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The Structural Requirements Of Histone Deacetylase (Hdac) Inhibitors: Suberoylanilide Hydroxamic Acid (Saha) Analogues Modified At C3, C6, And C7 Positions Enhance Selectivity, Sun Ea Choi

Wayne State University Dissertations

Histone deacetylase (HDAC) proteins are targets for drug design towards the treatment of cancers since overexpression of HDAC is linked to cancer. Several HDAC inhibitors, including the FDA approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat), have cleared clinical trials and emerged as anti-cancer drugs. However, SAHA inhibits all of the 11 metal ion-dependent HDAC proteins. Therefore, we synthesized several libraries of small molecule HDAC inhibitors based on SAHA to help understand the structural requirements of inhibitory potency and isoform selectivity.

In previous work, SAHA analogues functionalized at the C2 position (C2-SAHA analogues) near the metal binding hydroxamic acid displayed decreased …

Design, Synthesis, And Biological Evaluation Of Indole-Based 1,4-Disubstituted Piperazines As Cytotoxic Agents, Meri̇ç Köksal Akkoç, Mi̇ne Yarim Yüksel, İrem Durmaz, Rengül Çeti̇n Atalay

Turkish Journal of Chemistry

A series of 3-[(4-substitutedpiperazin-1-yl)methyl]-1H-indole derivatives were synthesized, and their structures were confirmed by spectral analysis. All the compounds were tested for their cytotoxic activity in vitro against 3 human tumor cell lines: human liver (HUH7), breast (MCF7), and colon (HCT116). Among the designed derivatives, most of the compounds showed significant cytotoxicity against liver and colon cancer cell lines with lower IC_{50} concentrations than the standard drug 5-fluorouracil. Compound 3s, with 3,4-dichlorophenyl substituent on the piperazine ring, was the most active in suppressing the growth of all screened cancer cells.

Design, Synthesis, And Biological Evaluation Of Novel Polyamine Transport System Probes And Their Application To Human Cancers, Aaron Muth

Electronic Theses and Dissertations

The mammalian polyamine transport system (PTS) has been of interest due to its roles in cancer and maintaining cellular homeostasis. Polyamines are essential growth factors which are tightly controlled via a balance of biosynthesis, metabolism, import, and export. This work focused on the development and biological testing of polyamine transport probes to help understand the molecular requirements of the PTS. This was mediated through the use of a CHO (PTS active) and CHO-MG* (PTS deficient) screen, where compounds demonstrating high toxicity in CHO and low toxicity in CHO-MG* were considered PTS selective. The first chapter focused on the development of …

Mechanism Of Inhibition Of The Glua2 Receptors By N-3 Derivatives Of 2,3-Benzodiazepines With C-4 Methyl Group, Congzhou Wang

Legacy Theses & Dissertations (2009 - 2024)

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one of the three subtypes of ionotropic glutamate receptors. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system (CNS). Over-activation of calcium permeable AMPA receptors causes intracellular calcium overload, which leads to neurodegeneration and cell death. As such, AMPA receptors have been implicated in a number of neurological disorders and diseases, such as epilepsy, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. 2,3-Benzodiazepine derivatives (or GYKI compounds) are a group of structurally similar compounds synthesized as inhibitors of AMPA receptors, and they have been used as potential drug candidates for the treatment of various …

Effects Of Vector Migration On Sylvatic Trypanosoma Cruzi Transmission, Britnee A. Crawford

Mathematics Dissertations - Archive

Vector-borne diseases have had a major impact on global health concerns since their discovery in the 1800's. A vector-borne disease is one transmitted to human or animal host via an invertebrate vector (usually an insect). Chagas' disease, caused by the parasite Trypanosoma cruzi, is transmitted via insect vectors from the Triatoma family. Although human infection with Chagas' is of importance, the disease is maintained in sylvatic (in the wild) transmission cycles. This study examines the effects of vector migration on the spread of T. cruzi in certain sylvatic cycles in the southeastern U.S. and Mexico from several angles. First, a …

Biomass And Mass Balance Isotope Content Of Mussel Seep Populations, Philip Martin Riekenberg

LSU Master's Theses

Cold seep mussels, Bathymodiolus childressi, are common cold seep constituents that form large populations at upper continental slope (500-1000 m) cold seep sites in the Northern Gulf of Mexico. These mussels utilize methane present through symbiotic relationships with methanotrophic bacteria. This study uses a coupled isotope technique to determine the relative incorporation of respiratory carbon in the shell as a measure of the availability of methane between different seep sites. This method indicates a higher abundance of methane at the Brine Pool site than at the Bush Hill site which appears significantly more resource limited and that changes in methane …

Syntheses And Characterization Of Water-Soluble Phythalocyanines For Diagnosis And Treatment Of Cancer, Benson Getenga Ongarora

LSU Doctoral Dissertations

Ongarora, Benson Getenga, B.S., Moi University, 2005 Doctor of Philosophy, Fall Commencement, 2012 Major: Chemistry Syntheses and Characterization of Water-Soluble Phthalocyanines for Diagnosis and Treatment of Cancer Dissertation directed by Professor M.Graҫa H. Vicente Pages in dissertation, xi. Words in abstract, 251. ABSTRACT Chapter 1 describes the general properties of phthalocyanines, synthesis of metallo-phthalocyanines, their photophysical features and their uses. The concepts of PDT and targeted therapeutics are also introduced. Chapter 2 describes the syntheses, characterization, photophysical studies and biological evaluation of cationic phthalocyanines. The trimethylaminophenoxy substituted phthalocyanines were synthesized through statistical condensation method, which gave a statistical mixture of …

Synthesis, Cellular Studies, And Computational Analysis Of Porphyrin And Bodipy Conjugates With Affinity For Epidermal Growth Factor Receptor, Alecia Michelle Mccall

LSU Doctoral Dissertations

Chapter 1 is a description of the basic fundamental concepts of porphyrins and BODIPYs, (including synthetic methodologies), a general mechanism of the processes of EGFR, and computational concepts that are elaborated upon in future chapters. Chapter 2 is a discussion solely on the porphyrins that were synthesized to be used as fluorophores for EGFR-targeted conjugates, both peptidic and non-peptidic. The porphyrins were primarily synthesized via the Lindsey method as well as by O-alkylation of tetrahydroxy porphyrins. Synthesis of PEG linkages are discussed as well through three methodologies. Chapter 3 is a presentation of the synthesis, characterization, cellular studies, and computational …

Total Synthesis Of A Virotoxin And Analogs For Conformational Studies, Benson Jumba Edagwa

LSU Doctoral Dissertations

This dissertation describes the first total synthesis of alloviroidin in trace amounts, along with that of three analogs containing L-proline (Pro), trans-3-hydroxyproline (3-Hyp) or cis-4-hydroxyproline (4-hyp) residue substituting for 2,3-trans-3,4-trans-dihydroxyproline in the natural product. We report herein an efficient strategy that provides a dipeptide containing a (2S,4S)-4,5-dihydroxyleucine (dihyLeu) residue, including a diastereoselective dihydroxylation. Nα-Carbobenzyloxy-(2S)-4,5-dehydroleucine was coupled with valine ethyl ester to give a dipeptide that was subjected to a Sharpless asymmetric dihydroxylation to introduce the diol. The relative configuration at C4 was assigned as S by X-ray crystallography after derivatization as an α-amino-γ-lactone hydrochloride salt. The preparation of the 2-(methylsulfonyl)tryptophan …

Single-Molecule Detection Of Molecular Beacons Generated From Ldr On Thermoplastic Microfluidic Device For Bioanalysis, Zhiyong Peng

LSU Doctoral Dissertations

Current clinical techniques for nucleic acid detection and analysis often involve PCR, lacking adequate specificity or sensitivity to meet the stringent requirements in certain applications. This research aims to develop an innovative molecular assay and the associated hardware to rapidly signal the presence of certain targets using reporter sequence found in their genome without requiring PCR. This assay coupled the sensitivity of single-pair fluorescence resonance energy transfer (spFRET) with the specificity of ligase detection reaction (LDR) to provide near real-time readout of target biomarkers. Heightened concerns on potential bioterrorism threats, such as rapid dissemination of pathogenic bacteria or viruses into …

Scale Invariant Object Recognition Using Cortical Computational Models And A Robotic Platform, Danny Voils

Dissertations and Theses

This paper proposes an end-to-end, scale invariant, visual object recognition system, composed of computational components that mimic the cortex in the brain. The system uses a two stage process. The first stage is a filter that extracts scale invariant features from the visual field. The second stage uses inference based spacio-temporal analysis of these features to identify objects in the visual field. The proposed model combines Numenta's Hierarchical Temporal Memory (HTM), with HMAX developed by MIT's Brain and Cognitive Science Department. While these two biologically inspired paradigms are based on what is known about the visual cortex, HTM and HMAX …

Chemical, Biological, And Preliminary In Vitro Studies Of Novel Vanadium(Iv) Complexes With Schiff Bases And Thiosemicarbazone Ligands, Nerissa Abigail Lewis

Master's Theses

9-Anthraldehyde-N(4)-methylthiosemicarbazone (MeATSC), potassium (E)-2-(2-hydroxybenzylideneamino)-3-(1H-indol-3-yl)propanoate (K[(Sal-L-tryp)] and 2-(2-hydroxybenzylamino)-3-(1H-indol-3-yl)propanoic acid (the reduced Schiff base) were prepared using known synthetic procedures. Two novel thiosemicarbazone ligands, (E)-N-ethyl-2-(4-hydroxy-3-methoxybenzylidene)hydrazinecarbothioamide (N-Ethhymethohcarbthio) and (E)-N-ethyl-2-(1-(thiazol-2-yl)ethylidene)hydrazinecarbothioamide (acetylethTSC), were also prepared. All ligands were characterized by FT IR and electrochemistry. N-Ethhymethohcarbthio were characterized by elemental analysis whereas the reduced Schiff base and K[(Sal-L-tryp)] were characterized by ESI MS. X-ray crystallography was also used to characterize acetylethTSC. The ligands were then reacted with [VO(Sal-L-tryp)(H2O)] (1) (Sal-L-tryp = N-salicylidene-L-tryptophanate) to produce the …

Ray Wilson, Ray Wilson, Daniel Maurer 2012

All oral histories

Ray Wilson taught courses in the Physics Department from 1962-1997. He continues to teach during May Term through the present (as of 2012).

A Mathematician Weighs In On The Evolution Debate, Kris H. Green

Journal of Humanistic Mathematics

There are a variety of reasons underlying the lack of public acceptance for the theory of evolution in the United States. An overlooked cause is related to problems with the mathematics curriculum in the K-12 setting. In this essay, we examine this relationship and propose changes to the mathematics curriculum that could improve mathematical thinking while also providing a basis for understanding theories, like evolution, that are poorly understood.

Fabrication And Selective Functionalization Of Amine-Reactive Polymer Multilayers On Topographically Patterned Microwell Cell Culture Arrays, Adam H. Broderick, Samira M. Azarin, Maren E. Buck, Sean P. Palecek, David M. Lynn

Chemistry: Faculty Publications

We report an approach to the fabrication and selective functionalization of amine-reactive polymer multilayers on the surfaces of 3-D polyurethane-based microwell cell culture arrays. "Reactive" layer-by-layer assembly of multilayers using branched polyethyleneimine (BPEI) and the azlactone- functionalized polymer poly(2-vinyl-4,4′-dimethylazlactone) (PVDMA) yielded film-coated microwell arrays that could be chemically functionalized postfabrication by treatment with different amine-functionalized macromolecules or small molecule primary amines. Treatment of film-coated arrays with the small molecule amine d-glucamine resulted in microwell surfaces that resisted the adhesion and proliferation of mammalian fibroblast cells in vitro. These and other experiments demonstrated that it was possible to functionalize different structural …

The Utility Of Transient Sensitivity For Wildlife Management And Conservation: Bison As A Case Study, Michael Buhnerkempe, Nathanial Burch, Sarah J. Hamilton, Kerry M. Byrne, Eddie Childers, Kirstin A. Holfelder, Lindsay Mcmanus, Matthew I. Pyne, Greg Schroeder, Paul F. Doherty

Mathematics, Statistics and Computer Science Faculty Research and Publications

Developing effective management strategies is essential to conservation biology. Population models and sensitivity analyses on model parameters have provided a means to quantitatively compare different management strategies, allowing managers to objectively assess the resulting impacts. Inference from traditional sensitivity analyses (i.e., eigenvalue sensitivity methods) is only valid for a population at its stable age distribution, while more recent methods have relaxed this assumption and instead focused on transient population dynamics. However, very few case studies, especially in long-lived vertebrates where transient dynamics are potentially most relevant, have applied these transient sensitivity methods and compared them to eigenvalue sensitivity methods. We …

National Park Service Cave And Karst Resources Management Case Study: Great Smoky Mountains National Park, Daniel C. Nolfi

Masters Theses & Specialist Projects

As discussed in the National Parks Service’s (NPS) Directors Orders/Natural Resources Management Reference Manual #77 and the 2006 NPS Management Policy Handbook, implementing a management plan specifically for cave and karst resources within a national park is paramount to afford these resources appropriate protection. With support from the Federal Cave Resources Protection Act and the National Park Service Organic Act of 1906, management actions protecting caves has begun to place significant importance outside the traditional cave environment onto a broader karst landscape. The need to understand and protect the karst environment and caves as a karst resource has taken a …

A Biosynthetic Membrane-Anchor/Protein System Based On A Genetically Encoded "Aldehyde Tag", Chaojie Zhen

Renée Crown University Honors Thesis Projects - All

Lipid membranes or bilayers serve as barriers for the cell and its organelles. A distinguishing feature of cellular function is the ability to monitor and process the biochemical information between the cells’ intra and extracellular environments in order to maintain the homeostatic reactions that are essential to life. Surface membrane proteins play a key role in mediating this information exchange by functionalizing the bilayer. As a result of their importance in living systems, proteins are integrated into biomimetic membrane systems to replicate their natural functions in biomedical technologies. Current protein integration methods are limited by the selection of commercially available …

Yongzhi Village: An Example For Sustainable Tourism And Development In Deqin County, Kiersten Brown

Independent Study Project (ISP) Collection

Nestled beneath misty mountain peaks, among the Salween, Mekong, and Yangtze rivers, a beautiful Tibetan village lies. Alongside low-lying mountain creeks and waterfalls this village is in Deqin County of Yunnan’s Deqin Tibetan Autonomous Prefecture (Deqin TAP). The Deqin TAP is the most Northwest prefecture of Yunnan. Deqin boasts that 33% of its population is comprised of the dominant minority group, Tibetans. Deqin prefecture is comprised of three counties, Shangrila County, Deqin County, and Weixi County. Deqin County is mostly comprised of small Tibetan towns and villages like Yongzhi. About 100 families inhabit Yongzhi. The village is placed right along …

41st Annual Wku Student Research Conference, Student Research Council, Western Kentucky University

Student Research Conference Select Presentations

No abstract provided.

Microfluidic Paper-Based Analytical Devices: From Pocket To Paper-Based Elisa, Andres W. Martinez

Chemistry and Biochemistry

Microfluidic paper-based analytical devices (microPADs) began as a simple idea with an ambitious goal. The idea was to make microfluidic devices out of paper instead of plastic or glass. The goal was to develop low-cost and portable paper-based diagnostic devices to improve healthcare in developing countries. Over the past 6 years, many developments have been made in the emerging field of paper-based microfluidic devices. Reviewing the development of these devices in the Whitesides group at Harvard University (Cambridge, MA, USA) can provide some insight into the future of the field and encourage scientists from a variety of backgrounds to contribute …

Profiles In Science For Science Librarians: "What Lives Where, And Why": Alfred Russel Wallace, And The Field Of Biogeography, Charles H. Smith

DLPS Faculty Publications

Biogeography, the study of animal and plant distribution, has a history extending back to at least the eighteenth century. But it was not until the work of Charles Darwin and Alfred Russel Wallace in the mid-nineteenth century that it really came into its own as a science. Darwin’s importance notwithstanding, it was really Wallace who put the field on the map, and many of today’s research threads can be traced back to his influence. This article provides a summary review of Wallace’s life and work and biogeography as a field of study, including Wallace’s role in its development.

Proceedings Of The 123rd Annual Meeting Of The Iowa Academy Of Science [Program, 2011], Iowa Academy Of Science

Iowa Academy of Science Documents

Contents:

Program Summary --- 2-3
Acknowledgements --- 4
Contents --- 5
Welcome --- 5
Iowa Junior Academy of Science Competition --- 6
Geology Special Event Using Geographic Information Systems in Iowa's K-16 Classrooms --- 7
General Session I-Roaming Mars, a Personal Perspective --- 8
Iowa Junior Academy of Science Award Luncheon --- 9
Iowa Academy of Science Business Meeting --- 9
Iowa Academy of Science Volunteers for 2010-2011 --- 10
Symposium A-Unintended Health & Environmental Consequences of Confinement Agriculture --- 11
Symposium B-Investigating Forensic Science --- 12
Symposium C-150th Anniversary-Science and the Civil War --- 13
Symposia Speakers --- 14-15 …

Constituents Of Plantago Major Subsp. Intermedia With Antioxidant And Anticholinesterase Capacities, Ufuk Kolak, Mehmet Boğa, Emi̇ne Akalin Uruşak, Ayhan Ulubelen

Turkish Journal of Chemistry

The methanol extract of Plantago major subsp. intermedia (Gilib.) Lange afforded 4 known compounds, namely isomartynoside (1), 10-hydroxymajoroside (2), \beta -sitosterol (3), and ursolic acid (4). Their structures were established by spectroscopic methods. After determination of the total phenolic and flavonoid contents of the methanol extract, the antioxidant potentials of the crude extract and isolated compounds 1-4 were determined by \beta -carotene bleaching, DPPH free radical and ABTS cation radical scavenging, and cupric reducing antioxidant capacity methods. The methanol extract, rich in phenolic contents, indicated the same DPPH free radical scavenging activity (72\% inhibition) as a standard compound, butylated hydroxytoluene, …

Single Cell Analysis For The Characterization Of Cell Populations Using A Live Cell Array, Maureen Ann Walling

Legacy Theses & Dissertations (2009 - 2024)

In the past decade, the shift from whole cell population analyses towards single cell measurement methods and techniques is based on experimental results that reveal significant levels of non-genetic heterogeneity in clonal cell populations. This heterogeneity manifests in multiple aspects of cell activity and is, in part, a result of stochastic noise in processes leading to gene expression, namely transcription and translation. The growing understanding of this occurrence has led to the development of methods to monitor and analyze heterogeneity for a more thorough description of cell populations and overall activity.

Preparation And Studies Of Ratiometric Fluorescent Chemosensors Based On The Attenuation Of Excitation Energy Transfer, Jiba Raj Acharya

LSU Doctoral Dissertations

Molecular devices possessing pi-electron conjugated scaffold demonstrate unique capabilities as fluorescent chemosensors for the trace detection of analytes in a variety of environments. Important properties of these compounds such as charge transport and exciton migration, emission intensity etc. can be simply attenuated by external stimuli or analyte binding, leading to considerable changes in observable signals. The main goal of this Ph.D. dissertation was to study the possibility to control excitation energy migration in conjugated systems. Towards this goal, we designed surface-immobilized monodispersed oligo(p-phenylene ethynylene)s (OPEs) as a general basis for thin-film ratiometric fluorescent chemosensors. The sensor molecules have been functionalized …

Synthesis, Biological And Photophysical Studies Of Novel Compounds For Cancer Therapy, Edith Khavwajira Amuhaya

LSU Doctoral Dissertations

Cancer remains the second most common cause of death in the United States. It is therefore imperative that a lot of effort be put into finding a cure for this dreadful disease that shows no discrimination, and virtually anybody is at risk of developing the disease. Chapter 1 introduces basic facts about cancer and the available treatments, including PDT and BNCT. Our focus will be on these two bimodal therapies, which form the basis of my research work, which involves the synthesis of potential sensitizers to be used either in PDT or BNCT or both. In Chapter 2, I discuss …

Formation And Stabilization Of Combustion-Generated Environmentally Persistent Free Radicals On Transition Metal Oxides Supported On Silica, Eric Warren Pimentel Vejerano

LSU Doctoral Dissertations

The formation of environmentally persistent free radicals in combustion system was investigated from chemisorptions of chlorine- and hydroxy-substituted benzenes on transition metal oxide surface under post-combustion conditions. This manuscript reports the formation of EPFRs on silica particles containing 5% Fe(III)2O3, Ni(II)O, and Zn(II)O. The EPFRs are formed by the chemisorption of substituted aromatic molecular adsorbates on the metal cation center followed by electron transfer from the adsorbate to the metal ion at temperatures from 150 to 400 oC. Depending on the nature of the adsorbate and the temperature, two organic EPFRs were formed: a phenoxyl-type radical, which has a lower …

Gene Network Inference And Expression Prediction Using Recurrent Neural Networks And Evolutionary Algorithms, Heather Y. Chan

Theses and Dissertations

We demonstrate the success of recurrent neural networks in gene network inference and expression prediction using a hybrid of particle swarm optimization and differential evolution to overcome the classic obstacle of local minima in training recurrent neural networks. We also provide an improved validation framework for the evaluation of genetic network modeling systems that will result in better generalization and long-term prediction capability. Success in the modeling of gene regulation and prediction of gene expression will lead to more rapid discovery and development of therapeutic medicine, earlier diagnosis and treatment of adverse conditions, and vast advancements in life science research.

The Synthesis, Characterization, And Electrochemical Study Of Tris(Pyrazolyl)-Type Iron(Ii) Complexes, Iron(Ii) Sulfur- And Selenium-Containing Complexes, And Tris(Pyrazolyl)-Type Ruthenium(Ii) Complexes, Christopher Underwood

All Theses

Highly reactive radical species such as hydroxyl radical cause oxidative stress, resulting in chronic or degenerative diseases. In the biological Fenton reaction, iron(II) generates hydroxyl radical, OH, but only within a specific electrochemical potential window (-324 mV to 640 mV). Selenium and sulfur compounds have been extensively studied for their antioxidant properties, and they may exert their effects by binding iron(II) and shifting its electrochemical potential out of this window. This work has investigated the synthesis and electrochemical characterization of iron(II) chalcogenate complexes and iron(II) chalcogenone complexes. Cyclic voltammetry (CV) of [Fe(EPh)4][(PPh4)2] (E = S, Se) complexes shows Fe2+/3+ redox …