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A Conjugate of an EGFR-Binding Peptide and Doxorubicin Shows Selective Toxicity to Triple-Negative Breast Cancer Cells
Get PDFSelective targeting of cancer cells via overexpressed cell-surface receptors is a promising strategy to enhance chemotherapy efficacy and minimize off-target side effects. In this study, we designed peptide 31 (YHWYGYTPERVI) to target the overexpressed epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) cells. Peptide 31 is internalized by TNBC cells through EGFR-mediated endocytosis and shares sequence and structural similarities with human EGF (hEGF), a natural EGFR ligand. Unlike hEGF, peptide 31 does not induce cell migration in TNBC cells. A novel conjugate of peptide 31 with doxorubicin (Dox) retains selectivity for TNBC cells and exhibits significant toxicity comparable to that of unconjugated Dox. Importantly, this conjugate shows no toxicity toward normal breast epithelial cells up to a high concentration (25 μM). Thus, peptide 31 serves as a versatile targeting ligand for developing novel conjugates with high selectivity for EGFR-positive cancers
Probing Functional Allosteric States and Conformational Ensembles of the Allosteric Protein Kinase States and Mutants: Atomistic Modeling and Comparative Analysis of AlphaFold2, OmegaFold, and AlphaFlow Approaches and Adaptations
No full textThis study reports a comprehensive analysis and comparison of several AlphaFold2 adaptations and OmegaFold and AlphaFlow approaches in predicting distinct allosteric states, conformational ensembles, and mutation-induced structural effects for a panel of state-switching allosteric ABL mutants. The results revealed that the proposed AlphaFold2 adaptation with randomized alanine sequence scanning can generate functionally relevant allosteric states and conformational ensembles of the ABL kinase that qualitatively capture a unique pattern of population shifts between the active and inactive states in the allosteric ABL mutants. Consistent with the NMR experiments, the proposed AlphaFold2 adaptation predicted that G269E/M309L/T408Y mutant could induce population changes and sample a significant fraction of the fully inactive I2 form which is a low-populated, high-energy state for the wild-type ABL protein. We also demonstrated that other ABL mutants G269E/M309L/T334I and M309L/L320I/T334I that introduce a single activating T334I mutation can reverse equilibrium and populate exclusively the active ABL form. While the precise quantitative predictions of the relative populations of the active and various hidden inactive states in the ABL mutants remain challenging, our results provide evidence that AlphaFold2 adaptation with randomized alanine sequence scanning can adequately detect a spectrum of the allosteric ABL states and capture the equilibrium redistributions between structurally distinct functional ABL conformations. We further validated the robustness of the proposed AlphaFold2 adaptation for predicting the unique inactive architecture of the BSK8 kinase and structural differences between ligand-unbound apo and ATP-bound forms of BSK8. The results of this comparative study suggested that AlpahFold2, OmegaFold, and AlphaFlow approaches may be driven by structural memorization of existing protein folds and are strongly biased toward predictions of the thermodynamically stable ground states of the protein kinases, highlighting limitations and challenges of AI-based methodologies in detecting alternative functional conformations, accurate characterization of physically significant conformational ensembles, and prediction of mutation-induced allosteric structural changes
\u3cem\u3eGarland v. Cargill\u3c/em\u3e: It’s a Duck! Except at the Supreme Court . . .
Get PDFGarland v. Cargill may go down as one of the most notorious cases ever handed down by the Supreme Court. By a 6-3 tally, “bump stocks”—which essentially turn semi-automatic weapons into machine guns—were deemed outside the purview of the National Firearms Act of 1934 (NFA). Initially, the Bureau of Alcohol, Tobacco, Firearms, and Explosives (ATF) determined that bump stock-converted weapons did not fall within the statutory definition of a machine gun. Amidst a bipartisan outcry following the 2017 Las Vegas Massacre, the ATF changed course, determining that bump stock conversions were indeed “machine guns” and therefore prohibited by the NFA. In her dissent, Justice Sotomayor called it like it was: “When I see a bird that walks like a duck, swims like a duck, and quacks like a duck, I call that bird a duck.”
Whether intended or not, Cargill greenlights the path by which would-be assassins and insurrectionists can easily and legally arm themselves with the functional equivalent of machine guns. Cargill also enables both madmen and common criminals to up their firepower to match or even best that of law enforcement. While Congress presumably could reinstate the ban, that window could be closing under the “dangerous and unusual” Second Amendment carveout. Gun lobbyists are already floating arguments that, so long as an item is readily commercially available, it is not “unusual,” and therefore protected against categorical prohibition.
This Article argues for a change in the social and legal rhetoric surrounding gun reform to center indirect victims. Surprisingly, that corresponds to historical limitations on the scope of the Second Amendment. Of course, the individual and societal right to be free from undue terror needs to be balanced against the right to bear arms. That balance existed at the Founding. The open issue regarding the continued legality of bump stocks arguably offers the perfect baby step to return to the ideals of the Founders, set aside tribalism, and come together for the common good
Gift of the Town & Gown Endowment for the Arts, Humanities, and Social Sciences 2024
No full textA bibliography of the books that Chapman University\u27s Town & Gown donated to the Leatherby Libraries\u27 collections for 2024
Board 125: Work in Progress: Faculty Experiences and Learning Through Oral-Assessment Implementation in Engineering Courses
No full textThis WIP qualitative research paper explores faculty experiences with implementing oral exams in high-enrollment undergraduate engineering courses at a research university. With a primary goal to improve conceptual mastery, as well as a desire to ensure academic integrity in the sudden move to remote instruction at the height of the pandemic, a group of faculty in Mechanical and Aerospace Engineering and Electrical and Computer Engineering departments implemented oral assessments in their own engineering courses across several quarters. They formed a research group with educational developers in a teaching and learning center on campus, and investigated the impact of oral assessments on student learning, as well as the impact on faculty. To examine the impact on faculty, 90-minute semi-structured interviews were conducted with six faculty members to explore how the implementation of oral assessments informed: 1) Their perspectives of teaching and learning and their teaching practices; and 2) how oral assessments contributed to faculty/student interactions with undergraduate students in their courses and graduate student Instructional Assistants. Applying growth mindset (Dweck, 2006) as a framework, data were analyzed by using grounded theory guidelines. This WIP paper highlights how the growth-oriented mindset of faculty enabled student-centered instructional design for deeper conceptual mastery, connections between students and the instructional team, and faculty’s own growth in their teaching journey (or, reflective teaching practices). It also highlights the benefits and challenges experienced by faculty and recommendations for implementing oral assessments for others interested in implementing oral assessments for similar purposes. We would like this WIP paper to be considered for a poster presentation at ASEE 2024
How Misogyny in Gaming Affects Black Women/POC
Get PDFThis research query explores the gaming industry and how its misogynistic issues affect the Black community in its forums. Research has shown that there has been a suppressed issue of prejudice against women of color in many gaming spaces in the last 20 years. Video games, created for healing and interactive spaces for communities seemingly have normalized its harming nature to minority groups. My research will look into aspects of how gender bias and racism mix into the gaming industry and cause distress among its players. I will research how misrepresentation in the character personas in video games lead to stereotypical forms of perception for women of color. Using the methods outlined in the Information Literacy portion of the FFC program, I will be researching this topic using a variety of methods. My research will involve using real life accounts of women players who have dealt with the consequences of false perception in gaming, and scholarly peer reviewed sources of experts in gender and racial bias. I also plan to include portions from books, articles, and studies about harm in gaming communities. I anticipate that the research will prove that there is an underlying issue for women of color in the gaming industry, that is being normalized to avoid conflict. Evidence of this can be shown in low demographic rates of players, hostile gaming forums, and stereotyped characters in video games
MoViAn: Advancing Human Motion Analysis with 3D Visualization and Annotation
No full textHuman motion analysis, including data visualization and annotation, is crucial for understanding human behavior and intentions during various activities, aiding in the development of innovative tools that support independent living. Current wearable sensing technology provides rich 3D spatial movement data but generates multimodal complex datasets that require specialized skills for effective analysis. Despite the need, limited research exists on tools for effective visualization and easy annotation of such complex motion data. MoViAn (Motion Data Visualization and Annotation) is an innovative 3D data analysis system offering enriched visual representations of 3D human motion data (e.g., gaze, hand movements), along with an interactive user interface for data annotation. This paper presents a user study with 11 participants and demonstrates that MoViAn facilitates data annotation of human motion effectively through both quantitative and qualitative assessments. Specifically, gaze visualization improves annotation accuracy by 18.23%, while hand-tracing visualization increases annotation speed by 28.05% compared to a controlled setting. These findings highlight MoViAn’s potential for handling multimodal human motion data, paving the way for developing innovative tools that provide real-time monitoring and assessment of physical activities to support independent living
Smartphone Haptics Can Uncover Differences in Touch Interactions Between ASD and Neurotypicals
Get PDFUtilizing touch interactions from smartphones for gathering data and identifying digital markers for screening and monitoring neurological disorders, such as Autism Spectrum Disorder (ASD), is an emerging area of research. Smartphones provide multiple benefits for this kind of study, including unobtrusive data collection via built-in sensors, integrated haptic feedback systems, and the capability to create specialized applications. Acknowledging the significant yet understudied presence of tactile processing differences in individuals with ASD, we designed and developed Feel and Touch, a mobile game that leverages the haptic capabilities of smartphones. This game provides vibrotactile feedback in response to touch interactions and collects data on these interactions. We conducted a deployment study with 83 Mexican children who played Feel and Touch to capture their interactions with the game. Our analysis, comparing touch interactions between children with ASD and neurotypical (NT) peers, uncovered three digital markers based on phone tilt and touch patterns that distinguish the two groups. Additionally, we demonstrated the ability of a machine learning model to accurately classify these interactions between ASD and NT children. Our findings discuss the implications in terms of accessibility and ubiquity, as well as the possibilities for the development of digital markers and their application in pervasive computing for healthcare
Racing \u3cem\u3eLatinidad\u3c/em\u3e
No full textThis chapter argues that the terms “Latinx” and “latinidad” are messy signifiers that allow us to contend with Latinx’s complicated racial history. While the term Latinx continues to be controversial, and scholars such as Tatiana Flores have examined the case for cancelling latinidad, “Racing Latinidad” points to how latinidad can signify particular political commitments and affinities. Through readings of Manuel Muñoz’s What You See in the Dark (2011) and Dahlma Llanos-Figueroa’s Daughters of the Stone (2009), this chapter illuminates how excavating racial histories outside the logic of the state is a way to summon a politics to imagine a people. Within this framework, “Racing Latinidad” ultimately argues for embracing the incoherence of latinidad as term that resists legibility and visibility and thus institutionalization and state management.https://digitalcommons.chapman.edu/english_books/1043/thumbnail.jp
Transparency and Authority Concerns with Using AI to Make Ethical Recommendations in Clinical Settings
Get PDFIn response to recent proposals to utilize artificial intelligence (AI) to automate ethics consultations in healthcare, we raise two main problems for the prospect of having healthcare professionals rely on AI-driven programs to provide ethical guidance in clinical matters. The first cause for concern is that, because these programs would effectively function like black boxes, this approach seems to preclude the kind of transparency that would allow clinical staff to explain and justify treatment decisions to patients, fellow caregivers, and those tasked with providing oversight. The other main problem is that the kind of authority that would need to be given to the guidance issuing from these programs in order to do the work set out for them would mean that clinical staff would not be empowered to provide meaningful safeguards against it in those cases when its recommendations are morally problematic