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Friday, November 28, 2014
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High Content Analysis of Neural Stem Cell Expansion and Differentiation
Oksana Sirenko, Allan C. Powe, Steven L. Stice, Karen Cook, Nick Callamaras, Jayne Hesley, Xin Jiang and Evan F. Cromwell

Automated assay methods for monitoring neural stem cell expansion and differentiation using stem cell derived neural cell lines and high content imaging systems have been described.

High-Throughput Campaign to Identify Reversible Small Molecule Inhibitors of p97
Kelin Li, Tsui-Fen Chou, Kevin Frankowski, Brian E. Nordinc, Patrick Porubsky, Mathew P. Patricellic, Han-Jie Zhou, Sam Gerritz, Raymond J. Deshaies, Jeffrey Aubé, Frank J. Schoenen*

The AAA ATPase p97 is a critical factor in maintaining protein homeostasis in eukaryotic cells. Two probe compounds ML240 and ML241 were developed that both inhibit p97 ATPase activity with an IC50 of approximately 100 nM, and block degradation of p97-dependent proteasome substrate with an IC50 of approximately 900 nM and 3500 nM, respectively. They specifically targeted p97, exhibited markedly different potencies for activating executioner caspases and blocking cell growth.

Using the Promega GloSensor™ cAMP technology on the FLIPR® Tetra system for live cell Gi- and Gs- coupled GPCR second messenger assays
J. Pschorr, S. Lydford, C. Crittenden and Y.-W. Chen

Detection of Gs- and Gi-coupled GPCR second messenger signal activity has been traditionally accomplished using endpoint assays such as radioactive binding or cAMP assays that require cell lysis. This poster demonstrates the use of the modified luminescent firefly luciferase-based Promega GloSensor™ cAMP Assay on the FLIPR® Tetra system to enable detection of cAMP mediated Gs- and Gi-coupled GPCR activity in a true kinetic assay.

Neurotoxicity Assays Using iPSC-Derived Neurons and High Content Imaging
Oksana Sirenko, Susan DeLaura, Lucas Chase, Jayne Hesley and Evan F. Cromwell

Neurotoxicity can cause temporary or permanent damage of brain or peripheral nervous system and has been found to be a major cause of neurodegenerative diseases such as Alzheimer’s or Parkinson’s. Accordingly, there is a great interest in developing more predictive, disease relevant cell-based models and efficient screening tools for assessing the neurotoxicity of chemical compounds, drug candidates and environmental agents.

SpectraMax® Microplate Readers: A complete solution for Transcreener® assays
Cathleen Salono, Caroline Cardonnel, Kasia Proctor and Cathy Olsen

Transcreener® ADP2 Assays are homogenous assays with fluorescent readouts that enable the detection and screening of established drug targets including protein and lipid kinases, as well as emerging targets such as carbohydrate kinases, triphosphatases, heat shock proteins and other ATPases.

Live Cell Beating Assay Using Human iPSC-derived Cardiomyocytes for Evaluation of Drug Efficacy and Toxicity
Oksana Sirenko, Carole Crittenden, Blake Anson, Jayne Hesley, Yen-Wen Chen, Nick Callamaras and Evan F. Cromwell

A large percentage of new drugs fail in clinical studies due to cardiac toxicity. Development of highly predictive in vitro assays suitable for screening, safety assessment or other environments is therefore extremely important for drug development. Human cardiomyocytes derived from stem cell sources can greatly accelerate the discovery of cardiac drugs and improve drug safety by offering more clinically relevant cell-based models than those presently available.

Identification of novel autoantigensin patients with liver autoimmune diseases by Protein MicroArray
C. Zingaretti1, M. Arigò1, A. Cardaci1, A. Sinisi1, L. Muratori3, P. Colombatto4, F. Bonino2, P. Invernizzi5, , A.L. Zignego6 MC. Crosti1, M. Moro1, J. Geginat1, Pagani M.1, R. De Francesco1, S. Abrignani1. & M. Bombaci1

The characterization of autoimmune disease-specific biomarkers are of primary importance for the development of diagnostic tools and the comprehension of pathogenetic mechanisms leading to autoimmunity. To this aim a protein microarray was employed to analyze serum samples from patients with autoimmune hepatitis (e.g. AIH & PBC) and of healthy as controls. A panel of autoantigens able to discriminate among the groups of patients was identified for potential use as biomarkers.

Attempts of facilitated DelF508-CFTR trafficking to the plasma membrane
Sergey Shityakov, Massimo Micaroni, Alexander A. Mironov, Alberto Luini

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the CF transmembrane conductance regulator protein (CFTR), a cAMP-regulated chloride channel. One of the most common CFTR mutations is the deletion of phenylalanine in 508 position (DelF508-CFTR). This mutation induces small conformational change hence the CFTR trafficking is no more effective. The main idea is to find a molecule to facilitate the DelF508-CFTR trafficking to the plasma membrane.

Production of Naturally Compressed Screening Arrays
Steven A Trim.

Animal venoms and toxins are a rich source of novel biologics with several making the progression from tool to therapeutic such as FDA approved Integrilintm (Eptifibatide) (Millennium pharmaceuticals)1 derived from Rattlesnake venom for unstable angina.

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Scientific News
Two Studies Identify A Detectable, Pre-Cancerous State In The Blood
Findings pave way for new lines of cancer research focused on detection and prevention.
Antibiotic Resistance Threatens Future of Modern Medicine
Overuse and misuse of antibiotics, one of the key contributors to antimicrobial resistance (AMR).
Powerful Method To Speed Cancer Drug Discovery Unveiled
The new method lets researchers identify weak and previously undetectable interactions between proteins inside living cells.
Translating Research: New Drugs from Fish Oil Could Aid Artery Repair
Every year, more than a half-million Americans undergo procedures to have a narrowed coronary artery propped open with a small metal mesh tube, or stent.
Direct Drug Screening Of Biopsies Could Overcome Resistance
Combining genetic with pharmacologic screening of tumors may enable truly individualized treatment regimens.
Almac Announces Launch of CLIA Validated Next Generation Sequencing Assay
P53 considered important biomarker for cancer drug discovery.
Next-Gen Melanoma Drug Excels in Lab Tests
Anti-cancer activity was reported in 10 out of 11 patient tumor samples grown in mice and treated with the experimental drug TAK-733.
Blood Test Could Reduce Antibiotic Use
A new blood biomarker test that indicates whether bacteria is the cause of a patient’s lung infection is now being studied at UPMC Presbyterian.
New Targets and Test to Develop Treatments for Memory Disorders
The study focuses on kinesin, a molecular motor protein that plays a role in the transport of other proteins throughout a cell.
Drugging the Undruggable
Discovery opens up possibility of slowing cancer spread.
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