Biochemistry, Biophysics, and Structural Biology Commons^™

A New Multivariate Optical Computing Microelement And Miniature Sensor For Spectroscopic Chemical Sensing In Harsh Environments: Design, Fabrication, And Testing, Christopher M. Jones, Bin Dai, Jimmy Price, Jian Li, Megan Pearl, Bill Soltmann, Michael L. Myrick

Faculty Publications

Multivariate optical computing (MOC) is a compressed sensing technique with the ability to provide accurate spectroscopic compositional analysis in a variety of different applications to multiple industries. Indeed, recent developments have demonstrated the successful deployment of MOC sensors in downhole/well-logging environments to interrogate the composition of hydrocarbon and other chemical constituents in oil and gas reservoirs. However, new challenges have necessitated sensors that operate at high temperatures and pressures (up to 230 °C and 138 MPa) as well as even smaller areas that require the miniaturization of their physical footprint. To this end, this paper details the design, fabrication, and …

Exposure Characterization Of Haloacetic Acids In Humans For Exposure And Risk Assessment Applications: An Exploratory Study, Shahid Parvez, Jeffrey L. Ashby, Susana Y. Kimura, Susan D. Richardson

Faculty Publications

Disinfected water is the major source of haloacetic acids (HAAs) in humans, but their inter- and intra-individual variability for exposure and risk assessment applications is under-researched. Thus, we measured HAAs in cross-sectional and longitudinal urine and water specimens from 17 individuals. Five regulated HAAs—mono-, di-, and trichloroacetic acid (MCAA, DCAA, and TCAA) and mono- and dibromoacetic acid (MBAA and DBAA)—and one unregulated HAA—bromochloroacetic acid (BCAA)—were measured. Urinary DCAA, MBAA, DBAA, and BCAA levels were always below the limits of detection (LOD). Measured levels and interindividual variability of urinary MCAA were higher than urinary TCAA. Longitudinal urinary specimens showed MCAA levels …

Solvation Thermodynamic Mapping In Computer Aided Drug Design, Steven Ramsey

Dissertations, Theses, and Capstone Projects

The displacement of water from surfaces upon biomolecular recognition and association makes a significant contribution to the free energy changes of these processes. We therefore posit that accurate characterization of local structural and thermodynamic molecular water properties can improve computational model accuracy and predictivity of recognition and association processes. In this thesis, we discuss Solvation Thermodynamic Mapping (STM) methods that we have developed using inhomogeneous fluid solvation theory (IST) to better characterize active site water structural and thermodynamic properties on protein surfaces and the open source tools that we have developed, GIST-CPPTRAJ and SSTMap, which implement these methods which we …

Pretargeted Radioimmunotherapy Utilizing The Inverse Electron Demand Diels-Alder Reaction, Rosemery Membreno

Dissertations, Theses, and Capstone Projects

Radioimmunotherapy capitalizes on the specificity and affinity of antibodies for their antigens to localize radioactivity at the tumor site. One limitation in using antibodies is their long circulation time, which can take days to weeks to fully clear from blood circulation. When a radioisotope is directly conjugated to this immunoglobulin vector, the red marrow and other healthy organs are receiving a constant radiation dose while it is in blood circulation. This not only harms healthy organs, but limits the dose of radioactivity that can be administered thus prolonging treatment. A promising alternative to limit the radiation dose to non-tumor tissue …

Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang

Dissertations, Theses, and Capstone Projects

Interactions between proteins play a key role in nearly all cellular process, and therefore, disruption of such interactions may lead to many different types of cellular dysfunctions. Hence, pathologic protein-protein interactions (PPIs) constitute highly attractive drug targets and hold great potential for developing novel therapeutic agents for the treatment of incurable human diseases. Unfortunately, the identification of PPI inhibitors is an extremely challenging task, since traditionally used small molecule ligands are mostly unable to cover and anchor on the extensive flat surfaces that define those binary protein complexes. In contrast, large biomolecules such as proteins or peptides are ideal fits …

Analysis Of Oxygen-18 Labeled Phosphate To Study Positional Isotope Experiments Using Lc-Qtof-Ms, Sujatha Chilakala, Iteen Cheng, Ireen Lee, Yan Xu

Chemistry Faculty Publications

A method is proposed in this paper for the determination of oxygen-18 labeled phosphate so that positional isotope experiments using sensitive and rapid liquid chromatography–QTOF–mass spectrometry (LC-QTOF-MS) experiments can be carried out. The positional isotope exchange technique is a useful tool in understanding the mechanisms and kinetics of many enzyme-catalyzed reactions. Detection of the positions and concentration of these exchanged isotopes is the key. Gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance imaging are commonly used analytical techniques for measurement of ¹⁸O/¹⁶O, ³¹P and ¹⁵N isotope enrichment. Since these techniques either require a time-consuming derivatization …

Catalytic Mechanism For The Conversion Of Salicylate Into Catechol By The Flavin-Dependent Monooxygenase Salicylate Hydroxylase, Débora M. A. Costa, Stefanya V. Gómez, Simara S. De Araújo, Mozart S. Pereira, Rosemeire B. Alves, Denize C. Favaro, Alvan C. Hengge, Ronaldo A. P. Nagem, Tiago A. S. Brandão

Chemistry and Biochemistry Faculty Publications

Salicylate hydroxylase (NahG) is a flavin-dependent monooxygenase that catalyzes the decarboxylative hydroxylation of salicylate into catechol in the naphthalene degradation pathway in Pseudomonas putida G7. We explored the mechanism of action of this enzyme in detail using a combination of structural and biophysical methods. NahG shares many structural and mechanistic features with other versatile flavin-dependent monooxygenases, with potential biocatalytic applications. The crystal structure at 2.0 Å resolution for the apo form of NahG adds a new snapshot preceding the FAD binding in flavin-dependent monooxygenases. The k_cat/K_m for the salicylate reaction catalyzed by the holo form is …

Speciated And Total Emission Factors Of Particulate Organics From Burning Western Us Wildland Fuels And Their Dependence On Combustion Efficiency, Coty N. Jen, Lindsay E. Hatch, Vanessa Selimovic, Robert J. Yokelson, Robert Weber, Arantza E. Fernandez, Nathan M. Kreisberg, Kelley C. Barsanti, Allen H. Goldstein

Chemistry and Biochemistry Faculty Publications

Western US wildlands experience frequent and large-scale wildfires which are predicted to increase in the future. As a result, wildfire smoke emissions are expected to play an increasing role in atmospheric chemistry while negatively impacting regional air quality and human health. Understanding the impacts of smoke on the environment is informed by identifying and quantifying the chemical compounds that are emitted during wildfires and by providing empirical relationships that describe how the amount and composition of the emissions change based upon different fire conditions and fuels. This study examined particulate organic compounds emitted from burning common western US wildland fuels …

Chemistry & Biochemistry Guest Lecture Series, Desmond Murray

Andrews Agenda: Campus News

No abstract provided.

Dual Geometry Schemes In Tetrel Bonds: Complexes Between Tf4(T = Si, Ge, Sn) And Pyridine Derivatives, Wiktor Zierkiewicz, Mariusz Michalczyk, Rafał Wysokiński, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

When an N-base approaches the tetrel atom of TF4(T = Si, Ge, Sn) the latter moleculedeforms from a tetrahedral structure in the monomer to a trigonal bipyramid. The base can situateitself at either an axial or equatorial position, leading to two different equilibrium geometries.The interaction energies are considerably larger for the equatorial structures, up around 50 kcal/mol,which also have a shorter R(T··N) separation. On the other hand, the energy needed to deform thetetrahedral monomer into the equatorial structure is much higher than the equivalent deformationenergy in the axial dimer. When these two opposite trends are combined, it is the axial …

Analyzing Neuronal Dendritic Trees With Convolutional Neural Networks, Olivier Trottier, Jonathon Howard

Yale Day of Data

In the biological sciences, image analysis software are used to detect, segment or classify a variety of features encountered in living matter. However, the algorithms that accomplish these tasks are often designed for a specific dataset, making them hardly portable to accomplish the same tasks on images of different biological structures. Recently, convolutional neural networks have been used to perform complex image analysis on a multitude of datasets. While applications of these networks abound in the technology industry and computer science, use cases are not as common in the academic sciences. Motivated by the generalizability of neural networks, we aim …

Development Of Ultrafast Broadband Electronic Sum Frequency Generation For Charge Dynamics At Surfaces And Interfaces, Gang-Hua Deng, Yuqin Qian, Yi Rao

Chemistry and Biochemistry Faculty Publications

Understandings of population and relaxation of charges at surfaces and interfaces are essential to improve charge collection efficiency for energy conversion, catalysis, and photosynthesis. Existing time-resolved surface and interface tools are limited to either under ultrahigh vacuum or in a narrow wavelength region with the loss of spectral information. There lacks an efficient time-resolved surface/interface-specific electronic spectroscopy under ambient conditions for the ultra fast surface/interface dynamics. Here we developed a novel technique for surface/interface-specific broadband electronic sum frequency generation (ESFG). The broadband ESFG was based on a stable two-stage BiB₃O₆ crystal-based optical parametric amplifier, which generates a …

Fabrication Of Miniaturized Paper-Based Microfluidic Devices (Micropads), E. Brandon Strong, Spencer A. Schultz, Andres Martinez, Nathaniel W. Martinez

Chemistry and Biochemistry

Microfluidic paper-based analytical devices (microPADs) are emerging as cost-effective and portable platforms for point-of-care assays. A fundamental limitation of microPAD fabrication is the imprecise nature of most methods for patterning paper. The present work demonstrates that paper patterned via wax printing can be miniaturized by treating it with periodate to produce higher-resolution, high-fidelity microPADs. The optimal miniaturization parameters were determined by immersing microPADs in various concentrations of aqueous sodium periodate (NaIO₄) for varying lengths of time. This treatment miniaturized microPADs by up to 80% in surface area, depending on the concentration of periodate and length of the reaction …

Differential Binding Of Tetrel-Bonding Bipodal Receptors To Monatomic And Polyatomic Anions, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Previous work has demonstrated that a bidentate receptor containing a pair of Sn atoms can engage in very strong interactions with halide ions via tetrel bonds. The question that is addressed here concerns the possibility that a receptor of this type might be designed that would preferentially bind a polyatomic over a monatomic anion since the former might better span the distance between the two Sn atoms. The binding of Cl⁻ was thus compared to that of HCOO⁻, HSO₄⁻, and H₂PO₄⁻ with a wide variety of bidentate receptors. A pair …

Identifying C-Mannosylatedproteins In Raw264.7 Cells Via In Vitro Hsc70 Co-Immunoprecipitation Strategies, Nicholas Ryan Kegley

Theses, Dissertations and Capstones

C-mannosylation is a specific type of glycosylation in which α-mannose is covalently bound to the C2 atom of a tryptophan via a carbon-carbon bond. Presently, it is known to occur on proteins that contain the W-x-x-W-x-x-W/C motif found within the Thrombospondin Type-1 Repeat (TSR), with ‘x’ denoting any amino acid. C-mannosylation has been implicated in a number of cellular functions, including protein secretion and type I cytokine receptor function. Previous research has shown that exogenous C-mannosylated peptides derived from TSR-containing proteins upregulate the production of the pro-inflammatory cytokine Tumor Necrosis Factor alpha (TNF-α) in RAW264.7 macrophage cells. This upregulation is …

Characterizing The Effects Of Environmental Stressors On The Photosynthetic Capacity Of Chlorella Vulgaris, Amanda Louise Smythers

Theses, Dissertations and Capstones

Chlorella vulgaris is a unicellular green algae grown throughout the world. Due to its multiple trophic modes as well as its ability to maintain high rates of growth under adverse conditions, it has been of global interest for use in ecological contamination studies, biofuel feedstock optimization, and studies of photosynthetic electron transfer. Using a wide-range of methods for physiological and photosynthetic characterization, the studies within seek to further extend the usefulness of C. vulgaris in a variety of environmentally important studies. Once the protocols were optimized specifically for this alga, they could be applied in both ecologically relevant and biodiesel …

Isolation And Identification Of Hsc70 Conjugates In Raw264.7 Murine Macrophage-Like Cells, Michael Arland Parsons

Theses, Dissertations and Capstones

IL12R- β2 is a Type I cytokine receptor and contains the WXXW (WSNWS) sequence that often predicates the post-translational addition of mannose to a tryptophan residue via a carbon-carbon bond. This study will stimulate expression of IL12R- β2 in RAW 264.7 Macrophage-Like Cells by shutting down the extracellular signal kinase (ERK) pathway and introducing inflammatory agents lipopolysaccharide and CpG DNA in order to collect a concentrated sample of IL12R- β2. These samples will be analyzed for the presence of C-mannosyltryptophan residue

Development Of A Hek293 Cell Line To Show Inhibition Of Tau Aggregation, Justin Ray Shady

Electronic Theses and Dissertations

Intracellular deposition of aggregated tau is the hallmark of several different tauopathies, the most widespread of these being Alzheimer's disease. Tau is a highly soluble, intrinsically disordered, microtubule associated protein. Tau's native function is to stabilize microtubule formation in the axons of neurons. Post translational modification such as hyperphosphorylation as well as several familial mutations allow tau to nucleate and form fibrils. These fibrils can recruit healthy monomers onto their ends in a fashion described as template-assisted growth. Tau has 6 isoforms that vary by the inclusion or exclusion of two N-terminal repeats and the inclusion or exclusion of the …

Urban Aerobiological Risk Mapping Of Ornamental Trees Using A New Index Based On Lidar And Kriging: A Case Study Of Plane Trees, Raúl Pecero-Casimiro, Santiago Fernández-Rodríguez, Rafael Tormo-Molina, Alejandro Monroy-Colín, Inmaculada Silva-Palacios, Juan Pedro Cortés-Pérez, Ángela Gonzalo-Garijo, J. M. Maya-Manzano

Articles

Ornamental trees bring benefits for human health, including reducing urban pollution. However, some species, such as plane trees (Platanus sp.), produce allergenic pollen. Consequently, urban maps are a valuable tool for allergic patients and allergists, but they often fail to include variables that contribute to the “building downwash effect”, such as the width and shape of streets and the height of buildings. Other factors that directly influence pollen dispersion (slopes and other geographical features) also have not traditionally been discussed. The LiDAR (Laser Imaging Detection and Ranging) technique enables one to consider these variables with high accuracy. This work proposes …

Synthesis Of Trisubstituted Indolizines From 2-Propargyloxypyridines, Colin T. Hartgerink, Jaimie E. Van De Burg, Carolyn E. Anderson

Summer Research

• Indolizines are a versatile heterocyclic core that occurs frequently in pharmaceutical leads for a variety of indications, including: anti-bacterial1 and anti-tumor agents,2 and targets for the treatment of Alzheimer’s disease,3 asthma,4 erectile dysfunction,5 and inflammation related to respiratory or cardiovascular disease.
• While evaluating the scope of a Au(I)-catalyzed rearrangement of 2- propargyloxypyridine 1, 7 substituted indolizine 4 was discovered as an unexpected by-product (Scheme 1). The structure of indolizine 4 was confirmed by NMR and Xray analysis. Investigations revealed that acetophenone, originally present as an impurity in the reaction, is a key reagent. The use of acetophenone as the solvent, …

Split Probe Detection Of The Influenza A Virus For Improved Diagnostics In A Point Of Care System, Tamar Yishay

Honors Undergraduate Theses

A group of Influenza viruses, RNA containing viruses of the Orthomyxoviridae family, consists of Influenza virus types A-D and has been known to cause the Flu, a respiratory illness associated with numerous detrimental symptoms that can lead to death. Influenza A virus (IAV) is constantly changing and is capable of causing pandemics. Currently used diagnostic methods include virus culturing, immunoassays including rapid influenza detection tests (RIDTs), and molecular assays including those based on RT-PCR. Most of the methods can be only performed in the certified diagnostic laboratories equipped with sophisticated instrumentation and/or special biosafety facilities. The results using these methods …

Urinalysis Screening Of Drugs In Adulterated Samples Via Direct Analysis In Real Time -- High Resolution/ Mass Spectrometry (Dart-Hr/Ms), Bianca E. Olivieri

Honors Undergraduate Theses

Current screening methods for drug analysis with urine samples includes examination of the sample with an immunoassay. These methods are used to determine the concentration of drug metabolites contained within the sample prior to further confirmatory testing. Drug testing plays a crucial role in maintaining safe workplace environments and safety of individuals. However, a positive result can lead to heavy consequences for the employee including suspension or removal from the workplace. Therefore, a majority of individuals add commonly known products into the sample to evade detection by developing a false negative result. Although specimen integrity examinations are performed to identify …

Seven Coordinate Molybdenum And Tungsten Complexes Containing Tpm And Tpm Derivatives And The Impact Of Ligand Substitution On Nmr Chemical Shifts, Cole Seager

Undergraduate Honors Thesis Collection

A series of known and new seven coordinate molybdenum and tungsten complexes of tris(pyrazolyl)methane (Tpm) and substituted Tpm, [TpmM(CO)3X]+, have been synthesized. Depending on the identity of X, (bromo, iodo, hydrido) and the substitution of the Tpm ligand, substantial chemical shift differences are observed for the hydrogen on the central carbon of the Tpm ligand. Factors impacting the chemical shift of the hydrogen on the central carbon of the Tpm ligand, such as the electron donating ability of the Tpm ligand and the electronegativity of the additional ligand on the metal, will be discussed.

Wetland Biogeochemical Responses To Predicted Climate Change Scenarios, Angela R. Shaffer

College of Graduate Studies: Theses & Dissertations

Wetlands are one of the world's largest known carbon sinks while comprising only a small amount of the Earth's surface. However, the amount of carbon sequestered by wetlands is shrinking as droughts and human disturbance increases. Carbon in wetlands is stored through the contrast of decomposition and sedimentation of organic matter and absorption of CO₂ from the atmosphere by soil microbes. Understanding how changing hydrological regimes and increased wildfires will affect wetland soil and microbial processes is important in the face of predicted climate change for future wetland conservation practices. Specifically, I seek to understand the response of southeastern …

Dinitrogen Fixation Across Physico-Chemical Gradients Of The Eastern Tropical North Pacific Oxygen Deficient Zone, C. R. Selden, M. R. Mulholland, P.W. Bernhardt, B. Widner, A. Macías-Tapia, Q. Ji, A. Jayakumar

OES Faculty Publications

The Eastern Tropical North Pacific Ocean hosts one of the world's largest oceanic oxygen deficient zones (ODZs). Hot spots for reactive nitrogen (N_r) removal processes, ODZs generate conditions proposed to promote N_r inputs via dinitrogen (N₂) fixation. In this study, we quantified N₂ fixation rates by ¹⁵N tracer bioassay across oxygen, nutrient, and light gradients within and adjacent to the ODZ. Within subeuphotic oxygen‐deplete waters, N₂ fixation was largely undetectable; however, addition of dissolved organic carbon stimulated N₂ fixation in suboxic (μmol/kg O₂) waters, suggesting that diazotroph communities are …

Ebullition Of Oxygen From Seagrasses Under Supersaturated Conditions, Matthew H. Long, Kevin Sutherland, Scott D. Wankel, David J. Burdige, Richard C. Zimmerman

OES Faculty Publications

Gas ebullition from aquatic systems to the atmosphere represents a potentially important fraction of primary production that goes unquantified by measurements of dissolved gas concentrations. Although gas ebullition from photosynthetic surfaces has often been observed, it is rarely quantified. The resulting underestimation of photosynthetic activity may significantly bias the determination of ecosystem trophic status and estimated rates of biogeochemical cycling from in situ measures of dissolved oxygen. Here, we quantified gas ebullition rates in Zostera marina meadows in Virginia, U.S.A. using simple funnel traps and analyzed the oxygen concentration and isotopic composition of the captured gas. Maximum hourly rates of …

Biometal-Induced Structural Consequences Of Α-Synuclein – The Parkinson’S Disease Protein, Dinendra L. Abeyawardhane

Theses and Dissertations

The pre-synaptic protein α-Synuclein (αS) is often linked to the pathology of Parkinson’s disease (PD), an age-related neurodegenerative disorder. Lewy bodies, the cytopathological hallmarks of PD, are found to be rich in aggregates of misfolded αS protein. Metal dyshomeostasis has also been linked to PD due to the accumulation of iron in the substantia nigra pars compacta, and diminished copper levels reported in this same region. Metal dyshomeostasis in the brain coupled with oxidative stress can enhance the aggregation of αS. Recently, it was confirmed that mammalian αS is universally acetylated at the N-terminus, a common post-translational modification in …

Case Studies Of Potential Reference Materials In Cultural Heritage Science, Heidi Kastenholz

Undergraduate Honors Thesis Collection

The study of cultural heritage objects requires reference materials for comparison in order to determine the identity of chemical compounds in historically/culturally significant artifacts. The reference materials available today can be inaccurately labeled, can contain inauthentic compounds, or can simply be formed differently than what the labeled material should be. Utilizing the laboratory at the Indianapolis Museum of Art at Newfields, three case studies were conducted over three different potential reference materials in order to properly identify each of the three materials being focused on here. Based on the analysis, the labels for these materials often do not match the …

Measuring Trace Element Concentrations In Artiodactyl Cannonbones Using Portable X-Ray Fluorescence, Joshua L. Henderson

All Master's Theses

Artiodactyl bones are the most common faunal remains found in Washington prehistoric archaeology sites, but they are often too fragmented to accurately identify a family, genus, or species. Traditional faunal analysis can only organize unidentifiable bone fragments into size class, and chemical methods often require the destruction of bone samples. In this thesis research, I tested a new, nondestructive faunal analysis technique using portable X-ray fluorescence (pXRF) to measure trace element concentrations in comparative collection and archaeological bone samples. Using cannonbones from five different artiodactyl species, I collected trace element data from 50 comparative collection specimens and 18 archaeological specimens …

Assessment Of Quantity And Quality Of Microplastics In The Sediments, Waters, Oysters, And Selected Fish Species In Key Sites Along The Bombong Estuary And The Coastal Waters Of Ticalan In San Juan, Batangas, Emilyn Q. Espiritu, Sophia Angeli Sn Dayrit, Annabel Soledad O. Coronel, Natasha Sophia C. Paz, Pilar Isabel L. Ronquillo, Virgil Christian G. Castillo, Erwin P. Enriquez

Chemistry Faculty Publications

Microplastics (or MPs; < 5 mm in size) pollution is largely unstudied in the Philippines. From an environmental sustainability standpoint, it is important to understand the characteristics, abundance, and environmental fate of plastic debris of various sizes, and these include microplastics that are not more easily and readily detected. In this study, we assessed the extent of microplastics contamination in the sediments, waters, oysters, and selected fishes found in the rivers and coastal areas of Ticalan, Batangas, which were identified from water quality parameters as Class C and CS, respectively. The microplastics were extracted from these samples by chemical digestion of the matrix, series of filtration, and separation by flotation through a density gradient to finally isolate the microplastics which were not dissolved by chemical digestion. The isolated samples were imaged by optical microscopy and characterized based on their descriptive attributes. The results showed the presence of microplastics in all the samples tested, which were found mostly in the form of filaments, fragments, films, and pellets – with most showing weathered, degraded, or angular and irregular surfaces. Identification was done through spectral matching of the Fourier transform infrared spectra of isolated fragments with that of known plastics, although identification in some cases is made uncertain by possibility of degradation of the plastics in the environment. The majority of the isolates showed signature absorption bands of the C-H stretching vibrations of polyethylene-based plastics.