Life Sciences Commons^™

In Silico And Toxicological Evaluation Of Crescentia Cujete Aqueous Extract: Potential Anticancer Activity Against Breast Cancer, Rahma Diyan Martha, Fatimah Fatimah, Syahputra Wibowo, Bantari Wisynu Kusuma Wardhani, Josephine Elizabeth Siregar, Elisabeth Farah Novita Coutrier, Alfia Fitrianita, Andri Pramesyanti Pramono, Ita Margaretha Nainggolan, Yudhi Nugraha, Danar Danar, Naufal Abiyyu, Lalu Unsunnidhal, Aswin Rafif Khairullah, Arif Nur Muhammad Ansori, Hesty Parbuntari, Wimbuh Tri Widodo

Makara Journal of Science

Majapahit plant (Crescentia cujete), commonly found in Indonesia, has not been extensively explored for its medicinal properties. Given that many cancer treatments are derived from plants, this study aimed to examine the effects of plants on cancer chemical composition of the C. cujete fruit pulp extract, identify its primary compounds, and assess its potential as an antioxidant, anticancer agent, particularly for breast cancer. An insilico approach was used to evaluate the toxicity and interactions, of the compounds with cancer biomarker proteins, in addition to an in vivo Brine Shrimp Lethality Test (BSLT) for BSLT, toxicity screening using six …

Rna G-Quadruplexes Function As A Tunable Switch Of Fus Phase Separation, Jenny L. Carey, Miyuki Hayashi, Emily A. Welebob, Laura R. Ganser, Huan Wang, Kerry Buckhaults, Jacquelyn A. Depierro, Zheng Shi, James Shorter, Sua Myong, Aaron R. Haeusler, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Fused in sarcoma (FUS) undergoes liquid-liquid phase separation (LLPS) to support essential cellular functions, but aberrant phase transitions promote toxic aggregation in neurodegenerative disease. Short RNA oligonucleotides can reverse this behavior, yet the structural determinants that govern RNA activity remain poorly defined. Here, we identify RNA G-quadruplexes (rG4s) as tunable structural motifs that potently modulate FUS LLPS. rG4 activity depends on its concentration and is modulated by rG4 length and stability: increasing repeat number switches rG4s from inhibitor to nucleator of FUS assembly, whereas chemical modifications that stabilize rG4 enhance inhibitory function and render these activities resilient to ionic perturbation. …

Advancing Paradigm Of Quantitative Synthetic Biology And Strengthening Mission-Oriented Basic Research, Chenli Liu

Bulletin of Chinese Academy of Sciences (Chinese Version)

Synthetic biology is an important frontier in the life sciences, yet its further development remains constrained by limited capacity for rational design. Quantitative synthetic biology, which iteratively integrates quantitative modeling with the construction and analysis of synthetic systems, offers a promising paradigm for addressing this challenge. In this perspective, the study discusses the background and motivations underlying the emergence of this field and summarizes recent developments and exploratory efforts. Considering the unique characteristics of quantitative synthetic biology, it is suggested that progress in the field may benefit from strategically organized collaborative research that balances mission-oriented goals with investigator-driven exploration. On …

Histone Deacetylases In Kidney Injury: Distribution, Injury-Specific Regulation, And Fibroblast Hdac1 Function, Huy Nguyen

ETDs from 2020-2029

Acute kidney injury (AKI) is increasingly recognized as a major contributor to the development of chronic kidney disease (CKD) through maladaptive repair and interstitial fibrosis. Epigenetic regulation has emerged as a critical factor of kidney injury responses, however the injury-specific and cell-type specific roles of histone deacetylases (HDACs) remain poorly defined. This dissertation investigates the regulation and functional significance of HDACs in kidney injury, with a particular focus on fibroblast HDAC1 as a mediator of interstitial fibrosis development following AKI. In my cisplatin-induced AKI model, a single dose of cisplatin caused a significant decline in kidney function in both male …

Main-Chain Ion-Pair Polybenzimidazole Membranes Enabling Reduced-Temperature Ht-Pemfc Operation (Down To 120°C), Brian C. Benicewicz, Huina Lin

Faculty Publications

Proton exchange membrane (PEM) fuel cells are promising for clean and efficient energy conversion across diverse applications. High-temperature PEM fuel cells (HT-PEMFCs) using phosphoric acid (PA)-doped polybenzimidazole (PBI) can operate up to 200°C, but at lower temperatures, water-induced PA loss often leads to performance degradation and reduced durability. In this work, we present a new class of main-chain ion-pair PBI membranes by integrating the imidazolium-biphosphate ion-pair units directly into the PBI backbone. This design results in membranes with high acid content, stronger acid-polymer interactions and stabilized acid retention. In single-cell tests, the Im+-PBI15-3 wt.% exhibits peak power densities of 0.79 …

Elucidating The Mechanisms Of Complex Flavoprotein Dehydrogenases, Tyler Alt

Dissertations

Flavins are ubiquitous redox active cofactors that can catalyze electron transfer between substrates. They offer the advantage of being able to stabilize a range of oxidation and protonation states, as well being amenable to covalent modification, which can further alter their activity. As such, the scope of reactions catalyzed by flavoproteins is broad and flavin has implications in a range of biological processes. The two predominant forms of flavin that serve as redox active cofactors are flavin adenine mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are functionally homologous. A major complication of studying flavoprotein dehydrogenases, and one that has …

Influence Of Smoking On Mlh1 Gene Polymorphism: Insights Into Colorectal Cancer Incidence, Ali Mohammed Al-Abedi, Rand Muhammed Abdul-Hussein Al-Husseini

Al-Bahir

Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The MutL Homolog 1 (MLH1) gene plays a critical role in DNA mismatch repair (MMR). Evidence suggests cigarette smoking increases CRC risk, potentially interacting with genetic factors.

Materials and Methods: This case-control study involved 50 Iraqi CRC patients and 50 age- and gender-matched healthy controls. The PCR-RFLP technique was employed for genotyping the -93G/A (rs1800734) polymorphism. Statistical analysis included Chi-square, Fisher's Exact Test, and logistic regression adjusted for confounders. Hardy-Weinberg Equilibrium (HWE) was assessed in controls.

Results: The frequency of the rs1800734 variant was significantly higher in CRC …

A Rho5-Cnc1-Dnm1 Signalling Module Coordinates Multi-Organelle Execution Of Regulated Cell Death In Yeast, Justin Bauer

Theses and Dissertations

Regulated cell death is a conserved process with major implications for health and disease, yet how yeast cells integrate stress signals to determine survival versus death remains unclear. This thesis investigates Cyclin C (Cnc1), a conserved Mediator kinase module component with both transcriptional and mitochondrial roles. Together with Cdk8 Cnc1 primarily represses stress response genes, while upon stress it translocates to the mitochondria to induce mitochondrial fragmentation with the dynamin-related GTPase Dnm1. Using structure-guided separation-of-function mutants, I demonstrate that Cnc1-dependent death requires its mitochondrial function rather than its transcriptional role, and that its effector Dnm1 acts as a signaling node …

Elucidating The Function Of Yedk In Response To Dna Damage, Hank Munro

University Honors Theses

Apurinic/Apyrimidinic (AP) sites are one of the most prevalent forms of DNA damage. These lesions arise spontaneously or during base excision repair of modified DNA bases and are potentially mutagenic in both mammalian and bacterial cells. 5-hydroxymethylcytosine binding, ES cell specific (HMCES), a protein found in eukaryotic cells, has been shown to form a stable DNA-protein crosslink with AP sites in single stranded DNA and to reduce the number of AP sites occurring either spontaneously or after alkylative DNA damage, resulting in increased genome stability. YedK, the Escherichia coli ortholog of HMCES exhibits some of the same biochemical properties as …

The Neuroprotective Effect Of Cdc42 Inhibition In The G93a Mutant Hsod1 Mouse Model Of Als, Andrea Koly

Undergraduate Theses, Capstones, and Recitals

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by the selective loss of upper and lower motor neurons, leading to muscle weakness, neuromuscular junction (NMJ) degeneration, paralysis, and eventual death due to respiratory failure. Despite extensive research, effective disease-modifying therapies remain limited, underscoring the need to identify novel molecular targets involved in ALS pathogenesis. Dysregulation of Rho family GTPases has been implicated in neurodegeneration, with Rac and Rho exerting opposing effects on neuronal survival; however, the role of the closely related GTPase Cdc42 remains poorly understood in ALS. In this study, the therapeutic potential of inhibiting …

Allosteric And Uncompetitive Inhibition Of Yeast Alcohol Dehydrogenase Identified By Enzyme Kinetics, Dylan Jeremy Harrison, Jenny A. Cappuccio

IdeaFest: Interdisciplinary Journal of Creative Works and Research from Cal Poly Humboldt

Enzyme kinetics is a powerful technique used to quantify the rate at which an enzyme converts a substrate into a product and to identify potential inhibitors. In this study, kinetic analysis was employed to assess the activity of yeast alcohol dehydrogenase (YADH) in the presence and absence of sweeteners commonly found in alcoholic beverages. YADH catalyzes the oxidation of ethanol to acetaldehyde using NAD⁺ as a cofactor; the reduction to NADH can be monitored spectrophotometrically at 340 nm. Based on structural similarities to the ribose moiety of NAD⁺, it was hypothesized that sucrose and sucralose could directly interact with the …

A Computational Micropatterning Approach To Study Caveolae And Protein Localization In Vascular Biology, Andrew B. Grespin

Electronic Theses and Dissertations

Caveolae are specialized, flask-shaped membrane invaginations highly expressed in endothelium and dysregulated in atherosclerosis. Caveolae play a central role in buffering membrane tension, yet the principles governing their spatial organization remain elusive. Thus, we sought to generate the most comprehensive and systematic analysis of blood vessel caveolar spatial organization. However, cell culturing, the backbone of human-focused biological research, does not standardly do well to model physiologically relevant cell behaviors such as migration or polarity-based tissue formation, particularly for punctate proteins and structures like caveolae. Micropatterns are cell-adhesive shapes that biophysically confine cell(s) to a user defined geometry which stereotype organelle …

Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni

Biochemistry and Molecular Biology

Cryptosporidium parvum, the etiological agent of Cryptosporidiosis (diarrheal illness) represents a significant global health burden, particularly affecting immunodeficient and pediatric populations. Since the parasite has a highly reduced mitochondrion and relies on glycolysis, enzymes such as C. parvum malate dehydrogenase (CpMDH), which are believed to be indispensable for parasite viability due to their pivotal roles in NAD⁺ regeneration and redox balance, remain largely unexplored as therapeutic targets. The present study employed a multifaceted experimental and computational strategy to evaluate the inhibitory activity of two lead-like and drug-like small molecules, referred to as compound 1.8 and compound 1.5, against the cofactor …

High Mobility Group Motif Proteins’ Role In Fibrosis, Inflammation, And Vascular Injury In Systemic Sclerosis, Fabian A. Mendoza, Sonsoles Piera-Velazquez, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

Systemic Sclerosis (SSc) is an idiopathic systemic autoimmune disease characterized by progressive cutaneous and systemic fibrosis, severe vasculopathy, and multiple humoral and cellular immunological alterations. The pathogenesis of SSc is highly complex and remains incompletely elucidated. The fibrotic process is a crucial component of SSc and is responsible for organ failure and high mortality. Although an increasing understanding of the fibrotic process has enabled the clinical development of antifibrotic therapeutic agents, these agents have limited clinical efficacy. Recently, the potential role of a group of transcription factors containing a High Mobility Group (HMG) motif, in the development and pathological manifestations …

Terrestrial Abiotic Synthesis Of Simple Precursor Molecules Starting From Two Approaches: The Universality Of Carbon Reduction, Eloi Camprubi, Ben K.D. Pearce, Martina Preiner

School of Integrative Biological & Chemical Sciences Faculty Publications

To address the chemistry responsible for life’s emergence, we examine the simple chemicals accessible on early Earth and the processes that could have transformed them. We focus on carbon reduction as a process central to the direct precursors of life. Two main approaches for the emergence of life’s building blocks and their associated functions are discussed. One approach investigates chemical routes for forming life’s building blocks via processes that worked differently from those of extant life, referred to as “unrestricted” prebiotic chemistries. The other approach establishes a direct mechanistic connection between prebiotic building blocks and extant biochemistry, referred to as …

Synthesis And Characterization Of Synergistic Bioactive– Organometallic Condensation Polymers, Francesca Isabel Mosca

Electronic Theses and Dissertations 2020 - Present

This research focuses on the synthesis and structural characterization of polymers with anticipated anticancer and antiviral properties by combining metal-containing Lewis acids, organotin dichlorides (R2SnCl2), Group 4 metallocene dichlorides (Cp2TiCl2, Cp2ZrCl2 and Cp2HfCl2), and triphenyl Group 15 metal dichlorides (Ph3AsCl2, Ph3SbCl2 and Ph3BiCl2), with biologically active Lewis bases, lamivudine, a synthetic nucleoside, and camphoric acid, a dicarboxylic acid, to achieve synergistic effect.

Five classes of polymers were synthesized using interfacial polymerization: lamivudine and organotin dichlorides, lamivudine and Group 4 metallocene dichlorides, camphoric acid and triphenyl Group 15 metal dichlorides, camphoric acid and organotin dichlorides, and camphoric acid and Group 4 …

Synthesis And Characterization Of Organometallic Polymers And Their Cytotoxicity Towards Human Cancer Cell Lines, Paul Peter Slawek

Electronic Theses and Dissertations 2020 - Present

This research aimed to synthesize organometallic polymers from dialkyl (methyl, ethyl, butyl, cyclohexyl, and octyl) and diaryl (phenyl) tin dichlorides and three organic monomers, dipicolinic acid (DPA), chloramphenicol (CH), and isomannide (IS), using interfacial polymerization. Structure-activity relationships were investigated through physicochemical characterization (light-scattering photometry, proton NMR, and IR spectroscopy) and cytotoxicity was evaluated against six human cancer cell lines (AsPC-1, PANC-1, MCF-7, MDA-MB-231, HT-29, PC-3), with cisplatin serving as the reference standard.

Five DPA/tin polymers were synthesized, with IC₅₀ values in the range of 0.60–0.71 μg/mL. Their cytotoxicity was significantly lower than that of cisplatin (0.0023-0.044 μg/mL), suggesting that …

Chromatin Insulators Homie And Nhomie Can Interact With Distant Copies Either Together Or Separately, With Distinct Outcomes For Enhancer-Promoter Interactions, Miki Fujioka, Wenfan Ke, Paul Schedl, James B. Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

Chromatin insulators, a.k.a. boundary elements, separate regions of the chromosome with distinct chromatin characteristics, including distinct histone modifications. This activity affects gene expression by allowing chromatin domains to be stably regulated and maintained. Insulators also block enhancer-promoter interactions and, somewhat paradoxically, facilitate other interactions, particularly when they stitch together distant regions of the chromosome by pairing with specific partners. Here we explore how long-range interactions facilitated by insulator pairing are affected by the presence of two potentially competing partners. Our results show that when two partners are present, they can reduce each other's effects on distant gene expression, suggesting that …

Targeting Inflammatory And Growth Signaling Pathways In Breast Cancer Through Diet, Microbiome, And Metabolite Interactions, Brittany Lorraine Witt

ETDs from 2020-2029

Breast cancer (BC) accounts for 1 in 3 (or 30%) of all new female cancers each year and is the most common malignant cancer in women in the United States. Since the 1990s, there has been a 44% decrease in BC, but there is still a significant gap between certain groups in terms of mortality rates. Black women have a higher mortality rate and risk for triple-negative breast cancer (TNBC). This may be due to social (inadequate access to health care facilities, insurance, or completion of therapy) and biological (genetic mutations, tumor characteristics, or comorbidity) factors between races and other …

Napier Grass (Pennisetum Purpureum) Meal Modulates Growth Efficiency, Gut Morphology, And Systemic Health In Broiler Chickens, Eric Lim Teik Chung, Yee Lyn Ong, Nazri Nayan, Muhamad Faris Ab Aziz, Faez Firdaus Abdullah Jesse, Faizal Andri, Arissara Sopawong

The Thai Journal of Veterinary Medicine

Grass and leaf meals, which include vital phytocompounds, have the potential to be a natural and safe alternative to antibiotics in the poultry industry. Therefore, this study aims to assess Pennisetum purpureum leaf meal and its phytocompounds on the health performances of colored-broilers. A total of 216 unsexed Sasso chicks were assigned to six diet groups. The negative control (T1) received a commercial basal diet without antibiotics, while the positive control (T2) received the same diet with oxytetracycline (100 mg/kg). Groups T3 to T6 received no antibiotics and included P. purpureum meal at 1.25, 2.50, 3.75, or 5.00 grams per …

Detection And Evaluation Of Hazardous Mercury Contamination In Various Biological Samples, Krish Italiya

Biochemistry and Molecular Biology

Mercury is a toxic environmental pollutant that threatens ecosystems and human health. This study investigates mercury contamination in Lactuca sativa (lettuce) and selected fish species, including tuna and salmon, focusing on plant responses and the limitations of X-ray fluorescence (XRF) analysis. In a controlled experiment, lettuce plants were exposed to mercury to evaluate uptake and toxicity, and XRF spectroscopy was used for quick, non-destructive elemental analysis. Results confirmed mercury accumulation in lettuce, along with visible stress symptoms such as leaf yellowing, purple pigmentation, and tissue damage. Mercury was not detected in tuna and salmon samples, likely due to concentrations below …

Elucidating The Role Of The Rnf20 Histone Modifier In Pancreatic Beta Cells, Tanya Hans Pierre

ETDs from 2020-2029

Diabetes is defined as a loss of functional beta cell mass. It is classically categorized into Type 1 Diabetes (T1D), immune-mediated beta cell destruction and Type 2 Diabetes, which is characterized by whole body insulin resistance alongside beta cell dysregulation. The incidence of diabetes worldwide has risen annually. Despite the presence of therapeutic interventions, diabetes’ heterogeneity can prompt ineffective glycemic control and the development of diabetes-associated comorbidities. For that reason, new approaches to glycemic control for individuals with diabetes are required. One approach to restore glucose homeostasis is beta cell replacement therapy, in which stem cells are programmed into beta-like …

Dock7 Is A Novel Modifier Of Duchenne Muscular Dystrophy Pathology, Katherine English

ETDs from 2020-2029

Duchenne muscular dystrophy (DMD) is a progressive, x-linked neuromuscular disorder affecting 1/5000 male births every year. DMD results from mutations in DMD, a critical structural protein within the muscle. In the absence of Dystrophin, the muscle degrades, increasing inflammation, destabilizing the cell membrane and going through constant cycles of regeneration which depletes the stem cell population. Over time, muscle tissue is replaced by fibrosis and adipose tissue, leading to loss of ambulation, respiratory and cardiac failure leading to death by early 20s. The standard of care for DMD patients is corticosteroid treatment. However, gene therapies have recently emerged which present …

Developing A High-Resolution Off-Axis Common-Mode Digital Holographic Microscope, Lucy Cook

University Honors Theses

Off-axis digital holographic microscopy (DHM) is a powerful tool for 3D, non-invasive live-cell tracking without moving parts. However, traditional setups face an inherent dilemma: split-path interferometers offer high spatial resolution but poor temporal stability, while more stable common-mode configurations are historically limited to lower numerical aperture (NA) regimes. This thesis bridges that gap by scaling a common-mode DHM architecture into a high-resolution benchtop instrument featuring NA = 0.65 objectives, paired with a high-power 520 nm laser source to combat transmission losses and sustain imaging frame rates across an expanded optical footprint. We map the multi-variable design space required to satisfy …

Hydroxamate Formation In The Lipopeptide Containing Siderophore Taiwachelin, Aaron J. Gringer, Kernen P. Agwaza, Isabel Da Fonseca, Pablo Sobrado

Chemistry Faculty Research & Creative Works

Cupriavidus taiwanensis is a nitrogen-fixing bacterium found in root nodules of the invasive tropical weed Mimosa pudica . C. taiwanensis has been shown to grow in environments contaminated with heavy metals such as Pb, Cu, and Cd. Taiwachelin, a recently identified siderophore produced by C. taiwanensis , is an iron chelator that contains a hydroxamate functional group for metal binding. In its biosynthesis, a flavin-dependent N-monooxygenase (NMO) was predicted to hydroxylate l -ornithine, leading to formation of the metal binding hydroxamate moiety. Here, we report the cloning, expression, and biochemical characterization of this enzyme, herein referred to as CtNMO. CtNMO …

Computational Insights Into Nucleosome Dynamics In Epigenetics Using Molecular Dynamics Simulations, Rutika Patel

Dissertations, Theses, and Capstone Projects

Nucleosome core particles (NCP) are the building blocks that form a highly organized and compact chromatin structure. Nucleosomes package DNA in the nucleus of eukaryotic cells. The NCP consists of about 147 base pairs of DNA wrapped around the histone octamer, with 1.65 superhelical turns in a left-handed manner. The histone octamer is composed of two copies of H3, H4, H2A, and H2B. Together with histone H1 and linker DNA, they further assemble into a higher-order chromatin structure. The nucleosome complex is stabilized by electrostatic interactions between positively charged histone residues and the negatively charged DNA backbone. To effectively access …

Mapping Nucleosome Stability: Linking Oncogenic Structural Alterations To Long-Range Allosteric Communication, Augustine C. Onyema

Dissertations, Theses, and Capstone Projects

The nucleosome core particle (NCP) is essential for chromatin structure and function, serving as the fundamental unit of eukaryotic chromatin. Oncogenic mutations in core histones disrupt chromatin dynamics, altering DNA repair and transcription processes. How DNA communicates with histones, and how this information propagates through the histone, has been suggested to be a cooperative process. Here, I investigate the molecular consequences of two mutations, H2BE76K and H4R92T, using 36 µs of all-atom molecular dynamics simulations on Anton2. I also characterize the kinetic correlation within histone/DNA domains via conditional activity (CONDACT) using the dihedral angle as our degrees of …

Identifying Textual Predictors Of Early Termination In Clinical Trials In Medicine: An Explainable Machine-Learning Study, Rohan Ramnarain

Dissertations, Theses, and Capstone Projects

About one in five clinical trials in medicine ends early, wasting valuable resources and reducing the evidence available for developing life-saving medical treatments. This project uses a method called Trial2Vec, which is a self-supervised machine-learning method that converts clinical trial documents into dense numerical representations that capture their key design and clinical characteristics, to turn each proposed clinical trial’s written protocol into a compact numerical profile (a process referred to as embedding). These profiles are then paired with a predictive machine learning models to identify the words and phrases in the trial documents that can signal a higher risk of …

Supramolecular Assembly In Short Peptide Systems For Selective Metabolite Recognition And Drug Nanoencapsulation, Maithreyi Ramakrishnan

Dissertations, Theses, and Capstone Projects

Short peptides can form adaptive supramolecular assemblies, and understanding how minimal sequences organize around neurometabolites or hydrophobic cancer drugs enables the rational design of functional materials. This thesis combines molecular dynamics with experimental validation to establish design rules linking peptide sequence to emergent structure and function. Chapter 1 outlines the molecular determinants governing peptide assembly. Chapter 2 reviews computational workflows that reveal sequence-dependent conformations and supramolecular organization. Chapter 3 applies these principles to Dynamic Peptide Libraries which identify tetrapeptides that selectively interact with neurometabolites. Chapter 4 extends the same interaction-driven framework to design tryptophan-rich pentapeptides that co-assemble with kinase inhibitors …

Immunomodulatory And Signaling Molecules From Plant-Associated Bacteria: Toll-Like Receptor 4 Agonist Adjuvants And Diketopiperazine-Mediated Communication, Marian Romaine

Dissertations, Theses, and Capstone Projects

Medicinal plants and their associated microbiomes constitute a rich source of bioactive natural products with applications in immunotherapy and microbial ecology. Herbal formulations have long been valued for safe immune enhancement, while bacterial signaling molecules govern community behaviors critical to pathogenesis, symbiosis, and environmental processes. Bacterial lipopolysaccharides (LPS) from plant-associated Gram-negative bacteria have emerged as potent TLR4 agonists, yet their endotoxic potential limits direct use, and diketopiperazines (DKPs) serve as versatile quorum-sensing mediators capable of modulating biofilms in mixed microbial systems.

The work in this thesis comprises two independent but complementary research strands. The first strand pursued the engineering of …