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Skip to comments.The History and Meaning of "Palestine" and "Palestinians"
Posted on 04/05/2002 3:31:40 PM PST by oswegodeee
The History and Meaning of "Palestine" and "Palestinians"
Presented by: A Time To Speak (firstname.lastname@example.com) "There is no such thing as a Palestinian Arab nation . . . Palestine is a name the Romans gave to Eretz Yisrael with the express purpose of infuriating the Jews . . . . Why should we use the spiteful name meant to humiliate us? The British chose to call the land they mandated Palestine, and the Arabs picked it up as their nation's supposed ancient name, though they couldn't even pronounce it correctly and turned it into Falastin a fictional entity." Golda Meir quoted by Sarah Honig, Jerusalem Post, 25 November 1995
Palestine has never existed . . . as an autonomous entity. There is no language known as Palestinian. There is no distinct Palestinian culture. There has never been a land known as Palestine governed by Palestinians. Palestinians are Arabs, indistinguishable from Jordanians (another recent invention), Syrians, Lebanese, Iraqis, etc. Keep in mind that the Arabs control 99.9 percent of the Middle East lands. Israel represents one-tenth of one percent of the landmass. But that's too much for the Arabs. They want it all. And that is ultimately what the fighting in Israel is about today . . . No matter how many land concessions the Israelis make, it will never be enough. from "Myths of the Middle East", Joseph Farah, Arab-American editor and journalist, WorldNetDaily, 11 October 2000
From the end of the Jewish state in antiquity to the beginning of British rule, the area now designated by the name Palestine was not a country and had no frontiers, only administrative boundaries . . . . Professor Bernard Lewis, Commentary Magazine, January 1975 Talk and writing about Israel and the Middle East feature the nouns "Palestine" and Palestinian", and the phrases "Palestinian territory" and even "Israeli-occupied Palestinian territory". All too often, these terms are used with regard to their historical or geographical meaning, so that the usage creates illusions rather than clarifies reality.
What Does "Palestine" Mean?
It has never been the name of a nation or state. It is a geographical term, used to designate the region at those times in history when there is no nation or state there.
The Philistines were not Arabs, they were not Semites. They had no connection ... with Arabia or Arabs.
The word itself derives from "Peleshet", a name that appears frequently in the Bible and has come into English as "Philistine". The name began to be used in the Thirteenth Century BCE, for a wave of migrant "Sea Peoples" who came from the area of the Aegean Sea and the Greek Islands and settled on the southern coast of the land of Canaan. There they established five independent city-states (including Gaza) on a narrow strip of land known as Philistia. The Greeks and Romans called it "Palastina".
The Philistines were not Arabs, they were not Semites. They had no connection, ethnic, linguistic or historical with Arabia or Arabs. The name "Falastin" that Arabs today use for "Palestine" is not an Arabic name. It is the Arab pronunciation of the Greco-Roman "Palastina" derived from the Peleshet.
How Did the Land of Israel Become "Palestine"?
In the First Century CE, the Romans crushed the independent kingdom of Judea. After the failed rebellion of Bar Kokhba in the Second Century CE, the Roman Emperor Hadrian determined to wipe out the identity of Israel-Judah-Judea. Therefore, he took the name Palastina and imposed it on all the Land of Israel. At the same time, he changed the name of Jerusalem to Aelia Capitolina.
The Romans killed many Jews and sold many more in slavery. Some of those who survived still alive and free left the devastated country, but there was never a complete abandonment of the Land. There was never a time when there were not Jews and Jewish communities, though the size and conditions of those communities fluctuated greatly.
The History of Palestine
Thousands of years before the Romans invented "Palastina" the land had been known as "Canaan". The Canaanites had many tiny city-states, each one at times independent and at times a vassal of an Egyptian or Hittite king. The Canaanites never united into a state.
After the Exodus from Egypt probably in the Thirteenth Century BCE but perhaps earlier the Children of Israel settled in the land of Canaan. There they formed first a tribal confederation, and then the Biblical kingdoms of Israel and Judah, and the post-Biblical kingdom of Judea.
Israel-Judah-Judea has the only united, independent, sovereign nation-state that ever existed in "Palestine" west of the Jordan River.
From the beginning of history to this day, Israel-Judah-Judea has the only united, independent, sovereign nation-state that ever existed in "Palestine" west of the Jordan River. (In Biblical times, Ammon, Moab and Edom as well as Israel had land east of the Jordan, but they disappeared in antiquity and no other nation took their place until the British invented Trans-Jordan in the 1920s.)
After the Roman conquest of Judea, "Palastina" became a province of the pagan Roman Empire and then of the Christian Byzantine Empire, and very briefly of the Zoroastrian Persian Empire. In 638 CE, an Arab-Muslim Caliph took Palastina away from the Byzantine Empire and made it part of an Arab-Muslim Empire. The Arabs, who had no name of their own for this region, adopted the Greco-Roman name Palastina, that they pronounced "Falastin".
In that period, much of the mixed population of Palastina converted to Islam and adopted the Arabic language. They were subjects of a distant Caliph who ruled them from his capital, that was first in Damascus and later in Baghdad. They did not become a nation or an independent state, or develop a distinct society or culture.
In 1099, Christian Crusaders from Europe conquered Palestina-Falastin. After 1099, it was never again under Arab rule. The Christian Crusader kingdom was politically independent, but never developed a national identity. It remained a military outpost of Christian Europe, and lasted less than 100 years. Thereafter, Palestine was joined to Syria as a subject province first of the Mameluks, ethnically mixed slave-warriors whose center was in Egypt, and then of the Ottoman Turks, whose capital was in Istanbul.
During the First World War, the British took Palestine from the Ottoman Turks. At the end of the war, the Ottoman Empire collapsed and among its subject provinces "Palestine" was assigned to the British, to govern temporarily as a mandate from the League of Nations.
The Jewish National Home
Travellers to Palestine from the Western world left records of what they saw there. The theme throughout their reports is dismal: The land was empty, neglected, abandoned, desolate, fallen into ruins
Nothing there [Jerusalem] to be seen but a little of the old walls which is yet remaining and all the rest is grass, moss and weeds. English pilgrim in 1590
The country is in a considerable degree empty of inhabitants and therefore its greatest need is of a body of population British consul in 1857
There is not a solitary village throughout its whole extent [valley of Jezreel] not for 30 miles in either direction. . . . One may ride 10 miles hereabouts and not see 10 human beings. For the sort of solitude to make one dreary, come to Galilee . . . Nazareth is forlorn . . . Jericho lies a moldering ruin . . . Bethlehem and Bethany, in their poverty and humiliation . . . untenanted by any living creature . . . .
A desolate country whose soil is rich enough, but is given over wholly to weeds . . a silent, mournful expanse . . . a desolation . . . . We never saw a human being on the whole route . . . . Hardly a tree or shrub anywhere. Even the olive tree and the cactus, those fast friends of a worthless soil, had almost deserted the country . . . .
Palestine sits in sackcloth and ashes . . . desolate and unlovely . . . . Mark Twain, The Innocents Abroad, 1867
Their [the Jews] labors created newer and better conditions and opportunities
The restoration of the "desolate and unlovely" land began in the latter half of the Nineteenth Century with the first Jewish pioneers. Their labors created newer and better conditions and opportunities, which in turn attracted migrants from many parts of the Middle East, both Arabs and others.
The Balfour Declaration of 1917, confirmed by the League of Nations Mandate, commited the British Government to the principle that "His Majesty's government view with favour the establishment in Palestine of a Jewish National Home, and will use their best endeavors to facilitate the achievement of this object. . . . " It was specified both that this area be open to "close Jewish settlement" and that the rights of all inhabitants already in the country be preserved and protected.
Mandate Palestine originally included all of what is now Jordan, as well as all of what is now Israel, and the territories between them. However, when Great Britain's protégé Emir Abdullah was forced to leave the ancestral Hashemite domain in Arabia, the British created a realm for him that included all of Manfate Palestine east of the Jordan River. There was no traditional or historic Arab name for this land, so it was called after the river: first Trans-Jordan and later Jordan.
By this political act, that violated the conditions of the Balfour Declaration and the Mandate, the British cut more than 75 percent out of the Jewish National Home. No Jew has ever been permitted to reside in Trans-Jordan/Jordan.
Less than 25 percent then remained of Mandate Palestine, and even in this remnant, the British violated the Balfour and Mandate requirements for a "Jewish National Home" and for "close Jewish settlement". They progressively restricted where Jews could buy land, where they could live, build, farm or work.
After the Six-Day War in 1967, Israel was finally able to settle some small part of those lands from which the Jews had been debarred by the British. Successive British governments regularly condemn their settlement as "illegal". In truth, it was the British who had acted illegally in banning Jews from these parts of the Jewish National Home.
Who Is A Palestinian?
During the period of the Mandate, it was the Jewish population that was known as "Palestinians" including those who served in the British Army in World War II.
Jews who might have developed the empty lands of 'Palestine' ... instead died in the gas chambers of Europe
British policy was to curtail their numbers and progressively limit Jewish immigration. By 1939, the White Paper virtually put an end to admission of Jews to Palestine. This policy was imposed the most stringently at the very time this Home was most desperately needed after the rise of Nazi power in Europe. Jews who might have developed the empty lands of Palestine and left progeny there, instead died in the gas chambers of Europe or in the seas they were trying to cross to the Promised Land.
At the same time that the British slammed the gates on Jews, they permitted or ignored massive illegal immigration into Western Palestine from Arab countries Jordan, Syria, Egypt, North Africa. In 1939, Winston Churchill noted that "So far from being persecuted, the Arabs have crowded into the country and multiplied . . . ." Exact population statistics may be problematic, but it seems that by 1947 the number of Arabs west of the Jordan River was approximately triple of what it had been in 1900.
The current myth is that these Arabs were long established in Palestine, until the Jews came and "displaced" them. The fact is, that recent Arab immigration into Palestine "displaced" the Jews. That the massive increase in Arab population was very recent is attested by the ruling of the United Nations: That any Arab who had lived in Palestine for two years and then left in 1948 qualifies as a "Palestinian refugees".
Casual use of population statistics for Jews and Arabs in Palestine rarely consider how the proportions came to be. One factor was the British policy of keeping out Jews while bringing in Arabs. Another factor was the violence used to kill or drive out Jews even where they had been long established.
For one example: The Jewish connection with Hebron goes back to Abraham, and there has been an Israelite/Jewish community there since Joshua long before it was King David's first capital. In 1929, Arab rioters with the passive consent of the British killed or drove out virtually the entire Jewish community.
It is now often proposed as a principle of international law and morality that all places that the British and the Arabs rendered Judenrein must forever remain so.
For another example: In 1948, Trans-Jordan seized much of Judea and Samaria (which they called The West Bank) and East Jerusalem and the Old City. They killed or drove out every Jew.
It is now often proposed as a principle of international law and morality that all places that the British and the Arabs rendered Judenrein must forever remain so. In contrast, Israel eventually allotted 17 percent of Mandate Palestine has a large and growing population of Arab citizens.
From Palestine To Israel
What was to become of "Palestine" after the Mandate? This question was taken up by various British and international commissions and other bodies, culminating with the United Nations in 1947. During the various deliberations, Arab officials, spokesmen and writers expressed their views on "Palestine".
"There is no such country as Palestine. 'Palestine' is a term the Zionists invented. . . . Our country was for centuries part of Syria. 'Palestine' is alien to us. It is the Zionists who introduced it." Local Arab leader to British Peel Commission, 1937
"There is no such thing as Palestine in history, absolutely not" Professor Philip Hitti, Arab historian to Anglo-American Committee of Inquiry, 1946
"It is common knowledge that Palestine is nothing but southern Syria." Ahmed Shukairy, United Nations Security Council, 1956 By 1948, the Arabs had still not yet discovered their ancient nation of Falastin. When they were offered half of Palestine west of the Jordan River for a state, the offer was violently rejected. Six Arab states launched a war of annihilation against the nascent State of Israel. Their purpose was not to establish an independent Falastin. Their aim was to partition western Palestine amongst themselves.
They did not succeed in killing Israel, but Trans-Jordan succeeded in taking Judea and Samaria (West Bank) and East Jerusalem, killing or driving out all the Jews who had lived in those places, and banning Jews of all nations from Jewish holy places. Egypt succeeded in taking the Gaza Strip. These two Arab states held these lands until 1967. Then they launched another war of annihilation against Israel, and in consequence lost the lands they had taken by war in 1948.
During those 19 years, 1948-1967, Jordan and Egypt never offered to surrendar those lands to make up an independent state of Falastin. The "Palestinians" never sought it. Nobody in the world ever suggested it, much less demanded it.
Finally, in 1964, the Palestine Liberation Movement was founded. Ahmed Shukairy, who less than 10 years earlier had denied the existence of Palestine, was its first chairman. Its charter proclaimed its sole purpose to be the destruction of Israel. To that end it helped to precipitate the Arab attack on Israel in 1967.
The outcome of that attack then inspired an alteration in public rhetoric. As propaganda, it sounds better to speak of the liberation of Falastin than of the destruction of Israel. Much of the world, governments and media and public opinion, accept virtually without question of serious analysis the new-sprung myth of an Arab nation of Falastin, whose territory is unlawfully occupied by the Jews.
Since the end of World War I, the Arabs of the Middle East and North Africa have been given independent states in 99.5 percent of the land they claimed. Lord Balfour once expressed his hope that when the Arabs had been given so much, they would "not begrudge" the Jews the "little notch" promised to them.
[Note: Some of the material cited above is drawn from the book From Time Immemorial by Joan Peters.]
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There is no "p" sound in Arabic---hence foreign language words imported into Arabic have to substitute either "b" (as in "Boutros" for Greek "Petros" or "Peter"), or "f" as in "Falastin" for Palestine.
A very good article indeed---full of useful and incontestable historical facts about the artificial land of "Palestine" and its make-believe people, the "Palestinians."
Confucias Leni say, "People who don't read history, BECOME history!"
Great post--thank you.
No matter what insanity might prevail to allow these vagabonds that call themselves Palestinians to establish a terrorist state, it will never be enough, and has never been their aim. Their aim is destruction of Israel, and the bannishment of the Jewish population. The international community ruined South Africa, by muddling in the affairs of the founders of that civilization that became overrun with migrants living off the need of the populace for cheap labor, much like is happening in the SW United States at the present time and is happening in Israel and has happened in the Balkins.
I destest the attitude that the capable must make way for the third world to take over their honest hard work and bring it back to a wasteland as seen in Afghanistan, when these people are so much easier to kill than to deal with.
Then, too, virtually 100% of all the Arab and Jewish occupied areas in the Middle East were part of the various and successive Turkish empires for about 90% of a millenium.
It would be ridiculous to say that the Egyptians, the Arabs and the Jews didn't really exist because of these events.
Unfortunately, the article posted here comes to that conclusion with respect to the Palestinians.
It's time to give it up folks. Living human beings do not cease to be living human beings because someone else is able to misarrange words on a piece of paper.
Italian nationalism did not develop until the 19th century, and there was no independent political entity called Italy until then, yet Italy, even at its birth, was no less a nation than France, which had had its sense of national identity since the middle ages. There is no language called "Austrian," yet Austria is very much a distinct nation from Germany.
But I do grant the author of this article one thing: he is a good sophist.
The article does not come to that conclusion. The article only points out that there is no traditional "Palestinian" state or culture. You mentioned the Egyptians not having a native-born leader for many years, but that fact did not change the fact that Egypt had a distinct land and culture. You mentioned that the Turkish empires controlled much of the Middle East for many years, but you don't tell what point this fact is supposed to support. The article says that while the Ottoman Empire controlled the land, no one actually lived in what people are trying to call "Palestine."
The conclusion of the article is that this land was uninhabited wasteland until the beginning of the last century. When the Arabs heard that it was to be given to the Jews, they moved there first to keep the Jews from having it. While I feel sorry for the descendants of the people who moved for such spiteful reasons, the notion that they have a traditional attachment to the land is silly. To the extent that they share the "don't give the Jews a place to live" attitude of their parents, they certainly don't have any moral claim on any land.
If you can refute the content of this article, you will have a point. As it is, your post doesn't seem to add much light to the subject.
So the Jews bought all the land west of the Jordan? Are you seriously asserting that all the Arabs living there now are renters?
Are you seriously asserting that Jews own all the land in Palestinian cities such as Bethlehem or Jerico? I'm sure that's news to the people who live there.
it is their land, it always has been their land and always will be.
If it was always their land, why did they have to buy it, as you claim?
Before the British took over Palestine and began the process of colonizing it with Jews, there were approximately 700,000 inhabitants, a tiny poriton of whom were Jews. I must say that your usage of the word uninhabbited is quite unconventional.
The significance is that today, the Palestinians (and the arab states in general) are peddling the myth that there used to be a "Palestinian" nation and homeland, and that the Israelis stole it. This myth is at the base of all arguments that the Israelis are "occupying" territory that allegedly rightly belongs to the Palestinians. It's why the arab world is so rabidly adamant about throwing out those nasty Israelis (or outright killing them all) and "retaking" the territory, as if it rightly belongs to the Palestinians.
No one's denying that the Palestinians have a national identity *now*, or that they'd like to establish their own nation somewhere. But the point is that what they can rightly do about those feelings depends heavily upon whether they have a historic "rightful" homeland, or whether they need to go off and find some land that isn't already someone *else's* homeland (e.g., Israel).
I insist that you state clearly what region you are describing as "Palestine" in the above statement, and cite your source for the population figure you claim.
Facts to deal with:
1. Isreal has been, and will always be.
2. "Occupied lands" is an invention of the Arabs. Reconquered is the accurate adjective.
3. "Peace" will be a chimera as long as "Palestine" is not so considered.
If your statement is true, then you have raised a legitimate argument against the article. However, as Dan Day states in another post, you need to define what you are calling "Palestine" and what the source for your figure is. I was using "uninhabited" based on the claims of the article, and based on those claims, it is an accurate description.
The British census of Palestine of 1922 shows 752,048. Of that number 83,790 were Jews.
You can get Ottoman census data from the late 19th century. In 1878 the Turks counted 462,465 people, 15,011 of them Jews.
To my knowledge, there is no data available on population figures immediately prior to 1917, when the British took over, but it cannot have changed much from 1917 to 1922, so around 700,000 is a good estimate. Clearly the population did not increase by 300,000 people in 5 years.
Anyway, even if we stick to the Ottoman number, 450,000 souls may be sparesly populated, but it is not unihabited.
Turkish and British census data for these years are readily available.
Israel only existed as an independent state for a few hundred years during the era of the kings, and then for a very brief time before the Roman conquest. Arabs have been living in Palestine since the 7th century.
Also, the land upon which the ancient state of Israel established itself took it from the Caananites, whom the Bible said the Israelites mercilessly slaughted.
2. "Occupied lands" is an invention of the Arabs. Reconquered is the accurate adjective.
Israel did not annex the occupied territories. Even the Israeli government does not consider them to be part of Israel.
3. "Peace" will be a chimera as long as "Palestine" is not so considered.
So what are you proposing to do with the people who beleive themselves to be the nation of Palestine? Perhaps the same fate as the Caananites?
By whom exactly? And if your answer is God, read Romans 11. The Israelites ceased being God's chosen people when they rejected teh Messiah, who established a New Covenent that supercedes the Old.
History Bump
"After the Exodus from Egypt probably in the Thirteenth Century BCE but perhaps earlier the Children of Israel settled in the land of Canaan."
IMO the Exodus began in 1628BC during the explosion of the island of Thera, the island was populated by Minoians (The Sea People) an advanced people.
The Minoian survivors of the explosion made their way to the Gaza area and established a 'beachhead' while the Jews were wandering around in the desert following the plume ('Staff by day' torch by night') of the erupting Thera.
Once the Jews arrived in Israel they were totally dependent on the Philistines (The Sea People) for all their metal works, even metal repairs.
During periods of conflict between the Jews and the Philistines, the Philistines would with-hold all metal works and supplies to the Jews. ( I assume that the Minoians were eventually assimilated into the surrounding population...and yes I do know that Minoian is mis-spelled). Also, I think there have been a number of different groups of people (at different times and places) who have been known as 'The Sea People.'
"After the Exodus from Egypt probably in the Thirteenth Century BCE but perhaps earlier the Children of Israel settled in the land of Canaan."
IMO the Exodus began in 1628BC during the explosion of the island of Thera, the island was populated by Minoians (The Sea People) an advanced people.
The Minoian survivors (soon to be called the Philistines) of the explosion made their way to the Gaza area and established a 'beachhead' while the Jews were wandering around in the desert following the plume ('Staff by day' torch by night') of the erupting Thera.
Once the Jews arrived in Israel they were totally dependent on the Philistines (The Sea People) for all their metal works, even metal repairs.
During periods of conflict between the Jews and the Philistines, the Philistines would with-hold all metal works and supplies to the Jews. ( I assume that the Minoians were eventually assimilated into the surrounding population...and yes I do know that Minoian is mis-spelled). Also, I think there have been a number of different groups of people (at different times and places) who have been known as 'The Sea People.'
A friend of mine has called me 'one of those sea people', she says even my sneakers smell like saltwater. :-)
Sounds like "Palistine" is a convenient funneling area for terrorist insurgents.
I do understand. The greatest distance I ever lived from salt water was when I lived in Houston, 'The Bayou City.'
Have a great weekend!
You have been reading far too many Muslim rags evidently. The British Empire re-established a homeland for the Jews, they had the authority to do so as they had conquered all that land. The Jews went into the land that was established as theirs and bought out those Arabs that claimed, without any proof in many cases at inflated prices.
As far as Jericho, Ramallah, Gaza, the West Bank goes those belong to Isreal by conquest just as much as the land previously belonged to Britian. The one strong enough to hold the land, owns the land, it has been thus since the dawn of man, or didn't you know that?
The error Israel made was in allowing anyone besides Israelies to remain there. Now it's time to toss the rabble out. And the international community should back off and shut it's pie hole until this is accomplished.
As far as Jericho, Ramallah, Gaza, the West Bank goes those belong to Isreal by conquest just as much as the land previously belonged to Britian. The one strong enough to hold the land, owns the land, it has been thus since the dawn of man, or didn't you know that?
I see, so the land is rightfully Israel's because they conquered it. Tell me then: if Israel gained the land by conquering it, why is it wrong for the Arabs to try to do the same? Furthermore, if Israel's claim is based on nothing more than the right of conquest, why is the US or any other Western power morally obliged to support Israel?
The error Israel made was in allowing anyone besides Israelies to remain there. Now it's time to toss the rabble out. And the international community should back off and shut it's pie hole until this is accomplished.
2 points:
1) I see you are on record advocating ethnic cleansing of Palestinians. If you honestly beleive such a plan is politically feasible, you are in need of a serious reality check.
2) The International Community will back off when Israel stops taking all the free money it gets from the West. Until then the West, specifically the US, gets to tell Israel what to do.
Jeff, this is the information I was trying to explain to that lady at dinner last friday...she said she was going to register.
Maybe you can give her the url for this thread next week if you and Mama_Bear go to Fresno. She was very interested in knowing this info, even called her husband from the dinner table if I remember correctly...
Please. The Arabs tried many times to do the same, and they got their butts kicked. They gambled for more land, and lost the gamble. Now they are trying to get it back - without risking anything - by convincing the ignorant that the Israelis are the Bad guys and should just hand the land over.
Still, as unreasonable as that is, consider how the Israelis handled the deal with Egypt. The Palis could do the same if they would be as reasonable as Egypt was.
Ethnic Cleansing has bad connotations, but it does not have to be cruel. The fact is, unless the Palestinians stop the terrorists in their midst, they have no right to expect the Israelis to treat them as friends. Unless that happens quickly, the best thing that could happen would be for the 2 parties to live apart.
BTW, what do you think would happen to the Jews who did not choose to be "ethnically cleansed" from the future Palestinian state?
They didn't move to Palestine out of spite, and it wasn't simply a desolate wasteland since the days of Bar Kochba.
The primary posting in this thread perpetrates a false image of Palestine, Israel and the Levant. That image is then used to deligitimize the right of the non-Israeli population to live there, or to have any rights - that includes the Syrian Orthodox priests who have been around since the foundations of Christianity. That should demonstrate conclusively that the objective is not necessarily to deligitimize Yasser Arafat and the PA, or the Westbankers, but to deligitimize both Christianity and Islam from a presence in Israel or adjacent territories.
I believe Thera could well have been the cover under which the early Israelites who left by sea (aka the Proto-Celts) escaped, the rest escaping by land in the traditional EXODUS a century or two later.
In any case, none of these Iraelites were Jews. They were just Israelites, and not even divided into Northern and Southern Kingdoms at this point. The designation "Jew" for a small percentage of these Israelites offspring was not in common use until 500 BC, over a thousand years later.
For the details, click on my Profile.
You have taught me this and I agree. However, when I am making a 'quick' statement I think it is more widely understood when I use the word Jew....besides, I knew you'd be around shortly to correct the record, thanks. (smile) Now, I have to go out and continue cutting the grass. That's all I've done this week, cut grass. (ugh)
... assume that the Minoians were eventually assimilated into the surrounding population
I go real slow on assuming any population was "assimilated" into any other population. While
this certainly could have happened, and assimilation is not unknown, I think its claim is widely abused, and used mostly when the author simply doesn't know what happened. The story isn't complete without some final "explanation".
The most blatant of these "assimilation" errors, involving by far the LARGEST group of people, is the claim that the Lost Tribes of Israel were "assimilated" by their captors,
the Assyrians, and that's the end of their story. After even the most superficial examination of their history, the application of this "explanation" strains credulity.
When the Lost Tribes of Israel joined with the Medes and Persians to whip their
Assyrian captors, about 600 BC, their population was over 5 MILLION, and that was almost 10 Percent of the Global population! Ten percent of the global population is not easily assimilated by anyone, and it has to be someone even bigger, or at least more powerful. There weren't many Ten Percents around that part of the world to do such assimilating!
Since the previously totally unknown CELTS just happened to suddenly appear in massive quantity at the same time and the same place the Lost Tribes of Israel disappear, the only "assimilation" I can find is in their renaming. (But this does step on a number of oh-so-sensitive toes...)
For more details , see my Profile.
That's what happens when you OWN 28% of the State!
This is the best post of the lot. All of this is interesting and, as illustrated in the posts, subject to endless debate. The bottom line is who has the power to take and hold territory. No borders are permanent. Look at the old Soviet Union, (not to mention the Roman, Ottoman and British empires). India and Pakistan are legal creations. People have been fighting over land in Europe for centuries. Someday the U.S. borders might not be as they are today.
I don't understand how we think that the U.S. government has some moral obligation to "restrain" Israel when they are doing exactly what we would do. Jimmy mentions Texas in his post. Can you imagine what U.S. public opinion would be if Mexican extremists were launching suicide bombing missions against U.S. Civilians from "occupied" Mexico in south Texas? We'd hunt them down, kill them and break their stuff. Exactly what Israel is trying to do now.
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text: Posted March 13, 2013 I wouldn't mind being cremated, and my ashes mixed into brick mix. My kids can then use the bricks made with my ashes to build a walkway or something. Hell my great grand kids can even piss on the bricks if they want to. Whatever. Share this post Link to post Share on other sites

subset: commoncrawl


text:
Annual Message to Congress:
"The policy of emancipation, and of employing black soldiers, gave to the future a new aspect, about which hope, and fear, and doubt contended in uncertain conflict." In his 1863 annual message to the Congress, Lincoln underscored his reluctance to adopt emancipation as a war aim and to recruit African Americans as soldiers. Both had been unwanted experiments forced upon Lincoln and a majority of the North by the war. The wisdom of the move, the president asserted, was nevertheless manifest in the results: success on the battlefield and the enemy's loss of the labor of a hundred thousand slaves. But Lincoln, despite ample proof of black heroism in battles at Port Hudson and Milliken's Bend, Louisiana, at Fort Wagner, and along the South Carolina coast, chose only to say, "So far as tested, it is difficult to say they are not as good soldiers as any." Revealing his expectations, Lincoln expressed relief that "No servile insurrection, or tendency to violence or cruelty, has marked the measures of emancipation and arming the blacks." For those black soldiers who gave their lives for the Union and for an end to slavery—and at half the pay of the lowest-ranking white private—such praise was even more insulting than was Lincoln's continued support for colonization.
December 8, 1863
… The preliminary emancipation proclamation, issued
in September, was running its assigned period to the be-
ginning of the new year. A month later the final procla-
mation came, including the announcement that colored
men of suitable condition would be received into the war
service. The policy of emancipation, and of employing
black soldiers, gave to the future a new aspect, about which


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- ParaguayFoodFunding via Fundación Paraguaya
JorgelinaParaguayFoodFunding via Fundación Paraguaya
Saguazu GroupParaguayFoodFunding via Fundación Paraguaya
La Esperanza Group
One of these women is Sra. Maria. She generates sales from a small food pantry that is well-stocked with all types of products that her neighbors need. Maria tries to keep everything they like on hand so that they will continue to visit her shop. Thanks to her work, Maria is able to help her family and provide everything they need to have a decent life and not feel deprived.
Maria is requesting a loan in order to buy dairy products, baked goods, vegetables, and other items so that she can continue to restock her business. This will enable her to offer her customers the variety of items that they are accustomed to having.
Una de ellas es la Sra. Maria, quien se dedica a las ventas. Tiene una pequeña despensa bien surtida con todos los productos que sus vecinos necesitan. Siempre trata de tener todo para que ellos se sientan a gusto y sigan yendo a su local. Gracias a su trabajo Maria ayuda a su familia y les da todo lo que necesitan para poder tener una vida digna y sin privaciones.
Solicita de este crédito para la compra de lácteos, panificados, verduras, y demás insumos para poder seguir surtiendo su negocio y de esa forma dar a sus clientes la variedad a la que están acostumbrados.
Additional Information
More information about this loan
This loan is part of the innovative "Poverty Stoplight" program developed by Fundación Paraguaya for women living in poverty. A "stoplight" measurement tool is used to help borrowers self-identify the type of poverty that affects them most (lack of income, dearth of financial opportunities, poor living conditions etc.). Borrowers rate 50 areas of their life as green (not poor), yellow (poor) or red (extremely poor). Together with their loan officer, they come up with a plan to resolve yellow and red indicators. Through this program, Fundación Paraguaya hopes to lift 9,000 women and their families out of poverty by 2017.
To learn more about this unique approach to eliminating poverty, you can read this article on Fundación Paraguaya's website.
About Fundación ParaguayaFundación Paraguaya is a financially self-sustaining social enterprise that promotes entrepreneurship in urban and rural areas through microfinance, education programs, and more. Its focus on agriculture has helped many farmers boost their crop yields. And a number of other borrowers have taken out loans to start and grow social businesses that have helped deliver eyeglasses, medicines and other helpful services in their local communities.
This is a Group Loan
In a group loan, each member of the group receives an individual loan but is part of a larger group of individuals. The group is there to provide support to the members and to provide a system of peer pressure, but groups may or may not be formally bound by a group guarantee. In cases where there is a group guarantee, members of the group are responsible for paying back the loans of their fellow group members in the case of delinquency or default.
Kiva's Field Partners typically feature one borrower from a group. The loan description, sector, and other attributes for a group loan profile are determined by the featured borrower's loan. The other members of the group are not required to use their loans for the same purpose.
About Paraguay
49View loans »
Success!! The loan was 100% repaid
- Repayment Term
- 6 months (Additional Information)
- Repayment Schedule
- Monthly
- Pre-Disbursed:
- Feb 27, 2013
- Listed
- Mar 20, 2013
- Currency Exchange Loss:
- Covered
- Ended:
- Jul 17, 2013


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Earn hundreds of CEUs, educate your patients, expand your clinical expertise, improve outcomes. It's all included in the annual subscription.
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John Kiesel, PT, DPT
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text:
Meanwhile, the struggling South Korean ocean carrier said in a statement Sunday it expects to reach an agreement with ship owners regarding charter rate renegotiations "soon."
The Baltic Exchange, which had revenues of just $8.8 million last year, is more of a market-information service these days, generating indexes so members can work out fair cargo transport prices, according to Bloomberg's David Fickling and Andy Mukherjee.
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The proposed alliance would become a dominant player in the three major east-west trades, beating out total capacity currently offered by the 2M Alliance on those trade lanes, according to an analysis from BlueWater Reporting.


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Hello Second Graders!!
I would like to first introduce myself. I am Kim Blankenship and I am super excited to be your child's second grade teacher! This is my fifth year teaching, my fifth year at Sterling Elementary, and my second year in teaching second grade! One of the many reasons that I love teaching at Sterling Elementary is because I am from the area. I went to Guilford Elementary, Sterling Middle, and I graduated from Park View High School. I am a 2011 graduate of Radford University with my degree in Elementary Education.
We will be having a Back to School Night on Thursday, August 27 at 6pm. We are asking that only parents attend this session so that you are able to get to know me and ask any questions. We will be having an Open House on Friday, August 28 from 1:00pm-2:30pm. Students are welcome during this session. They will be able to drop off supplies, see where they will be sitting, and get to know the classroom. I'm excited to meet each and every one you and learn about your lives. For more information about the 2015-2016 school year, check out my welcome letter.
Kim Blankenship
You can email me at email@example.com


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Glitter Miss To Mrs Banner - 5 inch Letters with Hearts - Bridal Shower Decor Bridal Shower Banner Bachelorette Garland Bachelorette Party
Product Info
Celebrate the soon to be Mrs with a glittery gold banner! Banner is handmade to order in your choice of glitter cardstock and will be shipped within 3-5 business days from purchase date. If you have a time sensitive order, please contact me before ordering to find out my current turnaround time.
Banner will be made from 5 inch tall letters die-cut from a heavyweight glitter cardstock in your choice of color (see 4th photo). This is a premium coated cardstock which does not shed its glitter or make a mess and is white on the backside. The hearts are 4 inches tall and then banner will be strung with your choice of twine (see 5th photo).
MISS TO MRS with two hearts measures approximately 46 inches long (almost 4 feet for the wording) and then I'll include an additional 3 feet of twine on each end for hanging. There is plenty of room to slide the letters along the twine and space pieces to your preference.
You'll find glitter cardstock and twine color charts in the last two photos above. Banner in photos was made in gold glitter cardstock letters, red glitter cardstock hearts and then strung with solid black twine. If no color choices are left at check-out, then your banner will be made in the shown colors.
At check-out, please leave a message in "note to seller" with your color choices for the following:
1. letter glitter cardstock color
2. heart glitter cardstock color
3. twine color
Please allow 3-5 business days (Mon-Fri) for me to hand make your banner and have it in the mail. Then First Class/Standard shipping takes about an additional 3-5 business days within the USA. Locations within the USA can choose Priority Mail shipping upgrade at check-out for quicker delivery. Due to customs, International First Class shipping times vary. Please allow 2-6 weeks for your International delivery to arrive. Shipping times are not guaranteed and are only estimates provided by USPS.
If you have a time sensitive order, please contact me before purchasing to find out my current production time. Orders are worked on in the order payment is received, so my production time changes daily.
If you would like your banner to say something else, please contact me about creating a reserved custom listing just for you. 5 inch tall gold glitter letters or 4 inch tall hearts like this listing are $1.75 each. Feel free to contact me with any questions!
● 11 piece banner
● letters are 5 inches tall and vary in width
● hearts are 4 inches tall and 4.5 inches wide
● Packaged in a clear, poly bag for storage or gift giving
● Items are shipped in a rigid, cardboard mailer
Find my shipping, shop policies & FAQ's here:
Thanks for shopping Fresh Lemon Blossoms!


text:
|Numķro de publication
|Type de publication
|Numķro de demande
|Date de publication
|1 juil. 2008
|Date de dķp¶t
|14 sept. 2005
|Date de prioritķ
|14 sept. 2004
|╔tat de paiement des frais
|Autre rķfķrence de publication
|Numķro de publication
|Barbara P Chan, Kwok Fai So
|Cessionnaire d'origine
|The University Of Hong Kong
|Exporter la citation
|BiBTeX, EndNote, RefMan
|Citations de brevets (5), Citations hors brevets (53), Rķfķrencķ par (6), Classifications (21), ╔vķnements juridiques (4)
|Liens externes: USPTO, Cession USPTO, Espacenet
This non-provisional application claims the benefit of priority to U.S. provisional application 60/609,600 filed Sep. 14, 2004.
Not Applicable.
Not Applicable.
(1) Field of the Invention
The present invention relates generally to crosslinked collagen scaffolds. More particularly, it relates to the method of crosslinking and producing collagen-based scaffolds with improved properties using light and photosensitizing reagent, and to the products produced by the method.
(2) Description of Related Art
Collagen is the most abundant protein in the extracellular matrix of human tissue and plays important roles in providing structural support as well as performing other functions in tissue growth and regeneration. Apart from collagen, other types of extracellular matrix components such as proteoglycans, elastin, etc. also play important roles in maintaining tissue structure and function. Producing scaffolds simulating natural tissue is an essential enabling technology in the tissue engineering industry.
Collagen is the best natural biomaterial for tissue engineering because of its close resemblance to nature, and its negligible immunogenecity and excellent biocompatibility. However, unprocessed collagen usually has insufficient mechanical properties for it to be useful in engineering tissues in particular the weight-bearing tissues such as tendons, ligaments, intervertebral discs, etc. Unprocessed collagen is also difficult to manipulate and put sutures through during the implantation process. Further, unprocessed collagen is highly water swellable and is vulnerable to enzymatic digestion and thermal denaturation.
Crosslinking has been used to improve the properties of collagen and therefore is crucial in the tissue engineering industry. Tissue engineering companies have disclosed various methods for crosslinking collagen constructs and scaffolds using chemical methods such as treatment with glutaraldehyde (Cavallaro, U.S. Pat. No. 5,718,012 for "Method of Strength Enhancement of Collagen Constructs") and physical methods such as lyophilization (Kemp et al., U.S. Pat. No. 5,256,418 for "Collagen Constructs") to enhance the strength and stability of the structures. Other physical crosslinking methods such as ultraviolet (UV) and gamma irradiation and dehydrothermal treatment have also been reported.
However, both chemical and physical crosslinking methods have encountered problems. Chemical crosslinking of collagen using a reagent such as glutaraldehyde, although efficient, compromises the biocompatibility of scaffolds because the toxic residual chemicals and degradation products induce cytotoxicity and calcification (Simmons D. M. et al., "Evaluation of Collagen Cross-Linking Techniques for the Stabilization of Tissue Matrices", Biotechnol Appl Biochem. 17 (Pt 1):23-9 (1993)). Physical crosslinking methods are time-consuming (Weadock K. S. et al., "Crosslinking of Collagen Fibers: Comparison of Ultraviolet Irradiation and Dehydrothermal Treatment", J Biomed Mater Res. 29(11):1373-9 (1995); and Billiar K. et al., "Effects of Carbodiimide Crosslinking Conditions on the Physical Properties of Laminated Intestinal Submucosa", J. Biomed Mater Res. 56(1):101-8 (2001)), and compromise the stability of scaffolds because UV and gamma irradiation, and the harsh processing conditions in the dehydrothermal treatment method denature the protein (Weadock et al., supra; Billiar et al., supra). As a result, a long-felt need has existed for alternative methods of enhancing the physico-chemical properties of collagen coupled with features such as rapid and efficient processing, nil toxic substances, non-thermal processing and absence of denaturation of collagen.
Previous studies involving light-activated processes to stabilize xenografts (heterografts) such as pericardial tissues, and heart values for transplantation have been reported (Adams A. K. et al., "Crosslink Formation in Procine Valves Stabilized by Dye-Oxidated Photooxidation", J. Biomed Mater Res, (57):582-587 (2001); Moore M. A. et al., "Stablization of pericardial tissue by dye-mediated photooxidation", J. Biomed Mater Res, 28(5):611-618 (1994)). These studies were aimed at further stabilizing intact tissues having extracellular matrix protein networks and the intrinsic mechanical properties thereof. The xenograft repair approach differs greatly from that used in tissue engineering, in which tissue-like scaffold structures are built from basic units such as extracellular matrix components, cells and growth-stimulating bioactive factors.
Studies on the crosslinking of collagen proteins in solution using light-activated processes have been reported (Pitts J. D. et al., "New Photoactivators for Multiphoton Excited Three-Dimensional Submicron Cross-Linking of Proteins: Bovine Serum Albumin and Type I Collagen", Photochem., Photobiol 76(2): 135-144). The average laser power used to create submicron structures ranged up to 1010 W/cm2. Although there was no evidence as to whether the collagen was denatured and whether the processed collagen structures have improved strength and stability, at such high power, collagen protein is very likely to coagulate and become denatured. Therefore, the crosslinking is based on thermal mechanism.
Mechanic, U.S. Pat. No. 5,147,514 for "Process for Crosslinking Collagenous Material and Resulting Products" describes a photooxidative process for crosslinking proteins using photocatalysts in the presence of oxygen. This patent discloses the oxygen dependence of the crosslinking process in that bubbling of air or oxygen, or stirring the reaction mixture vigorously was used to increase the concentration of oxygen. Further, a photocatalyst was used so that the compound did not change before and after the process. This is not the case for the photochemical crosslinking process of the present invention in that the photosensitive reagent participates in the crosslinking process. Moreover, the prior art crosslinking process does not strengthen or stiffen the crosslinked products and therefore cannot solve the major problem, namely, the inadequate mechanical properties of unprocessed collagen used as scaffolds for tissue engineering. Further, the patent does not reveal any intention to produce larger and thicker scaffolds. The thickness of collagen scaffolds to be crosslinked by irradiation is limited because of the depth of penetration of the light source.
The present invention provides a method for producing crosslinked collagen and composites scaffolds with enhanced properties such as strength and stability and maintains excellent biocompatibility. The method comprises (a) reconstitution of three-dimensional collagen extracellular matrix from collagen monomer solution using methods such as raising the pH of the solution for certain period of time; (b) cross-linking at least a portion of the matrix contacting it with a photosensitizing reagent at a particular concentration in darkness for certain period of time before or after reconstitution; (c) removing excess photosensitizing reagent; (d) irradiation of the scaffolds with a light source of sufficient energy for a certain period of time so as to form crosslinked scaffolds; and (e) dehydration of the crosslinked scaffolds. The method of the invention can further comprise laminating the rehydrated and crosslinked scaffolds for multiple times to produce large scaffolds. The method of the invention also enables incubation with other extracellular matrix component for making composites scaffolds and immobilization of bioactive factors or drugs that can be subsequently released from the scaffolds.
The collagen monomers can be of different collagen phenotypes including collagen type I, II, III and preferably type I, II, III which are abundant in human tissues. The collagen monomers can be isolated or extracted from various animal sources including but are not limited to rat tail, bovine Achilles tendon, porcine skin, human placenta. The collagen monomers can be from different fractions of collagen extraction from animal sources including but not limited to the acid-soluble fraction, pepsin digested fraction, or the insoluble fraction.
The reconstitution of collagen monomer solution can be induced by methods such as raising the pH of the solution, increasing the temperature of the solution and immersion in solutions with high ionic strength. The collagen reconstitution is induced preferably by raising the pH of the solution by exposing the solution in a chamber filled with an alkaline vapor or solution, preferably ammonia, for a period ranging from 3 minutes to 96 hours. The collagen monomer solution can be exposed to an alkaline solution, preferably ammonia water, through a semi-permeable membrane, including but are not limited to dialysis tubing, cellulose membrane, filter paper, etc., with a cut-off size smaller than collagen molecules.
If an alkaline solution-containing chamber is used to initiate reconstitution, the collagen monomer solution is sealed in a semipermeable membrane or its equivalent and immersed in alkaline solution such as ammonia water.
The photosensitizing reagent includes but is not limited to fluorescein, rose Bengal, methylene blue, eosin, and porphyrins. The concentration of the photosensitizing reagent varies from 0.000001% to 10%. The matrix is brought into contact with the photosensitizing reagent for a period ranging from 5 seconds to 100 hours before or after reconstitution. The excess photosensitizing reagent can be removed by multiple rinsing in water or isotonic solution.
The light source can be a UV or visible source, such as a laser, xenon light, light-emitting diode (LED), etc. The light source can be used to irradiate the scaffolds at an irradiance which varies from 0.0001 W/cm2 to 10 W/cm2. The mode of irradiation can be pulsed or continuous. The energy used for irradiation ranges from 0.0001 J to 10000 J. The period of irradiation ranges from 5 seconds to 100 hours.
The scaffolds can be placed in a container provided with a cooling means such as running cold water. The scaffolds are removed from the solution containing the photosensitizing reagent and rinsed several times in distilled water or isotonic solution prior to irradiation. The scaffolds are irradiated without bubbling air or oxygen into the reaction mixture or vigorous stirring.
The dehydration can be via air-drying, freeze-drying, vacuum drying, critical point drying, alcohol drying, acetone drying, centrifugation and compression against water absorbents and the like.
The invention is able to strengthen the scaffolds by imparting to them improved stress-strain relationship (
The invention also enables the formation of collagen scaffolds with fine microstructures with micron-sized pores and nano-sized fibers simulating that of the chemically crosslinked ones while the uncrosslinked scaffolds only have membrane-like macrostructures (
The method is able to chemically stabilize the scaffolds with better thermostability in terms of much higher denaturation or solubilization point than the uncrosslinked form in that the crosslinked scaffolds still retained the well-organized three-dimensional structure while the uncrosslinked ones are solubilized or melt at the end of thermal challenge due to the breakdown of the inter- and intra-molecular linkages. (
The method is able to chemically stabilize the scaffolds with improved resistance to in vitro biodegradability (e.g. collagenase digestion) (
The method also reduced the intrinsic thrombogenecity of collagen membranes in that the number of platelet adhesion was reduced significantly and the thrombin activation was completely prevented as compared with the uncrosslinked membranes (
The method of the invention reduces the swelling ratio of the scaffolds while gradually increasing the swelling ratio in a time-dependent manner. The effect can be controlled by varying factors such as the dosimetry of the light source such as the fluence (
The photochemical reagent to be used and its concentration are the key controlling variables for the process.
The light source to be used and its fluence and irradiance are another key controlling variables for the process.
The status of the biomaterials, either in solution form, or reconstituted gel form, or rehydrated biomaterials, to be used for crosslinking, affect the properties of the scaffolds. The presence of other small molecules able to be the crosslinkers such as pyridinoline also affect the resultant properties of the materials.
The concentration of the collagen monomer or other extracellular matrix components also affects the resultant properties.
The method affords a way to laminate layers of scaffolds, in particular, laminating the crosslinked products with the collagen monomer solution during reconstitution and is followed by repeating the method.
The method is able to produce three-dimensional structures of appropriate thickness, ranging from 50 μm to theoretically unlimited thickness with enhanced mechanical properties such as compression moduli (
The photochemical crosslinking method described and claimed herein is able to produce collagen scaffolds and composites of different shapes, forms and dimensions, with enhanced strength, thermostability and resistance to proteolytic digestion, as well as reduced swelling ratio. Swelling ratio is the ratio of the difference between the wet and the dry weight of the scaffold to its dry weight. These scaffolds and composites are adapted to be delivered by methods such as implantation and injection, to repair or replace defective tissues including but not limited to tendons, ligaments, intervertebral discs, nerves, and blood vessels. The reduced swelling ratio and increased stability of the scaffolds also enables controlled release of molecules or drugs, which can be growth-stimulating, anti-inflammatory, hemostatic, etc, when they are immobilized in the scaffolds.
The present invention enables the production of collagen scaffolds, in different shapes, forms and sizes, with improved properties such as enhanced strength, thermostability, resistance to proteolytic digestion, reduced swelling ratio, improved haematocompatibility and excellent biocompatibility. Collagen scaffolds with enhanced strength are useful in providing structural and functional supports in engineered tissues, particularly weight-bearing tissues such as tendons, ligaments, intervertebral discs and the like. Collagen scaffolds with enhanced chemical and thermal stability are less vulnerable to denaturation or destabilization during other processing such as sterilization. Collagen scaffolds with increased resistance to proteolytic digestion and chemical stability are less vulnerable to disintegration in physiological and proteolytic environments upon implantation at the repair site and therefore have longer life span to allow better tissue growth and regeneration. Crosslinked collagen scaffolds with good cell and tissue compatibility prevents unfavorable inflammatory events and enhances cell adhesion and growth and thus allows better tissue regeneration after implantation. Collagen scaffolds with improved haematocompatibility or reduced thromogenicity can be used in vascular tissue engineering that uncrosslinked collagen is inherently not suitable for making artificial blood vessels because it is known to be the most thrombogenic component of the extracellular matrix inducing platelet adhesion and thrombin activation upon contact with blood.
Collagen scaffolds have solid three-dimensional structures and are obtained from collagen monomers in solution form, isolated or extracted or prepared from any animal sources, such as rat tail, porcine skin, bovine Achilles tendon, and human placenta. The collagen monomers can be from different fractions during collagen extraction, acid-soluble, pepsin-soluble or insoluble. The collagen monomer solution is made into appropriate concentrations ranging from 0.1 to 100 mg/ml depending on the type of tissue to be built. Collagen monomer solution, preferably at a concentration of 1-10 mg/ml, degassed by methods such as centrifugation, is placed into a container, preferably an inert and non-adherent container made for a material including but not limited to glass, polystyrene, and silicone rubber. Any air bubbles generated during the process are removed by puncturing the air bubble with a sharp object such as a fine syringe needle. The collagen monomer solution is induced to reconstitute itself into collagen gel consisting of fibrils by methods including but not limited to pH change, preferably an increase from acidic pH to alkaline pH, temperature change, preferably an increase from 4░ C. to 37░ C., a change in ionic strength, by contact with a solution of high ionic strength. A preferred method is to use an alkaline chamber filled with ammonia vapor. The container with the collagen monomer solution is then placed into the chamber sealed for a period, of preferably 30 mins. The duration of exposure to the alkaline vapor is a factor affecting the mechanical properties of the collagen scaffolds. If a pH change is to be used to induce reconstitution of the membrane in a solution, a semi-permeable membrane or material is place at the interface between the alkaline solution and the collagen monomer solution or at the interface between an inner and an outer chamber as described in U.S. Pat. No. 5,256,418, supra. The colorless collagen monomer solution becomes opaque upon successful reconstitution.
The reconstituted collagen gel or scaffold is rinsed in distilled water or isotonic (physiological saline) solution to remove excess alkalinity. The collagen scaffold can form composite scaffolds with other extracellular matrix components including but not limited to other collagen subtypes and proteoglycans. If composite scaffolds are to be produced, extracellular matrix component other than collagen can be suspended in the collagen solution during reconstitution or the collagen gel is equilibrated with a solution containing the second extracellular matrix component at appropriate concentration for a certain period before photochemical crosslinking.
Collagen is also a good candidate for a drug delivery system, particularly of protein drugs because of its excellent biocompatibility, its interaction with the protein drug that protects the drug from disintegration, and the fact that it sometimes potentiates the bioactivities of drugs such as growth factors. However, collagen gel becomes highly swollen in water and uncrosslinked collagen is vulnerable to proteolytic digestion and disintegration upon implantation. Both swelling and disintegration are the mechanisms for drug release in the polymer network. As a result, drug molecules when immobilized within the collagen network, release rapidly without controlled release. This limits the applicability of collagen gel as a device to control the delivery of drugs, including but not limited to proteins, growth factors, antibiotics, and anti-inflammatory drugs. Controlling the matrix variables such as the concentration and density of collagen gel carriers, extent of crosslinking of the collagen gel, etc. enables one to exert control over the release pattern and the kinetics of drugs immobilized within the collagen network. The photochemical crosslinking method of the present invention has reduced the swelling ratio and increased the resistance of the collagen carrier to proteolytic disintegration and therefore has the potential to control the release of drugs.
Dehydration is an important mechanism for increasing the density of collagen scaffolds and is itself an efficient means for stabilizing and strengthening collagen scaffolds. The dehydration means employed greatly affect material and mechanical properties. Air-drying produces scaffolds with minimal levels of porosity (
Photosensitizing reagents are chromophores able to be activated by photons at particular wavelengths, including but not limited to fluorescein, eosin, rose Bengal, and methylene blue. Photosensitizing reagents for use in the present invention include rose Bengal, which has a spectrum of absorption up to approximately 600 nm. Apart from the UV region, there are two absorption peaks at approximately 320 nm and 550 nm. Rose Bengal has high absorption efficiency and therefore is a very efficient photosensitizing reagent. Rose Bengal is a vital dye that has been used in clinical diagnostic for ophthalmologic diseases for decades (Lansche R. K., "Vital Staining in Normal Eyes and in Keratoconjunctivitis Sicca", Am. J. Ophthalmol. 60(3):520-5 (1965)). It is a safe reagent to use. Rose Bengal is a fluorescent photosensitizing reagent that is water soluble. However, aggregates may form at high concentration such as >1% (w/v) and therefore rose Bengal, preferably ranged from 0.00001% to 0.01% was used in the present invention. Rose Bengal solution was prepared in darkness using a solution such as distilled water, PBS and ethanol. Since photochemical crosslinking only occurs at sites where the substrates for crosslinking, the photosensitizing reagent and the light all present, by controlling the site where the photosensitizing reagent is present and where the light irradiates, the site for crosslinking can be selected. The rate of diffusion of rose Bengal solution in different biomaterials including collagen scaffolds is different and is proportional to the density of the materials and the concentration of the photosensitizing reagent. As a result, controlling the time of exposure of the collagen scaffolds to rose Bengal solution controls the site where photochemical crosslinking occurs. If the surface of the collagen scaffolds instead of the bulk materials is to be crosslinked, rose Bengal solution can be delivered through brushing or painting, or placing the surface for crosslinking of the collagen scaffold on top of a thin layer of absorbent, including but are not limited to kimwipe, tissue paper, cellulose membrane, filter paper, for a certain period of time. Or, it can be done by forming collagen layer by layer where the layers have different concentrations of photosensitizing reagent immobilized. Since the extent of crosslinking is dependent on the dose of the photosensitizing reagent, a gradient of crosslinking within the collagen scaffolds is also possible. Other methods of delivery of the photosensitizing reagent to the collagen scaffolds such as injection are possible. Excess photosensitizing reagent can be removed by blotting the collagen scaffolds on a dry absorbent material such as tissue paper or thorough rinsing in a diluent such as distilled water. The photosensitizing reagent can be brought into contact with collagen before and after reconstitution, or before and after dehydration of reconstituted scaffolds.
The materials are preferably maintained in darkness during the process. When excess reagent is removed by rinsing, the hydrated material will be brought to a light source, be it a UV source, a laser, LED or other source of visible light. The amount and power intensity of the light affect the extent of crosslinking as it is proportional to the number of photons. Suitable light sources for use in the present invention include an argon laser, at a wavelength of 514 nm, or multiline green laser. Other lasers which the rose Bengal absorbs can also be used. The spot size of the irradiation needs to be large enough to cover the material, or a scanning light source that is able to scan the material at controllable speed, or multiple light delivery devices such as optic fibers can be used to deliver light for crosslinking scaffolds with irregular shape. The argon laser useful in the present invention can be continuous or pulsed. The Ultima 2000 argon laser (Coherent Medical) generates laser pulses at 0.2 W with duration of 1 second. The total energy of light delivered to crosslink collagen scaffolds in the present presentation ranged from 12.5 J to 200 J and therefore 62.5 to 1000 pulses were delivered.
Light penetration has a limit of depth in all materials including collagen. An example is the degree of light penetration at a wavelength of around 500 nm in human fair skin, which is around 350 micrometer. See, Douven L. F., "Retrieval of Optical Properties of Skin From Measurement and Modeling the Diffuse Reflectance, Proc. SPIE 3914:312 (2000). Previous studies on the total transmittance of light at around 500 nm have shown that light can penetrate porcine skin dermis and bovine Achilles tendon to a depth of approximately 700 micrometers. Although light penetration should be better in reconstituted collagen gel compared to skin and tendon tissue, which have closely packed connective tissue networks and intrinsic chromophores such as melanin and haemoglobin, the limit of light penetration depth still restricts the thickness of scaffolds to be crosslinked and produced. The method disclosed in the present invention is able to solve this problem. Production of thick collagen scaffolds is enabled by (1) laminating the first crosslinked scaffold with the second layer during the reconstitution step where the monomer solution is gelated to form solid gel; (2) photochemically crosslinking the reconstituted collagen gel and laminating the two scaffold layers; (3) dehydrating the two scaffold layers together and (4) repeating the process multiple times until scaffolds of appropriate size are produced. Other methods such as modifying the optical properties of tissue or materials to be photochemically crosslinked such as immersing in glycerine solution as described in Pendl et al. U.S. Pat. No. 5,817,153 for "Method of Photo-Oxidative Treatment of Tissues Containing Collagen" can be used.
The whole process can be performed under sterile conditions in that the collagen monomer solution is sterile, the photosensitizing reagent is filtered by 0.22 micron filter or autoclaved, the ammonia chamber is prepared in a safety cabinet, and the light source is irradiated through a container with good transparency that is made of materials such as glass and polystyrene, etc. Or, the collagen scaffolds are preferably sterilized by alcohol treatment or other methods such as ethylene oxide gas treatment after production of the scaffolds but prior to implantation.
An acid-soluble rattail collagen type I solution at a concentration of 4 mg/ml is degassed and 1.5 ml of it is carefully laid down onto a plastic container 1.5 cm in diameter, and any air bubbles generated are removed. The pH of the solution is raised by placing the solution in a chamber containing ammonia vapor for 30 minutes. Opague solid collagen gel is formed from colorless solution. A collagen matrix of approximately 7.5 mm thick and 15 mm diameter is obtained and then thoroughly rinsed with water. The gel is immersed in rose Bengal at a concentration ranging from 0.000078125% to 0.01% for 2 hours. Control collagen gel is immersed in water. Excess photosensitizing reagent is removed by thorough rinsing with water. Fully swollen collagen gel is then photochemically crosslinked by exposing it to an argon laser (Coherent Medical, Ultima 2000). Laser pulses of is duration and a power of 0.2 W were used. The total energy input was from 12.5 J to 200 J. The control collagen scaffolds are kept in darkness during the crosslinking process. Fully swollen collagen scaffolds are dehydrated by air-drying on a non-adherent surface for more than 24 hours. Dry collagen membranes are rehydrated in phosphate buffered saline at neutral pH for more than 24 hours and fully swollen collagen membranes of thickness around 100-200 micrometers are obtained for use in subsequent tests. Alternatively, crosslinked collagen scaffolds were freeze-dried to produce porous structures.
Crosslinked dry collagen scaffold prepared by the method of Example 1 is rehydrated in PBS (pH7.4) or water for 30 minutes. The rehydrated collagen membrane prepared as in Example 1 is rinsed in water or other isotonic solution and the water on the surface of the rehydrated scaffolds is removed by blotting dry using kimwipes or other absorbants. The scaffold is carefully laid down at the bottom of a container for reconstitution of collagen gel as described in Example 1. The container has a dimension of 15 mm diameter and approximately 7.5 mm thick. 1.5 ml of degassed acid-soluble rattail collagen solution type I at 4 mg/ml is carefully casted onto the collagen membrane. Any air bubbles generated during this process are removed. The membrane-containing collagen solution is then placed in the ammonia chamber for 30 minutes. Procedures described in Example 1 were repeated to obtain bi-layered crosslinked collagen membranes. The scaffold was dehydrated by air-drying for more than 24 hours. By repeating procedures in Example 1 and 2, collagen scaffolds appropriate thickness can be obtained. For instance, 6- or 10-layer collagen scaffold of approximately 1-2 mm thickness produced by the method disclosed in the present invention can be used for intervertebral disc tissue engineering.
Rehydrated collagen membranes as prepared in Example 1 are carved into a dumbbell shape with a gauge length of 0.5 cm, marked with a dye and the width approximately 0.3 cm. The dimension (thickness and width) is measured by a Mitutoyo QUICKVISION PRO system with a precision up to 0.00001 mm. Both ends of the samples are attached with PBS soaked tissue paper and are carefully mounted onto the custom-made fixtures with care. A Lloyd machine attached to a 10N load cell is used to perform the uniaxial tensile test at a strain rate of 5 mm/min. The data acquisition rate is 50 data points per second and the force displacement data are obtained from the machine. A CCTV camera is used to record the tensile process at the samples with a video capture card at a rate of 25 fps. The images were analyzed for strain till rupture (
Dry collagen membranes are weighed and approximately 1.0-2.5 mg of dry collagen sample is used for differential scanning calorimetry analysis. In brief, the collagen sample is rehydrated in phosphate buffered saline at neutral pH for more than 24 hours at room temperature. Rehydrated samples are cut into small pieces and sealed in an aluminum pan. A thermoscan is performed using a Perkin Elmer DSC7 from 25░ C. to 140░ C. at a scan rate of 5░ C. min, against a reference pan. Thermograms of collagen samples are obtained as shown in
Dehydrated collagen membranes are weighed as W1 and rehydrated in 0.1M Tris-HCl buffer with 5 mM CaCl2 (pH7.4) for more than 24 hrs at room temperature. Collagenase (C-6885, Sigma, 425 U/mg) is prepared to 10 U/ml in the same buffer solution. Collagen membranes are soaked into the collagenase solution at 2 U/mg dry weight and incubated in darkness with regular shaking at 37░ C. for 2 hrs. At the end of incubation, an equal volume of 20 mM EDTA (final conc 10 mM) is supplied into the reaction mixture to stop collagenase activity. The supernatant is collected for total protein determination while the remaining membranes are dehydrated using a speed-vac overnight until a constant dry weight W2 is obtained. The weight loss of collagen membranes is calculated as follows and regarded as the resistance to collagenase digestion:
Weight loss (%)=(W 1 −W 2)ū100%
As shown in
Collagen membranes with a dry weight (W0) ranging from 2.5 mg to 4 mg are immersed in distilled water in darkness for 0.5, 1, 2, 4, 8, 24, 48, 72 and 96 hours. The wet weights of the membranes are recorded at each time point (Wt) after removing the surface water by blotting on kimwipe for several times. The swelling ratio or the water binding capacity of the collagen membranes is calculated as follows:
Swelling ratio=[(W t −W 0)/W 0]
The swelling ratio of the collagen membranes in different fluence dosage groups against time is plotted in
Swelling is one of the mechanisms for controlled drug release from polymer networks. By controlling the swelling ratio of collagen membranes using the photochemical crosslinking method of the present invention, the release of drugs immobilized in the collagen matrix can be controlled so that a sustained release of the drugs can be attained after implantation of the scaffolds. On the other hand, both the uncrosslinked and chemically crosslinked collagen scaffolds are not suitable for controlled release of drugs because the former release rapidly while the latter permanently bound drugs immobilized in the scaffolds.
The multi-lamellae collagen structures made in example 2 have been fully swollen in phosphate buffered saline at pH 7.4 for 2 weeks. Uncrosslinked structures swell extensively to form a soft gel-like structure with a thickness of around 2 mm. The structures were so weak that they can not be manipulated with forceps and sutures can not be put through. On the other hand, structures processed by the methods disclosed here swell moderately to a thickness of around 1 mm and were tough. The structures were then mounted on the sample stage of a MTS Bionix microforce testing machine fitted with a 100N load cell. After preloading with a force of around 0.1N, the strain was set to zero and dynamic compression cycles at a frequency of 0.1 Hz and a maximal strain of 0.5 were conducted. The load and unload-diaplacement curves were evaluated while the curve at the 20th cycle was used for data analysis. The compression moduli normalized by the dimension of the samples were obtained. The stress-strain curves of the uncrosslinked and crosslinked structures were shown in
Reconstituted collagen gel was photochemically crosslinked by varying the photosensitizing reagent and fluence dosage. Glutaraldyhyde was used as a positive control for chemical crosslinking. The treated structures were freeze-dried. Cross-sections of the collagen scaffolds were sputtered with gold for SEM analysis of the porous structures.
Multilayered collagen scaffolds prepared by method in the present invention as illustrated in Example 2 were sterilized by soaking in 70% ethanol for 3 days. Adult SD rats (250 g) were anesthetized and shaved at the back. Subcutaneous pockets were created and the scaffolds were implanted for up to 6 months. The collagen scaffolds were harvested for histological analysis. Collagen scaffolds were completely retrieved and remain intact and covered by a thin (˜40 μm) connective tissue capsule.
Rattail collagen gel (3 mg/ml) was reconstituted and photochemically crosslinked according to the present invention. Platelet adhesion test using human platelet rich plasma obtained from local blood bank was conducted by incubating the rehydrated membranes with the plasma for 1 hour before thorough rinsing. The samples were fixed in 0.25% glutaraldehyde before processed for SEM analysis. Ten fields were randomly selected from each sample for platelet counts and morphology analysis. Uncrosslinked collagen membranes have intrinsic thrombogenicity that more platelets adhered to the surface (57▒28 per unit area) (
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|Brevet citant
|Date de dķp¶t
|Date de publication
|13 juin 2013
|12 avr. 2016
|The University Of Hong Kong
|Materials and methods for filling biological cavities and preventing leakage of injected therapeutic agents
|16 nov. 2012
|22 mai 2014
|The Johns Hopkins University
|Platform for Creating an Artificial Blood Brain Barrier
|27 janv. 2010
|28 juil. 2011
|UROTEC GmbH, 01069
|Vernõhbares Gewebetransplantatkonstrukt zur Rekonstruktion eines menschlichen oder tierischen Organs
|25 janv. 2011
|4 ao¹t 2011
|UroTec GmbH
|Tissue graft structure that can be sutured for reconstructing a human or animal organ
|21 sept. 2011
|29 mars 2012
|Virginia Commonwealth University
|Preparation rich in growth factor-based fibrous matrices for tissue engineering, growth factor delivery, and wound healing
|21 sept. 2011
|14 juin 2012
|Virginia Commonwealth University
|Preparation rich in growth factor-based fibrous matrices for tissue engineering, growth factor delivery, and wound healing
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|20 mars 2008
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text:
NAHA, OKINAWA PREF. – About 22,000 residents around the U.S. Kadena Air Base in Okinawa filed a lawsuit Thursday to demand a nighttime flight ban and a combined ¥44.6 billion in compensation from the Japanese government, arguing their health has been affected by aircraft noise.
In the third suit, filed with the Naha District Court, over noise pollution at the Kadena base, the plaintiffs from around 7,500 households complained that the noise disturbs their sleep and has caused them hearing disorders, according to the lawyers representing them.
In the past two similar lawsuits, it was ruled that the noise levels were beyond the tolerable limit at Kadena. However, the plaintiffs argue that having taken no countermeasures, the state must pay compensation and ban the night-to-early morning flights.
Toshio Ikemiyagi, who leads the group of lawyers representing the plaintiffs, said the suit was part of a struggle to change Okinawa's current situation, in which it is forced to host the bulk of the U.S. military presence in Japan.
Shusei Arakawa, head of the plaintiffs' group, said the number of plaintiffs sharply increased as the noise levels around Kadena base have worsened and residents have had their tolerance pushed too far.
The first suit was filed in 1982 by some 900 plaintiffs, while the second, in 2000, had 5,500 plaintiffs. In both cases, the state was ordered to pay compensation, but the demand for a flight ban was rejected.
According to the town of Kadena, the base, which spans around 20 sq. km, typically has around 90 aircraft stationed there.
In February 2009, the Fukuoka High Court expanded the scope of noise levels subject to compensation to 75 decibels or more as measured in the weighted equivalent continuous perceived noise level — an international yardstick for gauging aircraft noise — from the 85 db in a lower court ruling. The standard was upheld by the Supreme Court in January this year.
The plaintiffs in the latest lawsuit are from five municipalities experiencing noise levels of 75 db or more.
The government also adopts the gauge for its environment assessment, setting the maximum at 70 db for residential areas and 75 db for commercial and industrial zones.
Okinawa Gov. Hirokazu Nakaima said he will keep a careful watch on the suit.


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just left the one in my home town, packed, could not use the drive through had ten or more cars, waited in line for ten minutes inside, could not get a table, the place was busy to say the least
I go to the one on 75th and Plainfield in Willowbrook as well.. always very busy
Similar experiences here. I ask to leave for lunch at 10:45 am to beat the line when I go there twice a week.


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