bluuebunny/crossref_metadata_2025 huggingface dataset:
Question-based text summarization
Authors:   , Liu Mengwen , Hu Xiaohua , An Yuan
Published: July 2021

In the modern information age, finding the right information at the right time is an art (and a science). However, the abundance of information makes it difficult for people to digest it and make informed choices. In this thesis, we aim to help people who want to quickly capture the main idea of a piece of information before they read the details through text summarization. In contrast with existing works, which mainly utilize declarative sentences to summarize a text document, we aim to use a few questions as a summary. In this way, people would know what questions a given text document can address and thus they may further read it if they have similar questions in mind. A question-based summary needs to satisfy three goals, relevancy, answerability, and diversity. Relevancy measures whether a few questions can cover the main points that discussed in a text document; answerability measures whether answers to the questions are included in the text document; and diversity measures whether there is redundant information carried by the questions. To achieve the three goals, we design a two-stage approach which consists of question selection and question diversification. The question selection component aims to find a set of candidate questions that are relevant to a text document, which in turn can be treated as answers to the questions. Specifically, we explore two lines of approaches that have been developed for traditional text summarization tasks, extractive approaches and abstractive approaches to achieve the goals of relevancy and answerability, respectively. The question diversification component is designed to re-rank the questions with the goal of rewarding diversity in the final question-based summary. Evaluation on product review summarization tasks for two product categories shows that the proposed approach is effective for discovering meaningful questions that are representative for individual reviews. This thesis opens up a new direction in the intersection of information retrieval and natural language processing. Despite the evaluation on the product review domain, the thesis provides a general solution for question selection for many interesting applications and discusses the possibility of extending the problem to other domain-specific question-based text summarization tasks.
The Trust Factor between Meteorologists and Viewers and the Effects on Local Television Audience Retention
Authors:   , Nix-Crawford Brittney , Tedesco Albert S. , McHugh Michelle
Published: July 2021

Consumers have more options than ever when it comes to how they receive information pertaining to the weather, both locally and regionally. Because of the myriad of options, television and media managers across all markets in the United States are constantly fine-tuning their strategies to gain and retain viewers' trust. For many of those managers, that strategy relies heavily on audience members' impressions of the station's meteorologists. Specifically, trust is one thing that evokes a person's loyalty, leaving consumers with a positive impression. To understand the trust factor between the viewer and meteorologists in large media markets and how it impacts television managers' hiring and programming strategies, this research examines the three components that can be used to create and maintain trust between meteorologists and viewers. This research also examined meteorologists and executives at NBC 10, WCAU-TV in Philadelphia, the nation's fourth largest media market.
Interaction Between the AAA+ ATPase p97 and Its Cofactor Ataxin3 in Health and Disease
Authors:   , Rao Maya V. , Loll Patrick J.
Published: July 2021

p97 is an essential ATPase associated with various cellular activities (AAA+) that functions as a segregase in diverse cellular processes, including the maintenance of proteostasis. p97 interacts with different cofactors that target it to distinct pathways; an important example is the deubiquitinase ataxin3, which collaborates with p97 in endoplasmic reticulum associated degradation. However, the molecular details of this interaction have been unclear. We have characterized the binding of ataxin3 to p97, showing that ataxin3 binds with low-micromolar affinity to both wild-type p97 and mutants linked to degenerative disorders known as multisystem proteinopathy 1 (MSP1); we further showed that the stoichiometry of binding is one ataxin3 molecule per p97 hexamer. We have mapped the binding determinants on each protein, demonstrating that ataxin3's p97/VCP-binding motif (VBM) interacts with the inter-lobe cleft in the N-domain of p97. We also probed the nucleotide dependence of this interaction, confirming that ataxin3 and p97 associate in the presence of ATP and in the absence of nucleotide, but not in the presence of ADP. Our experiments suggest that an ADP-driven downward movement of the p97 N-terminal domain dislodges ataxin3 by inducing a steric clash between the D1-domain and ataxin3's C-terminus. In contrast, MSP1 mutants of p97 bind ataxin3 irrespective of their nucleotide state, indicating a failure by these mutants to translate ADP binding into a movement of the N-terminal domain. Our model provides a mechanistic explanation for how nucleotides regulate the p97-ataxin3 interaction and why atypical cofactor binding is observed with MSP1 mutants.
Crossing Cultural Barriers
Authors:   , Constancia Anna Maria , Schelly Hill Ellen
Published: July 2021

An overwhelming majority of studies focused on identity development in the U. S have been performed with predominantly or solely European American populations. In the U. S our ideas of mental health, including our assessment tools, diagnoses and treatment interventions, focus on the needs of the dominant European American culture, including those used in dance/movement therapy (DMT). This presents a limitation for therapists who work with ethnic minorities, since a large number of people who seek therapy do not identify themselves as part of the dominant [European American] culture (Dosamantes-Beaudry, 1997). This analysis of ethnic identity literature provides information about the verbal and nonverbal processes of ethnic identity formation, with a targeted focus on Mexican American identity development. While reviewing ethnic identity models and factors to consider in ethnic identity development, this thesis will analyze nonverbal communication and somatic experiences within the Hispanic culture to assess how Hispanic identity is shaped somatically and what differences, if any, exist between Hispanic identity and European American identity. A further analysis of the literature will reveal if factors can be identified that specifically influence Mexican American ethnic identity development. With the Hispanic population being the largest ethnic minority group in the U. S, and those of Mexican heritage making up the majority of this group, it is important for dance/movement therapists to be aware of the experiences of the Hispanic and Mexican American culture. This literature review explores the somatic experiences of the Hispanic population to discover concepts of body boundaries, body image, embodied racism and how these body experiences can influence the Hispanic population to possibly develop a different sense of the self.
Symphonic relevancy
Authors:   , Davis Lucretia , Brody Jean
Published: July 2021

Symphonic Relevancy is a case study on the Education and Community Engagement Programs of the Roanoke Symphony and Virginia Symphony Orchestras. The paper explores how two orchestras of the eight geographic regions from the state of Virginia provide education and community engagement services to their respective markets in a quest to stay relevant to their communities. The Roanoke Symphony is situated in the southwestern portion of the state and the Virginia Symphony Orchestra is positioned in the southeastern region of the state. This research examines each orchestra's role in its community for youth and adults, educational programming, community engagement activities, and the challenges that lie within. Data has been drawn from in-depth interviews, field research, and document analysis on the issues within each orchestra as it seeks to provide an accessible and enduring musical arts education in today's changing world. The predominant theme of Symphonic Relevancy is the need to educate. It is the education of our youth in school, young adults in college, and adults in the community that is an ongoing process for each orchestra. It is revealed that symphony orchestras play a vital role in their community, and solidifying the role each orchestra plays is heavily dependent on its location. It is proven that geography is a major component in each community's demographics and resources. Each orchestra will fulfil the needs of its community in a unique way, reveal the challenges presented, and work to remain relevant in its community.
Dance preservation archives
Authors:   , Dusell Kathryn A. , Brody Jean
Published: July 2021

Organizations that archive dance documentation assert that the use of archival materials can benefit many aspects of the creative process as well as the education of future dancers and choreographers. This thesis explores the relationship between choreographers and archivists and how current technology has affected access. This research looks at four different types of organizations to examine the state of dance preservation. I gathered data through phone interviews and reviewed online archive databases of the New York Public Library for the Performing Arts, the Library of Congress, Jerome Lawrence and Robert E. Lee Theatre Research Institute at Ohio State University, and Jacob's Pillow Dance. For archivists, keeping up with changing technology will be an ongoing challenge. Archivists will need to start working with choreographers and dance companies earlier in their careers to preserve digital materials before they disappear.
Motivating Millennial Volunteers in Arts and Cultural Organizations
Authors:   , Melczer Amanda Joy , Brody Jean
Published: July 2021

Millennials can be valuable assets to arts and cultural organizations. Through volunteerism, these organizations can build a strong relationship with this generation that can last into the future. Until this point, however, little research has been done to determine how arts and cultural organizations can motivate millennials to volunteer with their organizations. Through an online survey of millennials and interviews with volunteer managers and volunteers for arts and cultural organizations in Philadelphia, a model for best practices to motivate and maintain millennial volunteers can be developed. Arts organizations should focus on visibility of their volunteer opportunities highlighting their potential impact, providing flexible options for participation, and building a strong community within their organizations to appeal to this demographic.
Narrative Information Extraction with Non-Linear Natural Language Processing Pipelines
Authors:   , Valls Vargas Josep , Ontañón Santiago
Published: July 2021

Computational narrative focuses on methods to algorithmically analyze, model, and generate narratives. Most current work in story generation, drama management or even literature analysis relies on manually authoring domain knowledge in some specific formal representation language, which is expensive to generate. In this dissertation we explore how to automatically extract narrative information from unannotated natural language text, how to evaluate the extraction process, how to improve the extraction process, and how to use the extracted information in story generation applications. As our application domain, we use Vladimir Propp's narrative theory and the corresponding Russian and Slavic folktales as our corpus. Our hypothesis is that incorporating narrative-level domain knowledge (i.e., Proppian theory) to core natural language processing (NLP) and information extraction can improve the performance of tasks (such as coreference resolution), and the extracted narrative information. We devised a non-linear information extraction pipeline framework which we implemented in Voz, our narrative information extraction system. Finally, we studied how to map the output of Voz to an intermediate computational narrative model and use it as input for an existing story generation system, thus further connecting existing work in NLP and computational narrative. As far as we know, it is the first end-to-end computational narrative system that can automatically process a corpus of unannotated natural language stories, extract explicit domain knowledge from them, and use it to generate new stories. Our user study results show that specific error introduced during the information extraction process can be mitigated downstream and have virtually no effect on the perceived quality of the generated stories compared to generating stories using handcrafted domain knowledge.
A Thematic Analysis of Interviews with the Southeast Asian Refugees
Authors:   , Rahapsari Satwika , Schelly Hill Ellen
Published: July 2021

The purpose of this study is to understand Southeast Asian (SEA) refugees' resilience within their resettlement experience in the United States. Challenges to coping in the resettlement country for SEA refugees include stress, unemployment, lack of vocational skills, discriminations, and language barrier. However, despite the experience of adversity, survivors often show resiliency. This qualitative research used verbal interview methods combined with a movement elicitation (ME) procedure as the data collection method. Movement elicitation is guided expressive movement that is engaged within the verbal interview. Utilizing ME involved probing the interview response to clarify and deepen the themes related to resilience in SEA refugees. A thematic analysis method was conducted to identify themes within the interviews affecting resilience in SEA refugees. Eight themes emerged from the analysis of verbal interviews. Four of the themes pertained to the adversities during the resettlement experience: financial and employment-based problems; racial issues and discrimination; challenges in adjustment and acculturation process; the impact of rough, unsafe neighborhoods. Four themes described the elements promoting the SEA refugees resilience: acquired functional skills; drawing upon personal qualities; finding a sense of identity in family and beliefs; accepting social supports. The author discussed the implications of the themes for the use of dance/movement therapy support for SEA refugees during their resettlement process, and for future study.
Expression and Purification of The Hepatitis B Virus X Protein
Authors:   , Fakhoury Guila , Loll Patrick J.
Published: July 2021

The hepatitis B virus (HBV) genome is made of a small partially double-stranded, circular DNA that encodes four open-reading frames. One important protein encoded by the smallest open reading frame of the viral genome is HBV protein X; this protein has been shown to be essential for HBV replication. It has also been shown that the X protein plays an important role in the development of HBV-associated HCC. To this date, there is no three-dimensional structure available for HBx, and this may be due to the presence of disordered regions in HBx. Understanding the structure of X is essential for understanding its ordered and disordered boundaries as well as when using in-vitro assays to understand HBx functions. We propose expressing different truncated version of protein X in bacterial system, using different vectors that help stabilize the protein during purification. We expressed eight different versions of protein X plus, including the full-length protein, in three different vectors using BL21 bacterial cells as hosts. Our goal was to test the expression of these versions of the protein using small test-expression to see if any of the regions of the protein can be expressed. We use the same conditions used on large-scale expression. Our results show low expression of three different constructs in one of the vectors used in this experiment. Conditions can be optimized to yield higher expression. Overall, we have promising results that if optimized could lead to a better expression and for the first time give us information about HBx three-dimensional structure.
Maintaining One's Health While Homeless
Authors:   , Cline Jennifer , Giarelli Ellen
Published: July 2021

Background and Significance: The interdependence of housing and health is substantial. A lack of housing is an independent risk factor for indiscriminate use of acute health services by homeless adults that is not offset by coverage with health insurance. Crisis driven service access leads to poor health outcomes with higher morbidity and mortality. Current recommendations, policies, and processes to address these issues are largely based upon the perceived needs of homeless adults from the viewpoint of service providers and are compounded by stereotype bias. Less known are the practical strategies homeless persons use to maintain their health and how they prioritize their health needs. This topic exposes an important informational gap. The purposes of this project were to a) uncover health related experiences of homeless adults, b) identify resource assets and deficits as perceived by homeless adults, and c) determine best practices for assisting a person who is homeless to meet their health care needs. The conceptual framework for this project was participatory action research. Methods: A mixed methods approach was used that combined Photovoice with a pre/post assessment of health self-efficacy. Evaluation: Pre and post scores on the Health Self-Efficacy scale were compared for any change in perception related to study participation. In depth interviews with participants were facilitated by critical discussion of the photographs they took. The interviews were recorded, transcribed verbatim, and then thematic analysis applied. Clinical Implications and Summary: The findings offer insight into best practices for improving health outcomes and informing policy and advocacy initiatives. Keywords: Photovoice, participatory action research, homeless, health, housing, policy, health disparities, self-efficacy, stereotype bias
Decrease Catheter Associated Urinary Tract Infections with Leader Rounding Using a Checklist
Authors:   , Menschner Elizabeth , Rundio Al
Published: July 2021

It has been estimated that each year, more than 13,000 deaths are associated with CAUTI's (Magill et al., 2014). Decreasing use of indwelling catheters through removal when no longer clinically indicated is the key to decreasing or eliminating CAUTI. Approximately 12%-16% of adult hospitalized inpatients will have an indwelling urinary catheter at some time during their inpatient admission. Each day the indwelling urinary catheter remains, a patient has a 3% to 7% increased risk of acquiring a CAUTI (Burton, Edwards, Srinivasan, Fridkin, & Gould, 2011). The purpose of this project was to determine if nurse leader rounding using a checklist to prompt removal when indwelling urinary catheters are no longer clinically indicated would decrease catheter days and CAUTI infections compared to nurse leaders not rounding. The study site was a 722- bed licensed academic medical center located in a major city in Pennsylvania. A Focused PDCA approach was used for a six-week performance improvement project. Data was collected from the daily patient census in two intensive care units. No demographic information was collected. Patients were assigned control numbers and the nurse leader completed the checklist during daily rounds. A Fisher's exact test (Polit &Beck, 2017) was conducted and demonstrated no correlation between the use of a checklist and leader rounding versus no leader rounding or use of a checklist. Outcomes of this study were shared with the study site and CAUTI committee.
A Comparison of News Coverage on the Arabic and English Versions of the Al Jazeera Websites
Authors:   , AlSamrin Hamad , Salas Philip W. , Tedesco Albert S.
Published: July 2021

Al Jazeera is a controversial network; its English language website and Arabic language website have significant differences. After collecting data for seven weeks, this study uses analytical methods to show that Al Jazeera Arabic and Al Jazeera English have different political or ideological orientations in their news reporting.
Kinetics and Mechanics of Blood Clot Contraction
Authors:   , Tutwiler Valerie J. , Weisel John , Spiller Kara Lorraine
Published: July 2021

Thrombotic conditions such as heart attacks and strokes are leading causes of death and disability worldwide. Clot contraction, which is the volume shrinkage of the blood clot, has been implicated to play a role in hemostasis, wound healing, and the restoration of blood flow past otherwise obstructive thrombi. Despite these clinical implications, clot contraction is the least studied area of the coagulation process, which can be largely attributed to a previous lack of methodology. To address this need, we developed a novel optical tracking system that allows for the quantitative assessment of clot contraction. These studies revealed that clot contraction is a three-phase process that can be differently affected by platelets, fibrin, and erythrocytes. Platelet count and function have the ability to enhance the extent of clot contraction while increased erythrocytes and fibrin dampen the extent of clot contraction. We developed a three-element active poroviscoelastic model to improve the understanding of how composition of the clot, particularly the presence of erythrocytes, affects the process of clot contraction. We determined that erythrocytes influence clot contraction through both a tensile and compressive resistance, which resulted in a decrease in the extent of contraction coupled with an apparently paradoxical increase in generation of contractile force. The knowledge that blood composition can influence clot contraction coupled with the clinical importance of thrombotic conditions such as stroke and heart attack revealed a need for studies of clot contraction in patients with (pro)-thrombotic conditions. We examined clot contraction in the blood of patients with ischemic stroke, sickle cell disease, and deep vein thrombosis. Interestingly, in all three pathologies we have observed a significant reduction in the extent of clot contraction. With respect to ischemic stroke and deep vein thrombosis, this reduction in clot contraction correlates with a lower platelet count and platelet dysfunction. Whereas, the reduction in contraction in sickle cell disease patients can be attributed to their increased erythrocyte rigidity. Ultimately after a clot is formed it needs to be resolved, which occurs through the enzymatic process of fibrinolysis. Here we examined influence of clot contraction on rate of physiologic or internal fibrinolysis and clinical thrombolysis or external fibrinolysis. Interestingly, clot contraction enhanced the rate of internal fibrinolysis while decreasing the rate of external fibrinolysis. Collectively, these findings provide new information about basic mechanisms of clot contraction and point to its importance with respect to thrombotic conditions, and have the potential to lead to the development of diagnostic assays or therapeutic targets.
Control Physicochemical Properties of Nanoparticle Surfaces to Modulate Immune-Cell Recruitment to Scaffolds
Authors:   , Bady Stephen C. , Schauer Caroline L.
Published: July 2021

Although many complex tissue engineering scaffolds have been developed, the number of translated treatments remains stagnant. Successful applications of scaffolds in regenerative medicine often requires scaffolds to elicit minimal host immune response and controlled release of bioactive molecules. Nanoparticles have shown great promise in the controlled release of therapeutics to aid tissue engineering. However, nanoparticles incorporated in tissue engineering scaffolds causes extra inflammatory responses. Although the release of anti-inflammatory drugs has been shown to reduce the foreign body response to scaffolds in vivo, the drugs also interfere with immune cells that are vital for tissue regeneration. Proposed here is a nanoparticle embedded scaffold drug delivery system designed to minimize the host immune response by controlling the physiochemical properties of nanoparticles. This system embeds PLGA nanoparticles with or without encapsulated immunosuppressant drugs in the walls of alginate scaffolds. The effects of surface modification and release of dexamethasone on immune cell recruitment to scaffolds in vivo were explored. Red Blood Cell Membrane (RBCM) coating on PLGA nanoparticles showed a decrease in neutrophil recruitment as well as an increased number of CD4+ T cells in the scaffolds, which are important for tissue regeneration. Our approach is a new strategy in minimizing the induced foreign body inflammatory response of nanoparticles used for tissue regeneration.
Synthesis of MXene-Epoxy Nanocomposites
Authors:   , Shah Jay B. , Gogotsi Yury
Published: July 2021

This thesis explores the synthesis of MXene-epoxy nanocomposites. MXenes are a family of two-dimensional materials which display versatile chemistries that allow the material to be tuned for applications that include electrochemical storage devices, electromagnetic interference shielding devices, and catalysts, to name a few. Composites of MXenes with a variety of polymers have been produced, and they show enhanced mechanical and electrical properties. In this work, epoxy composites with MXenes are synthesized, because the use of a platelet-like filler allows property enhancements such as 2D stress transfer, and the formation of diffusion barriers and percolating thresholds. Complete exfoliation of the multilayered MXenes into their 2D sheets is desired in order to realize these property improvements. Two different techniques of producing MXene-epoxy composites are evaluated. The first is a tradition in situ polymerization technique, which involves the dispersion of the filler in a volatile solvent. Acetone was used to disperse Ti3CNTx into single layers, before the dispersion was mixed with epoxy. The other technique involves the application of laminar shear stress on multilayered Ti₃C₂T_x particles, in order to exfoliate them into single layers dispersed in the epoxy matrix. In this system, a room temperature ionic liquid (RTIL) is used as the dispersant for the filler and the initiator for epoxy cure. The problems associated with MXene exfoliation, nanoparticle dispersion, and nanocomposite synthesis are considered while evaluating these methods of synthesizing these composites. It was found that while a few single layers of Ti3CNTx were successfully exfoliated, a majority of the particles were still multilayered. The physical performance of the composite was lackluster as a result of this poor exfoliation and dispersion. The lack of covalent bonding between Ti3CNTx and epoxy, and the lack of wettability of the filler are also areas of concern. In the Ti₃C₂T_x-epoxy-RTIL composites, the exfoliation of single layers was also not accomplished. Despite approximate shear stresses experienced by the particles being higher than the theoretically predicted interlayer coupling, stacked Ti₃C₂T_x particles were observed. Instead, the Ti₃C₂T_x particles had undergone swelling, which resulted from the intercalation of the RTIL. Upon application of sufficient shear stress, intercalation of bigger molecules was observed. Better properties were also obtained, leading us to hypothesize that epoxy intercalation has occurred. The reasons for poor exfoliation and poor dispersion are detailed, and future areas of study for better understanding of the MXene-epoxy system are proposed.
Drawing and Disclosure of Experienced Events in an Art Therapy Investigative Interview Process with School Aged Children
Authors:   , Cohen-Liebman Marcia Sue , Gerber Nancy E.
Published: July 2021

The purpose of this study was to explore how drawing as an open ended prompt in an investigative interview enhances recall and facilitates evidentiary disclosure. More specifically, this study explored the use of drawing as a primary resource in an investigative interview process that is based on art therapy principles and practices. The research question for this study was; "How does drawing facilitate disclosure of experienced events of school aged children in an art therapy based investigative interview process when compared to a verbal investigative interview process?" The Common Interview Guideline (CIG), a Forensic Art Therapy Investigative Interview process was both the investigative tool as well as the object of study. Secondarily, underlying mechanisms culled from the literature associated with the drawing effect were explored from an art therapy perspective. The study sought to retrieve data that was rich and descriptive thus, a qualitative comparative analogue design was used in which data between two study conditions; CIG with drawing and CIG without drawing were compared. The analogue design encompassed the topic of bullying which was presented through the use of two short animated videos featuring McGruff, the Crime Dog and his anti-bullying platform. The videos provided the context for the investigative interviews. Content Analysis was used to organize, code, aggregate and analyze textual and imaginal data. Dedoose, a data analysis software program was used to assist in the identification and acquisition of meaningful insights through highlighting units of analysis which included words, phrases, and imaginal data. Three overarching themes emerged from the data; Fact-Finding, Imagery and Relationality. The themes were congruent with the CIG which is predicated upon rapport building, attunement to a child's developmental capabilities, fact-finding and minimization of re-traumatization (Cohen-Liebman, 1999, 2003, Gussak & Cohen-Liebman, 2001). The findings suggest that the use of imagery whether mental, visual or pictorial enhanced memory recall and facilitated enhanced disclosure. Seven underlying mechanisms associated with the facilitative effect of drawing culled from the literature were identified by the children as contributing to enhanced recall. The rationale for using the CIG as the investigative tool for this study is to explore how drawing facilitates recall and disclosure (evidence) in investigative interviews (a dialogical process) of school aged children when used as an open ended prompt (imagery) in a Forensic Art Therapy Investigative interview (a relational process) as compared to a verbal process.
Health Needs Assessment of the Theravada Buddhist Monastic Community in the Northeast USA
Authors:   , Abeyratna Chandupa , Massey Philip
Published: July 2021

The Theravada Buddhist monastics community living in the northeastern United States of America is a vulnerable population that is not given much attention in the sphere of public health. This needs assessment sought to start laying the foundation for future research and projects to help this population. Information collected through this study has shown that there are some issues within the monastic community, such as a lack of knowledge regarding having regular wellness and care visits and lack of awareness of available community health care services. Additionally, the relationship between the monastic code of conduct and health outcomes was apparent. The results of this needs assessment and potential further areas of study on this population are discussed.
An fMRI investigation of the neuroanatomical correlates of script processing in healthy subjects
Authors:   , Gallo Jennifer L. , Chute Douglas L.
Published: July 2021

Scripts are over-learned motor programs for routine, goal-directed activities. Script knowledge includes the actions, objects, and sequence of steps associated with reaching the goal of an activity. Errors in script activities have been studied almost exclusively in neurologically impaired patients, which can lead to misguided assumptions about the source of errors in script activities. Using functional brain imaging, this research gathered data on 9 undergraduate students asked to read a series of brief descriptions of script activities embedded with either semantic or sequencing errors. Semantic errors were associated with problems involving the knowledge of objects and actions pertinent to achieving the goal of a script activity. Scripts suggestive of semantic errors included either substitution with an inappropriate object or an inappropriate action. Sequencing errors were associated with errors related to the order in which script steps are completed. Scripts suggestive of sequencing errors included an order of steps that made the script either physically impossible or conceptually inappropriate to perform in the presented order. Subject-level and group-level analyses were conducted with a series of volumetric t-tests using statistic parametric mapping. In general, when participants viewed scripts, semantic errors activated more posterior cortical and subcortical networks, and sequencing errors activated more anterior cortical networks. More specifically, with respect to semantic aspects of script processing, action errors resulted in more bilateral activation of primary occipital, inferior and middle temporal, and prefrontal cortex, as well as lentiform nucleus, and object errors resulted in more right than left hemisphere activation of parietal, premotor, prefrontal, and limbic cortex, as well as parahippocampal gyrus and cerebellum. With respect to sequential aspects of script processing, physical errors resulted in right hemisphere activation of prefrontal cortex and cingulate gyrus plus left angular gyrus, and conceptual errors resulted in right hemisphere activation of prefrontal cortex and posterior commissure. Though not without limitations, these results suggest that neurologically intact individuals engage diffuse yet distinct neural networks when they encounter different types of script errors, and that regional activations associated with script errors may be best understood in relation to activation associated with correct script processing.
Unraveling design principles of signaling pathways and controlling output signals using non-equilibrium thermodynamics and sensitivity analysis
Authors:   , Hu Dawei , Yuan Jian-Min
Published: July 2021

The network of Ras signaling pathways is known to be related to at least 30% of human cancers. In view of its importance, we investigate a mathematical model of the coupled mitogen activated protein kinase (MAPK)-phophatidylinoisitol 3'-kinase (PI3K) pathways, two better-known pathways of the Ras network. The objectives are to understand the dynamics, the effects of cross-talks, and design principles of these pathways using dynamic sensitivity analysis and non-equilibrium thermodynamics. Based on the knowledge gained in these analyses, we may be able to suggest means to control output signals. Sensitivity analysis has been widely used in the studies of complicated chemical reaction and biological networks, for example, in combustion studies and metabolic control analysis of pathways. In the latter cases, the responses of system properties at steady states with respect to changes of parameters, such as initial concentrations and rate constants, are often expressed as sensitivities. Besides steady-state sensitivities, time dependent sensitivities should be useful; however, the explicit use of them in analyzing complicated biological systems has so far been limited. Using the coupled MAPK and PI3K pathways as an example, we show that time-dependent sensitivities are useful for the studies of complex biological systems. They provide, for example, the following information: (a) multiple time scales existing in a complex system involving cross-talks and feedback loops; (b) the signs and strengths of responses to perturbations; (c) beyond concentration dynamics, sensitivities revealing further details about the intricate dynamics and the effects of the cross-talks; (d) ranking of vulnerability of nodes of a biological network using integrated sensitivity - first step toward the identification of drug targets; (e) reduced sensitivity serving as a measure of the stability or robustness of pathways. Our results indicate that the role of the PI3K branch in the coupled pathways is to enhance the robustness of the MAPK pathway. More importantly, they demonstrate that time-dependent sensitivity analysis can be a valuable tool in systems biology. Thermodynamics is a branch of physics to treat macroscopic systems using a few variables. It would be interesting to use it to reduce the complexity of biochemical systems, such as signaling pathways. However, biological systems are usually not in equilibrium and are often far from equilibrium. To study such systems, we need nonequilibrium thermodynamics. Therefore, in the present work we have applied the modern concepts of non-equilibrium thermodynamics, such as, affinities, fluxes, dissipated energy, and efficiency to the studies of signaling pathways, in particular, the present coupled MAPK-PI3K system. Motivated by the dynamics of these variables and using knowledge from sensitivity analysis, we can achieve certain degree of control of the output signals, which are related to cell growth and differentiation.
Development of a pattern recognition approach for analyzing flow cytometric data
Authors:   , Quinn John R. , Hrebien Leonid
Published: July 2021

Background: Flow cytometry is used to study the properties of individual cells. Combining cellular markers for viability with cell surfaces marker expression is routinely used to study various cell lineages. Current classification methods use strict thresholds, or "gates", on the fluorescent intensity of these markers. These techniques are subjective in nature and may not fully elucidate phenotypes of interest. Described in this thesis is the development of objective criteria for phenotypic boundary recognition through statistical pattern recognition, and the application of this approach to multiple studies targeted at understanding in vivo erythropoesis, apoptosis, and the role of the hormone erythropoietin (EPO). Methods: Artificial neural networks (ANNs) were trained to recognize subsets of cells with known phenotypes, and to determine decision boundaries separating these subsets based on statistical measures of similarity. The ANNs were trained with samples whose class membership is known with high probability. The method was developed using an in vitro cultured cell system engineered to be dependent on EPO for survival, and a set of parameters correlated to cellular viability. These ANNs were then applied to classify cells by viability and lineage phenotype from several ex vivo studies, and ultimately to analyze late-stage erythroid progenitor viability in response to exogenous recombinant human EPO (rhEPO). Results: The best performing network was a radial basis function multilayer perceptron (RBFP) as measured by multiple performance indices. Classification of the in vivo data confirmed a dependence on EPO for continued survival in the cultured cells. In vivo, treatment with rhEPO increased the fraction of erythroid precursors in the bone marrow. However, there was no change in the number of apoptotic late erythroid precursors and a statistically significant increase in the number of dead erythroid precursors. Further in vivo studies produced no significant differences in erythropoetic state between control and experimental groups in a murine system with defects in the genes that control production of a receptor-ligand combination believed to be critical for the initiation of apoptosis. Conclusions: A statistical pattern recognition approach was demonstrated to provide an objective rationale for setting decision boundaries for classification in cytometric data. Using this approach we have confirmed that rhEPO inhibits apoptosis and cell death in an EPO dependent cell line, but failed to do so in a murine model of anemia. Our results also suggest that rhEPO may not act as a simple anti-apoptotic agent in the bone marrow. Rather, homeostatic mechanisms may regulate the pharmacodynamic response to rhEPO. Further study of this system revealed additional complexities, most notably that there may be redundancy among the receptor-ligand combinations that initiate apoptosis.
Towards a targeted surfactant stabilized ultrasound contrast agent
Authors:   , Thomas Marlon Sheldon , Wheatley Margaret A.
Published: July 2021

Gas-filled microbubbles are highly effective when used as ultrasound contrast agents due to the large difference in acoustic impedance between the gas in the bubble and the surrounding blood. The surfactant-based contrast agent ST68 (Span 60, Tween 80) developed in our laboratory (US Patent # 5, 352, 436) and filled with sulfur hexafluoride (SF6), was modified in an attempt to make the agent target specific. Modifications to the agent were done by incorporation an anchor molecule, phosphatidylethanolamine (PE), into the shell of the microbubles. This anchor molecule will serve as a ligand attachment site for a targeting moiety such as a monoclonal antibody. Fluorescent microscopy and phosphate assays were used to evaluate the extent of PE incorporation. NBD (7-Nitro-2-1, 3-benzoxadiazol-4-yl) labeled PE was used to visually confirm that PE was being incorporated into the microbubble shell and a phosphate assay revealed that the optimum PE concentration of 0.21mM in HEPES buffer. The storage stability of the agent at -5oC and -20oC were assessed. SF6-filled ST68 samples prepared in PBS were storage at both temperatures under a SF6 atmosphere. Samples were thaw and both physical and acoustic properties examine over a period of 10 days. Analysis using the coulter multisizer II revealed that the agent stored at -5oC was more stable than the agent stored at -20oC. The acoustic backscatter of the reconstituted samples incubated at -5oC was consistent over the 10 days however, there was variation in the acoustic backscatter of the sample stored at -20oC. An in vivo study was done to evaluate the effectiveness of the agent.
Identifying regions of difference in flow cytometric data
Authors:   , Achuthanandam Ramasubramaniam , Hrebien Leonid
Published: July 2021

We propose a pattern recognition framework for the identification of biologically interpretable regions of difference between groups of flow cytometric data samples. The identification of regions of difference is reduced to a problem of feature selection. We propose the use of a filter-based feature selection method using the two sample t-test to identify relevant features. We compare the performance of our method to an existing alternative, Frequency Difference Gating (FDG), and to other commonly used feature selection methods including filter-based methods such as a non-parametric Mann-Whitney test, a non-parametric resampling based Welch t-test, the Pearson's square correlation coefficient and a wrapper method using support vector machine based recursive feature elimination. We evaluate the performance of the various methods using commonly used feature selection metrics, feature selection accuracy and classification accuracy. We also present the use of a metric from signal detection theory, the area under the Receiver Operating Characteristic curve (AUC), to evaluate the feature selection performance. Using these metrics, we demonstrate that the pattern recognition framework using the filter based tests outperform FDG and the wrapper based method. We show the performance using synthetically generated data and real biological data obtained from treating mice with an agonistic anti-CD3 antibody to determine activation levels in CD4+ and CD8+ T-cells. We find that our method is able to identify all the regions of differences between the two groups of samples. The pattern recognition framework is also used to analyze regions of differences in data collected from mice treated with an agonist (drug), erythropoietin (EPO). The regions of difference detected represent cells known to be affected by EPO. Using a possibilistic clustering algorithm, we identify the presence of four cluster of cells within our regions of difference, that respond differentially to EPO. The identity of the cells was determined by physically separating the cells of interest from the mixture and studying their morphology. In this experiment the technique provided us with information that EPO acts by stimulating and expanding basophilic erythroblasts in mice bone marrow.
Automated parallel mesh adaptation methods for transient flowfield analyses with fixed or moving boundaries
Authors:   , Cavallo Peter Angelo , Cernansky Nicholas Peter
Published: July 2021

Transient flowfields appear in many applications of interest and present numerous challenges to current simulation methods. Such problems include shock propagation and reflection, bluff body wakes with periodic shedding, and pulsatile flows generated by flow control devices. Also of interest are cases where boundaries are in relative motion, as found in weapons separation from aircraft, valve and piston motion in internal combustion engines, and rotor/stator interactions. The task of providing a computational mesh that is adequate to capture evolving flow structures as they change in time is an important and difficult aspect of this class of simulations. In moving body applications, the problem is compounded by the need to accommodate topology changes in the mesh. The issue of spatial resolution in transient flows has been addressed by various researchers using adaptive mesh refinement. However to date such strategies have largely been ad hoc and problem-dependent. The simulation of bodies undergoing relative motion has typically been performed using overset grid methods, which require considerable expertise and can be significantly labor intensive, particularly when generating overlapping grids for realistic geometries. This work presents new approaches for performing unstructured mesh adaptation for transient flows with fixed or moving boundaries. Notable advances in parallel mesh adaptation methods are made to facilitate the integration of mesh coarsening and refinement within the iteration loop, operating directly on the decomposed domains used by the parallel flow solver. A novel method is developed which modifies the mesh automatically at variable intervals according to how rapidly the solution is changing, rather than relying on a predefined, constant frequency. The new approach is founded on the concept of projecting refinement of solution errors ahead of their current location, and subsequently monitoring their accumulation. For moving boundary problems, a formal mesh deformation matrix analysis is employed to direct where corrective coarsening and refinement are required. Automation of mesh corrections for such problems is based on the deformation history of the mesh. These advances are demonstrated on controlled, unit problems as well as more complex problems of interest involving stationary and moving geometries.