email Access and Use
Any sensitive data sent via email must be encrypted
Reasonable and limited personal use is allowed during lunch, breaks, etc
Email is monitored and logged
Don't use external messaging systems such as Facebook and Twitter to contact members
Removable Media
Removable media such as CD's, DVD's, flash drives, cameras, and phones should not be connected to the PC's
Social Media
Do not share sensitive company info on social media
Do not mention members or employees in a negative context
If you blog about an industry related topic use a disclaimer to announce your opinions are not affiliated with the company
Do no share sensitive info
Do not mention members or employees in a negative context
Electronic Device
Electronic devices must be authorized to access company data
Don't connect electronic devices to the company network
WIFI is provided at some branches for your convenience
Clean Desk
Sensitive information must be locked or stored securely
All sensitive documents must be shredded
Security Tokens
Security tokens must be stored in a secured area when unused
All files and computer use can be monitored, don't store anything you wouldn't want someone else to see
Present Remotely
Send the link below via email or IMCopy
Present to your audienceStart remote presentation
- Invited audience members will follow you as you navigate and present
- People invited to a presentation do not need a Prezi account
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Security Awareness
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David Shepherdon 19 November 2014
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text:
Savannah Throw in Grey with Fringe
The Savannah Throw with Fringe comes in an eye-catching shade of grey. The throw showcases the traditional basket-weave technique with a fresh twist—the weave is alternated with the twill to create a medium to heavy-weight blanket with a textural stripe. The resulting pattern is just as appealing as it is cozy.
50"W x 72"L
Composition: 100% Cotton
Care: Machine wash and dry recommended. Wash cold separately and tumble dry low heat. Do not bleach. Warm iron if necessary.
We Also Recommend


text:
Opened 5 years ago
Last modified 5 months ago
#9073 confirmed Bug
ImageUpload callback can not be called cross-domain.
|Reported by:
|Owned by:
|File Browser
window.parent.CKEDITOR.tools.callFunction(CKEditorFuncNum, uploadedImageUrl, sucessMessage);
Change History (3)
comment:1 Changed 5 years ago by j.swiderski
- Component changed from General to File Browser
- Status changed from new to confirmed
- Version set to 3.0
We are aware of this problem but this will be done with window.postMessage (E.g. https://developer.mozilla.org/en/DOM/window.postMessage) and not with scripts.
comment:2 Changed 5 months ago by riczha
Hi there, I am using the 4.6.0 version and I am still hitting the same issue. just wondering if there is any workaround?
It seems the my server (different domain) uploading part is fine but the callFunction is blocked due to the XORS limitation.
any update on this ticket?
comment:3 Changed 5 months ago by j.swiderski
I'm sorry but no one is working on this ticket at the moment.


text:
Two hours and eleven minutes after sunset Siyyid `Alí-Muhammad makes His declaration to Mullá Husayn-i-Bushrú'í.
Táhirih is sent back to Baghdád from Karbalá. She is lodged first in the house of Shaykh Muhammad Shíbl and then in the house of the Muftí of Baghdád. During her time in Iraq she enlists a considerable number of followers and makes a number of enemies among the clergy [B162; DB271]
The governor offers all of his resources to try to win the Sháh over to His Cause but the Báb declines his offer saying that the Cause will triumph through the `poor and lowly'. [B115–16; DB212–13]
Some accounts maintain that the prime minister intervened in the correspondence between the Báb and the Sháh. En route to Tabríz the Báb writes to various people, including the Grand Vizier, the father and uncle of Táhirih, and Hájí Sulaymán Khán. Hujjat learns of this last letter and sends a message to the Bábís of Zanján to rescue the Báb. The Báb declines their assistance. [B124–5; DB235–6]
At the beginning of the Báb's incarceration the warden `Alí Khán keeps the Báb strictly confined and allows no visitors. He has a vision of the Báb engaged in prayer outside of the prison gates, knowing that the Báb is inside. He becomes humble and permits the Bábís to visit the Báb. [B129–31; DB245–8]
The winter the Báb spends in Máh-Kú is exceptionally cold. [DB252]
Many of the Báb's writings are revealed in this period. [GPB24–5]
Arrived in Qazvín, Táhirih refuses her estranged husband's attempts at reconciliation and lives with her father. Her father-in-law Hájí Mullá Taqí, feels insulted and denounces the Shaykhís and Bábís. [B166; DB2736]
BBRSM22 says the murder took place towards the end of October.
Mullá `Abdu'lláh confesses to the murder of Hájí Mullá Muhammad Taqí and is helped to escape. [BKG41–2; DB278]
Mullá Husayn proceeds to Mashhad and builds a `Bábíyyih', a centre for the Bábís, as instructed by Quddús. He and Quddús take up residence in it and begin to teach the Bábí religion.
Bahá'u'lláh, who hosts and directs the event, rents three gardens, one for Quddús, another for Táhirih and the third for Himself. [B168; GPB31, 68; MF200]
The conference coincides with the removal of the Báb to Tabríz for interrogation in July.
It is held near the village of Sháhrúd in Semnan province. [BBRSM23; DB292]
Táhirih is arrested and is later taken to Tihrán where she is held in the home of Mahmúd Khán, the Kalántar of Tihrán, until her martyrdom in August 1852.
Mullá Husayn leaves the army camp near Mashhad where he has been a guest of a brother of the Sháh. He plans to make a pilgrimage to Karbalá. While making preparations for the journey he receives a Tablet from the Báb instructing him to go to Mázindarán to help Quddús, carrying a Black Standard before him. He is also instructed to wear the Báb's own green turban and to take the new name Siyyid `Alí. [B171; BKG50; DB324; MH174]
Mírzá Taqí Khán-i-Faráhání takes up post as prime minister. [BBR482]
DB 368 says this occurred on 21 December 1848.
At daybreak the soldiers mount a counter-attack. [DB367; MH258–9]
In the morning the Báb is taken to the homes of the leading clerics to obtain the death-warrants. [B155; DB508]
At noon the Báb and Anís are suspended on a wall in the square in front of the citadel of Tabríz. They are shot by 750 soldiers in three ranks of 250 men. [B157; DB512]
The Báb and Anís are suspended a second time. A new regiment, the Násirí, has been found to undertake the execution. After the volley, the bodies of the Báb and Anís are shattered. [B158; DB514]
At night, the bodies are thrown onto the edge of the moat surrounding the city. Soldiers stand guard over them and, nearby; two Bábís, feigning madness, keep vigil. [B159; TN27]
A few days later, Bahá'u'lláh leaves Tihrán for Karbalá on pilgrimage. [BKG66; DB587]
He is then taken 'on foot and in chains, with bared head and bare feet' to Tihrán where He is cast into the Síyáh-Chál. [BKG77; DB606–7; ESW20; GPB71; TN31]
Eighty–one, of whom 38 are leading members of the Bábí community, are thrown into the Síyáh-Chál. [BKG77]
The martyrdom of Táhirih in Tihrán. [BBR172–3; BBRSM:30; BW18:382; BKG87; MF203]
Many Bábís are tortured and killed in the weeks following the attempt on the life of the Sháh. [BKG84]
Bahá'u'lláh's half-brother Mírzá Yahyá flees to Tákur and goes into hiding. He eventually goes to Baghdád. [BKG90, 107]
Hájí Ákhúnd (Mullá 'Alí-Akbar-i-Shahmírzádí), Hand of the Cause, becomes a Bábí in Mashhad. [EB266]
Mullá Sádiq-i-Muqaddas-i-Khurásání (Ismu'láhu'l-Asdaq), a Bábí and father of Ibn Asdaq, meets Bahá'u'lláh in Baghdád and becomes a follower. [BKG18]
Some Bábís are imprisoned in Tihrán. [BW18:382]
'Abdu'l-'Alí Khán-i-Marághi'í is killed in Tihrán on the order of Násiri'd-Dín Sháh. [BW18:382]
On learning that Bahá'u'lláh is to leave Baghdád, large numbers visit Him. The house is too small for the purpose. Najíb Páshá puts his garden-park, Najíbíyyih, at Bahá'u'lláh's disposal. [RB1:259]
Bahá'u'lláh and His party arrive at Firayját, about three miles away on the banks of the Tigris. [BKG176]
Upheaval at Najafábád.
Bahá'u'lláh reveals the Súriy-i-Ghusn (Tablet of the Branch) in which 'Abdu'l-Bahá's future station is foreshadowed. [BBD218; BKG250; GPB177]
In this period the extent of the Faith is enlarged, with expansion in the Caucasus, the establishment of the first Egyptian centre and the establishment of the Faith in Syria. [GPB176]
The greeting Alláh-u-Abhá' supersedes the Islamic salutation and is simultaneously adopted in Persia and Adrianople. [BKG250; GPB176]
The phrase 'the people of the Bayán', which now denotes the followers of Mírzá Yahyá, is discarded and is supplanted by the term 'the people of Bahá. [BKG250; GBP176]
Nabíl-i-A'zam is despatched to Iraq and Iran to inform the Bábís of the advent of Bahá'u'lláh. He is further instructed to perform the rites of pilgrimage on Bahá'u'lláh's behalf in the House of the Báb and the Most Great House in Baghdad. [BKG250; EB224; GPB176–7]
The first pilgrimages to the residence of Bahá'u'lláh take place. [GPB177]
Persecutions begin anew in Ádharbáyján, Zanján, Níshápúr and Tihrán. [GPB178]
He was elevated to a Hand of the Cause of God in 1951 and passed away in Tubingen, Germany in 1955 while taking a treatment for an illness. [BW13p831-834]
The first phase, from1941 through 1955, was a period characterized by physical danger, during which Baha'is were scapegoated in the interactions among the government, the clerics and the people, and experienced several bloody incidents, the culmination of which was the 1955 anti-Baha'i campaign and its aftermaths.
The second phase, from the late 1950s to around 1977, marked almost two decades of relative respite from physical attacks, during which Baha'is enjoyed more security than before, without ever being officially recognized as a religious community and while their existence as Baha'is was essentially ignored or denied.
The last two years of the reign of the Shah comprised the third phase, the revival of a bloody period. [Towards a History of Iran's Baha'i Community During the Reign of Mohammad Reza Shah, 1941-1979 by
Mina Yazdani]
Concurrent with the Forty-Five Month Plan Iran launches a Women's Plan.
1 Consolidation of all local Bahá'í communities.
2. Reestablishment of 62 dissolved Assemblies. (93 LSAs formed)
3. Formation of 22 groups.(37 established)
4. Creation of 13 new centres. (24 localities established)
5. Development of Assemblies from groups located in Kabul, Afghanistan, Mecca, Arabia and Bahrein Island, Persian Gulf.
6. Sending pioneers to India and 'Iráq to assist in the formation of new groups.
The Bahá'ís of Tehran were called upon to send out 50 families into the pioneer field. (160 arose) Every individual Bahá'í was included in the operation of the Plan-as a volunteer, by deputizing a pioneer, by contributing funds, by circuit teaching or by providing hospitality to students whose parents had become pioneers.
[The Baháʾí World 11, pp. 34-36]
First arrested in 1995, Mr. Mahrami served in the civil service but at the time of his arrest was making a living installing venetian blinds, having been summarily fired from his job like thousands of other Baha'is in the years following the 1979 Iranian revolution. Although Iranian officials have asserted that Mr. Mahrami was guilty of spying for Israel, court records clearly indicate that he was tried and sentenced solely on charge of being an "apostate," a crime which is punishable by death under traditional Islamic law. While Mr. Mahrami had been a lifelong Baha'i, the apostasy charge apparently came about because a civil service colleague, in an effort to prevent Mr. Mahrami from losing his job, submitted to a newspaper an article stating that he had converted to Islam. When it later became clear to Iranian authorities that Mr. Mahrami remained a member of the Baha'i community, they arrested him and charged him with apostasy for allegedly converting from Islam to the Baha'i Faith. On 2 January 1996, he was sentenced to death by the Revolutionary Court, a conviction that was later upheld by the Iranian Supreme Court.
The death sentence against Mr. Mahrami stirred an international outcry. The European Parliament, for example, passed a resolution on human rights abuses in Iran, making reference to Mr. Mahrami's case. The governments of Australia, Brazil, Canada, France, Germany, the United Kingdom, and the United States also registered objections.
Statement: English Translation
Faezeh Hashemi is the activist daughter of former President Akbar Hashemi Rafsanjani and she previously shared a prison cell with Kamalabadi in Evin Prison. Hashemi is strongly condemned by politicians and religious leaders. A high-ranking member of the Iranian Judiciary vows that action will be taken against her. Despite the widespread criticism she has received from powerful quarters in Iran, Faezeh Hashemi publicly defends her decision to meet with Kamalabadi. [Iran Press Watch, from NY Times, BWNS1108]
And at the age of sixty-three, that pure soul, that radiant and magnanimous soul, offered up his life in absolute meekness, hoisted the
ensign of martyrdom and attained his Beloved's presence in the realms above, and in the Abha Kingdom joined the company of the other martyrs of this Faith--among whom number his own noble father and six other relatives who, sixty-one
years ago in Hurmuzak, near Yazd, sacrificed their lives in the path of the Blessed Beauty.


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A couple of days have passed since NCDevCon (May 22nd – 23rd) and everything is starting to sink in. Before I get into a recap of my experience, I just want to give a little background on the event. NCDevCon is a free conference in Raleigh, NC. The focus of the conference was Flex/Flash, Air, Javascript, Design, Coldfusion, and overall web development. The promoters, Dan Wilson and Jim Priest with backup by the TACFUG, do an outstanding job in putting together a quality conference. And they do it so that attendees do not have to pay a dime to attend the conference. Phenomenal, effort. Continue reading
Monthly Archives: May 2010
Grails and Flex Presentation for NCDevCon 2010
We just wrapped up the first day at NCDevCon. What a great day and an equally awesome conference. If you missed it you can find all the sessions online, including one that I am partial to, Rapid Development With Grails and Flex
Video of the Grails and Flex Presentation – http://bit.ly/9yXN1W
Slide deck and source code coming soon.
If you have never written Groovy/Grails then you are really missing out. Give it a try and check out www.grails.org
I enjoyed the opportunity to present this topic, it was a lot of fun to prepare for and the audience was awesome. I do want to give special thanks to Jason Rudolph for his guidance and his book Getting Started With Grails – available in free PDF format, but help an author out and purchase the book as well. We want authors to keep writing and inspiring us. They can't keep doing it for free.
I also want to throw a big shout out to all those in the Groovy/Grails Community for providing a fun and useful language and framework.


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This Ibis hotel is in central Mainz, just 500 ft from the Rhine River and the Romisches Theater S-Bahn Station. It features well-equipped rooms and a 24-hour bar.
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Centrally located in Mainz, just 100 metres from the main railway station, this family-run, non-smoking hotel features a free sauna and free Wi-Fi internet access.
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Situated just 300 metres from Mainz Train Station, this hotel offers modern studios with kitchens and free WiFi. GuestHouse Mainz is an ideal base for exploring the Rhine-Main region.
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Just 200 metres away from the main railway station, this hotel in Mainz city centre offers modern accommodation, a charming bar and a daily breakfast buffet.
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This 4-star-Superior hotel features air-conditioned rooms and a spa area with an indoor swimming pool. It is located in Mainz city centre, a 10-minute walk from the main railway station.
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Hotel Roemerstein offers free parking, traditional food and a gym. It is located in the Zahlbach district of Mainz, beside the university and close to buses.
"Very cozy and friendly. Hotel and room very clean …ay from hustle and bustle of city streets. Nice."
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Situated beside the river Rhine in Mainz, family-run Favorite Parkhotel features an indoor pool, an outdoor hot tub, and a gym overlooking the Old Town.
"Lovely hotel with wonderful staff. Room and breakf… This hotel is unpretentious but excellent value."
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This modern 3-star hotel in Mainz offers barrier-free rooms with balconies, free WiFi, complimentary breakfast, and good transport links. The historic Schillerplatz square is 5 minutes away by tram.
"Not quite central but relatively close to the cent… and accommodating. I would certainly stay again."
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Season 07, Episode 01 – "Hiraeth"
Frank wakes up after a month-long coma to find no one missed him. Worried she isn't a good mother, Debbie takes a criminal approach to making sure Franny grows up wealthy. Meanwhile, Lip successfully completes rehab and is determined to stay "sober;" Carl looks into surgery after learning he's the only uncircumcised brother; and Ian gets a bad feeling about Caleb's friend Denise.
Chicagoan Frank Gallagher is the proud single dad of six smart, industrious, independent kids, who without him would be… perhaps better off. When Frank's not at the bar spending what little money they have, he's passed out on the floor. But the kids have found ways to grow up in spite of him. They may not be like any family you know, but they make no apologies for being exactly who they are.
(17 downloads) Aired September 24, 2016
(12 downloads) Aired September 24, 2016


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The author(s) have made the following declarations about their contributions: Conceived and designed the experiments: RB RC WV SNC SG. Performed the experiments: RB RC CT FP CM YL. Analyzed the data: RB RC CT FP CM WV SG. Contributed reagents/materials/analysis tools: RB RC FP CM YL SG. Wrote the paper: RB RC WV SNC SG.
Thrombopoietin (TPO) via signaling through its cognate receptor MPL is a key cytokine involved in the regulation of megakaryocyte differentiation leading to platelet production. Mature megakaryocytes are polyploid cells that have arrested DNA replication and cellular proliferation but continue sustained protein synthesis. Here, we show that TPO induces cell-cycle arrest in the megakaryocytic UT7-MPL cell line by the activation of the ERK/MAPK pathway, induction of p21CIP transcription, and senescence markers through EGR1 activation. A similar senescence-like process was also detected in normal primary postmitotic megakaryocytes. In contrast, senescence was not observed in malignant megakaryocytes derived from primary myelofibrosis patients (a form of chronic myeloid hemopathy). Our data indicate that polyploid mature megakaryocytes receive signals from TPO to arrest cell proliferation and enter a senescent-like state. An escape from this physiological process may be associated with certain myeloproliferative neoplasms leading to abnormal megakaryocytic proliferation.
Megakaryocytes are huge bone marrow cells that shed platelets into the blood stream to promote clotting at sites of injury. Mature megakaryocytes differentiate from precursor cells in response to a hormone called thrombopoetin. Here, we show that as part of this normal differentiation process mature megakaryocytes enter a state called senescence in which cell division stops—a feature normally associated with cell aging and death. By studying megakaryocytes in culture, we were able to determine the biochemical pathway induced by thrombopoetin that leads to gene activation associated with senescence. We conclude that thrombopoietin acts differently at two steps in megakaryocyte differentiation: in the early stages it induces megakaryocyte proliferation, and at a latter stage it arrests the cell division cycle leading to platelet production by these cells. Interestingly, certain malignant megakaryocytes did not undergo senescence in response to thrombopoetin, which might explain the abnormal proliferation of these cancerous cells.
Hematopoietic stem cells (HSCs) in adults are maintained in a long term-quiescence state. On rare occasion HSCs may enter the cell cycle, and their proliferative state is usually coupled to a differentiation process regulated by both intrinsic and extrinsic factors such as cytokines (reviewed in [1]). In most somatic cells, proliferation is dependent on mitogen-activated protein kinase (MAPK) signaling, shown to be involved in the transition through the early G1 phase of the cell cycle (reviewed in [2]). Particularly, prolonged MAPK signaling is also a potent inducer of differentiation and thus links proliferation and developmental progression in somatic cells [3],[4]. However, when mature cells are produced, they are maintained in a post-mitotic state by mechanisms not yet fully understood.
Megakaryopoiesis is the hematopoietic differentiation process that leads to platelet production. The arrest of megakaryocyte proliferation is followed by ploidization resulting from endomitosis. During endomitosis, cell size and protein production per cell increase. Indeed, endomitosis corresponds to a mitosis with a failure of late cytokinesis but is still associated with DNA replication [5],[6] and transcription [7]. Usually, when megakaryocytes become 16N, the endomitosis process stops and is followed by terminal differentiation leading to cytoplasmic fragmentation and platelet shedding. The main regulator of megakaryocyte differentiation is the cytokine thrombopoietin (TPO: GeneID: 7066). TPO binds to and activates the TPO receptor (MPL: GeneID: 4352) signaling to regulate both early and late stages of differentiation [8].
Cellular senescence is a state of permanent cell-cycle arrest contributing to tissue aging and has been considered in recent years as an intrinsic barrier against tumorigenesis (reviewed in [9]–[11]). Recently, multiple secreted inflammatory cytokines, their cognate receptors, and induced transcription factors have been identified as key mediators of oncogene-induced senescence (OIS) [12]–[14]. Besides prevention of tumor outgrowth from benign lesions, other roles of OIS in non-oncogenic processes are emerging such as the fibrogenic response to acute tissue damage [15]. Senescence can be triggered by activated oncoproteins such as BRAFE600 or RASV12 and occurs in a variety of cell types [14],[16]–[18]. OIS is accompanied by an up-regulation of CDK inhibitors, for instance p15 (GeneID: 1030) (also known as INK4B), p16 (GeneID: 1029) (also known as INK4A), and p21 (GeneID: 1026) (also known as Cip1), and is associated with an increase in the senescence-associated β-galactosidase (SA-β-Gal) activity [19]–[22]. Moreover, the senescence process is recognized as a physiologically irreversible mechanism, yet some cancer cells can escape this process [23],[24].
It has been suggested that a possible link between senescence and terminal differentiation might exist. It is well known that TPO, via binding to MPL and activation of associated tyrosine kinase JAK2 (GeneID: 371), induces a high and sustained RAS/MAPK activation in megakaryocyte precursors and mature megakaryocytes [4]. Thus we hypothesized that such a mechanism may be involved in the proliferative arrest observed in mature megakaryocytes.
The erythro-megakaryocytic cell line UT7 does not naturally respond to TPO due to very low expression of the TPO receptor MPL but responds to GM-CSF, a hematopoietic cytokine mediating its effects on the neutrophil lineage as well as on hematopoietic progenitors, but it does not appear to have a role in basal hematopoiesis. The UT7 cell line expresses GM-CSF receptors and proliferates in response to this cytokine. We transduced the cells with a retroviral vector encoding MPL and selected a clone called UT711oc1, which expresses high level of MPL. Proliferation of UT711oc1 cells was stimulated by GM-CSF (Figure 1a). Surprisingly, in presence of TPO, UT711oc1 cells proliferated over a 2-d period before stopping (Figure 1a). This was a marked difference with the previously described UT7/MPL cells, which were selected for their growth in presence of TPO [25] but similar to other previously UT7 cell line described by Porteu et al. [26]. UT711oc1 cells could be maintained in culture for 3 wk (unpublished data). These differences are probably related to the selection processes of the clones: i.e., long term selection at a low dose of TPO for the UT7/MPL Komatsu's cells and viral transduction of mpl for Porteu's and our cells. These UT711oc1 cells were blocked in the DNA replication process (Figure 1b) and underwent morphological changes characterized by large cytoplasm and nucleus (Figure 1c). Exposure to TPO for 3 d was sufficient to render the cell unresponsive to further stimulation by GM-CSF (Figure 1e), suggesting that cell-cycle arrest was not reversible. Moreover, we did not detect any Annexin V staining in UT711oc1 cells stimulated with TPO (Figure S1a), nor were the PARP and caspase 3 cleaved (Figure S1b). On the other hand, these cells exhibited HP1gamma foci (Figure 1g), SA-β-galactosidase staining (Figure 1d), and expressed cell-cycle inhibitors such as p21CIP and p27KIP (GeneID: 102) (Figure 1f), as previously reported [27], 3 senescence-associated markers. These results were confirmed in two other MPL-overexpressing UT7 cell lines (Figure S1c). In order to confirm that TPO was able to induce senescence, other markers of senescence were analyzed. Cathepsin D (GeneID: 1509) mRNA up-regulation has been previously proposed as a senescence marker [28]. We observed a drastic increase in cathepsin D mRNA expression in TPO-exposed cells (Figure S1d). To confirm the senescence phenotype, we determined TPO-induced gene expression in 24 h TPO-exposed cells relative to that of GM-CSF-stimulated cells by micro-array analysis. The TPO-induced gene expression profile was then compared to the published molecular signature of oncogenic ras-induced senescence [29]. A gene set enrichment analysis (GSEA) comparing these two sets of genes revealed a significant enrichment for TPO-induced gene expression in senescent fibroblast genes (Figure 1h). This enrichment was highly significant for up-regulated genes. The coincident 30 most up- and down-regulated genes are depicted (Figure S2). Among the most up-regulated coincident genes, we found genes involved in inflammation (CXCL2 (GeneID: 292), PTGS2 (GeneID: 574), IL6 (GeneID: 356), IL8 (GeneID: 3576), CXCL3 (GeneID: 2921), IL1B (GeneID: 3553)) that agree with recent literature linking OIS to an interleukin-dependent inflammatory network and among the most down-regulated coincident genes appeared genes involved in DNA replication and cell proliferation. Lastly, senescent cells are able to secrete cytokines and chemokines. We analyzed TPO-exposed UT711oc1 supernatant cytokine concentrations compared to GM-CSF-exposed UT711oc1 supernatant. MCP1 (GeneID: 6347), IL-1, IL-10 (GeneID: 3586), and VEGF (GeneID: 7422) are secreted by TPO-exposed cells when compared to GM-CSF stimulated cells, cytokines previously reported to be secreted by senescent cells (Figure S1e) [30]–[33]. There are various types of senescence including the senescence induced by short telomeres and OIS. While the first mechanism is linked to long-term culturing, OIS can quickly be induced in cell lines after small GTPase RAS overstimulation. TPO has been shown to induce a high and sustained level of the RAS/MAPK signaling (Figure 1f). Altogether, these data indicate that TPO per se is able to induce a senescence process in UT711oc1 cells. We investigated the implication of MAPK activity in TPO-induced senescence.
In order to determine whether TPO-induced senescence was RAS/MAPK dependent, we used MAPK pathway inhibitors. RAS/MAPK inhibition either by PD98059 or U0126 reversed the TPO-induced cell proliferation arrest (Figure 2a) as previously reported [4], restored DNA replication (Figure 2b), and decreased the SA-β-galactosidase staining (Figure 2c), p21CIP level (Figures 2d and S3a), and cathepsin D expression (Figure S3b) but did not induce recurrent changes in p27KIP, p53 (GeneID: 7157), or p16INK4a expression (Figure S3c). These results illustrate that TPO-induced senescence is MAPK-dependent. In order to clearly demonstrate that the senescence phenotype was a direct consequence of sustained RAS/MAPK-pathway activation, we over-expressed a constitutively active form of MEK (MEK1-S218D/S222D) in UT711oc1 cells and cultured cells in presence of GM-CSF. We observed a proliferative arrest (Figure 2e) as previously reported [34], a DNA replication arrest (Figure 2f), an increased SA-β-galactosidase staining (Figure 2g), a rise in the p21CIP cell-cycle inhibitor transcript (Figure S3d) and protein (Figure 2h), and an up-regulation of cathepsin D mRNA (Figure S3e), but it did not affect p27KIP expression (Figure S3f). Of note, TPO stimulation or active form of MEK did not change total ERK protein expression (Figure S7). We concluded that TPO-induced senescence was a direct consequence of the ERK activation.
To clarify the implication of cell-cycle inhibitors in TPO-induced senescence, we knocked down cell-cycle inhibitors (p27KIP, p21CIP, p16INK4a) and p53 in the UT711oc1 cell line using lentiviral shRNA expression. Specific shRNAs were functional at the protein level (Figure 3a). TPO induced a decrease in cell proliferation and in DNA replication in the shRNA-expressing cell lines except for p21CIP shRNAs (Figure 3b and c). Moreover, SA-β-galactosidase staining was high in all cell lines but in UT711oc1 cells expressing p21CIP shRNAs (Figure 3d). This demonstrated that TPO-induced senescence is p21CIP-dependent but p27KIP-, p16INK4a-, and p53-independent.
We next investigated whether p21CIP was transcriptionally regulated by the MAPK pathway. We detected significant p21CIP protein expression 4 h after addition of TPO (unpublished data), suggesting the possible involvement of a transcription factor regulated by ERK. Expression of p21CIP is known to be directly regulated by several transcription factors. We proposed the early growth response protein 1 (EGR1 (GeneID: 1958)) as a candidate for TPO-induced p21CIP-dependent senescence because (i) EGR1 has been implicated in cell-cycle arrest [35], (ii) EGR1 can be activated by the RAS/MAPK pathway [36], and (iii) EGR1 regulates p21CIP transcription [37]. We first analyzed EGR1 expression in UT711oc1 cells stimulated by either GM-CSF or TPO and after ERK chemical inhibition. EGR1 was expressed in UT711oc1 cells only after TPO stimulation. Moreover, its expression was abrogated by PD98059 and U0126 inhibitors (Figure 4a). Thus, in UT71oc1 cells, EGR1 expression is regulated by TPO in a MAPK-dependent mechanism. We analyzed whether ERK signaling was the main pathway regulating EGR1 expression in our system. UT711oc1 cells infected with a constitutively active MEK (MEK1-SS/DD) and cultured in presence of GM-CSF presented an increase in EGR1 expression (Figure 4b). EGR1 is found either in the cytoplasm or the nucleus. We studied EGR1 localization after TPO stimulation using Western blotting (Figure 4c) and immunolabeling coupled with confocal microscopy (Figure 4d). Based on both these approaches we showed that EGR1 was localized in the nucleus after 2 h TPO stimulation and thus was presumably active. To examine whether EGR1 could regulate p21CIP expression following TPO stimulation, UT711oc1 cells were transduced with lentiviral vectors expressing EGR1 shRNAs. These shRNAs induced a knockdown of EGR1 at the mRNA and protein levels (Figures 4e and S4a) resulting in a decrease in expression of p21CIP after 2 h TPO stimulation (Figure 4f). Inactivation of EGR1 reversed, at least in part, the DNA replication arrest of UT711oc1 cells after TPO exposure (Figure S4b) and decreased the proportion of cells with SA-β-Galactosidase staining (Figure 4g). In order to demonstrate that EGR1 directly regulates p21CIP, chromatin immunoprecipitation ChIP analysis was performed. Briefly, after EGR1 immunoprecipitation, we detected binding to DNA sequences belonging to the p21CIP promoter. We observed an increase in EGR1 binding to p21CIP promoter after TPO stimulation (Figure 4h). Altogether these results confirmed that after TPO stimulation EGR1 was activated by the RAS/MAPK pathway, translocated to the nucleus, bound to p21CIP promoter, and activated p21CIP transcription, finally inducing senescence.
We studied whether TPO-induced senescence in UT711oc1 cells was a phenomenon widespread to normal megakaryocyte differentiation. Lin− cells isolated from C57/Bl6 mice were cultured for 6 d with TPO and were found to display a high SA-β-galactosidase activity (Figure 5a). To extend these findings to human, CD34+ cells were cultured in vitro in megakaryocytic differentiation condition. We observed an increase in SA-β-galactosidase staining 10 to 16 d after the start of the culture (Figure 5b), when megakaryocytes were polyploid and initiating platelet production. Cathepsin D mRNA expression was also induced during megakaryocytic differentiation (Figure S5c). To determine whether the senescence observed in culture was associated to cell maturation, we analyzed p21CIP expression during megakaryocytic cell culture, along with CD41, CD42, and von Willebrand factor megakaryocytic markers. p21CIP expression was very low in immature cells (day 0 to day 3 of culture) and increased at day 6 and day 9. Interestingly, the peak in p21CIP expression was reached approximately 3 d after the maximum level of ERK phosphorylation (Figure 5c). There was a marked increase in megakaryocyte differentiation measured by the rising proportion of mature (CD41+/CD42+) versus progenitors (CD41−/CD42−) and immature megakaryocytes (CD41+/CD42−) at days 3, 6, and 9 (Figures 5d and S5a). CD41+ cells were positive for von Willebrand factor (Figure S5b) and this megakarycocyte differentiation was correlated with the progressive increase in cathepsin D mRNA expression (Figure S5c). Chemical inhibition of ERK activation in human megakaryocytic cultures demonstrated a decrease in p21CIP mRNA and protein expression (Figure S6a and S6b). To confirm that senescence could be defined as a physiological process happening during megakaryocyte differentiation, we sorted human mature normal CD41+/CD42+ megakaryocytes from human bone marrow aspirations and tested these cells for expression of markers of senescence. Using this approach, we confirmed that SA-β-galactosidase activity was also present in vivo in mature megakaryocytes (Figure 5e).
Cellular senescence is a permanent state of cell-cycle arrest and is emerging as an intrinsic barrier against tumorigenesis. Primary myelofibrosis (PMF) is a myeloproliferative disorder induced in 50% of cases by an acquired JAK2V617F mutation leading to spontaneous kinase activation. In PMF, this mutation is present in all myeloid cells including the megakaryocytic cell line. Thus, we investigated whether such malignant megakaryocytes could escape to TPO-induced physiological senescence. Human PMF and normal CD34+ cells were cultured with TPO for 12 d. PMF compared to normal megakaryocytes exhibited a lower SA-β-galactosidase staining as revealed by the intensity of staining and the percentage of SA-β-galactosidase-positive cells (Figure 5f). This result suggests a defect of TPO-induced senescence in these malignant megakaryocytes. We examined whether p21CIP was down-regulated in PMF megakaryocytes and analyzed its expression in 10 d cultured normal and PMF megakaryocytes. After 10 d of culture p21CIP mRNA and protein expressions were lower in PMF than in normal megakaryocytes (Figure 5g and 5h). The down-modulation of p21CIP expression may play a role in the resistance to the physiological TPO-induced senescence process, thus leading to the increase in megakaryocyte hyper-proliferation in these myeloproliferative diseases.
Hematopoietic cytokines are commonly considered as proliferative and anti-apoptotic proteins regulating blood cell production in basal or stress conditions. TPO is a specific megakaryocytic cytokine that induces proliferation and cell differentiation and regulates platelet production. In addition, in HSCs TPO induces quiescence of primitive HSCs and proliferation of the multipotent progenitors. Thus, TPO seems to have proliferative and anti-proliferative actions, depending on the cell type (reviewed in [38]). Megakaryopoiesis is a multiple stage differentiation process under the control of TPO. Megakaryocytic precursors proliferate, switch to polyploidization, and stop DNA replication before terminal differentiation leading to platelet shedding. Here, we report that UT7 cells genetically modified to over-express the TPO receptor respond to TPO by inducing senescence and that a similar process occurs in normal megakaryocytes. It was recently demonstrated that senescence is partially related to the release of inflammatory cytokines such as IL-6 and IL-8 [13],[30],[31],[33]. Upon secretion by senescent cells, these cytokines can trigger and maintain the senescence process. Our observations support the notion that TPO, a non-inflammatory cytokine, recapitulates the OIS mechanisms by inducing a high and sustained RAS/MAPK activation and consequently transcription of EGR1, leading to synthesis of the p21CIP CDKi. In addition, a recent study suggests that increased reactive oxygen species (ROS) promote megakaryopoiesis [39]. ROS accumulation driving megakaryocyte maturation could also participate in DNA damage observed in megakaryocytes (γH2AX foci observed in megakaryocytes in our laboratory) (Ali A and Debili N, unpublished data), cumulative oxidative damage lastly contributing to cellular senescence (Figure 6). This TPO-induced senescence could be a key mechanism for post-mitotic arrest without cell death, allowing these cells to respond to different stimuli with biological effects other than proliferation. In this work, we have shown the important role of p21CIP in the proliferative arrest of the UT711oc1 cells. Similarly, induction of p21CIP was also found during megakaryocyte differentiation. It is worth noting that the mouse knock-out of p21CIP does not abrogate the post-mitotic arrest during normal megakaryocyte differentiation [40], suggesting the possible involvement of other CDKis, such as p19INK4d (GeneID: 1032) [41]. Furthermore, based on our results on primary cells from healthy donors and from myeloproliferative patients, it is possible that the heterochromatin changes associated with TPO-induced senescence might be more important in normal differentiation. Induction of several CDKis might occur differently in function of the differentiation stages and allow transmission of signals in a reversible manner in terminally differentiated megakaryocytes. It is possible that depending on the stage of differentiation, there will be differences in MPL and JAK2 expression levels resulting in different levels of TPO-induced ERK/MAPK signaling.
Senescence is a biological process that limits oncogenic transformation. Immature hematopoietic cells (progenitors or HSCs) have a very high proliferative capacity and linking senescence to proliferation could efficiently limit "high-risk" oncogenic processes in these cells. However, hematopoietic tissues are still the targets of oncogenic processes (i.e. leukemia and myeloproliferative disorders). Cancer cells can be defined as cells that escape the senescence process induced by an oncogene. The mechanisms leading to such an escape remain unclear. We hypothesize that in malignant megakaryocytic cells, depending on MPL signaling for their proliferation, TPO-induced senescence may be deficient due to events that counteract the MPL/MAPK/EGR1/p21CIP pathway. In favor of this hypothesis, we found that PMF megakaryocytes have lost their senescence ability in response to TPO due to a p21CIP down-expression. The entire mechanisms leading to such repression of p21CIP expression are actually not defined.
In conclusion, we describe in this report a mechanism leading to proliferation arrest in mature hematopoietic cells, the TPO-induced senescence, that is not operative in malignant megakaryocytic cells.
UT711oc1 cells were seeded at a density of 1×105 cells/mL and grown in Dulbecco's modified Eagle's medium (DMEM; Invitrogen, Cergy Pontoise, France) or in methylcellulose medium. Both media were supplemented with 10% fetal bovine serum (FBS), antibiotics (100 IU/ml penicillin and 50 mg/ml streptomycin), and GM-CSF (5 ng/mL) or recombinant human TPO (hTPO) (10 ng/mL). The MAPK inhibitors PD98059 and U0126 were used at 10 µM (Calbiochem, San Diego, CA, USA). Human CD34+ cells and mouse C57/Bl6 Lin− cells were purified and seeded as previously described [42].
MEK1-S218D/S222D cDNA was cloned into the bicistronic retroviral vector pMIGR-IRES-GFP. pGIPZ plasmids containing p21CIP shRNA (no. V2LHS-203118 and V2LHS-230370), p27KIP shRNA (no. V2LHS-262973), p53 shRNA (no. V2LHS-217), p16INK4a shRNA (no. V2LHS-195839), and EGR1 shRNA (no. V2LHS-262011, no. V2LHS-151347, and no. V2LHS-151348) were purchased from Open Biosystem (Thermo Scientific products, Surrey, UK). Vesicular stomatitis virus glycoprotein pseudotyped Viral particles were produced into 293EBNA or 293T cells as previously described [8],[43]. UT711oc1 cells were infected with concentrated retrovirus or lentivirus supernatants for 2 h at a multiplicity of infection of 10 and sorted by flow cytometry (FACS Vantage, BD Biosciences, Mountain View, CA) 48 h later based on eGFP expression.
For microarray analysis, a published data set of senescent fibroblasts (Mason et al. [29]) was used. Raw global gene expression values (from Affymetrix GeneChip) for 24 h TPO-exposed UT711oc1 cells samples and GM-CSF-exposed samples were collected. We then processed these samples with the robust multiarray analysis (RMA) algorithm using BioConductor software, version 2.3. Using the processed data, GSEA (http://www.broad.mit.edu/gsea/) was performed to look for enrichment of the Senescent-fibroblast list. Moreover, gene-array results were analyzed using Ingenuity Pathways Analysis.
Annexin V fluorescein isothiocyanate (FITC)-positive staining was determined by FACS analysis according to the manufacturer's recommendations (BD Pharmingen, Franklin Lakes, NJ, USA).
5-Bromo-2-deoxyuridine (BrdU) labeling was performed using FITC BrdU Flow Kit (BD Biosciences, Le Pont de Claix, France) according to the manufacturer's protocol. Cells were labeled during 30 min with BrdU at 37°C in 5% CO2 atmosphere. Human cultured CD34+ cells were rinsed in PBS, stained for 30 min at 4°C with anti-CD41–APC (Allophycocyanin) or anti-CD42–FITC (BD Biosciences) antibodies. Control cells were incubated with an irrelevant mouse immunoglobulin G1 (IgG1) antibody. Cell samples were analyzed by FACS.
Proteins were extracted in RIPA buffer with 1% Triton X-100 (Sigma-Aldrich, St. Louis, MO, USA) and supplemented with protease inhibitor mixture tablets (Complete, Roche Diagnostics, Meylan, France). Proteins (20–40 µg per lane) were separated on SDS–polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride (PVDF) membranes by a standard procedure. Antibodies used for immunoblotting were: Actin (Sigma-Aldrich), p21CIP (no. 2947), p16INK4a (no. 4824), PARP (no. 9542), phosphoERK (no. 9101), EGR1 (no. 4153) (Cell Signaling, Beverly, MA, USA), p27KIP (no. 510242) (BD Biosciences), p53 (no. SC-6243), and Caspase 3 (no. 7148) (Santa Cruz Biotechnology, Heidelberg, Germany). Bands were revealed using enhanced chemiluminescence (ECL, Pierce Perbio, Brebières, France). The nuclear and cytoplasmic protein separations were realized as previously described [43].
Total RNA was extracted using a Trizol RNA isolation kit according to the manufacturer's protocol (Invitrogen). Transcription into cDNA was performed using random hexamers and SuperScript II reverse transcriptase (Invitrogen) according to the manufacturer's instructions. All PCR reactions used Taqman PCR Master Mix (Applied Biosystems, Foster City, CA, USA) to a final volume of 20 µl. Each cDNA sample was analyzed in triplicate in the ABI PRISM 7900 Sequence Detection System (Applied Biosystems).
Fixation and immunofluorescence were performed on UT711oc1 cells. The following antibodies were used: anti-HP1γ (no. 2619), anti-EGR1 (no. 4153) (cell signaling), and anti-human Von Willebrand Factor (A0082) (DakoCytomation). The appropriate secondary antibodies were conjugated with Alexa 488 or Alexa 546 (Molecular Probes-Invitrogen, Cergy-Pontoise, France). TOTO-3 iodide (Molecular Probes) or DAPI was applied for nucleus staining. Cells were examined under a Zeiss LSM 510 laser scanning microscope (Carl Zeiss, Le Pecq, France) with a 63×/1.4 numeric aperture (NA) oil objective.
Chromatin immunoprecipitations (ChIP) assays were performed using a ChIP assay kit (cell signaling) with anti-EGR1 Ab (cell signaling). These assays were performed using UT711oc1 chromatin samples. Quantification of precipitated DNA fragments was carried out on an ABI PRISM 7000 sequence detection system using Taqman probes (Eurogentec, Angers, France). Relative occupancy of the immunoprecipitated factor at a locus was calculated using the following equation: 2(CtNegCtl−CtTarget), where CtNegCtl and CtTarget are mean threshold cycles of PCR done in duplicate on DNA samples from negative control ChIP (using non-immune IgG) and targeted ChIP (specific antibody).
Detection of SA-β-galactosidase activity was performed at pH=6 as previously described [18].
UT711oc1 cells were cultured with either GM-CSF or TPO for 6 d and secreted factor concentrations were measured in the supernatants using Procarta Protein Profiling Assays according to the manufacturer's protocol.
We performed the t test for all experiment. p indicates value of Student's t test.
Thrombopoietin induces cellular senescence of UT711oc1 and not apoptosis. (a) TPO and GM-CSF induce similar levels of apoptosis in UT711oc1 cells. Cells were treated with TPO for 3 and 6 d and compared to GM-CSF-cultured cells for Annexin V labeling. (b) No difference in PARP and Caspase 3 cleavage between TPO- and GM-CSF-treated cells. UT711oc1 were cultured in presence of GM-CSF or TPO as indicated and PARP and Caspase 3 proteins were analyzed by Western blotting. The "W/O Cytokine" condition represents 24 h cytokine starvation and serves as a positive control for PARP and Caspase 3 cleavage. (c) Two other over-expressing MPL UT7 cell lines, called clone 5.1 and clone 86, were generated and SA-β-galactosidase activity was evaluated after 5 d of exposure to TPO or GM-CSF. (d) TPO up-regulates cathepsin D mRNA. Cells were exposed to TPO or GM-CSF for 3 to 6 d and cathepsin D mRNA expression determined by Taqman. (e) UT711oc1 supernantants of 48 h TPO-exposed and GM-CSF-exposed cells (1 million cells/ml) were collected and cytokine concentrations were measured (in pg/ml). Three independent experiments for each apoptosis assay were performed.
Top coincident genes when TPO-induced gene expression profile was compared to the molecular signature of oncogenic ras-induced senescence established in fibroblasts by Mason et al. [29]. (a) Top coincident up-regulated genes and their involvement in "growth, proliferation, and apoptosis"; "inflammation"; or "DNA replication, recombination, and repair," when total coincident genes were analyzed using Ingenuity Pathways Analysis. (b) Top coincident down-regulated genes and their involvement in "growth, proliferation, and apoptosis," "inflammation," or "DNA replication, recombination, and repair."
p21 mRNA expression is up-regulated by TPO via the RAS/MAPK pathway. (a) p21 mRNA expression in UT711oc1 cells. Cells were treated with GM-CSF or TPO in presence of PD98056 and U0126 inhibitors and assayed for gene expression by Taqman. (b) Cathepsin D mRNA expression in UT711oc1 cells. Cells were treated with GM-CSF or TPO in presence of PD98056 and U0126 inhibitors and assayed for gene expression by Taqman. (c) p53, p16, and p27 protein expressions were analyzed by Western blotting. Cells were treated in the same conditions as in (a). (d) p21 mRNA expression is up-regulated in UT711oc1 cells over-expressing a spontaneous active form of MEK (MEK1 SS/DD). (e) Cathepsin D mRNA expression is up-regulated in UT711oc1 cells over-expressing a spontaneous active form of MEK (MEK1 SS/DD). (f) p27 protein expression stays unchanged in presence of active MEK. Error bar represents the standard deviation of three independent experiments.
EGR1 shRNAs are functional and re-induce cell proliferation after TPO exposure. (a) EGR1 shRNAs inhibit EGR1 protein expression after TPO exposure. (b) BrdU incorporation at 5 d of culture shows a significant (but partial) increase in DNA replication with TPO when cells express EGR1 shRNAs. Error bar represents the standard deviation. We performed three independent experiments.
Cathepsin D and megakaryocytic differentiation markers in normal human megakaryocytes. (a) Proportion of CD41 and CD42 expressing cells during the megakaryocytic culture. (b) Co-expression of vWF and CD41 markers in megakaryocytes after 12 d of cell culture. (c) Cathepsin D mRNA expression during megakaryocytic differentiation process of human cytapheresis CD34+ cells.
Inhibition of ERK decreases p21 expression in human megakaryocytes. Human megakaryocytes were cultured for 10 d in presence of TPO and 10 µM of U0126 MAPK inhibitor. U0126 inhibited ERK phosphorylation (b) and p21 protein (b) and mRNA expression (a). We performed three independent experiments.
TPO and MEK1SS/DD expression induces ERK phosphorylation without any changes in total ERK expression. (a) UT711oc1 cells were treated with GM-CSF or TPO ± PD98059 or UO126 for 2 d. ERK phosphorylation and total ERK expression were then evaluated by WB. (b) UT711oc1 cells transduced with either empty retroviral vector (pMigr) or the vector encoding for a spontaneously active MEK (MEK1-SS/DD) were cultured in presence of GM-CSF for 3 to 6 d. ERK phosphorylation and total ERK expression were then evaluated by WB.
The authors are grateful to Philippe Dessen, Justine Guégan, and Thomas Robert from the Unité de Génomique fonctionnelle for gene-array and GSEA analysis.
The authors have declared that no competing interests exist.
This work was supported by grants from the INSERM and la Ligue Nationale contre le Cancer. Funding to SNC was from Fondation Salus Sanguinis, the Action de Recherche Concertée (ARC) MEXP31C1 of the Université catholique de Louvain, the Fondation contre le cancer, the Atlantic Philanthropies, New York, the PAI Program BCHM61B5, Belgium and the Fonds National de la Recherche Scientifique (FNRS), Belgium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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páscoa 6 50-Elegant-Easter-Window-Decoration-21
Here is another bunny template found online, cute bent ear! Why not mix up the bunnies, and cut them out of old boxes?
Bunny Banners. Colorful bunny templates with cotton tails - An easy and kid-friendly Easter decoration, from Joyful Family Life.
Kartki wielkanocne DIY - inspiracje, fot. Pinterest
Twinkl Resources >> Easter Egg Templates >> Printable resources for Primary, EYFS, KS1 and SEN. Thousands of classroom displays and teaching aids! Topics, Easter, Colouring, Easter Eggs
Easter Art and Craft ideas found on the net and pinned by Clever Classroom!
DIY Bunny Envelope for Easter
easter egg dying tricks
Create a FUN breakfast for the kids during Easter, Very easy to make & will surely put a smile on the little ones faces.


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When I wrote Help Your Dog Fight Cancer, I hoped it would reach everyone trying to give their dog a chance to survive cancer. I love that Bullet's book is helping so many people and dogs their fight cancer. I hate that there is such a tremendous demand for that help.
The tens of thousands of copies sold are an indication of the overwhelming statistics. Canine cancer is affecting millions of dogs at this very moment. I am haunted by thoughts of all of the people who have dogs with cancer but who cannot afford treatment. After completing the first printing of Help Your Dog Fight Cancer, I founded the Magic Bullet Fund to help these people and their dogs. My donations from book proceeds were the first influx to the fund and they continue although now they are dwarfed by the generous donations of so many others.<> By the second printing of this book in 2005, Bullet had left me, taken by old age, still cancer free.
In the 2nd Edition, released summer of 2008, I updated medical information and added a final chapter to discuss palliative care, euthanasia and grief. People who have dogs with cancer are hungry for information. The first 2 editions of this book were a crash course to help dog lovers get an initial grasp of the situation and understand their options, and to provide moral support.
The 3rd Edition of Help Your Dog Fight Cancer contains medical updates of course and a great deal of added information. The new subtitle, "Empowerment for Dog Owners," promises that the book is full of information that readers will probably never hear from a vet. Information that will help them make decisions on behalf of their dog that will benefit their dog, not the medical team. Your dog, your money, your decisions!
Magic Bullet Fund is Bullet's Legacy. The Magic Bullet Fund provides financial assistance to families that have a dog with cancer but cannot afford treatment costs. At best. the fund gives dogs a chance to beat cancer. At least, the fund allows owners time to create more precious memories and have a long goodbye with their beloved friend and have peace of mind knowing that they did do everything possible to help their dog survive cancer.
Laurie Kaplan is the author of "Help Your Dog Fight Cancer: An Overview of Home Care Options." This book, Bullet's legacy, has helped thousands of dogs and caretakers in their fight against cancer.
Laurie Kaplan is the administrator of The Magic Bullet Fund, a program of the 501(C)(3) Perseus Foundation. The Magic Bullet Fund helps caretakers with financial constraints get cancer treatment for dogs with good prognoses. Apply or donate online HERE or by mail: Magic Bullet Fund, PO Box 2574, Briarcliff NY 10510.
Laurie co-authored "Canine and Feline Geriatric Oncology." Blackwell Publishing, Inc.Jan 2007. Order using author's discount code PRGC67. Book covers cancer treatment for veterinary school students and veterinarians. Published by Blackwell Publishing, Inc., Jan 2007.
Not Today and Not Without a Fight!
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© 2017 JanGen Press. All rights reserved.


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let's root for each other
Today I was hit hard by how much judgment we deal. We evaluate appearances, actions and words; we trash talk backgrounds we don't understand. We break each other down so that we can climb up on the broken spirits of people we've deemed lesser. Worse, we do it because it amuses us to tear another person down. At some point, cynicism and sarcasm has been deemed the cooler, better alternative to optimism and genuine enthusiasm. It's no wonder we feel insecure in our place in this world with hawks gauging our every move. Let's move away from that.
These days I've been getting more involved in the Tone It Up community. I've slowly been posting on Instagram and Twitter and I am addicted. I am addicted to the camaraderie these women have for each other. Here are strangers from around the world connected by the single desire to encourage each other on their individual journeys to fitness. To see such open and raw encouragement was…hard. I couldn't fathom such openness and lightheartedness but I could feel the cheeriness working on my own heart.
Let's root for each other. We can start with our friends.
I find birthdays to be the perfect time to reflect on your relationship and on what it is about the person that makes her or him such an invaluable part of your life. And then tell them. Talk about how excited you are to have found someone who loves the same niche movie, express your admiration of her sweet consideration for others, indulge in the memories you've had in the past year. Share your feelings on the day where this person came into the world and entered your life, changing it for the better. Because, although you may have an unspoken understanding that you are kindred spirits, to voice that love is a beautiful thing. It is necessary.


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12320 North 32nd Street, Suite 1
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If you're looking for dentures that look great and last, look no further than Dameron and Team located in the Phoenix, AZ area. Brett Dameron, D.D.S. will assess your needs and fit you with durable, comfortable, natural-looking dentures - at a price you can afford.
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We know affordable dental treatment is important to you. At Dameron and Team, your long term oral health is our top concern.
A negative self image can be detrimental to many facets of your life. Phoenix area dentist Dr. Brett Dameron understands the positive life-changing power that a healthy and beautiful smile can bring to you. Here at Dameron and Team, we don't want you to be embarrassed any longer. Why not take your smile - and even your life - to a new level of self-confidence and beauty?
One of the first things people notice is your smile. All it takes is a single appointment or two with Phoenix area dentist Brett Dameron, D.D.S., and you, too, can have the winning, healthy-looking smile you've always wanted. The beautiful cosmetic results you'll get from Dameron and Team can be immediate and dramatic!
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For a quality porcelain crown in the Anthem, AZ area, Dr. Darren Flowers is known for natural-looking results. At Darren L. Flowers, DMD, we use quality materials to restore your smile.
Your new tooth colored crown will blend in with the rest of your teeth. Our state-of-the-art techniques will make your smile look healthy and natural again.
For comfortable dental hygiene treatment in the Anthem, Arizona area, Dr. Darren Flowers is known for having a gentle touch. The friendly team at Darren L. Flowers, DMD provides teeth cleaning for a whiter smile.
Maintaining good dental hygiene is the foundation for healthy teeth and gums. We're committed to helping you have a lifetime of oral health.
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If you're interested in natural-looking bridges and dentures, look no further than Darren Flowers, D.M.D. who practices in the Anthem, Arizona area. Using modern materials and techniques, Dr. Flowers can achieve the natural look you seek. You will be very pleased with the comfortable, long-lasting results.
At Darren L. Flowers, DMD we aim to maximize your insurance benefits and make any remaining balance easily affordable. Anthem area dentist Dr. Darren Flowers and his knowledgeable staff can help answer any of your insurance questions.
We accept most insurance carriers. Please check with us prior to your appointment, but it's safe to say we likely accept the type of insurance you carry.
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The friendly, caring staff of Agave Dental in the Phoenix, Arizona area strive to make you feel comfortable and well-cared for at your dentist appointment. Beth Hamann, D.D.S. is committed to serving you and your family's dental needs, year after year. Come and see what we have to offer in a professional setting where top-notch customer service still matters.
If you're interested in natural-looking bridges and dentures, look no further than Beth Hamann, D.D.S. who practices in the Phoenix, Arizona area. Using modern materials and techniques, Dr. Hamann can achieve the natural look you seek. You will be very pleased with the comfortable, long-lasting results.
Have you ever considered natural-looking, permanent dental implants instead of uncomfortable dentures? Incredible recent advances in technology allow Phoenix area dental implants dentist Dr. Beth Hamann to create tooth implants just for you that can be permanently anchored to your jaw. This is a great option to consider if you've had negative experiences with dentures in the past.
Would you like your smile to be a bit brighter than it is right now? We can make it happen at Agave Dental, with professional tooth whitening for brighter natural looking teeth. Dr. Beth Hamann's Phoenix, AZ area office can effectively lighten your stained or discolored tooth enamel. Whiter teeth not only look great, they improve your self-confidence.
A negative self image can be detrimental to many facets of your life. Phoenix area dentist Dr. Beth Hamann understands the positive life-changing power that a healthy and beautiful smile can bring to you. Here at Agave Dental, we don't want you to be embarrassed any longer. Why not take your smile - and even your life - to a new level of self-confidence and beauty?
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Female cosmetic dentist in 13088
dental crowns cost in Fountain Valley CA
San Diego teeth bonding before and after
Choice is a wonderful thing. It can mean the opportunity to look a dozen years younger than your actual age. Which, in this youth-obsessed culture, gives you extra advantages, whether you're thirty-something or a grandparent.
These choices include your teeth. Not just movie stars, but adults in all walks of life, are opting for cosmetic dental care that restore youthful vitality to their skin and faces. You might be surprised by the role fresh "young" teeth play in creating that overall first impression.
Your cosmetic dentist can bring you up to date on the incredible and youth-restoring dental options, like dental crowns and veneers, that are available to you. Options available at a fraction of the cost of risky and invasive surgery such as, say, a face-lift.
Whichever restorative dentistry procedure you agree to, or decline, is your personal choice. For example, suppose you're missing teeth. Maybe the gap doesn't show, and you've lived with it for awhile. Replacement with dental crowns or dental bridges might be recommended. The consequences of living with missing teeth are important, but the choice to replace that missing tooth and get one step closer to a beautiful smile is yours.
Just the same, it's your mouth and your decision. Whenever you have questions about your care, ask your local dentist and together you can do what's right for you.
Maybe the reason we find an eight-year-old's gapped teeth smile so adorable is...we know it's not permanent. Soon the grown-up teeth will be poking through, clean and new. All part of the mouth's natural evolution.
It's not often that nature gives us a second chance, but when it comes to teeth it does just that. For many children it can be a wake-up call to start taking dental hygiene seriously. As the old saying goes, "God gives you two sets of teeth, but you have to buy the third."
It may be time though to change that outdated piece of wisdom to: "Teeth are like friends...ignore them and their needs and they'll go away. Be kind to them and they'll stick with you forever."
That's why regular hygiene appointments and a gum disease examination are so important. Barring injury, there's simply no reason why most of us should be missing teeth as we grow older. Call it a "10,000 smile checkup," insuring all your parts are in good working order.
Once your cosmetic dentist knows that your teeth are healthy and the gums are sound, he or she can do a little restorative dentistry to evolve your smile to an even higher level. Things like dental bonding to close the gaps…or invisible dental crowns or veneers for front teeth…even teeth bleaching for a truly dazzling and beautiful smile.
Give your cosmetic dentistry professional a call. He or she can help you see to it that your mouth does the job it was intended to for a lifetime. And look drop-dead sensational at the same time!


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Propeller 9x6 ElectriFly PowerFlow Slo Flyer (2)
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The annual Pharmaceutical/Chemical Practice Seminar, includes practice tips, guidance, legal updates and summaries from leading experts.
This CLE event, to be held on Wednesday, November 8th at the APA Hotel Woodbridge at Metropark.
Members in good standing automatically receive a discount to NJIPLA programs. To review or update your membership status, log in at: www.njipla.org.
© 2013 New Jersey Intellectual Property Law Association


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HR Generalist - Coordinator Jobs
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- Church Pension Group
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The Benefits Outreach Coordinator will oversee and manage life events in support of the Pension, Health and Welfare and Church Life services. The Benefits Outreach Coordinator ensures the adherence to procedures and policies ensuring the effective delivery of benefits to eligible Participants, Admin... More Details
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This is a continuous recruitment with an initial review date of July 12, 2017Applications received after July 11, 2017 may not receive consideration. The UW-Milwaukee Title IX Coordinator oversees and coordinates UW-Milwaukee's compliance with Title IX of the Education Amendments of 1972 and works c... More Details


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A lot of the time, Cassie and Charles Kelley can be found on the road—he belongs to the music group Lady Antebellum; she blogs on fashion, food, and travel at womanista.com. During the summer, when they are at home in Nashville, they like to entertain alfresco. We caught up with the duo as they hosted four close friends at their home. A soft color palette of pinks, greens, and golds complements the summer evening light. Cassie says she loves "romance and sparkle" but insists "it's important to keep it easy and not too fussy." Here, she shares her tips.
Cassie Kelley and her husband, Charles—of the band Lady Antebellum—take entertaining outside to make the most of Southern summer nights


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Free personalized radio that
plays the music you love
Ain't No Future In Yo' Frontin'
Ah yeah
(Ya don't stop) --> Flavor Flan
Sound good to me
Features of This Trackhardcore rap influence
west coast rap roots
club rap influences
r&b influences
funk influences
danceable beats
syncopated beats
funk beats
unmetered speech
peripheral vocals
clear pronunciation
boastin' lyrics
a bumpin' kick sound
light percussion fills
the heavy use of funk samples
the heavy use of R&B samples
subtle use of turntables
synth riffs
vinyl ambience
These are just a few of the hundreds of attributes cataloged for this track by the Music Genome Project.show more
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Oui! tea towel (second)
- 100% Unbleached Cotton
- Hang Tag Included
A design by Darling Clementine
Oooo oui! I'll share a pot of tea with you, monsieur! Sucre? Non, merci... I'm sweet enough!
We are delighted to have been able to collaborate with Norwegian design agency, Darling Clementine, transforming their Parisian-inspired designs into a range of très-chic tea towels.
Like what you see? Then why not find out a bit more about Darling Clementine...
Approx dimensions: 48cm x 76cm
Please note! This tea towel is a second. It was printed on a lighter unbleached cotton than the rest of the Paris range (don't ask!). The towel is marked as a second on the back of the packet with a small sticker (which you could always peel off before you give it as a present if you're feeling generous but on a budget).


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Parent Organization: Registered Student Organizations
Young Americans for Liberty (YAL) is the largest, most active, and fastest-growing pro-liberty organization on America's college campuses. With more than 300 chapters and 26,000 student activists nationwide, YAL seeks to recruit, train, educate, and mobilize
students on the ideals of liberty and the Constitution.
Advisor's Missouri State E-mail
Address 3141 W Countryside Dr
Springfield, MO 65807
United States
Springfield, MO 65807
United States
Phone Number P:(417) 554-0014


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is currently backordered. You may still purchase it now but we won't be able to ship it until it becomes available again.
Coastal, set of two pinewood cranes with realistic coloring. Complementary poses with one crane looking upward and the other down.
Materials: Solid Pine
Dimensions: 27.75-31.5"h x 4.75"
Item number: 50894-2
Please note: This item is hand made and sizes are approximate. Slight color variations and imperfections are the characteristics of hand craftsmanship. Decorative purposes only. This item is non-refundable unless it is defective or shipped incorrectly.