UNIVERSITY OF CALIFORNIA SAN DIEGO

The Risk of Living from Your Heart

A thesis submitted in partial satisfaction of the requirementsfor the degree

in

Master of Fine Arts in Acting

by

Jordan C. Smith

Committee in charge:Ursula Meyer, Chair Marc Alexander Barricelli Stephen W Buescher Manuel Rotenberg

2022

©Jordan C. Smith, 2022 All rights reserved.

The Thesis of Jordan C. Smith is approved, and it is acceptable in quality and form for publication on microfilm and electronically: _____________________________________________________________ _____________________________________________________________ _____________________________________________________________ _____________________________________________________________ _____________________________________________________________ Chair

University of California, San Diego 2022 DEDICATION Lee Kenneth Richardson

TABLE OF CONTENTSSignature Page................................................................................................................ iii Dedication....................................................................................................................... iv Table of Contents............................................................................................................ v Acknowledgements........................................................................................................ vi Abstract of the Thesis..................................................................................................... vii Bibliography……………………………………………………………………………viii

ACKNOWLEDGEMENTS To the entire Theatre & Dance Faculty at University of California, San Diego including Eva Barnes, Marco Barricelli, Kyle Blair, Stephen Buescher, Jennifer Chang, Allen Gilmore, Carla Harding, Ursula Meyer, Richard Robichaux, Eileen Troberman, Linda Vickerman, Kim Walsh

Special Thanks to my mother Iris L. Sykes and father Richard C. Smith Jr. thank you doesn’t seem like a sufficient word to describe my gratitude for y’all. I hope to continuously make y’all proud as I progress through my career.

To my grandparents Richard C. Smith Sr. and Theresa Smith I am the artist who I am today because you’ve lived your artistic truth fully and boldly.

To my grandmother Patricia D. Henderson for the words of encouragement and reminding me of who I am when I wanted to give up.

Lastly, special thanks To Lee Kenneth-Richardson, the greatest acting teacher I ever had. I hope from heaven I am making you proud.

ABSTRACT OF THE THESIS

The Risk of Living From Your Heart

By

Jordan C. Smith Master of Fine Arts in Theatre and Dance (Acting) University of California San Diego 2022 Ursula Meyer, Chair

Sticks and stones may break my bones but words will never hurt me. A common phrase I heard growing up. As I’ve gotten older I’ve realized how ironic it is that I was conditioned to not take words to heart yet words come from the heart. There is a magnetic power that words hold as saying a certain string of words produces a feeling like that of certain musical chords evoke a feeling. It is estimated that Shakespeare invented over 1700 words in the English language that we still use today. The words are found in plays that are near and dear to millions of people. Examples include Hamlet, Macbeth, Taming of the Shrew, and so much more. Performing Shakespeare has always been often debated and I don’t have an answer for one clear way to perform Shakespeare but there is a belief that Shakespeare wrote in correlation to a character's thoughts in most of his works. In the modern 21st century we’ve been conditioned to think before we speak and to not really express what you are really thinking in the moment so you won’t be perceived as uncouth. But Shakespeare ploys soliloquies in his text as moments where the character goes down the rabbit hole of their thoughts. John Barton who inspired esteemed English Director Michael Langham, believed that Shakespeare’s text was meant to be trusted and surrendered to. That if an actor and director allowed themselves to be guided by the text that there would be a freedom instead of a fear of the verse being a threat to throw the actor off. Living Thought is a concept that is notably known as a character grappling with the giving circumstance of what's happening and finding the words in the moment. This is something that isn’t foreign to your average person. When probed with a question our eyes look away or in the distance to search for the words that will answer that question accordingly. It's the same in Shakespeare the words spitball and spitball and what the character might have thought would be two sentences turns into a monologue. The character is living the thoughts out loud instead of keeping it in their head. There is a huge risk and fear of performing text with this concept. “What if I forget my lines?” “Maybe I should learn my lines in a pattern so that I don’t throw myself or my cast mates off?” But what I’ve learned from this is that is exactly what the character feels. In embracing that fear and that risk it adds to the discovery and wonder in living in the moment of finding the words to say just as the characters are in the moment of their circumstance. And in doing that feelings and emotions pour out not because you are enforcing a feeling but because an actor is surrendering to the words holding the weight of something stronger than sticks and stones, your heart.

Bibliography

Recent advances in liquid biopsy analysis have gravitated towards the utilization of cell-free DNA (cfDNA) in biofluids for cancer screening and treatment guidance. Many non-mutation aspects of cell-free DNA, such as fragment size and methylation, have demonstrated promising clinical utility for cancer detection. However, the presenting populations of cfDNA are influenced by pre-analytical steps such as DNA extraction and library preparation. We hypothesized that conventional workflows excluded a substantial portion of short fragment cfDNA in plasma. In this thesis, we detail the development of a next-generation sequencing pipeline, "Broad Range Cell-free DNA Sequencing" (BRcfDNA-Seq), which combines low-molecular weight nucleic acid extraction with a single-stranded library preparation to circumvent fragment size and strandedness limitations of conventional sequencing. In plasma, using BRcfDNA-Seq revealed the presence of ~50nt ultrashort cell-free DNA (uscfDNA) in addition to 167bp double-stranded mononucleosomal cell-free DNA (mncfDNA). Molecular and genomic analysis showcased that uscfDNA is distinct from mncfDNA in that it is single-stranded, is enriched in regulatory elements such as promoters, exons, and introns, and contains substantial G-quadruplex sequences. We examine if these unique uscfDNA features could be used as potential biomarkers to differentiate between plasma samples from non-cancer and non-small cell lung carcinoma subjects (NSCLC). We observed significant differences in functional element peaks, fragmentomics, end-motif profiles, and G-quadruplex abundance between the uscfDNA of these cohorts. Next, we investigated the methylation characteristics of uscfDNA by introducing a novel method of appending single-stranded premethylated adapters to cfDNA fragments prior to bisulfite conversion, preventing degraded genomic DNA from artificially occluding shorter cfDNA. We observed that the CpG sites of uscfDNA fragments were 15% hypomethylated compared to mncfDNA. Using a deconvolution algorithm, we inferred that uscfDNA derives from eosinophils, neutrophils, and monocytes. Later, we showed that the methylation characteristics of uscfDNA can be used to distinguish NSCLC and non-cancer subjects through differentially methylated region analysis and hypermethylated patterns of promoters, 5' UTR, and exon elements. Collectively, these studies support the uniqueness of the uscfDNA population from mncfDNA. Both genomic and epigenetic characteristics of uscfDNA demonstrate its potential clinical utility as an additional biomarker for liquid biopsy for NSCLC detection.

Organic photovoltaics are a potential source for cheap renewable energy. However one

of the main limitations to the field thus far has been scalability. Power conversion

efficiencies of photovoltaic films made on the laboratory scale of a couple of mm2

can be as high as 10%. However when the device area is increased to even tens of mm2

power conversion efficiency plummets. This work presented in this dissertation focuses

on understanding and circumventing the issues limiting the expansion of photovoltaic

processing to larger device areas.

One method of maintaining photovoltaic efficiency over a large range of device areas

is to use self-assembling materials to control the active layer morphology. These

materials should give the preferred morphology regardless of substrate size. I first study

photovoltaic devices utilizing self-assembling fullerenes designed to form nanometerscale wires within the film active layer. I show that fullerene that are able to form these nano-wires give a higher device range electron mobility through measuring the space charge limited current through a photovoltaic device. However the photovoltaic efficiencies of devices using these fullerenes remains low. I use time resolved microwave conductivity to measure the local nm-scale mobility of these fullerenes to show that there exists two ranges of mobilities in organic photovoltaic films. The nm-scale moiibility, governed by electronic overlap of neighboring molecules, and the device range mobility, governed by film morphology. I show that device performance is maximized when both mobility scales are taken into account.

Self-assembly is not the only method to achieve scalable organic photovoltaic devices.

Next, I show that the fabrication method of sequential processing can give identical

device performance between films fabricated on 7.2 mm2 and 34 mm2 substrates.

This is because films produced by sequential processing allows the polymer layer to

form prior to fullerene deposition, giving higher film quality. I show this scalability is

not seen in films that are fabricated through blendcasting, where the donor and acceptor

materials are blending together in solution and deposited together onto the substrate.

Sequential processing proves to be a powerful fabrication technique in making scalable

organic photovoltaic films. Therefore I develop a method of selecting fullerene

deposition solvents that are compatible with any donor polymer. I show that polymer

swelling is a key step in sequential processing film formation. I provide a procedure

on tuning the c interaction parameter between the fullerene deposition solvent and the

polymer layer. This is done by mixing a good polymer solvent with a poor polymer

solvent.This ensures the fullerene deposition solvent swells, but does not dissolve the

polymer film. By selecting the correct polymer solvent/non-solvent pair and ratio films

fabricated by sequential processing can reach device performances matching those fabricated by traditional blendcasting.

Introduction: Undiagnosed congenital heart disease and management of pediatric cardiogenic shock presents a diagnostic challenge for the emergency clinician. These diagnoses are rare and require a high index of suspicion given the overlap with more common pediatric pathology. Point-of-care ultrasound can assist in differentiating these presentations. We present a case of neonatal cardiogenic shock secondary to a previously undiagnosed congenital heart disease, specifically Shone complex, detected using point-of-care ultrasound. 

Case Report: A six-week-old female presented with severe respiratory distress and was found to be in cardiogenic shock secondary to a previously undiagnosed congenital heart defect.

Conclusion: Initial diagnosis of congenital heart disease is uncommon in the emergency department, but it should be recognized by clinicians given the high associated morbidity and mortality. Point-of-care ultrasound is a powerful tool to assist in evaluating for cardiac abnormalities as an etiology for undifferentiated shock in the pediatric population.

The human and mouse genomes share a number of long, perfectly conserved nucleotide sequences, termed ultraconserved elements(1). Whereas these regions can act as transcriptional enhancers when upstream of genes, those within genes are less well understood. In particular, the function of ultraconserved elements that overlap alternatively spliced exons of genes encoding RNA-binding proteins is unknown(1,2). Here we report that in every member of the human SR family of splicing regulators, highly or ultraconserved elements are alternatively spliced, either as alternative 'poison cassette exons' containing early in-frame stop codons, or as alternative introns in the 3' untranslated region. These alternative splicing events target the resulting messenger RNAs for degradation by means of an RNA surveillance pathway called nonsense-mediated mRNA decay. Mouse orthologues of the human SR proteins exhibit the same unproductive splicing patterns. Three SR proteins have been previously shown to direct splicing of their own transcripts, and one of these is known to autoregulate its expression by coupling alternative splicing with decay(3-5); our results suggest that unproductive splicing is important for regulation of the entire SR family. We find that unproductive splicing associated with conserved regions has arisen independently in different SR genes, suggesting that splicing factors may readily acquire this form of regulation.