cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Chinese University Students’ Perspectives on Help-Seeking and Mental Health Counseling
Creators: name: Ning, Xuan
name: Wong, Pui-Hing
name: Huang, Silang
name: Fu, Yina
name: Gong, Xiaojie
name: Zhang, Lizeng
name: Hilario, Carla T.
name: Fung, Po-Lun
name: Yu, Miao
name: Poon, Kwong-Lai
name: Cheng, Shengli
name: Gao, Jianguo
name: Jia, Cun-Xian
Publisher: name: Multidisciplinary Digital Publishing Institute
Year: 2023

description: Psychological distress and mental illness have become increasingly pervasive among Chinese university students. However, many university students who need mental health treatment or psychological support do not actively seek help from professional counselors or service providers, which could lead to poor mental health outcomes. To promote help-seeking, we undertook a qualitative study to understand Chinese university students’ perspectives on help-seeking and mental health counseling. We conducted 13 focus group interviews with students in six universities in Jinan, China, and altogether 91 (62%) female students, and 56 (38%) male students participated in the study. Our results indicate that students’ misconception and distrust of on-campus counseling, stigma of mental illness, low mental health literacy, and hard-to-access mental health services are the major barriers that impede students help-seeking behaviors. Internal struggles and systematic and organizational barriers are identified to shed light on future work to promote mental health literacy among Chinese university students.
Iron-Catalyzed Amino-Oxygenation and Aminofluorination of Olefins
Creators: name: Sears, Jeffrey
Publisher: name: Georgia State University
Year: 2015

description: The first chapter of the thesis describes an iron(II)-catalyzed intermolecular amino-oxygenation of alkenes. This amino-oxygenation method is found to be compatible with a broad range of synthetically valuable alkenes and affords the corresponding 1,2-amino alcohols with excellent regio- and diastereoselectivity. Additionally, practical synthetic procedures for the amino-oxygenation of styrene, a fully functionalized glycal, and indene are described. The second chapter of the thesis describes a regioselective and diastereoselective iron(II)-catalyzed intermolecular aminofluorination of alkenes using nucleophilic fluorinating reagents. This method affords new vicinal amino fluorides that were previously difficult to prepare. In both the amino-oxygenation and aminofluorination reactions, bench-stable hydroxylamine derivatives functioned as both the oxidant and amination reagents. Preliminary mechanistic studies suggested that an iron-nitrenoid is a possible reactive intermediate on both reaction pathways. These new difunctionalization strategies represent efficient alternatives to current amino-oxygenation and aminofluorination methods.
Observation Of Spectral Changes To Trp-214 Residue In Human Serum Albumin Upon Binding With Mangiferin And Near Infrared Dyes
Creators: name: Novak, Jennifer
Publisher: name: Georgia State University
Year: 2015

description: A novel approach of using near infrared region (NIR) dyes is applied to elucidate the binding interaction between human serum albumin (HSA) and mangiferin (MGF). HSA is a blood carrier protein used for drug delivery, while mangiferin is a natural polyphenol found in mangoes that possesses numerous beneficial health properties. The NIR dyes are used as a probe to investigate MGF binding interaction with HSA via monitoring fluorescence of Trp-214 residue. Molecular modeling is used for docking and semi-empirical analysis. The investigation of the binding interaction between Trp-214 and MGF is significant, for it may offer broader pharmacological insight and applications for the polyphenol. Mangiferin in proposed to bind with a 2:1 stoichiometric ratio with HSA to the Trp-214 residue in subdomain IIA and another possible binding site to be determined in future studies. Spectral changes suggest a stabilized protein conformation upon mangiferin binding with the addition of NIR dye E-06 and MHI-06.
An Investigation of Autoxidation and DNA Thermal Cleavage by Polymethine Cyanine Dyes and Analogs in Aqueous Solutions
Creators: name: Li, Ziyi
Publisher: name: Georgia State University
Year: 2015

description: Studies on a series of polymethine cyanine dyes and analogs (1-24) show that certain near-infrared cyanines are capable of damaging DNA in the absence of light and external reducing agents. Experimental results imply that in this DNA thermal cleavage, the cyanine reduces Cu(II) to Cu(I) which reacts with O2 to generate the reactive oxygen species (ROS) O2—- and —OH. The formation of these ROS is also thought to be responsible for the irreversible bleaching of the dyes in aqueous solutions. A correlation between structural features and DNA thermal cleavage activity as well as dye bleaching is suggested. Long polymethine chains appear to confer instability to cyanines in aqueous solutions and further contribute to undesired thermal DNA cleavage. These drawbacks can be overcome by introducing an electron-withdrawing group to the polymethine bridge of the cyanine dye.
Cyanine Dyes Targeting G-quadruplex DNA: Significance in Sequence and Conformation Selectivity
Creators: name: Huynh, Hang
Publisher: name: Georgia State University
Year: 2015

description: Small molecules interacting with DNA is an emerging theme in scientific research due to its specificity and minimal side-effect. Moreover, a large amount of research has been done on finding compounds that can stabilize G-quadruplex DNA, a non-canonical secondary DNA structure, to inhibit cancerous cell proliferation.  G-quadruplex DNA is found in the guanine-rich region of the chromosome that has an important role in protecting chromosomes from unwinding, participate in gene expression, contribute in the control replication of cells and more.  In this research, rationally designed, synthetic cyanine dye derivatives, which were tested under physiologically relevant conditions, were found to selectively bind to G-quadruplex over duplex DNA and are favored to one structure over another.  The interactions were observed using UV-Vis thermal melting, fluorescence titration, circular dichroism titration, and surface plasmon resonance analysis.  For fluorescence and selectivity properties, cyanine dyes, therefore, have the potential to become the detections and/or therapeutic drugs to target cancers and many other fatal diseases.
A Novel Method for Bioanalysis of Dye Covalently Encapsulated in Silica Nanoparticles and Characterization of NIR Dyes for Future Approach
Creators: name: Emer, Kyle
Publisher: name: Georgia State University
Year: 2015

description: Silica nanoparticles with dyes-encapsulated has been characterized by TEM and DLS, which were employed in biological applications with A. castellanii. Amoebae have pathogenic properties that can cause sight-threatening keratitis and granulomatous encephalitis. Phagocytosis of dye-covalently encapsulated in silica nanoparticles has shown promise in vitro and could be employed in vivo for detection. Time-dependent analysis of the SiNPs and A. castellanii displays micrographs of cellular components in the process of endocytosis and exocytosis. Alive and potentially deceased investigation of A. castellanii with SiNP uptake was evaluated to indicate detection with altered variables. Spectroscopic analyses were conducted on NIR dyes that will be essential for nanoparticle synthesis for in vivo and in vitro imaging.
Spectroscopic Investigation into Minor Groove Binders Designed to Selectively Target DNA Sequences
Creators: name: Walton, Joseph
Publisher: name: Georgia State University
Year: 2015

description: Recently, there has been increasing focus toward the development of small molecules designed to target a specific sequences of double stranded DNA for therapeutic purposes1. Minor groove binding compounds have been shown to be capable of selectivity target GC sites in AT tract DNA2. In this research, binding selectivity was investigated using absorption, fluorescence and circular dichroic properties of selected DB minor groove binders in the presence of two unique DNA sequences. Further insight was gained by comparing the electrostatic potential maps and optimized structures of the compounds of interest. Using the results presented, potential selective minor groove binders can be selected for further investigation and kinetic studies.
Mechanistic Investigation of the Flavin-Neighboring Residues S45, A46 and I335 in Pseudomonas aeruginosa D-arginine Dehydrogenase
Creators: name: Ouedraogo, Daniel
Publisher: name: Georgia State University
Year: 2015

description: Pseudomonas aeruginosa ?-arginine dehydrogenase (PaDADH) is a flavin-dependent enzyme. The enzyme catalyzes the oxidative deamination of a broad range of ?-amino acids to their corresponding imino-acids, which are non-enzymatically hydrolyzed to …-keto-acids and ammonia. A46, S45 and I335 residues are located in flexible loops, which form a flask-like substrate-binding pocket. In this study, I335, A46, and S45 were mutated to histidine, glycine, and alanine, respectively and individually, through site-directed mutagenesis, to investigate their role in binding and catalysis in PaDADH. The results showed that A46 and S45 residues participate in the optimal orientation of the substrate …-amino group and I335 modulate the active site flexibility.
Protein Modification of Designed MRI Contrast Agents
Creators: name: Purser, Corrie
Publisher: name: Georgia State University
Year: 2015

description: Protein based contrast agents (ProCAs) developed by the Yang lab exhibit unique capabilities in enabling magnetic resonance imaging (MRI) with significantly improved sensitivity and targeting capabilities by utilizing biomarkers which can target various carcinomas in animals. Further clinical in vivo human applications require modifications of these designed contrast agents to further improve organ and tissue biodistribution, biomarker and cell targeting capabilities, and reduction of immunogenicity. The aim of this thesis is to develop a novel protein modification on ProCA by glycosylation to improve liver distribution by targeting liver receptor, asialoglycoprotein receptor (ASGPR). Rat and humanized first generation and humanized third generation ProCA were expressed and purified using either glutathione s-transferase (GST) tagged or taggless methods. Rat ProCA1, rProCA1, was then used to optimize glycan modification with glycosylation achieved at the highest level using a 100:1 molar ratio and three lysine residues. Similar to non-modified rProCA1 and PEGylated rProCA1, metal binding affinity of gadolinium for glycan modified rProCA1, Glyco-rProCA1, was found to be 9.49 x 10-12 M, and relaxivity was found to be greater than clinically available contrast agents with 34.08 and 42.67 mM-1s-1 for r1 and r2 respectively. Glycosylation of rProCA1 has significantly increased human serum stability, and we have achieved significant liver MRI enhancement via tail vein injection due to high ASGPR expression in the liver altering biodistribution of glycan modified ProCA, and we have also imaged uptake in the secretory glands. These biodistribution changes were noted by immunohistochemistry (IHC) staining which was found to stain liver sinusoid with spaces in between. The distribution to the liver was further confirmed via inductively coupled plasma optical emission spectrometry (ICP-OES) which shows Glyco-rProCA1 has significant uptake of gadolinium in the liver tissue.  This study represents the first achievement of in vivo liver imaging by glycosylation using a lactose targeting moiety covalently bonded to protein contrast agents for MRI showing promise for future more specific targeting or whole body imaging capabilities.
Investigation Of A Novel Mammalian Thiol Dioxygenase Structure: Human Cysteamine Dioxygenase
Creators: name: Xiong, Tseng
Publisher: name: Georgia State University
Year: 2016

description: In 2007, a gene homolog of CDO encoded by the gene Gm237 in the DUF164 family was identified as cysteamine dioxygenase (ADO). ADO is one of the only known thiol dioxygenases found in mammals. Both ADO and its partner cysteine dioxygenase (CDO) are non-heme iron dependent enzymes that play a crucial role in the biosynthesis of taruine/hypotaurine by insertion of a dioxygen molecule. However, ADO has been overshadowed by CDO as heavy research focus on CDO over the past decade has led to the elucidation of its structure and possible mechanistic properties. In an effort to further understand ADO?s mechanism and regulating role in vivo, this work will be focused on the mammalian hADO and trying to gain further insight on hADO?s structural features via crystallography work. Investigation of the crystallization parameters for hADO has elucidated several potential conditions. Detailed work on these crystallization parameters will be presented.
Modifications To The Benzophenoxazine Architecture: Synthesis And Characterization
Creators: name: Martinez, Vincent
Publisher: name: Georgia State University
Year: 2016

description: Nile red and Nile blue are intensely colored fluorescent dyes from the benzophenoxazine family. Modification of the donor amine with varying alkyl substituents was achieved with the principle aim being to investigate differences, both optical and physical, between dye scaffolds outfitted with secondary amines versus tertiary amines. These changes to the dyes? architectural framework gave holistic effects to the bulk molecule by modulating hydrophobicity, optical properties, and protein binding constants to human serum albumin.
Study Of The DNA Packaging Protein From A Phage That Replicates Under Extreme Conditions
Creators: name: Lessans, Philip
Publisher: name: Georgia State University
Year: 2016

description: Bacteriophages are viruses that infect bacteria. Phage DNA packaging is one process in the assembly of mature phages that is not well characterized. Elucidating the mechanism of this process would enhance our understanding of the biological significance of the machinery. A previous study suggested that the protein gp74 from bacteriophage HK97 functions as an HNH endonuclease and is required for phage DNA packaging. In this thesis the functionality was assessed for a protein from a phage that replicates under extreme conditions. Our data suggest that the endonuclease activity may not be essential for the role of gp74 in phage DNA packaging.
Spectroscopic and Thermodynamic Characterization of Human 3-Hydroxyanthranilate-3,4-Dioxygenase
Creators: name: Henry, Calmour
Publisher: name: Georgia State University
Year: 2016

description: 3-Hydroxyanthranilate-3,4-dioxygenase (HAO) is a non-heme iron dependent enzyme that catalyzes the oxidative ring opening of 3-hydroxyanthranilate (HAA) which is an intermediate in the kynurenine pathway and its ring opening is the final enzymatic step from tryptophan to quinolinic acid (QUIN). QUIN functions as an N-methyl-D-aspartate (NMDA) receptor agonist and elevated brain levels of QUIN have been observed in neurodegenerative diseases. Reducing QUIN levels is of pharmacological importance. Kinetic and calorimetric studies were performed on human HAO using UV/Vis spectroscopy and isothermal titration calorimetry to understand its stability and behavior using its natural substrate (3-HAA) and neurological inhibitors such as acetylsalicylic acid (aspirin). This study reveals the first analysis of human HAO and facilitates understanding of its binding dynamics and enzymatic activity which will later support discovering suitable pharmacological compounds.
Synthetic Development of Cyanine Dyes and Investigation of Their Interaction with Duplex DNA
Creators: name: Holder, Cory
Publisher: name: Georgia State University
Year: 2016

description: This thesis outlines two projects that examine interactions between DNA and cyanine dyes: 1) Investigation of monomethine cyanine dye through the synthesis and optical characteristics with a goal to synthetically manipulate these systems to develop a fluorescent biological probe. Several asymmetric and one symmetrical monomethine cyanine dyes were synthetically prepared and their optical properties versus structural changes were explored. Representative dyes were selected for spectroscopically investigating DNA binding to enhance existing probe designs. 2) Early stage development of a non-metalated photosensitizer for photodynamic therapy (PDT) by screening experimentally derived cleavage activities of a number of polymethine cyanine dyes with various adjoining heterocycles. Structural characteristics of these dyes which promoted cleavage in the dark were identified and eliminated to allow for more selective photo-induced cleavage to enhance the candidacy of these compounds as photosensitizing agents. All compounds were purified through recrystallization or column chromatography and were characterized via 1H and 13C nuclear magnetic resonance (NMR). Compounds from the first chapter were further characterized using mass spectrometry.
Synthesis and Determination of Optical Properties of Selected Pentamethine Carbocyanine Dyes
Creators: name: Dost, Tyler
Publisher: name: Georgia State University
Year: 2016

description: This thesis begins with a brief review about the role and importance of the small molecules containing fluorine atoms in medicine and imaging. Then, the first part of the thesis will discuss the synthesis, purification and characterization of pentamethine cyanine dyes. The structure identification of the final dyes is done by using 1H NMR, 13C NMR, 19F NMR, and mass spectrometry. The studies performed after full characterization were the determination of optical and physicochemical properties. After these properties were performed, the fluorophores were evaluated to be good candidates for in vivo testing.
Optical Property Enhancement And Characterization Of Fluorescent Protein Based Intracellular Calcium Probes
Creators: name: Goolsby, Demesheka
Publisher: name: Georgia State University
Year: 2016

description: Calcium (Ca2+), a crucial effector for many biological systems, has been associated with diseases such as cardiovascular disease, Alzheimer?s, Parkinson?s, cancer, and osteoporosis. It is important to develop calcium sensors to measure intracellular Ca2+ dynamics at various biological and pathological states. Our lab has engineered such probes by designing a Ca2+ binding site into fluorescent proteins such as Enhanced Green Fluorescent Protein (EGFP) and mCherry. In this thesis, we aim to improve optical properties and metal binding properties of green EGFP-based sensor CatchER and mCherry based red sensors by site-directed mutagenesis and protein engineering, various spectroscopic methods and cell imaging. The green EGFP-based sensor CatchER, with a Ca2+ binding pocket charge of -5, displays the greatest affinity for Ca2+ and has the greatest fluorescence intensity change with Ca2+ when compared to its variants with a less negative binding pocket charge. In addition, we have also designed several SR/ER targeting CatchER variants using Ryanodine receptor and Calnexin transmembrane domains. These constructs were shown to display a strong presence in the SR/ER lumen and further designed for a new luminal orientation. Further, we have shown that the optical properties of two red calcium sensors can be significantly improved by modifying the local environment of the chromophore.
Establishing the Relationship Between Function and Dynamics Within the Gated Mechanism of D-arginine Dehydrogenase
Creators: name: Souffrant, Michael
Publisher: name: Georgia State University
Year: 2016

description: Enzymes are ubiquitous in biological systems. They catalyze chemical reactions and are involved in many biochemical processes. The enzyme of interest is Pseudomonas aeruginosa D-arginine dehydrogenase (PaDADH). This flavin-dependent enzyme is composed of approximately 375 amino acid residues and has a broad substrate specificity with D-amino acids. A water recognition motif, observed in roughly 1200 non-redundant protein data bank (PDB) structures, was revealed to be embedded near the active site of PaDADH. This motif coincides with the conformational changes of the enzyme?s gated mechanism. Molecular dynamics simulations were carried out to study the gated properties and structural characteristics of PaDADH in solution. Single amino acid mutations were undertaken to further understand the dynamics of the gated mechanism of this enzyme. In addition, pKa,shift analyses were evaluated to probe for the basic catalytic amino acid residue that is suggested to trigger the catalytic mechanism of PaDADH.
Synthesis of 2SeU-RNAs and RNA Squares
Creators: name: Chen, Xinghua
Publisher: name: Georgia State University
Year: 2016

description: In this paper, an improved method [1] for the chemical synthesis of 2SeU-RNA was reported using a streamlined strategy employs 2'-O-Thiomopholine-4-carbothioate protecting group. And single step deprotection of the resulting oligoribonucleotide product using 1,2-diamines/toluene under anhydrous conditions would retain the Selenium atom introduced on the 2-possiton of the modified Uracil. The process is doable with most standard heterobase protection and deprotection, it greatly simplifies the synthesis of 2SeU-RNAs and can be applied to other Selenium modified RNAs synthesis. It makes the synthesis of RNA become as simple and efficient as the chemical synthesis of DNA. Furthermore, the design and synthesis of self-assembling 2SeU-RNA square are reported which enable further structure studies and application of unique 2SeU-RNAs.
DNA Photo-Cleavage and Interactions by Quinoline Cyanine Dyes; Towards Improving Photodynamic Cancer Therapy
Creators: name: Fatemipouya, Tayebeh
Publisher: name: Georgia State University
Year: 2016

description: Photodynamic therapy (PDT) is a cancer treatment method in which a photosensitizer, light of a particular wavelength, and also oxygen are used to destroy cancerous cells. Cancer cells absorb the photosensitizing agent which is injected into the body, and it is triggered to cause cell destruction upon absorption of light. This occurs because of the excitation of the photosensitizer produces reactive oxygen species that induce a cascade of cellular and molecular events in the body. Photosensitizing agents that can photo-cleave DNA at long wavelengths are highly demanded in PDT, because the long wavelengths of light can penetrate through tissue deeply compared to visible light. While most of the photosensitizers are activated at wavelengths less than 690 nm, penetration of light continues to increase at increasing wavelengths. In this thesis, photosensitizers that can be activated to oxidize DNA with long wavelengths of light will be discussed. Using quinoline cyanine dyes, here we report the first example of DNA photocleavage at a wavelength of light above 800 nm.
An Investigation of the DNA Interactions of Polyamine Anthracene Conjugates under High Ionic Conditions
Creators: name: Nguyen, Khoa
Publisher: name: Georgia State University
Year: 2016

description: Six polyamine anthracene conjugates (Ants) were studied that take advantage of the polyamine transporter system (PTS) to target specific cancer. The structural features of the Ants involve planar aromatic anthracene that has highly cytotoxicity properties and a polyamine chain similar to natural polyamine, which is taken up by eukaryote cells expressing the PTS actively. Experimental data show that Ants with di-substituted polyamine chains have significantly higher DNA binding affinities than the mono-substituted anthracene conjugates. The high ionic conditions (~150 mM NaCl and 260 mM KCl) in the eukaryote cell nucleus extensively impair the apparent DNA binding of the Ants, but may further reinforce DNA structural stability. Combining the published cytotoxicity of the PTS data with the DNA interaction data reported here, the di-substituted polyamine anthracene conjugates have the highest potential to, after cellular uptake via PTS, bind to DNA.
Exploring HIV Integrase 3'-processing Using Designed DNA Substrates  and Structural Study of HIV DNA Hairpins
Creators: name: Li, Qiushi
Publisher: name: Georgia State University
Year: 2016

description: In the HIV viral integration procedure, 3?-processing of the viral DNA by the integrase enzyme is an essential first step which is followed by the integration of viral DNA into the host genome. In 3?-processing, the integrase cleaves the backbone of the DNA substrate on the 3? end of a conserved CA dinucleotide motif and inserts a helix between the two DNA strands, forcing them apart (Hare, S., 2012). Our study confirms that the presence of a G-amino group is crucial for 3?-processing. Substituting inosine for G in the CA step removes this amino group and results in loss of enzyme activity. Further work showed that the presence of a terminal duplex segment is not required for 3?-processing. Additional substrate modifications are studied in order to evaluate the actual importance of the CA step.
Chemoenzymatic Synthesis of UDP-GlcNAc and UDP-GalNAc Derivatives for Chemoenzymatic Labeling
Creators: name: Zheng, Yuan
Publisher: name: Georgia State University
Year: 2017

description: Glycans are macromolecules that contain several classes. Glycans can play an important role in biological activities. Studying the cell surface glycans can provide a very powerful way to understand the fundamental process. Also it could help to regulate expected cell response. Thus it is very necessary to have a method to detect cell- surface glycans efficiently.
An efficient method for glycan detection is necessary. Metabolic glycan labeling and chemoenzymatic glycan labeling are most commonly used. Chemoenzymatic glycan labeling is a rapid and sensitive method which also has high specificity. This method can be applied in both vitro and vivo. However the availability of unnatural sugar nucleotides functioned by bioorthogonal groups is the main limitation for chemoenzymatic labeling.
In this thesis, UDP-GlcNAc and UDP-GalNAc derivatives were prepared for further chemoenzymatic labeling by using chemoenzymatic synthesis method.
Investigation and Characterization of Novel Pentamethine Cyanine Dyes for Use as Photosensitizers in Photodynamic Therapy
Creators: name: Kiernan, Kaitlyn
Publisher: name: Georgia State University
Year: 2017

description: Cyanine dyes that absorb light in the near infrared to far red region of the electromagnetic spectrum are desirable as photosensitizers for photodynamic cancer therapy. Light of wavelengths in this range is able to deeply penetrate tissue allowing for practical in vivo use of these dyes. A series of three structurally similar pentamethine cyanine dyes that absorb light ~800 nm to ~500 nm was tested to determine the effects of structural influences on the yields of supercoiled DNA photo-converted to nicked or linear forms. Possible mechanisms and optimal parameters for near- quantitative DNA photocleavage with a symmetrical quinoline pentamethine cyanine dye are discussed.
An Introduction to Dynamic Data Governance
Creators: name: Spencer, Sam
Publisher: name: Zenodo
Year: 2025
Subjects: subject: Data Governance
subject: Data Management
subject: Metadata

description: Welcome to Dynamic Data Governance  - a people-first approach where everyone in the organisation plays a role in informing the CDO and governance leaders about data: what they have, where it is, and what it means. It’s about everyday contributions and upskilling the specialists who guide the way. It’s the mindset shift where everyone contributes to governance, and specialists uplift their skills to drive consistent, valuable, and secure data practices across the organization. This webinar introduces the MAST Methodology -  a practical, proven framework to make this shift happen in your organisation.

This webinar told how to register for the MAST Methodology Micro-Certification at IASSIST 2025. This credential will help you lead better governance practices across your teams and enhance data outcomes. 

Sam Spencer is a long-standing member of the IASSIST community, CEO and co-founder of Aristotle Metadata, and leader in government data management and data governance.
Optimized Green Extraction of Polyphenols from Cassia javanica L. Petals for Their Application in Sunflower Oil: Anticancer and Antioxidant Properties
Creators: name: Younis, Mohamed Ibrahim
name: Ren, Xiaofeng
name: Alzubaidi, Azalldeen Kazal
name: Mahmoud, Khaled Fahmy
name: Altemimi, Ammar B.
name: Cacciola, Francesco
name: Raza, Husnain
name: Pratap-Singh, Anubhav
name: Abedelmaksoud, Tarek Gamal
Publisher: name: Multidisciplinary Digital Publishing Institute
Year: 2023

description: The total phenolic content (TPC) from Cassia javanica L. petals were extracted using ethanolic solvent extraction at concentrations ranging from 0 to 90% and an SCF-CO₂ co-solvent at various pressures. Ultrasound-assisted extraction parameters were optimized using response surface methodology (RSM). Antioxidant and anticancer properties of total phenols were assessed. An SCF-CO₂ co-solvent extract was nano-encapsulated and applied to sunflower oil without the addition of an antioxidant. The results indicated that the best treatment for retaining TPC and total flavonoids content (TFC) was SCF-CO₂ co-solvent followed by the ultrasound and ethanolic extraction procedures. Additionally, the best antioxidant activity by β-carotene/linoleic acid and DPPH free radical-scavenging test systems was observed by SCF-CO₂ co-solvent then ultrasound and ethanolic extraction methods. SCF-CO₂ co-solvent recorded the highest inhibition % for PC3 (76.20%) and MCF7 (98.70%) and the lowest IC50 value for PC3 (145 µ/mL) and MCF7 (96 µ/mL). It was discovered that fortifying sunflower oil with SCF-CO₂ co-solvent nanoparticles had a beneficial effect on free fatty acids and peroxide levels. The SCF-CO₂ method was finally found to be superior and could be used in large-scale processing.
Prognostic implications of tumor laterality in renal cell carcinoma
Creators: name: Grassauer, Jacob
name: Chou, Wesley
name: Chakiryan, Nicholas
Publisher: name: Oregon Health and Science University
Year: 2024
Subjects: subject: Carcinoma, Renal Cell
subject: Prognosis
subject: Kaplan-Meier Estimate
subject: Demography
subject: FOS: Sociology
subject: Kidney
subject: Kidney Neoplasms

description: Major anatomical differences between the left and right kidneys may impact the development, detection, and progression of renal cell carcinoma (RCC). There remains debate as to whether laterality has prognostic implications. Some studies suggest that right-sided tumors have better overall outcomes while others propose variations in outcome are likely due to the detection of more indolent disease. Our primary objective was to evaluate tumor characteristics and outcomes related to laterality in RCC.
Insulin Nucleation Using Voltage Clamping and Current Clamping Techniques
Creators: name: Bowen, Michael
Publisher: name: Georgia State University
Year: 2017

description: Crystallization of proteins is the prerequisite to obtaining three-dimensional molecular structures; by X-ray crystallography. The knowledge of protein structures is foundational and could pave ways to the understanding of a protein?s functions. However, obtaining single crystals is challenging and often a bottleneck let alone the need of satisfactory diffraction quality.
 In this thesis, quartz nanopipettes are used to spatially confine the location of nucleation and crystal growth at a nanometer scale. Current and voltage clamping techniques are employed to induce phase transition and subsequent crystal formation via external controls. Throughout the process, we can monitor and control the electrical current/potential that controls mass transport for local concentration adjustment.
Synthesis & Evaluation Of Thiophene Derivatives As CXCR4 Antagonists
Creators: name: Garcia, Francisco
Publisher: name: Georgia State University
Year: 2017

description: There is a lack of good CXCR4 inhibitors that treat cancer cell metastasis and autoimmune diseases without serious drawbacks. AMD3100 and WZ811 are the CXCR4 antagonists that were the initial structural basis for our new potential therapeutics. Molecular modeling and the principles of drug discovery and design were used to plan the synthesis of the compounds presented here. These compounds were synthesized via reductive amination, and then purified via flash column chromatography or preparatory thin layer chromatography. The small molecules were then characterized via melting point, high resolution MS, 13C, and 1H NMR spectroscopy. The Matrigel invasion assay and binding affinity assay were used to screen the potency of the compounds. Compounds that showed high potency in these assays were then subjected to the carrageenan mouse paw edema test. Two lead compounds have emerged as candidates for further testing (2v, and 2a).
DNA Encoded Libraries (DEGL) of Glycan Antigens to Detect Antibodies: An Approach Towards Next Generation Functional Glycomics
Creators: name: Parameswaran, Aishwarya
Publisher: name: Georgia State University
Year: 2017

description: Structure and functional study of glycans are highly challenging due to the difficulties in analyzing glycans and limited availability of samples for study. These limitations could be resolved by attaching DNA barcode to the glycan, which virtually represent glycan in further application, by increasing the sensitivity of detection by polymerase chain reaction (PCR), requiring minimal samples for analysis. Assuming bigger arena of DNA Encoded Glycan Libraries (DEGL) in future, we propose here a method for uniquely coding all glycans using computer program that can convert the structural information of glycans to DNA barcode. A unique and universal coding for glycans will benefit both synthesis and analysis of DEGLs. As a proof of principle study, a small DNA Encoded Glycan Library (DEGL) of blood and globo series glycan antigen and its application was demonstrated in detecting blood group and breast cancer from plasma.
Atomistic Insights into Binding Pocket Dynamics and Regulation in the Interleukin-2 T-Cell Kinase SH2 Domain
Creators: name: Momin, Mohamed
Publisher: name: Georgia State University
Year: 2017

description: Although the regulation of proteins functions by allosteric interactions has been identified in many subcellular processes, long-range conformational changes in proteins are also known to be induced by molecular switches. A molecular switch based on the cis-trans isomerization of a peptidyl-prolyl bond is capable of inducing a conformational change directly to the protein backbone, which is then propagated throughout the system. However, these switches are elusive and difficult to identify due to their intrinsic dynamics in the biomolecules where they are found. Herein, we explore the conformational dynamics and free energy landscape of the SH2 domain of Interleukin-2-inducible T-Cell Kinase (ITK) to fully understand the conformational coupling between the distal cis-trans molecular switch, and its phosphotyrosine binding pocket. Using multiple microsecond-long all-atom molecular dynamics simulations in explicit water for over a total of 60 ?s, we show that the cis-trans isomerization of the Asn286-Pro287 peptidyl-prolyl bond is directly correlated to the dynamics of the phosphotyrosine binding pocket, in agreement with previous NMR studies. While the cis state is localized to a single free energy basin and less dynamic, the trans state samples two distinct conformations of its binding pocket ? one that recognizes the phosphotyrosine motif, and another that is similar the cis state. These results provide an atomic-level description of a less-well understood allosteric regulation by a peptidyl-prolyl cis-trans molecular switch that could aid in the understanding of normal and aberrant sub-cellular process and the identification of these elusive molecular switches in other proteins.
Synthesis Of Novel Organic Carbon Monoxide Prodrugs With Tunable Release For Biological Applications
Creators: name: Chittavong, Vayou
Publisher: name: Georgia State University
Year: 2017

description: Carbon monoxide (CO) is an endogenous signaling molecule and has therapeutic values. However, the application of CO in the development of therapeutic options is hampered by the lack of pharmaceutically acceptable delivery methods. Inhalation of CO is not an ideal option for wide-spread clinical applications. Existing CO releasing molecules (CORMs) are mostly metal complexes, which have toxicity concerns to overcome. Some metal free CORMs have been developed. However, they all require light as a trigger to release CO, which limits their applications in vivo. Herein, we describe a metal-free CO prodrug approach using an intramolecular inverse electron-demanded Diels-Alder reaction. Such prodrugs can release CO spontaneously under physiological conditions with tunable release rates with the concomitant formation of a fluorescent reporter after CO releases. This intramolecular ?click and release? strategy represents a milestone in the development of CO based therapeutics.
Design and Synthesis of Inhibitors of Hypoxia Inducible Factor-1-mediated Functions
Creators: name: Yang, Lingyun
Publisher: name: Georgia State University
Year: 2017

description: Hypoxia Inducible Factors (HIFs) are very important transcription factors that can respond to low oxygen concentrations in the cellular environment. Inhibition of HIF?s transcriptional activity represents a promising approach to new anticancer compounds. Herein, we describe the design and synthesis of a series of HIF-1 inhibitors. Evaluation of these inhibitors using a cell-based luciferase assay led to the discovery compounds with sub-micromolar potency.
Biophysical Heme Binding Studies of Corynebacterium diphtheriae and Streptococcus pyogenes
Creators: name: Thompson, Stephanie
Publisher: name: Georgia State University
Year: 2017

description: Gram-positive pathogenic bacteria utilize cell-surface anchored proteins to bind and transport heme into the cell. These bacteria acquire iron from host proteins containing heme e.g., hemoglobin. Proteins like HmuT from Corynebacterium diphtheriae bind and help transport heme into the cell. Residues His136 and Tyr235 are utilized as the axial ligands, with a conserved Arg237 residue acting as the hydrogen bonding partner to the axial Tyr235. Similarly, Streptococcus pyogenes utilizes the cell anchored protein Shr to transfer heme into the cell. Shr-NEAT2 is hexacoordinated by two axial methionines and is prone to autoreduction where lysines are the most likely source of electrons. Lastly, PefR of Group A Streptococcus is a DNA transcription factor which regulates protein expression. Preliminary studies indicate a cysteine may coordinate the heme. A combination of UV-visible, resonance Raman, and magnetic circular dichroism spectroscopies shows these proteins play a crucial role heme transport and regulation.
Computational Studies of Liver Receptor Homolog 1 in the Presence of Small Molecule Agonists: Allosteric Communication and Virtual Screening for New Potential Drug Candidates
Creators: name: Scott, Bernard
Publisher: name: Georgia State University
Year: 2017

description: Liver Receptor Homolog 1 (LRH-1) is a nuclear receptor whose dysfunction is affiliated with diseases such as diabetes and cancer.  Recent investigations demonstrate that higher levels of activation and modulation of its activity can be achieved through its interaction with phospholipids (PLs) and synthetic small molecules.  We employed molecular dynamics (MD) simulations to understand more about the structural basis of LRH-1?s activity when bound to small molecule agonist RJW100 as well as the RJW100 derivative 65endo.  We find that RJW100 and derivative 65endo can trigger allosteric communication in LRH-1 despite the RJW100 scaffold inducing motions that differ from those induced by PLs.  We also provide supporting evidence that a key threonine residue and a water network may be important in RJW100?s ability to activate LRH-1.  Finally, in a campaign to identify new LRH-1 lead compounds, virtual screening was performed against RJW100, 65endo, and a second RJW100 derivative, 8AC.
Pirin Allosterically Modulates The Dynamics And Interactions Of The Kappa B DNA In The  NF-Kappa B Supramolecular Complex
Creators: name: Adeniran, Charles
Publisher: name: Georgia State University
Year: 2017

description: The NF-KB family of transcription factors controls a number of essential cellular functions. Pirin is a non-heme iron (Fe) redox specific co-regulator of NF-KB (p65) and has been shown to modulate the affinity between the homodimeric p65 and the DNA. The allosteric effect of the active Fe(III) form of Pirin on the DNA is not known and has not been investigated. We carry out multiple microsecond-long molecular dynamics simulations of the free DNA, p65-DNA complex, and the Pirin-p65-DNA supramolecular complexes in explicit water. We show that, unlike the Fe(II) form of Pirin, the Fe(III) form in the Pirin-p65-DNA supramolecular complex enhances the interactions and affinity between p65 and the DNA, in agreement with experiments. The results further provide atomistic details of the effect of the Fe(III) form of Pirin on the DNA upon binding to p65 to form the supramolecular complex.
Determination of Dynamical Conservation in Human Cyclophilin Isoforms
Creators: name: Vu, Phuoc Jake
Publisher: name: Georgia State University
Year: 2017

description: Among the peptidyl prolyl isomerases, the Cyclophilin family of proteins has been linked to various cellular activities such as regulation of homeostasis, mitochondrial permeability, and cell death. Their functionality spans throughout the cell and throughout all cell types as different isoforms. Previous studies done on Cyclophilin A revealed an interesting contact ensemble when bound to a substrate. Because of the similarity of CypA to its homologues, it is believed that they too will exhibit the same contact dynamics. We have defined the dynamics of cyclophilin isoforms through Molecular Dynamics simulations and determined their contact dynamics, characterizing their contact ensembles, and their relative dynamical conservation to each other.
Analysis Of DNA Interactions and Photocleavage by Phenyl Meso Substituted Cyanine Dyes In The Near-Infrared Range
Creators: name: Fischer, Christina
Publisher: name: Georgia State University
Year: 2017

description: Cyanine dyes are attractive photosensitizers for photodynamic therapy due to their ease of structure modification and intense absorption in the near-infrared range. Photosensitizers that can bind to DNA and absorb at long enough wavelengths of light to deeply penetrate biological tissue are in high demand for treatment of cancer and other diseases. The following study analyzes the DNA interactions of three pentamethine cyanine dyes with very similar structures, all of which absorb light at wavelengths longer than 800 nm. The work described involves an extensive study of the photocleavage abilities and DNA binding characteristics of these dyes. Our lead compound was a bromophenyl meso substituted symmetrical quinoline cyanine dye. Spectroscopic data, gel electrophoresis experiments and other studies were used to provide evidence of DNA binding mode, ROS production, and of dye-sensitized DNA photocleavage at the unprecedented wavelength of 850 nm.
Organic Carbon Monoxide Prodrugs
Creators: name: Aghoghovbia, Robert
Publisher: name: Georgia State University
Year: 2017

description: Ongoing efforts towards the development of CO-based therapeutics have resulted in the generation of novel CO prodrugs that release CO via different triggers or stimuli. Here in, we designed and synthesized organic CO prodrugs with a tethered cytotoxic agent to achieve a co-delivery of CO and the cytotoxic drug under physiological conditions by leveraging on the inverse electron-demand Diels-Alder reaction as the trigger. We also attempted to characterize, kinetically and spectroscopically, some of the organic CO prodrugs synthesized by our lab. The results showed that these prodrugs released CO under near physiological condition with controllable and tunable release rate.
Cation Adsorption and Exchange at the Mineral-Water Interface: The Role of Hydration and Hydrolysis
Creators: name: Allen, Nicholas
Publisher: name: Georgia State University
Year: 2017

description: This work examines the interactions of cations with two mineral surfaces, quartz (SiO2) and corundum (Al2O3) to gain mechanistic insights into those interactions through the use of flow microcalorimetry, quartz crystal microbalance measurements, and density functional theory.  The adsorption and exchange of alkali and alkaline earth cations onto the quartz mineral surface was conducted at pH 4.0 and 8.0.  The heats of adsorption and exchange were found to increase along the lyotropic series, Li+ < Na+ < K+ < Rb+ < Cs+ and Mg2+ < Ca2+ < Sr2+ < Ba2+, and were strongly correlated with the cation bulk hydration enthalpy.    The adsorption of Al3+, Cr3+, and Mn2+ was investigated on the quartz and corundum mineral surfaces at pH 3.8.  Adsorption behavior was seen for all cations on both surfaces, with the exception of Mn2+ on quartz.  The adsorption of these cations was a function of both cation hydration and hydrolysis.
Cloning, Purification, and Biochemical Characterization of PA1225, a Novel FAD Containing NADPH:Quinone Reductase from Pseudomonas aeruginosa PAO1
Creators: name: Flores, Elias
Publisher: name: Georgia State University
Year: 2017

description: The gene product of pa1225 found in the opportunistic bacterium Pseudomonas aeruginosa strain PAO1 is currently annotated as a putative NAD(P)H dehydrogenase. Prior investigation of LysR (PA4203), which regulates the transcription of detoxifying enzymes, revealed PA1225 to be the most upregulated gene in the LysR deletion mutant in PAO1. A combination of steady-state and rapid kinetics was used to investigate the enzymatic properties of PA1225, which may play a potential role in the viability of P. aeruginosa PAO1 in toxic environments. In this study, it was experimentally determined that PA1225 catalyzes the oxidation of NADPH and NADH to reduce one- and two-ring quinones. PA1225 has a clear preference for NADPH as the reducing substrate as determined by a 50-fold difference in kcat/Km with respect to NADH at pH 6.0. The effect of pH was also investigated with NADPH and NADH to elucidate changes in kred and Kd.
Investigation of Low-Temperature Effects on DNA Photocleavage Using a Novel Thioether Substituted Cyanine Dye
Creators: name: Clay, Andrew
Publisher: name: Georgia State University
Year: 2018

description: The implications of temperature effects on photochemical processes when it comes to near-infrared DNA photosensitizing agents are discussed in addition to the unique spectroscopic features of a sulfur meso-substituted heptamethine cyanine dye relative to oxygen and nitrogen analogues. Specifically, reactive oxygen scavenger experiments, preliminary kinetic data, and absorption spectra are considered in this continued investigation. Additionally, binding and stability studies indicate that the general structure of the cyanine dye can be further optimized to potentially improve DNA photocleavage yields at physiological temperatures while employing the exceptional properties of sulfur-incorporated polymethine dyes.