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@@ -524,14 +524,8 @@ Beyond that, what I'm mainly interested in is feedback on the content.
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the results I'm trying to show? Do you feel that the claims in the results
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the results I'm trying to show? Do you feel that the claims in the results
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and discussion sections are well-supported? There's no need to suggest
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and discussion sections are well-supported? There's no need to suggest
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improvements; just note areas that you feel need improvement.
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improvements; just note areas that you feel need improvement.
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- Additionally, while I am well aware that Chapter 1 (the introduction) contains
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- many un-cited claims, all the other chapters (2,3, and 4)
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-\emph on
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-should
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-\emph default
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- be fully cited.
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- So if you notice any un-cited claims in those chapters, please flag them
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- for my attention.
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+ Additionally, if you notice any un-cited claims in any chapter, please
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+ flag them for my attention.
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Similarly, if you discover any factual errors, please note them as well.
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Similarly, if you discover any factual errors, please note them as well.
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\end_layout
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\end_layout
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@@ -559,7 +553,7 @@ also
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\begin_layout Standard
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\begin_layout Standard
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My thesis is due Thursday, October 10th, so in order to be useful to me,
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My thesis is due Thursday, October 10th, so in order to be useful to me,
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- I'll need your feedback at least a few days before that, ideally by Monday,
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+ I'll need your feedback at least several days before that, ideally by Monday,
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October 7th.
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October 7th.
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If you have limited time and are unable to get through the whole thesis,
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If you have limited time and are unable to get through the whole thesis,
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please focus your efforts on Chapters 1 and 2, since those are the roughest
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please focus your efforts on Chapters 1 and 2, since those are the roughest
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@@ -580,11 +574,30 @@ Thanks again for your help, and happy reading!
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Introduction
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Introduction
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\end_layout
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\end_layout
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-\begin_layout Section
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-Background & Significance
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+\begin_layout Section*
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+Structure of the thesis
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\end_layout
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\end_layout
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-\begin_layout Subsection
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+\begin_layout Standard
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+\begin_inset Flex TODO Note (inline)
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+status open
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+
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+\begin_layout Plain Layout
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+This section might even go before the Chapter 1 header
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+\end_layout
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+
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+\end_inset
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+
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+
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+\end_layout
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+
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+\begin_layout Section
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+\begin_inset CommandInset label
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+LatexCommand label
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+name "sec:Biological-motivation"
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+
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+\end_inset
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+
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Biological motivation
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Biological motivation
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\end_layout
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\end_layout
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@@ -601,7 +614,7 @@ Rethink the subsection organization after the intro is written.
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\end_layout
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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Rejection is the major long-term threat to organ and tissue allografts
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Rejection is the major long-term threat to organ and tissue allografts
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\end_layout
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\end_layout
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@@ -947,12 +960,17 @@ literal "false"
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and regulation is required.
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and regulation is required.
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\end_layout
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\end_layout
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+\begin_layout Subsubsection
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+MSC infusion to improve transplant outcomes (prevent/delay rejection)
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+\end_layout
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+
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\begin_layout Standard
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\begin_layout Standard
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\begin_inset Flex TODO Note (inline)
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\begin_inset Flex TODO Note (inline)
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status open
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status open
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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-Some kind of transition into bioinformatics would be good here
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+Do I still talk about this? It's the motivation for chapter 4, but I don't
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+ actually present any work related to MSCs.
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\end_layout
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\end_layout
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\end_inset
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\end_inset
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@@ -960,7 +978,73 @@ Some kind of transition into bioinformatics would be good here
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\end_layout
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\end_layout
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-\begin_layout Subsection
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+\begin_layout Itemize
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+Demonstrated in mice, but not yet in primates
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+\end_layout
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+
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+\begin_layout Itemize
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+Mechanism currently unknown, but MSC are known to be immune modulatory
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+\end_layout
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+
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+\begin_layout Itemize
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+Characterize MSC response to interferon gamma
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+\end_layout
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+
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+\begin_layout Itemize
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+IFN-g is thought to stimulate their function
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+\end_layout
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+
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+\begin_layout Itemize
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+Test IFN-g treated MSC infusion as a therapy to delay graft rejection in
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+ cynomolgus monkeys
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+\end_layout
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+
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+\begin_layout Itemize
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+Monitor animals post-transplant using blood
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+\begin_inset Flex Glossary Term
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+status open
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+
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+\begin_layout Plain Layout
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+RNA-seq
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+\end_layout
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+
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+\end_inset
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+
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+ at serial time points
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+\end_layout
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+
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+\begin_layout Subsubsection
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+Investigate dynamics of histone marks in CD4 T-cell activation and memory
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+\end_layout
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+
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+\begin_layout Itemize
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+Previous studies have looked at single snapshots of histone marks
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+\end_layout
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+
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+\begin_layout Itemize
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+Instead, look at changes in histone marks across activation and memory
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+\end_layout
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+
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+\begin_layout Subsubsection
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+High-throughput sequencing and microarray technologies
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+\end_layout
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+
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+\begin_layout Itemize
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+Powerful methods for assaying gene expression and epigenetics across entire
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+ genomes
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+\end_layout
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+
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+\begin_layout Itemize
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+Proper analysis requires finding and exploiting systematic genome-wide trends
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+\end_layout
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+
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+\begin_layout Section
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+\begin_inset CommandInset label
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+LatexCommand label
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+name "sec:Overview-of-bioinformatic"
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+
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+\end_inset
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+
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Overview of bioinformatic analysis methods
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Overview of bioinformatic analysis methods
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\end_layout
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\end_layout
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@@ -968,6 +1052,19 @@ Overview of bioinformatic analysis methods
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\begin_inset Flex TODO Note (inline)
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\begin_inset Flex TODO Note (inline)
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status open
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status open
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+\begin_layout Plain Layout
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+Some kind of transition into bioinformatics would be good here
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+\end_layout
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+
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+\end_inset
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+
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+
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+\end_layout
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+
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+\begin_layout Standard
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+\begin_inset Flex TODO Note (inline)
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+status open
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+
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\begin_layout Plain Layout
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\begin_layout Plain Layout
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Also cite somewhere: R, Bioconductor
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Also cite somewhere: R, Bioconductor
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\end_layout
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\end_layout
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@@ -987,7 +1084,7 @@ The studies presented in this work all involve the analysis of high-throughput
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they work.
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they work.
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\end_layout
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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\begin_inset Flex Code
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\begin_inset Flex Code
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status open
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status open
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@@ -1266,7 +1363,7 @@ limma
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random effect correlation.
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random effect correlation.
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\end_layout
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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\begin_inset Flex Code
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\begin_inset Flex Code
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status open
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status open
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@@ -1529,7 +1626,7 @@ literal "false"
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.
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.
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\end_layout
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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ChIP-seq Peak calling
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ChIP-seq Peak calling
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\end_layout
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\end_layout
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@@ -1916,7 +2013,7 @@ literal "false"
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.
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.
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\end_layout
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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Normalization of high-throughput data is non-trivial and application-dependent
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Normalization of high-throughput data is non-trivial and application-dependent
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\end_layout
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\end_layout
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@@ -2262,7 +2359,7 @@ literal "true"
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regions are generally preferred whenever possible.
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regions are generally preferred whenever possible.
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\end_layout
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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ComBat and SVA for correction of known and unknown batch effects
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ComBat and SVA for correction of known and unknown batch effects
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\end_layout
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\end_layout
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@@ -2412,7 +2509,7 @@ s in the linear model in a similar fashion to known batch effects in order
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to subtract out their effects on each feature's abundance.
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to subtract out their effects on each feature's abundance.
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\end_layout
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\end_layout
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-\begin_layout Subsubsection
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+\begin_layout Subsection
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Factor analysis: PCA, MDS, MOFA
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Factor analysis: PCA, MDS, MOFA
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\end_layout
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\end_layout
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@@ -2443,102 +2540,6 @@ PCA
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is informative, but careful application is required to avoid bias
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is informative, but careful application is required to avoid bias
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\end_layout
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\end_layout
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-\begin_layout Section
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-Innovation
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-\end_layout
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-
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-\begin_layout Standard
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-\begin_inset Flex TODO Note (inline)
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-status open
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-
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-\begin_layout Plain Layout
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-Is this entire section redundant with the Approach sections of each chapter?
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- I'm not really sure what to write here.
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-\end_layout
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-
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-\end_inset
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-
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-
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-\end_layout
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-
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-\begin_layout Subsection
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-MSC infusion to improve transplant outcomes (prevent/delay rejection)
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-\end_layout
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-
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-\begin_layout Standard
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-\begin_inset Flex TODO Note (inline)
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-status open
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-
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-\begin_layout Plain Layout
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-Do I still talk about this? It's the motivation for chapter 4, but I don't
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- actually present any work related to MSCs.
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-\end_layout
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-
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-\end_inset
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-
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-
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-\end_layout
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-
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-\begin_layout Itemize
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-Demonstrated in mice, but not yet in primates
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-\end_layout
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-
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-\begin_layout Itemize
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-Mechanism currently unknown, but MSC are known to be immune modulatory
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-\end_layout
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-
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-\begin_layout Itemize
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-Characterize MSC response to interferon gamma
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-\end_layout
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-
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-\begin_layout Itemize
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-IFN-g is thought to stimulate their function
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-\end_layout
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-
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-\begin_layout Itemize
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-Test IFN-g treated MSC infusion as a therapy to delay graft rejection in
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- cynomolgus monkeys
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-\end_layout
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-
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-\begin_layout Itemize
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-Monitor animals post-transplant using blood
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-\begin_inset Flex Glossary Term
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-status open
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-
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-\begin_layout Plain Layout
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-RNA-seq
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-\end_layout
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-
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-\end_inset
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-
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- at serial time points
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-\end_layout
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-
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-\begin_layout Subsection
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-Investigate dynamics of histone marks in CD4 T-cell activation and memory
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-\end_layout
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-
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-\begin_layout Itemize
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-Previous studies have looked at single snapshots of histone marks
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-\end_layout
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-
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-\begin_layout Itemize
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-Instead, look at changes in histone marks across activation and memory
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-\end_layout
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-
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-\begin_layout Subsection
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-High-throughput sequencing and microarray technologies
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-\end_layout
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-
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-\begin_layout Itemize
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-Powerful methods for assaying gene expression and epigenetics across entire
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- genomes
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-\end_layout
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-
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-\begin_layout Itemize
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-Proper analysis requires finding and exploiting systematic genome-wide trends
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-\end_layout
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-
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\begin_layout Chapter
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\begin_layout Chapter
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Reproducible genome-wide epigenetic analysis of H3K4 and H3K27 methylation
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Reproducible genome-wide epigenetic analysis of H3K4 and H3K27 methylation
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in naïve and memory CD4 T-cell activation
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in naïve and memory CD4 T-cell activation
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@@ -2773,20 +2774,6 @@ literal "false"
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Methods
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Methods
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\end_layout
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\end_layout
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-\begin_layout Standard
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-\begin_inset Flex TODO Note (inline)
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-status open
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-
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-\begin_layout Plain Layout
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-Look up some more details from the papers (e.g.
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- activation method).
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-\end_layout
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-
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-\end_inset
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-
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-
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-\end_layout
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-
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\begin_layout Standard
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\begin_layout Standard
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A reproducible workflow was written to analyze the raw
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A reproducible workflow was written to analyze the raw
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\begin_inset Flex Glossary Term
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\begin_inset Flex Glossary Term
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@@ -2837,11 +2824,11 @@ ChIP-seq
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\end_inset
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\end_inset
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- from CD4 T-cells cultured from 4 donors.
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+ from CD4 T-cells from 4 donors.
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From each donor, naïve and memory CD4 T-cells were isolated separately.
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From each donor, naïve and memory CD4 T-cells were isolated separately.
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- Then cultures of both cells were activated [how?], and samples were taken
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- at 4 time points: Day 0 (pre-activation), Day 1 (early activation), Day
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- 5 (peak activation), and Day 14 (post-activation).
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+ Then cultures of both cells were activated with CD3/CD28 beads, and samples
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+ were taken at 4 time points: Day 0 (pre-activation), Day 1 (early activation),
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+ Day 5 (peak activation), and Day 14 (post-activation).
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For each combination of cell type and time point, RNA was isolated and
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For each combination of cell type and time point, RNA was isolated and
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sequenced, and
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sequenced, and
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\begin_inset Flex Glossary Term
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\begin_inset Flex Glossary Term
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