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Characterization Of Glyt1 Expression And Glycinergic Circuits
No full textGlycine is one of the main inhibitory neurotransmitters in the central nervous system. Glycine is regulated by the glycine transporters 1 and 2 (GlyT1 and GlyT2, respectively) in the synaptic cleft. Both transporters participate in glycinergic inhibitory neurotransmission. Moreover, GlyT1 also participates in glutamatergic excitatory neurotransmission. GlyT2 is devoted to caudal regions of the brain and is used as a marker for glycinergic neurons. In contrast, GlyT1 is expressed across the brain in the rostrocaudal axis and is highly associated with GlyT1-positive glial cells. Data from our laboratory has identified GlyT1-positive neurons in the rodent brain. Therefore, we hypothesize that GlyT1-positive neurons are present in different regions across the CNS of rodents, and these regions use glycine to communicate. Three different aims were established to test this hypothesis and develop this new concept of having GlyT1-positive neurons in the rodent brain. The first includes using antibodies to detect GlyT1 and other markers for cell identification. The second aim is to identify glycinergic circuits within circuitries that are already established but have never been associated with glycine. The last aim involves exploring the DTR ablation cell system that has not been used in rats before. To do so, GlyT1-Cre knock-in line mice and rats were used to analyze the distributions of cells expressing the glycine transporter by labeling with Cre-dependent fluorescent reporters. Immunohistochemistry experiments were performed in the GlyT1-Cre dependent mouse line that expresses tdTomato under the promoter of GlyT1. Tissue was stained with various antibodies, such as glial fibrillary acidic protein (GFAP) and neuronal nuclear protein (NeuN), to identify GlyT1-positive astrocytes and neurons, respectively. GlyT1 and Glutamate Decarboxylase 67 (GAD67) antibodies were also used to identify GlyT1-positive neurons and GABAergic neurons. Tract-tracing studies were performed using the GlyT1-Cre dependent mice and rats. Adeno-Associated Virus (AAV) particles were delivered in different brain regions to assess their GlyT1-positive projections. Finally, a pilot study using the DTR system was performed to evaluate the role of striatal GlyT1-positive neurons in voluntary motor control. Results from these experiments showed GlyT1-positive neurons and glial cells in the striatum, globus pallidus external and internal segments (GPe and GPi), hippocampus subregions (CA1, CA3, dentate gyrus (DG)), and reticular nucleus of the thalamus (RT). Tract-tracing experiments demonstrated GlyT1-positive anatomical connections from the lateral hypothalamic area (LHA), RT, zona incerta (ZI), and hippocampus to other forebrain regions. Results from the DRT system provided the basis for an optimization of the experimental design in rats, a rodent model not tested in published work. Overall, results from this project provide the identification of cells and projection patterns of GlyT1-positive neurons in different brain regions. Future directions include mapping the expression patterns into a high-resolution atlas such as the Allen Reference Atlas (ARA) and the Brain Maps 4.0 (BM 4.0) for mouse and rat, respectively. More restrictive AVV injections will be performed in the different brain areas of interest, and their projection patterns mapped to the previously mentioned atlases. Changes to the DTR experimental design will be made to evaluate the role of GlyT1-positive neurons in the striatum during behavioral assays that will test their contributions to voluntary motor control. Altogether, this study characterizes GlyT1 cells\u27 phenotypes and projections across the rodent CNS
From Text to Utility: Distance-Aware Contrastive Learning for Detection-Ready and Shareable Malware Descriptions
No full textThe rapid rise of sophisticated malware variants poses significant challenges for cybersecurity analysts, particularly due to the scarcity of data on newly emerging threats. Due to privacy, legal, and operational constraints, malware samples are often not shareable; instead, organizations publish cyber threat intelligence (CTI) in natural language. However, these reports are typically unstructured and inconsistent, limiting their utility in machine learning (ML) models. This thesis explores whether high-fidelity, shareable threat intelligence can be automatically generated from structured malware behaviors to supplement ML models when direct access to malware samples is limited. Two central questions are addressed:(i) How can descriptions be made both representative and shareable, avoiding personally identifiable information (PII) or sensitive traits? (ii) Can these descriptions support downstream tasks such as few-shot malware classification in low-data conditions? To address these, a distance-aware contrastive loss improves alignment between behavioral data and text, while a privacy-aware penalty reduces sensitive content. The generated descriptions are used in a Model-Agnostic Meta-Learning (MAML) pipeline, with distilled knowledge improving downstream performance. Evaluations on CIC-AndMal-2020 and BODMAS show up to 42% improvement over pre-trained LLMs in few-shot classification, and a 10-20% gain through multimodal fusion. Gains are also reflected in semantic metrics such as RAGAS Answer Correctness and Similarity. By enabling the automated generation of task-relevant CTI, this work facilitates secure sharing of anonymized behavioral profiles, thereby advancing collaborative threat detection, improving integration into real-world security systems, and empowering organizations to crowdsource effective defense strategies against emerging threats
Rhetorical Hermeneutics After the Posthuman Turn
No full textThis dissertation revisits Steven Mailloux\u27s (1989) concept of rhetorical hermeneutics, according to which persuasion always conditions our interpretive practices. Seeking to bring Mailloux\u27s insights into conversation with rhetorical theory\u27s posthuman turn, my inquiry begins with the following questions: How might posthuman theories of meaning-making allow us to extend or reimagine rhetoric\u27s relation to interpretation? How might recourse to rhetorical hermeneutics help us understand posthuman rhetoric? Can we indeed theorize a posthuman rhetorical hermeneutics? If so, what does it entail? What are its affordances? What are its contexts? How does it affect our understanding of rhetorical situations and the artifacts produced within them? To answer those questions, I consider George Kennedy\u27s (1992) influential proposal that rhetoric is energy and merge his ideas with Jakob von Uexküll\u27s (2010) analysis of animal sign systems. From there, I bring biosemiotics, material semiotics, and material rhetorics, three subfields from various disciplines, into dialogue with one another. Further, following similar moves by Hayles (2017) and Romele (2919; 2020), I attempt to translate our understanding of nature\u27s meaning-making processes into an understanding of digital meaning-making processes. I also examine Charging Bull, a popular statue located near the New York Stock Exchange. Building on the ecological models of rhetoric proposed by Edbauer (2005) and Boyle (2018), I explore the history of the sculpture by tracing the ceaseless interplay of persuasive and interpretative practices that maintain its rhetorical ecology. In sum, this dissertation proffers a broad theory of posthuman rhetorical hermeneutic
Multiscale Integration Of Receptor-Ligand Dynamics Into Discrete And Continuous Tumor Growth Models With Application To Tyrosine Kinase Inhibitor Treatment
No full textThe epidermal growth factor (EGF) receptor cascade plays a crucial role in the survival and proliferation of tumor cells. Tyrosine kinase inhibitors (TKIs) are a class of drugs that inhibit epidermal growth factor receptors (EGFRs), thereby preventing the downstream signal transduction. Despite their importance, models that link spatial receptor dynamics to tumor growth remain scarce. Further, TKIs act through selective mechanisms, inhibiting active, inactive, or all receptor states, which poses a challenge to traditional modeling approaches.
We propose to numerically study two mathematical models incorporating receptor-dynamics into cancer models to describe the impact of EGFR overexpression and TKIs. The first is a 3D multiscale model that was previously introduced to study the impact of EGFR overexpression. We refine this model by (i) modeling intracellular dynamics using a simple ordinary differential equation to speed up computations, (ii) improve the accuracy of the model by applying coarse-graining, and (iii) incorporating the effect of erlotinib, a TKI treatment, using an appropriate pharmacokinetics-pharmacodynamics model. Numerical simulations show the existence of a threshold for EGF concentration which limits tumor growth. Next, we validate the model against experimental data for the action of erlotinib and apply it to predict the evolution of the tumor under treatment. Additionally, we develop for the first time a continuous framework that stratifies tumor cells based on the number of active receptors. This approach provides a flexible way of integrating ligand-receptor dynamics - including association, dissociation and affinity - into continuous tumor growth models. We validate the model using numerical simulations for EGF-dependent tumor growth obtained using the multiscale model. Then, we use it to study the distribution of cells across active receptor states during the different stages of tumor evolution. This model will be extended to incorporate the action of TKIs and elucidate the conditions promoting the action of TKIs that bind to active, inactive, and all receptors
The Alchemy of Respect in the First-Year Composition Classroom
No full textIn this research, I wanted to understand how respect in the First-Year Composition classroom was understood, applied, and negotiated by undergraduate students. Also, I proposed a concept called the alchemy of respect, which describes the transformations, addition of value to students\u27 ideas, and the refinement of their abilities in the classroom. The study relied on three theoretical approaches: virtue ethics by John Duffy, community literacy by Linda Flower, and rhetoric of respect by Tiffany Rousculp. I found important concepts in their work, such as the analysis of morals in the decisions people make, the construction of communities across differences, and the change students experience when they write. I conducted the study in one RWS 01 or two RWS 02 classes. The research methodology was qualitative, using three data collection methods: observation, questionnaires, and a drawing activity. For the observation, I visited writing classrooms nine times and took notes. For the questionnaire, participating students answered twelve narrative questions. For the drawing activity, I asked students to draw respect and briefly describe it. I analyzed the data using Grounded Theory. From the observations, I found that respect encompasses various expressions such as trust, listening, time, inclusion, effort, kairos, and more. I gathered them in groups, and I called them signs of respect. From the questionnaire, some of these signs were confirmed again, but since the students\u27 responses inspired them, they were called principles of respect: listening, attention, equality, confidence, safety, comfort, group work, feedback, healthy environment, mutual support, and more. My findings suggest that the alchemy of respect is present in the FYC classroom, and it is expressed in different activities that constantly transform depending on how students feel, their academic responsibilities, and the classroom environment. Additionally, that respect is defined by the students\u27 knowledge, experiences, and actions
Jak1 V658f Drives Oncogenic Transformation Via Transcriptional Reprogramming Independent Of Y598 Phosphorylation And Canonical Jak-Stat Signaling
No full textT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and complex malignancy that accounts for 15% of pediatric acute lymphoblastic leukemia (ALL) cases in the United States. Tyrosine kinases control critical cellular processes, including the development, survival, and activation of T cells, and are established drivers of leukemia.Tyrosine kinases involved in hematological disorders include receptor tyrosine kinases and non-receptor tyrosine kinases family members such as SRC, ABL, FAK, and Janus kinases (JAKs). This study primarily focused on JAK1 gain-of-function (GoF) mutations. These mutations are recognized as hyperactivating mutations, maintaining kinase activity of JAKs on and essentially keeping downstream signaling effectors, like STATs (Signal Transducers and Activators of Transcription) phosphorylated. Employing in silico analysis, various GoF mutations associated with proliferative hematological diseases were identified in the structure of JAK proteins recognizing the JH2 pseudokinase domain as a hot spot , in specific the region of this domain crucial for dimerization and transactivation of JAKs. It was observed a change in amino acid polarity in most of the GoF mutations identified, indicating a structural-functional impact. In silico analysis demonstrated the heterogeneity of these mutations and the urge to characterize and understand the functional impact of these mutations, thus allowing for personalized treatments. One of the most common JAK1 GoF mutation in refractory cases of T-cell acute lymphoblastic/lymphocytic leukemia (T-ALL) is the JAK1 V658F. Further analysis was made focused on this mutation because its functional role and how it drives oncogenesis have been unclear. A mass spectrometry analysis of an auto-kinase of JAK1 V658F vs JAK1 WT revealed a higher phosphorylation of Y463, Y598, and Y967 in JAK1 V658F compared to JAK1 WT. When auto-kinase assays were used to assess activity, the phosphodeletion of Y598(F) in JAK1 V658F, a reduced auto-activation response was observed. In silico analysis of this site indicated its close proximity between the JAK1 V658 site and Y598 within the JAK1 dimerization region. A decrease in the binding free energy was noted when the non-phosphorylated JAK1 V658F was compared to its phosphorylated form (JAK1 V658F pY598) during dimerization with either JAK3 or JAK1 itself for transactivation process. Nevertheless, the JAK1 V658F homodimer, phosphorylated at Y598, showed increased hydrogen bonds and salt bridges. This finding suggests that due to the increment of energy needs in cancerous cells, JAK1 V658F homodimer could be more stable in activating the JAK-STAT proliferative pathway. To elucidate the role of JAK1 V658F Y598 on the IL-2 JAK-STAT pathway, HEKblue IL-2 cells overexpressing JAK1 V658F, pY598, or F598 variants were examined to determine how the downstream transcription factor STAT5 (Signal Transducer and Activator of Transcription 5) is activated. Interestingly, no significant difference in STAT5 activation was found between JAK1 V658F and JAK1 V658F Y598F. Furthermore, the proliferation rate was not diminished, neither was the case in the absence of IL-2 when JAK1 V658F Y598F was expressed in Kit225 cells. Since there was no difference in activation of JAK1 V658F pY598 or F598 in a complete cell system, nor the proliferation of cells, further analysis needs to be performed to understand possible mechanisms that drive leukemogenesis in T cells. RNA sequencing analysis was made to evaluate how JAK1 V658F impacts gene expression in Kit225 cells. MYC and BCL-2 were found to be upregulated when compared to overexpression of JAK WT, as well as JAK1 V658F. CD8 upregulation, as changes in morphology passing from L1 to L3, suggests that oncogenesis by this mutation goes beyond an impact on the JAK-STAT signaling pathway. The results indicate that the JAK1 V658F mutation affects gene expression, suggesting that its phosphorylation and the JAK-STAT pathway may not completely regulate the disease process in T-ALL cases
Until There Is Nothing Left: The Environmental And Social Impact Of Extractivist Industries In Grant County, New Mexico 1852-1999
No full textThis dissertation research expands and deepens our understanding of the environmental and social impact of the extractivist industries in Grant County, New Mexico, from 1852 to 1999. Much of the scholarship around mining in the historiography tends to focus on Arizona and Northern New Mexico, given the centralization of the mining industry in places like Taos and Santa Fe. The impact of the mining industry on the unique ecosystem and people who resided in Grant County, New Mexico, has not been as thoroughly researched by scholars. Thus, this dissertation extends the literature by revealing how the extractivist industries permanently changed this area of southern New Mexico and Grant County to suit their profit-oriented needs and shaped the social context as they solidified their regional presence. This research is also significant given that the variety and volume of minerals found in Grant County exceed what has been unearthed in other regions of the Southwest. In addition, the legacy of environmental destruction these companies wrought has had a sustained negative impact on the arid landscape, fauna, native peoples, working class, and underrepresented communities that lived in Grant County. Grant County was established in the 1850s as part of the New Mexico Territory acquired by the United States following the U.S. invasion of Mexico. However, the territory was considered an arid and desolate region. There was also a sense of danger in this region because of the hostilities that were created with the Indigenous people (e.g., the Chiricahua Apache), who had lived in this region for generations and were forced to defend their lands against settlement. Prospectors and mining corporations systematically entered Grant County to mine the abundant raw materials. These factions fueled the success of the rapidly industrializing United States and developed an economy around mining in Grant County. The Chino Mine was the most successful of these operations and is North America\u27s second-largest open pit mine today. The operations used by the mining industry slowly consumed the once-vast forests of the Pinos Altos and Mogollon Mountains. In addition, environmental hazards like air pollution, toxic waters, and debris from settling pools impacted the health and well-being of people, animals, and fauna in adjacent towns like Silver City and Bayard. Much of the flora was stripped away in the latter half of the 19th century, resulting in the famous flood of 1895, which ultimately destroyed part of the town of Silver City. The people who lived in these towns were at the behest of the mining corporations, as they dominated the economy and job opportunities in Grant County. Though the pull of the extraction industry was significant, by the late 1940s, people began to push back against the monopolies created by the mining industries. Unions like the International Union of Mine, Mill, and Smelter Workers were formed. They went on strike for higher wages and safer working conditions to address the toxic waste created by mining operations. The famous Empire Zinc strike of 1950 exemplified this. The union called for the right to sanitary living conditions, a reduction in pollution, and the elimination of exposure to the toxins that leached into their drinking water and sanitation systems. In the last half of the 20th century, efforts were made by community groups such as the New Mexico Wilderness Association, the Upper Gila Watershed Alliance, and the citizenry of Grant County to regulate the mining industries and find alternatives for economic growth This led to the emergence of health tourism, which was intended to offset the complete control of the mining industry in the region. Though mining is still a significant part of Grant County today, a conscious effort has been made to make small, consistent changes to clean up the environmental degradation that impacted Grant County. At the same time, social agreements were established to expand the rights of peoples displaced by these extractivist industries, such as the Chihenne Nde Nation, which has been focused on becoming a federally recognized tribe to protect ancestral lands impacted by mining. Thus, this dissertation uses an intersectional framework to extend our knowledge of how the physical and social environment was transformed in the arid region of Grant County and how the region\u27s Indigenous, Hispanic, and working poor suffered the consequences of processes used by the extractivist industries. â?
Perceptions Of Healthcare Students And Educators On Ai And Ar In Immersive Learning: A Phenomenological Study Of Empathy And Self-Efficacy Development In Palliative And End Of Life Care
No full textAs healthcare education evolves to address emotionally complex scenarios such as palliative and end-of-life care, there is an increasing need to integrate both technical and emotional competencies into training. This interpretive phenomenological study explored how artificial intelligence (AI) and augmented reality (AR)-enhanced immersive simulations shape healthcare students\u27 empathy and self-efficacy. Grounded in Rogers\u27 Client-Centered Theory and Bandura\u27s Social Cognitive Theory, the research investigated the lived experiences of healthcare students and educators who participated in emotionally realistic simulations using AI-driven manikins and auditory AR features. Data were collected through semi-structured interviews and analyzed using a hybrid inductive-deductive coding framework, incorporating in-vivo coding to preserve participant voice (Bhattacharya, 2017; Miles et al., 2013; Smith et al., 2021). Findings revealed that AI and AR technologies acted as emotional triggers and reflective mirrors, allowing learners to practice therapeutic communication, build clinical confidence, and navigate the affective dimensions of care. Participants reported enhanced self-awareness, emotional regulation, and professional identity development through these simulations
A Systems Engineering Approach For Mitigating Space Debris In Earth\u27s Orbital Regimes
No full textSpace debris in Earth\u27s orbital regimes is a complex threat that originates with human space activity and is maintained by Earth\u27s gravitational force. Space debris poses the risk of colliding with and destroying operational space assets. These collisions, in turn, pose the risk of compounding space debris fragments by turning operational space entities involved in collisions into additional space debris. In other words, the space debris impact does not end with a fragment colliding with a space entity. Instead, the collision is a new space-debris birth since the entities colliding are likely to become multiple fragments. Depending on the collision\u27s and resulting explosion\u27s magnitude, each entity could turn into scores of individual fragments. Each of these resulting fragments would also possess the capability to produce the same catastrophic event that produced it. This threat, along with the increasing space activity in Earth orbital regimes, further increases the risk of accidental collisions and explosions that increase space debris. This study addresses space sustainability concerns raised by space debris risks in Earth\u27s orbital regimes. Recent space activity includes deploying mega-constellations to LEO. This has increased congestion and collision risks. Furthermore, state actors have been performing catastrophic in-orbit ASAT testing that has added debris predicted to remain in Earthâ??s orbital regimes for decades or longer. Some ASAT debris has gone into MEO, whereas before, it remained in LEO. The debris that went to MEO will eventually gravitate to LEO, which means that this ASAT debris has impacted two orbital regimes, instead of just LEO. The debris problem in LEO has been known since 1978. Historically, the space debris problem has been and remains most severe in LEO. This is a major risk to space entities as LEO is the busiest of Earth\u27s orbital regimes since LEO is used by every space mission. Whether it be a satellite or a spacecraft orbiting the Earth or any other space entity en route to deep space, it must enter LEO. This thesis proposes a novel approach to managing space debris issues in Earth\u27s orbital regimes. The proposed solution was generated with a literature review and traditional SE tasks. The literature review was used to deduce stakeholders, their needs, and system requirements. Subsequently, the space system was analyzed in the context of human-based space missions. It was analyzed from the System-of-Systems Engineering (SoSE) perspective. This analysis verified that the proposed system\u27s operating environment is a SoS. This verification was obtained by using established SoS defining criteria. These criteria was used to establish if the operating environment is comprised of various complex systems operating independently, if they are managed independently, and if they would continue functioning if other systems failed or were removed from the environment. Furthermore, the SoSE analysis was used to validate that the proposed solution should be created as a collaborative system operating in a directed SoS environment. The proposed solution has been labeled as the Space Debris Management System (SDMS). This thesis describes the evolution that led to its design as a collaborative system that operates in a directed SoS environment. The literature review introduces the systems that interface with it. The stakeholder analysis introduces the stakeholders. The requirements analysis shows the rationale that led to the system functionality. Chapter 3 describes the analysis and corresponding design decisions used for selecting the SDMS architecture as an organizing and collaborating system operating in a directed collaborating SoS environment. The SDMS is explained using MagicGrid and UAF view specifications
Efecto de soles
No full textEn este texto quiero exponer cómo fue el proceso de creación de Efecto de soles, el cual se desarrolló entre los años 2022 y 2025. El libro presenta la cotidianidad de un barrio que un día se ve afectado por distintos cambios en la naturaleza cuando aparece un fenómeno particular: los soles de algunas casas se vuelven cuadrados y aumentan su nivel de alumbramiento. Esto hace que el entorno natural del barrio comience a cambiar: aparecen gusanos fosforescentes, las flores pierden su olor, la lluvia se vuelve negra, las mariposas se van y a los árboles les salen hojas de plásticos. El poemario está atravesado por lo absurdo, lo fantástico y lo irónico, y trabaja temas concretos como lo cotidiano, el cambio climático y la relación con la naturaleza. Todo está construido desde los objetos, los insectos, los alimentos y las personas que viven en el barrio. El libro tiene dos partes, en la primera, se presentan diferentes escenas que ocurren en el barrio; en la segunda, se muestran los cambios que empieza a sufrir la naturaleza y la forma en la que las personas reaccionan a ellos. Los habitantes tienen una relación directa con la naturaleza, sus formas de vida se ven afectadas por los cambios en ella, todos deben encontrar una nueva manera de estar en el barrio, de permanecer en él, y, muchas veces las soluciones que encuentran están cargadas de absurdo e ironía. Este libro es una mezcla entre poemas en verso libre, poemas en prosa, cuestionarios, listas y comunicados oficiales