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Articles 31 - 60 of 115
Full-Text Articles in Cancer Biology
Deep Learning-Based Technique For The Perception Of The Cervical Cancer, Aya Haraz, Hossam El-Din Moustafa, Abeer Twakol Khaleel, Ahmed H. Eltanboly
Deep Learning-Based Technique For The Perception Of The Cervical Cancer, Aya Haraz, Hossam El-Din Moustafa, Abeer Twakol Khaleel, Ahmed H. Eltanboly
Mansoura Engineering Journal
In third-world countries, cervical cancer is the most prevalent and leading cause of death. It is affected by a variety of factors, including smoking, poor nutritional status, immunological inadequacy, and prolonged use of contraception. The Pap smear test, which is intended to prevent cervical cancer, finds preneoplastic changes in cervical epithelial cells. This study framework classified cervical cancer cells from Pap smears into five specified cell types using machine learning-based classification algorithms. The SIPaKMeD database is used in this investigation. This public dataset, which was manually cropped from 966 cluster cell images taken from Pap smear slides, has 4045 isolated …
Hypothesis Testing And Parameter Estimation In Mixture Cure Models For Cancer Survival Data, Mohammod Mahmudur Rahman
Hypothesis Testing And Parameter Estimation In Mixture Cure Models For Cancer Survival Data, Mohammod Mahmudur Rahman
Graduate Theses and Dissertations
In oncology clinical trials, when a treatment is administered to the patient population, a certain subset of patients may respond to the treatment while the other does not. The positive responders with long-term survival are considered “statistically cured” and can be referred to as cured patients or long-term survivors. When a proportion of patients achieve long-term survival, the hazard functions of two arms (control vs. treatment) are no longer proportional. As a result, the traditional log-rank test, which is the most popular test to evaluate the effectiveness of a treatment in clinical trials, tends to lose its power. In this …
A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin
A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin
Electronic Theses and Dissertations
Computational modeling of metabolic reactions and cellular systems is evolving as a tool for quantitative prediction of metabolic parameters and reaction pathway analysis. In this work, the basics of computational cell biology are presented as well as a summary of physical processes within the cell, and the algorithmic methods used to find time dependent solutions. Protein-protein and enzyme-substrate interactions are mathematically represented via mass action kinetics to construct sets of linear differential equations that describe reaction rates and formation of protein complexes. Using mass action methods, examples of reaction networks and their solutions are presented within the Virtual Cell simulation …
The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz
The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz
Graduate Theses and Dissertations
Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored.
This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and …
Identification Of Lipid Species: Potential Biomarkers For Early Detection Of Hepatocellular Carcinoma, Kit Yee Leung, Kaylee Freitas
Identification Of Lipid Species: Potential Biomarkers For Early Detection Of Hepatocellular Carcinoma, Kit Yee Leung, Kaylee Freitas
Undergraduate Research Symposium Posters
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC is associated with cirrhosis. Poor survival rate of HCC is due to diagnosis of HCC at late stage.
The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez
The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez
Thinking Matters Symposium
In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …
Synthesis Of Thiol-Acrylate Hydrogels For 3d Cell Culture And Microfluidic Applications, Anowar Hossain Khan
Synthesis Of Thiol-Acrylate Hydrogels For 3d Cell Culture And Microfluidic Applications, Anowar Hossain Khan
LSU Doctoral Dissertations
Globally cell culture is an $18.98 billion industry as of 2020, with an 11.6 percent annual growth rate. Drug discovery has an estimated worth of $69.8 billion in 2020 and is predicted to grow to $110.4 billion by 2025. Three-dimensional (3D) cell culture of cancer cells is one of the rapidly growing felids since it better recapitulates in vivo conditions compared to two-dimensional (2D) models. However, it is challenging to grow 3D tumor spheroids outside the body, and some of the existing technology can generate these spheroids outside the human body but poorly mimic in vivo tumor models. Therefore, there …
Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov
Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov
Chemistry & Biochemistry Faculty Publications
n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds …
Upregulation Of Cd36, A Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis By Increasing Mmp28 And Decreasing E-Cadherin Expression, James Drury, Piotr G. Rychahou, Courtney O. Kelson, Mariah E. Geisen, Yuanyuan Wu, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Yekaterina Y. Zaytseva
Upregulation Of Cd36, A Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis By Increasing Mmp28 And Decreasing E-Cadherin Expression, James Drury, Piotr G. Rychahou, Courtney O. Kelson, Mariah E. Geisen, Yuanyuan Wu, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Yekaterina Y. Zaytseva
Surgery Faculty Publications
Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation …
Clinical Diagnosis Support With Convolutional Neural Network By Transfer Learning, Spencer Fogleman, Jeremy Otsap, Sangrae Cho
Clinical Diagnosis Support With Convolutional Neural Network By Transfer Learning, Spencer Fogleman, Jeremy Otsap, Sangrae Cho
SMU Data Science Review
Breast cancer is prevalent among women in the United States. Breast cancer screening is standard but requires a radiologist to review screening images to make a diagnosis. Diagnosis through the traditional screening method of mammography currently has an accuracy of about 78% for women of all ages and demographics. A more recent and precise technique called Digital Breast Tomosynthesis (DBT) has shown to be more promising but is less well studied. A machine learning model trained on DBT images has the potential to increase the success of identifying breast cancer and reduce the time it takes to diagnose a patient, …
Chemoimmunotherapy Treatment Strategies On A Mathematical Model Of Cancer Evolution, Sandra M. Lopez, Yolocuauhtli Salazar, Paul A. Valle
Chemoimmunotherapy Treatment Strategies On A Mathematical Model Of Cancer Evolution, Sandra M. Lopez, Yolocuauhtli Salazar, Paul A. Valle
Annual Symposium on Biomathematics and Ecology Education and Research
No abstract provided.
Neural Network Controller Vs Pulse Control To Achieve Complete Eradication Of Cancer Cells In A Mathematical Model, Joel A. Quevedo, Sergio A. Puga, Paul A. Valle
Neural Network Controller Vs Pulse Control To Achieve Complete Eradication Of Cancer Cells In A Mathematical Model, Joel A. Quevedo, Sergio A. Puga, Paul A. Valle
Annual Symposium on Biomathematics and Ecology Education and Research
No abstract provided.
Reconstructing Mathematical Models With Chaotic Attractors Via Genetic Algorithms, Luis A. Ramirez Islas, Paul A. Valle
Reconstructing Mathematical Models With Chaotic Attractors Via Genetic Algorithms, Luis A. Ramirez Islas, Paul A. Valle
Annual Symposium on Biomathematics and Ecology Education and Research
No abstract provided.
Determining Malignancy: Can Mammogram Results Help Predict The Diagnosis Of Breast Tumors?, Taylor Behrens
Determining Malignancy: Can Mammogram Results Help Predict The Diagnosis Of Breast Tumors?, Taylor Behrens
Symposium of Student Scholars
Even with advancements in treatment and preventative care, breast cancer remains an epidemic claiming more than 40,000 American male and female lives each year. The mammogram dataset that I am analyzing was initially complied in the early 1990s by a team from the University of Wisconsin - Madison. Past research diagnoses breast cancer from fine-needle aspirates. My research focuses on predicting whether we can determine breast cancer diagnoses without the use of invasive procedures and, in particular, whether we can predict breast cancer based on mammogram data. Do measures of gray-scale texture, radius, concavity, perimeter, compactness, area, and smoothness of …
Indicators Of Senescence And Their Relationship With The Antioxidant Response Element In Ovarian Cancer Cells—Toward A More Encompassing View Of Enzyme Activity Levels In Cells, Shaniqua Analycia Hayes
Indicators Of Senescence And Their Relationship With The Antioxidant Response Element In Ovarian Cancer Cells—Toward A More Encompassing View Of Enzyme Activity Levels In Cells, Shaniqua Analycia Hayes
LSU Doctoral Dissertations
Enzymes and other related proteins are promising targets as biomarkers for cancer diagnostics, and it is therefore important to be able to quantify intracellular enzyme activity levels, not just presence of enzyme. Thus, there is a great need for the development of methods that offer spatiotemporal quantification of intracellular enzyme activity levels in respiring 2- and 3-dimensional cultures or their sample-processed variants. Previous studies have demonstrated that ß-gal is upregulated in senescence and in select ovarian cancers, and its expression/activity is upregulated when cells are under oxidative stress conditions. To that end, the primary goal of this work was to …
Advancing The Preclinical Development Of Secondary Metabolites From Cacospongia Mycofijiensis For The Treatment Of Cancer, Joseph Morris
Advancing The Preclinical Development Of Secondary Metabolites From Cacospongia Mycofijiensis For The Treatment Of Cancer, Joseph Morris
Natural Sciences and Mathematics | Biological Sciences Master's Theses
The marine sponge Cacospongia mycofijiensis from the Indo-Pacific has proven to be a source of structurally diverse secondary metabolites that are biologically active against a variety of distinct targets. Current interest in the secondary metabolites of C. mycofijiensis largely stems from a) their potent and preferential cytotoxicity for cancer cell lines versus normal cells, making many of them promising leads as cancer therapeutics and b) the novel mechanisms of action responsible for their impressive cytotoxicity. However, limited compound availability has resulted in a paucity of studies aimed at advancing the preclinical development of these secondary metabolites from C. mycofijiensis for …
Influence Of Monovalent And Divalent Ions In The Conformational Change Of Caspase-Cleaved Par-4 (Cl-Par-4) Tumor Suppressor Protein, Krishna K. Raut, Komala Ponniah, Steven M. Pascal
Influence Of Monovalent And Divalent Ions In The Conformational Change Of Caspase-Cleaved Par-4 (Cl-Par-4) Tumor Suppressor Protein, Krishna K. Raut, Komala Ponniah, Steven M. Pascal
College of Sciences Posters
Prostate apoptosis response-4 (Par-4) is a pro-apoptotic tumor suppressor protein. We have shown that this 38 kDa full-length Par-4 (Fl-Par-4) protein is predominantly intrinsically disordered in vitro. In vivo, Par-4 is cleaved by caspase-3 at Asp-131 to generate a 24 kDa functionally active cleaved Par-4 (cl-Par-4) fragment. The cl-Par-4 protein inhibits the NF-κB-mediated cell survival pathway and causes selective apoptosis in various tumor cells. Our laboratory is interested in how the disorder-order balance within Fl-Par-4 and cl-Par-4 may be related to the balance between cell survival and cell death. Currently, we are using biophysical techniques such as circular …
Photodynamic Therapy Of Inorganic Complexes For The Treatment Of Cancer, Chloe B. Smith, Lindsay C. Days, Duaa R. Alajroush, Khadija Faye, Yara Khodour, Stephen J. Beebe, Alvin Holder
Photodynamic Therapy Of Inorganic Complexes For The Treatment Of Cancer, Chloe B. Smith, Lindsay C. Days, Duaa R. Alajroush, Khadija Faye, Yara Khodour, Stephen J. Beebe, Alvin Holder
Chemistry & Biochemistry Faculty Publications
Photodynamic therapy (PDT) is a medicinal tool that uses a photosensitiser and a light source to treat several conditions, including cancer. PDT uses reactive oxygen species (ROS) such as cytotoxic singlet oxygen 1O2 to induce cell death in cancer cells. Chemotherapy has historically utilized the cytotoxic effects of many metals, especially transition-metal complexes. However, chemotherapy is a systemic treatment so all cells in a patient's body are exposed to the same cytotoxic effects. Transition metal complexes have also shown high cytotoxicity as PDT agents. PDT is a potential localized method for treating several cancer types by using inorganic …
A New Mathematical Theory For The Dynamics Of Large Tumor Populations, A Potential Mechanism For Cancer Dormancy & Recurrence And Experimental Observation Of Melanoma Progression In Zebrafish, Adeyinka A. Lesi
Dissertations and Theses
Cancer, a family of over a hundred disease varieties, results in 600,000 deaths in the U.S. alone. Yet, improvements in imaging technology to detect disease earlier, pharmaceutical developments to shrink or eliminate tumors, and modeling of biological interactions to guide treatment have prevented millions of deaths. Cancer patients with initially similar disease can experience vastly different outcomes, including sustained recovery, refractory disease or, remarkably, recurrence years after apparently successful treatment. The current understanding of such recurrences is that they depend on the random occurrence of critical mutations. Clearly, these biological changes appear to be sufficient for recurrence, but are they …
Developing Synthetic Strategies For Multifaceted Applications Of Stable Gold-Based Complexes, Randall Tyler Mertens
Developing Synthetic Strategies For Multifaceted Applications Of Stable Gold-Based Complexes, Randall Tyler Mertens
Theses and Dissertations--Chemistry
Development of stable gold-based complexes has been a rapidly advancing field due to the popularity of gold complexes, particularly for use in biomedical research and catalytic transformations. Given that auranofin, a gold(I) complex with FDA approval for the treatment of rheumatoid arthritis is used in the clinic, the development of stable gold-based molecules of clinical relevance is urgently needed. Herein are reported, synthetic strategies used for the development of new classes of gold(I) and gold(III) complexes for advancement in mitochondrial modulation for use as chemotherapeutics as well as application to gold catalysis due to the unique geometry of complexes presented …
The Resistive Barrier Discharge: A Brief Review Of The Device And Its Biomedical Applications, Mounir Laroussi
The Resistive Barrier Discharge: A Brief Review Of The Device And Its Biomedical Applications, Mounir Laroussi
Electrical & Computer Engineering Faculty Publications
This paper reviews the principles behind the design and operation of the resistive barrier discharge, a low temperature plasma source that operates at atmospheric pressure. One of the advantages of this plasma source is that it can be operated using either DC or AC high voltages. Plasma generated by the resistive barrier discharge has been used to efficiently inactivate pathogenic microorganisms and to destroy cancer cells. These biomedical applications of low temperature plasma are of great interest because in recent times bacteria developed increased resistance to antibiotics and because present cancer therapies often are accompanied by serious side effects. Low …
Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls
Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls
Graduate Theses, Dissertations, and Problem Reports (ETD)
This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …
Conditional Distance Correlation Test For Gene Expression Level, Dna Methylation Level And Copy Number, Shanshan Zhang
Conditional Distance Correlation Test For Gene Expression Level, Dna Methylation Level And Copy Number, Shanshan Zhang
Graduate Theses and Dissertations
Over the past years, efforts have been devoted to the genome-wide analysis of genetic and epigenetic profiles to better understand the underlying biological mechanisms of complex diseases such as cancer. It is of great importance to unravel the complex dependence structure between biological factors, and many conditional dependence tests have been developed to meet this need. The traditional partial correlation method can only capture the linear partial correlation, but not the nonlinear correlation. To overcome this limitation, we propose to use the innovative conditional distance correlation (CDC), which measures the conditional dependence between random vectors and detect nonlinear relations. In …
Investigating Chitosan Modified With Triethylammonium Butanamide And Triethylphosphonium Butanamide As Non-Viral Gene Delivery Vectors By Examining Cytotoxicity And Transfection Efficiency, Deborah C. Ehie
Graduate Theses/Dissertations
Gene therapy is a very challenging field, especially with new emerging genetic disorders. Chitosan (CS), due to chitosan’s flexibility, biocompatibility, and biodegradability, has been of interest in the world of gene therapy especially as researchers are gravitating towards non-viral vectors due to the problems caused by viral vectors. Nevertheless, there are still issues regarding solubility, cellular uptake of cargos being transported in vitro or in vivo, increased cytotoxicity levels, as well as many other things that prevent chitosan from being an efficient gene delivery agent. Here I present five derivatives of chitosan, which were all modified with either triethylphosphonium …
Size-Dependent Inhibitory Effects Of Antibiotic Nanocarriers On Filamentation Of E. Coli, Preeyaporn Songkiatisak, Feng Ding, Pavan Kumar Cherukuri, Xiao-Hong Nancy Xu
Size-Dependent Inhibitory Effects Of Antibiotic Nanocarriers On Filamentation Of E. Coli, Preeyaporn Songkiatisak, Feng Ding, Pavan Kumar Cherukuri, Xiao-Hong Nancy Xu
Chemistry & Biochemistry Faculty Publications
Multidrug membrane transporters exist in both prokaryotic and eukaryotic cells and cause multidrug resistance (MDR), which results in an urgent need for new and more effective therapeutic agents. In this study, we used three different sized antibiotic nanocarriers to study their mode of action and their size-dependent inhibitory effects against Escherichia coli (E. coli). Antibiotic nanocarriers (AgMUNH–Oflx NPs) with 8.6 × 102, 9.4 × 103 and 6.5 × 105 Oflx molecules per nanoparticle (NP) were prepared by functionalizing Ag NPs (2.4 ± 0.7, 13.0 ± 3.1 and 92.6 ± 4.4 nm) with a monolayer …
9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association
9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association
Annual Postdoctoral Science Symposium Abstracts
The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.
The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.
In Vitro Evaluation Of Ovarian Cancer Tumorigenesis As A Function Of Quinone Oxidoreducatse-1 And Cell Phenotype, Milcah S. Jackson
In Vitro Evaluation Of Ovarian Cancer Tumorigenesis As A Function Of Quinone Oxidoreducatse-1 And Cell Phenotype, Milcah S. Jackson
LSU Doctoral Dissertations
In vitro multicellular spheroids are attractive model systems for assessing genetic and epigenetic changes that occur in diseased tissues. Understanding how such alterations in gene and subsequent protein expression affect disease progression and metastasis, drug resistance, and recurrence is of great interest in cancer research. In this regard, examining expression and activity of proteins, such as those with cytoprotective ability that are overexpressed in cancer cells, in addition to cell phenotype (i.e., stem-like, epithelial, mesenchymal, or mixed), are two ways to evaluate genetic and epigenetic changes. Moreover, determining the impact that cytoprotective proteins and cell phenotype have on tumor formation …
Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker
Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Development of machine learning solutions for prediction of functional and clinical significance of cancer driver genes and mutations are paramount in modern biomedical research and have gained a significant momentum in a recent decade. In this work, we integrate different machine learning approaches, including tree based methods, random forest and gradient boosted tree (GBT) classifiers along with deep convolutional neural networks (CNN) for prediction of cancer driver mutations in the genomic datasets. The feasibility of CNN in using raw nucleotide sequences for classification of cancer driver mutations was initially explored by employing label encoding, one hot encoding, and embedding to …
A Non-Natural Nucleotide Uses A Specific Pocket To Selectively Inhibit Telomerase Activity, Wilnelly Hernandez-Sanchez, Wei Huang, Brian Plucinsky, Nelson Garcia-Vazquez, Nathaniel J. Robinson, William P. Schiemann, Anthony J. Berdis, Emmanuel Skordalakes, Derek J. Taylor
A Non-Natural Nucleotide Uses A Specific Pocket To Selectively Inhibit Telomerase Activity, Wilnelly Hernandez-Sanchez, Wei Huang, Brian Plucinsky, Nelson Garcia-Vazquez, Nathaniel J. Robinson, William P. Schiemann, Anthony J. Berdis, Emmanuel Skordalakes, Derek J. Taylor
Chemistry Faculty Publications
Telomerase, a unique reverse transcriptase that specifically extends the ends of linear chromosomes, is up-regulated in the vast majority of cancer cells. Here, we show that an indole nucleotide analog, 5-methylcarboxyl-indolyl-2′-deoxyriboside 5′-triphosphate (5-MeCITP), functions as an inhibitor of telomerase activity. The crystal structure of 5-MeCITP bound to the Tribolium castaneum telomerase reverse transcriptase reveals an atypical interaction, in which the nucleobase is flipped in the active site. In this orientation, the methoxy group of 5-MeCITP extends out of the canonical active site to interact with a telomerase-specific hydrophobic pocket formed by motifs 1 and 2 in the fingers domain and …
Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan
Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan
COBRA Preprint Series
One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards …