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Real-Time Interactive Simulation Of Human Atrial Electrical Activity On Realistic 3d Atrial Structures Using Webgl, Abouzar Kaboudian, Yanyan Ji, Elizabeth Cherry, Flavio H. Fenton 2019 Georgia Institute of Technology

Real-Time Interactive Simulation Of Human Atrial Electrical Activity On Realistic 3d Atrial Structures Using Webgl, Abouzar Kaboudian, Yanyan Ji, Elizabeth Cherry, Flavio H. Fenton

Biology and Medicine Through Mathematics Conference

No abstract provided.


Synthesis And Antiproliferative Activities Of Conjugates Of Paclitaxel And Camptothecin With A Cyclic Cell-Penetrating Peptide, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Shang Eun Park, Keykavous Parang, Rakesh Tiwari 2019 Chapman University

Synthesis And Antiproliferative Activities Of Conjugates Of Paclitaxel And Camptothecin With A Cyclic Cell-Penetrating Peptide, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Shang Eun Park, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Cell-penetrating peptide [WR]5 has been previously shown to be an efficient molecular transporter for various hydrophilic and hydrophobic molecules. The peptide was synthesized using Fmoc/tBu solid-phase chemistry, and one arginine was replaced with one lysine to enable the conjugation with the anticancer drugs. Paclitaxel (PTX) was functionalized with an esterification reaction at the C20 hydroxyl group of PTX with glutaric anhydride and conjugated with the cyclic peptide [W(WR)4K(bAla)] in DMF to obtain the peptide-drug conjugate PTX1. Furthermore, camptothecin (CPT) was modified at the C(20)-hydroxyl group through the reaction with triphosgene. Then, it was ...


Coming Together To Define Membrane Contact Sites., Luca Scorrano, Maria Antonietta De Matteis, Scott Emr, Francesca Giordano, György Hajnóczky, Benoît Kornmann, Laura L. Lackner, Tim P. Levine, Luca Pellegrini, Karin Reinisch, Rosario Rizzuto, Thomas Simmen, Harald Stenmark, Christian Ungermann, Maya Schuldiner 2019 University of Padua

Coming Together To Define Membrane Contact Sites., Luca Scorrano, Maria Antonietta De Matteis, Scott Emr, Francesca Giordano, György Hajnóczky, Benoît Kornmann, Laura L. Lackner, Tim P. Levine, Luca Pellegrini, Karin Reinisch, Rosario Rizzuto, Thomas Simmen, Harald Stenmark, Christian Ungermann, Maya Schuldiner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Close proximities between organelles have been described for decades. However, only recently a specific field dealing with organelle communication at membrane contact sites has gained wide acceptance, attracting scientists from multiple areas of cell biology. The diversity of approaches warrants a unified vocabulary for the field. Such definitions would facilitate laying the foundations of this field, streamlining communication and resolving semantic controversies. This opinion, written by a panel of experts in the field, aims to provide this burgeoning area with guidelines for the experimental definition and analysis of contact sites. It also includes suggestions on how to operationally and tractably ...


Amphiphilic Polyanhydride-Based Recombinant Muc4Β-Nanovaccine Activates Dendritic Cells, Kasturi Banerjee, Shailendra K. Gautam, Prakash Kshirsagar, Kathleen A. Ross, Gaelle Spagnol, Paul Sorgen, Michael J. Wannemeuhler, Balaji Narasimhan, Joyce C. Solheim, Sushil Kumar, Surinder K. Batra, Maneesh Jain 2019 University of Nebraska Medical Center

Amphiphilic Polyanhydride-Based Recombinant Muc4Β-Nanovaccine Activates Dendritic Cells, Kasturi Banerjee, Shailendra K. Gautam, Prakash Kshirsagar, Kathleen A. Ross, Gaelle Spagnol, Paul Sorgen, Michael J. Wannemeuhler, Balaji Narasimhan, Joyce C. Solheim, Sushil Kumar, Surinder K. Batra, Maneesh Jain

Chemical and Biological Engineering Publications

Mucin 4 (MUC4) is a high molecular weight glycoprotein that is differentially overexpressed in pancreatic cancer (PC), functionally contributes to disease progression, and correlates with poor survival. Further, due to its aberrant glycosylation and extensive splicing, MUC4 is a potential target for cancer immunotherapy. Our previous studies have demonstrated the utility of amphiphilic polyanhydride nanoparticles as a useful platform for the development of protein-based prophylactic and therapeutic vaccines. In the present study, we encapsulated purified recombinant human MUC4-beta (MUC4β) protein in polyanhydride (20:80 CPTEG:CPH) nanoparticles (MUC4β-nanovaccine) and evaluated its ability to activate dendritic cells and induce adaptive immunity ...


Dynamic Molecular Changes During The First Week Of Human Life Follow A Robust Developmental Trajectory., Amy H. Lee, Casey P. Shannon, Nelly Amenyogbe, Tue B. Bennike, Joann Diray-Arce, Olubukola T. Idoko, Erin E. Gill, Rym Ben-Othman, William S. Pomat, Simon D. van Haren, Kim-Anh Lê Cao, Momoudou Cox, Alansana Darboe, Reza Falsafi, Davide Ferrari, Daniel J. Harbeson, Daniel He, Cai Bing, Samuel J. Hinshaw, Jorjoh Ndure, Jainaba Njie-Jobe, Matthew A. Pettengill, Peter C. Richmond, Rebecca Ford, Gerard Saleu, Geraldine Masiria, John Paul Matlam, Wendy Kirarock, Elishia Roberts, Mehrnoush Malek, Guzmán Sanchez-Schmitz, Amrit Singh, Asimenia Angelidou, Kinga K. Smolen, Diana Vo, Ken Kraft, Kerry McEnaney, Sofia Vignolo, Arnaud Marchant, Ryan R. Brinkman, Al Ozonoff, Robert E.W. Hancock, Anita H.J. van den Biggelaar, Hanno Steen, Scott J. Tebbutt, Beate Kampmann, Ofer Levy, Tobias R. Kollmann 2019 University of British Columbia

Dynamic Molecular Changes During The First Week Of Human Life Follow A Robust Developmental Trajectory., Amy H. Lee, Casey P. Shannon, Nelly Amenyogbe, Tue B. Bennike, Joann Diray-Arce, Olubukola T. Idoko, Erin E. Gill, Rym Ben-Othman, William S. Pomat, Simon D. Van Haren, Kim-Anh Lê Cao, Momoudou Cox, Alansana Darboe, Reza Falsafi, Davide Ferrari, Daniel J. Harbeson, Daniel He, Cai Bing, Samuel J. Hinshaw, Jorjoh Ndure, Jainaba Njie-Jobe, Matthew A. Pettengill, Peter C. Richmond, Rebecca Ford, Gerard Saleu, Geraldine Masiria, John Paul Matlam, Wendy Kirarock, Elishia Roberts, Mehrnoush Malek, Guzmán Sanchez-Schmitz, Amrit Singh, Asimenia Angelidou, Kinga K. Smolen, Diana Vo, Ken Kraft, Kerry Mcenaney, Sofia Vignolo, Arnaud Marchant, Ryan R. Brinkman, Al Ozonoff, Robert E.W. Hancock, Anita H.J. Van Den Biggelaar, Hanno Steen, Scott J. Tebbutt, Beate Kampmann, Ofer Levy, Tobias R. Kollmann

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Systems biology can unravel complex biology but has not been extensively applied to human newborns, a group highly vulnerable to a wide range of diseases. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data fromblood, a volume readily obtained from newborns. Indexing to baseline and applying innovative integrative computational methods reveals dramatic changes along a remarkably stable developmental trajectory over the first week of life. This is most evident in changes of interferon and complement pathways, as well as neutrophil-associated signaling. Validated across two independent cohorts of newborns from West Africa and Australasia ...


The Purification Of Human Adult Progenitor Cell Types To Promote Angiogenesis, Stephen E. Sherman 2019 The University of Western Ontario

The Purification Of Human Adult Progenitor Cell Types To Promote Angiogenesis, Stephen E. Sherman

Electronic Thesis and Dissertation Repository

Cellular transplantation strategies have aimed to combat critical limb ischemia (CLI) by inducing endogenous blood vessel regeneration. Transplantation of mesenchymal stromal cells (MSC) for CLI has proven safe and well-tolerated but demonstrated only modestly improved clinical outcomes explained in part by a lack of MSC survival and/or potency in ischemic tissues. This thesis focuses on the development of improved transplantation strategies for patients with CLI utilizing purified pro-angiogenic subsets of MSC and endothelial colony forming cells (ECFC) seeded within decellularized adipose tissue (DAT) bioscaffolds. First, I investigated whether purification of bone marrow-derived MSC based on a conserved stem cell ...


Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio 2019 Chapman University

Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

"Advanced therapy medicinal products (ATMPs), including gene therapy, cell therapy, and tissue engineering products, represent a paradigm shift in health care as they have great potential for preventing and treating many diseases (Food and Drug Administration (FDA), 2013). By way of example, only 367 (8.0%) of the 4,603 rare diseases and conditions listed by the NIH Genetic and Rare Diseases Information Center had at least one FDA-approved drug therapy in early 2018. An estimated 3,038 (66.0%) of those rare diseases and conditions are congenital and genetic diseases that could potentially be treated by gene therapy. There ...


Metabolism Reprogramming In Hexavalent Chromium-Induced Human Lung Carcinogenesis, James Tate Fortin Wise 2019 University of Kentucky

Metabolism Reprogramming In Hexavalent Chromium-Induced Human Lung Carcinogenesis, James Tate Fortin Wise

Theses and Dissertations--Pharmacology and Nutritional Sciences

Hexavalent chromium, Cr(VI), is an established human carcinogen that is a worldwide environmental health concern. It is well understood that reactive oxygen species, genomic instability, and DNA damage repair deficiency are important contributors to Cr(VI)-induced carcinogenesis. After decades of research some cancer hallmarks remain understudied for the mechanism of Cr(VI) carcinogenesis. Dysregulated cellular energetics have been established as a hallmark of cancer. Energy pathways that become dysregulated in cancer include mitochondrial respiration, lipogenesis, pentose phosphate pathway, one carbon metabolism, and increased anaerobic glycolysis in the presence of oxygen or ‘Warburg effect’.

To investigate metabolism changes in ...


Investigating The Role Of Endogenous Atf4 Upregulation On Neuronal Glutathione Level, Fatemeh Mirshafiei 2018 The University of Western Ontario

Investigating The Role Of Endogenous Atf4 Upregulation On Neuronal Glutathione Level, Fatemeh Mirshafiei

Electronic Thesis and Dissertation Repository

ATF4 is a transcription factor that is activated in response to integrated stress response (ISR). In neurons specifically, ATF4 has been suggested to act as a pro-apoptotic transcription factor. The expression of ATF4, as well as its downstream gene targets have been implicated in both in vivo and in vitro models of Alzheimer’s and Parkinson’s Disease. However, the mechanism by which ATF4 promotes cell death remains unclear. It was previously shown that overexpression of ATF4 in primary cortical neurons caused a reduction in glutathione levels, resulting in oxidative stress-induced cell death. The aim of this project was to ...


42 - Evaluating Erk Inhibitor Sensitivity In Hras-Mutant Head And Neck Squamous Cell Carcinoma, Da'Jhnae Gambrell-Sanders 2018 Clark Atlanta University

42 - Evaluating Erk Inhibitor Sensitivity In Hras-Mutant Head And Neck Squamous Cell Carcinoma, Da'jhnae Gambrell-Sanders

Georgia Undergraduate Research Conference (GURC)

Head and neck squamous cell carcinoma (HNSCC) is a significant public health problem and the prognosis is very poor. There are limited treatments. RAS is a membrane-associated GTP binding protein that is a well-established driver for cancer progression. One approach to target RAS is to inhibit the activity of its downstream effectors. Of many pathways that is downstream of RAS, a critical pathway in other cancers is the MAPK pathway. Activated RAS binds to RAF which in turns activates MEK1 and MEK2 protein kinases. Ultimately, the MEK1/2 protein kinases phosphorylate ERK1/2 which control critical cell processes. SCH772984 is ...


Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay 2018 Selected Works

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

David Turay, MD

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It ...


Cellular Network Modeling And Single Cell Gene Expression Analysis Reveals Novel Hepatic Stellate Cell Phenotypes Controlling Liver Regeneration Dynamics, Daniel Cook, Sirisha Achanta, Jan B. Hoek, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli 2018 Thomas Jefferson University; University of Delaware

Cellular Network Modeling And Single Cell Gene Expression Analysis Reveals Novel Hepatic Stellate Cell Phenotypes Controlling Liver Regeneration Dynamics, Daniel Cook, Sirisha Achanta, Jan B. Hoek, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Recent results from single cell gene and protein regulation studies are starting to uncover the previously underappreciated fact that individual cells within a population exhibit high variability in the expression of mRNA and proteins (i.e., molecular variability). By combining cellular network modeling, and high-throughput gene expression measurements in single cells, we seek to reconcile the high molecular variability in single cells with the relatively low variability in tissue-scale gene and protein expression and the highly coordinated functional responses of tissues to physiological challenges. In this study, we focus on relating the dynamic changes in distributions of hepatic stellate ...


Reducing O Negative Blood Product Usage In A Tertiary Care Academic Medical Center, Wendy Weiler, Tracy Cook, MMC Blood Bank, Mark Parker, Stephen Tyzik, Suneela Nayak, Ruth Hanselman, Amy Sparks 2018 Maine Medical Center

Reducing O Negative Blood Product Usage In A Tertiary Care Academic Medical Center, Wendy Weiler, Tracy Cook, Mmc Blood Bank, Mark Parker, Stephen Tyzik, Suneela Nayak, Ruth Hanselman, Amy Sparks

Operational Excellence

MANAGEMENT OF O NEGATIVE BLOOD USE

O registered blood cells are the universal donor but it comprises only 7% of the blood supply. As a result, inappropriate use can result in shortages.

At an academic tertiary care medical center, a performance improvement goal was established that O negative blood cells would make up less than 12% of all blood type transfused by the end of their fiscal year.

A root cause analysis established reasons for the use of O negative blood cells. A number of countermeasures were initiated using the plan, do, study, act (PDSA) problem solving model. Using newly ...


Generating Stable Bioluminescent Cell Lines By Retroviral Transduction, Jeffrey Hayashi, Andrew Gunderson, Tomoko Yamazaki, Kayla McCarty, Alejandro Alice, Michael Gough, Kristina Young 2018 University of Portland

Generating Stable Bioluminescent Cell Lines By Retroviral Transduction, Jeffrey Hayashi, Andrew Gunderson, Tomoko Yamazaki, Kayla Mccarty, Alejandro Alice, Michael Gough, Kristina Young

Biology Undergraduate Publications, Presentations and Projects

This project focuses on improving tumor in vivo imaging techniques. It is difficult to accurately in vivo image orthotopic tumors using CT scans alone. Muriglo provides the capability to visualize in vivo bioluminescent signals emanating from intact tissues. We can coregister CT scans captured with the SARRP with luciferase signals captured with the Muriglo and locate tumor isocenters for image-guided radiation. We may then direct radiation to neoplastic tissue while also sparing the maximum amount of healthy tissue. To do this we must genetically engineer cells to express luciferase. We propose a protocol to use a retrovirus to create stable ...


Mir-196b Target Screen Reveals Mechanisms Maintaining Leukemia Stemness With Therapeutic Potential., Sara E. Meyer, David E. Muench, Andrew M. Rogers, Tess J. Newkold, Emily Orr, Eric O'Brien, John P. Perentesis, John G. Doench, Ashish Lal, Patrick J. Morris, Craig J. Thomas, Judy Lieberman, Edwina McGlinn, Bruce J. Aronow, Nathan Salomonis, H. Leighton Grimes 2018 Thomas Jefferson University; Cincinnati Children’s Hospital Medical Center

Mir-196b Target Screen Reveals Mechanisms Maintaining Leukemia Stemness With Therapeutic Potential., Sara E. Meyer, David E. Muench, Andrew M. Rogers, Tess J. Newkold, Emily Orr, Eric O'Brien, John P. Perentesis, John G. Doench, Ashish Lal, Patrick J. Morris, Craig J. Thomas, Judy Lieberman, Edwina Mcglinn, Bruce J. Aronow, Nathan Salomonis, H. Leighton Grimes

Department of Cancer Biology Faculty Papers

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation ...


Rgs10 Shapes The Hemostatic Response To Injury Through Its Differential Effects On Intracellular Signaling By Platelet Agonists., Peisong Ma, Shuchi Gupta, Sara Sampietro, Daniel DeHelian, Valerie Tutwiler, Alan Tang, Timothy J. Stalker, Lawrence F. Brass 2018 Thomas Jefferson University; University of Pennsylvania School of Medicine

Rgs10 Shapes The Hemostatic Response To Injury Through Its Differential Effects On Intracellular Signaling By Platelet Agonists., Peisong Ma, Shuchi Gupta, Sara Sampietro, Daniel Dehelian, Valerie Tutwiler, Alan Tang, Timothy J. Stalker, Lawrence F. Brass

Department of Medicine Faculty Papers

Platelets express ≥2 members of the regulators of G protein signaling (RGS) family. Here, we have focused on the most abundant, RGS10, examining its impact on the hemostatic response in vivo and the mechanisms involved. We have previously shown that the hemostatic thrombi formed in response to penetrating injuries consist of a core of fully activated densely packed platelets overlaid by a shell of less-activated platelets responding to adenosine 5'-diphosphate (ADP) and thromboxane A2 (TxA2). Hemostatic thrombi formed in RGS10-/- mice were larger than in controls, with the increase due to expansion of the shell but not the core ...


The Effect Of Hyperthermia On Liver Cell Viability, Jada Grant 2018 Rockdale Magnet School

The Effect Of Hyperthermia On Liver Cell Viability, Jada Grant

The International Student Science Fair 2018

Hyperthermia is a treatment for liver cancer where the tumor is exposed to a relatively high heat temperature. This process is designed to make the tumor more susceptible to chemotherapy. My thought process was that if hyperthermia can kill cancerous cells, then there will be negative long term effects on the noncancerous cells surrounding the tumor. The project experimented on Kidney cells because the Kidney and Liver both go through the process of filtration. This means that the Kidney cells should give similar results that Liver cells would. Kidney cells were heated at 40 degrees Celsius for time amounts of ...


The Effect Of Hyperthermia On Liver Cell Viability, Jada Grant 2018 Rockdale Magnet School

The Effect Of Hyperthermia On Liver Cell Viability, Jada Grant

The International Student Science Fair 2018

Hyperthermia is a treatment for liver cancer where the tumor is exposed to a relatively high heat temperature. This process is designed to make the tumor more susceptible to chemotherapy. My thought process was that if hyperthermia can kill cancerous cells, then there will be negative long term effects on the noncancerous cells surrounding the tumor. The project experimented on Kidney cells because the Kidney and Liver both go through the process of filtration. This means that the Kidney cells should give similar results that Liver cells would. Kidney cells were heated at 40 degrees Celsius for time amounts of ...


A Humanized Hypertrophic Cardiomyopathy Model To Elucidate Molecular Mechanism In Disease Pathology, Ragavi Vijayakumar, Maxine Hong 2018 NUS High School of Mathematics and Science

A Humanized Hypertrophic Cardiomyopathy Model To Elucidate Molecular Mechanism In Disease Pathology, Ragavi Vijayakumar, Maxine Hong

The International Student Science Fair 2018

Hypertrophic cardiomyopathy (HCM), that clinically manifests as an enlarged heart is a highly prevalent cardiac disorder with propensity towards arrhythmia-induced sudden cardiac death. The mechanism of HCM remains poorly defined, necessitating further understanding of the disease for improved therapeutic strategies. As it is challenging to obtain cardiac biopsies from human subjects, using induced pluripotent stem cells technology, we generated cardiomyocytes (CMs) in a dish from HCM patients. These HCM-CMs presented the clinical manifestation in that they were significantly larger in size in comparison to control (healthy)-CMs. Furthermore, gene expression profiling of cardiac ion channels revealed increased transcripts encoding for ...


Concurrent Regulation Of Lkb1 And Camkk2 In The Activation Of Ampk In Castrate-Resistant Prostate Cancer By A Well-Defined Polyherbal Mixture With Anticancer Properties., Amber F. MacDonald, Ahmed Bettaieb, Dallas R. Donohoe, Dina S. Alani, Anna Han, Yi Zhao, Jay Whelan 2018 University of Tennessee, Knoxville

Concurrent Regulation Of Lkb1 And Camkk2 In The Activation Of Ampk In Castrate-Resistant Prostate Cancer By A Well-Defined Polyherbal Mixture With Anticancer Properties., Amber F. Macdonald, Ahmed Bettaieb, Dallas R. Donohoe, Dina S. Alani, Anna Han, Yi Zhao, Jay Whelan

Department of Cancer Biology Faculty Papers

BACKGROUND: Zyflamend, a blend of herbal extracts, effectively inhibits tumor growth using preclinical models of castrate-resistant prostate cancer mediated in part by 5'-adenosine monophosphate-activated protein kinase (AMPK), a master energy sensor of the cell. Clinically, treatment with Zyflamend and/or metformin (activators of AMPK) had benefits in castrate-resistant prostate cancer patients who no longer responded to treatment. Two predominant upstream kinases are known to activate AMPK: liver kinase B1 (LKB1), a tumor suppressor, and calcium-calmodulin kinase kinase-2 (CaMKK2), a tumor promotor over-expressed in many cancers. The objective was to interrogate how Zyflamend activates AMPK by determining the roles of ...


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