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Hyperspectral Image Reconstruction From Rgb Data And Its Biomedical Applications, Tae Hoon Kim
Hyperspectral Image Reconstruction From Rgb Data And Its Biomedical Applications, Tae Hoon Kim
Open Access Dissertations
Noninvasive label-free hyperspectral imaging of physiological changes in biological systems has been extensively used as invaluable tools in a variety of research areas, including medical and biological applications. However, conventional approach requires a critical, yet bulky, expensive, and slow optical component (i.e. a mechanical filter wheel, an imaging spectrograph, or a liquid crystal tunable filter) for capturing full spectral information. Therefore, this component limits development of compact, rapid, and cost-effective systems. In this respect, we propose to explore a possibility of spectrometerless (or spectrometer-free) hyperspectral imaging to map out detailed spatial distributions of biochemical absorption compounds or pigments, which are …
Development Of Transgenic Black Ash (Fraxinus Nigra) For Resistance To The Emerald Ash Borer, And Genome Editing For Reproductive Sterility, Junhyung Lee
Open Access Dissertations
Black ash (Fraxinus nigra Marsh.) is valued for commercial hardwood products such as cabinets, paneling, flooring, and veneer, and for food and habitat for wildlife, specifically in riparian areas. The wood is preferred by Native Americans for making splints for basketry. The emerald ash borer (EAB), an aggressive exotic wood-boring beetle from Asia, is threatening all North American ash species. Since the first EAB infestation in the United States was confirmed near Detroit, Michigan in 2002, it has spread rapidly. In order to manage the EAB and conserve Fraxinus spp., there is a need to develop ash trees with resistance …
Reciprocal Relationships Between Parental Psychological Aggression And Adolescent Behavioral Problems, Yoonyoung Kwak
Reciprocal Relationships Between Parental Psychological Aggression And Adolescent Behavioral Problems, Yoonyoung Kwak
Open Access Dissertations
An extensive body of research has shown that parents’ harsh parenting and children’s behavioral problems are bidirectionally associated. These findings are in line with the transactional process theoretical model. Parental psychological aggression (PPA) is a nonphysical type of harsh parenting that is more prevalent among adolescents than corporal punishment and has rarely been tested for bidirectional relationships with diverse behavioral problems. This dissertation includes an investigation of the bidirectional relationship between PPA and four adolescent behavioral problems (delinquency, alcohol use, smoking, and running away) separately using samples from two different cultural contexts. The first sample is 591 adolescents who had …
Design Of Microstructured Conducting Polymer Films For Enhanced Trace Explosives Detection, Jennifer S. Laster
Design Of Microstructured Conducting Polymer Films For Enhanced Trace Explosives Detection, Jennifer S. Laster
Open Access Dissertations
The detection of trace amounts of explosive material is critical to national security. Ion mobility spectrometer (IMS)-based contact sampling continues to be a common method employed for the detection of explosives in high security checkpoint applications, such as airport security. In this process a surface of interest, such as a passenger’s hands or luggage, is probed by a swab or particle trap to collect and transfer residue to an IMS for analysis. The collection of residue on a sampling swab has been shown to be a limiting step in this detection process. As such, there is significant need to develop …
Hydrophobic Hydration And Aggregation In Aqueous Solutions, Joshua A. Long
Hydrophobic Hydration And Aggregation In Aqueous Solutions, Joshua A. Long
Open Access Dissertations
Water mediated hydrophilic and hydrophobic interactions are important for biological systems, atmospheric, geological, and environmental chemistry, and pharmaceuticals formulation development. Open questions remain regarding the degree of water restructuring in hydrophobic cavities, the extent of hydration in self-assembled aggregates, and the influence of water restructuring on hydrophobic interactions. Here, we use Raman spectroscopy combined with multivariate curve resolution (Raman-MCR), partial molar volume, and fluorescence spectroscopic methods to detect and quantify changes in hydration extent and structure due to hydrophobic aggregation and hydrophobic cavity structure. Raman-MCR decomposes an aqueous solution spectrum into solvent (pure water) and solute-correlated spectra, the latter of …
Imaging Cholesterol Metabolism And Trafficking By Stimulated Raman Scattering Microscopy, Hyeon Jeong Lee
Imaging Cholesterol Metabolism And Trafficking By Stimulated Raman Scattering Microscopy, Hyeon Jeong Lee
Open Access Dissertations
Cholesterol is an essential component of mammalian cells which is tightly regulated. However, our understanding of cholesterol transport and metabolism is still incomplete, partly due to lack of suitable tools for studying cholesterol dynamics in living cells and organisms with spatio-temporal information. My dissertation work applied spectroscopic imaging of cholesterol in human tissues, living cells, and model organisms to unravel new insights of cholesterol metabolism and trafficking. Using stimulated Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues, we observed an aberrant accumulation of cholesteryl ester in metastatic lesions. Inhibition of cholesterol esterification in prostate cancer cells …
Exploring The Genomic Basis Of Traits Relevant To Evolution And Ecology Of Chestnuts (Castanea) Using High-Throughput Dna Sequencing And Bioinformatics., Nicholas R. Labonte
Exploring The Genomic Basis Of Traits Relevant To Evolution And Ecology Of Chestnuts (Castanea) Using High-Throughput Dna Sequencing And Bioinformatics., Nicholas R. Labonte
Open Access Dissertations
Introduced pests and pathogens have devastated forest ecosystems in the temperate zone; in eastern North America, introduced pests and pathogens have led to the elimination of most mature elms (Ulmus), ashes (Fraxinus), hemlocks (Tsuga) and chestnuts (Castanea) over large areas where these genera were formerly abundant and important for local ecosystems. The restoration of species affected by introduced pests and pathogens requires the development and propagation of trees that possess heritable resistance. High-throughput DNA sequencing and genomics provide opportunities for researchers to identify resistance gene candidates, screen germplasm, and develop markers for marker-assisted selection in breeding programs, with the goal …
Digestibility Of Calcium In Feed Ingredients And Digestible Calcium Requirements For Pigs, Fengrui Zhang
Digestibility Of Calcium In Feed Ingredients And Digestible Calcium Requirements For Pigs, Fengrui Zhang
Open Access Dissertations
The objective of this research was to compare different expressions for the digestibility of Ca in both pigs and chickens, and to determine the true total tract digestible (TTTD) Ca requirement for 10- to 20-kg and 20- to 40-kg pigs. In the first study, two experiments were conducted to compare apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of Ca in pigs. In Exp. 1, three semi-purified diets with soybean meal, canola meal or sunflower meal as the sole source of Ca were formulated. Eighteen cannulated pigs (initial BW = 66 ± 5 kg) were assigned in a …
Remote Sensing Of Soil Moisture With Signals Of Opportunity (Soop), Yao-Cheng Lin
Remote Sensing Of Soil Moisture With Signals Of Opportunity (Soop), Yao-Cheng Lin
Open Access Dissertations
The measurement of soil moisture is essential for studying the hydrological cycle. Passive microwave radiometry is the most mature technology for the remote sensing of soil moisture, as demonstrated on ESAs Soil Moisture and Ocean Salinity (SMOS) satellite and the Soil Moisture Active Passive (SMAP) mission from NASA. Global Navigation Satellite System-Reflectometry (GNSS-R) has been demonstrated as an alternative approach to the remote sensing of soil moisture, through several airborne and ground-based experiments. All of these systems operate in L-band (1575.42 MHz for GNSS) which has a penetration depth in soil of only a few cm. GNSS signals are also …
An Investigation Of The Neural Circuitry Of Cued Alcohol Behaviors In P And Wistar Rats., Aqilah Maryam Mccane
An Investigation Of The Neural Circuitry Of Cued Alcohol Behaviors In P And Wistar Rats., Aqilah Maryam Mccane
Open Access Dissertations
Alcohol-paired cues invigorate alcohol-seeking and drinking behaviors in both rodents and individuals with alcohol use disorder (AUD). Additionally, genetic susceptibility plays a key role in alcohol addiction behaviors. Alcohol preferring (P) rats model both genetic vulnerability and symptoms of AUD. The basolateral amygdala (BLA), prefrontal cortex (PFC), hippocampus (HC) and nucleus accumbens (NA) are important brain regions involved in cued alcohol seeking. These regions are interconnected and their functional connections are hypothesized to be critical in the expression of motivated behaviors. Electrophysiological recordings in these four regions were collected in P rats engaged in a cued alcohol task. Data were …
Wavetda: Bayesian Statistics, Wavelets And Topological Data Analysis To Title Assess Statistical Shape, Patrick S. Medina
Wavetda: Bayesian Statistics, Wavelets And Topological Data Analysis To Title Assess Statistical Shape, Patrick S. Medina
Open Access Dissertations
Advanced imaging and scanning technologies are providing an abundance of shape-based data that require novel approaches to understand the factors that generate them. This is especially true in modern agricultural practices where large quantities of highly detailed morphometric data are collected and used for studying genetic associations. Toward this end there is an immediate need for efficient algorithms that extract relevant geometric information from images in a form that can be used within a statistical framework. Topological Data Analysis (TDA) has shown to be both fast and effective for studying complex shapes, and can simultaneously reduce dimensionality into simpler topological …
Investigation Of Pore Formation In Lipid Bilayer By Antimicrobial Peptides, Yuan Lyu
Investigation Of Pore Formation In Lipid Bilayer By Antimicrobial Peptides, Yuan Lyu
Open Access Dissertations
As more and more microbes develop resistance to conventional antibiotics and the decline in the approval of new antibiotics in recent years, there is an increasing need for research on identification and design of new therapeutic alternatives. As a result, antimicrobial peptides (AMPs) are becoming one of the most promising alternative options to target pathogens without developing resistance. It is known that AMPs inactivate microorganisms by forming transmembrane pores in cell membrane through adsorption and aggregation. Understanding the detailed mechanism of inactivation by AMPs is necessary for developing new agent for antimicrobial treatment. This study mainly investigates antimicrobial peptides from …
Biophysics Of Dna Based Nanosystems Probed By Optical Nanoscopy, Jing Pan
Biophysics Of Dna Based Nanosystems Probed By Optical Nanoscopy, Jing Pan
Open Access Dissertations
A dynamic DNA nanosystem exploits the programmable structure and energy landscape of DNA self-assembly to encode designed processes in a fuctuating molecular environment. One type of such a dynamic system, DNA walker, is reminiscent of biological motor proteins that convert chemical energy into mechanical translocation. Typical DNA walker travels tens of nanometers at a speed orders of magnitude slower than motor proteins. Two major challenges limited the development of functional DNA walkers. First, there are no suitable characterization methods that o˙er adequate spatial and temporal resolution to extract walker kinetics. Second, no guidelines have been established for the design and …
Lab-Scale Exploration Of Abiotic Transformation Approaches For Groundwater Remediation Of Per- And Polyfluoroalkyl Acids, Saerom Park
Open Access Dissertations
Per- and polyfluoroalkyl acids (PFAAs), a group of per- and polyfluoroalkyl substances (PFASs), have been extensively used in relatively large amount since the 1950s for industrial and consumer applications such as surfactants, coatings, paper packing products, and fire-fighting foams (e.g., aqueous film-forming foams (AFFFs)) due to their unique surfactant property and extremely chemically and thermally stable nature. Of the known PFAAs, long chain perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have received increasing attention in recent years due to their global distribution, environmental persistence, biological recalcitrance, bioaccumulative properties, and potential toxicities. Recently, other PFAAs such as 6:2 fluorotelomer sulfonate (6:2 …
Development Of A Direct-Contact Triculture Model Of The Human Blood Brain Barrier And Potential Applications As A Preclinical Drug Screening Tool, Aimable Ngendahimana
Development Of A Direct-Contact Triculture Model Of The Human Blood Brain Barrier And Potential Applications As A Preclinical Drug Screening Tool, Aimable Ngendahimana
Open Access Dissertations
Given the high cost and emerging ethical and public concerns associated with the use of animal models, the use of in vitro techniques is gaining considerable attention in research programs related to CNS drug discovery and development. More specifically, various in vitro cell culture models for studying and predicting drug transport across the Blood-Brain Barrier (BBB) were developed as preclinical research tools for neurological drug discovery and development. The main goal of the present studies has been to improve conventional in vitro methods used in mimicking the BBB physiology and functions by allowing physiologically complex interactions of the human BBB …
Mechanisms Regulating Dna Methyltransferases, Christopher James Petell
Mechanisms Regulating Dna Methyltransferases, Christopher James Petell
Open Access Dissertations
The expression of specific genes that are regulated by transcription factors and epigenetic modifications is critical for normal cellular functioning and homeostasis. DNA methylation is an epigenetic modification that in mammals is crucial for the regulation of gene expression in a specific cell type. Aberrant loss or gain of DNA methylation is linked to cancer and several epigenetic disorders. DNA methylation is established by the de novo DNA methyltransferases Dnmt3a and Dnmt3b; however, the mechanisms underlying their target specificity remain to be fully understood. Dnmt3a and Dnmt3b can be regulated through interactions with other proteins, including histone modifications, and by …
Engineering Novel 3d Tumor-Stroma Models To Bridge The Gap Between Preclinical Drug Development And Human Clinical Outcomes, Theodore J. Puls
Engineering Novel 3d Tumor-Stroma Models To Bridge The Gap Between Preclinical Drug Development And Human Clinical Outcomes, Theodore J. Puls
Open Access Dissertations
While much progress has been made in the war on cancer, shortcomings in the drug development process have kept anti-cancer clinical trial success rates low. One of the many factors implicated in this is the lack of pathophysiologically relevant and predictive preclinical models. Specifically, traditional preclinical tumor models do not capture tumor microenvironment complexity and heterogeneity, while advanced three-dimensional (3D) models suffer from poor reproducibility, lack of relevant and standardized extracellular matrix (ECM), and inability to interface with automated, high-throughput systems. Because of this, it has been suggested that developing novel phenotypic tumor models which balance the need for complexity …
Laser-Assisted Processing Of Multilayer Films For Inexpensive And Flexible Biomedical Microsystems, Rahim Rahimi
Laser-Assisted Processing Of Multilayer Films For Inexpensive And Flexible Biomedical Microsystems, Rahim Rahimi
Open Access Dissertations
Flexible/stretchable electronics offer ideal properties for emerging health monitoring devices that can seamlessly integrate with the soft, curvilinear, and dynamic surfaces of the human body. The resulting capabilities have allowed novel devices for monitoring physiological parameters, improving surgical procedures, and human-machine interfaces. While the attractiveness of these devices are indubitable, their fabrication by conventional cleanroom techniques makes them expensive and incompatible with rapid large-scale (e.g., roll-to-roll) production. The purpose of this research is to develop inexpensive fabrication technologies using low-cost commercial films such as polyimide, paper, and metalized paper that can be utilized for developing various flexible/stretchable physical and chemical …
Determining Variation In Virulence, Persistence, And Stress Tolerance Among Salmonella Enterica And Listeria Monocytogenes From Food And Food-Associated Environments, Andrea J. (Ray) Etter
Determining Variation In Virulence, Persistence, And Stress Tolerance Among Salmonella Enterica And Listeria Monocytogenes From Food And Food-Associated Environments, Andrea J. (Ray) Etter
Open Access Dissertations
The U.S. food industry employs multiple strategies to prevent foodborne illness including the use of antimicrobials, sanitizers, and heat to reduce or eliminate pathogens in food products. However, Listeria monocytogenes and Salmonella enterica isolates have widely varying tolerance to common processing stresses. Additionally, both pathogens display considerable variation in virulence among serovars and strains. The goal of these studies was to characterize the range of virulence and persistence capabilities for L. monocytogenes and S. enterica isolates. To this end, we determined the prevalence of inlA mutations in L. monocytogenes collected from retail deli surfaces, and used PFGE to study the …
Bone Manganese As A Potential Biomarker Of Cumulative Manganese Exposure And Predictor Of Neurological Decline, Danelle A. Rolle-Mcfarland
Bone Manganese As A Potential Biomarker Of Cumulative Manganese Exposure And Predictor Of Neurological Decline, Danelle A. Rolle-Mcfarland
Open Access Dissertations
Research into the health effects of cumulative exposure to manganese (Mn) has been limited due to the lack of a biomarker that adequately represents cumulative exposure. In this cross-sectional study, we assessed the usefulness of bone Mn (BnMn) as a biomarker of cumulative Mn exposure and as an indicator of neurological decline. Our research group utilized a novel, transportable, in vivo Neutron Activation Analysis (NAA) system to analyze BnMn in a group of Chinese workers (N=60). In addition to bone, blood and fingernail samples were also collected from participants and analyzed for Mn. Participants completed a questionnaire that included work …
Epoxide Bonded Phases For Chromatography And Immunoprecipitation, Nicholas J. Sortedahl
Epoxide Bonded Phases For Chromatography And Immunoprecipitation, Nicholas J. Sortedahl
Open Access Dissertations
Biomarker discovery is a difficult process. The goal of this work is to improve upon current state-of-the-art separation and extraction technology using functional epoxide surfaces. Specific attention is paid to immunoprecipitation and DNA separations. Immunoprecipitation is an excellent option when clean protein capture is required. Magnetic particles allow these experiments to be conducted in a high throughput fashion necessary for biomarker validation studies. However, commercial magnetic immunoprecipitation particles suffer from low particle magnetization, low capacity, and high nonspecific binding. By designing a new acid stable silica coated magnetic particle (Fe3O4@SiO2) a two-fold increase in signal to nose, and almost three-fold …
New Multi-Harmonic Techniques For Sensing Tip-Sample Interactions And Nanomechanical Material Property Mapping In Dynamic Atomic Force Microscopy, Nurul Huda Shaik
New Multi-Harmonic Techniques For Sensing Tip-Sample Interactions And Nanomechanical Material Property Mapping In Dynamic Atomic Force Microscopy, Nurul Huda Shaik
Open Access Dissertations
The Atomic Force Microscope (AFM) is a versatile tool for studying and characterizing materials at the micro-and nano-scales. The microcantilever designs used in AFM, as well as the experimental and theoretical approaches for quantitative material characterization, are now well developed and understood. However, there are still certain experimental conditions where the conventional design of these probes and the existing material characterization methods limit the applicability of the tool. The challenges associated with the probe design are addressed by integrating additional degrees of freedom into these probes that enabled modification of the eigen-structure of the probes as desired. Designing, fabricating and …
Coherent Radiation In Atomic Systems, Robert Tyler Sutherland
Coherent Radiation In Atomic Systems, Robert Tyler Sutherland
Open Access Dissertations
Over the last century, quantum mechanics has dramatically altered our understanding of light and matter. Impressively, exploring the relationship between the two continues to provide important insights into the physics of many-body systems. In this thesis, we add to this still growing field of study. Specifically, we discuss superradiant line-broadening and cooperative dipole-dipole interactions for cold atom clouds in the linear-optics regime. We then discuss how coherent radiation changes both the photon scattering properties and the excitation distribution of atomic arrays. After that, we explore the nature of superradiance in in intially inverted clouds of multi-level atoms. Finally, we explore …
Micromechanics Based Failure Analysis Of Heterogeneous Materials, Hamsasew M. Sertse
Micromechanics Based Failure Analysis Of Heterogeneous Materials, Hamsasew M. Sertse
Open Access Dissertations
In recent decades, heterogeneous materials are extensively used in various industries such as aerospace, defense, automotive and others due to their desirable specific properties and excellent capability of accumulating damage. Despite their wide use, there are numerous challenges associated with the application of these materials. One of the main challenges is lack of accurate tools to predict the initiation, progression and final failure of these materials under various thermomechanical loading conditions. Although failure is usually treated at the macro and meso-scale level, the initiation and growth of failure is a complex phenomena across multiple scales. The objective of this work …
Computational And Theoretical Study Of The Physical Constraints On Chemotaxis, Julien Varennes
Computational And Theoretical Study Of The Physical Constraints On Chemotaxis, Julien Varennes
Open Access Dissertations
Cell chemotaxis is crucial to many biological functions including development, wound healing, and cancer metastasis. Chemotaxis is the process in which cells migrate in response to chemical concentration gradients. Recent experiments show that cells are capable of detecting shallow gradients as small as a 1% concentration difference, and multicellular groups can improve on this by an additional order of magnitude. Examples from morphogenesis and metastasis demonstrate collective response to gradients equivalent to a 1 molecule difference in concentration across a cell body. While the physical constraints to cell gradient sensing are well understood, how the sensory information leads to cell …
Associative Learning Of The Generalist Predator Podisus Maculiventris To Herbivore- Induced Plant Volatiles, Ulianova Vidal-Gómez
Associative Learning Of The Generalist Predator Podisus Maculiventris To Herbivore- Induced Plant Volatiles, Ulianova Vidal-Gómez
Open Access Dissertations
Following herbivore attack, plants produce volatile organic compounds (HIPVs for herbivore induced plant volatiles) that allow predators to find and consume herbivores. The generalist predator Podisus maculiventris likely uses HIPVs in its foraging decisions. I hypothesized that the behavioral responses of this predator to HIPVs are acquired via associative learning, as suggested by theoretical predictions linking natural enemy host range with odor preferences. To evaluate P. maculiventris learning capabilities across different levels of biological organization, I use the tri-trophic system consisting of tomato (Solanum lycopersicum), hornworm caterpillars (Manduca sexta), and the predaceous stinkbug Podisus maculiventris to answer the following questions: …
Structure-Based Design And Synthesis Of Novel Inhibitors Of Hiv-1 Protease And Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1, Heather L. Osswald
Structure-Based Design And Synthesis Of Novel Inhibitors Of Hiv-1 Protease And Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1, Heather L. Osswald
Open Access Dissertations
HIV-1 protease is a critical enzyme in the life cycle of the human immunodeficiency virus (HIV). Targeting this enzyme halts the processing of viral polyproteins into mature and active enzymes which make virulent virions to further spread the infection. The development of the first HIV-1 protease inhibitor (PI) marked the beginning of highly active antiretroviral therapy (HAART) in 1995. Since then, many other first- and second-generation PIs have been designed and clinically evaluated. Still, mutations of the viral enzyme have resulted in drug-resistant strains of HIV, making the development of new, highly potent PIs of dire importance. To this end, …
Investigation Of Interaction Between Peptide And Lipid Bilayer By Molecular Dynamics Simulation, Ning Xiang
Investigation Of Interaction Between Peptide And Lipid Bilayer By Molecular Dynamics Simulation, Ning Xiang
Open Access Dissertations
Antimicrobial peptides (AMPs) inactivate microbial cells through pore formation in cell membrane. Because of their different mode of action compared to antibiotics, AMPs can be effectively used to combat drug resistant bacteria in human health. AMPs can also be used to replace antibiotics in animal feed and immobilized on food packaging films. We developed a methodology based on mechanistic evaluation of peptide-lipid bilayer interaction to identify AMPs from soy protein. Production of AMPs from soy protein is an attractive, cost-saving alternative for commercial consideration, because soy protein is an abundant and common protein resource. This methodology is also applicable for …
A New Transduction Mechanism For Detecting Biological Radiation Damage Using Metabolic Response Of Yeast As A Surrogate Marker, Chang Keun Yoon
A New Transduction Mechanism For Detecting Biological Radiation Damage Using Metabolic Response Of Yeast As A Surrogate Marker, Chang Keun Yoon
Open Access Dissertations
Radiation was a serendipitous discovery in the late 19th century and since then has been an effective tool utilized in many different fields such as energy, weaponry, medical diagnosis/treatment, food sterilization, and archaeological. As its demand increased in multiple areas, it became necessary to control it more precisely and cautiously, and so began the accelerated development of radiation detectors. Such radiation sensors (or dosimeters) have existed since the beginning of the 20th century in various forms. Most radiation dosimeters in use today are targeted for healthcare and industrial workers who work around high levels of radiation (e.g., hospital personnel and …
Modulation Of Bcr Signaling By The Induced Dimerization Of Receptor- Associated Syk, Mark L. Westbroek
Modulation Of Bcr Signaling By The Induced Dimerization Of Receptor- Associated Syk, Mark L. Westbroek
Open Access Dissertations
Clustering of the B cell antigen receptor (BCR) by polyvalent antigens is transmitted through the SYK tyrosine kinase to the activation of multiple intracellular pathways that determine the physiological consequences of receptor engagement. To explore factors that modulate the quantity and quality of signals sent by the crosslinked BCR, I developed a novel chemical mediator of dimerization to induce clustering of receptor-associated SYK. To accomplish this, I fused SYK with E. coli dihydrofolate reductase (eDHFR), which binds the small molecule trimethoprim (TMP) with high affinity and selectivity, and synthesized a dimer of TMP with a flexible linker. The binding of …