Digital Commons Network^™

Pharmacy Involvement In Increased Access To Opioid Treatment Programs, Catherine O'Rourke

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The opioid epidemic still affects many Americans today. Despite approved medication treatments for opioid use disorder (OUD), a majority of the population with OUD have not received treatment. Since pharmacists are the most accessible health care professional and had an important role providing care during the COVID-19 pandemic, there has been a push to expand pharmacists’ scope of practice. The primary purpose of this investigation was to identify the benefits and barriers to community pharmacist-led treatment of OUD. The secondary purpose was to determine whether pharmacist participation in opioid treatment programs (OTPs) or office based opioid treatment (OBOT) would be …

The Effects Of Stigma Within The Prep Care Cascade Among People Who Inject Drugs In Rural Kentucky, Abby Burton

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background: Injection drug use has increased HIV burden in low-prevalence communities, specifically within rural Kentucky. Pre-exposure prophylaxis (PrEP) has been successful in terms of HIV prevention, yet uptake remains low among people who inject drugs (PWID). PWID living in rural areas face unique challenges to receiving PrEP care, including significant barriers of substance use- and HIV-related stigma. Recent studies have only started to explore the overlapping effects of these two stigmas. Considering the barriers each stigma independently poses to PrEP care, it is important to investigate their role in tandem for any compounding effects. This paper is a secondary analysis …

A Case Study In Program Evaluation, Lydia Williams

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The three core functions of public health are assessment, policy development, and assurance, and program evaluation falls under the latter category. A program is incomplete without an in-depth understanding of how well it works and what steps can be taken to make sure there is continuous progress and improvement.

In this case study, I developed an evaluation plan for the Lexington-Fayette County Health Department’s (LFCHD) infectious disease outbreak education program. The need for such a program was realized after a MRSA outbreak among a Kentucky high school football team. This case study employed the Center for Disease Control and Prevention …

Trust In Local Health Departments: A Cross-Sector Analysis Of Urban And Rural Communities, Kelsie Kwok

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Cross-sector collaboration is being looked to as best-practice for addressing complex issues. Given that trust is an important aspect of a well-functioning network, partners may have varying perceptions of trust regarding their counterparts. The primary objective is to examine partnerships and trust scores among six Kentucky communities (three urban, three rural) and their efforts to address unmet social needs. The secondary objective is to discuss differences among urban and rural communities regarding local health departments and the role of trust. A social network analysis (SNA) was conducted using the Program to Analyze, Record, and Track Networks to Enhance Relationships (PARTNER) …

Patterns Into Pathways For Improving Safety Culture: Refined Latent Class Analysis Informs Tailored Decision Support For South Carolina Dss Safety Culture Improvements, Michaela Voit

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The rising prevalence of exposures to adverse childhood experiences (ACEs) demands a coordinated public health response, as a significant body of research details the cumulative impact of ACEs on chronic morbidities contributing to reduced life expectancy. Child welfare workers (CWW) are embedded in this public health effort, tasked with preventing and mitigating the impacts of ACEs through family and prevention services. The National Partnership for Child Safety (NPCS) may improve the wellbeing of CWWs and the effectiveness of Child Welfare (CW) services by improving the quality of safety culture within CW organizations. To inform NPCS quality improvement efforts, our project …

Association Of Race, Ethnicity, And Gender To Disparities In Functional Recovery And Social Health After Major Lower Limb Amputation: A Cross-Sectional Pilot Study, Sheila M. Clemens, Kiarri N. Kershaw, Zoran Bursac, Szu Ping Lee

Physical Therapy Faculty Publications

Objective: To assess if evidence of disparities exists in functional recovery and social health post-lower limb amputation.

Design: Race-ethnicity, gender, and income-based group comparisons of functioning and social health in a convenience sample of lower limb prosthetic users.

Setting: Prosthetic clinics in 4 states.

Participants: A geographically diverse cohort of 56 English and Spanish speaking community-dwelling individuals with dysvascular lower limb amputation, between 18-80 years old.

Interventions: None.

Main Outcomes Measures: Primary outcomes included 2 physical performance measures, the Timed Up and Go test and 2-minute walk test, and thirdly, the Prosthetic Limb Users Survey of Mobility. The PROMIS Ability …

Combined Motivational Interviewing And Ecological Momentary Intervention To Reduce Hazardous Alcohol Use Among Sexual Minority Cisgender Men And Transgender Individuals, Carolyn Lauckner, Bryce Puesta Takenaka, Fidelis Sesenu, Jaime S. Brown, Sally J. Kirklewski, Erin Nicholson, Kimberly Haney, Reuben Adatorwovor, Donte T. Boyd, Keisa Fallin-Bennett, Arjee Javellana Restar, Trace Kershaw

Biostatistics Faculty Publications

Background: Sexual minority cisgender men and transgender (SMMT) individuals, particularly emerging adults (aged 18-34 years), often report hazardous drinking. Given that alcohol use increases the likelihood of HIV risk behaviors, and HIV disproportionately affects SMMT individuals, there is a need to test interventions that reduce hazardous alcohol use and subsequent HIV risk behaviors among this population. Ecological momentary interventions (EMIs), which use mobile phones to deliver risk reduction messages based on current location and behaviors, can help to address triggers that lead to drinking in real time. Objective: This study will test an EMI that uses motivational interviewing (MI), smartphone …

Bayesian And Frequentist Approaches To Rescuing Disrupted Trials, Cornelia Ursula Kunz, Sergey Tarima, Gary L. Rosner, Richard Emsley, Madeline Bauer, Christopher Jennison, James L. Rosenberger, Nigel Stallard, Sarah Zohar, Nancy Flournoy

Biostatistics Faculty Publications

The COVID-19 pandemic impacted clinical trials in ways never expected. However, similar challenges should now be expected going forward. These challenges made us aware of statistical problems arising from other types of disruptions that had not previously captured the attention of the statistical community. This article describes some frequentist and Bayesian statistical tools that can be used with future disruptions and illuminates issues that could benefit from more statistical research. Disruptions may threaten a clinical trial’s validity. Here, we address two resultant challenges: (a) performing an unplanned analysis with options to stop and/or change the sample size; and (b) changes …

Gwas Of Multiple Neuropathology Endophenotypes Identifies New Risk Loci And Provides Insights Into The Genetic Risk Of Dementia, Lincoln M.P. Shade, Yuriko Katsumata, Erin L. Abner, Khine Zin Aung, Steven A. Claas, Qi Qiao, Bernardo Aguzzoli Heberle, J. Anthony Brandon, Madeline L. Page, Timothy J. Hohman, Shubhabrata Mukherjee, Richard P. Mayeux, Lindsay A. Farrer, Gerard D. Schellenberg, Jonathan L. Haines, Walter A. Kukull, Kwangsik Nho, Andrew J. Saykin, David A. Bennett, Julie A. Schneider, Julie A. Schneider, Lindsay A. Farrer, Richard P. Mayeux, Subhabrata Mukherjee, Andrew J. Saykin, Walter A. Kukull

Biostatistics Faculty Publications

Genome-wide association studies (GWAS) have identified >80 Alzheimer’s disease and related dementias (ADRD)-associated genetic loci. However, the clinical outcomes used in most previous studies belie the complex nature of underlying neuropathologies. Here we performed GWAS on 11 ADRD-related neuropathology endophenotypes with participants drawn from the following three sources: the National Alzheimer’s Coordinating Center, the Religious Orders Study and Rush Memory and Aging Project, and the Adult Changes in Thought study (n = 7,804 total autopsied participants). We identified eight independent significantly associated loci, of which four were new (COL4A1, PIK3R5, LZTS1 and APOC2). Separately testing known ADRD loci, 19 loci …

Using Randomization Tests To Address Disruptions In Clinical Trials, Diane Uschner, Oleksandr Sverdlov, Kerstine Carter, Jonathan Chipman, Olga Kuznetsova, Jone Renteria, Adam Lane, Chris Barker, Nancy Geller, Michael Proschan, Martin Posch, Sergey Tarima, Frank Bretz, William F. Rosenberger

Biostatistics Faculty Publications

Recent examples for unplanned external events are the global COVID-19 pandemic, the war in Ukraine, or most recently Hurricane Ian in Puerto Rico. Disruptions due to unplanned external events can lead to violation of assumptions in clinical trials. In certain situations, randomization tests can provide nonparametric inference that is robust to violation of the assumptions usually made in clinical trials. The ICH E9 (R1) Addendum on estimands and sensitivity analyses provides a guideline for aligning the trial objectives with strategies to address disruptions in clinical trials. In this article, we embed randomization tests within the estimand framework to allow for …

Respiranalyzer, Teng Zhang, Xinzheng Dong, Dandan Wang, Chen Huang, Xiaohua Douglas Zhang

Biostatistics Faculty Publications

Motivation: The analysis of data obtained from continuous monitoring of respiratory signals (CMRS) holds significant importance in improving patient care, optimizing sports performance, and advancing scientific understanding in the field of respiratory health. Results: The R package RespirAnalyzer provides an analytic tool specifically for feature extraction, fractal and complexity analysis for CMRS data. The package covers a wide and comprehensive range of data analysis methods including obtaining inter-breath intervals (IBI) series, plotting time series, obtaining summary statistics of IBI series, conducting power spectral density, multifractal detrended fluctuation analysis (MFDFA) and multiscale sample entropy analysis, fitting the MFDFA results with the …

Individual-Network Based Predictions Of Microbial Interaction Signatures For Response To Biological Therapies In Ibd Patients, Federico Melograna, Padhmanand Sudhakar, Behnam Yousefi, Clara Caenepeel, Gwen Falony, Sara Vieira-Silva, Sreenikhitha Krishnamoorthy, David Fardo, Bram Verstockt, Jeroen Raes, Severine Vermeire, Kristel Van Steen

Biostatistics Faculty Publications

Inflammatory Bowel Disease (IBD), which includes Ulcerative Colitis (UC) and Crohn’s Disease (CD), is marked by dysbiosis of the gut microbiome. Despite therapeutic interventions with biological agents like Vedolizumab, Ustekinumab, and anti-TNF agents, the variability in clinical, histological, and molecular responses remains significant due to inter-individual and inter-population differences. This study introduces a novel approach using Individual Specific Networks (ISNs) derived from faecal microbial measurements of IBD patients across multiple cohorts. These ISNs, constructed from baseline and follow-up data post-treatment, successfully predict therapeutic outcomes based on endoscopic remission criteria. Our analysis revealed that ISNs characterised by core gut microbial families, …

Stigma And Efficacy Beliefs Regarding Opioid Use Disorder Treatment And Naloxone In Communities Participating In The Healing Communities Study Intervention, Nicky Lewis, Barry Eggleston, Redonna K. Chandler, Dawn Goddard-Eckrich, Jamie E. Luster, Dacia Beard, Emma Rodgers, Rouba A. Chahine, Philip M. Westgate, Shoshana N. Benjamin, Janae Holloway, Thomas Clarke, R. Craig Lefebvre, Michael D. Stein, Donald W. Helme, Jennifer Reynolds, Sharon L. Walsh, Darcy Freedman, Nabila El-Bassel, Kara Stephens, Anita Silwal, Michelle R. Lofwall, Janet E. Childerhose, Hilary L. Surratt, Brooke N. Crockett, Amy L. Farmer, James L. David, Laura Fanucchi, Judy Harness, Ben Wilburn, Kelli Bursey, Kristin Mattson, Sarah Mann, Rebecca D. Jackson, Aimee Shadwick, Katherine Calver, Deborah Chassler, Jennifer Kimball, Nancy Regan, Jeffrey H. Samet, Rachel Sword-Cruz, Michael D. Slater

Biostatistics Faculty Publications

Background The HEALing Communities Study (HCS) included health campaigns as part of a community-engaged intervention to reduce opioid-related overdose deaths in 67 highly impacted communities across Kentucky, Massachusetts, New York, and Ohio. Five campaigns were developed with community input to provide information on opioid use disorder (OUD) and overdose prevention, reduce stigma, and build demand for evidence-based practices (EBPs). An evaluation examined the recognition of campaign messages about naloxone and whether stigma and efficacy beliefs regarding OUD treatment and naloxone changed in HCS intervention communities.

Methods Data were collected through surveys offered on Facebook/Instagram to members of communities participating in …

A Case Study On Variations In Network Structure And Cross- Sector Alignment In Two Local Systems Serving Pregnant And Parenting Women In Recovery, Liza M. Creel, Yana Feygin, Madeline Shipley, Deborah Winders Davis, Tiffany Cole Hall, Chaly Downs, Stephanie Hoskins, Natalie Pasquenza, Scott D. Duncan

Biostatistics Faculty Publications

Objective: To describe network structure and alignment across organizations in healthcare, public health, and social services sectors that serve pregnant and parenting women with substance use disorder (SUD) in an urban and a rural community.

Data Sources and Study Settings: Two community networks, one urban and one rural with each including a residential substance use treatment program, in Kentucky during 2021.

Study Design: Social network analysis measured system collaboration and cross-sector alignment between healthcare, public health, and social services organizations, applying the Framework for Aligning Sectors. To understand the alignment and structure of each network, we measured network density overall …

Higher First 30-Day Dose Of Buprenorphine For Opioid Use Disorder Treatment Is Associated With Decreased Mortality, Feitong Lei, Michelle R. Lofwall, Jana Mcanich, Reuben Adatorwovor, Emily Slade, Patricia R. Freeman, Daniela Moga, Nabarun Dasgupta, Sharon L. Walsh, Rachel Vickers-Smith, Svetla Slavova

Biostatistics Faculty Publications

Objective: Buprenorphine is a medication for opioid use disorder that reduces mortality. This study aims to investigate the less well-understood relationship between the dose in the early stages of treatment and the subsequent risk of death.

Methods: We used Kentucky prescription monitoring data to identify adult Kentucky residents initiating transmucosal buprenorphine medication for opioid use disorder (January 2017 to November 2019). Average daily buprenorphine dose for days covered in the first 30 days of treatment was categorized as ≤8 mg, >8 to ≤16 mg, and >16 mg. Patients were followed for 365 days after the first 30 days of buprenorphine …

Slope Unit Maker (Sumak): An Efficient And Parameter-Free Algorithm For Delineating Slope Units To Improve Landslide Modeling, Jacob B. Woodard, Benjamin B. Mirus, Nathan J. Wood, Kate E. Allstadt, Benjamin A. Leshchinsky, Matthew M. Crawford

Faculty, Staff, and Affiliated Publications--KGS

Slope units are terrain partitions bounded by drainage and divide lines. In landslide modeling, including susceptibility modeling and event-specific modeling of landslide occurrence, slope units provide several advantages over gridded units, such as better capturing terrain geometry, improved incorporation of geospatial landslide-occurrence data in different formats (e.g., point and polygon), and better accommodating the varying data accuracy and precision in landslide inventories. However, the use of slope units in regional (> 100 km²) landslide studies remains limited due, in part, to the large computational costs and/or poor reproducibility with current delineation methods. We introduce a computationally efficient algorithm …

Rural And Urban Clinician Views On Covid- 19’S Impact On Substance Use Treatment For Individuals On Community Supervision In Kentucky, Carrie B. Oser, Maria Rockett, Sebastian Otero, Evan Joseph Batty, Marisa Booty, Rachel Gressick, Michele Staton, Hannah K. Knudsen

Sociology Faculty Publications

Background The COVID-19 pandemic produced system-level changes within the criminal legal system and community-based substance use disorder (SUD) treatment system with impacts on recovery efforts. This study examines rural and urban clinicians’ perspectives of COVID-19 on SUD treatment delivery for people on community supervision.

Methods Virtual qualitative interviews were conducted between April and October 2020 with 25 community supervision clinicians employed by Kentucky’s Department of Corrections (DOC), who conduct assessments and facilitate community-based treatment linkages for individuals on probation or parole. Transcripts were analyzed in NVivo using directed content analysis methods.

Results Clinicians were predominantly white (92%) and female (88%) …

Cultural Predictors Of Self-Esteem Among Black Women With Criminal Justice Involvement And Herpes Simplex Virus, Natalie Malone, Jardin N. Dogan-Dixon, Shemeka Thorpe, Shawndaya S. Thrasher, Paris Wheeler, Danelle Stevens-Watkins, Carrie B. Oser

Sociology Faculty Publications

Black women have disproportionately alarming HSV-2 infection rates yet receive little attention in sexual health literature. Using a strengths-based resilience framework, this study sought to determine culturally relevant protective predictors of self-esteem for Black women who are justice-involved and have HSV-2. The authors conducted secondary data analysis on data from the “Black Women in the Study of Epidemics (B-WISE) Project,” a longitudinal prospective study investigating health disparities and health services utilization among Black women with justice involvement. At baseline, N = 151 Black women with HSV-2 who were incarcerated or on probation completed survey measures assessing selfesteem, ethnic identity affirmation …

The State Of Coaching Of Staff In Licensed Childcare Centers, Kimberly Copeland

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

This study aimed to explore the coaching experiences of childcare staff working in licensed childcare centers by using an online survey. The survey questions sought to determine whether childcare staff had received coaching in the past 12 months, the sources of that coaching, its frequency and method of coaching, the topics covered, and the staff's perception of job-related coaching. Data from 52 participants reveals that: 92% of childcare staff have received job-related coaching from internal sources; 40% have received coaching from external sources. Most coaching occurs “In person in the classroom” and the largest percentage of coaching is delivered on …

Precision Application Of Water To Equine Racing Surfaces, Sydney Rae Cannon

Theses and Dissertations--Biosystems and Agricultural Engineering

As the horseracing industry has come under more scrutiny as of late, horse and rider safety has become a priority. The best was to keep a rider safe is to keep them on their horse, and the best way to do that is to keep the horse upright. This all comes down to consistency both between tracks and across a single track. The most important method of managing track consistency is through moisture content. This study examined how track design can impact moisture application, how moisture content can impact the surface material, and what design elements can be implemented to …

Development Of Fungal Hydrogels For 3d Bioprinting And Cellular Agriculture, Lauren E. Doyle

Theses and Dissertations--Biosystems and Agricultural Engineering

Hydrogel scaffolds are an important component to cellular agriculture. There is a need for a sustainable alternative to the commonly used gelatin-sodium-alginate hydrogels. Specific edible fungus species may provide a suitable alternative. Many fungi possess high protein contents, ease of cultivation, and strong functional properties. However, functional characterizations and application of fungal flour and protein extracts in cellular agriculture are lacking in the literature. Therefore, this study’s objectives were to 1) Develop processes to create functional fungal protein fractions from different fungal strains and evaluate their characteristics, and 2) Quantify the printability of the resulting fungal gels for the creation …

Pulse-Width Modulation Spray System Performance And Development Of A Novel System To Optimize Spray Use Efficacy, Prashanta Pokharel

Theses and Dissertations--Biosystems and Agricultural Engineering

The overarching objective of this research was to enhance our understanding of pulse width modulation (PWM) based nozzle control system and develop an intelligent nozzle control system for agricultural spray applications. This dissertation focused on measuring and analyzing the transient nozzle pressure characteristics and performance under PWM control. Additionally, it explored the development of an innovative multi-degree-of-freedom (DOF) nozzle control system for precise chemical applications in specialty crop systems.

The pressure dynamics of a PWM system were studied by developing an instrumentation system capable of operating a solenoid valve and recording pressure signals. A nozzle body and two manifolds of …

Caught In The Crosshairs Of Educational Reform: How Teacher Labor Markets Respond To Polarized Education Policies, Danielle Duffy Chipman

Theses and Dissertations--Public Policy and Administration

Since the passage of No Child Left Behind (NCLB) teachers have been caught in the crosshairs of political debates about education policy (Davis, 2014; EPE Research Center, 2013a; Steiner & Woo, 2021; Woo et al., 2022; Zubrzycki, 2016). As political polarization between parties increased in the 2000s, debates about education policy became more acrimonious impacting teachers’ work lives (Heltzel & Laurin, 2020; Iyengar, 2021; Layman et al., 2006). The topic of these debates ranges from curriculum changes such as Common Core and Critical Race Theory (CTR), school shootings and safety, battles over school choice and voucher programs, teacher activism about …

Extracting Social Network Model Parameters From Social Science Literature, Isaac Batts

Theses and Dissertations--Computer Science

When looking at computer modeling of social situations, much of the social science literature does not include ready-to-use statistics or parameters to be included in a social model. I explore studies related to speaking about racism (and other forms of bias), and interventions designed to diminish the occurrence of biased behavior, and use those readings to synthesize plausible parameters for a social computer model.

Tension Control And Interproximation Techniques Forshape Design And Rgb-Depth Segmentation Reconstruction And Modeling, Anastasia Kazadi

Theses and Dissertations--Computer Science

Human eyes possess remarkable capabilities to perceive and interpret a wealth of information about our environment; from discerning colors and depths to identifying object boundaries and navigating obstacles, our eyes serve as invaluable guides in our daily lives. Ongoing research in the fields of computer vision and computer graphics continuously explore the ways to replicate extraordinary human vision abilities in order to develop systems and frameworks which would enable computers to capture, analyze, and act upon discerned information. In this context, this dissertation seeks to investigate and automate various shape control and data processing techniques for 3D modeling and shape …

Detecting And Recovering From Player Preference Shifts In A Player Modeled Experience Management Environment, Anton Vinogradov

Theses and Dissertations--Computer Science

An important challenge in game design is understanding and maintaining player engagement. This is particularly crucial in both entertainment and educational games, where the player's commitment to the game directly impacts their experience and learning outcomes. However, quantifying engagement proves challenging due to the diverse interests of players. This dilemma is addressed through adaptive game design techniques where the game world is personalized to suit player preferences. In computer games, this personalization is facilitated through Experience Management and Player Modeling, where an intelligent agent gathers information on the player, including their preferences and actions, and takes actions to modify the …

Finding Hierarchies To Improve Learning In Hierarchical Reinforcement Learning, Roy Mobley

Theses and Dissertations--Computer Science

Reinforcement Learning (RL) is an approach to allowing computer agents to try and learn how to solve problems by learning what actions are best to take in a given situation. RL is effective for learning what to do in an environment, but as the problem grows larger, the amount of information needed grows exponentially, making RL less effective on complex problems. A big challenge, often called the curse of dimensionality, is that the number of states and possible number of actions in an environment can grow too large to sufficiently test every possible combination of state and action. One method …

An Archaeological Investigation Of Communities Of Practice Among Coastal Georgia Potters, Elizabeth Straub

Theses and Dissertations--Anthropology

The Mission period in the southeastern United States (beginning around 1565 AD) was characterized by dramatic social and demographic change. Coastal tribes, which include the Guale, Mocama, Orista, and Yamasee, among others, were simultaneously faced with the challenge of negotiating new relationships with Europeans and the global economy, the spread of new diseases, an influx of refugees displaced by violence, and the threat of increasingly prevalent slave raiding. Since most historical documents about this region were written by Spanish men, the experience of Native American women has been neglected. This project addresses this disparity by focusing specifically on one of …

Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht

Saha Cardiovascular Research Center Faculty Publications

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model.

Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice …

Transient Interactions Modulate The Affinity Of Nf-Κb Transcription Factors For Dna, Tianjie Li, Shandy Shahabi, Tapan Biswas, Oleg V. Tsodikov, Wenfei Pan, De-Bin Huang, Vivien Ya-Fan Wang, Yi Wang, Gourisankar Ghosh

Biology Faculty Publications

The dimeric nuclear factor kappa B (NF- κB) transcription factors (TFs) regulate gene expression by binding to a variety of κB DNA elements with conserved G:C-rich flanking sequences enclosing a degenerate central region. Toward defining mechanistic principles of affinity regulated by degeneracy, we observed an unusual dependence of the affinity of RelA on the identity of the central base pair, which appears to be noncontacted in the complex crystal structures. The affinity of κB sites with A or T at the central position is ~10- fold higher than with G or C. The crystal structures of neither the complexes nor …