Digital Commons Network^™

The Role Of The Infralimbic-Basal Forebrain Pathway In Fear Extinction, Carolina Maria Fernandes Henriques

Dissertations, Theses, and Capstone Projects

The medial prefrontal cortex (mPFC) is a key region for emotion regulation, and its failure to regulate extinction of aversive memories is associated with Post Traumatic Stress Disorder. Study of how the Infralimbic cortex (IL), a subregion of the mPFC, directly communicates with the Basolateral Amygdala (IL-BLA), has thus far failed to uncover the circuit mechanisms that lead to mPFC-mediated amygdala suppression of firing and diminished fear responses during extinction retrieval. One problem of this model is that it doesn’t incorporate indirect IL communication with the BLA. A key region to help understand how IL modulates extinction is the basal …

Studying Lake Surface Temperature Variabilities At Regional And Global Scales Using Remote Sensing And In-Situ Observations, Abdou Rachid Bah

Dissertations, Theses, and Capstone Projects

Surface temperature changes can be effectively monitored by employing remote sensing thermal infrared (TIR) data, offering advantages such as improved spatial and temporal coverage. Notably, this approach enables observation without disturbing the studied object and overcomes accessibility challenges in the study regions. The study utilizes remotely sensed data from Landsat 8, Geostationary Operational Environmental Satellites-R series (GOES-R), and the Moderate Resolution Imaging Spectroradiometer (MODIS) thermal infrared bands. These satellite TIR data are instrumental in model development and understanding patterns and processes in environmental systems. In my dissertation, I employed remote sensing tools, specifically Landsat 8, GOES-R, and MODIS Aqua temperature …

Stereospecific Cross-Coupling Reactions Of Vinyl Triflates And An Investigation Of The Synthesis And Reactivity Of Activated Alkyltricyclohexylstannanes, Pejman Ghaemimohammadi

Dissertations, Theses, and Capstone Projects

Organic chemistry exists in all aspects of everyday life from polymers to pharmaceutics. Formation of carbon-carbon bonds is essential for the synthesis of complex organic compounds. This goal can be achieved by using transition metal catalysts. Second-row transition metals such as Pd, Pt, Rh, and Ir have shown remarkable efficacy in these reactions. Metal-catalyzed cross-coupling reactions form carbon-carbon bonds between electrophiles and nucleophiles using transition metal catalysts. Pd is mainly used in this reaction.

Transition metal-catalyzed cross-coupling reactions that form a bond between two C(sp²) carbons have been widely studied over the past decades. C(sp²)-C(sp^{3 …}

Biomolecular Crystals As Functional Materials, Fahmeed Khan Sheehan

Dissertations, Theses, and Capstone Projects

The field of supramolecular chemistry has undergone significant evolution over the last few decades, progressing from fundamental studies of self-assembling systems to the rational design of functional materials with exceptional properties. Among these materials, short peptides have emerged as a chemically simple yet highly versatile class of biomimetic compounds. Initially, short peptides were used as model systems to understand larger protein interactions. As the field progressed, short peptides were found to have exceptional functionality, and are now explored as functional nanomaterials for diverse applications. In many cases, short peptide materials have displayed properties not found in biology, in some cases …

Abortion Politics And The Rise Of Movement Jurists, Robert L. Tsai, Mary Ziegler

Faculty Scholarship

This Article employs the Supreme Court's decision in Dobbs v. Jackson Women's Health Organization and litigation in its wake as the jumping off point to reconsider the connections between judges, the Constitution, and social movements. That movements influence constitutional law, and that judicial pronouncements in turn are reshaped by politics, is well-established. But, while these accounts of legal change depend upon judges to embrace movement ideas, less has been written about the conditions under which judicial entrenchment can be expected to take place. There may, in fact, be different types of judicial dispositions towards external political phenomena.

In this Article, …

The Dichotomy Of Threat And Deprivation As Subtypes Of Childhood Maltreatment: Differential Functional Connectivity Patterns Of Threat And Reward Circuits In An Adult Trauma Sample, Michael T. Liuzzi, Farah Harb, Kevin Petranu, Ashley A. Huggins, E. Kate Webb, Jacklynn M. Fitzgerald, Jessica L. Krukowski, Tara A. Miskovich, Terri A. Deroon-Cassini, Christine L. Larson

Psychology Faculty Research and Publications

Background

Childhood maltreatment is associated with reduced activation of the nucleus accumbens, , a central region in the reward network, and overactivity in the amygdala, a key region in threat processing. However, the long-lasting impact of these associations in the context of later-life stress is not well understood. The current study explored the association between childhood threat and deprivation and functional connectivity of threat and reward regions in an adult trauma sample.

Methods

Trauma survivors (N = 169; mean age [SD] = 32.2 [10.3] years; female = 55.6%) were recruited from a level I trauma center. Two weeks after …

Experiences Of Racial Discrimination And Adverse Gene Expression Among Black Individuals In A Level 1 Trauma Center Sample, Claire M. Bird, E. Kate Webb, Steven W. Cole, Carissa W. Tomas, Jennifer M. Knight, Sydney C. Timmer-Murillo, Christine L. Larson, Terri A. Deroon-Cassini, Lucas Torres

Psychology Faculty Research and Publications

Up to 40% of individuals who sustain traumatic injuries are at risk for posttraumatic stress disorder (PTSD) and the conditional risk for developing PTSD is even higher for Black individuals. Exposure to racial discrimination, including at both interpersonal and structural levels, helps explain this health inequity. Yet, the relationship between racial discrimination and biological processes in the context of traumatic injury has yet to be fully explored. The current study examined whether racial discrimination is associated with a cumulative measure of biological stress, the gene expression profile conserved transcriptional response to adversity (CTRA), in Black trauma survivors. Two-weeks (T1) and …

Low Shear In Short-Term Impacts Endothelial Cell Traction And Alignment In Long-Term, Mohanish Chandurkar, Nikhil Mittal, Shaina P. Royer-Weeden, Steven D. Lehmann, Yeonwoo Rho, Sangyoon J. Han

Michigan Tech Publications

Within the vascular system, endothelial cells (ECs) are exposed to fluid shear stress (FSS), a mechanical force exerted by blood flow that is critical for regulating cellular tension and maintaining vascular homeostasis. The way ECs react to FSS varies significantly; while high, laminar FSS supports vasodilation and suppresses inflammation, low or disturbed FSS can lead to endothelial dysfunction and increase the risk of cardiovascular diseases. Yet, the adaptation of ECs to dynamically varying FSS remains poorly understood. This study focuses on the dynamic responses of ECs to brief periods of low FSS, examining its impact on endothelial traction-a measure of …

Low Shear In Short-Term Impacts Endothelial Cell Traction And Alignment In Long-Term, Mohanish K. Chandurkar, Nikhil Mittal, Shaina P. Royer-Weeden, Steven D. Lehmann, Yeonwoo Rho, Sangyoon J. Han

Michigan Tech Publications

Within the vascular system, endothelial cells (ECs) are exposed to fluid shear stress (FSS), a mechanical force exerted by blood flow that is critical for regulating cellular tension and maintaining vascular homeostasis. The way ECs react to FSS varies significantly; while high, laminar FSS supports vasodilation and suppresses inflammation, low or disturbed FSS can lead to endothelial dysfunction and increase the risk of cardiovascular diseases. Yet, the adaptation of ECs to dynamically varying FSS remains poorly understood. This study focuses on the dynamic responses of ECs to brief periods of low FSS, examining its impact on endothelial traction—a measure of …

Gene-Specific Acmg/Amp Classification Criteria For Germline Apc Variants: Recommendations From The Clingen Insight Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel\, Isabel Spier, Xiaoyu Yin, Marcy Richardson, Marta Pineda, Andreas Laner, Deborah Ritter, Julie Boyle, Pilar Mur, Thomas V O Hansen, Xuemei Shi, Khalid Mahmood, John-Paul Plazzer, Elisabet Ognedal, Margareta Nordling, Susan M Farrington, Gou Yamamoto, Stéphanie Baert-Desurmont, Alexandra Martins, Ester Borras, Carli Tops, Erica Webb, Victoria Beshay, Maurizio Genuardi, Tina Pesaran, Gabriel Capellá, Sean V Tavtigian, Andrew Latchford, Ian M Frayling, Sharon E Plon, Marc Greenblatt, Finlay A Macrae, Stefan Aretz, Insight-Clingen Hereditary Colon Cancer/Polyposis Variant Curation Expert Panel

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome.

Methods: Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants.

Results: The APC-specific criteria …

Utility Of A Low-Cost 3-D Printed Microscope For Evaluating Esophageal Biopsies, Daniel G Rosen, Evandro Sobroza De Mello, Sadhna Dhingra, Sanford M Dawsey, Joe Knapper, Richard Bowman, Sharmila Anandasabapathy

Center for Medical Ethics and Health Policy Staff Publications

In this manuscript we assessed the utility of a low-cost 3D printed microscope to evaluate esophageal biopsies. We conducted a comparative analysis between the traditional microscope and our 3-D printed microscope, utilizing a set of esophageal biopsy samples obtained from patients undergoing screening endoscopy. Two pathologists independently examined 30 esophageal biopsies by light microscopy and digital images obtained using a low-cost 3D printed microscope (Observer 1 and 2). The glass slide consensus diagnosis was compared to the findings of 2 additional pathologist who independently just reviewed the digital images (Observer 3 and 4). The intra-observer agreement was substantial to almost …

Deep Learning Prediction Boosts Phosphoproteomics-Based Discoveries Through Improved Phosphopeptide Identification, Alexander B Saltzman, Eric J Jaehnig, Jonathan T Lei, Qiang Gao, Bing Zhang

Faculty, Staff and Students Publications

Shotgun phosphoproteomics enables high-throughput analysis of phosphopeptides in biological samples. One of the primary challenges associated with this technology is the relatively low rate of phosphopeptide identification during data analysis. This limitation hampers the full realization of the potential offered by shotgun phosphoproteomics. Here we present DeepRescore2, a computational workflow that leverages deep learning-based retention time and fragment ion intensity predictions to improve phosphopeptide identification and phosphosite localization. Using a state-of-the-art computational workflow as a benchmark, DeepRescore2 increases the number of correctly identified peptide-spectrum matches by 17% in a synthetic dataset and identifies 19% to 46% more phosphopeptides in biological …

Distribution Of P2y And P2x Purinergic Receptor Expression Within The Intestine, Jacob L Perry, Sue E Crawford, Joseph M Hyser

Faculty, Staff and Students Publications

Nucleotides are potent extracellular signaling molecules during homeostasis, infection, and injury due to their ability to activate purinergic receptors. The nucleotide ATP activates P2X receptors (P2RXs), whereas the nucleotides ADP, ATP, UTP, and UDP-glucose selectively activate different P2Y receptors (P2RYs). Several studies have established crucial roles for P2 receptors during intestinal inflammatory and infectious diseases, yet the most extensive characterization of purinergic signaling has focused on immune cells and the central and enteric nervous systems. As epithelial cells serve as the first barrier against irritants and infection, we hypothesized that the gut epithelium may express multiple purinergic receptors that respond …

Proteome Analysis For Inflammation Related To Acute And Convalescent Infection, Suzanne M Mcdermott, Cecilia S Lindestam Arlehamn, Kristy O Murray, Linda K Bockenstedt, Maggie Kerwin, Elaine F Reed, Eva Harris, Ken Stuart, Bjoern Peters, Ana Sesma, Ruth R Montgomery, Minnie M Sarwal

Faculty, Staff and Students Publications

Infectious diseases are a significant burden in global healthcare. Pathogens engage with different host defense mechanisms. However, it is currently unknown if there are disease-specific immune signatures and/or if different pathogens elicit common immune-associated molecular entities to common therapeutic interventions. We studied patients enrolled through the Human Immunology Project Consortium (HIPC), which focuses on immune responses to various infections. Blood samples were collected and analyzed from patients during infection and follow-up time points at the convalescent stage. The study included samples from patients with Lyme disease (LD), tuberculosis (TB), malaria (MLA), dengue virus (DENV), and West Nile virus (WNV), as …

Zika Virus Co-Opts Microrna Networks To Persist In Placental Niches Detected By Spatial Transcriptomics, David N Moorshead, Michael D Jochum, Trang Do, Derek S O'Neil, Melissa A Suter, Kjersti M Aagaard

Faculty, Staff and Students Publications

BACKGROUND: Zika virus congenital infection evades double-stranded RNA detection and may persist in the placenta for the duration of pregnancy without accompanying overt histopathologic inflammation. Understanding how viruses can persist and replicate in the placenta without causing overt cellular or tissue damage is fundamental to deciphering mechanisms of maternal-fetal vertical transmission.

OBJECTIVE: Placenta-specific microRNAs are believed to be a tenet of viral resistance at the maternal-fetal interface. We aimed to test the hypothesis that the Zika virus functionally disrupts placental microRNAs, enabling viral persistence and fetal pathogenesis.

STUDY DESIGN: To test this hypothesis, we used orthogonal approaches in human and …

Regulation Of Androgen Receptor Stability By The Β1pix/Stub1 Complex

Faculty, Staff and Students Publications

The Androgen Receptor (AR) is essential in the development and differentiation of testes and male genitalia. AR expression is tightly regulated at the translational and posttranslational levels. AR posttranscriptional regulation is a major determinant of AR availability since AR is a direct target of E3 ubiquitin ligase STUB1. Our work indicated that the Rac/Cdc42 guanosine triphosphatase guanine nucleotide exchange factor, β1Pix, enhanced AR levels after AR stimulation in HEK293 and HeLa cells. AR stimulation decreased AR ubiquitination which is accompanied by increased β1Pix binding to AR. Ectopic expression of β1Pix decreased AR ubiquitination in Tm4 and HEK293 cells. We demonstrated …

Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium

Faculty, Staff and Students Publications

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( …

Loss Of The Auxiliary Α2Δ1 Voltage-Sensitive Calcium Channel Subunit Impairs Bone Formation And Anabolic Responses To Mechanical Loading, Julia M Hum, Alexander G Robling, Mary C Farach-Carson, William R Thompson

Faculty, Staff and Student Publications

Voltage-sensitive calcium channels (VSCCs) influence bone structure and function, including anabolic responses to mechanical loading. While the pore-forming (α1) subunit of VSCCs allows Ca2+ influx, auxiliary subunits regulate the biophysical properties of the pore. The α2δ1 subunit influences gating kinetics of the α1 pore and enables mechanically induced signaling in osteocytes; however, the skeletal function of α2δ1 in vivo remains unknown. In this work, we examined the skeletal consequences of deleting Cacna2d1, the gene encoding α2δ1. Dual-energy X-ray absorptiometry and microcomputed tomography imaging demonstrated that deletion of α2δ1 diminished bone mineral content and density in both male and female …

Infant Hedonic/Anhedonic Processing Index (Hapi-Infant): Assessing Infant Anhedonia And Its Prospective Association With Adolescent Depressive Symptoms, Jessica L. Irwin, Elysia Poggi Davis, Curt A. Sandman, Tallie Z. Baram, Hal S. Stern, Laura M. Glynn

Psychology Faculty Articles and Research

Background

Anhedonia, an impairment in the motivation for or experience of pleasure, is a well-established transdiagnostic harbinger and core symptom of mental illness. Given increasing recognition of early life origins of mental illness, we posit that anhedonia should, and could, be recognized earlier if appropriate tools were available. However, reliable diagnostic instruments prior to childhood do not currently exist.

Methods

We developed an assessment instrument for anhedonia/reward processing in infancy, the Infant Hedonic/Anhedonic Processing Index (HAPI-Infant). Exploratory factor and psychometric analyses were conducted using data from 6- and 12-month-old infants from two cohorts (N = 188, N = 212). …

Epigenetic Regulation In Cancer, Xiaohong Liu, Xing Wang, Feihan Zhou, Ruiling Xiao, Xiyuan Luo, Lei You, Yupei Zhao

Faculty, Staff and Student Publications

Epigenetic modifications are defined as heritable changes in gene activity that do not involve changes in the underlying DNA sequence. The oncogenic process is driven by the accumulation of alterations that impact genome's structure and function. Genetic mutations, which directly disrupt the DNA sequence, are complemented by epigenetic modifications that modulate gene expression, thereby facilitating the acquisition of malignant characteristics. Principals among these epigenetic changes are shifts in DNA methylation and histone mark patterns, which promote tumor development and metastasis. Notably, the reversible nature of epigenetic alterations, as opposed to the permanence of genetic changes, positions the epigenetic machinery as …

2024 February, Morehead State University. Office Of Communications & Marketing.

Morehead State Press Release Archive, 1961 to the Present

Press releases for February of 2024.

Identification Of Tungiasis Infection Hotspots With A Low-Cost, High-Throughput Method For Extracting Tunga Penetrans (Siphonaptera) Offhost Stages From Soil Samples–An Observational Study, Abneel K. Matharu, Paul Ouma, Margaret M. Njoroge, Billy L. Amugune, Ayako Hyuga, Francis Mutebi, Jürgen Krücken, Hermann Feldmeier, Lynne Elson, Ulrike Fillinger

All Peer-Reviewed Publications

Background The sand flea, Tunga penetrans, is the cause of a severely neglected parasitic skin disease (tungiasis) in the tropics and has received little attention from entomologists to understand its transmission ecology. Like all fleas, T. penetrans has environmental off-host stages presenting a constant source of reinfection. We adapted the Berlese-Tullgren funnel method using heat from light bulbs to extract off-host stages from soil samples to identify the major development sites within rural households in Kenya and Uganda. Methods and findings Simple, low-cost units of multiple funnels were designed to allow the extraction of >60 soil samples in parallel. We …

Deciphering The Intricate Hierarchical Gene Regulatory Network: Unraveling Multi-Level Regulation And Modifications Driving Secondary Cell Wall Formation, Zhigang Wei, Hairong Wei

Michigan Tech Publications

Wood quality is predominantly determined by the amount and the composition of secondary cell walls (SCWs). Consequently, unraveling the molecular regulatory mechanisms governing SCW formation is of paramount importance for genetic engineering aimed at enhancing wood properties. Although SCW formation is known to be governed by a hierarchical gene regulatory network (HGRN), our understanding of how a HGRN operates and regulates the formation of heterogeneous SCWs for plant development and adaption to ever-changing environment remains limited. In this review, we examined the HGRNs governing SCW formation and highlighted the significant key differences between herbaceous Arabidopsis and woody plant poplar. We …

Investigating The Mass Mortality Induced Factors Of Pearl Oyster (Pinctada Radiata) At Abu Dhabi Pearls Farm, Uae, Hamad Ahmed Almansoori

Theses

The aquaculture of shellfish plays a crucial role in enhancing maritime environments by mitigating algal blooms and improving water quality through the filtration of organic matter, nutrients, and bacteria. This study investigated the environmental factors influencing oyster (Pinctada radiata) mortalities through a comprehensive analysis of water quality in Al Mirfa and Al Mughirah farming sites of Abu Dhabi (UAE), from February 2021 to February 2022. To reach such understanding of the main factors led to mass mortalities of cultivated oysters, different monthly sampling and both chemical and biological analyses of the farm water, sediments as well as for both living …

Fy24 Usability Program Test #4: Assessing Perceptions Of Research Consultations, Lindsey Skaggs

Faculty and Staff Publications – Milner Library

The FY24 Usability Testing Program was designed to iteratively assess user experience at Milner Library. The program gathers data through usability testing of the library's website and discovery layer, as well as survey questions about users' experiences with library services. Test #4 gathers information from library users about their perceptions of research consultations to inform service development. Takeaways and recommendations are included in the report.

Psychological Impacts Of The Covid-19 Pandemic In A Hispanic Sample: Testing The Buffering Role Of Resilience And Perceived Social Support, Michiyo Hirai, Laura L. Vernon, Elizabeth N. Hernandez

Psychological Science Faculty Publications

The current study examined the effects of specific COVID-19 stressors (i.e., family member’s death due to COVID-19, COVID-19 infection, and school/financial stressors) on stress, anxiety, and depression and the potential buffering roles of resilience and perceived social support in the association between COVID-19 stressors and psychological symptoms in a Hispanic university student sample (n = 664). Participants were classified in three stressor groups: those reporting a family member’s death due to COVID-19 (15.7%), those reporting their own or a family member’s COVID-19 infection but no COVID-19 death (35.5%), and those reporting only school and/or financial stressors due to the …

Accessing Reactive Metal Hydrides Through Designed Heterometallic Bridges, Fernando Gonzalez, Edgardo De Leon, Manar M. Shoshani

School of Integrative Biological & Chemical Sciences Faculty Publications

A methodology to access reactive hydride moieties is highly desirable, yet limited. Multimetallic hydride fragments are notable for their heightened reactivity and catalysis, but deliberate access to these species is lacking. In this highlight, we discuss recent developments by our group in the design of a new heterometallic complex that invokes an architecture designed to provide modular access to reactive hydride moieties by leveraging metal hydrides in combination with pendent donors to a model heterotrimetallic Ni–(Al–H)2 complex. An amplification of insertion-based reactivity has been examined in the hydrofunctionalization of quinolines, and our complex substantially outperformed the parent aluminum hydride LAlH …

Validating Indigenous Farmers’ Practice In The Management Of The Fall Armyworm Spodoptera Frugiperda (J. E. Smith) In Maize Cropping Systems In Africa, Saliou Niassy, Evanson Rigan Omuse, John Emanuel Khang’Ati, Ines Bächinger, David Mfuti Kupesa, Xavier Cheseto, Benjamin W. Mbatha, Robert S. Copeland, Samira Abuelgasim Mohamed, Mphatso Gama, Joyce Mulila Mitti, Yeneneh Belayneh, Nicolas Delabays, François Lefort, Sunday Ekesi, Sevgan Subramanian

All Peer-Reviewed Publications

Before the invasion of the fall armyworm (FAW) Spodoptera frugiperda into Africa, smallholder farmers had been using indigenous practices such as applying fish soup to plants to manage stemborer pests. Although farmers have since begun adapting this practice against FAW, no attempt has been made to scientifically evaluate this practice. Therefore, we assessed the efficacy of applying fish soup to maize plants that were artificially infested with FAW under semi-field conditions. Our results showed that foliar damage is inversely correlated with the concentration of a fish soup and sugar solution, with the highest (100%) concentration resulting in the lowest foliar …

Transmission Of Amyloid-Β Pathology In Humans: A Perspective On Clinical Evidence, Celso S G Catumbela, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

Therapeutic Potential Of Combating Cancer By Restoring Wild-Type P53 Through Mrna Nanodelivery., Divya Kamath, Tomoo Iwakuma, Stefan H. Bossmann

Manuscripts, Articles, Book Chapters and Other Papers

Among the tumor suppressor genes, TP53 is the most frequently mutated in human cancers, and most mutations are missense mutations causing production of mutant p53 (mutp53) proteins. TP53 mutations not only results in loss of function (LOH) as a transcription factor and a tumor suppressor, but also gain wild-type p53 (WTp53)-independent oncogenic functions that enhance cancer metastasis and progression (Yamamoto and Iwakuma, 2018; Zhang et al., 2022). TP53 has extensively been studied as a therapeutic target as well as for drug development and therapies, however with limited success. Achieving targeted therapies for restoration of WTp53 function and depletion or repair …