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A Ceramic Zoomorphic Figurine From Tel Bet Yeraḥ, Nadeshda B. Knudsen

'Atiqot

A well-made ceramic zoomorphic figurine was recovered from a domestic EB IB context (Stratum V) in the southern part of Tel Bet Yeraḥ. The physical characteristics of this figurine suggest that it was intended to represent an equid, possibly a donkey. Such animal figurines are common at Early Bronze Age sites, usually representing familiar domesticate animals. The purpose of these figurines remains obscure, with multiple suggestions offered, including their use as toys, talismans, teaching aids, exchange tokens, or for rituals.

Key Virulence Factors Responsible For Differences In Pathogenicity Between Clinically Proven Live-Attenuated Japanese Encephalitis Vaccine Sa14-14-2 And Its Pre-Attenuated Highly Virulent Parent Sa14, Byung-Hak Song, Sang-Im Yun, Joseph L. Goldhardt, Jiyoun Kim, Young-Min Lee

Animal, Dairy, and Veterinary Science Student Research

Japanese encephalitis virus (JEV), a neuroinvasive and neurovirulent orthoflavivirus, can be prevented in humans with the SA₁₄-14-2 vaccine, a live-attenuated version derived from the wild-type SA₁₄ strain. To determine the viral factors responsible for the differences in pathogenicity between SA₁₄ and SA₁₄-14-2, we initially established a reverse genetics system that includes a pair of full-length infectious cDNAs for both strains. Using this cDNA pair, we then systematically exchanged genomic regions between SA14 and SA₁₄-14-2 to generate 20 chimeric viruses and evaluated their replication capability in cell culture and their pathogenic potential in …

The Continuing Search For A Better Mouse Trap: Two Tests Of A Practical, Low-Cost Camera Trap For Detecting And Observing Small Mammals, Raymond D. Dueser, John H. Porter, Nancy D. Moncrief

Wildland Resources Faculty Publications

The advent of digital wildlife cameras has led to a dramatic increase in the use of camera traps for mammalian biodiversity surveys, ecological studies and occupancy analyses. For cryptic mammals such as mice and shrews, whose small sizes pose many challenges for unconstrained digital photography, use of camera traps remains relatively infrequent. Here we use a practical, low-cost small mammal camera platform (the “MouseCam”) that is easy and inexpensive to fabricate and deploy and requires little maintenance beyond camera service. We tested the MouseCam in two applications: a study of small mammal species composition on two transects across a barrier …

Evaluations Of Hand-Arm Vibration (Hav) Exposure And Related Vascular And Musculoskeletal Heath Effects Among Groundskeeping Workers In Southeastern U.S., Nathan Chen

All ETDs from UAB

Long-term, excessive exposure to hand-arm vibration (HAV) may induce vascular, neurological, and musculoskeletal disorders, collectively known as hand-arm vibration syndrome (HAVS). However, concerns arise when adopting the currently available guidelines and standards to protect workers who regularly use vibrating tools due to the lack of standardized exposure assessment methods for HAV and reliable health indicators for HAVS. The existing exposure-response relationship addressed in ISO 5349-1 was developed based on epidemiological studies predominantly performed in temperate zones. Thus, this dissertation aimed to evaluate the HAV exposure levels and vascular and muscular health effects from vibration exposure among groundskeepers in the southeastern …

Gene Model For The Ortholog Of Glys In Drosophila Simulans, Madeline L. Gruys, Madison A. Sharp, Zachary Lill, Caroline Xiong, Amy T. Hark, James J. Youngblom, Chinmay P. Rele, Laura K. Reed

Faculty Journal Articles

Gene model for the ortholog of glycogen synthase ( Glys ) in the Drosophila simulans May 2017 (Princeton ASM75419v2/DsimGB2) Genome Assembly (GenBank Accession: GCA_000754195.3 ). This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

The Sow Vaginal And Gut Microbiota Associated With Longevity And Reproductive Performance, Ziyu Liu, Tsungcheng Tsai, Samantha Howe, Jason E. Farrar, Christopher E. Randolph, Charles V. Maxwell, Jiangchao Zhao

Animal Science Faculty Publications and Presentations

BackgroundSow longevity and reproductivity are essential in the modern swine industry. Although many studies have focused on the genetic and genomic factors for selection, little is known about the associations between the microbiome and sows with longevity in reproduction.ResultsIn this study, we collected and sequenced rectal and vaginal swabs from 48 sows, nine of which completed up to four parities (U4P group), exhibiting reproductive longevity. We first identified predictors of sow longevity in the rectum (e.g., Akkermansia) and vagina (e.g., Lactobacillus) of the U4P group using RandomForest in the early breeding stage of the first parity. Interestingly, these bacteria in …

Impact Of Achromobacter Xylosoxidans Infection On The Cf Lung In Single-Species And Polymicrobial Infection With Pseudomonas Aeruginosa, Caitlin E. Billiot

All ETDs from UAB

Achromobacter xylosoxidans is a Gram-negative bacillus that acts as an opportun- istic pathogen in those with cystic fibrosis (CF). Infection with A. xylosoxidans in these populations is associated with decreased lung function. Thus, this raises the question of the role of A. xylosoxidans in CF disease progression. CF is a polymicrobial disease and A. xylosoxidans is oftentimes isolated alongside Pseudomonas aeruginosa, a major CF colonizer. In the context of CF disease, it is important to understand the implications of polymicrobial infection as altered infection dynamics are observed when multiple microbes colonize together. In the first half of this work, we …

Transcriptomic Transformations And Epigenetic Elements: The Heart Of The Matter Across Diverse Cardiac Pathophysiologies, Sayan Bakshi

All ETDs from UAB

Cardiovascular disease (CVD) comprises a complex array of disorders affecting the heart and blood vessels, representing the leading cause of mortality worldwide. This multifaceted nature of CVD has prompted extensive research into its molecular underpinnings and etiological diversity. Despite significant advances, the majority of CVD management strategies are guideline-based symptomatic treatment. This necessitates extensive research studies on therapeutic interventions aimed at disease prevention or cure. In this dissertation, we have employed next-generation sequencing (NGS) techniques to elucidate the cardiac transcriptional and epigenetic landscape across various conditions, including ischemic heart failure (IHF), Cardiogenic shock (CS), and diabetic heart failure (DHF). Our …

Characterization Of Dhdds Rp59 Knock-In Mouse Models Of Retinitis Pigmentosa, Mai Ngoc Nguyen

All ETDs from UAB

Cis-prenyltransferase (CPT), a prenyl chain elongation enzyme made up of two copies of dehydrodolichyl diphosphate synthase (DHDDS) and two copies of Nogo-B Receptor (NgBR), condenses metabolites from the mevalonate pathway to create dolichol, a sugar carrier required for glycosylation in all cells of the body. However, certain missense mutations in DHDDS cause non-syndromic retinitis pigmentosa (RP59). Three missense mutations, K42E, T206A, and R98W have been found in RP59 patients that present the cardinal phenotypes of RP – diminished ERG responses, attenuated retinal vessels, bone spicule-like pigmentation, and retinal thinning due to photoreceptor loss. However, no global changes in glycosylation are …

Targeted Inhibition Of Aurora Kinase A Promotes Immune Checkpoint Inhibition Efficacy In Human Papillomavirus-Driven Cancers, Soma Ghosh, Madison P O'Hara, Pragya Sinha, Tuhina Mazumdar, Lacin Yapindi, Jagannadha K Sastry, Faye M Johnson

Faculty, Staff and Student Publications

Background: Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes. In a previous study, we demonstrated that Aurora kinase A (AURKA, Aurora A) inhibitors lead to apoptosis of human HPV-positive cancer cells in vitro and in vivo. Here, we explored the potential of Aurora A inhibition to enhance response to ICIs in immune-competent …

Genetics And Biology Of Pancreatic Ductal Adenocarcinoma, Haoqiang Ying, Alec C Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A Depinho

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology. We further summarize and synthesize breakthroughs in single-cell and metabolic profiling technologies that have illuminated the complex cellular composition and heterotypic interactions of the PDAC tumor microenvironment, with an emphasis on metabolic cross-talk across cancer and …

Sstr2-Targeted Theranostics In Hepatocellular Carcinoma, Majid Momeny, Solmaz Aghaamiri, Servando Hernandez Vargas, Belkacem Acidi, Sukhen C Ghosh, Tyler M Bateman, Jack T Adams, Vahid Khalaj, Ahmed O Kaseb, Hop S Tran Cao, Ali Azhdarinia

Faculty, Staff and Student Publications

Background: While the clinical use of radiolabeled somatostatin analogs is well established in neuroendocrine tumors, there is growing interest in expanding their application to other somatostatin receptor 2 (SSTR2)-expressing cancers. This study investigates the potential utility of SSTR2-targeted theranostics in hepatocellular carcinoma (HCC).

Methods: SSTR2 expression in HCC cell lines and clinical samples was evaluated using qRT-PCR, Western blot analysis, and a public dataset. 67Ga-DOTATATE uptake was measured, 177Lu-DOTATATE cytotoxicity was assessed, and 68Ga-DOTATATE tumor targeting was evaluated in HCC animal models and a patient via PET/CT imaging.

Results: SSTR2 expression was confirmed in HCC cell lines and clinical samples. …

Development Of Sacb-Based Counterselection For Efficient Allelic Exchange In Fusobacterium Nucleatum, Peng Zhou, Bibek G C, Bo Hu, Chenggang Wu

Faculty, Staff and Student Publications

Fusobacterium nucleatum, prevalent in the oral cavity, is significantly linked to overall human health. Our molecular comprehension of its role in oral biofilm formation and its interactions with the host under various pathological circumstances has seen considerable advancements in recent years, primarily due to the development of various genetic tools for DNA manipulation in this bacterium. Of these, counterselection-based unmarked in-frame mutation methods have proved notably effective. Under suitable growth conditions, cells carrying a counterselectable gene die, enabling efficient selection of rare, defined allelic exchange mutants. The sacB gene from Bacillus subtilis, encoding levansucrase, is a widely used …

Evaluation Of Green Tea Yoghurt Enriched With Lacticaseibacillus Paracasei E1 Microcapsules On Macrophage M1 Profile In High Fat-Fructose Diet Mice, Esha Ardiansyah, Nur Alfi Maghfirotus Sa’Adah, Rahmi Izati, Belinda Nabiila Al Faizah, Dawama Nur Fadlilah, Septhyanti Aprilia Kavitarna, Mochammad Fitri Atho’Illah, Siti Nur Arifah, Yoga Dwi Jatmiko, Muhaimin Rifa’I

Karbala International Journal of Modern Science

Obesity is caused by an energy imbalance that increases chronic low-grade inflammation, including macrophage cell infiltration. Adipose tissue macrophages are polarized into pro-inflammatory macrophage type 1 (M1), secrete large amounts of pro-inflammatory cytokines, and activate transcription factors. Yoghurt with probiotics is popular at all ages for its health benefits and must be protected by microencapsulation. Green tea (Camellia sinensis L.) fortification provides yoghurt nutrients while improving its functional qualities and bioactivity. This study aimed to evaluate the effect of microencapsulation of Lacticaseibacillus paracasei E1 in green tea yoghurt (GTY) on the profile of M1 macrophages in mice fed a …

Monitoring And Assessment Of Population, Reproductive, And Health Effects In Colonial Waterbirds Breeding At Contaminated Great Lakes Sites In Michigan, Keith A. Grasman, Mandy Annis, Carly Eakin, Jeremy Moore, Lisa L. Williams

University Faculty Publications and Creative Works

Immunological, reproductive, and population endpoints were assessed in fish-eating birds during 2010–2019 in the Saginaw River and Bay and River Raisin Areas of Concern (AOCs) and Grand Traverse Bay, which are ecosystems historically contaminated with polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans. Reference sites were in the lower St. Marys River (herring gulls and Caspian terns), eastern Lake Superior (terns), and eastern Lake Huron (black-crowned night herons). Relative risk ratios for embryonic nonviability (from both infertility and mortality) in gull embryos were 2–3-fold higher than the reference site in both AOCs and Grand Traverse Bay. Twelve of 13 deformed embryos and chicks …

Circakb: A Comprehensive Knowledgebase Of Circadian Genes Across Multiple Species, Xingchen Zhu, Xiao Han, Zhijin Li, Xiaobo Zhou, Seung-Hee Yoo, Zheng Chen, Zhiwei Ji

Faculty, Staff and Student Publications

Circadian rhythms, which are the natural cycles that dictate various physiological processes over a 24-h period, have been increasingly recognized as important in the management and treatment of various human diseases. However, the lack of sufficient data and reliable analysis methods have been a major obstacle to understanding the bidirectional interaction between circadian variation and human health. We have developed CircaKB, a comprehensive knowledgebase of circadian genes across multiple species. CircaKB is the first knowledgebase that provides systematic annotations of the oscillatory patterns of gene expression at a genome-wide level for 15 representative species. Currently, CircaKB contains 226 time-course transcriptome …

Metabolic And Physiological Characteristics Of Diet Manipulation And Genetic Modification In Two Rat Models Of Aging, Soe Maung Maung Phone Myint

All ETDs from UAB

As society and human civilization advances, humans have begun to live longer and most people live to be longer than 60, which was not the case several decades ago. According to the World Health Organization(WHO), by the turn of the next decade at 2030, 1 in 6 people will be 60 years or older, accounting for almost 1.4 billion people. Aging affects people differently but in general, it has a propensity to induce widespread and progressive molecular and cellular damage which leads to a myriad of diseases and eventually death. The greatest risk factor for most of the chronic diseases …

Investigating The Thermodynamic Properties Of Fat10 And Fat10ylated Proteins, Aravind R

Theses and Dissertations

Degradation of proteins by the proteasome is crucial in regulating protein levels in the cell. Post-translational modifications, such as ubiquitylation and Fat10ylation, trigger proteasomal degradation of the substrate proteins. While ubiquitylation orchestrates multiple cellular processes, Fat10ylation is primarily involved in the inflammatory response. Unlike ubiquitin, recycled upon substrate degradation, Fat10 is degraded along with its substrate. Although the thermodynamic properties of the substrate are critical for effective proteasomal degradation, they remain poorly understood for the Fat10-proteasome pathway.

Here, we demonstrate that Fat10 exhibits markedly lower thermodynamic stability and faster unfolding kinetics compared to ubiquitin. This is due to the absence …

Selectivity Of Invasive Species Suppression Efforts Influences Control Efficacy, Rae Fadlovich, Kevin Landom, Timothy E. Walsworth

Watershed Sciences Student Research

1. Highly fecund invaders and size-selective suppression efforts often limit the effectiveness of invasive species control programs, as compensatory processes can allow suppressed populations to recover. While population models have long explored how demographic characteristics impact management feasibility, there is a growing need to evaluate how the selectivity of suppression efforts might impact the long-term feasibility of control.
2. We use a simulation framework that integrates age-based selectivity to evaluate the effect of increasing the range of ages selected for during harvest-based invasive species control. We applied this approach to common carp in Utah Lake, the location of one of the world's …

Role Of Ring-Box E3 Ligases In Runx2 And Sp7 Protein Turnover During Osteoblast Differentiation, Abeera Sikandar

All ETDs from UAB

The bone matrix synthesis by osteoblast during skeletogenesis is regulated by several transcription factors and signaling pathways. Runx2 and Sp7 are master regulators of osteoblast differentiation and bone formation. Deletion of both genes in mice results in the complete failure of ossification. In humans, Sp7 and Runx2 genes mutations cause osteogenesis imperfecta and cleidocranial dysplasia, respectively. The progression of osteoblast differentiation requires a coordinated and temporal expression of Runx2 and Sp7 genes. Posttranslational modifications regulate the cellular levels and function of Runx2 and Sp7 proteins. Ubiquitination controls protein turnover through targeted degradation. The multi-subunit SCF-complex is the largest class of …

Alternative Splicing In The Brain: Across Disease States, Sexes, Regions, And Cell Types, Emma Finn Jones

All ETDs from UAB

Molecular phenotype heterogeneity is prevalent across multiple contexts and is mediated by mRNA expression differences and the gene and isoform level. Isoform-level mRNA complexity in the brain is essential for healthy neurodevelopment, and perturbations in AS are associated with many neurological and psychiatric disorders. While previous research has examined how AS changes in the brain, there is still a gap in using newer techniques to study these changes with greater specificity. Therefore, we address this gap by using long-read and scRNA-seq technologies to study isoform-level diversity in AS across four contexts (i.e., disease, sex, region, and cell type) in the …

Cytotoxic, Genotoxic, And Metabolic Effects Of Dihydroxyacetone In Heart, Liver And Lung Models, Arlet Hernandez

All ETDs from UAB

Dihydroxyacetone (DHA) is a triose sugar found as an active ingredient in sunless tanning products (STPs) and by-product in electronic cigarettes (e-cigarettes). DHA can rapidly be absorbed into cells and tissues and incorporated into several metabolic pathways through its conversion into dihydroxyacetone phosphate (DHAP). Previous studies have shown that DHA promotes cytotoxicity and genotoxicity primarily characterized in skin models. The extent of these effects in systemic models is highly cell-type specific. Here we investigate the cytotoxic, genotoxic, and metabolic effects of DHA across several cell models. First, we investigated the effects of DHA in a metabolically active cell line, hepatocellular …

The Evolutionary Ecology Of Reproductive System Variation In Haploid-Diploid Freshwater Red Macroalgae, Sarah Connelly

All ETDs from UAB

Reproductive systems describe the relative rates of sexual versus asexual reproduction and selfing versus outcrossing, governing the transmission of genetic diversity between generations and shaping evolutionary responses to environmental change. Though sex has inherent costs, it contributes to the reproductive system for most eukaryotes, generating incredible life cycle diversity. Life cycles are expected to be correlated with different reproductive systems. Diploid life cycles should be associated with outcrossing, whereas life cycles with a long-lived haploid phase are hypothesized to be associated with selfing and asexual reproduction. To test this hypothesis, we used ten polymorphic microsatellite loci to genotype 311 gametophytes …

Targeted Exon Skipping Of Nf1 Exon 52 As A Mutation Specific Therapeutic For Neurofibromatosis Type 1, Cameron Lee Church

All ETDs from UAB

Modification of pre-mRNA splicing using antisense oligonucleotides (ASOs) can be used to skip one or more exons carrying pathogenic DNA sequence variants. Our previ-ously published data indicates NF1 exon 52 is a good target for exon skipping as a cDNA screen indicates an NF1 isoform lacking exon 52 maintains both high neurofi-bromin expression and the ability to suppress Ras activity. To develop an exon skipping approach, we designed antisense phosphorodiamidate morpholino oligomers (PMOs) to skip exon 52. Our lead PMO has a low IC50 of 45nM and is able to restore NF1 expres-sion and Ras-suppression in a cell line with …

Single Nucleus Multiomics Reveals The Drought-Driven Gene Regulatory Atlas In Arabidopsis, Jinbao Liu

All ETDs from UAB

The regulation of gene expression in plant responses to drought has been thoroughly in-vestigated in previous studies. Despite this, a detailed understanding of the cell type-specific regulatory mechanisms, encompassing multi-layered biological processes, is lack-ing. In this study, we report the use of single nucleus multiomic analysis in Arabidopsis seedlings in response to drought stress. Our single-nuclei RNA (snRNA) analysis deline-ated 14 distinct clusters representing major root and shoot cell types and discovered new cell type-specific drought markers. Integration of snRNA with single-nuclei ATAC (snATAC) data in leaf epidermis, root endodermis, and guard cells revealed accessible chromatin regions (ACRs)-linked genes predominantly …

Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate, Talia Fargason

All ETDs from UAB

The protein Serine-Arginine-rich Splicing Factor 1 (SRSF1) is essential in multiple stages of the mRNA lifecycle, including alternative splicing, nonsense-mediated decay, and nuclear export. SRSF1’s dysfunction is linked to cancers, viral evasion, and developmental disorders. Its function depends on interactions between structured and unstructured regions, modulated by phosphorylation. However, the unstructured regions, while critical for regulation, contribute to protein insolubility, hindering full-length studies. Prior to the work presented here, structural studies of SRSF1 were limited to analysis of its isolated domains. This dissertation develops new techniques to characterize SRSF1, focusing on its intermolecular interactions driving phase separation and intramolecular interactions …

Diurnal Function And Expression Of Aquaporins In The Mouse Kidney, Phi Hung Nguyen

All ETDs from UAB

Aquaporins (AQPs) are a family of proteins that play a major role in maintaining water homeostasis. Aquaporin 2 (AQP2) and aquaporin 3 (AQP3) are expressed in the collecting duct and regulated by the antidiuretic hormone arginine vasopressin (AVP) through the AVPR2 receptor. It is well known that biological circadian rhythms are critical for maintaining homeostasis. In both humans and rodents, the kidneys exhibit time-of-day-dependent changes in function. We hypothesized that there is a diurnal pattern in urine and/or plasma osmolality, and that this may reflect changes in kidney aquaporins in mice. Male and female C57BL/6J mice (10-11 weeks old) were …

Effects Of Whole-Food, Plant-Centered Diets On Glycemic Control, Medication Use, Ectopic Fat, And Cardiovascular Health In Adults With Type 2 Diabetes, Cody Hanick

All ETDs from UAB

Type 2 diabetes (T2D) is a global health and economic concern. Safe and effective treatments for T2D, including dietary approaches, are limited. Additionally, it remains unclear whether dietary carbohydrate quality or quantity matters more for managing T2D. Most nutrient-dense carbohydrate quality sources—such as fruit, vegetables, legumes, and whole grains—come from plant foods and are recommended for people with T2D by the American Diabetes Association. Furthermore, when these food groups are combined into a dietary pattern, a whole-food, plant-based (WFPB) diet is created. However, few studies have tested the effects of a WFPB diet or carbohydrate-rich food groups in people with …

The Manipulation Of Odor Availability Of Training Aids Used In Detection Canine Training, Katylynn B. Sloan, Michele N. Maughan, Caitlin E. Sharpes, Robin R. Greubel, Shawna F. Gallegos, Aleksandr E. Miklos, Lindsay D. Waldrop

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Detection canines can identify numerous substances for which they have been trained. Historically, and a point of ongoing contention, detection canine threshold (i.e., sensitivity or limit of detection) training has primarily focused on changing the weight of the training aid substance used. There has been minimal focus on other principles, such as surface area, confinement, and temperature, which can be manipulated to affect odor availability. That said, trainers have been manipulating odor availability for years without necessarily understanding the governing scientific principles. The aim of this review is to highlight the principles that control odor availability of a substance and …

Crisprofft: Comprehensive Database Of Crispr/Cas Off-Targets, Grant Wang, Xiaona Liu, Aoqi Wang, Jianguo Wen, Pora Kim, Qianqian Song, Xiaona Liu, Xiaobo Zhou

Faculty, Staff and Student Publications

The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated protein) programmable nuclease system continues to evolve, with in vivo therapeutic gene editing increasingly applied in clinical settings. However, off-target effects remain a significant challenge, hindering its broader clinical application. To enhance the development of gene-editing therapies and the accuracy of prediction algorithms, we developed CRISPRoffT (https://ccsm.uth.edu/CRISPRoffT/). Users can access a comprehensive repository of off-target regions predicted and validated by a diverse range of technologies across various cell lines, Cas enzyme variants, engineered sgRNAs (single guide RNAs) and CRISPR editing systems. CRISPRoffT integrates results of off-target analysis from 74 studies, encompassing …