Deconvolution of Membrane Protein-Detergent Complex Interactions

Membrane proteins are important in many biological functions such as cell-cell recognition, transport, and signaling; yet the study of these proteins is stunted due to their excessive aggregation in aqueous solutions. Detergents have been extensively exploited to mitigate this aggregation, and accomplish this by protecting the hydrophobic exterior of the membrane protein with their hydrophobic tails, while the polar heads of the detergents interact with the surrounding aqueous environment. Although detergents are of fundamental importance in many membrane protein studies, their selection is primarily done by trial and error screening. In this thesis, I will describe a method to utilize steady state fluorescence polarization to look at the desolvation of detergents from various membrane proteins. The overall goal is to create a methodology that can be employed broadly to map the kinetic fingerprints of various detergents with distinct membrane proteins. This map could potentially be used to build a model that would allow for the better selection and design of amphipols and detergents. Using this newly described florescence polarization anisotropy method, I examine the quantitative contributions of the adhesive protein-detergent and the cohesive detergent-detergent interactions for four beta barrel proteins in five distinct detergents. Further highlighting the generalizable nature of this method, I show the feasibility of this method by using two single pass alpha helical membrane proteins SELENOK and SELENOS. Next, we utilize real time kinetic reads of detergent desorption by describing two distinct phases of the desorption process. The kinetic reads allow the exploration of these interactions and the description of the inferred rate constants of association and dissociation of various detergent-protein complexes. Taken together, I will also explore the intricacies of these protein detergent complexes by describing their dependence on both the biophysical architecture of the membrane protein and the physiochemistry of the detergent itself

Beyond a Company of Soldiers: Exploring Phenotypic Integration across the Multivariate Human Growth and Development Phenotype

Traditional studies exploring the interrelationships between growth and development traits have lacked the data necessary to fully describe the multivariate growth and development phenotype and the statistical methodology to quantify the complex interrelationships between varied trait types. Subsequently, human growth and development are often defined by a series of contrasts via the juxtaposition of seemingly disjoint processes in skeletal diaphyseal growth, skeletal ossification and fusion, and development of the dentition. In conjunction with robust data sources from the Subadult Virtual Anthropology Databases (SVAD), this work introduces a Mixed Discrete-Continuous Gaussian copula to explore the multivariate human growth and development phenotype. A copula is a probabilistic function that explicitly models the interrelationships between traits and describes the joint structure of the multivariate relationships.Fifty-four growth traits are collected from the United States sample in SVAD (n = 1,316). These traits include 18 measurements associated with diaphyseal dimensions collected from six long bones, 20 scores of both epiphyseal fusion and primary ossification centers, and 16 scores of dental development across the left-sided mandibular and maxillary dentition. All data are collected from computed tomography (CT) images and includes demographic information such as an individual’s chronological age and biological sex. The joint probability distribution of the 54 growth traits and the underlying dependency structure are fit to a Mixed Discrete-Continuous Gaussian copula using the gradient-based Markov Chain Monte Carlo algorithm known as Hamiltonian Monte Carlo within the Stan probabilistic programming environment. Six total copula models are fit: the first model utilizes the full dataset, the next three models use subsets of the full dataset representing the individual developmental stages of infancy, childhood, and juvenile/adolescence, and the last two models use subset of the full dataset representing biological males and females.Results from the full model show that relationships are strongest within each growth module. Further, traits that develop across similar developmental windows show stronger positive correlations as compared to traits that grow and develop during separate periods. These relationships are similar between males and females suggesting that, independent of age, multivariate growth and development processes are the same across the sexes. When considering developmental stages, the results show that the multivariate phenotype presents with different relationships between variables across ontogeny with the strongest relationships between growth and development modules tied to active growth and development periods. Importantly, the skeletal growth, skeletal development, and dental development modules can be further divided into additional units that themselves have various levels of dependence.The copula demonstrates that the relationships between broad growth modules cannot be summarized via a few pairwise correlations taken at one point during ontogeny. Instead, analyses should be conducted with as much trait information as possible and at various points throughout ontogeny. In the future, copulas could also be extended to additional applications in biological anthropology including research in bioarchaeology and paleoanthropology, method formation in forensic anthropology, and the estimation and imputation of missing data. In sum, the Mixed Discrete-Continuous Gaussian copula provides the most comprehensive analysis to date of the multivariate human growth and development phenotype and lays the groundwork for future research into the growing, developing, multivariate human

Sex Specific Responses to Perceptually Regulated Work-to-Rest Ratios during Resistance Training

Recovery has long been an important training variable, receiving increased attention within the scientific literature. While there has been considerable attention to intersession recovery, less is known about optimizing intrasession recovery. Additionally, growing evidence suggest women may experience relatively less fatigue with greater acute recovery as opposed to men when exercising at similar intensities. However, relatively little is known regarding the impact of self-regulated within session recovery between men and women during resistance training. PURPOSE: Therefore, the purpose of the research is to examine the sex specific responses to perceptually regulated work-to-rest ratios during strength training. METHODS: Participants (n = 14; 7 men, 7 women) completed two sessions. Session one consisted of obtaining each individual’s one-repetition maximum (1RM) for squat (SQ) and bench press (BP) using the National Strength and Conditioning Association standardized procedures. Following a minimum of 48 hours of recovery, participants performed 5 sets of 6 repetitions at 80% of their 1RM for SQ and BP (experimental session). Immediately following each set of work (SW), rating of perceived exertion (RPE) using the OMNI RPE scale for resistance training was recorded. Participants utilized the Perceived Recovery Status (PRS) scale to guide their recovery. Participants were instructed that when they reach a ‘7’ (out of 10) begin their next set. Following completion of the SQ participants were given 15 minutes before completing the same procedure for the BP. RESULTS: Results from an 1-Way ANOVA, indicate no statistically different (SQ: SW1 =0.88; SW2 p=0.18; SW3 p=0.53; SW4 p=0.19; BP: SW1 =0.09; SW2 p=0.07; SW3 p=0.28; SW4 p=0.25) time to recovery between men (SQ: SW2 109.6 ± 40.4; SW3 136.9 ± 37.4 ; SW4 191 ± 82.5; SW5 178.7 ± 79.7; BP: SW2 137.3 ± 45.9; SW3 173.6 ± 88.3; SW4 170.6 ± 133.5; SW5 194.7 ± 133.1) and women (SQ: SW2 115.6 ± 89.9; SW3 109 ± 36.5 ; SW4 111 ± 53.9; SW5 122.6 ± 69.4; BP: SW2 94.4 ± 39.3; SW3 102.1 ± 88.3; SW4 109 ± 56.2; SW5 127.4 ± 54.4). However, there was a large effect size of sex time to recovery as calculated by Cohen’s d (SQ: SW1 d =0.09; SW2 d=0.74; SW3 d =1.19; SW4 d =0.76; BP: SW1 d =1.02; SW2 d =1.15; SW3 d =0.65; SW4 d =0.72). While no statistical difference was found, the self-selected recovery time between men and women indicated women self-select shorter recovery periods on both SQ and BP, with no differences in volume of work. CONCLUSION: These findings support the notion that women may experience either relatively less fatigue during exercise or can recovery from similar intensities faster than men. Further work is needed to determine optimal work-to-rest ratios between men and women during resistance training and what implications this may have on training adaptations

Identifying the clinical domains of fibromyalgia: Contributions from clinician and patient delphi exercises

Objective In evaluating the effectiveness of fibromyalgia (FM) therapies, it is important to assess the impact of those therapies on the full array of domains considered important by both clinicians and patients. The objective of this research was to identify and prioritize the key clinically relevant and important domains impacted by FM that should be evaluated by outcome assessment instruments used in FM clinical trials, and to approach consensus among clinicians and patients on the priority of those domains to be assessed in clinical care and research. Methods Group consensus was achieved using the Delphi method, a structured process of consensus building via questionnaires together with systematic and controlled opinion feedback. The Delphi exercises involved 23 clinicians with expertise in FM and 100 patients with FM as defined by American College of Rheumatology criteria. Results The Delphi exercise revealed that the domains ranked most highly by patients were similar to the domain rankings by clinicians. Pain was consistently ranked highest by both panels. Fatigue, impact on sleep, health-related quality of life, comorbid depression, and cognitive difficulty were also ranked highly. Stiffness was ranked highly by patients but not clinicians. In contrast, side effects was important to clinicians but was not identified as important in the patient Delphi exercise. Conclusion The clinician and patient Delphi exercises identified and ranked key domains that need to be assessed in FM research. Based on these results, a conceptual framework for measuring patient-reported outcomes is proposed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60452/1/23826_ftp.pd

Generation of broad spectral components from midwave infrared ultrashort pulse laser propagation through ZnSe and ZnS

We investigate the nonlinear optical properties of ZnSe and ZnS using ultrashort (pulse duration approximately 200 fs) midwave infrared laser pulses between 3 and 4 mu m. Multiple harmonic generation in both materials was observed, as well as significant spectral modification of the fundamental pulse. Simulations using a nonlinear polarization model enhanced with ionization compared favorably with experimental data. Random quasi phase matching in the materials is the likely generator of the observed harmonics.SURVICE [S17-095008/DOTC-17-01-INIT0086]; Air Force Office of Scientific Research (AFOSR) [FA9550-16-1-0069]; AFOSR multidisciplinary research program of the university research initiative (MURI) [FA9550-16-1-0013]; AFOSR [FA9550-16-1-0121]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Standardization of microbiome studies for urolithiasis: an international consensus agreement

Numerous metagenome-wide association studies (MWAS) for urolithiasis have been published, leading to the discovery of potential interactions between the microbiome and urolithiasis. However, questions remain about the reproducibility, applicability and physiological relevance of these data owing to discrepancies in experimental technique and a lack of standardization in the field. One barrier to interpreting MWAS is that experimental biases can be introduced at every step of the experimental pipeline, including sample collection, preservation, storage, processing, sequencing, data analysis and validation. Thus, the introduction of standardized protocols that maintain the flexibility to achieve study-specific objectives is urgently required. To address this need, the first international consortium for microbiome in urinary stone disease - MICROCOSM - was created and consensus panel members were asked to participate in a consensus meeting to develop standardized protocols for microbiome studies if they had published an MWAS on urolithiasis. Study-specific protocols were revised until a consensus was reached. This consensus group generated standardized protocols, which are publicly available via a secure online server, for each step in the typical clinical microbiome-urolithiasis study pipeline. This standardization creates the benchmark for future studies to facilitate consistent interpretation of results and, collectively, to lead to effective interventions to prevent the onset of urolithiasis, and will also be useful for investigators interested in microbiome research in other urological diseases

Intentional Technology For Teaching Practice

In today’s era, where educational technology is in a near-constant state of evolution, the imperative is not just to adopt technology, but to do so with a defined purpose and strategy. As educators within military education there is a growing need to discern which technological tools and practices align best with our mission and the goals we set for our students. Teaching is more than just transferring knowledge—it’s about fostering environments conducive to growth, critical thinking, and lifelong learning. This e-book contains collective insights, experiences, and reflections from faculty participating in a Faculty Learning Community (FLC) a yearlong, structured, community of practice, engaged in the thoughtful exploration of educational technology topics during the academic year of 2022-2023 at the Air Force Institute of Technology. Whether by leveraging social annotation tools to engage students in reading, formulating effective methods to produce and utilize educational content, innovating with game-based learning, or seamlessly integrating multiple applications for meaningful classroom experiences, our aim is to provide you with insights and actionable guidance for use within your own classrooms