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Bcl2 Mediated Targeted Drug Delivery for the Treatment of Kidney Fibrosis and Stomach Cancer
No full textApoptosis, the programmed death of cells, is primarily regulated by a delicate balance between pro-apoptotic and anti-apoptotic signals. The Bcl-2 (B-cell lymphoma 2) family of proteins acts as anti-apoptotic agents, promoting cell survival. Dysregulation of these proteins is a common occurrence in conditions such as cancer and fibrosis, where overexpression of anti-apoptotic members can foster tumor cell survival and fibroblast activation. In this study, our aim was to explore the therapeutic potential of Bcl-2 inhibitors, both as a small molecule (specifically Navitoclax (Navi)), inhibitor and as Bcl-2 siRNA, for targeted treatment. Intravenous administration of Navi often leads to thrombocytopenia, necessitating a precise delivery strategy to the diseased site while maintaining therapeutic efficacy and minimizing side effects. Our initial project focused on utilizing PLGA-based nanoparticles conjugated with Angiotensin 2 (AT2), a protein commonly overexpressed in kidney disease, to achieve targeted delivery. Intravenous administration of Navi-loaded, AT2-conjugated PLGA nanoparticles demonstrated selective kidney targeting without inducing thrombocytopenia. Histological analysis revealed a reversal of fibrosis post-treatment with targeted nanoparticles, corroborated by improved renal function and apoptosis induction in kidney tissues. Encouraged by these findings, our subsequent endeavor involved advancing the delivery system for Bcl2 siRNA in stomach cancer. While siRNA holds promise for cancer therapy due to its ability to target specific genes, oral delivery remains challenging due to instability in the intestinal environment. To address this, we employed β-Glucan (BG), a mucoadhesive polymer, to shield and stabilize siRNA orally. In vivo studies in a stomach cancer mouse model demonstrated that BG-mediated siRNA formulations effectively reduced Bcl2 expression and induced apoptosis, offering a promising avenue for cancer treatment. In conclusion, our findings underscore the potential of targeted delivery systems for Bcl-2 inhibitors in cancer and fibrosis therapy, providing a safe and effective means of inducing apoptosis at disease sites
Mechanical Adaptations to Anterior Load and Fall Risks in Nulliparous Women With Simulated Gestational Weight Gain
No full textApproximately twenty-five percent of pregnant women experience falls during pregnancy, posing significant risks to maternal and fetal health outcomes. However, research on falls in pregnant women remains limited. PURPOSE: This study aimed to address this gap by comparing static postural stability between pregnant and nulliparous women with simulated gestational weight gain (GWG), thus validating the use of simulated pregnancy; and to observe the mechanical influences of simulated GWG on postural stability in static and dynamic conditions. It was hypothesized that increasing simulated GWG would decrease postural stability in single-limb stance, bilateral standing, margin of stability during gait initiation, and dynamic stability during a slip perturbation. METHODS: Eleven nulliparous women completed four separate data collections while adorning an anteriorly loaded weight-vest with 0, 2.26, 9.07, and 15.88 kg. Participants performed repeated balance, gait initiation, and treadmill slip perturbations under each weighted condition. RESULTS: Pregnant women and simulated pregnant women exhibited similar postural stability characteristics. Static balance was found to only be affected in anteroposterior sway magnitude between baseline and simulated second trimester in bilateral standing. Margin of stability was not significantly different across simulated trimesters during gait initiation. Dynamic postural stability displayed significant decreases at each heel strike between baseline and second trimester, and additional significance at heel strike one and heel strike three between baseline and third trimester. CONCLUSION: Overall, these findings suggest that the mechanical influences of simulated GWG influence the compensatory performance of postural stability during dynamic movements. This study contributes to the understanding of the mechanical aspects of GWG and may translate to the pregnancy-related postural stability changes and fall-risks
Prediction Modeling of Foreign Object Impact Debris on Aircraft Through Digital Engineering
Get PDFThe contribution of the research made is derived into two sections. The first topic discusses the prediction modeling of Foreign Object debris (FOd) impact on aircraft structures through the use of digital engineering. The program used in this project is Ansys Explicit Dynamics to evaluate the stress and strain caused by the initial conditions of flight trajectory and impact created from FOd found inside of aircraft structures. The prediction modeling consists of creating a repetition of simulations with different FOds to evaluate the damage created to subsystems of the wing bay such as the fuel system and internal structures. The FOds used for this analysis are washers, fasteners, & plastic caps. By defining the solutions from the explicit dynamic environment, it can be concluded that such foreign objects (FO) can or cannot cause failure to the aircraft. The development of these simulations would be exported to Unity to create a model for in-depth analysis of impact and location of FOd after flight trajectory. With this research, it would assist engineers in how to prevent a major accident from happening while an aircraft is operating. The second topic focuses on the optimization of scanning parameters of Non-Destructive Equipment (NDE) and the development of different intentional defects on manufactured curved carbon fiber composites. Composites are made of carbon fiber and epoxy resin with placement of washers and teflon pieces layer by layer through compression pressing and molded vacuum bagging. The technique used for NDE is ultrasonic testing and the transducer used was a phased array probe and the NDE equipment was an Omniscanner SX. The use of this technique allows us to scan the composite row by row to detect handmade defects on composites at different locations. The Omniscanner SX would allow us to obtain high resolution scans for present research. By having different scans, an AI model is created and trained to automatically detect such defects at different depths and location on composites
Teacher Language Ideologies Concerning the Reclassification of Emergent Bilingual Students: Navigating the Levels of Power in Reclassification
Get PDFReclassification is a crucial educational student outcome when a school system determines that a student is English proficient and ready for mainstream instruction without language support services (Umansky et al., 2020). This study examined the relationship between crucial and complex language ideologies of dual language teachers and the reclassification of emergent bilingual students1.. Language ideologies were the theoretical framework for the study through which the voices of dual language teachers were captured. The analysis of data sources, including teacher interviews, classroom observations and evidence of biliteracy development, helped to understand and reveal how dual language teachers navigate the dynamics of reclassification and possible influences on reclassification. Five key themes emerged: (a) personal experiences and linguistic trauma on the border, (b) transformational ideologies and pedagogies, (c) tensions and contradictions caused by the goals of dual language programs and reclassification, (d) inconsistencies and lack of training in district reclassification policies, and(e) traumatic healing. The data demonstrated that all participants adhered to state, district, and campus requirements. However, they expressed a need for support, guidance, and a better understanding of the reclassification process. While they acknowledge the importance of emergent bilingual students demonstrating English language proficiency, their voices, thoughts, and feelings emerged regarding teaching and evaluating emergent bilingual students for English language proficiency in DLBE during the reclassification process.
1 The term Emergent Bilingual focuses on the unique potential for bilingualism possessed by students learning English in school (García & Li Wei, 2014). I use this terminology throughout this proposal as it demands that we take an asset-based view of the capabilities of emergent bilingual students, who are simultaneously acquiring a new set of linguistic capabilities in school and building on the valuable knowledge of their first language. Keywords: Reclassification, emergent bilingual students, dual language bilingual education, teacher language ideologies, academic language, academic architectur
The Daughters Of La Malinche: A Heideggerian Analysis Of The Pazian Archetypal Masks Portrayed In Art
Get PDFIn this thesis, I present a Heideggerian phenomenological analysis of the Pazian archetypal masks present in The Labyrinth of Solitude, such as El Macho, La Llorona, La Mala Mujer, La Chingada, and La Malinche, and how these masks are represented and depicted by women in art. I analyze the authentic or inauthentic identity and conditions expressed by Mexican women in art through a mimetic lens and extend that analysis to gendered concerns that have emerged in the past fifty or so years in Mexico and the U.S. Mexico border. Such issues include the pervasive machismo culture and the alarming increase in the rates of femicides as depicted in art. These issues are intrinsically linked to various female archetypes, a connection this study explores by analyzing the Pazian archetypal masks mentioned above. I utilize the art of Maria Izquierdo, Frida Kahlo, and Irisol Gonzalez-Vega to focus on the particularity of Mexican women. Drawing from Heidegger’s “Analytic of Dasein,” I grapple with issues such as authenticity and inauthenticity, thrownness, everydayness, and the overarching importance of care and guilt to explore how art paves a path for the authentic understanding of the other, specifically through the use of the Pazian archetypal masks mentioned above. Art, by disclosing and bringing to the forefront the thrown and inauthentic situations of the other, allows for a call of conscience in which the concepts of guilt, care, and love disclose the potential authentic Being of the Other
Talking About Sex: The Relationship Between Cultural Constructs and Sexual Behaviors Among Latina Emerging Adults
Get PDFEmerging adults account for a significant portion of yearly STI cases with Latinxs living in border regions often being disproportionally affected. Moreover, Latinas may hold much of the responsibility for sexual health when compared to their male counterparts; however, culture may serve as both a protective and risk factor for deleterious sexual behaviors. These disparities highlight the importance of assessing Latina sexual risk and to a further extent, perceptions of sexual and reproductive health services. The present study assessed how cultural constructs were associated with sexual risk and STI testing views among Latinas and how these associations may be moderated by parental sex messages. It was hypothesized that cultural constructs would be positively associated with sexual risk and negatively associated with STI testing perceptions; however, familial communication would moderate these relationships relative to the type of messages employed. Latina college students (N=444) were recruited from a Hispanic Serving Institution and completed the following measures: sociodemographics; the Attitudinal Familism Scale, the Marianismo Belief Scale, the Intragroup Marginalization Inventory, the Child and Adolescent Sexual Messages Scale, the Sexual Risk Survey, and the Adapted STI Testing Beliefs measure. Multiple hierarchical negative binomial and hierarchical regressions were conducted to test these associations. Five of the six hypotheses were partially supported highlighting nuances in these associations. These present findings indicate that cultural constructs may serve as both protective and risk factors for sexual behaviors, and familial messages about sex moderate these relationships. Latinas and their families may benefit from interventions focused on individualized sex communication to frame culture as a strength
Exploring the Barriers to Mental Health Treatment among Justice-Involved Women living in the U.S.-México border region
Get PDFFor women in the criminal justice system, mental illness is a complicated and prevalent factor, with rates ranging from 49.2% to 67.9% (Bronson & Berzofsky, 2017). To address the mental health care that justice-involved women need, scholars have called for a closer examination of barriers that hinder access to mental health and substance use treatment among this population (Winham et al., 2015; Wilfong et al., 2021). Barriers to treatment can be attitudinal (i.e., stigma and fear) or structural (i.e., transportation, cost of treatment), yet few, if any, studies have examined how these barriers present in a group of justice-involved women living in the U.S.-México border region. The current project explored the relationship of barriers to treatment among 85 justice-involved women living in the Paso del Norte border region located in El Paso, Texas, and surrounding areas. The project investigated (1) what barriers women frequently identified as hindering their treatment, (2) how the barriers contributed to receipt of services, and (3) whether internalized stigma mediated a relationship between endorsed attitudinal barriers and perceived public stigma. Findings show attitudinal barriers were more frequently endorsed as barriers to seeking treatment compared to structural barriers. For the second aim, attitudes and public stigma were at decreased odds for past treatment seeking, yet internalized stigma was associated with increased odds of past treatment seeking and future treatment seeking. However, structural barriers did not emerge as significant predictors for past, present, or future treatment seeking. Finally, internalized stigma was a significant mediator between public stigma and attitude barriers. Results suggest that stigma and attitudes, while complex, are associated with help-seeking and should be addressed to increase utilization of treatment services for justice-involved women in the Paso del Norte border region
Local Map of the Interstellar FUV Field
Get PDFThe strength of the far-ultraviolet field is an important parameter in determining the chemistry that takes place in star-forming regions. FUV radiation is produced by bright stars in the galaxy and absorbed by interstellar dust. By using newly available maps of the dust distribution, in conjunction with catalogs of stellar positions and spectra, we created a local map of the FUV field ranging from 6-13.6 eV. We find a value of 6.57*10^-14 erg/cm^3 at the location of the Sun. This value, alongside its spectra, follow previous measurements and estimates of the FUV field at the Sun. We further study the relationship between dust density and energy density
Bcl2 Mediated Targeted Drug Delivery For The Treatment Of Kidney Fibrosis And Stomach Cancer
Get PDFApoptosis, the programmed death of cells, is primarily regulated by a delicate balance between pro-apoptotic and anti-apoptotic signals. The Bcl-2 (B-cell lymphoma 2) family of proteins acts as anti-apoptotic agents, promoting cell survival. Dysregulation of these proteins is a common occurrence in conditions such as cancer and fibrosis, where overexpression of anti-apoptotic members can foster tumor cell survival and fibroblast activation. In this study, our aim was to explore the therapeutic potential of Bcl-2 inhibitors, both as a small molecule (specifically Navitoclax (Navi)), inhibitor and as Bcl-2 siRNA, for targeted treatment. Intravenous administration of Navi often leads to thrombocytopenia, necessitating a precise delivery strategy to the diseased site while maintaining therapeutic efficacy and minimizing side effects. Our initial project focused on utilizing PLGA-based nanoparticles conjugated with Angiotensin 2 (AT2), a protein commonly overexpressed in kidney disease, to achieve targeted delivery. Intravenous administration of Navi-loaded, AT2-conjugated PLGA nanoparticles demonstrated selective kidney targeting without inducing thrombocytopenia. Histological analysis revealed a reversal of fibrosis post-treatment with targeted nanoparticles, corroborated by improved renal function and apoptosis induction in kidney tissues. Encouraged by these findings, our subsequent endeavor involved advancing the delivery system for Bcl2 siRNA in stomach cancer. While siRNA holds promise for cancer therapy due to its ability to target specific genes, oral delivery remains challenging due to instability in the intestinal environment. To address this, we employed β-Glucan (BG), a mucoadhesive polymer, to shield and stabilize siRNA orally. In vivo studies in a stomach cancer mouse model demonstrated that BG-mediated siRNA formulations effectively reduced Bcl2 expression and induced apoptosis, offering a promising avenue for cancer treatment. In conclusion, our findings underscore the potential of targeted delivery systems for Bcl-2 inhibitors in cancer and fibrosis therapy, providing a safe and effective means of inducing apoptosis at disease sites
Niños Del Trópico: Una Colección De Relatos De Ciencia Ficción Sobre Juárez-El Paso
No full textEn esta tesis para obtener el grado de Master of Arts de la Universidad de Texas en El Paso, se encuentra una colección de cuentos en español de ciencia ficción, situados en la frontera Juárez-El Paso, con temáticas como los saltos en el tiempo, los posibles mañanas y la colonización de nuevos planetas, así como una evaluación crítica sobre las referencias bibliográficas, estructuras narrativas y el origen de cada una de las piezas, su tradición literaria dentro de la ciencia ficción y su paralelismo con la situación actual de la frontera entre Estados Unidos y México