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Warr Steve R C - - 2014
Microbioreactors are increasingly used within animal cell biotechnology to grow mammalian cells for cell line screening and to facilitate process development. Many such devices have been reported in the literature, but only a small number are available commercially. Microbioreactors range in complexity from simple plate-based systems to complex automated parallel ...
Goudar Chetan T - - 2014
Metabolic flux analysis with its ability to quantify cellular metabolism is an attractive tool for accelerating cell line selection, medium optimization, and other bioprocess development activities. In the stoichiometric flux estimation approach, unknown fluxes are determined using intracellular metabolite mass balance expressions and measured extracellular rates. The simplicity of the ...
Wahrheit Judith - - 2014
Sampling and quenching methods for intracellular metabolite analysis in mammalian cells in adherent and suspension culture are described. Quenching of adherent cells is achieved by application of hot air after removal of the supernatant by suction. For suspension cultures, the addition of excess ice-cold saline results in a rapid inactivation ...
Aranibar Nelly - - 2014
Metabolomics has become an important tool for measuring pools of small molecules in mammalian cell cultures expressing therapeutic proteins. NMR spectroscopy has played an important role, largely because it requires minimal sample preparation, does not require chromatographic separation, and is quantitative. The concentrations of large numbers of small molecules in ...
Duarte Tiago M - - 2014
(1)H-Nuclear magnetic resonance ((1)H-NMR) spectroscopy is a powerful technique to analyze the composition of complex mixtures based on the particular proton fingerprint of each molecule. Here we describe a protocol for exometabolome analysis of mammalian cells using this technique, including sample preparation, spectra acquisition, and integration. The potential of this ...
Hattori Koji - - 2014
Microfluidic perfusion culture is a novel technique to culture animal cells in a small-scale microchamber with medium perfusion. Polydimethylsiloxane (PDMS) is the most popular material to fabricate a microfluidic perfusion culture chip. Photolithography and replica molding techniques are generally used for fabrication of a microfluidic perfusion culture chip. Pressure-driven perfusion ...
Eibl Regine - - 2014
Disposable bioreactors have been increasingly implemented over the past ten years. This relates to both R & D and commercial manufacture, in particular, in animal cell-based processes. Among the numerous disposable bioreactors which are available today, wave-mixed bag bioreactors and stirred bioreactors are predominant. Whereas wave-mixed bag bioreactors represent the ...
Martens Dirk E - - 2014
Lab-scale stirred-tank bioreactors (0.2-20 l) are used for fundamental research on animal cells and in process development and troubleshooting for large-scale production. In this chapter, different configurations of bioreactor systems are shortly discussed and setting up these different configurations is described. In addition, online measurement and control of bioreactor parameters ...
Druzinec Damir - - 2014
Modern bioprocesses demand for a careful definition of the critical process parameters (CPPs) already during the early stages of process development in order to ensure high-quality products and satisfactory yields. In this context, online monitoring tools can be applied to recognize unfavorable changes of CPPs during the production processes and ...
Cremer Heike - - 2014
The use of baculoviruses has become a standard approach in many labs for recombinant protein production. In addition to giving a broad and practical overview of the technology, this chapter focuses in particular on two recent developments in the field and how these can be efficiently exploited for protein production: ...
Freitag Ruth - - 2014
The purification of the product, the so-called downstream process (DSP), tends to be one of the most costly aspects of modern bioprocessing, especially in the case of proteins. In such cases, chromatography is still the major tool on all levels of the DSP from the first capture to the final ...
Grein Tanja A - - 2014
Industrial manufacturing of cell culture-derived viruses or virus-like particles for gene therapy or vaccine production are complex multistep processes. In addition to the bioreactor, such processes require a multitude of downstream unit operations for product separation, concentration, or purification. Similarly, before a biopharmaceutical product can enter the market, removal or ...
Aguiar Derek - - 2014
The growing availability of inexpensive high-throughput sequence data is enabling researchers to sequence tumor populations within a single individual at high coverage. But, cancer genome sequence evolution and mutational phenomena like driver mutations and gene fusions are difficult to investigate without first reconstructing tumor haplotype sequences. Haplotype assembly of single ...
Badea Liviu - - 2014
We present a joint analysis method for mutation and gene expression data employing information about proteins that are highly interconnected at the level of protein to protein (pp) interactions, which we apply to the TCGA Acute Myeloid Leukemia (AML) dataset. Given the low incidence of most mutations in virtually all ...
Neto Elias Chaibub - - 2014
Computational efficiency is important for learning algorithms operating in the "large p, small n" setting. In computational biology, the analysis of data sets containing tens of thousands of features ("large p"), but only a few hundred samples ("small n"), is nowadays routine, and regularized regression approaches such as ridge-regression, lasso, ...
Gitter Anthony - - 2014
Advances in experimental techniques resulted in abundant genomic, transcriptomic, epigenomic, and proteomic data that have the potential to reveal critical drivers of human diseases. Complementary algorithmic developments enable researchers to map these data onto protein-protein interaction networks and infer which signaling pathways are perturbed by a disease. Despite this progress, ...
Hu Hao - - 2014
The two-hit model of carcinogenesis provides a valuable framework for understanding the role of DNA repair and tumor suppressor genes in cancer development and progression. Under this model, tumor development can initiate from a single somatic mutation in individuals that inherit an inactivating germline variant. Although the two-hit model can ...
Jang In Sock - - 2014
Large-scale pharmacogenomic screens of cancer cell lines have emerged as an attractive pre-clinical system for identifying tumor genetic subtypes with selective sensitivity to targeted therapeutic strategies. Application of modern machine learning approaches to pharmacogenomic datasets have demonstrated the ability to infer genomic predictors of compound sensitivity. Such modeling approaches entail ...
Morgan Alexander A - - 2014
We propose and discuss a method for doing gene expression meta-analysis (multiple datasets) across multiplex measurement modalities measuring the expression of many genes simultaneously (e.g. microarrays and RNAseq) using external control samples and a method of heterogeneity detection to identify and filter on comparable gene expression measurements. We demonstrate this ...
Blucher Aurora S - - 2014
Repurposing an existing drug for an alternative use is not only a cost effective method of development, but also a faster process due to the drug's previous clinical testing and established pharmokinetic profiles. A potentially rich resource for computational drug repositioning approaches is publically available high throughput screening data, available ...
Brubaker Douglas - - 2014
The revolution in sequencing techniques in the past decade has provided an extensive picture of the molecular mechanisms behind complex diseases such as cancer. The Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Project (CGP) have provided an unprecedented opportunity to examine copy number, gene expression, and mutational information ...
Ng Clara - - 2014
The emergence of multi-drug and extensive drug resistance of microbes to antibiotics poses a great threat to human health. Although drug repurposing is a promising solution for accelerating the drug development process, its application to anti-infectious drug discovery is limited by the scope of existing phenotype-, ligand-, or target-based methods. ...
Yang Fan - - 2014
In silico prediction of unknown drug-target interactions (DTIs) has become a popular tool for drug repositioning and drug development. A key challenge in DTI prediction lies in integrating multiple types of data for accurate DTI prediction. Although recent studies have demonstrated that genomic, chemical and pharmacological data can provide reliable ...
Yera Emmanuel R - - 2014
We present a probabilistic data fusion framework that combines multiple computational approaches for drawing relationships between drugs and targets. The approach has special relevance to identifying surprising unintended biological targets of drugs. Comparisons between molecules are made based on 2D topological structural considerations, based on 3D surface characteristics, and based ...
Darabos Christian - - 2014
With the rapid increase in the quality and quantity of data generated by modern high-throughput sequencing techniques, there has been a need for innovative methods able to convert this tremendous amount of data into more accessible forms. Networks have been a corner stone of this movement, as they are an ...
Hall Molly A - - 2014
Environment-wide association studies (EWAS) provide a way to uncover the environmental mechanisms involved in complex traits in a high-throughput manner. Genome-wide association studies have led to the discovery of genetic variants associated with many common diseases but do not take into account the environmental component of complex phenotypes. This EWAS ...
Williams Sarah R - - 2014
This article reviews important literature on the FAST and E-FAST examinations in adults. It also reviews key pitfalls, limitations, and controversies. A practical "how-to" guide is presented. Lastly, new frontiers are explored.
Wu Teresa S - - 2014
Critically ill patients require rapid, accurate assessments and appropriate therapeutic interventions to maximize their chances of recovery. Often the cause of a patient's decompensation is not readily apparent based solely on history and physical examination findings. The Concentrated Overview of Resuscitative Efforts (CORE scan) is a compilation of targeted bedside ...
Mulholland R Stephen - - 2014
This article reviews the broad range of effective options for the nonexcisional rejuvenation of the neck. It discusses the relevant noninvasive anatomy of the neck, classification of the procedural options for the aesthetic cervical physician, and specific anatomic management strategies for each category of cosmetic cervical therapy. This article is ...
Parikh Ankur P - - 2014
Simultaneously reverse engineering a collection of condition-specific gene networks from gene expression microarray data to uncover dynamic mechanisms is a key challenge in systems biology. However, existing methods for this task are very sensitive to variations in the size of the microarray samples across different biological conditions (which we term ...
Perina Alessandro - - 2014
The immune system gathers evidence of the execution of various molecular processes, both foreign and the cells' own, as time- and space-varying sets of epitopes, small linear or conformational segments of the proteins involved in these processes. Epitopes do not have any obvious ordering in this scheme: The immune system ...
Zhe Shandian - - 2014
A key step for Alzheimer's disease (AD) study is to identify associations between genetic variations and intermediate phenotypes (e.g., brain structures). At the same time, it is crucial to develop a noninvasive means for AD diagnosis. Although these two tasks-association discovery and disease diagnosis-have been treated separately by a variety ...
Clark Wyatt T - - 2014
We propose a new kernel-based method for the classification of protein sequences and structures. We first represent each protein as a set of time series data using several structural, physicochemical, and predicted properties such as a sequence of consecutive dihedral angles, hydrophobicity indices, or predictions of disordered regions. A kernel ...
Funk Christopher S - - 2014
Identifying genetic variants that affect drug response or play a role in disease is an important task for clinicians and researchers. Before individual variants can be explored efficiently for effect on drug response or disease relationships, specific candidate genes must be identified. While many methods rank candidate genes through the ...
Malinowski Jennifer - - 2014
Electronic medical records (EMRs) are becoming more widely implemented following directives from the federal government and incentives for supplemental reimbursements for Medicare and Medicaid claims. Replete with rich phenotypic data, EMRs offer a unique opportunity for clinicians and researchers to identify potential research cohorts and perform epidemiologic studies. Notable limitations ...
Vembu Shankar - - 2014
Label propagation methods are extremely well-suited for a variety of biomedical prediction tasks based on network data. However, these algorithms cannot be used to integrate feature-based data sources with networks. We propose an efficient learning algorithm to integrate these two types of heterogeneous data sources to perform binary prediction tasks ...
Ito Kenichiro - - 2014
Site-selective scission of genomes is quite important for future biotechnology. However, naturally occurring restriction enzymes cut these huge DNAs at too many sites and cannot be used for this purpose. Recently, we have developed a completely chemistry-based artificial restriction DNA cutter (ARCUT) by combining a pair of pseudo-complementary PNA (pcPNA) ...
Stacey Glyn N - - 2014
The history of the culture of animal cell lines is littered with published and much unpublished experience with cell lines that have become switched, mislabelled, or cross-contaminated during laboratory handling. To deliver valid and good quality research and to avoid waste of time and resources on such rogue lines, it ...
Costa Ana Rita - - 2014
Fed-batch processes are a current preference for the production of recombinant proteins in mammalian cells. The use of nutrient feeding prevents the depletion of important medium components and results in improved culture longevity and high cell and product yields. To take maximum advantage of these effects, it is important to ...
Butler Michael - - 2014
The accurate determination of cell growth and viability is pivotal to monitoring a bioprocess. Direct methods to determine the cell growth and/or viability in a bioprocess include microscopic counting, electronic particle counting, image analysis, in situ biomass monitoring, and dieletrophoretic cytometry. These methods work most simply when a fixed volume ...
Babitzky Alexander - - 2014
This protocol regards a microscopic application and software for image-guided monitoring of mammalian cells which grow in suspension cultures. It has been developed in order to establish an automated microscopic application for in situ and at-line cell monitoring in bioreactors (Akin et al., Biosens Bioelectron 26:4532-4537, 2011; Babitzky et al., ...
Frahm Björn - - 2014
For the production of biopharmaceuticals a seed train is required to generate an adequate number of cells for inoculation of the production bioreactor. This seed train is time- and cost-intensive but offers potential for optimization. A method and a protocol are described for the seed train mapping, directed modeling without ...
Genzel Yvonne - - 2014
The production of viral vaccines in cell culture can be accomplished with primary, diploid, or continuous (transformed) cell lines. Each cell line, each virus type, and each vaccine preparation require the specific design of upstream and downstream processing. Media have to be selected as well as production vessels, cultivation conditions, ...
Mayba Oleg - - 2014
Cancer cells derived from different stages of tumor progression may exhibit distinct biological properties, as exemplified by the paired lung cancer cell lines H1993 and H2073. While H1993 was derived from chemo-naive metastasized tumor, H2073 originated from the chemo-resistant primary tumor from the same patient and exhibits strikingly different drug ...
Min Martin Renqiang - - 2014
Disrupted or abnormal biological processes responsible for cancers often quantitatively manifest as disrupted additive and multiplicative interactions of gene/protein expressions correlating with cancer progression. However, the examination of all possible combinatorial interactions between gene features in most case-control studies with limited training data is computationally infeasible. In this paper, we ...
Zhu Qian - - 2014
Computational drug repositioning leverages computational technology and high volume of biomedical data to identify new indications for existing drugs. Since it does not require costly experiments that have a high risk of failure, it has attracted increasing interest from diverse fields such as biomedical, pharmaceutical, and informatics areas. In this ...
Desantis Stacia M - - 2014
Determining the effectiveness of different treatments from observational data, which are characterized by imbalance between groups due to lack of randomization, is challenging. Propensity matching is often used to rectify imbalances among prognostic variables. However, there are no guidelines on how appropriately to analyze group matched data when the outcome ...
Feldman Greg - - 2014
Distress tolerance (DT) is a proposed transdiagnostic factor in psychopathology, yet sources of individual differences in DT are largely unknown. The present study examined mindfulness and rumination facets as predictors of persistence on a standardized DT task (mirror tracing). Acting with awareness (a facet of mindfulness) and reflection (a potentially ...
Sadrozinski Hartmut F-W - - 2013
Selected particle detectors are described which find an application in medicine and have been the topic of presentations at the 2013 Vienna Conference of Instrumentation (VCI).
Bookstaver P Brandon - - 2013
Published stability and compatibility data on a growing array of solutions used for antimicrobial lock therapy (ALT) are reviewed. ALT involves the instillation of a highly concentrated antimicrobial, often in combination with an anticoagulant, into a central venous catheter (CVC) lumen; this technique is often used for prophylaxis after CVC ...
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