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Exosomes and Encapsulated ExomiRs in Breast Cancer: Theragnostic Applications and Clinical Implications
No full textExosomes, released by cells, are small vesicles that have emerged as critical theranostic tools in breast cancer due to their unique ability to transport diverse biomolecules such as proteins, lipids, and RNAs, including microRNAs (ExomiRs). These vesicles are critical in modulating the tumor microenvironment, driving processes like cancer proliferation, invasion, metastasis, and drug resistance. Exosomal microRNAs such as ExomiR-21, ExomiR-1246, and ExomiR-155, with their profound influence on the gene expressions in the recipient cells, are the unsung heroes in tumor progression and immune modulation. This chapter delves into exosome\u27s dual diagnostic and therapeutic potential in breast cancer. It highlights their role as noninvasive biomarkers for early cancer detection, providing reassurance and confidence in their potential and application in personalized treatments. Furthermore, cross-biological barriers make them ideal candidates for targeted drug delivery systems, offering new avenues to overcome drug resistance. The chapter also explores the latest advancements in exosome-mediated gene therapy, such as using engineered exosomes to deliver therapeutic genes. It discusses how exosome cargo, beyond microRNAs, contributes to cancer progression and immune evasion. Finally, the chapter addresses the current challenges in exosome research, including standardization and clinical translation issues, and examines the future potential of exosome-based personalized therapies. Focusing on their theranostic capabilities, this exploration positions exosomes as a transformative force in breast cancer diagnosis and treatment, instilling hope and optimism about the future of cancer care, particularly in precision medicine.https://digitalcommons.chapman.edu/pharmacy_books/1029/thumbnail.jp
The Discouraging Effect of Overconfidence
No full textOverconfidence is often viewed as encouraging entrepreneurs and CEOs to follow risky strategies such as entering new markets, engaging in innovation, or pursuing mergers and acquisitions. While such undertakings can generate excess returns and profits, overconfidence is frequently offered as an explanation for why so many business ventures fail. However, we show that in a setting where the decision maker does not know whether success is possible, theoretically, overconfidence can also have a discouraging effect, causing one to give up too soon. This counterintuitive result is driven by effectively misattributing one\u27s own failure to an elevated assessment of the chance that success is not possible. In a controlled laboratory experiment, we find general support for the theoretical predictions, although empirically, participants are overly reluctant to engage in repeated innovation attempts
“We Aren’t Dying Yet, but We’re on the Hospital Bed.” An Analysis of Scottish Culture and Desire for Independence
Get PDFScottish culture has long often been associated with barbaric clans and whiskey; however, there is much more to this culture than meets the eye. After centuries of oppression and pushback on expressing cultural aspects of Scottish identity post the Union of the Crowns in 1603, Scotland has now emerged as a leader in re-establishing its culture and protecting it as well. This paper will aim to analyze how Scotland\u27s cultural pride over time has changed and how this uptick in pride has also led to a political movement for independence. I argue that the aftermath of the Battle of Culloden, the repression of Scottish culture, has been used as a narrative for the modern independence movement in Scotland. This paper is essential for understanding the intersection of culture and politics and how all aspects of culture, such as language, dress, and food, can shape political movements. Previous research has analyzed the natural heritage and symbols of each ethnic group in the United Kingdom, finding differences between English and Scottish views. Past research has also examined how the persecution of the native language of Scottish Gaelic and Highland dress has influenced devolution and increasing referendums in the country. There will also be a focus on the historical oppression faced by Scottish people in the Highlands, also known as Highlanders, after the Battle of Culloden in 1746. This paper will focus on the case study of the 2014 referendum and look into the complexities of the political and social context of that time for Scotland. I have used secondary sources to analyze these two events and primary sources of excerpts of the battle and political movement utilizing the National Archives of Scotland. Understanding the historical importance of the events that occurred after this battle will be used as a context for the 2014 political movement for independence
Charting a New Vision: Lessons on \u3cem\u3eVision & Change\u3c/em\u3e from a Network of Biology Educators
Get PDFThe 2011 Vision & Change report outlined several recommendations for transforming undergraduate biology education, sparking multiple pedagogical reform efforts. Among these was the Promoting Active Learning and Mentoring (PALM) network, an NSF-funded program that provided mentorship and training to instructors on implementing active learning in the classroom. Here, we provide a perspective on how members of the biology education community in PALM view the recommendations of Vision & Change, drawing upon our experiences both as members of PALM and as leaders of an associated project funded by another NSF grant that hosted PALM alumni at various conferences. These efforts have allowed us to gain insight into how our alumni think of Vision & Change, including how they interpret its recommendations, the challenges and opportunities that they view for implementing these recommendations, and the areas they see as critical to be addressed in future national reports for supporting undergraduate biology education. We synthesize these voices here, providing perspectives from a diverse group of biology instructors on what they think about Vision & Change, and provide recommendations for the biology education community based upon these PALM community voices
Feasibility and Acceptability of the \u3cem\u3eMazi Umntanakho\u3c/em\u3e Digital Tool in South African Settings: A Qualitative Evaluation
Get PDFTo address the need for interventions targeting social emotional development and mental health of young children in South Africa, the Mazi Umntanakho (‘know your child’) digital tool was co-designed, and piloted with caregivers and 3–5-year-old children involved in home visiting programmes promoting early childhood development. The aim of this study was to qualitatively evaluate the feasibility and acceptability of this tool in four urban and four rural low-income communities, from the perspective of home visitors and caregivers. Focus groups were conducted with home visitors (n = 117) and caregivers (n = 72). Issues relating to the feasibility of implementing the tool included timing of using the tool, technical and social implementation challenges, WhatsApp as the preferred platform, and participants\u27 recommendations for future implementation. Overall, the tool was acceptable for home visitors and caregivers and was perceived to have a positive impact on children\u27s development, and the relationship between caregivers and children
Scaling Arctic Landscape and Permafrost Features Improves Active Layer Depth Modeling
Get PDFTundra ecosystems in the Arctic store up to 40% of global below-ground organic carbon but are exposed to the fastest climate warming on Earth. However, accurately monitoring landscape changes in the Arctic is challenging due to the complex interactions among permafrost, micro-topography, climate, vegetation, and disturbance. This complexity results in high spatiotemporal variability in permafrost distribution and active layer depth (ALD). Moreover, these key tundra processes interact at different scales, and an observational mismatch can limit our understanding of intrinsic connections and dynamics between above and below-ground processes. Consequently, this could limit our ability to model and anticipate how ALD will respond to climate change and disturbances across tundra ecosystems. In this paper, we studied the fine-scale heterogeneity of ALD and its connections with land surface characteristics across spatial and spectral scales using a combination of ground, unoccupied aerial system, airborne, and satellite observations. We showed that airborne sensors such as AVIRIS-NG and medium-resolution satellite Earth observation systems like Sentinel-2 can capture the average ALD at the landscape scale. We found that the best observational scale for ALD modeling is heavily influenced by the vegetation and landform patterns occurring on the landscape. Landscapes characterized by small-scale permafrost features such as polygon tussock tundra require high-resolution observations to capture the intrinsic connections between permafrost and small-scale land surface and disturbance patterns. Conversely, in landscapes dominated by water tracks and shrubs, permafrost features manifest at a larger scale and our model results indicate the best performance at medium resolution (5 m), outperforming both higher (0.4 m) and lower resolution (10 m) models. This transcends our study to show that permafrost response to climate change may vary across dominant ecosystem types, driven by different above- and below-ground connections and the scales at which these connections are happening. We thus recommend tailoring observational scales based on landforms and characteristics for modeling permafrost distribution, thereby mitigating the influences of spatial-scale mismatches and improving the understanding of vegetation and permafrost changes for the Arctic region
Increasing Atmospheric Evaporative Demand Across the Tibetan Plateau and Implications for Surface Water Resources
Get PDFThe Tibetan Plateau, known as the “Asian water tower,” is a hotspot for complex hydroclimatic changes. We reveal that the previously decreasing atmospheric evaporative demand (Eo) trend at the end of the 20th century has reversed over the last two decades. Although both wind stilling and solar dimming have persisted, their effects on Eo rates have been overshadowed by increasing air temperatures and decreasing relative humidity, leading to a net rise in Eo for 1980−2015. Using the empirical “top-down” Budyko approach, we estimate that across seven sub-catchments draining the Tibetan Plateau, a 10% increase in annual-averaged precipitation, assuming all other factors remain constant, would lead to a 15%–19% increase in streamflow. Conversely, a 10% increase in annual-averaged Eo would decrease streamflow by 5%–9%. Our findings provide a deeper understanding of the accelerating hydroclimatic changes and their impact on surface water resources in the Tibetan Plateau
Uncovering the Binding Mechanism of Mutated Omicron Variants via Computational Strategies
Get PDFThe COVID-19 pandemic, triggered by the SARS-CoV-2 virus, has resulted in nearly 630 million cases and 6.60 million fatalities globally, as of November 2022. SARS-CoV-2, a species of the Coronaviridae family, has a single-stranded positive-sense RNA genome as well as four main structural proteins (S, E, M, and N) required for viral entrance into target cells. The spike protein (S) influences this entry through interactions with human angiotensin-converting enzyme 2 (hACE2) receptor. The World Health Organization (WHO) recognized numerous variants of concern (VOCs) that involve Alpha, Beta, Gamma, Delta, and Omicron, having multiple mutations within the spike protein, altering infection rates and immunity evasion. The Omicron variant, featuring 50 mutations, mainly within the spike protein’s receptor-binding domain (RBD), has a higher transmission rate as compared to other variants. This study focused on two recent Omicron subvariants, XBB.1.5 and CH.1.1, which are known for their high affinity for the human ACE2 receptor. Utilizing an in silico strategy, a total of 1.65 μs molecular dynamics (MD) simulations were performed to assess the stability as well as binding details of these subvariants along with the wild-type Omicron variants. The comprehensive structural stability of the spike protein–hACE2 complexes was evaluated by using numerous parameters including root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and principal component analysis (PCA). Moreover, the binding free energies have been determined using the MM-GBSA approach to provide insights into the binding affinities of these variants. Evaluation revealed that the unbound mutant frameworks (SM and TM) displayed higher degrees of instability in comparison to the wild-type (WT) Omicron variant. In contrast, the WT–hACE2 of the Omicron variant complex was less stable than the subvariants, SM–hACE2 and TM–hACE2 complexes. Binding free energy calculations employing MM-PBSA disclosed higher binding energy values for the SM–hACE2 and TM–hACE2 complexes, suggesting a more stable and ordered binding interaction. The observed increase in transmissibility of the new XBB.1.5 and CH.1.1 subvariants, in comparison to the wild-type Omicron, appears to be due to this greater stability and ordered binding
