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Contributions Of Arginine And Nitrosative Stress To Huntington’S Disease Progression, Ian D. Gaudet

Electronic Theses and Dissertations 2020 - Present

Neuroinflammation is a well-established component of Huntington's disease (HD) pathogenesis, yet the intricate molecular mechanisms that govern this process remain a topic of ongoing research and debate. This dissertation elucidates a novel pathway linking arginine metabolism and nitrosative stress to core HD pathology. We found that the arginine transporter SLC7A2 is selectively upregulated in various HD cellular models and patient samples. Our findings reveal that this upregulation drives an overactive inflammatory response, leading to abnormally high inducible nitric oxide synthase (iNOS) induction and subsequent nitric oxide (NO) production, which causes excessive protein nitrosylation and an increase in mitochondrial fragmentation.

To …

Towards The Synthesis Of Dragonamide E And Analogs Thereof, Dante Glover

Chemistry Theses

Leishmaniasis is a disease caused by a parasite spread through the female sand fly. It is categorized as a Neglected Tropical Disease and can cause very severe symptoms, even death, if left untreated. Symptoms include skin lesions that can cause permanent scarring, and mucosal membrane infections that can cause facial deformities. More aggressive forms of leishmaniasis can lead to infections of internal organs like the liver and/or spleen and can lead to death. Drug resistance of these parasites has rendered treatment limited and the side effects of which can be harmful as well.

Scientists looking towards new treatments for tropical …

Recognition Of Autism Characteristics In Females: An Examination Of Stakeholders, Laurel Lyn Bishop

Theses and Dissertations

Autism is a neurodevelopmental communication disorder, characterized by differences in social communication, attention, interests, and sensory perception. Diagnostic criteria have historically applied to males, but clinical diagnostic criteria beginning in 2022 now include slight differences in traits comprising the female phenotype. Until recently, autistic females may be missed by the professional and education community or diagnosed later than males. Like their autistic male counterparts, they face an increased risk of suicidal ideation, but they also face more difficulties in peer relationships, academic problems, and increased anxiety and depressive symptoms, but may not get supports. School-age girls spend their days with …

Non-Enzymatic Hepatic Abhd6 Interacts With Akt-Foxo1 Axis To Regulate Metabolic Health, Guannan Li, Laurence T Maeyens, Jiyuan Yin, Jan-Bernd Funcke, Chanmin Joung, Ruizhen Li, Ziying Xu, Ting Wu, Xin Li, Nisi Jiang, Mbolle Ekane, Maria Paula Lopez, Pengju Cao, Sijia He, Adam B Salmon, S R Murthy Madiraju, Marc Prentki, Juli Bai, James F Nelson, Xianlin Han, Yi Zhu, Shangang Zhao

Children’s Nutrition Research Center Staff Publications

The enzymatic role of ABHD6 in insulin secretion and resistance is well documented. However, its non-enzymatic function, especially its effects on metabolic health, including selective hepatic insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD), is poorly understood. To define the role of ABHD6 in liver physiology, we generated liver-specific ABHD6 knockout mice, as well as liver-specific native and enzymatically inactive mutant ABHD6 overexpression mouse models. We demonstrate that non-enzymatic ABHD6 contributes to the regulation of selective hepatic insulin resistance and MASLD progression. Mechanistically, we show that ABHD6 localizes to the nucleus and interacts with Akt/FoxO1 axis to regulate insulin …

Responsivity Education Reflection Packet For Multigenerational Caregivers, Natalie Holsky

Honors Projects

Caregivers play an essential role in supporting their child’s language development. Through everyday routines, caregivers have countless opportunities to foster strong language skills. Extensive research has examined the influence of caregiver input on language development. Comparatively little research has explored how historical trends in parenting advice across generations may shape caregivers’ use of language facilitation practices. The purpose of my honors project was to examine how generational parenting trends could inform the development of a clinic-to-home language facilitation resource. This resource was designed to help caregivers incorporate language facilitation strategies into everyday routines to increase language-rich interactions at home. A …

Behavioral Indicators Of Stress In Wild Savanna-Dwelling Chimpanzees (Pan Troglodytes) In Fongoli, Senegal, Leah T. Williams

Theses and Dissertations

Stress influences health, reproduction, social relationships, and survival in primates. I identified behavioral indicators of stress in wild chimpanzees (Pan troglodytes) and determined whether coping strategies varied between behavioral contexts. Coping behavior differed significantly across contexts and behaviors, indicating that coping behaviors are strategically utilized in different contexts and provide insight into the emotional regulation of chimpanzees.

Queer Postsecular Conocimiento: Anzaldúan Readings Of Time, Spirituality, And Transformation In Nugent, Vuong, And Herrera, Joshua A. Swem

Theses and Dissertations

An overreliance on secularism within the field of queer theory and a denial of spiritual epistemologies prevent deep, alternative, and transformative strategies of analyzing literature. It can regurgitate oppressive ideology in academia. In this work, I synthesize Gloria Anzaldúa’s theoretical concepts of mestiza consciousness, nepantla, la facultad, and el cenote with José Esteban Muñoz’s queer temporality and futurity as a framework to engage with literary texts in queer, postsecular ways, freeing up fresh insights and polysemic perspectives. I argue that in  "Smoke, Lilies, and Jade" by Richard Bruce Nugent, Signs Preceding the End of the World by Yuri …

The Introduction Of High-Speed Rail And Its Impact On Mode Choice The Case Of Morocco’S Al Boraq, Michael Stewart

Theses and Dissertations

Morocco's Al Boraq, Africa's first high-speed rail line, reshaped mode choice along the Casablanca-Tangier corridor. Drawing on ONCF ridership data, 234 rider surveys, and nine months of fieldwork, this ex-post assessment finds accelerated passenger growth, substantial induced demand, and mode shift from automobiles, informing Global South HSR development.

Bdelloid Rotifers Harbor A Voltage-Gated Proton Channel With Distinct Mechanistic Features, Liang Yan, Chiara Boschetti, Liang Hong

School of Biological and Marine Sciences

Bdelloid rotifers are renowned for their extraordinary resilience. They can survive desiccation and long-term freezing and revive once favorable conditions return. Such remarkable survival abilities suggest that the evolution of specialized molecular adaptations sustain pH homeostasis under extreme environmental stress. In the present study, we identify and functionally characterize an isoform of the voltage-gated proton channel (Hv) from the bdelloid rotifer Adineta ricciae, which we name ArHv2. Unlike its paralog ArHv1 and human Hv1 that activate only at positive membrane potentials and contribute modestly to proton extrusion under normal conditions, the ArHv2 activates even at negative potentials, enabling rapid and …

Vetiver Phytoremediation Of Nitrate-Rich Munition Wastewater: Biomass Valorization Within A Circular Economy Framework, Arash Aliasghar, Rupali Datta, Zhiming Zhang, Christos Christodoulatos, Dibyendu Sarkar

Michigan Tech Publications

Industrial munition facilities generate nitrate-rich wastewater that requires effective and sustainable treatment before discharge. While vetiver grass (Chrysopogon zizanioides)-based phytoremediation has shown promise in nitrogen removal, most studies have been limited to small-scale experiments under low nitrogen concentrations, providing limited guidance for system-level design under elevated loading. This study evaluates a greenhouse-scale phytoremediation system using vetiver grass to treat wastewater containing 1000 mg N/L nitrate and 50 mg/L COD. Plant coverage densities of 2%, 4%, and 6% (w/v) were assessed to quantify optimum density as a design parameter for optimizing nitrate removal. A 6% coverage achieved the highest efficiency, reducing …

Fang Zhu’S Shen-Mie-Lun And Contemporary Physicism: A Cross-Cultural Dialogue, Soo Lam Wong

Comparative Philosophy

Fan Zhen’s 范缜 “Shen-Mie-Lun 神灭论” can be read as a debate between a physicalist and a dualist in the philosophy of mind. Many of Fan’s arguments found in the “Shen-Mie-Lun” correspond to contemporary physicalism in Western analytic philosophy. My aim in this essay is to bring Fan's “Shen-Mie-Lun” into conversation with contemporary physicalism in the following way: (1) offer an outline of Fan’s physicalism as presented in the “Shen-Mie-Lun” (2) map his view onto the key positions and concepts of contemporary physicalism, (3) show how his view is (a) incompatible with eliminative …

Can Skepticism Be Politically Progressive? An Approach From Zhuang Zi, Tammo Lossau

Comparative Philosophy

Ancient skeptics, both in the West and East, suggest their philosophy as a form of life. One reservation about living as a skeptic is that it turns us into political conformists—this is also Jonathan Ichikawa’s (2024) objection to philosophical skepticism. Skeptics take their own perspective on the world to be limited, and in this sense they will be hesitant to fully embrace a conservative ideology. But the Pyrrhonian skeptic Sextus Empiricus recommends that in their actions, skeptics will follow existing laws and common moral beliefs. In this paper, I want to develop a different conception of skepticism based on the …

Jing (敬) And Respect, Wenyang Gao

Comparative Philosophy

Jing (敬) is often translated as “respect”. Some scholars argue for a “perception of worth” reading, conceiving jing as a deontic normative attitude akin to “respect” in the Western tradition. Others propose a “directing attention” reading, holding that jing is a virtue. This article clarifies the meaning and normative structure of jing, arguing that it has three dimensions:  (1) a state of mind characterized by seriousness, (2) an intentional, respectful feeling, and (3) respectful conduct aligned with ritual propriety (Li禮). While the “directing attention” reading correctly identifies jing as a virtue, insisting that jing does …

Applications And Insights Of The Use Of Ethnographic Research In A Local Context Of Nepal, Dipak Raj Rai, Sunita Dangol, Megh Raj Dangal

The Qualitative Report

This paper expounds on ethnographic research in comprehending the cultural, economic, and social nuances in the Nepali local community. The paper also emphasizes the significance of ethnographic research in providing profound insights into the daily lives, traditions, and interactions of cultural groups. This writing aims to describe the historical concept of ethnography, its philosophical standpoint, types of ethnography, fields of ethnographic research and commonly used methods for collecting ethnographic data. The main idea of the paper is to present the methods employed such as participant observation, ethnographic interviews, self-reporting, and artifacts that enable the researcher to obtain the true lived …

Formalization Of Nomenclatural Acts Proposed In Tang (2026) (Scorpiones: Buthidae, Chaerilidae, Scorpiopidae), Victoria Tang

Euscorpius

Several nomenclatural, taxonomic, and faunistic decisions put forth in Tang (2026) are formalized herein: (1) four nomina dubia, Chaerilus tessellatus Qi et al., 2005, Scorpiops langxian Qi et al., 2005, S. pococki Qi et al., 2005, and Isometrus (Reddyanus) wenjieae Huang et al., 2025; (2) two junior subjective synonyms, Scorpiops langxian = S. pococki = S. tibetanus Hirst, 1911 syn. n.; (3) one new “aspidonym”, Scorpiops obluda Tang, 2026 sp. indet. nomen nudum; and (4) removal of Scorpiops hardwickii (Gervais, 1843) and S. petersii Pocock, 1893 from the Chinese scorpiofauna. Reddyanus tibetanus (Lourenço & Zhu, 2008) is maintained …

Measuring Health System Readiness In Saint Lucia Using International Health Regulations Capacity Indicators, Melissa Steele

Walden Dissertations and Doctoral Studies

Emerging infectious diseases continue to challenge national health systems, particularly in small island developing states with limited preparedness resources. Limited evidence comparing the International Health Regulations (2005) State Party Self-Assessment Annual Reporting (IHR SPAR) capacities of small island developing states with those of high-income countries limits efforts to identify preparedness gaps and strengthen health systems. The purpose of this quantitative comparative study was to evaluate Saint Lucia's preparedness using IHR SPAR indicators, compare its preparedness with the United States, and assess changes between 2023 and 2024. Guided by the World Health Organization Health System Framework, a quantitative cross-sectional design using …

Fisheries Research Report No. 365: Recreational Fishing For Marron In South-West Western Australia In 2026, Claire B. Smallwood, Karina L. Ryan, Eva Lai

Fisheries Research Reports

The smooth marron (Cherax cainii) (‘marron’) is endemic to freshwater dams and rivers of south-west Western Australia. Marron are managed as a single stock within the South-West Recreational Freshwater Resource and are highly vulnerable to overexploitation due to the biological characteristics of the species (e.g., low fecundity, localised populations) as well as environmental (e.g., habitat loss, reduction in rainfall) and human (e.g., fishing, land clearing) pressures on freshwater ecosystems.

Due to this vulnerability, this species has been the focus of research, monitoring and management since the 1970’s. Since 2000, annual phone-recall (2000 – 2021) and online-recall (2022 – 2026) surveys …

Baseline Nutrition Knowledge And Feasibility Of A Whatsapp-Delivered Nutrition Education Intervention Among California Wildland-Urban Interface Firefighters, Lauren E. Anderson

Master's Theses

Wildland firefighters perform physically demanding work under challenging environmental conditions that place substantial demands on nutritional health and occupational performance. Despite the importance of nutrition in supporting physical performance, recovery, and long-term health, limited research has examined nutrition knowledge and dietary behaviors among California wildland firefighters or evaluated the feasibility of remotely delivered nutrition education interventions within this occupational population. Therefore, the purpose of this pilot study was to assess baseline nutrition knowledge, nutrition self-efficacy, and dietary behaviors while evaluating the feasibility of a 12-week WhatsApp-delivered nutrition education intervention among California wildland firefighters.

Twenty-four firefighters completed the baseline assessment and …

Mir155, Triplicated In Down Syndrome, Regulates The Development Of Neural Stem Cells And Gabaergic Interneurons In Alzheimer's Disease Mouse And Human Ipsc Models., Xiaodong Zhu, Jean-Vianney Haure-Mirande, Mesude Bicak, Pengfei Dong, Ilya Kruglikov, Aiqun Li, Aisha Al-Subaie, Valentina Fossati, Scott Noggle, Sam Gandy, Michelle E Ehrlich

Faculty Research 2026

INTRODUCTION: Dysfunctional microRNAs and GABAergic interneurons are features of Alzheimer's disease (AD). The role of neuronal microRNA155 (miR155), elevated in both AD and Down syndrome (DS), remains unknown.

METHODS: We utilized in silico analyses of published databases, MIR155-deleted and -overexpressing human induced pluripotent stem cell (hiPSC)-derived cells, cortical organoids, and amyloid beta precursor protein (APP)/PS1-miR155 knockout mouse.

RESULTS: MIR155HG (miR155 host gene) colocalizes with APP in a neuron-specific, topologically associated domain (TAD) in chromosome 21. In human neural stem cells (NSCs), neurons, and cortical organoids, MIR155 deletion enhanced NSC proliferation and GABAergic interneuron generation. MIR155 overexpression inhibited NSC marker expression …

The Past, The Present, And The Future Of Preclinical Mouse Models For Alzheimer's Disease And Related Dementias., Adrian L Oblak, Michael Sasner, Gregory W. Carter, Gareth R Howell, Stacey J Sukoff Rizzo, Karina Leal, Paul R Territo, Bruce T Lamb

Faculty Research 2026

Over the past decade, the Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease (MODEL-AD) consortium has transformed preclinical Alzheimer's disease (AD) research by addressing critical limitations in traditional mouse models that failed to translate to human disease. By leveraging human genetic discoveries, MODEL-AD has developed > 70 genetically informed mouse models, standardized phenotyping pipelines, and an open-access data infrastructure aligned with late-onset AD biology. These models incorporate human risk variants, environmental factors, and aging to better capture disease complexity, including emerging recognition of mixed pathologies such as vascular contributions, Lewy body disease, and TDP-43 proteinopathy. Despite substantial progress, key challenges …

Stromal Cell Senescence Augments Haematopoietic Cell Fitness In Clonal Haematopoiesis., Jayna J Mistry, Kira Young, Anna Navarro Figueredo, Gibran Edun, Alicia G Aguilar-Navarro, Patricia A Colom Díaz, Maria Telpoukhovskaia, Inés Fernández Maestre, Sheng F Cai, Katharina S Götze, Anastasia N Tikhonova, Ross L Levine, Jennifer J. Trowbridge

Faculty Research 2026

Microenvironment remodelling impacts tumour growth and metastasis, but whether remodelling promotes pre-malignant clonal fitness remains unknown. Here, using single-cell RNA-sequencing of the bone-marrow microenvironment in a mouse model of DNMT3A-mutant clonal haematopoiesis (CH), we identify mesenchymal stromal cells (MSCs) in a molecular state of cellular senescence. Elevated bone-marrow MSC senescence is also observed in humans with CH driven by several common somatic mutations. MSC senescence is induced by mutant haematopoietic cells in a contact-independent manner through production of soluble factors including TNF-α and IL-6. These cytokines activate a Stat3-driven pathway that is necessary and sufficient for MSC senescence induction. Genetic …

A Collaborative Framework For Uncovering Molecular And Cellular Drivers Of Vcid: Foundations For Future Interventions In Dementia., M Luisa Iruela-Arispe, Jason D Hinman, Andrew C Yang, Fabrice Dabertrand, Jin-Moo Lee, Gareth R Howell, The Vcid Centers Without Walls Network

Faculty Research 2026

Vascular-related factors are now considered major contributors to most forms of dementia, including Alzheimer's disease. However, the degree to which vascular deficits contribute to risk, onset, and progression of cognitive impairment and dementia has only recently been appreciated. Our understanding of the mechanisms by which vascular deficits drive cognitive decline in dementia is still limited. Further, the testing of therapeutic approaches to prevent vascular deficits to treat dementia are few. These factors motivated the establishment of the Vascular Contributions to Cognitive Impairment and Dementia (VCID) Center Without Walls (CWOW) network, comprising institutes across the United States. We describe the current …

Inhibition Of Moesin And Cd44 In Stem Cell-Derived Neurons Affects The Pathological Genetic Signature Associated With Alzheimer's Disease., Eiden H Brewer, Charles A Williams, Gregory Cary, Ranjita Betarbet, Inez K A Pranoto, Elizabeth L Zoeller, Haian Fu, Allan I Levey, Jesse C Wiley, Gregory W. Carter, Jessica E Young, Treat-Ad Consortium

Faculty Research 2026

INTRODUCTION: Post mortem proteomic analysis of Alzheimer's disease (AD) brain tissue has identified novel target genes and proteins for potential therapeutic development. Moesin (MSN) and CD44 were identified as candidate targets. Using human induced pluripotent stem cells (hiPSCs)-derived neurons, we assayed how reducing gene expression of MSN and CD44 affected amyloid beta secretion, tau phosphorylation, and transcriptional state.

METHODS: Knockdown of MSN and CD44 in hiPSC-derived neurons was performed using short hairpin RNA (shRNA). Amyloid precursor protein processing and intracellular tau phosphorylation was measured using chemiluminescent ELISA assays. Global gene expression was analyzed by bulk RNA sequencing (RNA-seq).

RESULTS: Knockdown …

Finding Balance: School-Based Yoga Interventions And Their Alignment Within Multi-Tiered Systems Of Support, Ursula Vogt

Educational Specialist, 2020-current

School-based interventions that support emotional regulation and student well-being are increasingly emphasized within Multi-Tiered Systems of Support (MTSS). Yoga has emerged as a potential school-based practice; however, its outcomes, alignment with MTSS frameworks, and implementation characteristics remain unclear. This systematized review examined (a) psychological, emotional, and behavioral outcomes associated with school-based yoga interventions, (b) their alignment with Tier 1 and Tier 2 supports, and (c) implementation characteristics that support feasibility in school settings. A systematic search identified 21 U.S.-based studies, which were analyzed using thematic analysis. Findings indicated that yoga interventions were associated with improvements in emotional regulation, stress and …

Cellular Senescence Links Muscle Atrophy And Posttraumatic Osteoarthritis After Acl Injury, Alexander R. Keeble, Allison Owen, Sara Gonzalez-Velez, Nicholas T. Thomas, Camille R. Brightwell, Peyton J. Balawender, Madeline G. O'Daniel, Helena C. Weiss, Haley Noehren, Heather Thompson, Karen Sofia Zuluaga-Osorio, Zane T. Bates, Lauren Gottlieb, Douglas E. Long, Douglas Harrison, Philip Kern, Caitlin E. Conley, Michael A. Samaan, Stephen Duncan, Austin Stone, Darren Johnson, Yuan Wen, Brian Noehren, Cory Dungan, Christopher Fry

Biology Faculty Publications

Traumatic knee injury leads to posttraumatic osteoarthritis (PTOA) and significant skeletal muscle weakness, resulting in chronic disability. The current standard of care frequently fails to prevent musculoskeletal dysfunction, underscoring the need to identify therapeutic mechanisms of PTOA. Using an established preclinical anterior cruciate ligament (ACL) transection model of PTOA and leveraging an innovative SPiDER-senescence-associated β-galactosidase stain to discern senescent cells, we investigated cellular senescence at single-cell resolution and identified anti-inflammatory macrophages as a predominant contributor to the senescent cell burden in both muscle and knee joint after injury. Clearance of senescent cells using the senolytic dasatinib and quercetin (D + …

The True Scope Of Trusting Your Gut: A Study Into The Enteric Nervous System And The Relationship Between The Gut-Brain Axis And The Mind, Bryan Pham

Theses & ETDs

Since the early days of medicine, the “gut” had been associated as a seat of emotions and intuition, but as modern science marched forward, the brain itself was given complete dominion over mental health. But thanks to research into the enteric nervous system (ENS), which innervates the digestive tract and bilaterally communicates with the brain as a secondary function, we now know that, in a sense, the gut does indeed have a substantial impact on mental health outside of its primary functions. This profound discovery could potentially cause a massive rewrite for decades of modern neuroscience-based medicine. Overall, the study …

Molecular Refinement Of The Taxonomy Of Pyrgulopsis Springsnails In Western North America, Michael K. Young, Kristine L. Pilgrim, Eric S. Miskow, Chante L. Lundskog, Kathryn E. Perez, Michael K. Schwartz

School of Integrative Biological & Chemical Sciences Faculty Publications

Springsnails in the genus Pyrgulopsis in western North America have long been a dilemma for taxonomists. Defining species boundaries has been complicated by the presence of undiscovered or cryptic taxa, range over- or underestimation, species complexes representing an unknown number of species, and named species synonymous with other taxa. To address these issues, we conducted an array of molecular species delimitation analyses using sequences from up to 2 mitochondrial and 2 nuclear genes from over 5000 specimens representing 140 of the 151 currently recognized taxa. These analyses reaffirmed most species hypotheses, favored synonymy for some taxa and redrawing of species …

Examining Social Anxiety And Barriers To Engagement In School-Based Mental Health Services Among Black American Adolescents, Taylor Walls

Theses, Dissertations and Culminating Projects

Social anxiety is common among Black American adolescents, though research examining the experience of social anxiety among this population is very limited. Furthermore, few studies have explored how sociocultural factors, such as racial discrimination and mental health stigma, may shape Black American adolescents’ perceptions of social anxiety and school-based mental health services. Using qualitative methods, the present study explored Black American adolescents’ perceptions of social anxiety, barriers to help-seeking, and views regarding school-based mental health services. A total of 15 Black American high school students in the northeastern United States (ages 14-15 years; M=16.0, SD=1.2) participated in focus groups and …

Temperature And Salinity Effects On The Physiology Of Bullfrog Tadpoles (Lithobates Catesbeianus) From A Suburban Temperate Wetland, Angela Brown

Theses, Dissertations and Culminating Projects

One of the most robust amphibians is the American Bullfrog, Lithobates catesbeianus, which is a widespread species that is invasive worldwide, and is broadly tolerant of a range of environmental conditions. Despite this tolerance, survival and performance of adult L. catesbeianus can be negatively affected by increasing temperatures and salinity resulting from anthropogenic impacts, such as climate change and road salts. This study focuses on the effects of acute salinity exposure (mimicking road salt influx into a pond) on L. catesbeianus tadpoles at different larval stages. Increased salinity was predicted to negatively affect two physiological performance measures. Critical maximum temperature …

Harnessing Kenyan Aquaculture Through Social Media: Impacts, Challenges And Strategic Directions, Domitila Kyule, Jonathan Munguti, Mavindu Muthoka, Esther Magondu, Menaga Meenakshisundaram, Chrysantus M. Tanga, Kevin Obiero, Cecilia Githukia

All Peer-Reviewed Publications

Aquaculture is increasingly important for food, nutrition and livelihoods in Kenya, but the sector still faces persistent constraints in extension delivery, farmer learning, input access, market coordination and information reliability. This review examines how social media and related digital communication tools are shaping aquaculture development in Kenya, with attention to impacts, challenges, governance needs and strategic directions. A systematic literature review of studies and institutional sources published between 2015 and 2025 was conducted. The search identified 388 records, of which 45 sources were included in the final synthesis after screening, eligibility assessment and quality appraisal. Because the evidence was heterogeneous, …