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White Papers

Company	White Paper

Eppendorf	Eppendorf ThermoMixerTM C – Features, Options, Applications Katrin Käppler-Hanno, Eppendorf AG, Hamburg, Germany Executive Summary Primarily used in the field of life sciences, the Eppendorf ThermoMixerTM C is a device for the temperature control and mixing of liquids or samples. The device offers a wide temperature control range (1 °C–100 °C), high flexibility with the use of diverse tube and plate formats and advanced mixing performance with the 2DMix-Control technology and a mixing speed of 3000 rpm. With the new technology condens.protect®, the Eppendorf ThermoTop® prevents condensation on tube lids or plate sealing foils.

SDIX^®	SDIX ^® mAb Discovery Engine SDIX^® has developed an antibody engine (mAb discovery engine) for discovery of antibodies to transmembrane proteins like G-protein coupled receptors (GPCRs). The mAb discovery engine generates panels of diverse antibodies in terms of sequence, somatic hypermutation, epitopes, and performance. The mAb discovery engine is a platform that is capable of routinely generating antibody candidates that are diverse, functional and novel.

Mirus Bio, LLC	From Reprogramming to Differentiation – Transfection Applications for Stem Cell Research Differentiation and reprogramming techniques are imperative in stem cell research and require virus-free applications for biotherapeutic and new drug development. Mirus Bio presents a suite of TransIT® Transfection Reagents and an Ingenio® Electroporation Kit that are high efficiency, low toxicity DNA and RNA delivery solutions validated for a variety of stem cell applications.

Singulex	Application Note: Cardiotoxicity This application note describes the utility of the Erenna Immunoassay System and the Erenna cTnI Assay towards early assessment of cardiotoxicity in rats. Due to its unique highdefinition technology, elevated levels of cTnI in serum can be detected earlier with the Erenna Immunoassay System

Hamilton Company	Rapid, High Throughput Extraction and Purification of Genomic DNA from Whole Blood Using the Akonni TruTip® Extraction System on the Hamilton Microlab® STAR Liquid Handling System Akonni Biosystems has developed the simple and effective ultra-rapid TruTip® automated extraction method designed to isolate genomic DNA from low volumes of whole blood for downstream genetic testing including any type of PCR, sequencing and microarray detection. The tip-based extraction technology is paired with the advanced, proven and reliable Hamilton Microlab STAR liquid handling system for high throughput sample processing.

Applied Photophysics Ltd	Automated Circular Dichroism with Dynamic Multimode Spectroscopy: a powerful tool for establishing conformational stability of cloned proteinsn Abstract The relative stabilities of the 9th-10th type III domain pair of fibronectin (FIII9-10) and two mutants thereof, all of which have immunoglobulin-like beta-sandwich domains, were investigated using dynamic multimode spectroscopy (DMS) with automated circular dichroism (ACD). It is shown that the mutants are significantly more stable than the wild-type, that the folded and unfolded protein conformations for all variants are similar, and that aggregation accompanies unfolding.

Waters	Guidelines for Routine Use and Maintenance of Ultra-Performance Size-Exclusion and Ion-Exchange Chromatography Systems By: Paula Hong and Kenneth J. Fountain To decrease the frequency of system repairs and contamination, a series of steps have been outlined for maintenance and care of a chromatographic system and columns used for the analysis of biomolecules.

AMRI	Evolving Intelligence By Wendy Quinn-Decatur, M.S.I.S., Associate Librarian, AMRI As Contract Research and Contract Manufacturing Organizations (CROs and CMOs) continue to evolve and provide increasingly important contributions to their customer’s discovery and development priorities, implementing a customer-focused approach to corporate library services can turn a repository for dated literature into an invaluable information center for the library’s constituents.

Waters Corp.	Application Note Metabolite Identification Workflows: A Flexible Approach to Data Analysis and Reporting

Gilson, Inc	Analyzing catecholamines and their metabolites in patient urine samples is important for sympathoadrenal system tumor diagnosis. This application note discusses the automation of sample preparation and solid phase extraction (SPE) with the CIinRep Complete Kit (RECIPE Chemicals + Instruments GmbH) using the Gilson ASPECTMXL or GX-274 Liquid Handler. Following SPE, fractions were analyzed via HPLC for analytes VMA, HVA, and 5-HIAA using an electrochemical detection (ECD) method.

Applied Photophysics Ltd	CHIRASCAN SERIES APPLICATION NOTE: Protein Stability by Chemical Denaturation Abstract Automated Circular Dichroism (ACD) was used to determine the thermodynamic stability of a protein by chemical denaturation. ► Incubation of samples ensures equilibrium is reached, eliminating systematic error ► Short path lengths extend the accessible wavelength range ► Automation significantly increases productivity and reduces human error

INDIGO Biosciences, Inc.	Retinoid Receptors: Overview and Tools for Researchers 　 Retinoids are a class of chemical compounds related to vitamin A. The two predominant and most studied retinoids are all-trans retinoic acid (ATRA) (the acid form of vitamin A also known as Tretinoin) and 9-cis-retinoic acid (9-cis RA or Alitretinoin). Retinoids have many important and diverse functions throughout the body, including roles....

Bio-Rad Laboratories	Effect of Conductivity on DBC on CEX Resin In an effort to improve the antibody manufacturing platform, newer cation exchange resins were evaluated in this study. Dynamic binding studies were conducted using 2 different monoclonal antibodies at a stable pH and varying conductivities across nine resins to determine the differences in binding capacity.

Shimadzu Scientific Instruments	The Perfinity Workstation: Automating Mass Spec Sample Preparation This paper presents the Perfinity Workstation, a fully-integrated online protein sample preparation workstation, combining the selectivity of immunoassay approaches with the resolution of HPLC. It utilizes multiple proteomic approaches to rapidly and reproducibly perform affinity selection, buffer exchange, trypsin digestion, desalting of the sample and reverse phase LC analysis. All of these processes enable the generation of purified peptides ready for LC-MS analysis in about 10 minutes, and result in peptide maps of exceptional reproducibility (<10% CVs).

Gilson, Inc	This application note provides a quick comparison of three pharmaceutical compounds using high pressure normal phase and low pressure flash chromatography on the Gilson PLC 2020 Personal Purification System. Comparison of peak shape, peak retention time, chromatography run time, fraction volume, and solvent consumption were all studied to determine the most efficient and optimal chromatography method.

Bio-Rad Laboratories	Composite Profiling of Angiogenic Factors Using Bio-Plex Pro Human Cancer Biomarker Panel 1 The Bio-Plex Pro human cancer biomarker panel 1 is a unique blend of magnetic bead-based multiplex assays designed to meet the needs of the most discerning preclinical and clinical researchers. The multiplex format enables robust and reproducible measurement of 16 soluble proteins involved in disease processes such as: Angiogenesis, Metastasis, Cell proliferation, Cell adhesion/migration, Apoptosis and Inflammation

Applied Photophysics Ltd	Strategies to compare far-UV Circular Dichroism spectra of similar proteins using Chirascan™-plus ACD Circular Dichroism (CD) spectroscopy is an extremely sensitive technique to analyse the conformation of proteins in solution and can be used as a fingerprint of a particular protein structure [Greenfield, 2006]. Due to the very low sample volumes required and the simplicity of the measurement, it is a powerful comparative tool to detect differences in structure between proteins. This paper discusses how Chirascan™-plus ACD presents easy-to-obtain, highly reproducible results while achieving high throughput, previously not available for Circular Dichroism. Using advanced robotics combined with the 96 or 384-well plates, Chirascan™-plus ACD can rapidly prepare many replicates and perform multiple measurements for clear determination of standard deviations.

BIOSEARCH TECHNOLOGIES	Stellaris RNA FISH: Detection, Localization, and Quantification of mRNA at the Cellular Level Presented here is a new method for in situ RNA detection, the Stellaris™ FISH technology, which enables simultaneous detection, localization, and quantification of individual RNA molecules at the cellular level. This technique provides a high degree of specificity and sensitivity, is ideal for applications that analyze transcription site activity, protein- RNA interactions and mRNA translocation events, and holds promise for future diagnostic applications.

InhibOx	Large Custom Databases Unlocking the Potential of your Chemistry Investment Too often, virtual screening has failed to deliver useful results. The data from your past projects is high quality, but may be focused on the wrong area and lack diversity. This new white paper from InhibOx describes how companies can build and rapidly search very large, high quality virtual libraries, starting from their own reagent collections and chemistries, providing a platform for successful virtual screening.

JMP Clinical	A Primer on JMP® Clinical Incidence Screens JMP Clinical has a number of analytical processes (APs) that calculate and compare the incidence of events between two or more treatment groups in a clinical trial. Interventions Incidence Screen enables you to compare the incidence of concomitant medications or substances. AE Incidence Screen enables you to compare the incidence of adverse events. DS/MH Incidence Screen enables you to compare disposition events (e.g., randomization or completion status) or medical history terms (which, technically, is a comparison of prevalence). Finally, AE Resolution Screen enables you to examine the resolution of adverse events. Most of these APs operate in a similar manner. In this white paper, we use AE Incidence Screen with sample data to illustrate the common functionality of these APs. We also point out important differences among the other APs at the end of the example

Lucigen Corporation	Expresso^® Cloning and Protein Expression Systems enable you to effortlessly clone your gene and express protein the next day. PCR amplicons are directly mixed with cloning-ready vectors and competent cells to yield >90% recombinants, with no ligation step. Expression is tightly controlled. The optional SUMO fusion tag increases solubility.

EMD Millipore	The Importance of Being Profiled: Improving Drug Candidate Safety and Efficacy Using Cross-target Profiling Profiling of putative lead compounds against a representative panel of important enzymes, receptors, ion channels and transporters is an excellent way to establish a preliminary view of potential issues that might later hamper development. An early idea of which off-target activities must be minimized can save valuable time and money during the preclinical lead optimization phase if pivotal questions are asked beyond the usual profiling at hERG. The best data for critical evaluation of activity at GPCRs and ion channels is obtained using functional assays, since binding assays cannot detect all interactions and do not provide information on whether the interaction is that of an agonist, antagonist, or allosteric modulator. This overview discusses the benefits of in vitro assays, specific decision points where profiling can be of immediate benefit, and highlights relevant profiling services offered by EMD Millipore.

DiscoveRX	DAWN OF A NEW ERA FOR KINASE DRUG DISCOVERY: KINOME WIDE PROFILING AND SCREENING SOLUTIONS COUPLED TO FUNCTIONAL CELL-BASED ASSAYS ENABLE LAUNCH OF SELECTIVE AND FUNCTIONAL KINASE INHIBITORS

INDIGO Biosciences	Live Cell Multiplex Assay For use in combination with INDIGO’s 3x32-, 2x48-, or 1x96-well format Nuclear Receptor Reporter Assay Systems

SABiosciences, a QIAGEN company	RT2 Profiler™ PCR Arrays Pathway-Focused Gene Expression Profiling with qRT-PCR This paper evaluates the performance of the newest technique for monitoring the expression of a panel of pathway- or disease-specific genes: the RT2 Profiler PCR Array System from SABiosciences. The PCR Array System combines the quantitative performance of SYBRR Green-based real-time PCR with the multiple gene profiling capabilities of a microarray. The PCR Array is a 96- or 384-well plate containing RT2 qPCR Primer Assays for a set of 84 related genes, plus five housekeeping genes, and three controls.

Trevigen, Inc	DNA Repair Deficient Cell Lines- Tools to Study Genomic Instability- White Paper DNA repair proteins maintain the stability of the genome. When repair protein function is impaired through mutations, the genome may become unstable which is a hall mark of solid tumors. Trevigen, Inc. is pleased to announce the availability of nineteen DNA repair gene knockdown cell lines, encompassing the Base Excision Repair pathway. The availability of this panel of target specific LN428 glioblastoma shRNA lentivirus transduced cell lines will permit scientists to study the molecular etiology of tumor genomic instability and to exploit it in oncology research.

DiscoveRX	Propelling GPCR drug Discovery through innovative products Focus: Cutting edge portfolio and how it has led to new learnings

Caliper Life Sciences	Fragment-Based Screening using the LabChip EZ Reader - White Paper Introduction Fragment-based lead discovery is establishing itself as valuable approach for the discovery of novel small molecule leads. It relies on establishing a better understanding of the binding mechanism of a ligand for its binding partner by probing for “hot spots “on the protein target with small molecule fragments (typically <300 Daltons). Its simplicity is in the principle of building a pharmacophore from the ground up. Successful selection requires data on binding affinity as well as extensive SAR information provided by a variety of techniques . . .

Caliper Discovery Alliances & Services	CDAS has created GPCRFunctional™ Label Free service programs to offer more relevant assay development, screening, drug activity and receptor characterization studies in a more physiological cellular context.

Ariadne Genomics	Mechanistic Disease Modeling Developing mechanistic models that can help drive hypotheses and explain disease and its progression is a challenge for drug discovery and development companies. This white paper discusses how an in silico approach to defining punitive disease models can assist researchers in their efforts to find novel drug targets, elucidate drug toxicities and find new indications for existing therapies.

Gilson, Inc	Pipetting Hot and Cold

SABiosciences, a QIAGEN company	PCR Array: A Simple and Quantitative Method for Gene Expression Profiling The RT² Profiler™ PCR Array System is the most reliable and sensitive gene expression profiling technology for analyzing a panel of genes in signal transduction pathways, biological processes, or disease related gene networks. From Sample Preparation to Data Analysis, the PCR Array system employs four components that Guarantee assay performance, yielding high-quality, reproducible, and reliable gene expression data.

Accuri Cytometers, Inc.	The Accuri^® C6 Flow Cytometer^® represents a dramatic step forward in flow cytometry and cell analysis. Now researchers have access to a high-capability analytical cytometer at an affordable price. The benchtop-sized C6 makes a powerful research tool available to a much wider range of life scientists. This article examines a variety of biological applications that take advantage of the C6’s cellular analysis capabilities.

MD Biosciences, Inc	Progressing pipelines withPre-clinical CRO Partnerships. A case study in successful outsourcing to meet objectives in licensing/acquisitions, repositioning/therapeutic expansion and customized applications for screening of NCE/biologics.

Invitrogen by Life Technologies	Measure inhibitor binding to non-activated kinases The LanthaScreen® Eu Kinase Binding Assay is an easy to optimize kinase assay for screening and multiple downstream application. This modular assay format has been validated for use with over 200 kinase targets. In this application note, we present examples of compound affinity comparisons for active and non-active kinase forms, including kinase inhibitors with various binding mechanisms

Accuri Cytometers, Inc.	A Powerful and Cost Effective Solution for Today’s Research Laboratory The Accuri C6 Flow Cytometer^®System represents a dramatic step forward in flow cytometry.

BioTek Instruments, Inc.	Automated Magnetic Bead Washing of Metabolic Hormone Assays Using the ELx405™ Magnetic Bead Washer to Wash MILLIPLEX™ MAP Assays

Invitrogen by Life Technologies	Simple off-rate measurements with the LanthaScreen® Eu Kinase Binding Assay The LanthaScreen® Eu Kinase Binding Assay is an easy to optimize kinase assay for screening and multiple downstream application. This modular assay format has been validated for use with over 200 kinase targets. In this application note, we present a simple for measuring inhibitor off-rates.

SABiosciences	Biomarker Discovery from Paraffin Embedded Samples- Successful Principles for Addressing FFPE-associated Real-time PCR Challenges

R&D Systems, Inc.	Using Proteome Profi ler™ Antibody Macroarrays to Assess Kinase Phosphorylation and Activation

Millipore	Unlocking the Mystery of Cancer: Do the Mutant p110α Subunits of PI3-Kinase Hold the Key?

R&D Systems, Inc.	Using Cell-Based ELISAs to Measure the Levels of Two Proteins Simultaneously in Whole Cells

Trevigen, Inc.	2^nd Generation PARP in vivo Pharmacodynamic Assay: In this article we present information regarding Trevigen’s 2nd Generation PARP Pharmacodynamic Assay. We provide validation data and accelerated shelf life data regarding key assay components for the new assay format which features: a 96 well assay plate pre-coated with PAR capture antibody, extended dynamic range, and high signal to noise ratios.

SANYO Biomedical	Use of Narrow Bandwidth Ultraviolet Light and Copper-Enriched Stainless Steel Construction to Achieve Active Background Contamination Control in a Cell Culture CO₂ Incubator (1.9 MB pdf file)

Caliper Life Sciences	Faster Innovation Cycles from Microfluidics Technology (103kb pdf file)

The Baker Company	Terminology Changes in the 2002 Revision of NSF 49 NSF/ANSI Standard #49 - 2002 Class II Biological Safety Cabinets Types (62kb pdf file)

Back West, Inc. and Jumpstart Biodevelopment	Significant advantage can be gained by organizations utilizing high performing virtual teams working with early stage drug development projects. This paper chronicles the experiences of Dr. Whitehouse and Mr. Smith with such high performing virtual teams in early stage drug development projects and provides lessons to others seeking to deploy similar models.

AstraZeneca LP	Emerging Business and Operational Models In The Pharmaceutical Industry (69KB pdf file)

Adeptia Inc.	Business Process Management (BPM) has emerged as a proven technology that helps companies meet objectives and gain competitive advantage.

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