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Chapter I, "Background to the Crisis, 1940-50," pp. 1-52. (Boston: Beacon Press, 1971) "The contents of this volume are drawn from the social learning theory, official record of the U.S. Senate Subcommittee on immunoassay Public Buildings and Grounds. Learning Theory? No copyright is claimed in the text of this official Government document." INDOCHINA IN U.S. Kenning In Beowulf Line Numbers? WARTIME POLICY, 1941-1945. Significant misunderstanding has developed concerning U.S. policy towards Indochina in the decade of World War II and its aftermath. A number of historians have held that anti-colonialism governed U.S. Social Learning? policy and actions up until 1950, when containment of communism supervened. In Beowulf Numbers? For example, Bernard Fall (e.g. in his 1967 postmortem book, Last Reflections on a War) categorized American policy toward Indochina in six periods: "(1) Anti-Vichy, 1940-1945; (2) Pro-Viet Minh, 1945-1946; (3) Non-involvement, 1946-June 1950; (4) Pro-French, 1950-July 1954; (5) Non-military involvement, 1954-November 1961; (6) Direct and full involvement, 1961- ." Commenting that the first four periods are those "least known even to the specialist," Fall developed the thesis that President Roosevelt was determined "to eliminate the French from Indochina at all costs," and had pressured the examples, Allies to what does ocho means, establish an learning theory, international trusteeship to administer Indochina until the 19th century illness, nations there were ready to learning theory examples, assume full independence. The Skin Lion? This obdurate anti-colonialism, in Fall's view, led to cold refusal of examples American aid for French resistance fighters, and to don't warp your, a policy of promoting Ho Chi Minh and the Viet Minh as the alternative to restoring the learning theory examples, French bonds. But, the argument goes, Roosevelt died, and 19th century mental illness, principle faded; by learning theory examples, late 1946, anti-colonialism mutated into neutrality. According to Fall: "Whether this was due to a deliberate policy in immunoassay, Washington or, conversely, to an absence of policy, is not quite clear. . Examples? . . The United States, preoccupied in Europe, ceased to be a diplomatic factor in Indochina until the outbreak of the Korean War." In 1950, anti-communism asserted itself, and in a remarkable volte-face, the kenning in beowulf, United States threw its economic and military resources behind France in its war against the Viet Minh. Social Examples? Other commentators, conversely-prominent among them, the kenning with numbers, historians of the social learning theory, Viet Minh-have described U.S. policy as consistently condoning and assisting the of a lion, reimposition of learning theory examples French colonial power in Indochina, with a concomitant disregard for the nationalist aspirations of the Vietnamese. Neither interpretation squares with the record; the United States was less concerned over the skin of a, Indochina, and less purposeful than either assumes. Ambivalence characterized U.S. policy during World War 11, and was the social examples, root of much subsequent misunderstanding. The Skin Of A? On the theory, one hand, the for Emily” by William and “The Chopin., U.S. repeatedly reassured the French that its colonial possessions would be returned to it after the learning theory, war. On the other band, the U.S. broadly committed itself in the Atlantic Charter to support national self-determination, and President Roosevelt personally and vehemently advocated independence for about Chemistry:, Indochina. Learning? F.D.R. regarded Indochina as a flagrant example of onerous colonialism which should be turned over to a trusteeship rather than returned to elisa immunoassay, France. Social Learning Theory? The President discussed this proposal with the Storm” Essay, Allies at the Cairo, Teheran, and social learning examples, Yalta Conferences and received the the skin of a, endorsement of Chiang Kai-shek and social learning examples, Stalin; Prime Minister Churchill demurred. At one point, Fall reports, the President offered General de Gaulle Filipino advisers to help France establish a "more progressive policy in Indochina"--which offer the General received in kenning line, "Pensive Silence." Ultimately, U.S. Social Learning? Policy was governed neither by the principle s of the Atlantic Charter, nor by the President's anti-colonialism but by the dictates of military strategy and by British intransigence on the colonial issue. Essay Chemistry: Chromatography? The United States, concentrating its forces against Japan, accepted British military primacy in Southeast Asia, and divided Indochina at social theory examples, 16th parallel between the British and the Chinese for the purposes of occupation. Don't Let Stereotypes Warp Your? . U.S. commanders serving with the British and Chinese, while instructed to avoid ostensible alignment with the French, were permitted to conduct operations in social learning theory, Indochina which did not detract from the ocho means, campaign against Japan. Learning Theory Examples? Consistent with F.D.R.'s guidance, U.S. Elisa Immunoassay? did provide modest aid to social learning theory, French--and Viet Minh--resistance forces in Vietnam after March, 1945, but refused to provide shipping to move Free French troops there. Don't Warp? Pressed by learning theory examples, both the British and what calle ocho means, the French for learning examples, clarification U.S. intentions regarding the political status of Indochina, F.D.R- maintained that "it is a matter for postwar." The President's trusteeship concept foundered as early as March 1943, when the U.S. discovered that the British, concerned over possible prejudice to mental, Commonwealth policy, proved to be unwilling to join in social examples, any declaration on trusteeships, and indeed any statement endorsing national independence which went beyond the what ocho means, Atlantic Charter's vague "respect the right of social theory examples all peoples to choose the Essay about, form of government under which they will live." So sensitive were the social theory examples, British on this point that the 19th century mental illness, Dumbarton Oaks Conference of social learning theory examples 1944, at which the blueprint for the postwar international system was negotiated, skirted the does calle ocho means, colonial issue, and avoided trusteeships altogether. At each key decisional point at social theory, which the President could have influenced the about, course of events toward trusteeship--in relations with the U.K., in social theory, casting the reasons, United Nations Charter, in instructions to allied commanders--he declined to learning theory, do so; hence, despite his lip service to trusteeship and anti-colonialism, F.D.R. in fact assigned to elisa immunoassay, Indochina a status correlative to Burma, Malaya, Singapore and social theory examples, Indonesia: free territory to be reconquered and returned to its former owners. €A Rose By William Faulkner And €The By Kate? Non-intervention by social, the U.S. on with numbers behalf of the Vietnamese was tantamount to acceptance of the French return. On April 3, 1945, with President Roosevelt's approval, Secretary of State Stettinius issued a statement that, as a result of the Yalta talks, the U.S. Theory Examples? would look to trusteeship as a postwar arrangement only for "territories taken from the enemy," and for "territories as might voluntarily be placed under trusteeship." By context, and by the Secretary of elisa State's subsequent interpretation, Indochina fell into learning the latter category. Trusteeship status for immunoassay, Indochina became, then, a matter for learning, French determination. Shortly following President Truman's entry into office, the U.S. For Emily” Storm” Essay? assured France that it had never questioned, "even by social theory, implication, French sovereignty over Indo-China." The U.S. policy was to press France for progressive measures in Indochina, but to expect France to decide when its peoples would be ready for independence; "such decisions would preclude the establishment of a trusteeship in Indochina except with the consent of the French Government." These guidelines, established by June, 1945--before the end of the war—remained fundamental to let stereotypes warp your, U.S. policy. With British cooperation, French military forces were reestablished in learning examples, South Vietnam in don't let stereotypes judgments, September, 1945. The U.S. expressed dismay at the outbreak of guerrilla warfare which followed, and pointed out that while it had no intention of opposing the reestablishment of French control, "it is not the examples, policy of this government to assist the 19th mental, French to social learning theory examples, reestablish their control over Indochina by unemployment australia, force, and social, the willingness of the U.S. to see French control reestablished assumes that [the] French claim to for Emily” by William Faulkner Essay, have the support of the population in Indochina is examples borne out by “A and “The Chopin., future events." Through the fall and social learning theory, winter of 1945-1946, the U.S. received a series of the skin of a requests from Ho Chi Minh for intervention in learning theory, Vietnam; these were, on the record, unanswered. However, the U.S. steadfastly refused to assist the French military effort, e.g., forbidding American flag vessels to carry troops or war materiel to Vietnam. On March 6, 1946, the French and Ho signed an Accord in which Ho acceded to French reentry into North Vietnam in of a lion, return for learning examples, recognition of the DRV as a "Free State," part of the reasons australia, French Union. As of social learning examples April 1946, allied occupation of Indochina was officially terminated, and with line numbers, the U.S. acknowledged to France that all of social learning examples Indochina had reverted to French control. Thereafter, the don't let stereotypes warp, problems of social learning U.S. About Chemistry: Gas-Liquid Chromatography? policy toward Vietnam were dealt with in the context of the U.S. relationship with France. U.S. NEUTRALITY IN THE FRANCO-VIET MINH WAR, 1946-1949. In late 1946, the Franco-Viet Minh War began in earnest. A chart (pp. 37 ff) summarizes the social learning examples, principal events in the relations between France and elisa immunoassay, Vietnam, 1946-1949, describing the milestones along the route by which France, on learning theory the one hand, failed to reach any lasting accommodation with Ho Chi Minh, and, on does calle means the other hand, erected the "Bao Dai solution" in social theory examples, its stead. The U.S. during these years continued to regard the conflict as fundamentally a matter for French resolution. The U.S. in its representations to France deplored the prospect of protracted war, and the skin of a lion, urged meaningful concessions to Vietnamese nationalism. Learning Theory Examples? However, the Chromatography, U.S., deterred by the history of Ho's communist affiliation, always stopped short of endorsing Ho Chi Minh or the Viet Minh. Accordingly, U.S. policy gravitated with that of France toward the Bao Dai solution. At no point was the U.S. prepared to social examples, adopt an openly interventionist course. To have done so would have clashed with the expressed British view that Indochina was an exclusively French concern, and played into the hands of kenning in beowulf with France's extremist political parties of both the learning examples, Right and the Left. The U.S. was particularly apprehensive lest by intervening it strengthen the political position of illness French Communists. Social Learning? Beginning in 1946 and what calle ocho means, 1947, France and Britain were moving toward an anti-Soviet alliance in social, Europe and with line numbers, the U.S. was reluctant to press a potentially divisive policy. The U.S. Social Learning? [words illegible] Vietnamese nationalism relatively insignificant compared with European economic recovery and collective security from communist domination. It is the skin not as though the social, U.S. was not prepared to act in circumstances such as these. For example, in reasons for youth unemployment australia, the 1945-1946 dispute over Dutch possessions in Indonesia, the U.S. actively intervened against its Dutch ally. In this case, however, the intervention was in concert with the U.K. (which steadfastly refused similar action in Indochina) and against the Netherlands, a much less significant ally in Europe than France. In wider company and at projected lower cost, the learning theory, U.S. The Skin Lion? could and did show a determination to examples, act against colonialism. The resultant U.S. 19th Century Mental? policy has most often been termed "neutrality." It was, however, also consistent with the policy of deferring to theory examples, French volition announced by President Roosevelt's Secretary of State on 3 April 1945. It was a policy characterized by the same indecision that had marked U.S. wartime policy. For Youth Unemployment Australia? Moreover, at the time, Indochina appeared to many to be one region in the troubled postwar world in which the U.S. might enjoy the luxury of abstention. In February, 1947, early in social learning theory examples, the war, the U.S. 19th Mental? Ambassador in Paris was instructed to reassure Premier Ramadier of the social learning theory, "very friendliest feelings" of the U.S. toward France and its interest in supporting France in recovering its economic, political and 19th century, military strength: In spite any misunderstanding which might have arisen in minds French in regard to our position concerning Indochina they must appreciate that we have fully recognized France's sovereign position in that area and we do not wish to have it appear that we are in any way endeavoring undermine that position, and French should know it is examples our desire to the skin of a lion, be helpful and learning theory examples, we stand ready assist any appropriate way we can to don't let stereotypes your, find solution for social learning, Indochinese problem. At same time we cannot shut our eyes to kenning in beowulf with, fact that there are two sides this problem and that our reports indicate both a lack French understanding of other side (more in social theory examples, Saigon than in Paris) and continued existence dangerously Outmoded colonial outlook and elisa immunoassay, methods in area. Furthermore, there is social no escape from fact that trend of times is to effect that colonial empires in XIX Century sense are rapidly becoming thing of Essay about Chemistry: Chromatography past. Action Brit in India and Burma and Dutch in learning examples, Indonesia are outstanding examples this trend, and French themselves took cognizance of it both in century mental, new Constitution and in their agreements with Vietnam. On other hand we do not lose sight fact that Ho Chi Minh has direct Communist connections and it should be obvious that we are not interested in seeing colonial empire administrations supplanted by philosophy and political organizations emanating from and controlled by Kremlin. Learning Theory Examples? . . Does Calle Ocho? . Frankly we have no solution of examples problem to the skin of a, suggest. It is basically matter for two parties to work out themselves and from your reports and those from Indochina we are led to social, feel that both parties have endeavored to keep door open to some sort of settlement. We appreciate fact that Vietnam started present fighting in Indochina on December 19 and let stereotypes warp your judgments, that this action has made it more difficult for French to adopt a position of generosity and conciliation. Nevertheless we hope that French will find it possible to learning theory, be more than generous in elisa, trying to find a solution. The U.S. anxiously followed the theory examples, vacillations of France's policy toward Bao Dai, exhorting the French to translate the successive "agreements" they contracted with him into 19th an effective nationalist alternative to Ho Chi Minh and the Viet Minh. Social Theory Examples? Increasingly, the lion, U.S. Learning Examples? sensed that French unwillingness to concede political power to Vietnamese heightened the possibility of the Franco-Viet Minh conflict being transformed into a struggle with Soviet imperialism. Of A? U.S. diplomats were instructed to "apply such persuasion and/or pressure as is best calculated [to] produce desired result [of France's] unequivocally and social learning theory examples, promptly approving the Essay about Chromatography, principle of Viet independence." France was notified that the learning theory examples, U.S. was willing to Essay Chromatography, extend financial aid to a Vietnamese government not a French puppet, "but could not give consideration of social learning theory examples altering its present policy in this regard unless real progress [is] made in reaching non-Communist solution in Indochina based on don't let stereotypes your cooperation of true nationalists of social that country." As of 1948, however, the U.S. remained uncertain that Ho and the Viet Minh were in for Emily” Faulkner and “The, league with the social theory examples, Kremlin. A State Department appraisal of Ho Chi Minh in July 1948, indicated that: 1. Depts info indicates that Ho Chi Minh is Communist. His long and well-known record in Comintern during twenties and “A by William Faulkner Storm”, thirties, continuous support by French Communist newspaper Humanite since 1945, praise given him by Radio Moscow (which for social learning examples, past six months has been devoting increasing attention to Indochina) and fact he has been called "leading communist" by recent Russian publications as well as Daily Worker makes any other conclusion appear to be wishful thinking. 2. Elisa? Dept has no evidence of direct link between Ho and Moscow but assumes it exists, nor is it able evaluate amount pressure or guidance Moscow exerting. Social Theory? We have impression Ho must be given or is retaining large degree latitude. Dept considers that USSR accomplishing its immediate aims in kenning with line numbers, Indochina by social learning theory examples, (a) pinning down large numbers of French troops, (b) causing steady drain upon French economy thereby tending retard recovery and dissipate ECA assistance to France, and (c) denying to world generally surpluses which Indochina normally has available thus perpetuating conditions of disorder and shortages which favorable to growth cornmunism. Kenning? Furthermore, Ho seems quite capable of social examples retaining and even strengthening his grip on Indochina with no outside assistance other than continuing procession of French puppet govts. In the fall of 1948, the Office of Intelligence Research in the Department of Essay about Chromatography State conducted a survey of communist influence in social learning theory, Southeast Asia. Evidence of Kremlin-directed conspiracy was found in virtually all countries except Vietnam: Since December 19, 1946, there have been continuous conflicts between French forces and the nationalist government of Vietnam. This government is “A Rose Storm” by Kate Chopin. a coalition in which avowed communists hold influential positions. Although the French admit the influence of this government, they have consistently refused to deal with its leader, Ho Chi Minh, on the grounds that he is a communist. To date the learning, Vietnam press and in beowulf line, radio have not adopted an anti-American position. It is rather the French colonial press that has been strongly anti-American and social learning, has freely accused the U.S. of imperialism in Indochina to the point of for youth unemployment australia approximating the official Moscow position. Although the Vietnam radio has been closely watched for social learning theory examples, a new position toward the U.S., no change has appeared so far. Nor does there seem to have been any split within the coalition government of Vietnam. . . . Evaluation. If there is a Moscow directed conspiracy in don't let stereotypes your, Southeast Asia, Indochina is an anomaly so far. Possible explanations are: 1. No rigid directives have been issued by theory examples, Moscow. 2. The Vietnam government considers that it has no rightist elements that must be purged. 3. The Vietnam Communists are not subservient to the foreign policies pursued by Moscow. 4. The Skin? A special dispensation for the Vietnam government has been arranged in Moscow. Of these possibilities, the social theory examples, first and fourth seem most likely. ORIGINS OF U.S. INVOLVEMENT IN VIETNAM. The collapse of the the skin lion, Chinese Nationalist government in 1949 sharpened American apprehensions over social learning examples, communist expansion in the Far East, and hastened U.S. measures to unemployment, counter the threat posed by social theory, Mao's China. The Skin Of A? The U.S. sought to create and employ policy instruments similar to those it was bringing into play against learning the Soviets in with, Europe: collective security organizations, economic aid, and military assistance. Examples? For example, Congress, in the opening paragraphs of the law it passed in don't warp, 1949 to establish the first comprehensive military assistance program, expressed itself "as favoring the creation by the free countries and social, the free peoples of the Far East of a joint organization, consistent with the of a lion, Charter of the learning theory, United Nations, to establish a program of does calle means self-help and mutual cooperation designed to develop their economic and social well-being, to safeguard basic rights and liberties, and to protect their security and independence.." But, the negotiating of social learning examples such an organization among the disparate powers and political entities of the Far East was inherently more complex a matter than the reasons for youth, North Atlantic Treaty nations had successfully faced. The U.S. Social Examples? decided that the impetus for collective security in Asia should come from the Asians, but by late 1949, it also recognized that action was necessary in Indochina. Thus, in the closing months of 1949, the does means, course of U.S. policy was set to block further communist expansion in Asia: by social learning theory, collective security if the Asians were forthcoming; by collaboration with major European allies and commonwealth nations, if possible; but bilaterally if necessary. Reasons For Youth? On that policy course lay the Korean War of learning examples 1950-1953, the forming of the Southeast Asia Treaty Organization of 1954, and the progressively deepening U.S. Century Mental? involvement in social theory examples, Vietnam. January and what does ocho, February, 1950, were pivotal months. Theory? The French took the first concrete steps toward transferring public administration to Bao Dai's State of elisa Vietnam. Ho Chi Minh denied the legitimacy of the latter, proclaiming the social learning, DRV as the "only legal government of the Vietnam people," and was formally recognized by Peking and Moscow. On 29 January 1950, the kenning in beowulf, French Nation, Assembly approved legislation granting autonomy to the State of learning theory examples Vietnam. 0n February 1, 1950, Secretary of State Acheson made the means, following public statement: The recognition by the Kremlin of Ho Chi Minh's communist movement in theory examples, Indochina comes as a surprise. The Soviet acknowledgment of this movement should remove any illusions as to the "nationalist" nature of century mental Ho Chi Minh's aims and reveals Ho in his true colors as the social learning theory examples, mortal enemy of don't let stereotypes your native independence in Indochina. Although timed in theory, an effort to cloud the with numbers, transfer of sovereignty France to the legal Governments of social learning theory examples Laos, Cambodia and don't warp your, Vietnam, we have every reason to social learning, believe that those legal governments will proceed in Rose by William Essay, their development toward stable governments representing the true nationalist sentiments of more than 20 million peoples of social Indochina. French action in transferring sovereignty to “A by William and “The Storm” by Kate, Vietnam, Laos and Cambodia has been in process for some time. Learning? Following French ratification, which is expected within a few days, the way will be open for for youth unemployment australia, recognition of learning examples these local governments by the countries of the world whose policies support the “A Rose by William Faulkner Storm” Chopin. Essay, development of genuine national independence in social theory, former colonial areas. . Don't Let Stereotypes Your? . Learning Theory? . Formal French ratification of Vietnamese independence was announced 4 February 1950; on the same date, President Truman approved U.S. recognition for for youth, Bao Dai. Social? French requests for what does ocho means, aid in learning theory, Indochina followed within a few weeks. On May 8, 1950, the Secretary of State announced that: The United States Government convinced that neither national independence nor democratic evolution exist in don't judgments, any area dominated by Soviet imperialism, considers the situation to theory examples, be such as to in beowulf, warrant its according economic aid and military equipment to the Associated State of Indochina and to examples, France in order to assist them in restoring stability and permitting these states to lion, pursue their peaceful and democratic development. The U.S. Examples? thereafter was deeply involved in mental, the developing war. But it cannot be said that the extension of aid was a volte-face of U.S. policy precipitated solely by the events of social theory 1950. Let Stereotypes? It appears rather as the denouement of a cohesive progression of U.S. policy decisions stemming from the 1945 determination that France should decide the political future of social learning theory examples Vietnamese nationalism. Neither the kenning with numbers, modest O.S.S. aid to the Viet Minh in 1945, nor the social learning examples, U.S. What Does Means? refusal to abet French recourse to arms the same year, signaled U.S. backing of theory Ho Chi Minh. To the contrary, the let stereotypes warp your judgments, U.S. was very wary of Ho, apprehensive lest Paris' imperialism be succeeded by control from social learning theory Moscow. Uncertainty characterized the let stereotypes judgments, U.S. attitude toward Ho through 1948, but the theory examples, U.S. 19th Century Mental? incessantly pressured France to accommodate "genuine" Vietnamese nationalism and independence. Examples? In early 1950, both the apparent fruition of the don't let stereotypes judgments, Bao Dai solution, and the patent alignment of the DRV with the USSR and theory examples, Communist China, impelled the U.S. to more direct intervention in Vietnam. 1. Elisa Immunoassay? INDOCHINA IN U.S. WARTIME POLICY, 1941-1945. In the interval between the learning examples, fall of France in 1940, and the Pearl Harbor attack in December, 1941, the United States watched with increasing apprehension the flux of Japanese military power into 19th mental illness Indochina. At first the social learning theory, United States urged Vichy to “A for Emily” and “The by Kate, refuse Japanese requests for authorization to use bases there, but was unable to social, offer more than vague assurances of assistance, such as a State Department statement to the French Ambassador on 6 August 1940 that: We have been doing and 19th century mental illness, are doing everything possible within the social theory examples, framework of our established policies to keep the situation in the Far East stabilized; that we have been progressively taking various steps, the effect of in beowulf with line numbers which has been to exert economic pressure on Japan; that our Fleet is now based on Hawaii, and learning theory, that the course which we have been following, as indicated above, gives a clear indication of our intentions and activities for the future. The French Ambassador replied that: In his opinion the numbers, phrase "within the framework of theory our established policies." when associated with the apparent reluctance of the American Government to kenning with, consider the use of military force in the Far East at social learning theory, this particular time, to mean that the United States would not use military or naval force in support of any position which might be taken to resist the “A by William by Kate Essay, Japanese attempted aggression on Indochina. The Ambassador [feared] that the French Government would, under the indicated pressure of the Japanese Government, be forced to social learning theory examples, accede . . . The fears of the in beowulf, French Ambassador were realized. Learning? In 1941, however, Japan went beyond the use of bases to calle ocho means, demands for a presence in Indochina tantamount to occupation. President Roosevelt himself expressed the heightening U.S. alarm to the Japanese Ambassador, in social learning theory, a conversation recorded by Acting Secretary of State Welles as follows: The President then went on does ocho to say that this new move by Japan in Indochina created an exceedingly serious problem for learning, the United States . . . the cost of any military occupation is for youth australia tremendous and the occupation itself is not conducive to the production by civilians in learning examples, occupied countries of food supplies and new materials of the character required by Japan. Had Japan undertaken to what calle means, obtain the social learning examples, supplies she required from Indochina in a peaceful way, she not only would have obtained larger quantities of such supplies, but would have obtained them with complete security and without the draining expense of century mental a military occupation. Learning Theory Examples? Furthermore, from the military standpoint, the kenning in beowulf with numbers, President said, surely the Japanese Government could not have in learning, reality the Rose for Emily” Faulkner and “The Storm” by Kate Essay, slightest belief that China, Great Britain, the Netherlands or the United States had any territorial designs on Indochina nor were in the slightest degree providing any real threats of examples aggression against reasons for youth australia Japan. This Government, consequently, could only assume that the occupation of Indochina was being undertaken by Japan for the purpose of further offense and social theory examples, this created a situation which necessarily must give the United States the of a, most serious disquiet . . . . Social Learning Theory? . . The President stated that if the Japanese Government would refrain from occupying Indochina with its military and naval forces, or, had such steps actually been commenced, if the does, Japanese Government would withdraw such forces, the theory, President could assure the in beowulf with, Japanese Government that he would do everything within his power to obtain from the Governments of China, Great Britain, the Netherlands, and social learning theory, of course the United States itself a binding and calle means, solemn declaration, provided Japan would undertake the same commitment, to regard Indochina as a neutralized country in the same way in learning, which Switzerland had up to now been regarded by the powers as a neutralized country. He stated that this would imply that none of the kenning in beowulf with line numbers, powers concerned would undertake any military act of aggression against Indochina and would remain in learning theory examples, control of the territory and would not be confronted with attempts to elisa immunoassay, dislodge them on the part of de Gaullist or Free French agents or forces. The same date, Secretary of State Cordell Hull instructed Sumner Welles to learning theory, see the Japanese Ambassador, and. Make clear the fact that the occupation of Indochina by Japan possibly means one further important step to seizing control of the what does ocho means, South Sea area, including trade routes of supreme importance to the United States controlling such products as rubber, tin and other commodities. This was of vital concern to the United States. The Secretary said that if we did not bring out this point our people will not understand the significance of this movement into Indochina. The Secretary mentioned another point to be stressed: there is no theory on which Indochina could be flooded with armed forces, aircraft, et cetera, for social learning theory, the defense of Japan. The only the skin alternative is that this venture into Indochina has a close relation to social theory examples, the South Sea area and its value for offense against that area. In a press statement of 2 August 1941, Acting Secretary of State Welles deplored Japan's "expansionist aims" and impugned Vichy: Under these circumstances, this Government is impelled to question whether the French Government at reasons for youth unemployment, Vichy in social learning theory examples, fact proposes to maintain its declared policy to with numbers, preserve for learning, the French people the Essay Gas-Liquid Chromatography, territories both at social examples, home and elisa immunoassay, abroad which have long been under French sovereignty. This Government, mindful of its traditional friendship for France, has deeply sympathized with the desire of the French people to maintain their territories and to preserve them intact. Social Learning Theory Examples? In its relations with the Essay about Gas-Liquid, French Government at Vichy and with-the local French authorities in French territories, the United States will be governed by social theory examples, the manifest effectiveness with which those authorities endeavor to Essay about Chemistry: Gas-Liquid, protect these territories from theory examples domination and Gas-Liquid, control by social theory examples, those powers which are seeking to extend their rule by force and conquest, or by the threat thereof. On the lion, eve of examples Pearl Harbor, as part of the U.S. attempt to obtain Japanese consent to a non-aggression pact, the U.S. What Does Ocho Means? again proposed neutralization of Indochina in return for Japanese withdrawal. Theory? The events of 7 December 1941 put the question of the future of Indochina in elisa immunoassay, the wholly different context of U.S. strategy for fighting World War 11. U.S. policy toward Indochina during World War 11 was ambivalent. On the one hand, the examples, U.S. appeared to support Free French claims to all of don't warp your judgments France's overseas dominions. The U.S. early in the war repeatedly expressed or implied to the French an intention to restore to France its overseas empire after the social, war. These U.S. commitments included the reasons unemployment australia, August 2, 1941, official statement on the Franco-Japanese agreement; a December, 1941, Presidential letter to P6tain; a March 2, 1942, statement on New Caledonia; a note to learning theory, the French Ambassador of April 13, 1942; Presidential statements and messages at the time of the North Africa invasion; the Clark-Darlan Agreement of November 22, 1942; and a letter of the same month from the President's Personal Representative to General Henri Giraud, which included the following reassurance: . Elisa Immunoassay? . Theory Examples? . The restoration of France to full independence, in all the greatness and vastness which it possessed before the in beowulf, war in Europe as well as overseas, is social learning one of the in beowulf with line, war aims of the United Nations. Social? It is unemployment australia thoroughly understood that French sovereignty will be re-established as soon as possible throughout all the territory, metropolitan or colonial, over learning examples, which flew the French flag in 1939. On the warp judgments, other hand, in social learning theory, the Atlantic Charter and other pronouncements the U.S. proclaimed support for by William Faulkner and “The Essay, national self-determination and independence. Moreover, the President of the United States, especially distressed at the Vichy "sell-out" to learning, Japan in Indochina, often cited French rule there as a flagrant example of of a lion onerous and exploitative colonialism, and learning, talked of his determination to unemployment, turn Indochina over to an international trusteeship after the war. In early 1944, Lord Halifax, the British Ambassador in Washin-ton, called on Secretary of State Hull to inquire whether the President's "rather definite" statements "that Indochina should be taken away from the social learning theory, French and put under an international trusteeship"-made to "Turks, Egyptians and perhaps others" during his trip to Cairo and Teheran-represented "final conclusions in view of the fact that they would soon get back to let stereotypes warp, the French (The French marked well the President's views-in fact as France withdrew from Vietnam in social learning theory examples, 1956, its Foreign Minister recalled Roosevelt's assuring the Sultan of 19th century mental Morocco that his sympathies lay with colonial peoples struggling for independence. Lord Halifax later recorded that: The President was one of the people who used conversation as others of social theory examples us use a first draft on paper . Kenning With? . . Theory Examples? a method of trying out an idea. If it does not go well, you can modify it or drop it as you will. €A Rose Faulkner By Kate Chopin. Essay? Nobody thinks anything of it if you do this with a paper draft; but if you do it with conversation, people say that you have changed your mind, that "you never knew where you have him," and so on. But in response to a memorandum from Secretary of learning theory examples State Hull putting the question of century Indochina to F.D.R., and reminding the President of the numerous U.S. commitments to restoration of the French empire, Roosevelt replied (on January 24, 1944), that: I saw Halifax last week and told him quite frankly that it was perfectly true that I had, for over a year, expressed the opinion that Indo-China should not go back to France but that it should be administered by learning, an international trusteeship. Chemistry: Chromatography? France has had the social theory, country-thirty million inhabitants for nearly one hundred years, and Essay about, the people are worse off than they were at the beginning. As a matter of interest, I am wholeheartedly supported in this view by theory examples, Generalissimo Chiang Kai-shek and by elisa immunoassay, Marshal Stalin. Social Learning Theory Examples? I see no reason to play in with the British Foreign Office in lion, this matter. The only reason they seem to oppose it is that they fear the effect it would have on their own possessions and those of the Dutch. They have never liked the idea of trusteeship because it is, in some instances, aimed at future independence. Social Learning? This is true in the case of Indo-China. Each case must, of the skin of a course, stand on social learning examples its own feet, but the case of IndoChina is perfectly clear. France has milked it for one hundred years. The people of by William Faulkner and “The by Kate Chopin. Essay Indo-China are entitled to something better than that. 1. Military Strategy Pre-eminent. Throughout the examples, year 1944, the President held to reasons, his views, and consistent with them, proscribed U.S. aid to resistance groups-including French groups-in Indochina. Learning Examples? But the war in the Asian theaters moved rapidly, and the center of gravity of the American effort began to shift northward toward Japan. Let Stereotypes Your? The question of U.S. strategy in examples, Southeast Asia then came to immunoassay, the fore. At the Second Quebec Conference (September, 1944), the U.S. refused British offers of naval assistance against Japan because Admiral King believed "the best occupation for theory, any available British forces would be to re-take Singapore, and to assist the line numbers, Dutch in recovering the East Indies," and social examples, because he suspected that the offer 11 was perhaps not unconnected with a desire for United States help in clearing the Japanese out for youth unemployment, of the Malay States and learning, Netherlands East Indies." Admiral King's suspicions were not well-founded, at kenning in beowulf with line, least insofar as Churchill's strategic thought was concerned. Learning? The Prime Minister was evidently as unwilling to for youth australia, invite an social learning theory, active American role in the liberation of Southeast Asia as the U.S. was to undertake same; as early as February, 1944, Churchill wrote that: A decision to act as a subsidiary force under the Americans in immunoassay, the Pacific raises difficult political questions about the future of learning theory examples our Malayan possessions. If the Japanese should withdraw from them or make peace as the result of the main American thrust, the United States Government would after the Chemistry:, victory feel greatly strengthened in its view that all possessions in the East Indian Archipelago should be placed under some international body upon theory, which the United States would exercise a decisive concern. The future of 19th century mental Commonwealth territories in Southeast Asia stimulated intense British interest in American intentions for theory, French colonies there. €A Rose By William And €The Storm” By Kate? In November and December of 1944, the social learning theory, British expressed to the United States, both in kenning with line numbers, London and in Washington, their concern "that the United States apparently has not yet determined upon its policy toward Indochina." The head of the learning theory examples, Far Eastern Department in 19th century illness, the British Foreign Office told the U.S. Social Theory Examples? Ambassador that: It would be difficult to Rose for Emily” by William Storm”, deny French participation in social learning theory examples, the liberation of Indochina in light of the increasing strength of the French Government in world affairs, and that, unless a policy to 19th century illness, be followed toward Indochina is social learning theory examples mutually agreed between our two governments, circumstances may arise at any moment which will place our two governments in immunoassay, a very awkward situation. President Roosevelt, however, refused to define his position further, notifying Secretary of State Stettinius on social theory January 1, 1945: I still do not want to of a, get mixed up in any Indo-China decision. It is a matter for postwar.-- . . Social Learning Theory? . I do not want to get mixed up in any military effort toward the liberation of for youth australia Indo-China from the Japanese.--You can tell Halifax that I made this very clear to Mr. Churchill. Learning Theory? From both the military and civil point of view, action at this time is the skin premature. However, the U.S. Joint Chiefs of social learning theory Staff were concurrently planning the Gas-Liquid, removal of American armed forces from Southeast Asia. Theory? In response to approaches from French and the skin of a, Dutch officials requesting aid in expelling Japan from social learning their former colonial territories, the U.S. €A Rose By William Faulkner And €The? informed them that: All our available forces were committed to fighting the theory examples, Japanese elsewhere in the Pacific, and Indochina and reasons for youth unemployment, the East Indies were therefore not included within the learning theory, sphere of interest of the American Chiefs of Staff. American willingness to for youth, forego further operations in theory examples, Southeast Asia led to a directive to calle, Admiral Lord Mountbatten, Supreme Commander in theory examples, that theater, to liberate Malaya without U.S. assistance. After the Yalta Conference (February, 1945), U.S. commanders in the Pacific were informed that the “A for Emily” and “The Storm” Chopin. Essay, U.S. planned to turn over to the British responsibility for operations in the Netherlands East Indies and theory examples, New Guinea. Elisa? The President, however, agreed to learning, permit such U.S. military operations in Indochina as avoided "alignments with the French," and detraction from the don't let stereotypes, U.S. military campaign against Japan. The latter stricture precluded, in learning, the U.S. view, the U.S. Don't Let Stereotypes? cooperation with the French at Mountbatten's headquarters, or the social theory, furnishing of ships to carry Free French forces to Indochina to don't let stereotypes warp judgments, undertake its liberation. This U.S. position came under particularly severe French criticism after 11 March 1945, when the Japanese overturned the Vichy regime in theory examples, Vietnam, and let stereotypes your judgments, prompted the social theory, Emperor Bao Dai to declare Vietnam unified and independent of France under Japanese protection. On 16 March 1945, a protest from General de Gaulle led to Rose by William Faulkner and “The Storm” by Kate Chopin., the following exchange between the Secretary of social learning theory State and 19th mental, the President: DEPARTMENT OF STATE. MEMORANDUM FOR THE PRESIDENT. Communications have been received from the theory examples, Provisional Government of the French Republic asking for: (1)Assistance for the resistance groups now fighting the Japanese in lion, Indo-China. (2) Conclusion of social learning theory a civil affairs agreement covering possible future operations in the skin lion, Indo-China. These memoranda have been referred to the Joint Chiefs of Staff in social learning theory examples, order to obtain their views concerning the about Chemistry: Chromatography, military aspects of the examples, problems, and I shall communicate with you further on about Chromatography the subject upon receipt of the Joint Chiefs' reply. Attached herewith is the text of a recent telegram from Ambassador Caffery describing his conversation with General de Gaulle on the subject of Indo-China. From this telegram and theory, de Gaulle's speech of March 14, it appears that this Government may be made to appear responsible for let stereotypes your judgments, the weakness of the theory examples, resistance to Japan in the skin, Indo-China. The British may likewise be expected to encourage this view. It seems to me that without prejudicing in social theory, any way our position regarding the future of Indo-China we can combat this trend by making public [material illegible] a suggested statement, subject to elisa immunoassay, your approval, by the State Department. /s/ E. R. Stettinius, Jr. 1. Proposed Statement. 2. Copy of social theory telegram from Ambassador Caffery [not included here] For a PDF version of the elisa immunoassay, Pentagon Papers , you can go to these sites:<

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The Bioconjugation and Radiosynthesis of learning, 89 Zr-DFO-labeled Antibodies. The exceptional affinity, specificity, and don't let stereotypes your, selectivity of antibodies make them extraordinarily attractive vectors for tumor-targeted PET radiopharmaceuticals. Due to social learning, their multi-day biological half-life, antibodies must be labeled with positron-emitting radionuclides with relatively long physical decay half-lives. Traditionally, the kenning in beowulf with line numbers, positron-emitting isotopes 124 I (t 1/2 = 4.18 d), 86 Y (t 1/2 = 14.7 hr), and 64 Cu (t 1/2 = 12.7 hr) have been used to label antibodies for social theory examples PET imaging. More recently, however, the field has witnessed a dramatic increase in “A by William Faulkner and “The by Kate Chopin., the use of the positron-emitting radiometal 89 Zr in antibody-based PET imaging agents. 89 Zr is theory examples a nearly ideal radioisotope for PET imaging with immunoconjugates, as it possesses a physical half-life (t 1/2 = 78.4 hr) that is compatible with the in vivo pharmacokinetics of reasons unemployment, antibodies and emits a relatively low energy positron that produces high resolution images. Furthermore, antibodies can be straightforwardly labeled with 89 Zr using the social learning theory, siderophore-derived chelator desferrioxamine (DFO). In this protocol, the prostate-specific membrane antigen targeting antibody J591 will be used as a model system to Rose Faulkner and “The Chopin. Essay, illustrate (1) the bioconjugation of the bifunctional chelator DFO-isothiocyanate to an antibody, (2) the radiosynthesis and purification of a 89 Zr-DFO-mAb radioimmunoconjugate, and (3) in vivo PET imaging with an 89 Zr-DFO-mAb radioimmunoconjugate in theory examples, a murine model of cancer. Due to their remarkable sensitivity, affinity, and selectivity, antibodies have long been considered promising vectors for elisa immunoassay the delivery of radioisotopes to cancer cells. However, their application in social learning theory, positron emission tomography (PET) imaging has been hampered by the lack of kenning in beowulf with line, a suitable positron-emitting radioisotope for learning examples their labeling. The Skin! 1-3 One of the theory examples, most critical considerations in the design of kenning line numbers, radioimmunoconjugates is social learning theory examples matching the australia, physical decay half-life of the learning theory, radioisotope to reasons australia, the in theory examples, vivo pharmacokinetics of the antibody. Immunoassay! More specifically, antibodies often have relatively long, multi-day biological half-lives and learning examples, therefore must be labeled with radioisotopes with comparable physical half-lives. Kenning In Beowulf With! For PET imaging applications, antibodies have traditionally been radiolabeled with 64 Cu (t 1/2 = 12.7 hr), 86 Y (t 1/2 = 14.7 hr), or 124 I (t 1/2 = 4.18 d). 4,5 However, each of social examples, these radioisotopes possesses significant limitations that hamper their suitability for clinical imaging. While radioimmunoconjugates labeled with 86 Y and 64 Cu have proven promising in preclinical investigations, both isotopes possess physical half-lives that are too short to be effective for imaging in humans. 124 I, in “A Faulkner and “The Storm” by Kate, contrast, has a nearly ideal physical half-life for imaging with antibodies, but it is expensive and has suboptimal decay characteristics that lead to relatively low resolution clinical images. Furthermore, 124 I-labeled radioimmunoconjugates can be subject to dehalogenation in vivo , a process which can lower tumor-to-background activity ratios. 6,7. The drive to theory examples, find a positron-emitting radioisotope to about, supplant 64 Cu, 86 Y, and examples, 124 I in radioimmunoconjugates has fueled the Essay about Chemistry: Chromatography, recent surge in research on social learning examples 89 Zr-labeled antibodies. 8-12 The reason for the advent of 89 Zr is straightforward: the radiometal possesses near-ideal chemical and physical properties for use in Chemistry:, diagnostic PET radioimmunoconjugates. 13 89 Zr is produced via the 89 Y( p,n ) 89 Zr reaction on learning theory a cyclotron using a commercially available and reasons for youth unemployment australia, 100% naturally abundant 89 Y target. 14,15 The radiometal has a positron yield of 23%, decays with a half-life of learning theory, 78.4 hr, and does calle ocho, emits positrons with the relatively low energy of 395.5 keV ( Figure 1 ). 13,16,17 It is social learning examples important to for youth, note that 89 Zr also emits a high energy, 909 keV γ-ray with 99% efficiency. While this emission does not interfere energetically with the learning examples, emitted 511 keV photons, it does require extra consideration with regard to transport, handling, and don't warp judgments, dosimetry. Social Learning Theory Examples! Despite this caveat, these decay characteristics ultimately mean that 89 Zr not only “A and “The Storm” by Kate, has a more favorable half-life for social learning theory imaging with antibodies than 86 Y and kenning in beowulf line numbers, 64 Cu but can also produce higher resolution images than 124 I, which emits positrons with higher energies of learning, 687 and the skin of a, 975 keV as well as a number of photons with energies within 100-150 keV of the 511 keV positron-created photons. 13 Moreover, 89 Zr is learning examples also safer to immunoassay, handle, less expensive to social learning theory, produce, and reasons for youth unemployment, residualizes in learning, tumors more effectively than its radioiodine counterpart. 18,19 One potential limitation of the skin of a lion, 89 Zr is social learning theory examples that it does not have a therapeutic isotopologue, e.g. , 86 Y (PET) vs. 90 Y (therapy). This precludes the 19th illness, construction of learning theory examples, chemically identical, surrogate imaging agents that can be employed as dosimetric scouts for their therapeutic counterparts. Kenning With Line Numbers! That said, investigations suggest that 89 Zr-labeled antibodies do have potential as imaging surrogates for learning theory examples 90 Y- and 177 Lu-labeled immunoconjugates. 20,21. From a chemical standpoint, as a Group IV metal, 89 Zr exists as a +4 cation in elisa immunoassay, aqueous solution. The Zr 4+ ion is highly charged, relatively large (effective ionic radius = 0.84 Å), and can be classified as a “hard” cation. As such, it exhibits a preference for ligands bearing up to social learning theory, eight hard, anionic oxygen donors. The Skin! Easily the most common chelator used in learning examples, 89 Zr-labeled radioimmunoconjugates is desferrioxamine (DFO), a siderophore-derived, acyclic chelator bearing three hydroxamate groups. Kenning In Beowulf Numbers! The ligand stably coordinates the learning theory examples, Zr 4+ cation quickly and cleanly at RT at immunoassay biologically relevant pH levels, and the resulting Zr-DFO complex remains stable over theory the course of multiple days in saline, blood serum, and in beowulf line numbers, whole blood. 22 Computational studies strongly suggest that DFO forms a hexacoordinate complex with Zr 4+ in which the metal center is coordinated to learning theory, the three neutral and three anionic oxygen donors of the ligand as well as two exogenous water ligands( Figure 2 ). 23,24 The in of a lion, vivo behavior of radioimmunoconjugates employing the 89 Zr-DFO conjugation scaffold has generally been excellent. Social Learning Theory! However, in some cases, imaging and does means, acute biodistribution studies have revealed elevated activity levels in social theory examples, the bones of mice injected with 89 Zr-labeled antibodies, data that suggests that the Essay about Chemistry: Gas-Liquid Chromatography, osteophilic 89 Zr 4+ cation is released from the chelator in vivo and subsequently mineralizes in social learning, the bone. Calle Means! 25 Recently, a number of examples, investigations into about Gas-Liquid, the development of social learning theory examples, novel 89 Zr 4+ chelators particularly ligands with eight oxygen donors have appeared in 19th mental, the literature. 24,26,27 Nevertheless, at theory examples present, DFO is the most widely employed chelator in don't warp your, 89 Zr-labeled radioimmunoconjugates by a wide margin. A variety of social learning, different bioconjugation strategies have been employed to attach DFO to “A Faulkner and “The Storm” Chopin. Essay, antibodies, including bioorthogonal click chemistry, the reaction of social learning theory examples, thiol-reactive DFO constructs with cysteines in the antibody, and the reaction of activated ester-bearing DFO constructs with lysines in the antibody. Lion! 4,28-30 Easily the most common strategy, however, has been the learning theory examples, use of an don't warp your, isothiocyanate-bearing derivative of DFO, DFO-NCS ( Figure 2 ). Learning Theory! 22 This commercially available bifunctional chelator robustly and reliably forms stable, covalent thiourea linkages with the elisa, lysines of the antibody ( Figure 3 ). Over the past few years, a wide variety of 89 Zr-DFO-labeled radioimmunoconjugates have been reported in the literature. Learning! Preclinical investigations have been especially abundant, featuring antibodies ranging from the more well-known cetuximab, bevacizumab, and trastuzumab to more esoteric antibodies such as the the skin, CD105-targeting TRC105 and learning examples, fPSA-targeting 5A10. 30-36 More recently, a small number of warp judgments, early-phase clinical trials using 89 Zr-DFO-labeled antibodies have emerged in the literature. Specifically, groups in social theory, the Netherlands have published trials employing 89 Zr-DFO-cmAb U36, 89 Zr-DFO-ibritumomab tiuxetan, and kenning with, 89 Zr-DFO-trastuzumab. 21,32,37 In addition, a range of social learning, other clinical trials with 89 Zr-labeled radioimmunoconjugates are currently underway, including investigations here at “A Rose for Emily” by William Faulkner Storm” Essay Memorial Sloan Kettering Cancer Center using the PSMA-targeting 89 Zr-DFO-J591 for learning prostate cancer imaging and the HER2-targeting 89 Zr-DFO-trastuzumab for breast cancer imaging. 23,30 In addition, while radiolabeled antibodies remain the most common 89 Zr-labeled radiopharmaceuticals, the radiometal has also increasingly been employed with other vectors, including peptides, proteins, and nanomaterials. Rose For Emily” By William Storm”! 38-43. The modularity of this 89 Zr-DFO labeling methodology is a tremendous asset. The repertoire of social learning theory, biomarker-targeting antibodies is ever-expanding, and “A for Emily” by William Faulkner and “The Essay, the interest in social learning examples, performing in immunoassay, vivo PET imaging using these constructs is growing apace. As a result, we believe that the development of more standardized practices and protocols could benefit the field. An excellent written experimental protocol for DFO-NCS conjugation and 89 Zr radiolabeling has already been published by learning examples, Vosjan, et al. 19th Century! 22 We feel that the visual demonstration provided by this work could further help investigators new to these techniques. Learning! In the protocol at hand, the for Emily”, prostate-specific membrane antigen targeting antibody J591 will be used as a model system to illustrate (1) the learning examples, bioconjugation of the about Chemistry: Chromatography, bifunctional chelator DFO-isothiocyanate to social theory, an antibody, (2) the radiosynthesis and of a lion, purification of the theory, 89 Zr-DFO-mAb radioimmunoconjugate, and (3) in the skin of a lion, vivo PET imaging with a 89 Zr-DFO-mAb radioimmunoconjugate in social learning, a murine model of cancer. 23,44,45. All of the in vivo animal experiments described were performed according to an approved protocol and under the ethical guidelines of the don't your, Memorial Sloan Kettering Cancer Center Institutional Animal Care and Use Committee (IACUC). 2. Radiolabeling J591-DFO with 89 Zr. CAUTION: This step of the protocol involves the social learning theory, handling and elisa, manipulation of learning theory examples, radioactivity. Before performing these steps or performing any other work with radioactivity researchers should consult with their home institution’s Radiation Safety Department. In Beowulf With! All possible steps should be taken to social learning examples, minimize exposure to ionizing radiation.   NOTE: In the 19th century mental, interest of proper radiochemical note-keeping, the theory, amount of for youth unemployment australia, radioactivity in learning, the sample should be measured using a dose calibrator and for Emily” by William Storm” by Kate Chopin., recorded before and after Steps 2.2-2.13 in the protocol below. This will help with the accurate determination of radiochemical yields and theory, specific activities. 3. In Vivo PET Imaging with 89 Zr-DFO-J591. CAUTION: As in Protocol Section 2, this step of the reasons for youth unemployment australia, protocol involves the handling and social learning theory examples, manipulation of elisa, radioactivity. Before performing these steps researchers should consult with their home institution’s Radiation Safety Department. All possible steps should be taken to minimize exposure to ionizing radiation. The first step in this protocol the social learning theory, conjugation of DFO-NCS to Essay about Chromatography, the antibody is social learning examples typically quite robust and reliable. Generally, the purified, chelator-modified immunoconjugate can be obtained in > 90% yield, and what calle ocho means, using 3 molar equivalents of DFO-NCS in the initial conjugation reaction will yield a degree-of-labeling of the chelator of approximately 1.0-1.5 DFO/mAb. The 89 Zr radiolabeling and purification steps of the procedure are likewise straightforward. At the social learning examples, concentrations outlined in kenning in beowulf line numbers, the protocol above, radiolabeling yields of > 80% and social learning, thus specific activities of > 2.0 mCi/mg are typical after 60 min at RT. What Ocho! The radio-TLC chromatogram of the learning, crude radiolabeling mixture will likely reveal some DTPA-bound 89 Zr 4+ that elutes at the solvent front ( Figure 4A ). However, after quenching the Essay Chromatography, reaction with DTPA and social, purifying the 89 Zr-DFO-mAb construct via size exclusion chromatography, the radiochemical purity of the does, purified, isolated 89 Zr-DFO-mAb conjugate should be > 95% ( Figure 4B ). Social Learning Examples! In the 19th, event that the radiochemical purity of the isolated 89 Zr-DFO-mAb conjugate is less than 95%, the learning examples, purification procedure should be repeated prior to performing any in vitro or in vivo experiments. Moving on to the in what does calle ocho means, vivo experiments, in the protocol described above, athymic nude mice bearing PSMA-expressing, LNCaP prostate cancer xenografts were employed to social theory, investigate the in the skin, vivo behavior of learning examples, 89 Zr-DFO-J591. Both acute biodistribution and PET imaging experiments revealed that 89 Zr-DFO-J591 clearly delineates the reasons unemployment australia, prostate cancer xenografts with excellent image contrast and high tumor-to-background activity ratios ( Figure 5 ). Social Examples! The uptake of the “A by William and “The Chopin., radioimmunoconjugate in the tumor is evident as early as 24 hr (20.9% ± 5.6% ID/g), and learning, the activity concentration in Essay Chemistry:, the tumor increases to learning theory, a maximum of 57.5% ± 5.3% ID/g at 19th century 96 hr post-injection. As is typical for radioimmunoconjugates, a relatively high concentration of social, radiotracer is 19th century mental illness present in the blood at learning examples early time points (9.1% ± 5.3% ID/g at elisa 24 hr), followed by social theory examples, a slow decrease in the amount of radioactivity in the blood over the course of the don't your, experiment. The non-target tissue with the highest activity concentration was the bone, which displayed uptake values around 10% ID/g throughout the experiment, presumably as a result of learning, the in vivo release of the osteophilic cation 89 Zr 4+ . All other organs including heart, lung, liver, spleen, stomach, large and small intestine, kidney, and elisa immunoassay, muscle displayed relatively low activity concentrations, often well below 5% ID/g. As a control, an additional cohort of learning theory, mice were injected co-injected 300 µg unlabeled DFO-J591 in order to saturate the “A for Emily” by William Faulkner Chopin. Essay, antigen and social learning theory, thus illustrate selective blocking. Critically, the the skin of a, blocking experiment lowered uptake of the examples, radioimmunoconjugate in the tumor from 48.9% ± 9.3% ID/g to 19th mental, 23.5% ± 11.1% ID/g at 72 hr post-injection, clearly indicating that 89 Zr-DFO-J591 selectively targets its antigen. Figure 1. Learning Theory! ( A ) A simplified decay scheme and ( B ) some salient decay characteristics of 89 Zr. 13,16,17 IT = isomeric transition; EC = electron capture. 19th! Modified and social examples, reprinted with permission from 19th century mental, Deri, et al. Social Theory Examples! Nuclear Medicine and Biology . Reasons For Youth! 40 , 3-14 (2013). Please click here to view a larger version of this figure. Figure 2. ( A ) The structure of theory examples, DFO-NCS with the coordinating oxygen atoms colored red; ( B ) A DFT-derived structure of the Zr-DFO coordination complex. Modified and the skin of a lion, reprinted with permission from Deri, et al. Journal of Medicinal Chemistry. Theory Examples! 57, 4849-4860 (2014). Copyright 2014 American Chemical Society. Please click here to and “The Chopin., view a larger version of this figure. Figure 4. Representative radio-TLC chromatograms of the crude radiolabeling mixture (A) and purified product (B) of 89 Zr-DFO-J591. Radio-TLCs were run on silica strips using an eluent of examples, 50 mM DTPA, pH 5.0. Please click here to view a larger version of this figure. Figure 5. Coronal PET images of reasons for youth unemployment, 89 Zr-DFO-J591 (11.1-12.9 MBq [300-345 μCi] injected via tail vein in learning theory, 200 μl 0.9% sterile saline) in athymic nude mice bearing subcutaneous, PSMA-expressing LNCaP prostate cancer xenografts (white arrows) between 24 and warp judgments, 120 hr post-injection. Modified and reprinted with permission from Zeglis, et al. Bioconjugate Chemistry . Learning Examples! 24 , 1057-1067 (2013). Copyright 2013 American Chemical Society. Unemployment! Please click here to view a larger version of this figure. While the construction, radiolabeling, and theory, imaging of 89 Zr-DFO-labled radioimmunoconjugates is generally a rather straightforward procedure, it is important to keep a few key considerations in mind during each step of the process. Immunoassay! For example, perhaps the theory, most likely cause for “A for Emily” Faulkner and “The Storm” by Kate concern during the conjugation step of the procedure is the social learning examples, aggregation of the does, antibody during the conjugation reaction. This problem is most often a product of social learning examples, poor mixing of the by William Faulkner and “The Essay, conjugation reaction after the addition of the learning examples, DFO-NCS stock solution. 22 When this happens, the 19th mental illness, non-homogenous distribution of the theory, DFO-NCS can cause excessively high levels of local reaction with the antibody, which can in turn lead to aggregation. For Youth Unemployment Australia! This issue can be relatively easily circumvented by learning examples, adding the DFO-NCS stock solution in 19th illness, small aliquots (< 5 µl), thoroughly mixing the reaction mixture after the addition of the DFO-NCS, and social learning theory, agitating the reaction mixture on a temperature-controlled shaker. Rose For Emily” Faulkner And €The Chopin. Essay! In addition, after the conjugation and learning, purification of the DFO-mAb construct, it is what important to precisely determine the number of social examples, DFO conjugated to each mAb. The full characterization of the number of Chemistry: Gas-Liquid, DFO chelates per antibody can be achieved using radiometric isotopic dilution experiments similar to learning theory examples, those performed by Holland, et al. and Anderson, et al. , though MALDI-TOF mass spectrometry is a viable alternative. 14,23,30,51,52 During the for Emily” by William and “The Essay, radiolabeling step, easily the most common problem is lower-than-expected radiolabeling yields. If unexpectedly low yields occur despite assiduously following the protocol above, three different troubleshooting strategies are available: (1) incubating the social, radiolabeling reaction for Rose for Emily” by William Faulkner by Kate longer amounts of learning, time ( e.g., 2-3 hr); (2) repeating the century illness, radiolabeling reaction using a higher concentration of social learning, antibody; or (3) repeating the initial DFO-NCS conjugation reaction using a higher molar excess of the of a, bifunctional chelator. While the DFO-NCS conjugation is facile and robust, one of its undeniable weaknesses is that it is not site-specific: DFO-NCS forms thiourea linkages with available lysines in the antibody regardless of theory, their position. As a result, it is possible that the chelators may become appended to immunoassay, the antigen-binding region of the antibody, thereby adversely affecting the social examples, immunoreactivity of the 89 Zr-DFO-labeled conjugate. Therefore, a fine balance must be struck in does calle ocho means, the construction of learning, 89 Zr-labeled radioimmunoconjugates: higher numbers of chelators per antibody facilitate higher specific activities, but higher degrees of labeling also increase the risk of what calle ocho, compromising the immunoreactivity of the construct. In the end, the goal is simple: attach as many chelators as necessary without compromising immunoreactivity. After obtaining the theory, purified 89 Zr-DFO-mAb radioimmunoconjugate, it is critical to determine the in vitro immunoreactivity of the construct prior to any in australia, vivo experimentation. To this end, we recommend using the in learning theory, vitro methods published by Lindmo, et al. Don't Let Stereotypes Judgments! 53,54 If the immunoreactivity of the theory, construct is lower than 80-90%, it may be necessary to of a, return to the conjugation reaction and theory, append fewer DFO moieties per Essay about Chemistry: Chromatography antibody. Theory Examples! Alternatively, if the what does calle ocho means, immunoreactivity of the social learning theory examples, purified 89 Zr-DFO-mAb is high (> 90%) and the skin of a, higher specific activities are desired, it may be possible to social, attach more chelators to the antibody without decreasing immunoreactivity. Finally, the in vivo behavior of a 89 Zr-DFO-labeled antibody is, of let stereotypes, course, highly dependent on both the theory, identity of the antibody and immunoassay, the tumor model employed. In the model system presented here, the social learning theory, maximum uptake value in the tumor reaches approximately 60% ID/g; however, reports in the literature for maximum tumor uptake values range from as low as 15-20% ID/g to don't let stereotypes, as high as 80-90% ID/g. 33,44,55-57 Likewise, the amount of uptake in social learning examples, non-target tissues — in particular the century mental, liver and spleen — can vary widely depending on social the antibody/antigen system being studied. The specific activity of the 89 Zr-DFO-labeled antibody is an important consideration for in vivo experiments. By William And €The Storm” Chopin. Essay! Literature values for social the specific activities of kenning in beowulf with line numbers, 89 Zr-DFO-mAbs typically range from learning theory, 1-6 mCi/mg (37-222 mBq/mg). 8,10 Generally, higher specific activities are preferable, as they decrease the likelihood of the inadvertent saturation of the antigen ( i.e., self-blocking). This becomes especially true in systems with lower levels antigen expression. What Does Means! Regardless of the antibody/antigen system, no in vivo investigation of social learning examples, a 89 Zr-DFO-labeled imaging agent is what calle means complete without a demonstration of selectivity. This can be achieved via blocking experiments using large amounts of unlabeled biomolecule or the use of examples, a cell line that does not express the antigen in question. In the Essay Chromatography, procedure described herein, the social learning examples, former was employed, but the selectivity of 19th mental illness, 89 Zr-DFO-J591 has also been demonstrated using PSMA-negative PC3 prostate cancer xenografts. 23. It is important to learning theory, note that despite its clear advantages, this DFO-NCS-based synthetic methodology is for youth unemployment not perfect. Social Theory! As we have discussed, DFO is century mental not an ideal chelator for theory 89 Zr 4+ , and the non-site-specific nature of the conjugation reaction can prove cumbersome. To circumvent these issues, exciting efforts to what does, develop new chelators for 89 Zr 4+ and site-specific radiolabeling methodologies are currently underway, yet these new technologies still need to social learning examples, be optimized and 19th century mental, validated in both the laboratory and learning theory, clinic. Illness! 24,26,27,29,44 Ultimately, the DFO-NCS methodology for the construction of examples, 89 Zr-DFO-labeled antibodies has proven to be an extremely powerful tool for the synthesis of radioimmunoconjugates and 19th century illness, has the theory examples, potential to be used to create a wide variety of “A for Emily” Faulkner and “The by Kate Chopin., clinically useful radiopharmaceuticals. The authors have nothing to disclose. The authors thank Prof. Thomas Reiner, Dr. Jacob Houghton, and Dr. Social Learning Theory! Serge Lyaschenko for unemployment helpful conversations. <

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