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////////////////////////////////////////////////////////////////////////////
////////////////////////////////////////////////////////////////////////////
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  </span><span style=3D'position:absolute;top:17.75%;left:19.28%;width:74.9=
%;
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bullet;
 display:none;color:#0078F0;mso-color-index:4;font-family:Wingdings;font-si=
ze:
 85%'>o</span><span style=3D'font-size:50%;display:none'>&#13;</span></div>
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on of
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n></span></div>
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ullet;
 display:none;color:#0078F0;mso-color-index:4;font-family:Wingdings;font-si=
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 display:none;color:#0078F0;mso-color-index:4;font-family:Wingdings;font-si=
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 85%'>o</span><span style=3D'font-size:36%;display:none'>&#13;</span></div>
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s;
 font-size:85%'>o</span><span style=3D'font-size:50%'>Rockefeller Institute=
 for
 Medical Research <br>
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 display:none;color:#0078F0;mso-color-index:4;font-family:Wingdings;font-si=
ze:
 85%'>o</span><span style=3D'font-size:50%'><span
 style=3D'mso-spacerun:yes'>&nbsp;&nbsp;&nbsp;&nbsp; </span>d. 1944&nbsp;&#=
13;</span></div>
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bullet;
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;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&n=
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bsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp=
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dian
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 16
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plant
 Immunology </span><span style=3D'position:absolute;top:36.25%;left:23.03%;
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an><span
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 <div v:shape=3D"_x0000_s53250" class=3DT style=3D'position:absolute;top:12=
.25%;
 left:19.28%;width:74.9%;height:8.25%'>Immunological responses</div>
 <div v:shape=3D"_x0000_s53251" class=3DB><span style=3D'position:absolute;
 top:30.0%;left:23.03%;width:71.16%;height:6.0%'><span class=3DBB
 style=3D'position:absolute;left:-5.26%;top:.16em'>o</span>Rejection : proh=
ibits
 the grafting of </span><span style=3D'position:absolute;top:36.25%;left:23=
.03%;
 width:80.14%;height:6.0%'>tissues between individuals of different </span>=
<span
 style=3D'position:absolute;top:42.25%;left:23.03%;width:71.16%;height:6.0%=
'>genetic
 make-up&#13;</span><span style=3D'position:absolute;top:49.75%;left:23.03%;
 width:79.21%;height:6.0%'><span style=3D'color:#FFCC00;mso-color-index:7'>=
<span
 class=3DBB style=3D'position:absolute;left:-4.72%;top:.16em'>o</span></spa=
n><span
 style=3D'color:#FFCC00;mso-color-index:7'>Tolerance</span> : a non-reactiv=
ity
 caused by </span><span style=3D'position:absolute;top:56.0%;left:23.03%;
 width:76.02%;height:6.0%'>exposing animals to antigenic stimuli </span><sp=
an
 style=3D'position:absolute;top:62.25%;left:23.03%;width:71.16%;height:6.0%=
'>before
 they were old enough to </span><span style=3D'position:absolute;top:68.5%;
 left:23.03%;width:80.52%;height:6.0%'>undertake an immunological
 response.&#13;</span>
 <div style=3D'position:absolute;top:75.5%;left:19.28%;width:74.9%;height:4=
.5%'><span
 style=3D'mso-special-format:nobullet;display:none;color:#0078F0;mso-color-=
index:
 4;font-family:Wingdings;font-size:85%'>o</span><span style=3D'font-size:71=
%'><span
 style=3D'mso-spacerun:yes'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp=
;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&n=
bsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp=
;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&n=
bsp;
 </span>&#13;</span></div>
 <div style=3D'position:absolute;top:80.75%;left:19.28%;width:83.7%;height:=
4.5%'><span
 style=3D'mso-special-format:nobullet;display:none;color:#0078F0;mso-color-=
index:
 4;font-family:Wingdings;font-size:85%'>o</span><span style=3D'font-size:71=
%'><span
 style=3D'mso-spacerun:yes'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp=
;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&n=
bsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp=
;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
 </span>Nobel lecture Dec. 12, 1960</span></div>
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.25%;
 left:19.28%;width:83.14%;height:8.25%'>Immunosuppression timeline</div>
 <div v:shape=3D"_x0000_s39939" class=3DB><span style=3D'position:absolute;
 top:30.0%;left:23.03%;width:82.77%;height:6.0%'><span class=3DBB
 style=3D'position:absolute;left:-4.52%;top:.16em'>o</span>Tolerance to self
 antigens: described by </span><span style=3D'position:absolute;top:36.25%;
 left:23.03%;width:80.14%;height:6.0%'>MacFarlane Burnet as theory of Clona=
l </span><span
 style=3D'position:absolute;top:42.25%;left:23.03%;width:71.16%;height:6.0%=
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 style=3D'position:absolute;top:49.75%;left:23.03%;width:71.16%;height:6.0%=
'><span
 class=3DBB style=3D'position:absolute;left:-5.26%;top:.16em'>o</span>Nobel=
 Prize
 in 1960 (shared with </span><span style=3D'position:absolute;top:56.0%;
 left:23.03%;width:76.96%;height:6.0%'>Medawar) for demonstrating Immune </=
span><span
 style=3D'position:absolute;top:62.25%;left:23.03%;width:71.16%;height:6.0%=
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 style=3D'position:absolute;top:69.75%;left:23.03%;width:82.77%;height:6.0%=
'><span
 class=3DBB style=3D'position:absolute;left:-4.52%;top:.16em'>o</span>Immune
 Tolerance seen as the platform </span><span style=3D'position:absolute;
 top:76.0%;left:23.03%;width:71.16%;height:6.0%'>for transplanting solid
 organs.</span></div>
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 <div style=3D'position:absolute;top:30.0%;left:19.28%;width:74.9%;height:6=
.0%'><span
 style=3D'position:absolute;top:0%;left:5.0%;width:95.0%;height:100.0%'><sp=
an
 style=3D'visibility:hidden'><span class=3DBB style=3D'position:absolute;le=
ft:-5.26%'>o</span></span>&#13;</span></div>
 <div style=3D'position:absolute;top:37.5%;left:19.28%;width:74.9%;height:6=
.0%'><span
 style=3D'position:absolute;top:0%;left:5.0%;width:95.0%;height:100.0%'><sp=
an
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ft:-5.26%'>o</span></span>&#13;</span></div>
 <span style=3D'position:absolute;top:44.75%;left:19.28%;width:88.57%;heigh=
t:
 6.0%'><span style=3D'mso-special-format:nobullet;display:none;color:#0078F=
0;
 mso-color-index:4;font-family:Wingdings;font-size:85%'>o</span><span
 style=3D'mso-spacerun:yes'>&nbsp;&nbsp; </span><u>Clonal Deletion</u>: The=
 loss
 of lymphocytes </span><span style=3D'position:absolute;top:51.0%;left:23.0=
3%;
 width:80.71%;height:6.0%'>of a particular specificity due to contact </spa=
n><span
 style=3D'position:absolute;top:57.25%;left:23.03%;width:79.21%;height:6.0%=
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 either self or artificially introduced </span><span style=3D'position:abso=
lute;
 top:63.5%;left:23.03%;width:71.16%;height:6.0%'>antigens</span></div>
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2.25%;
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%;
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den'><span
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#13;</span></div>
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%;
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ormat:
 bullet;color:#0078F0;mso-color-index:4;position:absolute;left:-7.2%;
 top:.16em;font-family:Wingdings;font-size:85%'>o</span>Tolerance to self
 antigens made sense&#13;</span></div>
 <div class=3DB style=3D'mso-margin-left-alt:336;position:absolute;top:44.7=
5%;
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den'><span
 style=3D'mso-special-format:bullet;color:#0078F0;mso-color-index:4;positio=
n:
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#13;</span></div>
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bsolute;
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l-format:
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 top:.16em;font-family:Wingdings;font-size:85%'>o</span>How did Medawar arr=
ive
 at the </span><span style=3D'position:absolute;top:58.49%;left:25.09%;
 width:78.46%;height:6.0%'>conclusion that tolerance to &#8216;Non-self&#82=
21; </span><span
 style=3D'position:absolute;top:64.75%;left:25.09%;width:68.91%;height:6.0%=
'>antigens
 was actually possible?</span></div>
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2.25%;
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 top:30.0%;left:23.03%;width:81.64%;height:6.0%'><span class=3DBB
 style=3D'position:absolute;left:-4.58%;top:.16em'>o</span>One of the most =
severe
 forms of sexual </span><span style=3D'position:absolute;top:36.25%;left:23=
.03%;
 width:71.16%;height:6.0%'>abnormality among cattle.&#13;</span><span
 style=3D'position:absolute;top:43.5%;left:23.03%;width:81.83%;height:6.0%'=
><span
 class=3DBB style=3D'position:absolute;left:-4.57%;top:.16em'>o</span>Causes
 infertility in the female calf born </span><span style=3D'position:absolut=
e;
 top:49.75%;left:23.03%;width:71.16%;height:6.0%'>twin to a male.&#13;</spa=
n><span
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'><span
 class=3DBB style=3D'position:absolute;left:-4.54%;top:.16em'>o</span>Due t=
o the
 sharing of the placenta, after </span><span style=3D'position:absolute;
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size:
 67%;position:relative;top:-.45em;mso-text-raise:30%'>th</span>.day of
 pregnancy&#13;</span><span style=3D'position:absolute;top:71.0%;left:23.03=
%;
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:-4.4%;
 top:.16em'>o</span>Exchange of blood and antigens carrying </span><span
 style=3D'position:absolute;top:77.25%;left:23.03%;width:71.16%;height:6.0%=
'>characteristics
 unique to each sex</span></div>
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 top:30.0%;left:23.03%;width:71.16%;height:6.0%'><span class=3DBB
 style=3D'position:absolute;left:-5.26%;top:.16em'>o</span>Myth :<span
 style=3D'mso-spacerun:yes'>&nbsp; </span>Fire breathing monster </span><sp=
an
 style=3D'position:absolute;top:36.25%;left:23.03%;width:81.08%;height:6.0%=
'>composed
 of a lion&#8217;s head, goat&#8217;s body </span><span style=3D'position:a=
bsolute;
 top:42.25%;left:23.03%;width:71.16%;height:6.0%'>and serpent&#8217;s
 tail.&#13;</span><span style=3D'position:absolute;top:49.75%;left:23.03%;
 width:71.16%;height:6.0%'><span class=3DBB style=3D'position:absolute;left=
:-5.26%;
 top:.16em'>o</span>Medical Science: A chimera is an </span><span
 style=3D'position:absolute;top:56.0%;left:23.03%;width:71.16%;height:6.0%'=
>individual
 having more than one </span><span style=3D'position:absolute;top:62.25%;
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ells
 </span><span style=3D'position:absolute;top:68.5%;left:23.03%;width:71.91%;
 height:6.0%'>that originated from more than one </span><span style=3D'posi=
tion:
 absolute;top:74.75%;left:23.03%;width:71.16%;height:6.0%'>zygote.&#13;</sp=
an><span
 style=3D'position:absolute;top:81.75%;left:23.03%;width:79.4%;height:4.5%'=
><span
 style=3D'font-size:71%'><span class=3DBB style=3D'position:absolute;left:-=
4.71%;
 top:.16em'>o</span></span><span style=3D'font-size:71%'>Mosaics have one o=
r more
 cytogenetically distinct cell </span></span><span style=3D'position:absolu=
te;
 top:86.25%;left:23.03%;width:71.16%;height:4.5%'><span style=3D'font-size:=
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 arising from a single zygote</span></span></div>
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.25%;
 left:19.28%;width:83.14%;height:8.25%'>Immunosuppression timeline</div>
 <div v:shape=3D"_x0000_s52227" class=3DB>
 <div style=3D'mso-line-spacing:"90 20 0"'><span style=3D'position:absolute;
 top:29.49%;left:23.03%;width:76.4%;height:6.0%'><span style=3D'mso-special=
-format:
 bullet;color:#0078F0;mso-color-index:4;position:absolute;left:-4.9%;
 top:.16em;font-family:Wingdings;font-size:85%'>o</span>Medawar described
 tolerance to skin </span><span style=3D'position:absolute;top:35.0%;left:2=
3.03%;
 width:74.53%;height:6.0%'>grafts between the male and female </span><span
 style=3D'position:absolute;top:40.5%;left:23.03%;width:84.64%;height:6.0%'=
>dizygotic
 twin cattle <span style=3D'font-size:71%'>(while retaining their ability t=
o </span></span><span
 style=3D'position:absolute;top:46.25%;left:23.03%;width:71.16%;height:4.5%=
'><span
 style=3D'font-size:71%'>reject skin grafts from other animals)&#13;</span>=
</span></div>
 <div style=3D'mso-line-spacing:"90 20 0"'><span style=3D'position:absolute;
 top:51.5%;left:23.03%;width:79.58%;height:6.0%'><span style=3D'mso-special=
-format:
 bullet;color:#0078F0;mso-color-index:4;position:absolute;left:-4.7%;
 top:.16em;font-family:Wingdings;font-size:85%'>o</span>Also between
 genetically non-identical </span><span style=3D'position:absolute;top:57.0=
%;
 left:23.03%;width:71.16%;height:6.0%'>mice.&#13;</span></div>
 <div style=3D'mso-line-spacing:"90 20 0"'><span style=3D'position:absolute;
 top:64.0%;left:23.03%;width:71.16%;height:6.0%'><span style=3D'color:#FFCC=
00;
 mso-color-index:7'><span style=3D'mso-special-format:bullet;color:#0078F0;
 mso-color-index:4;position:absolute;left:-5.26%;top:.16em;font-family:Wing=
dings;
 font-size:85%'>o</span></span><span style=3D'color:#FFCC00;mso-color-index=
:7'>&#8220;Tolerance
 is not an all-or-nothing </span></span><span style=3D'position:absolute;
 top:69.5%;left:23.03%;width:83.14%;height:6.0%'><span style=3D'color:#FFCC=
00;
 mso-color-index:7'>phenomenon: every degree of tolerance </span></span><sp=
an
 style=3D'position:absolute;top:75.0%;left:23.03%;width:83.7%;height:6.0%'>=
<span
 style=3D'color:#FFCC00;mso-color-index:7'>is to be found&#8221;</span><span
 style=3D'mso-spacerun:yes'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp=
;&nbsp;&nbsp;&nbsp;&nbsp;
 </span><span style=3D'font-size:64%'>Nobel lecture Dec. 12, 1960&#13;</spa=
n></span></div>
 <div style=3D'mso-line-spacing:"90 20 0";position:absolute;top:82.0%;left:=
19.28%;
 width:74.9%;height:6.0%'><span style=3D'mso-special-format:nobullet;displa=
y:
 none;color:#0078F0;mso-color-index:4;font-family:Wingdings;font-size:85%'>=
o</span><span
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s -
 in1950s&#13;</span>
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2.25%;
 left:19.28%;width:83.14%;height:8.25%'>Immunosuppression timeline</div>
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 <div style=3D'position:absolute;top:30.0%;left:19.28%;width:88.2%;height:6=
.0%'><span
 style=3D'position:absolute;top:0%;left:4.24%;width:95.75%;height:100.0%'><=
span
 class=3DBB style=3D'position:absolute;left:-4.43%;top:.16em'>o</span>&#8217=
;60s to
 1978 : Prednisone + Azathioprine&#13;</span></div>
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6.0%'><span
 style=3D'position:absolute;top:0%;left:4.66%;width:95.33%;height:100.0%'><=
span
 class=3DBB style=3D'position:absolute;left:-4.88%;top:.16em'>o</span>AZA i=
s still
 a useful drug (Pediatrics).&#13;</span></div>
 <span style=3D'position:absolute;top:44.75%;left:23.03%;width:83.52%;heigh=
t:
 6.0%'><span class=3DBB style=3D'position:absolute;left:-4.48%;top:.16em'>o=
</span>Pts
 on MMF have to be switched to AZA </span><span style=3D'position:absolute;
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 style=3D'position:absolute;top:58.49%;left:23.03%;width:76.4%;height:6.0%'=
><span
 class=3DBB style=3D'position:absolute;left:-4.9%;top:.16em'>o</span>Some o=
f the
 longest surviving kidney </span><span style=3D'position:absolute;top:64.75=
%;
 left:23.03%;width:82.39%;height:6.0%'>and liver transplant patients are on=
 AZA
 </span><span style=3D'position:absolute;top:71.0%;left:23.03%;width:71.16%;
 height:6.0%'>(&gt;40 years)</span></div>
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.25%;
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 <div style=3D'mso-line-spacing:"90 20 0";position:absolute;top:29.49%;
 left:19.28%;width:74.9%;height:6.0%'><span style=3D'position:absolute;
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mat:
 bullet;color:#0078F0;mso-color-index:4;position:absolute;left:-5.26%;
 top:.16em;font-family:Wingdings;font-size:85%'>o</span>Cyclosporin develop=
ed
 in 1970s&#13;</span></div>
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 top:36.25%;left:23.03%;width:80.52%;height:6.0%'><span style=3D'mso-specia=
l-format:
 bullet;color:#0078F0;mso-color-index:4;position:absolute;left:-4.65%;
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 late 70s and early </span><span style=3D'position:absolute;top:41.75%;
 left:23.03%;width:71.16%;height:6.0%'>80s.&#13;</span></div>
 <div style=3D'mso-line-spacing:"90 20 0";position:absolute;top:48.75%;
 left:19.28%;width:85.95%;height:6.0%'><span style=3D'position:absolute;
 top:0%;left:4.35%;width:95.64%;height:100.0%'><span style=3D'mso-special-f=
ormat:
 bullet;color:#0078F0;mso-color-index:4;position:absolute;left:-4.55%;
 top:.16em;font-family:Wingdings;font-size:85%'>o</span>First drug to
 selectively regulate T cells.&#13;</span></div>
 <div style=3D'mso-line-spacing:"90 20 0";position:absolute;top:55.5%;left:=
19.28%;
 width:80.89%;height:6.0%'><span style=3D'position:absolute;top:0%;left:4.6=
2%;
 width:95.37%;height:100.0%'><span style=3D'mso-special-format:bullet;color=
:#0078F0;
 mso-color-index:4;position:absolute;left:-4.85%;top:.16em;font-family:Wing=
dings;
 font-size:85%'>o</span>Accepted for commercial use in 1983&#13;</span></di=
v>
 <div style=3D'mso-line-spacing:"90 20 0"'><span style=3D'position:absolute;
 top:62.5%;left:23.03%;width:79.02%;height:6.0%'><span style=3D'mso-special=
-format:
 bullet;color:#0078F0;mso-color-index:4;position:absolute;left:-4.73%;
 top:.16em;font-family:Wingdings;font-size:85%'>o</span>Enabled transplanta=
tion
 without tissue </span><span style=3D'position:absolute;top:68.0%;left:23.0=
3%;
 width:71.16%;height:6.0%'>matching.&#13;</span></div>
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l-format:
 bullet;color:#0078F0;mso-color-index:4;position:absolute;left:-4.65%;
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 transplantation across the </span><span style=3D'position:absolute;top:80.=
5%;
 left:23.03%;width:71.16%;height:6.0%'>world.</span></div>
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an
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oy Calne
 (Cambridge, UK)&#13;</span></div>
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.0%'><span
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an
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ft:-5.26%'>o</span></span>&#13;</span></div>
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6.0%'><span
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an
 style=3D'visibility:hidden'><span class=3DBB style=3D'position:absolute;le=
ft:-5.26%'>o</span></span>&#13;</span></div>
 <div style=3D'position:absolute;top:52.24%;left:19.28%;width:74.9%;height:=
6.0%'><span
 style=3D'position:absolute;top:0%;left:5.0%;width:95.0%;height:100.0%'><sp=
an
 style=3D'visibility:hidden'><span class=3DBB style=3D'position:absolute;le=
ft:-5.26%'>o</span></span>&#13;</span></div>
 <div style=3D'position:absolute;top:59.75%;left:19.28%;width:74.9%;height:=
6.0%'><span
 style=3D'position:absolute;top:0%;left:5.0%;width:95.0%;height:100.0%'><sp=
an
 class=3DBB style=3D'position:absolute;left:-5.26%;top:.16em'>o</span>Thoma=
s Starzl
 (Pittsburgh, USA)&#13;</span></div>
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6.0%'><span
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an
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