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Development And Application Of Enhanced Sampling Techniques For Investigating Protein Interactions And Drug Discovery
No full textUnderstanding the dynamics of protein–protein and protein–ligand interactions is critical for elucidating biological function and guiding drug discovery. However, many such processes involve rare events and high energy barriers that are difficult to capture with conventional molecular dynamics (MD). Enhanced sampling techniques extend the reach of MD, enabling access to biologically relevant transitions and thermodynamic properties. In the first project, Gaussian accelerated MD (GaMD) was used to study the MEIG1–PACRG complex, a key regulator of sperm flagellar assembly. Simulations of wildtype and mutant MEIG1 (W50A, Y68A) revealed mutation-specific disruptions to the binding interface and identified druggable pockets, particularly on PACRG. Virtual screening and MD simulations were then applied to identify small-molecule inhibitors targeting this complex, yielding promising candidates stabilized by hydrogen bonding and π-π stacking interactions. The second project used ligand GaMD (LiGaMD) to investigate the unbinding of linoleic acid from the SARS-CoV-2 spike protein. Simulations captured eight dissociation events and revealed two dominant pathways influenced by RBD gating and glycan dynamics, offering insights into ligand regulation of spike–ACE2 binding. In the third project, a new method called Multiple Parameter Replica Exchange GaMD (MP-Rex-GaMD) was developed to improve sampling efficiency and energetic reweighting. Benchmarking on dialanine, chignolin, and HIV protease demonstrated enhanced conformational exploration and accurate free energy recovery. Together, these projects highlight the power of enhanced sampling MD to uncover molecular mechanisms, inform inhibitor design, and advance methodological innovation in biomolecular simulation
Latent Profiles Of Primary And Secondary Stress Appraisal: Interpreting Cortisol Response To An Acute Laboratory Stressor
No full textPsychological stress is an established precursor to disease risk. One physiological system responsive to stress and associated with disease is the hypothalamic-pituitary-adrenal axis whose product hormone is cortisol. However, the relationship between psychological stress and cortisol response is inconsistent despite both resulting from acute stress. This discrepancy may be due in part to limitations in the measurement of cognitive appraisal of stress. The Transactional Model of Stress and Coping (TMSC) posits that perceived threat of the stimulus (i.e., primary appraisal) and personal ability (i.e., secondary appraisal) are dynamic evaluations contingent upon each other to determine psychological stress. In four studies, this dissertation tested whether calculating the full combination of high and low scores of primary and secondary appraisals coincided with distinct patterns of cortisol activity to an acute stressor. A series of two pilot studies were conducted to first test the validity of a cognitive task administrated online. Pilot 1 found no differences in task difficulty or stress appraisal among an easy and two difficult conditions. The results of Pilot 2 indicated that a newly tested, third difficult condition was more difficult than the easy condition. This third condition was used in Study 1 among adults recruited from Prolific. Cognitive appraisal of the stressor was self-reported at three timepoints throughout the cognitive task. Latent profile analysis uncovered three appraisal groups at the mid-task timepoint: a Moderate Primary, High Secondary Appraisal group, a Moderate Primary & Secondary Appraisal group, and a Moderate Primary, Low Secondary Appraisal group. Convergent validity with self-efficacy and tense arousal suggested the groups reflected feeling Unperturbed, Challenged, and Threatened, respectively. The same groups were also found at the pre- and post-task timepoints. Latent transition analysis revealed that participants were more likely to remain in their original appraisal group than transition to another group throughout the cognitive task. Differences in appraisal groups were also tested with education, age, gender, and select psychological variables. Subsequently, Study 2 sought to replicate these appraisal groups and test their association with cortisol activity to the Trier Social Stress Test in a sample of adolescents from Detroit. Cluster analysis at the mid-task timepoint revealed three groups. Two groups – High Primary, High Secondary Appraisal and High Primary, Low Secondary Appraisal – were similar to Study 1, but the Low Primary, Moderate Secondary Appraisal group was unique to Study 2. In contrast to Study 1, participants were more likely to transition to another appraisal group than to remain in their original appraisal group throughout the TSST. The appraisal groups were not associated with cortisol reactivity slopes, peak levels, or recovery slopes to the TSST. In line with the TMSC, these studies provide evidence that stressors evoke multiple appraisals that are being overlooked by current methods of calculating cognitive stress appraisal. Replication with other stressors and larger samples is needed
Associations of CCR5Δ32 with COVID-19 in an Iraqi Kurdish Population and Global Allele Frequencies of CCR5Δ32
No full textChemokine receptor 5 Delta 32 (CCR5Δ32), a 32-nucleotide deletion in the receptor’s gene, is associated with infectious diseases (e.g., protection against HIV-1). Studies have yielded conflicting results regarding this receptor and Coronavirus Disease 19 (COVID-19) in various nations. No studies have investigated the CCR5 genetic polymorphisms in Kurdish populations. Few studies have been performed in Iraq regarding associations of CCR5 with infectious diseases including COVID-19. This study aims to investigate associations of CCR5Δ32 with COVID-19 in an Iraqi Kurdish population and global allele frequencies of the CCR5Δ32 associated with various diseases around the world.
Conventional polymerase chain reaction (PCR) was used to explore the CCR5Δ32 based on the PCR product size run on agarose gel electrophoresis. Comparisons of the wild-type (W) and the mutant (Δ32) genotypes were statistically analyzed between the control (n=114) and patient groups (n =125).
In the control group, 109 individuals (95.6%) carried the wild-type homozygous (W/W) genotype, while 5 individuals (4.4%) carried the heterozygous (W/Δ32) genotype. In the COVID-19 group, the homozygous (W/W) and heterozygous (W/Δ32) genotypes were 123 (98.4%) and 2 (1.6%), respectively. No homozygous mutants (Δ32/Δ32) were found in the control and patient groups. The allele frequencies of the CCR5Δ32 were 2.2% and 0.8% in the control and patient groups, respectively. However, the data analyzed were not statistically significant. The global allele frequency data showed that the CCR5Δ32 is controversially associated with several diseases, including COVID-19.
This is the first study showing the distribution of the CCR5Δ32 allele in Iraqi Kurds. Associations of this allele with COVID-19 infections were not significant, possibly due to the rarity of this deletion. Moreover, the first report of this allele’s frequency in an Iraqi Kurds is a Preprint version. Visit http://digitalcommons.wayne.edu/humbiol/ after publication to acquire the final version. unique and novel contribution to population genetics. However, it might still have a role in COVID-19 infections in a large scale of samples in other ethnic groups in which this allele is common. The results also indicated that this deletion, in Kurds, is neither as common as in Eurasian populations nor as seldom as in East Asian populations, but it is similar to African or American global frequency data. This highlights the significance of this allele acting as a protective or risk factor against infections, including Covid-19 and HIV
Wingless Bird: Femininity, Violence, and Disempowerment in a South Asian Fairy Tale
No full textIn some South Asian fairy tales, an ogre’s or witch’s “life” resides in the body of a bird. This article discusses the significance of the bird motif in “The Outcast Queens and the Ogress Queen.” While the story changes across its multiple iterations, in each instance, the reestablishment of order in the kingdom requires the destruction of a bird that holds the life of the antagonist. Through a critical analysis of the bird motif and other symbols of danger such as cannibalism and similar perversions of appetite, I argue that the tale offered a set of codes about gender-appropriate attitudes to power and justice within the cultures in which it circulated
The Influence of False Memories on Eyewitness Testimony
No full textThis paper examines the role that false memories play in eyewitness testimony. Though eyewitness testimonies are a direct source of evidence regarding a crime, they are often flawed due to the malleable and reconstructive nature of memory, leading to many wrongful convictions. This review synthesizes previous research on false memories and eyewitness testimony to analyze the factors that contribute to inaccuracies in eyewitness testimony. This paper examines the origination of false memories, highlighting key factors such as the misinformation effect, source misattribution, and retention intervals. Additionally, this review analyzes factors from previous research that increase susceptibility to false memories, the variables that contribute to the alignment of remembered testimony, and the impact of how testimony and evidence are perceived. This paper demonstrates that human memory is a reconstructive process that is prone to errors, often making eyewitness testimony an unreliable source. This paper concludes with a discussion of potential solutions to improve the accuracy of eyewitness testimony
Michigan Prevention Workforce Development Report 2025
No full textThe Substance Use Research Team from the School of Social Work at Wayne State University conducted the 2024 Substance Misuse Prevention Workforce Development Survey to gain insights on the experiences and training needs of substance misuse prevention providers in Michigan. This report presents results from 277 respondents who completed the online survey. Below, survey respondents\u27 background characteristics and key findings related to employment and benefits, retention and work obstacles, clinical supervision, and training needs are summarized. We encourage readers to view the full report to understand the depth and breadth of these findings
On A First Name Bias: A Bibliometric Study Of Six Writing Studies Journals
No full textOn a First Name Bias: A Bibliometric Study of Six Writing Studies Journals analyzes citation, authorship, source use, and other bibliometric patterns across a small collection of peer-reviewed journals featuring research from the academic field of writing studies (also known as rhetoric and composition). The study is grounded in a small but established tradition of RAD (replicable, aggregable, data-supported) scholarship in the field and uses bibliometric methods inspired by similar, primarily historiographic research studies within the field of writing studies and by critical inquiry from scholars across disciplines who have used bibliometric analysis to interrogate troubling patterns of publishing and citation when controlling for identities such as gender, race, ethnicity, or institutional affiliation. This study drew data from the citation lists and authorial records of research articles from two different sets of journals referred to as “old growth” and “new growth” journals. The old growth journals include three long-established, decades-old journals in the field and the new growth journals are more recently-established journals in their first decade of publication. To track published and cited author gender, race, and ethnicity, this study drew from sociological research that indicates first names are a reliable marker for identities such as gender, race, or ethnicity. This methodological approach to a bibliometric analysis is novel in writing studies. Major findings from this study include indications that scholars with feminine coded names are more likely to be published and to be cited in the field’s journals than they have been in the past; on the other hand, scholars with non-White coded names (i.e., Black, Hispanic, Asian and Pacific Islander, American Indian or Alaska Native) remain less prevalent as both published authors and across citation lists. The study concludes with a number of observations for future research, and argues that using first names as a coding strategy in resource thin environments (e.g., graduate directors, writing program administrators) is a practical tool for empirical intervention into articulated concerns or problems
Medical Aid In Dying: Physician Beliefs, Practices, And Respect For Autonomy
No full textMedical aid in dying (MAiD) consists of clinicians helping terminally ill persons seek, and if eligible, complete a medically assisted death. It is increasingly legal across the United States with two states eliminating residency requirements. Although opinion polls often show most Americans believe MAiD should be legal, the practice remains stigmatized. Opponents of it worry about abuse, coercion, and a change in culture that could lead to further devaluing disabled lives, while proponents hail MAiD as providing autonomy and choice. The bioethical value of respect for autonomy is closely related to the social work profession’s duty to respect and promote clients’ self-determination. Anthropologists studying MAiD have joined others in complicating the notion of the dying person’s independent autonomy in lived experiences of MAiD. With this complication in mind, this dissertation sought to explore MAiD physicians’ experiences (n = 20), practices, beliefs using ethnographic methods of narrative and semi-structured interview, participant-observation, and archival review. Interviews were also conducted with one caregiver and two advocates. Analyses are presented herein in three stand-alone chapters: The first chapter is a previously published excerpt (chapter and appendix entry) from a trade text serving as a guide to family caregivers for someone dying at home (Sankar & Cassady, 2024). This material incorporates the case study of a MAiD caregiver into difficult decisions and situations surrounding end-of-life. It puts MAiD situations and decisions alongside other treatment decisions and difficult situations, providing information and resources for those considering MAiD. The second chapter features an analysis of data regarding times from ingestion to death in MAiD. Here, physicians describe good care as shortening clock times or subjective times to death by identifying and re-placing agencies; capacities to act, rather than identifying individual autonomy. Physicians use clinical agency to manipulate pharmaceutical, biological, clinical, patient and family agencies in attempts to reduce uncertainty and suffering for family during the death vigil. Looking at cases that fit within the theme and then that don’t fit, this chapter asks important questions about what clinical practices reduce suffering and how the ability to do something is valued in death vigils in MAiD and beyond. The third chapter presents physician practice themes and discusses overlap with social work end-of-life roles. Practice guidance for social workers in the United States focuses primarily on ethical issues perceived in MAiD. Given that MAiD is likely discussed and considered widely beyond those completing a MAiD death, this article marshals practice data addressing goals MAiD discussions, hospice support, and family needs during the death vigil to show that social work professionals, leaders, and researchers need to move beyond the focus of ethics and towards what MAiD practice looks like. Finally, the implications for this research are discussed and future research topics relevant to both anthropology and social work are proposed
Demand Characterization For Real-Time Cyber-Physical Systems: Algorithms, Analysis, And Applications To Control Systems
No full textThis work adds novel co-design, demand characterization, and utilization bounding tools to the real-time community toolbox for the effective deployment of real-time, safety-critical cyber-physical systems. Specifically, this work exploits system dynamics for improved real-time analysis in: software-based short circuit detection, intelligent power distribution systems (IPDSes), robotic arm motion, and internal combustion engines (ICEs). In short detection, inductor sub-saturation back-EMF is exploited to link circuit size and task utilization. In the IPDS, sub-maximal loading is used to bound system utilization for variable-frequency current monitoring tasks. For the robotic arm, repeated motion and error-dependent worst-case execution time are leveraged for faster schedulability analysis. In the ICE, kinematic limitations (max speed, max acceleration) are exploited to reduce the search space for maximum demand and a corresponding fully polynomial time approximation scheme and parallelization regime for faster demand calculation. The techniques enumerate varied approaches on different cyber Physical Systems for improving analysis of real-time tasks with complex parameters
Managing Projects, Managing Emotions: Understanding Student Attitudes Towards Collaboration In Technical Communication Courses
No full textThis dissertation details the results of a mixed-methods study into student attitudes towards and emotions experienced during collaboration in technical communication courses at a large, urban research university. Survey results indicate that students are neutrally to positively disposed to the practice of collaboration. Student reflections further demonstrate that although students often feel nervous at the outset of collaborative projects, they rely on generative emotions like hope to motivate them during their process. This dissertation advocates that reflective writing occupy a larger place within technical communication classrooms in order to help students develop the flexibility necessary to succeed in workplace writing, which frequently involves collaboration. It provides an example of how emotional intelligence can be used as a framework for this purpose