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Development Of An Integrated Workflow For Nucleosome Modeling And Simulations, Ran Sun Mar 2024

Development Of An Integrated Workflow For Nucleosome Modeling And Simulations, Ran Sun

Doctoral Dissertations

Nucleosomes are the building blocks of eukaryotic genomes and thus fundamental to to all genetic processes. Any protein or drug that binds DNA must either cooperate or compete with nucleosomes. Given that a nucleosome contains 147 base pairs of DNA, there are approximately 4^147 or 10^88 possible sequences for a single nucleosome. Exhaustive studies are not possible. However, genome wide association studies can identify individual nucleosomes of interest to a specific mechanism, and today's supercomputers enable comparative simulation studies of 10s to 100s of nucleosomes. The goal of this thesis is to develop and present and end-to-end workflow that serves …


The Role Of Med31 And Med12 In Directing Adipogenesis Of Human Adult-Derived Mesenchymal Stem Cells, Joseph Straub May 2021

The Role Of Med31 And Med12 In Directing Adipogenesis Of Human Adult-Derived Mesenchymal Stem Cells, Joseph Straub

Doctoral Dissertations

Selective gene expression is crucial in maintaining the self-renewing and multipotent properties of stem cells. Mediator is a large, evolutionarily conserved, multisubunit protein complex that modulates gene expression by relaying signals from cell type-specific transcription factors to RNA polymerase II. In humans, this complex consists of 30 subunits arranged in four modules: head, middle, tail, and kinase. In our introduction, we show the state of the field of Mediator study with a focus on the critical kinase module. In the following chapters, we used siRNA knockdowns to investigate the roles of the highly-conserved core subunit MED31 and the kinase module …


Glial Endothelial Brain Cell Co-Cultures For Testing Signaling Response And Delivery Of Novel Materials Across Blood Brain Barrier, Neela Prajapati May 2021

Glial Endothelial Brain Cell Co-Cultures For Testing Signaling Response And Delivery Of Novel Materials Across Blood Brain Barrier, Neela Prajapati

Doctoral Dissertations

The brain accounts for 20% of overall energy metabolism in the body though it just comprises 2% of the total body mass but has a limited capacity of storing energy unlike other critical organs in the body such as the heart and liver. This energy along with oxygen and nutrients is supplied by cerebral blood flow (CBF), any interruption of which can cease the brain function within seconds with a potential irreversible neuronal injury, within minutes. Vascular cells along with astrocytes and neurons are a part of a recently developed concept known as the Neurovascular Unit responsible for Neurovascular coupling …


Engineered Coating Of Natural Fibers And Oil-Water Interfaces With Self-Assembly Of Clay Nanotubes, Abhishek Panchal Nov 2018

Engineered Coating Of Natural Fibers And Oil-Water Interfaces With Self-Assembly Of Clay Nanotubes, Abhishek Panchal

Doctoral Dissertations

Taking into consideration two different types of surfaces, this dissertation proposes techniques to coat the surface of natural fibers and oil-water interfaces by spontaneous self-assembly of halloysite clay nanotubes. The material of choice, halloysite clay, is a widely available natural resource and can be used after minimal processing. In regards to chemical composition, halloysite clay resembles aluminosilicate mineral kaolin; physically, a defect in the crystal structure ordering causes the sheets of kaolinite to roll into halloysite nanotubes. The dimensions of halloysite nanotubes are dependent on the source, but generally vary from 200 nm to 3 µm in length, 100-150 nm …


Improvement Of Fluorescence-Based Microfluidic Dna Analyzers, Collin Tranter Apr 2017

Improvement Of Fluorescence-Based Microfluidic Dna Analyzers, Collin Tranter

Doctoral Dissertations

A tremendous effort continues in the development of micro-total-analysis-systems; in support of this, many chemical passivation methods have been developed to enhance the biocompatibility of such microfluidic systems. However, the suitability of these passivation techniques to many fluorescence-based assays still remains inconsistent. This part of this work is focused on the performance of a third generation intercalating DNA dye when used within microfluidic devices treated with a select variety of passivating coatings. The results of these tests indicate that passivation coatings which are intended to shed DNA based on electrostatic repulsion will in fact imbibe the fluorescent DNA intercalating dye …


Genome Engineering In Mammalian Cells By Flp And Cre Dna Recombinase Variants, Riddhi Shah Jul 2016

Genome Engineering In Mammalian Cells By Flp And Cre Dna Recombinase Variants, Riddhi Shah

Doctoral Dissertations

Genome engineering relies on DNA modifying enzymes that are able to locate a DNA sequence of interest and initiate a desired genome rearrangement. Currently, the field predominantly utilizes site-specific DNA nucleases that depend on the host DNA repair machinery to complete a genome modification task. We show here that genome engineering approaches that employ self-sufficient, versatile site-specific DNA recombinase Flp and Cre can be developed into promising alternatives. We demonstrate that a Flp variant evolved to recombine an FRT-like sequence FL-IL10A, which is located upstream of the human interleukin-10 gene, can target this sequence in the model setting and native …


Nano Clay-Enhanced Calcium Phosphate Cements And Hydrogels For Biomedical Applications, Udayabhanu Jammalamadaka Jul 2016

Nano Clay-Enhanced Calcium Phosphate Cements And Hydrogels For Biomedical Applications, Udayabhanu Jammalamadaka

Doctoral Dissertations

Biomaterials are used as templates for drug delivery, scaffolds in tissue engineering, grafts in surgeries, and support for tissue regeneration. Novel biomaterial composites are needed to meet multifaceted requirements of compatibility, ease of fabrication and controlled drug delivery. Currently used biomaterials in orthopedics surgeries suffer limitations in toxicity and preventing infections. Polymethyl methacrylate (PMMA) used as bone cement suffers from limitations of thermal necrosis and monomer toxicity calls for development of better cementing biomaterials. A biodegradable/bioresorbable cement with good mechanical properties is needed to address this short coming. Metal implants used in fixing fractures or total joint replacement needs improvements …


Microbial Ecology Of Waterborne Pathogens In Sus Scofra And Odocoileus Virginianus In The Jackson Bienville Wildlife Management Area, Jaymes Hunter Collins Apr 2016

Microbial Ecology Of Waterborne Pathogens In Sus Scofra And Odocoileus Virginianus In The Jackson Bienville Wildlife Management Area, Jaymes Hunter Collins

Doctoral Dissertations

Previous studies have demonstrated that feral swine (Sus scofra ) are significant reservoirs for a number of pathogens that present a potential threat to wildlife and humans. Despite this, few studies have gone beyond quantifying the incidence of these pathogens to further probe their ecology within a specific habitat or ecosystem.

Overall, the objective of this study was to characterize three potential reservoirs in a feral swine infested habitat; two ungulates, and one aquatic reservoir. Our study area was the Jackson-Bienville Wildlife Management Area (J-B WMA). We chose four waterborne bacteria: Brucella spp., Leptospira interrogans, Salmonella enterica, and Helicobacter …


Clay Nanotube Composites For Antibacterial Nanostructured Coatings, Christen J. Boyer Apr 2016

Clay Nanotube Composites For Antibacterial Nanostructured Coatings, Christen J. Boyer

Doctoral Dissertations

A surging demand for the development of new antimicrobial nanomaterials exists due to the frequency of medical device-associated infections and the transfer of pathogens from highly touched objects. Naturally occurring halloysite clay nanotubes (HNTs) have shown to be ideal particles for polymer reinforcement, time-release drug delivery, nano-reactor synthesis, and as substrate material for nanostructured coatings.

This research demonstrates the feasibility of a novel method for coating HNTs with metals for antibacterial applications. The first ever ability to coat HNTs through electrolysis was developed for customizable and multi-functional antibacterial nanoparticle platforms. HNTs were investigated as substrate for the deposition of copper …


Mutlifunctional Platforms For Gene And Drug Delivery For Cancer Therapy, Jeffery J. Ambrose Jr. Apr 2016

Mutlifunctional Platforms For Gene And Drug Delivery For Cancer Therapy, Jeffery J. Ambrose Jr.

Doctoral Dissertations

The National Cancer Institute and the American Cancer Society estimate that 1.6 million new cancer incidences and over half a million cancer related deaths occur annually [1][2]. Cancer the second most common cause of death in the United States [1], [2]. Although the causes of cancer can vary depending on cell type, all or almost all instances of cancer arise from a mutation or from an abnormal activation of the cellular genes that control cell growth and mitosis [3].

Treatment of a given cancer type depends on the subtype, stage and progression of the cancer. Varieties of cancer therapy include …


Size Specific Transfection To Mammalian Cells By Micropillar Array Electroporation, Yingbo Zu Jan 2016

Size Specific Transfection To Mammalian Cells By Micropillar Array Electroporation, Yingbo Zu

Doctoral Dissertations

Electroporation serves as a promising non-viral gene delivery approach, while its current configurations carry drawbacks associated with high-voltage electrical pulses and heterogeneous treatment on individual cells. Here, we developed a new micropillar array electroporation (MAE) platform to advance the delivery of plasmid DNA and RNA to mammalian cells. By introducing well-patterned micropillar array on the electrode surface, the number of pillars each cell faces varies with its cell membrane surface area, despite their large population and random locations. In this way, cell size specific electroporation is conveniently done and contributed to a 2.5~3 fold increase on plasmid DNA transfection and …


Improvements On Segment Based Contours Method For Dna Microarray Image Segmentation, Yang Li Jul 2014

Improvements On Segment Based Contours Method For Dna Microarray Image Segmentation, Yang Li

Doctoral Dissertations

DNA microarray is an efficient biotechnology tool for scientists to measure the expression levels of large numbers of genes, simultaneously. To obtain the gene expression, microarray image analysis needs to be conducted. Microarray image segmentation is a fundamental step in the microarray analysis process. Segmentation gives the intensities of each probe spot in the array image, and those intensities are used to calculate the gene expression in subsequent analysis procedures. Therefore, more accurate and efficient microarray image segmentation methods are being pursued all the time.

In this dissertation, we are making efforts to obtain more accurate image segmentation results. We …


Selected Durability Studies Of Geopolymer Concrete With Respect To Carbonation, Elevated Temperature, And Microbial Induced Corrosion, Mohammad Sufian Badar Apr 2014

Selected Durability Studies Of Geopolymer Concrete With Respect To Carbonation, Elevated Temperature, And Microbial Induced Corrosion, Mohammad Sufian Badar

Doctoral Dissertations

This thesis reports a comprehensive study related to the experimental evaluation of carbonation in reinforced geopolymer concrete, the evaluation of geopolymer concretes at elevated temperature, and the resistance of geopolymer concrete to microbial induced corrosion (MIC).

Carbonation: Reinforced concretes, made of geopolymer, prepared from two class F fly ashes and one class C fly ash, were subjected to accelerated carbonation treatment for a period of 450 days. Electrochemical, microstructure and pore structure examinations were performed to evaluate the effect of corrosion caused due to carbonation. GPC specimens prepared from class F fly ash exhibited lower corrosion rates by a factor …


A Mathematical Model And Numerical Method For Thermoelectric Dna Sequencing, Liwei Shi Jul 2013

A Mathematical Model And Numerical Method For Thermoelectric Dna Sequencing, Liwei Shi

Doctoral Dissertations

DNA sequencing is the process of determining the precise order of nucleotide bases, adenine, guanine, cytosine, and thymine within a DNA molecule. It includes any method or technology that is used to determine the order of the four bases in a strand of DNA. The advent of rapid DNA sequencing methods has greatly accelerated biological and medical research and discovery. Thermoelectric DNA sequencing is a novel method to sequence DNA by measuring the heat that is released when DNA polymerase inserts a deoxyribonucleoside triphosphate into a growing DNA strand. The thermoelectric device for this project is composed of four parts: …


Multiscale Modeling Of Enzyme-Catalyzed Methanol Production By Particulate Methane Monooxygenase, Katherine K. Bearden Apr 2013

Multiscale Modeling Of Enzyme-Catalyzed Methanol Production By Particulate Methane Monooxygenase, Katherine K. Bearden

Doctoral Dissertations

In this work, the conversion of methane to methanol by the particulate Methane Monooxygenase (pMMO) enzyme is investigated using a multi-scale modeling approach. This enzyme participates in carbon cycling and aids in the removal of harmful atmospheric methane, converting it to methanol. The interaction between pMMO and a neighboring enzyme that is present in the same organism is studied, and the unknown pMMO active site is elucidated and tested for methane oxidation towards the production of methanol.

Fundamental knowledge of pMMO's mechanism is not fully understood. Understanding how this enzyme works in nature will provide information towards designing efficient synthetic …


The Measurement Of Auditory Interhemispheric Transfer Time (Ihtt) In Children With Normal Auditory Processing Abilities, Brittany Suzanne Keahey Apr 2013

The Measurement Of Auditory Interhemispheric Transfer Time (Ihtt) In Children With Normal Auditory Processing Abilities, Brittany Suzanne Keahey

Doctoral Dissertations

Interhemispheric transfer time (IHTT) is the time it takes for information to be transmitted from one hemisphere to the other. The goal of this study was to determine if differences existed in the IHTT of children 6 to 9 years of age with normal auditory processing abilities by the use of an objective measure (auditory late evoked potentials [ALEPs]), specifically waves P1, N1 and P2. It was hypothesized that there would be no difference in IHTT between the groups due to the age range of participants being tested. The 16 participants were divided into two groups based on age and …


Engineering Microenvironments To Modulate Calcium Information Processing In Neuronal Cells, Kinsey Cotton Kelly Jan 2013

Engineering Microenvironments To Modulate Calcium Information Processing In Neuronal Cells, Kinsey Cotton Kelly

Doctoral Dissertations

Tissue engineered microenvironments were constructed to test the effects glial cells have on calcium information processing, and to mimic conditions in vivo for tumor invasion and residual cancer after resection of tumor. Submaximal, nM, glutamate (GLU) stimuli were applied to the engineered environments, and the resulting calcium dynamic behavior of neuronal cells was measured to help predict and interpret chaotic systems in the experimental realm. Calcium is a key signaling ion which signals through the N-methyl-D-aspartate (NMDA) glutamate receptor on the neuronal membrane. GLU binding to the NMDA receptor (NMDAR) causes a large and dynamic increase in neuronal intracellular calcium. …


A Study Of Cellular Calcium Dynamics In Culture Using Fluorescence Microscopy – A Statistical And Mathematical Approach, Richard Adekola Idowu Oct 2012

A Study Of Cellular Calcium Dynamics In Culture Using Fluorescence Microscopy – A Statistical And Mathematical Approach, Richard Adekola Idowu

Doctoral Dissertations

Calcium in its ionic form is very dynamic, especially in excitable cells such as muscle and brain cells, moving from the high concentration exterior of the cell to much lower concentrations inside the cell, where calcium is used as a second messenger. In brain cells, and neurons especially, calcium is a key signaling ion involved in memory and learning with excitatory neurotransmitters such as glutamate turning neurons "on." Glutamate excites the neurons in part by causing large and dynamic changes in the intracellular calcium concentration. While these dynamics are essential for normal signaling in the brain, excessive and sustained elevations …


Real-Time Analysis Of Brain Tumor Cell Dynamics: Novel Thermoelectric Detection Of L-Glutamate And Cell Metabolism Using Microfluidics, Siva Mahesh Tangutooru Oct 2012

Real-Time Analysis Of Brain Tumor Cell Dynamics: Novel Thermoelectric Detection Of L-Glutamate And Cell Metabolism Using Microfluidics, Siva Mahesh Tangutooru

Doctoral Dissertations

This study describes the design, fabrication and applications of a novel thermoelectric microfluidic bio-sensor. The bio-sensor is used for real time detection of the L-glutamate (L-glu) dynamics and metabolism for brain tumor cells immobilized in a microfluidic device. The microfluidic device is fabricated using a polymer/glass laminating technique (Xurography). An antimony-bismuth thin-film thermopile (primary sensing element) is integrated to the microfluidic device. The brain tumor cells are immobilized over the thermopile covering measuring and reference junctions of the thermopile using a poly-l-lysine coating layer. L-glutamate oxidase (L-GLOD) is immobilized over the measuring junctions of the thermopile prior to the immobilization …


The Contribution Of Oxidative Stress In The Protein Damage And Dna Lesion In Alzheimer's Disease Neuropathology, Cheng Zhang Oct 2012

The Contribution Of Oxidative Stress In The Protein Damage And Dna Lesion In Alzheimer's Disease Neuropathology, Cheng Zhang

Doctoral Dissertations

Glutathione (GSH) plays an essential role in the intracellular antioxidant defense against the oxidant radicals, especially the ·OH radical. To understand the early and progressive cellular changes in Alzheimer's disease (AD) development, we investigated reduced glutathione/oxidized glutathione (GSH/GSSG) status in a double mutated AD transgenic mouse model (B6.Cg-Tg), which carries Swedish amyloid precursor protein mutation (APPswe) and exon 9 deletion of the PSEN1 gene. Likewise, S-glutathionylation (Pr-SSG) is a specific post-translational modification (PTM) of cysteine residues by the addition of glutathione. S-glutathionylated proteins induced by oxidative stress play an essential role in understanding the pathogenesis of the aging …


A Hybrid Brain-Computer Interface Based On Motor Intention And Visual Working Memory, Ching-Chang Kuo Oct 2012

A Hybrid Brain-Computer Interface Based On Motor Intention And Visual Working Memory, Ching-Chang Kuo

Doctoral Dissertations

Non-invasive electroencephalography (EEG) based brain-computer interface (BCI) is able to provide alternative means for people with disabilities to communicate with and control over external assistive devices. A hybrid BCI is designed and developed for following two types of system (control and monitor).

Our first goal is to create a signal decoding strategy that allows people with limited motor control to have more command over potential prosthetic devices. Eight healthy subjects were recruited to perform visual cues directed reaching tasks. Eye and motion artifacts were identified and removed to ensure that the subjects' visual fixation to the target locations would have …


Associative Pattern Mining For Supervised Learning, Harpreet Singh Apr 2010

Associative Pattern Mining For Supervised Learning, Harpreet Singh

Doctoral Dissertations

The Internet era has revolutionized computational sciences and automated data collection techniques, made large amounts of previously inaccessible data available and, consequently, broadened the scope of exploratory computing research. As a result, data mining, which is still an emerging field of research, has gained importance because of its ability to analyze and discover previously unknown, hidden, and useful knowledge from these large amounts of data. One aspect of data mining, known as frequent pattern mining, has recently gained importance due to its ability to find associative relationships among the parts of data, thereby aiding a type of supervised learning known …


Weight Gain Among Adults With Intellectual Disabilities Receiving Atypical Antipsychotics, Sherri Lyn Transier Jan 2010

Weight Gain Among Adults With Intellectual Disabilities Receiving Atypical Antipsychotics, Sherri Lyn Transier

Doctoral Dissertations

The present study assessed whether the atypical antipsychotic agents olanzapine, risperidone, and quetiapine are associated with significant weight gain among adults with intellectual disabilities after 6 months of drug treatment. The body weights of 79 participants were retrieved 6 months prior to the initiation of drug treatment, at the start of the atypical antipsychotic agent, and after 6 months of drug therapy. Each individual served as his or her own control by utilizing pretreatment baseline trends in weight change to calculate a dependent measure of adjusted posttreatment weight gain. Doing so allowed for a stringent determination of the liability for …


Micro, Nano Encapsulation Methods For Sustained Release Drug Formulations And Biomimetic Applications, Shantanu Balkundi Jul 2009

Micro, Nano Encapsulation Methods For Sustained Release Drug Formulations And Biomimetic Applications, Shantanu Balkundi

Doctoral Dissertations

The Layer-by-Layer (LbL) assembly technique was used to obtain a new type of protein/polyphenol microcapsule based on naturally occurring polyphenol (-)-epigallocatechin gallate (EGCG) and gelatin, type A. The dependence of permeability on the molecular weight of permeating substances was studied and compared with commonly used polyallylamine/polystyrene sulfonate capsules. A quartz crystal microbalance was used to monitor the regularities of EGCG adsorption in alternation with type A and B Gelatins and electrophoretic mobility measurements were used that indicated that the nature of assembly was dependent on Gelatin properties. It was shown that EGCG retains its antioxidant activity in the LbL assemblies. …


Discrete Nondeterministic Modeling Of Biochemical Networks, John R. Jack Apr 2009

Discrete Nondeterministic Modeling Of Biochemical Networks, John R. Jack

Doctoral Dissertations

The ideas expressed in this work pertain to biochemical modeling. We explore our technique, the Nondeterministic Waiting Time algorithm, for modeling molecular signaling cascades. The algorithm is presented with pseudocode along with an explanation of its implementation. The entire source code can be found in the Appendices. This algorithm builds on earlier work from the lab of Dr. Andrei Nun, the advisor for this dissertation. We discuss several important extensions including: (i) a heap with special maintenance functions for sorting reaction waiting times, (ii) a nondeterministic component for handling reaction competition, and (iii) a memory enhancement allowing slower reactions to …


An Examination Of Factors Affecting Weight And Health In Exercising Adults, Cynthia West Dupuis Apr 2009

An Examination Of Factors Affecting Weight And Health In Exercising Adults, Cynthia West Dupuis

Doctoral Dissertations

Obesity is a significant problem in American society with approximately 65% of the population classified as overweight and the obesity rate exceeding 30% of all American adults. Obesity is associated with widespread physical and mental health problems which lead to increased healthcare costs, increased work absenteeism, and decreased work productivity. The factors of genetics and diet have been studied extensively by researchers in relation to weight gain and health. Physical exercise also has been established as a factor that affects weight and health, but exercise programs of all types suffer from an average attrition rate of approximately 50%. The additional …


Integrated Mining Of Feature Spaces For Bioinformatics Domain Discovery, Pradeep Chowriappa Oct 2008

Integrated Mining Of Feature Spaces For Bioinformatics Domain Discovery, Pradeep Chowriappa

Doctoral Dissertations

One of the major challenges in the field of bioinformatics is the elucidation of protein folding for the functional annotation of proteins. The factors that govern protein folding include the chemical, physical, and environmental conditions of the protein's surroundings, which can be measured and exploited for computational discovery purposes. These conditions enable the protein to transform from a sequence of amino acids to a globular three-dimensional structure. Information concerning the folded state of a protein has significant potential to explain biochemical pathways and their involvement in disorders and diseases. This information impacts the ways in which genetic diseases are characterized …


Nanoengineered Templates For Controlled Delivery Of Bioactive Compounds, Nalinkanth Ghone Veerabadran Jul 2008

Nanoengineered Templates For Controlled Delivery Of Bioactive Compounds, Nalinkanth Ghone Veerabadran

Doctoral Dissertations

The significance of any drugs, therapeutic proteins, or any bioactive compounds, is based not only on their effects on diseases but also on how specifically, how readily, how controllable and how prolonged their effects on the disease without having any side effects. Thus the techniques involved in the drug encapsulation and its controlled release for a longer duration of time form one of the important processes of drug reformulation. In recent years nanoparticles have created overwhelming attention for delivering drugs by nanoencapsulation. The smaller size of nanoparticles has longer circulation time and higher cellular uptake when compared with larger size …


Gene Synthesis, Cloning, Expression, Purification And Biophysical Characterization Of The C2 Domain Of Human Tensin, Kiran Sukumar Gajula Oct 2007

Gene Synthesis, Cloning, Expression, Purification And Biophysical Characterization Of The C2 Domain Of Human Tensin, Kiran Sukumar Gajula

Doctoral Dissertations

Tensin is a large "docking" protein found in the adhesive junctions of animal cells and recruited early in the development of cell-substrate contacts. There it binds to the cytoplasmic domain of integrin β1 and caps the barbed ends of filamentous actin. This forms a rational basis for its implication in a direct role in the mechanics of membrane-cytoskeleton interactions. Tensin provides a physical link between the actin cytoskeleton, integrins, and other proteins at the cell-substrate contacts. Its overall biochemical properties are a function of its domain composition and architecture, i.e., the domains that are present and their relative positions in …


Biophysical Study Of The Sh2 Domain Of Human Tensin, Yogesh Mohan Kulkarni Oct 2007

Biophysical Study Of The Sh2 Domain Of Human Tensin, Yogesh Mohan Kulkarni

Doctoral Dissertations

Cell migration is a key characteristic of embryogenesis, inflammation, wound healing, tumor cell metastasis and a broad range of other normal and pathological processes. Accumulating evidence suggests that the protein tensin provides a physical link between transmembrane receptors, proteins commonly associated with signal transduction, and the actin cytoskeleton. Adhesion involves three broad classes of macromolecules: ExtraCellular Matrix (ECM) molecules, transmembrane adhesion receptors, and intracellular adhesion plaque proteins. Tensin is particularly enriched in Fibrillar Adhesions (FA's), though it is also present to a modest extent in Focal Contacts (FC's). Src Homology 2 (SH2) domains function in the transmission of molecular signals …