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Targeted Cancer Therapy Systems: An In Silico Study Of Radiohalogenated Ligands In The Estrogen Receptor And The Synthesis Of A Molecular Toolkit For The Fabrication Of Customizable Nanoparticles, Kelton Kerry Barnsley 2015 Northeastern University

Targeted Cancer Therapy Systems: An In Silico Study Of Radiohalogenated Ligands In The Estrogen Receptor And The Synthesis Of A Molecular Toolkit For The Fabrication Of Customizable Nanoparticles, Kelton Kerry Barnsley

Chemistry Master's Theses

Chemotherapy is often limited by off-target toxicity and the development of multi-drug resistance in response to treatment. Strategies which reduce off-target toxicity by passively or actively targeting cancer cells may improve the efficacy of chemotherapy. Herein, two projects relating to targeted therapy are described. In the first project, the binding modes of 1,1-bis(4-hydroxyphenyl)-2-phenylethylenes (THPEs), a class of synthetic estrogens previously developed by our group, in the human estrogen receptor alpha-ligand binding domain were studied using molecular modeling programs YASARA AutoDock and Schrodinger Glide. The results were internally consistent and supported the observation that a bromine or iodine ...


Dancing Through Life: Allosteric Transitions And Structural Analysis Of Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker 2014 Chapman University

Dancing Through Life: Allosteric Transitions And Structural Analysis Of Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker

Undergraduate Student Research Day Abstracts and Posters

The molecular chaperone protein Hsp70 is centrally involved in cellular homeostasis by assisting in the folding and degradation of protein substrates. Hsp70 is joined by co-chaperones, such as Hsp110, which contribute to specialized tasks of the Hsp70 complex. Imbalances of this heat shock protein system are believed to be involved with the deregulation of cancer pathways and other human diseases. Better understanding of how these heat shock proteins work at the molecular level, which has been investigated using molecular docking tools, will give more clues about biological function. Simulating the formation and function of Hsp70 based chaperone complexes could provide ...


Argument Map: Loewi's Argument That Neuro-Transmission Works With Chemical Signals Instead Of Eletrical (Short Version), Michael Hoffmann 2014 SelectedWorks

Argument Map: Loewi's Argument That Neuro-Transmission Works With Chemical Signals Instead Of Eletrical (Short Version), Michael Hoffmann

Michael H.G. Hoffmann

This argument shows how the hypothesis that muscles are probably stimulated exclusively by chemical signals and not by electrical ones can be justified by Loewi's experimentum crucis.


Swarna Ramaswamy_Thesis, Swarna S. Ramaswamy 2014 Texas Medical Center Library

Swarna Ramaswamy_Thesis, Swarna S. Ramaswamy

UT GSBS Dissertations and Theses (Open Access)

STRUCTURAL INVESTIGATIONS OF LIGAND GATED ION CHANNELS

Swarna Ramaswamy, B.S

Advisor: Vasanthi Jayaraman, Ph.D.

Ion channels form an integral part of membrane proteins. In the nervous system including the central and the peripheral nervous system, ligand gated ion channels form a very important part of intercellular communications. They receive chemical signals and convert them to electrical signal, mainly by allowing ion passage across the cell membrane. Ion passage also translates into downstream signaling events. Faithful translation of these signals and transmittance is crucial for several physiological functions, implying that irregular ion channel function could lead to serious consequences ...


Redesign Of Trans-Splicing Molecules For The Correction Of Dystrophia Myotonica Type 1 Toxic Rna Transcripts, Eleanor G. Harrison 2014 East Tennessee State University

Redesign Of Trans-Splicing Molecules For The Correction Of Dystrophia Myotonica Type 1 Toxic Rna Transcripts, Eleanor G. Harrison

Undergraduate Honors Theses

Dystrophia myotonica (DM1), one of the most common forms of muscular dystrophy, is caused by a repeated trinucleotide expansion in the DMPK gene. This mutation results in the accumulation of toxic cellular RNA transcripts. Spliceosome-mediated RNA trans-splicing (SMaRT) technology is a form of gene therapy that possesses the potential to correct these toxic RNA transcripts and thus cure the disease. Despite its promise, prior research applications of SMaRT technology to DM1 have been hampered by poor efficiency and have not been validated in a relevant model of the disease. In order to improve the efficiency of trans-splicing, this study examined ...


Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus A. Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh J. Byrne 2014 Dublin Institute of Technology

Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus A. Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh J. Byrne

Articles

A phenomenological rate equation model is constructed to numerically simulate nanoparticle uptake and subsequent cellular response. Polyamidoamine dendrimers (generations 4-6) are modelled and the temporal evolution of the intracellular cascade of; increased levels of reactive oxygen species, intracellular antioxidant species, caspase activation, mitochondrial membrane potential decay, tumour necrosis factor and interleukin generation is simulated, based on experimental observations.

The dose and generation dependence of several of these response factors are seen to well represent experimental observations at a range of time points. The model indicates that variations between responses of different cell-lines, including murine macrophages, human keratinocytes and colon cells ...


Microchip Thermal Gradient Gas Chromatography, Anzi Wang 2014 Brigham Young University

Microchip Thermal Gradient Gas Chromatography, Anzi Wang

All Theses and Dissertations

Although the airbath oven is a reliable heating method for gas chromatography (GC), resistive heating is needed for higher analytical throughput and on-site chemical analysis because of size, heating rate and power requirements. In the last thirty years, a variety of resistive heating methods were developed and implemented for both benchtop and portable GC systems. Although fast heating rates and low power consumption have been achieved, losses in column efficiency and resolution, complex construction processes and difficulties experienced in recovering damaged columns have also become problematic for routine use of resistively heated columns. To solve these problems, a new resistively ...


The ​Oestrogen Receptor Alpha-Regulated Lncrna ​Neat1 Is A Critical Modulator Of Prostate Cancer, Dimple Chakravarty, Andrea Sboner, Sujit S. Nair, Eugenia Giannopoulou, Ruohan Li, +16 additional authors 2014 Himmelfarb Health Sciences Library, The George Washington University

The ​Oestrogen Receptor Alpha-Regulated Lncrna ​Neat1 Is A Critical Modulator Of Prostate Cancer, Dimple Chakravarty, Andrea Sboner, Sujit S. Nair, Eugenia Giannopoulou, Ruohan Li, +16 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical ...


An Active Role For The Ribosome In Determining The Fate Of Oxidized Mrna, Carrie L. Simms, Benjamin H. Hudson, John W. Mosior, Ali S. Rangwala, Hani S. Zaher 2014 Washington University in St. Louis

An Active Role For The Ribosome In Determining The Fate Of Oxidized Mrna, Carrie L. Simms, Benjamin H. Hudson, John W. Mosior, Ali S. Rangwala, Hani S. Zaher

Biology Faculty Publications

Chemical damage to RNA affects its functional properties and thus may pose a significant hurdle to the translational apparatus; however, the effects of damaged mRNA on the speed and accuracy of the decoding process and their interplay with quality-control processes are not known. Here, we systematically explore the effects of oxidative damage on the decoding process using a well-defined bacterial in vitro translation system. We find that the oxidative lesion 8-oxoguanosine (8-oxoG) reduces the rate of peptide-bond formation by more than three orders of magnitude independent of its position within the codon. Interestingly, 8-oxoG had little effect on the fidelity ...


The Development Of A Valid And Reliable Biogeochemistry Concept Inventory, Chris Mead 2014 University of Nebraska - Lincoln

The Development Of A Valid And Reliable Biogeochemistry Concept Inventory, Chris Mead

DBER Speaker Series

Concept inventories are a commonly used tool to measure conceptual understanding. To date, concept inventories have been published for geology, chemistry, and biology, but no instrument has been designed to measure conceptual understanding at the intersection of those fields. To fill that gap, we constructed a 32‐item biogeochemistry concept inventory (BGC‐CI). Item response theory analysis, using the Rasch model, shows the BGC‐CI is a reliable and valid tool to measure the biogeochemistry knowledge of science majors. Because biogeochemistry is an interdisciplinary field, we were concerned about the unidimensionality of the instrument. However, our analysis showed the BGC ...


Argument Map: Devoloping Scientific Hypotheses And Experimental Designs In Form Of An Argumentation. Loewi's Crucial Experiment On Chemical Neurotransmission, Michael Hoffmann 2014 SelectedWorks

Argument Map: Devoloping Scientific Hypotheses And Experimental Designs In Form Of An Argumentation. Loewi's Crucial Experiment On Chemical Neurotransmission, Michael Hoffmann

Michael H.G. Hoffmann

This argument map presents Paul Loewi’s crucial experiment in which he showed that neural transmissions of signals are chemical in nature, not electrical, in form of an argumentation. The map can be used in science education to show how the formulation of hypotheses should be related to a corresponding determination of experimental designs.


Ribosomes Left In The Dust: Diverse Strategies For Peptide-Mediated Translation Stalling, Benjamin H. Hudson, Hani S. Zaher 2014 Washington University in St. Louis

Ribosomes Left In The Dust: Diverse Strategies For Peptide-Mediated Translation Stalling, Benjamin H. Hudson, Hani S. Zaher

Biology Faculty Publications

In two recent papers, Arenz et al. (2014a) and Bischoff et al. (2014) provide structural insights into drug-induced, peptide-mediated stalling of the ribosome.


Semi-Synthetic Development Of Mithramycin Analogues, Sterling Brooks, Allison Foster, Daniel Scott 2014 DePauw University

Semi-Synthetic Development Of Mithramycin Analogues, Sterling Brooks, Allison Foster, Daniel Scott

Science Research Fellows Posters

No abstract provided.


Helping Families With Rare Diseases: Finding Disease-Causing Variants In A Wealth Of Genomic Data, Tyler Huff 2014 DePauw University

Helping Families With Rare Diseases: Finding Disease-Causing Variants In A Wealth Of Genomic Data, Tyler Huff

Science Research Fellows Posters

No abstract provided.


Tandem Cancer Drug Delivery Via Gold Nanoparticle Targeting Platforms, Jeffrey Schulte, Sam Lohmar, Daniel Scott 2014 DePauw University

Tandem Cancer Drug Delivery Via Gold Nanoparticle Targeting Platforms, Jeffrey Schulte, Sam Lohmar, Daniel Scott

Science Research Fellows Posters

No abstract provided.


Anticancer Drug Delivery Via Unique Properties Of Gold Nanoparticles, Sam Lohmar, Jeffrey Schulte, Daniel Scott 2014 DePauw University

Anticancer Drug Delivery Via Unique Properties Of Gold Nanoparticles, Sam Lohmar, Jeffrey Schulte, Daniel Scott

Science Research Fellows Posters

No abstract provided.


Automatic Animation Of Molecular Motion Using Python And Cinema 4d, Diana Zajac, Nathaniel Smith, Dan Gurnon 2014 DePauw University

Automatic Animation Of Molecular Motion Using Python And Cinema 4d, Diana Zajac, Nathaniel Smith, Dan Gurnon

Science Research Fellows Posters

No abstract provided.


Er-Associated Degradation And Cadmium Dependent Rescue Of Pca1, Nathan Smith 2014 University of Nebraska - Lincoln

Er-Associated Degradation And Cadmium Dependent Rescue Of Pca1, Nathan Smith

Theses and Dissertations in Biochemistry

Protein synthesis and proper folding is an essential process for all organisms. In eukaryotes proteins of the secretory pathway are synthesized and inserted into the lumen or membrane of the endoplasmic reticulum. Eukaryotic cells maintain a mechanism for removal of proteins unable to fold properly. This process is known as ER-associated degradation (ERAD). A poorly functioning ERAD can lead to a build-up of misfolded proteins which has been implicated in several degenerative diseases such as Alzheimer’s, Amyotrophic lateral sclerosis, and Parkinson’s. Thus, the study of how proteins are recognized, extracted from the ER, and degraded is essential for ...


Cross-Disciplinary Sciences At Gettysburg College: Second Annual Poster Presentation, X-SIG 2014 Gettysburg College

Cross-Disciplinary Sciences At Gettysburg College: Second Annual Poster Presentation, X-Sig

Student Publications

This booklet includes Biology student presentations by: Taylor Bury, Abigail Dworkin-Brodsky, Mary Pearce, Jasper Leavitt, Morgan Panzer, Ellen Petley, Kalli Qutub, Taylor Randell, Samantha Eck, Lana McDowell, Jenn Soroka, Celina Harris, Natalie Tanke, Alexandra Turano, and Caroline Garliss.

This booklet includes Biochemistry & Molecular Biology student presentations by: Matthew Dunworth, Andrew Sydenstricker, Brianne Tomko, Albert Vill, Warren Campbell, David Van Doren, Kevin Mrugalski, Stacey Heaver, Alecia Achimovich, and Katherine Boas.

This booklet includes Chemistry student presentations by: Kristen Baker, Laura Lee, Kathryn Fodale, Daniel Ruff, Michael Counihan, Ida DiMucci, Joshua Sgroi, Celina Harris, and Natalie Tanke.

This booklet include Health Science ...


Ligand-Directed Signaling And Trafficking At The Nociceptin Opioid Peptide Receptor, Gina E. Migneco 2014 Washington University in St. Louis

Ligand-Directed Signaling And Trafficking At The Nociceptin Opioid Peptide Receptor, Gina E. Migneco

Undergraduate Research Symposium Posters & Abstracts

Traditional opioid receptors such as the μ and κ opioid receptors (MOR and

KOR) are well studied and are found to be common targets for pain and

stress therapies. The nociceptin opioid receptor (NOPR/ORL1) is a most

recently discovered opioid receptor whose complete function is still relatively

unknown, however is of great interest to researchers due to its analgesic

and antidepressant properties. NOPR activation due to ligand binding

triggers a variety of downstream effects, including G-protein signaling,

arrestin-mediated signaling, and receptor internalization. A variety of NOPR

ligands, both putative agonists and antagonists, were characterized by

further examination of these ...


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