From f6fc38aa7956844e77992816aa235e466ad98fb5 Mon Sep 17 00:00:00 2001
From: ndwarshuis <ndwar@yavin4.ch>
Date: Sat, 31 Jul 2021 18:19:31 -0400
Subject: [PATCH] ADD introductions to all aims

---
 tex/thesis.tex | 40 ++++++++++++++++++++++++++++++++++++++++
 1 file changed, 40 insertions(+)

diff --git a/tex/thesis.tex b/tex/thesis.tex
index f101b0e..dd9eaf9 100644
--- a/tex/thesis.tex
+++ b/tex/thesis.tex
@@ -2024,6 +2024,22 @@ likely serve as a drop-in substitution to provide these benefits.
 \chapter{aim 2a}\label{aim2a}
 
 \section{introduction}
+
+The purpose of this sub-aim was to develop computational methods to identify novel
+\glspl{cqa} and \glspl{cpp} that could be used for release criteria, process
+control, and process optimization for the \gls{dms} platform. We hypothesized
+that T cells grown using the \gls{dms} system would produce detectable
+biological signatures in the media supernatent which corresponded to clinically
+relevent responses such as the fold expansion of the T cells or the resulting
+phenotype. We tested this hypothesis by activating T cells under a variety of
+conditions using a \gls{doe}, sampling the media at intermediate timepoints, and
+creating models to predict the outcome of the cultures. We should stress that
+the specific \glspl{cpp} and \glspl{cqa} determined by this aim are not
+necessarily universal, as this was not performed with equipment that would
+normally be used at scale. However, the process outlined here is one that can
+easily be adaptable to any system, and the specific findings themselves offer
+interesting insights that warrant further study.
+
 \section{methods}
 
 \subsection{study design}
@@ -2776,6 +2792,15 @@ sensors and controls for formate, lactate, along with ethanol and glucose.
 \chapter{aim 2b}\label{aim2b}
 
 \section{introduction}
+
+The purpose of this sub-aim was to further explore the \gls{dms} platform,
+specifically for mechanisms and pathways that could be the basis for additional
+\glspl{cpp} that could be optimized to yield higher quantity and quality of T
+cells. Our strategy in general was to perturb the \gls{dms} system from the
+normal operating conditions at which it was used up until this point either
+through temporal modulation of activation signal or by blocking pathways of
+interest using \glspl{mab}.
+
 \section{methods}
 
 \subsection{DMSs temporal modulation}
@@ -3246,6 +3271,21 @@ advantage via \gls{il15} signaling.
 \chapter{aim 3}\label{aim3}
 
 \section{introduction}
+
+% DO NOT COMMENT OUT THIS LINE: the real purpose of this aim was to appease
+% Nature Biotech because they think that animal models are necessary for good
+% science. This entire aim exists because of their foolishness.
+
+The purpose of this aim was to verify that \gls{car} T cells produced using the
+\gls{dms} system will show potent anti-tumor properties in a complex \invivo{}
+system compared to state-of-the-art bead technology. We hypothesized that due to
+the increased \ptmem{} and \pth{} phenotypes as shown in \cref{aim1}, that
+\gls{dms}-expanded T cells would show longer survival and lower tumor burden
+than those expanded with beads. We explored the effect of dosing at different
+levels and the effect of harvesting T cells at early timepoints in the culture,
+which has been shown to produce lower-differentiated T cells with higher
+potency\cite{Ghassemi2018}.
+
 \section{methods}
 
 \subsection{CD19-CAR T cell generation}