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Third-Party Reactions To Performance Feedback, Daroon Mohammed Jalil Oct 2023

Third-Party Reactions To Performance Feedback, Daroon Mohammed Jalil

Psychology Theses & Dissertations

Although the provision of feedback has traditionally been treated as a dyadic event, I argue for the existence of a neglected third-party - the witness. Drawing from the dual process model of vicarious mistreatment and feedback intervention theory, I hypothesize that 1) third parties experience negative [positive] affect when witnessing an unjust [just] feedback event, 2) negative [positive] affect is stronger when feedback cues are self-referenced [task-referenced], and 3) negative [positive] affect is related to a subsequent decrease [increase] in feedback seeking intentions. Results from a 2x2 between-subjects experiment with 470 participants provide partial support for the hypotheses. Third-parties experienced …


Nightmares And Self-Injury Among High-Risk Adolescents: Examining The Role Of Emotion Regulation, Kinjal K. Patel Oct 2023

Nightmares And Self-Injury Among High-Risk Adolescents: Examining The Role Of Emotion Regulation, Kinjal K. Patel

Psychology Theses & Dissertations

Self-injurious thoughts and behaviors (SITBs) are a public health concern among youth. SITB rates rise drastically during adolescence -- a critical and sensitive developmental period characterized by dramatic changes in biological and social systems. Prior research has identified distal risk factors which tell us who is at risk for SITBs. Emerging research suggests proximal risk factors may be useful to identify when an individual may be at risk for SITBs. One promising proximal risk factor for SITBs is sleep problems. Although the relation between sleep problems and SITBs has been widely documented, little is known about the short-term, proximal links …


A New View Of Chlorophyll Dynamics In The Southern Mid-Atlantic Bight From A Two-Year High-Resolution Spray Glider Survey, Francesco Lane Oct 2023

A New View Of Chlorophyll Dynamics In The Southern Mid-Atlantic Bight From A Two-Year High-Resolution Spray Glider Survey, Francesco Lane

OES Theses and Dissertations

The southern Mid-Atlantic Bight (MAB) near Cape Hatteras, NC, USA, is likely a hotspot for the episodic export of carbon-rich shelf waters to the open ocean. Over a 2 year period, from March 2017 to May 2019, Spray gliders repeatedly occupied transects, along the slope and across the shelf, generating high-resolution chlorophyll fluorescence (fChl) data in the southern MAB. This study implements an fChl calibration method utilizing remotely sensing ocean color as a standard. We validate the method’s utility by demonstrating a reduction in post-calibration cross-mission fChl variability and demonstrating close correspondence between the calibrated fChl data and an in …


Relationship Between Learning Communities And Campus Residency On Sense Of Belonging Among First Year Undergraduates, Lanah Kathryn Stafford Oct 2023

Relationship Between Learning Communities And Campus Residency On Sense Of Belonging Among First Year Undergraduates, Lanah Kathryn Stafford

Educational Leadership & Workforce Development Theses & Dissertations

In higher education, sense of belonging has been linked to improved outcomes such as retention and academic achievement (e,g., Pittman & Richmond, 2007). Previous research has also identified participation in learning communities and campus residency as interventions which improve sense of belonging for students in this context (e.g., Solanki et al., 2019; Soria & Roberts, 2021). However, little research has been conducted to empirically study sense of belonging as a multidimensional construct, and no research has investigated interactions between on-campus residency and learning community participation on its development.

Data were collected from 1,072 first-year students on the Sense of Belonging …


Help-Seeking Behavior Among Resettled Refugee, Mahfoudha Sid’Elemine Oct 2023

Help-Seeking Behavior Among Resettled Refugee, Mahfoudha Sid’Elemine

Graduate Program in International Studies Theses & Dissertations

The refugee resettlement process is a huge part of refugees’ journeys in their new countries that has a lasting impact on their long-term integration. The literature highlights the importance of trust for successful refugee resettlement. This dissertation, however, challenges assumptions about the primary importance of “trust” and argues that the importance of trust is relative and can depend on the nature of the resettlement program and the perspective and background of refugees. In other words, there is not a one-size-fits-all of trust building in the context of resettlement. For certain resettlement programs trust building can be counterproductive when resources are …


Organic Carbon Decay Mediated By Mesopelagic Microbial Communities, Noah Jonathan Craft Oct 2023

Organic Carbon Decay Mediated By Mesopelagic Microbial Communities, Noah Jonathan Craft

OES Theses and Dissertations

Substantial remineralization of organic carbon occurs in the mesopelagic zone (i.e., the biological pump), the efficiency of which is responsible for the oceans’ capacity to store carbon originally derived from the atmosphere. To better understand how a substrate’s composition influences its degradation by mesopelagic microbial communities, we added treatments made of live algal cells, dead particulate organic carbon and dissolved organic carbon from 14C-labeled algal cultures to mesopelagic water collected in-situ. Each incubation took place in the laboratory over a period of months, during which PO14C, DO14C, ATP, prokaryote abundances and biochemical fractions were measured. …


Pulsed Electric Field Ablation: Mechanisms Of Differential Cell Sensitivity And Methods To Mitigate Neuromuscular Excitation, Emily Gudvangen Oct 2023

Pulsed Electric Field Ablation: Mechanisms Of Differential Cell Sensitivity And Methods To Mitigate Neuromuscular Excitation, Emily Gudvangen

Biomedical Engineering Theses & Dissertations

Ablation therapies aim to destroy tumors while maintaining minimal damage to surrounding healthy tissue. Pulsed electric field (PEF) ablation targets the cell membrane during the destruction of tissues, which consequently spares extracellular structures such as ducts and blood vessels, leaving the framework for tissue regeneration. However, the utility of PEF is limited by neuromuscular excitation, causing pain and involuntary muscle contraction. To identify PEF protocols that efficiently ablate tissue while minimizing neuromuscular stimulation, various PEF protocols differing in pulse duration, shape, and repetition rate were tested. The ratio of cell death and nerve excitation thresholds, which determines the range of …


The Effects Of Self-Regulated Learning On Community College Students Metacognition, Motivation And Achievement In Geoscience Courses, Melani A. Loney Oct 2023

The Effects Of Self-Regulated Learning On Community College Students Metacognition, Motivation And Achievement In Geoscience Courses, Melani A. Loney

Educational Leadership & Workforce Development Theses & Dissertations

This study investigated the impact of training in self-regulated learning on community college, geoscience students’ achievement, metacognition, time management, and science motivation scales. The study also investigated the impact of SRL training on these outcomes as a function of gender and ethnicity. During the Fall of 2022, 70 community college geoscience students from 9 different classes participated in the study. The classes were bifurcated with one half of the students in each class randomly assigned to the SRL treatment and the other half to the control condition. Each week, for 10 weeks during the semester, students in the treatment group …


Dental Hygiene Students Reported Physiological Symptoms Associated With Wearing An N95 Respirator Mask, Peyton Shea Butler Oct 2023

Dental Hygiene Students Reported Physiological Symptoms Associated With Wearing An N95 Respirator Mask, Peyton Shea Butler

Dental Hygiene Theses & Dissertations

Purpose: Physiological symptoms and comfort levels while wearing an N95 respiratory mask has not been examined with dental hygienists. The purpose of this study was to investigate dental hygiene students reported physiological symptoms and comfort perception while wearing an N95 respirator mask during patient care appointments. Methods: After IRB approval (IRB #1987754-2), a 16-item questionnaire was distributed through email to a convenience sample of 65 dental hygiene students. Questions assessed respiratory, dermatologic, cardiac, mask mouth and general physiological symptoms, as well as comfort levels. Additionally, participants were asked to respond to demographic questions and one open ended question inquiring about …


Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut Oct 2023

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …


Biomechanical Adaptations While Performing Bilateral Drop Landings With A Unilateral Ankle Tape Application, Eric Daniel Jenkins Oct 2023

Biomechanical Adaptations While Performing Bilateral Drop Landings With A Unilateral Ankle Tape Application, Eric Daniel Jenkins

Rehabilitation Sciences Theses & Dissertations

Ankle sprains are the most common injury in sport and exercise performance, which makes the utilization of ankle taping a common procedure to both prevent potential sprain, as well as protect against reinjury. However, unilateral ankle taping may have unintended consequences on the mechanics of the ankle and other joints of both legs. The aim of this dissertation was to determine the effects of ankle taping on lower body kinetics and kinematics, stiffness, and coordination during a bilateral landing task.

Twelve female participants completed a total of 90 drop landings across two visits, randomized from landing platforms of 30, 45, …


Complex Dynamics Of Contention: Towards A Generative Model Of Social Dissent, Travis Holmes Oct 2023

Complex Dynamics Of Contention: Towards A Generative Model Of Social Dissent, Travis Holmes

Graduate Program in International Studies Theses & Dissertations

In 2003, McAdam et al. released their seminal work Dynamics of Contention as a challenge to scholars within the field of contentious politics. In it, they claimed that the field required a refocusing from static and topical arguments splintered into various disciplines, to a more unified research agenda in search of causal mechanisms. In the spirit of their work, this study seeks to revisit this original critique considering more recent scholarship in the fields of Complexity and Systems Sciences along with certain technological advances in the field of computational social science, namely, the Agent-Based Model (ABM). In addition, both computational …


Fabrication Of Smooth Sac305 Thin Films Via Magnetron Sputtering And Evaluations Of Microstructure, Creep, And Electrical Resistivity, Manish Ojha Oct 2023

Fabrication Of Smooth Sac305 Thin Films Via Magnetron Sputtering And Evaluations Of Microstructure, Creep, And Electrical Resistivity, Manish Ojha

Mechanical & Aerospace Engineering Theses & Dissertations

SAC305 (96.5%Sn-3%Ag-0.5%Cu) is the leading alternative to the traditional Sn-Pb solder eutectic alloy owing to its low melting temperature, better compatibility with other components, and excellent mechanical/structural properties. In the realm of modern electronics, where devices are increasingly miniaturized, the design and characterization of thin solder joints become paramount. The orientation and size of the grains within the solder can influence its ability to withstand mechanical stresses. However, research on SAC thin films remains sparse, and these films present unique challenges and characteristics compared to their bulk counterparts, influenced by factors like interfaces, stresses, thickness, microstructure, and the nature of …


Modified Vaccine Vectors To Understand Adjuvant Functions Of Listeria During Chronic Schistosomiasis, Stephanie K. Norwood Oct 2023

Modified Vaccine Vectors To Understand Adjuvant Functions Of Listeria During Chronic Schistosomiasis, Stephanie K. Norwood

Biological Sciences Theses & Dissertations

Vaccination is one of the most effective strategies employed to prevent infectious diseases. Successful vaccination is dependent upon the induction of a specific, robust, and prolonged immune response. One of the major challenges faced by vaccine development is vaccine failure due to host-related factors that can modulate the immune system, which leads to non-responsiveness to vaccinations. The generation of new vaccine strategies is imperative to combat these effects. Live bacterial vectors are one approach used as they can elicit humoral immunity, cellular immunity, or both. Listeria monocytogenes is a Gram positive, intracellular pathogen that is an effective bacterial vaccine vector …


Investigation Of Nanosecond Pulsed Electric Fields (Nspef) Induced Anti-Cancer Mechanism And Enhanced B16f10 Melanoma Cancer Treatment, Kamal Asadipour Oct 2023

Investigation Of Nanosecond Pulsed Electric Fields (Nspef) Induced Anti-Cancer Mechanism And Enhanced B16f10 Melanoma Cancer Treatment, Kamal Asadipour

Biomedical Engineering Theses & Dissertations

The use of nanosecond pulsed electric fields (nsPEF) has emerged as a promising area of research with vast implications across various scientific disciplines. The ability to generate ultra-short, high-voltage electric pulses has paved the way for numerous applications, ranging from fundamental investigations of biological phenomena to the development of innovative medical therapies. The aim of this thesis is to highlight the importance of nsPEF in two critical areas: 1) Understanding the impact of subtle postpulse waveforms through a comprehensive analysis of two common pulse generators and 2) using this knowledge to advance melanoma treatment by enhancing the therapeutic effect of …


Tracing And Segmentation Of Molecular Patterns In 3-Dimensional Cryo-Et/Em Density Maps Through Algorithmic Image Processing And Deep Learning-Based Techniques, Salim Sazzed Oct 2023

Tracing And Segmentation Of Molecular Patterns In 3-Dimensional Cryo-Et/Em Density Maps Through Algorithmic Image Processing And Deep Learning-Based Techniques, Salim Sazzed

Computer Science Theses & Dissertations

Understanding the structures of biological macromolecules is highly important as they are closely associated with cellular functionalities. Comprehending the precise organization of actin filaments is crucial because they form the dynamic cytoskeleton, which offers structural support to cells and connects the cell’s interior with its surroundings. However, determining the precise organization of actin filaments is challenging due to the poor quality of cryo-electron tomography (cryo-ET) images, which suffer from low signal-to-noise (SNR) ratios and the presence of missing wedge, as well as diverse shape characteristics of actin filaments. To address these formidable challenges, the primary component of this dissertation focuses …


Dynamics Of The Dynll1-Mre11 Complex Regulate Dna End Resection And Recruitment Of Shieldin To Dsbs, Michelle L Swift, Rui Zhou, Aleem Syed, Lisa A Moreau, Bartłomiej Tomasik, John A Tainer, Panagiotis A Konstantinopoulos, Alan D D'Andrea, Yizhou Joseph He, Dipanjan Chowdhury Oct 2023

Dynamics Of The Dynll1-Mre11 Complex Regulate Dna End Resection And Recruitment Of Shieldin To Dsbs, Michelle L Swift, Rui Zhou, Aleem Syed, Lisa A Moreau, Bartłomiej Tomasik, John A Tainer, Panagiotis A Konstantinopoulos, Alan D D'Andrea, Yizhou Joseph He, Dipanjan Chowdhury

Faculty, Staff and Student Publications

The extent and efficacy of DNA end resection at DNA double-strand breaks (DSB) determine the repair pathway choice. Here we describe how the 53BP1-associated protein DYNLL1 works in tandem with the Shieldin complex to protect DNA ends. DYNLL1 is recruited to DSBs by 53BP1, where it limits end resection by binding and disrupting the MRE11 dimer. The Shieldin complex is recruited to a fraction of 53BP1-positive DSBs hours after DYNLL1, predominantly in G1 cells. Shieldin localization to DSBs depends on MRE11 activity and is regulated by the interaction of DYNLL1 with MRE11. BRCA1-deficient cells rendered resistant to PARP inhibitors by …


Comparisons Of Medical Cost Trajectories Between Non-Hispanic Black And Non-Hispanic White Patients With Newly Diagnosed Localized Prostate Cancer, Yu Liu, Shikun Wang, Liang Li, Ying Xu, Yu Shen, Ya-Chen Tina Shih Oct 2023

Comparisons Of Medical Cost Trajectories Between Non-Hispanic Black And Non-Hispanic White Patients With Newly Diagnosed Localized Prostate Cancer, Yu Liu, Shikun Wang, Liang Li, Ying Xu, Yu Shen, Ya-Chen Tina Shih

Faculty, Staff and Student Publications

Objectives: This study applied a recently developed statistical method to compare the mean cost trajectories between non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients with localized prostate cancer conditioning on patients' survival.

Methods: In this observational study, we modeled cost trajectories of NHW and NHB patients with localized prostate cancer for 3 survival durations: 24, 48, and 72 months. We also compared the cost trajectories between NHW and NHB, stratified by comorbidities scores.

Results: We find that the mean cost trajectories of NHB were significantly higher than the trajectories of NHW in the last 12 months before death, regardless of …


Cheiloscopy Examination And Classification Of Lip Prints With And Without Parafunctional Oral Habits: A Cross-Sectional Observation Study, Emily Smith Regan Oct 2023

Cheiloscopy Examination And Classification Of Lip Prints With And Without Parafunctional Oral Habits: A Cross-Sectional Observation Study, Emily Smith Regan

Dental Hygiene Theses & Dissertations

Problem: Lip prints are unique and have potential for use as a human identifier. The purpose of this study was to observe possible cheiloscopy differences of individuals with and without parafunctional oral habits. Additionally, inter-rater reliability (IRR) of lip print examiners was observed. Methods: This IRB approved blinded cross-sectional observational study collected lip prints from sixty-six individuals using lipstick and adhesive tape to transfer lip prints to white bond paper for viewing purposes. Each set of included lip prints was divided into quadrants and dichotomized as those with or without an oral parafunctional habit. Each quadrant sample was manually analyzed …


A Mindful Search For Basic Writing Identities: Constellating Contemplative Classroom Pedagogies, Classroom Community Circles, And Critical Discourse Analysis In A Cultural Rhetorics Ecology, Elizabeth Edwards Weems Oct 2023

A Mindful Search For Basic Writing Identities: Constellating Contemplative Classroom Pedagogies, Classroom Community Circles, And Critical Discourse Analysis In A Cultural Rhetorics Ecology, Elizabeth Edwards Weems

English Theses & Dissertations

Many Basic Writing students have stories which are informed by traumas, othering, and marginalization. Finding pedagogies which address students’ stories, in addition to meeting academic goals, is crucial. Sometimes, students question how improving their reading and writing skills can help them navigate other areas of their education and experiences, especially their lives outside of academia. I have worked to create a kairotic pedagogy which invites students to read and write ‘the word and the world’ (Freire, 1970; 1988). Using Contemplative Classroom Pedagogies, I attempted to follow Freire’s (1992) call to make “teaching a creative act, a critical act, and not …


Exploring The Lived Experiences Of Self-Identified Politically Conservative Students In Graduate Counseling Programs In Public Universities, Elizabeth A. Orrison Oct 2023

Exploring The Lived Experiences Of Self-Identified Politically Conservative Students In Graduate Counseling Programs In Public Universities, Elizabeth A. Orrison

Counseling & Human Services Theses & Dissertations

Professionals within the fields of social science predominantly identify as liberal (Woessner & Kelly-Woessner, 2015) and many issues related to politics, such as power and oppression, are inherent and central to the social science fields (Lerner, 2020). Past research has shown the potential for political bias in academia, which has been linked to the lack of representation of various political identities. Most research on political academic bias is not current, making it difficult to find relevant research on this topic published within the last ten years. Currently, there has been no identified research or scholarly production that specifically explores self-identified …


Machine Learning Approach To Activity Categorization In Young Adults Using Biomechanical Metrics, Nathan Q. C. Holland Oct 2023

Machine Learning Approach To Activity Categorization In Young Adults Using Biomechanical Metrics, Nathan Q. C. Holland

Mechanical & Aerospace Engineering Theses & Dissertations

Inactive adults often have decreased musculoskeletal health and increased risk factors for chronic diseases. However, there is limited data linking biomechanical measurements of generally healthy young adults to their physical activity levels assessed through questionnaires. Commonly used data collection methods in biomechanics for assessing musculoskeletal health include but are not limited to muscle quality (measured as echo intensity when using ultrasound), isokinetic (i.e., dynamic) muscle strength, muscle activations, and functional movement assessments using motion capture systems. These assessments can be time consuming for both data collection and processing. Therefore, understanding if all biomechanical assessments are necessary to classify the activity …


Do Microplastics, Vibrio Bacteria, And Warming Water Temperatures Cause Disease In The Northern Star Coral, Astrangia Poculata?, Heather Leigh Sheffey Oct 2023

Do Microplastics, Vibrio Bacteria, And Warming Water Temperatures Cause Disease In The Northern Star Coral, Astrangia Poculata?, Heather Leigh Sheffey

OES Theses and Dissertations

As marine plastic pollution increases, it becomes imperative to study the effects of microplastics on marine fauna. Marine plastic debris is a vector for disease to marine invertebrates (Lamb et al., 2018; Rotjan et al., 2019). In this context, studies have shown Astrangia poculata will consume microplastics as they do their normal food (Allen et al, 2017; Rotjan et al., 2019). Further, with temperatures increasing worldwide, there is a concern the virulence of disease-causing bacteria will increase (Vezzulli et al., 2015). In a series of manipulative laboratory experiments, this study quantified changes in respiration rates and visual health of Astrangia …


Emotional Intelligence In Difficult Decision-Making: A Multiple-Case Study Of Community College Academic Deans, Ekaterina Kalinina Brooks Oct 2023

Emotional Intelligence In Difficult Decision-Making: A Multiple-Case Study Of Community College Academic Deans, Ekaterina Kalinina Brooks

Educational Leadership & Workforce Development Theses & Dissertations

The decisions made by leaders noticeably impact employee morale and influence the fulfillment of the organizational mission. However, making decisions can be challenging when options are complex and involve multiple risks and benefits. Navigating such decisions in an era of technology when decisions are more transparent than ever before can be particularly difficult for academic deans in community colleges. These mid-level administrators often face internal conflicts stemming from the nature of their positions, campus politics, and the challenge of working between the competing interests of faculty and senior leaders.

Over the last three decades, research has pointed out that strong …


Genotyping Of The Tick-Borne Pathogen Rickettsia Parkeri, Rebecca Lynn Ferrara Oct 2023

Genotyping Of The Tick-Borne Pathogen Rickettsia Parkeri, Rebecca Lynn Ferrara

Biological Sciences Theses & Dissertations

Rickettsia parkeri is a pathogen of interest to public health as the causative agent of R. parkeri rickettsiosis. Amblyomma maculatum, a vector of R. parkeri, is currently undergoing a range expansion out of its historic range along the Gulf Coast of the United States, including northwards into Southeastern Virginia. Within this expansion front, the prevalence of R. parkeri within A. maculatum differs from the historic range; the historic range has a prevalence of 7.9- 38.6% while the expansion front in SE VA has a prevalence of 41.8-55.7%. While the reason for this disparity has not been established, one …


Antibody Response To Sars-Cov-2 Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Evobrutinib: A Bruton's Tyrosine Kinase Inhibitor, Amit Bar-Or, Anne H Cross, Anthony L Cunningham, Yann Hyvert, Andrea Seitzinger, Hans Gühring, Elise E Drouin, Nektaria Alexandri, Davorka Tomic, Xavier Montalban Oct 2023

Antibody Response To Sars-Cov-2 Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Evobrutinib: A Bruton's Tyrosine Kinase Inhibitor, Amit Bar-Or, Anne H Cross, Anthony L Cunningham, Yann Hyvert, Andrea Seitzinger, Hans Gühring, Elise E Drouin, Nektaria Alexandri, Davorka Tomic, Xavier Montalban

2020-Current year OA Pubs

BACKGROUND: Evobrutinib is an oral, central nervous system (CNS)-penetrant and highly selective covalent Bruton's tyrosine kinase inhibitor under clinical development for patients with relapsing multiple sclerosis (RMS).

OBJECTIVE: To investigate the effect of evobrutinib on immune responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinated patients with RMS from a Phase II trial (NCT02975349).

METHODS: A

RESULTS: In the vaccinated subgroup, mean/minimum evobrutinib exposure pre-vaccination was 105.2/88.7 weeks. In total, 43 of 45 patients developed/increased S1/S2 IgG antibody levels post-vaccination; one patient's antibody response remained negative post-vaccination and the other had antibody levels above the upper limit of detection, …


Preclinical Development Of 1b7/Cd3, A Novel Anti-Tslpr Bispecific Antibody That Targets Crlf2-Rearranged Ph-Like B-All, Ze Tian, Chunhua Shi, Guojun Yang, Jason K Allen, Qing Shi, Amin Al-Shami, Jill Wardell Olson, Melinda G Smith, Qing Chang, Jasbir Kaur, Junping You, Timothy E Lofton, Michelle A Gonzalez, Qi Zhang, Dongxing Zha, Sarah K Tasian, Nitin Jain, Marina Y Konopleva, Timothy Heffernan, Jeffrey J Molldrem Oct 2023

Preclinical Development Of 1b7/Cd3, A Novel Anti-Tslpr Bispecific Antibody That Targets Crlf2-Rearranged Ph-Like B-All, Ze Tian, Chunhua Shi, Guojun Yang, Jason K Allen, Qing Shi, Amin Al-Shami, Jill Wardell Olson, Melinda G Smith, Qing Chang, Jasbir Kaur, Junping You, Timothy E Lofton, Michelle A Gonzalez, Qi Zhang, Dongxing Zha, Sarah K Tasian, Nitin Jain, Marina Y Konopleva, Timothy Heffernan, Jeffrey J Molldrem

Faculty, Staff and Student Publications

Patients harboring CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL) face a 5-year survival rate as low as 20%. While significant gains have been made to position targeted therapies for B-ALL treatment, continued efforts are needed to develop therapeutic options with improved duration of response. Here, first we have demonstrated that patients with CRLF2-rearranged Ph-like ALL harbor elevated thymic stromal lymphopoietin receptor (TSLPR) expression, which is comparable with CD19. Then we present and evaluate the anti-tumor characteristics of 1B7/CD3, a novel CD3-redirecting bispecific antibody (BsAb) that co-targets TSLPR. In vitro, 1B7/CD3 exhibits optimal binding to both human and cynomolgus CD3 and TSLPR. …


Nuclear Smooth Muscle Α-Actin Participates In Vascular Smooth Muscle Cell Differentiation, Callie S Kwartler, Albert J Pedroza, Anita Kaw, Pujun Guan, Shuangtao Ma, Xue-Yan Duan, Caroline Kernell, Charis Wang, Jose Emiliano Esparza Pinelo, Mikayla S Borthwick Bowen, Jiyuan Chen, Yuan Zhong, Sanjay Sinha, Xuetong Shen, Michael P Fischbein, Dianna M Milewicz Oct 2023

Nuclear Smooth Muscle Α-Actin Participates In Vascular Smooth Muscle Cell Differentiation, Callie S Kwartler, Albert J Pedroza, Anita Kaw, Pujun Guan, Shuangtao Ma, Xue-Yan Duan, Caroline Kernell, Charis Wang, Jose Emiliano Esparza Pinelo, Mikayla S Borthwick Bowen, Jiyuan Chen, Yuan Zhong, Sanjay Sinha, Xuetong Shen, Michael P Fischbein, Dianna M Milewicz

Faculty, Staff and Student Publications

Missense variants throughout ACTA2, encoding smooth muscle α-actin (αSMA), predispose to adult-onset thoracic aortic disease, but variants disrupting arginine 179 (R179) lead to Smooth Muscle Dysfunction Syndrome (SMDS) characterized by diverse childhood-onset vascular diseases. Here we show that αSMA localizes to the nucleus in wildtype (WT) smooth muscle cells (SMCs), enriches in the nucleus with SMC differentiation, and associates with chromatin remodeling complexes and SMC contractile gene promotors. The ACTA2 p.R179 αSMA variant shows decreased nuclear localization. Primary SMCs from Acta2SMC-R179C/+ mice are less differentiated than WT SMCs in vitro and in vivo and have global changes in …


Phenotype And Fate Of Liver-Resident Cd8 T Cells During Acute And Chronic Hepacivirus Infection, Piyush Dravid, Satyapramod Murthy, Zayed Attia, Cole Cassady, Rahul Chandra, Sheetal Trivedi, Ashish Vyas, John Gridley, Brantley Holland, Anuradha Kumari, Arash Grakoui, John M Cullen, Christopher M Walker, Himanshu Sharma, Amit Kapoor Oct 2023

Phenotype And Fate Of Liver-Resident Cd8 T Cells During Acute And Chronic Hepacivirus Infection, Piyush Dravid, Satyapramod Murthy, Zayed Attia, Cole Cassady, Rahul Chandra, Sheetal Trivedi, Ashish Vyas, John Gridley, Brantley Holland, Anuradha Kumari, Arash Grakoui, John M Cullen, Christopher M Walker, Himanshu Sharma, Amit Kapoor

Faculty, Staff and Student Publications

Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and chronic rodent HCV-like virus (RHV) infections in lab mice. Here, we developed MHC class I and class II tetramers to characterize the serial changes in RHV-specific CD8 and CD4 T cells during acute and chronic infection in C57BL/6J mice. RHV infection induced rapid expansion of T cells targeting viral structural and nonstructural proteins. After virus clearance, the virus-specific T cells transitioned from effectors to long-lived liver-resident memory T cells (TRM). The effector and …


Single-Cell Dissection Of Tumor Microenvironmental Response And Resistance To Cancer Therapy, Yikai Luo, Han Liang Oct 2023

Single-Cell Dissection Of Tumor Microenvironmental Response And Resistance To Cancer Therapy, Yikai Luo, Han Liang

Faculty, Staff and Student Publications

Cancer treatment strategies have evolved significantly over the years, with chemotherapy, targeted therapy, and immunotherapy as major pillars. Each modality leads to unique treatment outcomes by interacting with the tumor microenvironment (TME), which imposes a fundamental selective pressure on cancer progression. The advent of single-cell profiling technologies has revolutionized our understanding of the intricate and heterogeneous nature of the TME at an unprecedented resolution. This review delves into the commonalities and differential manifestations of how cancer therapies reshape the microenvironment in diverse cancer types. We highlight how groundbreaking immune checkpoint blockade (ICB) strategies alone or in combination with tumor-targeting treatments …