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Myofibroblast Targeted Liposomes For The Treatment Of Skin Fibrosis
No full textContinuous overactivation of myofibroblasts leads to excessive deposition of profibrotic proteins, which in turn causes tissue stiffness and, ultimately, organ failure. One of those proteins, Cadherin-11 (CDH11), is reported to be overexpressed in the tissue of fibrotic skin, specifically on myofibroblasts. Similarly, chronic inflammation drives fibrosis progression in autoimmune-related illnesses like systemic sclerosis (SSc). Therefore, it is hypothesized that CDH11 could be a target for cell-specific delivery of antifibrotic therapies to fibrotic skin tissue. Here, a CDH11 peptide conjugated liposome loaded with Tofacitinib, a JAK inhibitor, was developed to understand the potential of targeted therapies to treat skin fibrosis. The physical characterization of the developed LPS was evaluated and analyzed for their therapeutic efficacy in vitro using dermal fibroblasts and in vivo using a skin fibrosis mouse model. The findings from the experiments confirmed that CDH11 targeted LPS have specificity for myofibroblasts, enhancing the cellular internalization of tofacitinib-loaded LPS in fibrotic cells and tissue, and demonstrated downstream effects inhibiting fibrotic disease progression. The research work here represents a novel LPS delivery approach exhibiting promising potential to treat skin fibrosis
Phosphene or 233 Reasons Why I Never Listened to ABBA
No full textA hybrid collection about gods and fathers, saviors and sons
*MFA theses don\u27t have abstracts. My critical preface is 20 plus pages
Functionalized Carbon Quantum Dots: A Promising Nanomaterial For Investigating Their Potential In Neurodegenerative Disease Treatment
No full textNeurodegenerative diseases such as Parkinson\u27s Disease (PD), Alzheimer\u27s Disease (AD), and Huntington\u27s Disease (HD) remain incurable, despite extensive research into therapeutic development. In the United States of America, the annual cost of PD and AD in terms of patient care and lost productivity is approximately $200 billion. Consequently, there is a critical and unaddressed need for the development of innovative drugs and drug delivery systems that can decelerate, stop, or ideally reverse neurodegenerative diseases. The dissertation presented here focuses on devising strategies to target PD through multiple mechanisms, including the inhibition of protein aggregation and the reduction of oxidative stress. This approach is significant because prior studies have shown that protein aggregation and oxidative stress mutually enhance each other\u27s detrimental effects in PD, leading to the death of neurons. In this study, we demonstrate that carbon nanodots CNDs disrupt the conversion of soluble amyloid proteins into toxic forms in a dose-responsive manner, achieving up to a 70% reduction in fibril formation at a concentration of 5 mg/mL. Additionally, CNDs did not affect mitochondrial membrane potential nor trigger apoptosis at concentrations up to 5 mg/mL. Notably, CNDs were effective in scavenging reactive oxygen species (ROS) even at low concentrations, with a 50% decrease in ROS at 100µg/mL when exposed to free radical generators. These findings suggest that CNDs have neuroprotective capabilities that could play a role in addressing complex neurodegenerative conditions like PD. The tolerance of SHSY-5Y cells to CNDs and their capacity to recover from induced apoptosis further corroborate this potential. Alongside biocompatibility data, CNDs present a promising single-step solution for the treatment of neurodegenerative diseases
Between
No full textA hybrid fiction story about a woman who navigates dating, marriage, motherhood, and making peace an unthinkable horror
Last Summer in the Present Tense
No full textThe novella, Last Summer in the Present Tense situates itself within contemporary queer literature through its exploration of the intersection of queer identity and transnational experiences, as seen in the journey of the protagonist, Sam, a 23-year-old American expat navigating personal growth in Madrid
From Criminal Bodies To Criminal Minds: The Texas Sodomy Statutes, Homosexuality, And The Politics Of A Criminal Status In Twentieth-Century Texas
No full textThis study shows how homosexuality became a crime in Texas. On one hand, the twentieth-century criminal definition of homosexuality and its applicability in Texas law is informed by centuries of both religious and legal understandings of and proscriptions for sodomy. On the other hand of this centuries-long legacy, criminalizing homosexuality in Texas has more recent connections, too. First of all, the ways in which a sodomitical other was imagined within the sodomy statuteâ??s enforcement and adjudication in Texas during the late nineteenth century was analogous to the deployment and protection of white supremacy in the South. Secondly, the criminalization of same-sex sexual desire was also very much rooted in the mid-twentieth century, specifically between 1943 and 1973. From wartime fears about vulnerable or misguided youth, to cold-war anxieties about secrecy or infiltration, and to the rise of the far right and the politicization of sexual identities, the effort to classify and incorporate a criminal definition of homosexuality into Texas law has been a misinformed endeavor and an injustice at every turn. During this thirty-year period the concept of a sodomitical other was reinvented, inscribed into new laws, and then used to classify and homogenize an otherwise heterogeneous group of people based solely on their individual sexualities. Ultimately, this study offers new insight into how criminal sodomy in Texas came to be reimagined within a heteronormative gaze as â??homosexual conductâ?? and provides a broader context for what is often labeled as a part of queer history. I resist classifying discrimination against the queer community in Texas or any state as queer history, however. This is a study of straight history, of its connections to colonialism, white supremacy, and nationalism at the intersection of antigay discrimination and the law
Why Pavement Cracks Are Mostly Longitudinal, Sometimes Transversal, and Rarely of Other Directions: A Geometric Explanation
No full textIn time, pavements deteriorate, and need maintenance. One of the most typical pavement faults are cracks. Empirically, the most frequent cracks are longitudinal, i.e., following the direction of the road; less frequent are transversal cracks, which are orthogonal to the direction of the road. Sometimes, there are cracks in different directions, but such cracks are much rarer. In this paper, we show that simple geometric analysis and fundamental physical ideas can explain these observed relative frequencies
Stochastic Dominance: Cases of Interval and P-Box Uncertainty
Get PDFTraditional decision theory recommendation about making a decision assume that we know both the probabilities of different outcomes of each possible decision, and we know the utility function -- that describes the decision maker\u27s preferences. Sometimes, we can make a recommendation even when we only have partial information about utility. Such cases are known as cases of stochastic dominance. In other cases, in addition to not knowing the utility function, we also only have partial information about the probabilities of different outcomes. For example, we may only known bounds on the outcomes (case of interval uncertainty) or bounds on the values of the cumulative distribution function (case of p-box uncertainty). In this paper, we extend known stochastic dominance results to these two cases
Rural Education Revitalized: Investigating And Resolving Specific Challenges In Rural Schools
Get PDFThis thesis paper investigates the multifaceted challenges and the potential solutions to the issues afflicting rural education. Despite being often marginalized in educational policy discussions, rural schools confront a plethora of unique issues that significantly impact the educational experiences of students and the overall well-being of their communities. This paper explores the elusive concept of “rurality”, emphasizing that rural communities are diverse and dynamic, shaped by different historical, cultural, and socioeconomic factors.
The review of the literature includes a historical analysis tracing the evolution of rural education, highlighting key turning points, legislation, and social forces that have contributed to rural education’s contemporary condition. By examining the intersectional nature of rurality with other identities, the paper reveals the complexity of the challenges faced by rural schools, which include resource accessibility, instructional quality, socioeconomic inequality, and policy decisions. Central to this inquiry is the role of community and the impact of educational policy on rural schools. The literature reveals the critical importance of community involvement and the influence that the implementation of informed pedagogical and policy approaches can have on rural communities. The findings underscore the necessity of collaboration among educators, policymakers, community members, and stakeholders to implement effective changes. Through a comprehensive assessment of existing literature, this thesis paper proposes strategies for addressing these challenges, advocating for educational equity and the empowerment of rural communities. By prioritizing educational equity and fostering community empowerment, rural communities can thrive through the transformative power of education, regardless of geographic location