WorldWideScience

Sample records for cell bioprocessing fundamentals

  1. Stem cell bioprocessing: fundamentals and principles.

    Science.gov (United States)

    Placzek, Mark R; Chung, I-Ming; Macedo, Hugo M; Ismail, Siti; Mortera Blanco, Teresa; Lim, Mayasari; Cha, Jae Min; Fauzi, Iliana; Kang, Yunyi; Yeo, David C L; Ma, Chi Yip Joan; Polak, Julia M; Panoskaltsis, Nicki; Mantalaris, Athanasios

    2009-03-06

    In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing. Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the 'omics' technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation. The timely development, integration and execution of various components will be critical-failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications.

  2. Developing a Continuous Bioprocessing Approach to Stromal Cell Manufacture.

    Science.gov (United States)

    Miotto, Martina; Gouveia, Ricardo; Abidin, Fadhilah Zainal; Figueiredo, Francisco; Connon, Che J

    2017-11-29

    To this day, the concept of continuous bioprocessing has been applied mostly to the manufacture of molecular biologics such as proteins, growth factors, and secondary metabolites with biopharmaceutical uses. The present work now sets to explore the potential application of continuous bioprocess methods to source large numbers of human adherent cells with potential therapeutic value. To this purpose, we developed a smart multifunctional surface coating capable of controlling the attachment, proliferation, and subsequent self-detachment of human corneal stromal cells. This system allowed the maintenance of cell cultures under steady-state growth conditions, where self-detaching cells were continuously replenished by the proliferation of those remaining attached. This facilitated a closed, continuous bioprocessing platform with recovery of approximately 1% of the total adherent cells per hour, a yield rate that was maintained for 1 month. Moreover, both attached and self-detached cells were shown to retain their original phenotype. Together, these results represent the proof-of-concept for a new high-throughput, high-standard, and low-cost biomanufacturing strategy with multiple potentials and important downstream applications.

  3. To Stretch the Boundary of Secondary Metabolite Production in Plant Cell-Based Bioprocessing: Anthocyanin as a Case Study

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2004-01-01

    Full Text Available Plant cells and tissue cultures hold great promise for controlled production of a myriad of useful secondary metabolites on demand. The current yield and productivity cannot fulfill the commercial goal of a plant cell-based bioprocess for the production of most secondary metabolites. In order to stretch the boundary, recent advances, new directions and opportunities in plant cell-based bioprocessing, have been critically examined for the 10 years from 1992 to 2002. A review of the literature indicated that most of the R&D work was devoted predominantly to studies at an empirical level. A rational approach to molecular plant cell bioprocessing based on the fundamental understanding of metabolic pathways and their regulations is urgently required to stimulate further advances; however, the strategies and technical framework are still being developed. It is the aim of this review to take a step forward in framing workable strategies and technologies for molecular plant cell-based bioprocessing. Using anthocyanin biosynthesis as a case study, an integrated postgenomic approach has been proposed. This combines the functional analysis of metabolic pathways for biosynthesis of a particular metabolite from profiling of gene expression and protein expression to metabolic profiling. A global correlation not only can thus be established at the three molecular levels, but also places emphasis on the interactions between primary metabolism and secondary metabolism; between competing and/or complimentary pathways; and between biosynthetic and post-biosynthetic events.

  4. Establishing new microbial cell factories for sustainable bioprocesses

    DEFF Research Database (Denmark)

    Workman, Mhairi; Holt, Philippe; Liu, Xiaoying

    2012-01-01

    . The application of biological catalysts which can convert a variety of substrates to an array of desirable products has been demonstrated in both ancient bioprocesses and modern industrial biotechnology. In recent times, focus has been on a limited number of “model” organisms which have been extensively exploited...... of products, it may be interesting to look to less domesticated strains and towards more non-conventional hosts in the development of new bioprocesses. This approach demands thorough physiological characterization as well as establishment of tools for genetic engineering if new cell factories......The demands of modern society are increasing pressure on natural resources while creating the need for a wider range of products. There is an interest in developing bioprocesses to meet these demands, with conversion of a variety of waste materials providing the basis for a sustainable society...

  5. Efficient and reproducible mammalian cell bioprocesses without probes and controllers?

    Science.gov (United States)

    Tissot, Stéphanie; Oberbek, Agata; Reclari, Martino; Dreyer, Matthieu; Hacker, David L; Baldi, Lucia; Farhat, Mohamed; Wurm, Florian M

    2011-07-01

    Bioprocesses for recombinant protein production with mammalian cells are typically controlled for several physicochemical parameters including the pH and dissolved oxygen concentration (DO) of the culture medium. Here we studied whether these controls are necessary for efficient and reproducible bioprocesses in an orbitally shaken bioreactor (OSR). Mixing, gas transfer, and volumetric power consumption (P(V)) were determined in both a 5-L OSR and a 3-L stirred-tank bioreactor (STR). The two cultivation systems had a similar mixing intensity, but the STR had a lower volumetric mass transfer coefficient of oxygen (k(L)a) and a higher P(V) than the OSR. Recombinant CHO cell lines expressing either tumor necrosis factor receptor as an Fc fusion protein (TNFR:Fc) or an anti-RhesusD monoclonal antibody were cultivated in the two systems. The 5-L OSR was operated in an incubator shaker with 5% CO(2) in the gas environment but without pH and DO control whereas the STR was operated with or without pH and DO control. Higher cell densities and recombinant protein titers were obtained in the OSR as compared to both the controlled and the non-controlled STRs. To test the reproducibility of a bioprocess in a non-controlled OSR, the two CHO cell lines were each cultivated in parallel in six 5-L OSRs. Similar cell densities, cell viabilities, and recombinant protein titers along with similar pH and DO profiles were achieved in each group of replicates. Our study demonstrated that bioprocesses can be performed in OSRs without pH or DO control in a highly reproducible manner, at least at the scale of operation studied here. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Cell bioprocessing in space - Applications of analytical cytology

    Science.gov (United States)

    Todd, P.; Hymer, W. C.; Goolsby, C. L.; Hatfield, J. M.; Morrison, D. R.

    1988-01-01

    Cell bioprocessing experiments in space are reviewed and the development of on-board cell analytical cytology techniques that can serve such experiments is discussed. Methods and results of experiments involving the cultivation and separation of eukaryotic cells in space are presented. It is suggested that an advanced cytometer should be developed for the quantitative analysis of large numbers of specimens of suspended eukaryotic cells and bioparticles in experiments on the Space Station.

  7. Bioprocessing research for energy applications

    Energy Technology Data Exchange (ETDEWEB)

    Scott, C.D.; Gaden, E.L. Jr.; Humphrey, A.E.; Carta, G.; Kirwan, D.J.

    1989-04-01

    The new biotechnology that is emerging could have a major impact on many of the industries important to our country, especially those associated with energy production and conservation. Advances in bioprocessing systems will provide important alternatives for the future utilization of various energy resources and for the control of environmental hazards that can result from energy generation. Although research in the fundamental biological sciences has helped set the scene for a ''new biotechnology,'' the major impediment to rapid commercialization for energy applications is the lack of a firm understanding of the necessary engineering concepts. Engineering research is now the essential ''bridge'' that will allow the development of a wide range of energy-related bioprocessing systems. A workshop entitled ''Bioprocessing Research for Energy Applications'' was held to address this technological area, to define the engineering research needs, and to identify those opportunities which would encourage rapid implementation of advanced bioprocessing concepts.

  8. Bioprocessing automation in cell therapy manufacturing: Outcomes of special interest group automation workshop.

    Science.gov (United States)

    Ball, Oliver; Robinson, Sarah; Bure, Kim; Brindley, David A; Mccall, David

    2018-04-01

    Phacilitate held a Special Interest Group workshop event in Edinburgh, UK, in May 2017. The event brought together leading stakeholders in the cell therapy bioprocessing field to identify present and future challenges and propose potential solutions to automation in cell therapy bioprocessing. Here, we review and summarize discussions from the event. Deep biological understanding of a product, its mechanism of action and indication pathogenesis underpin many factors relating to bioprocessing and automation. To fully exploit the opportunities of bioprocess automation, therapeutics developers must closely consider whether an automation strategy is applicable, how to design an 'automatable' bioprocess and how to implement process modifications with minimal disruption. Major decisions around bioprocess automation strategy should involve all relevant stakeholders; communication between technical and business strategy decision-makers is of particular importance. Developers should leverage automation to implement in-process testing, in turn applicable to process optimization, quality assurance (QA)/ quality control (QC), batch failure control, adaptive manufacturing and regulatory demands, but a lack of precedent and technical opportunities can complicate such efforts. Sparse standardization across product characterization, hardware components and software platforms is perceived to complicate efforts to implement automation. The use of advanced algorithmic approaches such as machine learning may have application to bioprocess and supply chain optimization. Automation can substantially de-risk the wider supply chain, including tracking and traceability, cryopreservation and thawing and logistics. The regulatory implications of automation are currently unclear because few hardware options exist and novel solutions require case-by-case validation, but automation can present attractive regulatory incentives. Copyright © 2018 International Society for Cellular Therapy

  9. Origins of Cell-to-Cell Bioprocessing Diversity and Implications of the Extracellular Environment Revealed at the Single-Cell Level.

    Science.gov (United States)

    Vasdekis, A E; Silverman, A M; Stephanopoulos, G

    2015-12-14

    Bioprocess limitations imposed by microbial cell-to-cell phenotypic diversity remain poorly understood. To address this, we investigated the origins of such culture diversity during lipid production and assessed the impact of the fermentation microenvironment. We measured the single-cell lipid production dynamics in a time-invariant microfluidic environment and discovered that production is not monotonic, but rather sporadic with time. To characterize this, we introduce bioprocessing noise and identify its epigenetic origins. We linked such intracellular production fluctuations with cell-to-cell productivity diversity in culture. This unmasked the phenotypic diversity amplification by the culture microenvironment, a critical parameter in strain engineering as well as metabolic disease treatment.

  10. Control of Bioprocesses

    DEFF Research Database (Denmark)

    Huusom, Jakob Kjøbsted

    2015-01-01

    The purpose of bioprocess control is to ensure that the plant operates as designed. This chapter presents the fundamental principles for control of biochemical processes. Through examples, the selection of manipulated and controlled variables in the classical reactor configurations is discussed, so...... are control objectives and the challenges in obtaining good control of the bioreactor. The objective of this chapter is to discuss the bioreactor control problems and to highlight some general traits that distinguish operation of bioprocesses from operation of processes in the conventional chemical process...... industries. It also provides a number of typical control loops for different objectives. A brief introduction to the general principles of process control, the PID control algorithm is discussed, and the design and effect of tuning are shown in an example. Finally, a discussion of novel, model-free control...

  11. Miniature Bioprocess Array: A Platform for Quantitative Physiology and Bioprocess Optimization

    National Research Council Canada - National Science Library

    Keasling, Jay

    2002-01-01

    .... The miniature bioprocess array is based on an array of 150-microliters wells, each one of which incorporates MEMS for the closed-loop control of cell culture parameters such as temperature, pH, and dissolved oxygen...

  12. Application of Raman Spectroscopy and Univariate Modelling As a Process Analytical Technology for Cell Therapy Bioprocessing

    Science.gov (United States)

    Baradez, Marc-Olivier; Biziato, Daniela; Hassan, Enas; Marshall, Damian

    2018-01-01

    Cell therapies offer unquestionable promises for the treatment, and in some cases even the cure, of complex diseases. As we start to see more of these therapies gaining market authorization, attention is turning to the bioprocesses used for their manufacture, in particular the challenge of gaining higher levels of process control to help regulate cell behavior, manage process variability, and deliver product of a consistent quality. Many processes already incorporate the measurement of key markers such as nutrient consumption, metabolite production, and cell concentration, but these are often performed off-line and only at set time points in the process. Having the ability to monitor these markers in real-time using in-line sensors would offer significant advantages, allowing faster decision-making and a finer level of process control. In this study, we use Raman spectroscopy as an in-line optical sensor for bioprocess monitoring of an autologous T-cell immunotherapy model produced in a stirred tank bioreactor system. Using reference datasets generated on a standard bioanalyzer, we develop chemometric models from the Raman spectra for glucose, glutamine, lactate, and ammonia. These chemometric models can accurately monitor donor-specific increases in nutrient consumption and metabolite production as the primary T-cell transition from a recovery phase and begin proliferating. Using a univariate modeling approach, we then show how changes in peak intensity within the Raman spectra can be correlated with cell concentration and viability. These models, which act as surrogate markers, can be used to monitor cell behavior including cell proliferation rates, proliferative capacity, and transition of the cells to a quiescent phenotype. Finally, using the univariate models, we also demonstrate how Raman spectroscopy can be applied for real-time monitoring. The ability to measure these key parameters using an in-line Raman optical sensor makes it possible to have immediate

  13. Application of Raman Spectroscopy and Univariate Modelling As a Process Analytical Technology for Cell Therapy Bioprocessing.

    Science.gov (United States)

    Baradez, Marc-Olivier; Biziato, Daniela; Hassan, Enas; Marshall, Damian

    2018-01-01

    Cell therapies offer unquestionable promises for the treatment, and in some cases even the cure, of complex diseases. As we start to see more of these therapies gaining market authorization, attention is turning to the bioprocesses used for their manufacture, in particular the challenge of gaining higher levels of process control to help regulate cell behavior, manage process variability, and deliver product of a consistent quality. Many processes already incorporate the measurement of key markers such as nutrient consumption, metabolite production, and cell concentration, but these are often performed off-line and only at set time points in the process. Having the ability to monitor these markers in real-time using in-line sensors would offer significant advantages, allowing faster decision-making and a finer level of process control. In this study, we use Raman spectroscopy as an in-line optical sensor for bioprocess monitoring of an autologous T-cell immunotherapy model produced in a stirred tank bioreactor system. Using reference datasets generated on a standard bioanalyzer, we develop chemometric models from the Raman spectra for glucose, glutamine, lactate, and ammonia. These chemometric models can accurately monitor donor-specific increases in nutrient consumption and metabolite production as the primary T-cell transition from a recovery phase and begin proliferating. Using a univariate modeling approach, we then show how changes in peak intensity within the Raman spectra can be correlated with cell concentration and viability. These models, which act as surrogate markers, can be used to monitor cell behavior including cell proliferation rates, proliferative capacity, and transition of the cells to a quiescent phenotype. Finally, using the univariate models, we also demonstrate how Raman spectroscopy can be applied for real-time monitoring. The ability to measure these key parameters using an in-line Raman optical sensor makes it possible to have immediate

  14. Application of Raman Spectroscopy and Univariate Modelling As a Process Analytical Technology for Cell Therapy Bioprocessing

    Directory of Open Access Journals (Sweden)

    Marc-Olivier Baradez

    2018-03-01

    Full Text Available Cell therapies offer unquestionable promises for the treatment, and in some cases even the cure, of complex diseases. As we start to see more of these therapies gaining market authorization, attention is turning to the bioprocesses used for their manufacture, in particular the challenge of gaining higher levels of process control to help regulate cell behavior, manage process variability, and deliver product of a consistent quality. Many processes already incorporate the measurement of key markers such as nutrient consumption, metabolite production, and cell concentration, but these are often performed off-line and only at set time points in the process. Having the ability to monitor these markers in real-time using in-line sensors would offer significant advantages, allowing faster decision-making and a finer level of process control. In this study, we use Raman spectroscopy as an in-line optical sensor for bioprocess monitoring of an autologous T-cell immunotherapy model produced in a stirred tank bioreactor system. Using reference datasets generated on a standard bioanalyzer, we develop chemometric models from the Raman spectra for glucose, glutamine, lactate, and ammonia. These chemometric models can accurately monitor donor-specific increases in nutrient consumption and metabolite production as the primary T-cell transition from a recovery phase and begin proliferating. Using a univariate modeling approach, we then show how changes in peak intensity within the Raman spectra can be correlated with cell concentration and viability. These models, which act as surrogate markers, can be used to monitor cell behavior including cell proliferation rates, proliferative capacity, and transition of the cells to a quiescent phenotype. Finally, using the univariate models, we also demonstrate how Raman spectroscopy can be applied for real-time monitoring. The ability to measure these key parameters using an in-line Raman optical sensor makes it possible

  15. Bioprocessing strategies for the large-scale production of human mesenchymal stem cells: a review.

    Science.gov (United States)

    Panchalingam, Krishna M; Jung, Sunghoon; Rosenberg, Lawrence; Behie, Leo A

    2015-11-23

    Human mesenchymal stem cells (hMSCs), also called mesenchymal stromal cells, have been of great interest in regenerative medicine applications because of not only their differentiation potential but also their ability to secrete bioactive factors that can modulate the immune system and promote tissue repair. This potential has initiated many early-phase clinical studies for the treatment of various diseases, disorders, and injuries by using either hMSCs themselves or their secreted products. Currently, hMSCs for clinical use are generated through conventional static adherent cultures in the presence of fetal bovine serum or human-sourced supplements. However, these methods suffer from variable culture conditions (i.e., ill-defined medium components and heterogeneous culture environment) and thus are not ideal procedures to meet the expected future demand of quality-assured hMSCs for human therapeutic use. Optimizing a bioprocess to generate hMSCs or their secreted products (or both) promises to improve the efficacy as well as safety of this stem cell therapy. In this review, current media and methods for hMSC culture are outlined and bioprocess development strategies discussed.

  16. Quantitative feature extraction from the Chinese hamster ovary bioprocess bibliome using a novel meta-analysis workflow

    DEFF Research Database (Denmark)

    Golabgir, Aydin; Gutierrez, Jahir M.; Hefzi, Hooman

    2016-01-01

    compilation covers all published CHO cell studies from 1995 to 2015, and each study is classified by the types of phenotypic and bioprocess data contained therein. Using data from selected studies, we also present a quantitative meta-analysis of bioprocess characteristics across diverse culture conditions...... practices can limit research re-use in this field, we show that the statistical analysis of diverse legacy bioprocess data can provide insight into bioprocessing capabilities of CHO cell lines used in industry. The CHO bibliome can be accessed at http://lewislab.ucsd.edu/cho-bibliome/....

  17. Disposable bioprocessing: the future has arrived.

    Science.gov (United States)

    Rao, Govind; Moreira, Antonio; Brorson, Kurt

    2009-02-01

    Increasing cost pressures are driving the rapid adoption of disposables in bioprocessing. While well ensconced in lab-scale operations, the lower operating/ validation costs at larger scale and relative ease of use are leading to these systems entering all stages and operations of a typical biopharmaceutical manufacturing process. Here, we focus on progress made in the incorporation of disposable equipment with sensor technology in bioprocessing throughout the development cycle. We note that sensor patch technology is mostly being adapted to disposable cell culture devices, but future adaptation to downstream steps is conceivable. Lastly, regulatory requirements are also briefly assessed in the context of disposables and the Process Analytical Technologies (PAT) and Quality by Design (QbD) initiatives.

  18. Virtual parameter-estimation experiments in Bioprocess-Engineering education

    NARCIS (Netherlands)

    Sessink, O.D.T.; Beeftink, H.H.; Hartog, R.J.M.; Tramper, J.

    2006-01-01

    Cell growth kinetics and reactor concepts constitute essential knowledge for Bioprocess-Engineering students. Traditional learning of these concepts is supported by lectures, tutorials, and practicals: ICT offers opportunities for improvement. A virtual-experiment environment was developed that

  19. HEK293 cell culture media study towards bioprocess optimization: Animal derived component free and animal derived component containing platforms.

    Science.gov (United States)

    Liste-Calleja, Leticia; Lecina, Martí; Cairó, Jordi Joan

    2014-04-01

    The increasing demand for biopharmaceuticals produced in mammalian cells has lead industries to enhance bioprocess volumetric productivity through different strategies. Among those strategies, cell culture media development is of major interest. In the present work, several commercially available culture media for Human Embryonic Kidney cells (HEK293) were evaluated in terms of maximal specific growth rate and maximal viable cell concentration supported. The main objective was to provide different cell culture platforms which are suitable for a wide range of applications depending on the type and the final use of the product obtained. Performing simple media supplementations with and without animal derived components, an enhancement of cell concentration from 2 × 10(6) cell/mL to 17 × 10(6) cell/mL was achieved in batch mode operation. Additionally, the media were evaluated for adenovirus production as a specific application case of HEK293 cells. None of the supplements interfered significantly with the adenovirus infection although some differences were encountered in viral productivity. To the best of our knowledge, the high cell density achieved in the work presented has never been reported before in HEK293 batch cell cultures and thus, our results are greatly promising to further study cell culture strategies in bioreactor towards bioprocess optimization. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  20. Development of a new bioprocess scheme using frozen seed train intermediates to initiate CHO cell culture manufacturing campaigns.

    Science.gov (United States)

    Seth, Gargi; Hamilton, Robert W; Stapp, Thomas R; Zheng, Lisa; Meier, Angela; Petty, Krista; Leung, Stephenie; Chary, Srikanth

    2013-05-01

    Agility to schedule and execute cell culture manufacturing campaigns quickly in a multi-product facility will play a key role in meeting the growing demand for therapeutic proteins. In an effort to shorten campaign timelines, maximize plant flexibility and resource utilization, we investigated the initiation of cell culture manufacturing campaigns using CHO cells cryopreserved in large volume bags in place of the seed train process flows that are conventionally used in cell culture manufacturing. This approach, termed FASTEC (Frozen Accelerated Seed Train for Execution of a Campaign), involves cultivating cells to high density in a perfusion bioreactor, and cryopreserving cells in multiple disposable bags. Each run for a manufacturing campaign would then come from a thaw of one or more of these cryopreserved bags. This article reviews the development and optimization of individual steps of the FASTEC bioprocess scheme: scaling up cells to greater than 70 × 10(6) cells/mL and freezing in bags with an optimized controlled rate freezing protocol and using a customized rack configuration. Flow cytometry analysis was also employed to understand the recovery of CHO cells following cryopreservation. Extensive development data were gathered to ensure that the quantity and quality of the drug manufactured using the FASTEC bioprocess scheme was acceptable compared to the conventional seed train process flow. The result of offering comparable manufacturing options offers flexibility to the cell culture manufacturing network. Copyright © 2012 Wiley Periodicals, Inc.

  1. [Progress in industrial bioprocess engineering in China].

    Science.gov (United States)

    Zhuang, Yingping; Chen, Hongzhang; Xia, Jianye; Tang, Wenjun; Zhao, Zhimin

    2015-06-01

    The advances of industrial biotechnology highly depend on the development of industrial bioprocess researches. In China, we are facing several challenges because of a huge national industrial fermentation capacity. The industrial bioprocess development experienced several main stages. This work mainly reviews the development of the industrial bioprocess in China during the past 30 or 40 years: including the early stage kinetics model study derived from classical chemical engineering, researching method based on control theory, multiple-parameter analysis techniques of on-line measuring instruments and techniques, and multi-scale analysis theory, and also solid state fermentation techniques and fermenters. In addition, the cutting edge of bioprocess engineering was also addressed.

  2. Bioprocessing of a stored mixed liquid waste

    Energy Technology Data Exchange (ETDEWEB)

    Wolfram, J.H.; Rogers, R.D. [Idaho National Engineering Lab., Idaho Falls, ID (United States); Finney, R. [Mound Applied Technologies, Miamisburg, OH (United States)] [and others

    1995-12-31

    This paper describes the development and results of a demonstration for a continuous bioprocess for mixed waste treatment. A key element of the process is an unique microbial strain which tolerates high levels of aromatic solvents and surfactants. This microorganism is the biocatalysis of the continuous flow system designed for the processing of stored liquid scintillation wastes. During the past year a process demonstration has been conducted on commercial formulation of liquid scintillation cocktails (LSC). Based on data obtained from this demonstration, the Ohio EPA granted the Mound Applied Technologies Lab a treatability permit allowing the limited processing of actual mixed waste. Since August 1994, the system has been successfully processing stored, {open_quotes}hot{close_quotes} LSC waste. The initial LSC waste fed into the system contained 11% pseudocumene and detectable quantities of plutonium. Another treated waste stream contained pseudocumene and tritium. Data from this initial work shows that the hazardous organic solvent, and pseudocumene have been removed due to processing, leaving the aqueous low level radioactive waste. Results to date have shown that living cells are not affected by the dissolved plutonium and that 95% of the plutonium was sorbed to the biomass. This paper discusses the bioprocess, rates of processing, effluent, and the implications of bioprocessing for mixed waste management.

  3. Mesoderm Lineage 3D Tissue Constructs Are Produced at Large-Scale in a 3D Stem Cell Bioprocess.

    Science.gov (United States)

    Cha, Jae Min; Mantalaris, Athanasios; Jung, Sunyoung; Ji, Yurim; Bang, Oh Young; Bae, Hojae

    2017-09-01

    Various studies have presented different approaches to direct pluripotent stem cell differentiation such as applying defined sets of exogenous biochemical signals and genetic/epigenetic modifications. Although differentiation to target lineages can be successfully regulated, such conventional methods are often complicated, laborious, and not cost-effective to be employed to the large-scale production of 3D stem cell-based tissue constructs. A 3D-culture platform that could realize the large-scale production of mesoderm lineage tissue constructs from embryonic stem cells (ESCs) is developed. ESCs are cultured using our previously established 3D-bioprocess platform which is amenable to mass-production of 3D ESC-based tissue constructs. Hepatocarcinoma cell line conditioned medium is introduced to the large-scale 3D culture to provide a specific biomolecular microenvironment to mimic in vivo mesoderm formation process. After 5 days of spontaneous differentiation period, the resulting 3D tissue constructs are composed of multipotent mesodermal progenitor cells verified by gene and molecular expression profiles. Subsequently the optimal time points to trigger terminal differentiation towards cardiomyogenesis or osteogenesis from the mesodermal tissue constructs is found. A simple and affordable 3D ESC-bioprocess that can reach the scalable production of mesoderm origin tissues with significantly improved correspondent tissue properties is demonstrated. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Modeling and simulation of the bioprocess with recirculation

    Directory of Open Access Journals (Sweden)

    Žerajić Stanko

    2007-01-01

    Full Text Available The bioprocess models with recirculation present an integration of the model of continuous bioreaction system and the model of separation system. The reaction bioprocess is integrated with separation the biomass, formed product, no consumed substrate or inhibitory substance. In this paper the simulation model of recirculation bioprocess was developed, which may be applied for increasing the biomass productivity and product biosynthesis increasing the conversion of a substrate-to-product, mixing efficiency and secondary C02 separation. The goal of the work is optimal bioprocess configuration, which is determined by simulation optimization. The optimal hemostat state was used as referent. Step-by-step simulation method is necessary because the initial bioprocess state is changing with recirculation in each step. The simulation experiment confirms that at the recirculation ratio a. = 0.275 and the concentration factor C = 4 the maximum glucose conversion to ethanol and at a dilution rate ten times larger.

  5. Allogeneic cell therapy bioprocess economics and optimization: single-use cell expansion technologies.

    Science.gov (United States)

    Simaria, Ana S; Hassan, Sally; Varadaraju, Hemanthram; Rowley, Jon; Warren, Kim; Vanek, Philip; Farid, Suzanne S

    2014-01-01

    For allogeneic cell therapies to reach their therapeutic potential, challenges related to achieving scalable and robust manufacturing processes will need to be addressed. A particular challenge is producing lot-sizes capable of meeting commercial demands of up to 10(9) cells/dose for large patient numbers due to the current limitations of expansion technologies. This article describes the application of a decisional tool to identify the most cost-effective expansion technologies for different scales of production as well as current gaps in the technology capabilities for allogeneic cell therapy manufacture. The tool integrates bioprocess economics with optimization to assess the economic competitiveness of planar and microcarrier-based cell expansion technologies. Visualization methods were used to identify the production scales where planar technologies will cease to be cost-effective and where microcarrier-based bioreactors become the only option. The tool outputs also predict that for the industry to be sustainable for high demand scenarios, significant increases will likely be needed in the performance capabilities of microcarrier-based systems. These data are presented using a technology S-curve as well as windows of operation to identify the combination of cell productivities and scale of single-use bioreactors required to meet future lot sizes. The modeling insights can be used to identify where future R&D investment should be focused to improve the performance of the most promising technologies so that they become a robust and scalable option that enables the cell therapy industry reach commercially relevant lot sizes. The tool outputs can facilitate decision-making very early on in development and be used to predict, and better manage, the risk of process changes needed as products proceed through the development pathway. © 2013 Wiley Periodicals, Inc.

  6. Potentials and limitations of miniaturized calorimeters for bioprocess monitoring.

    Science.gov (United States)

    Maskow, Thomas; Schubert, Torsten; Wolf, Antje; Buchholz, Friederike; Regestein, Lars; Buechs, Jochen; Mertens, Florian; Harms, Hauke; Lerchner, Johannes

    2011-10-01

    In theory, heat production rates are very well suited for analysing and controlling bioprocesses on different scales from a few nanolitres up to many cubic metres. Any bioconversion is accompanied by a production (exothermic) or consumption (endothermic) of heat. The heat is tightly connected with the stoichiometry of the bioprocess via the law of Hess, and its rate is connected to the kinetics of the process. Heat signals provide real-time information of bioprocesses. The combination of heat measurements with respirometry is theoretically suited for the quantification of the coupling between catabolic and anabolic reactions. Heat measurements have also practical advantages. Unlike most other biochemical sensors, thermal transducers can be mounted in a protected way that prevents fouling, thereby minimizing response drifts. Finally, calorimetry works in optically opaque solutions and does not require labelling or reactants. It is surprising to see that despite all these advantages, calorimetry has rarely been applied to monitor and control bioprocesses with intact cells in the laboratory, industrial bioreactors or ecosystems. This review article analyses the reasons for this omission, discusses the additional information calorimetry can provide in comparison with respirometry and presents miniaturization as a potential way to overcome some inherent weaknesses of conventional calorimetry. It will be discussed for which sample types and scientific question miniaturized calorimeter can be advantageously applied. A few examples from different fields of microbiological and biotechnological research will illustrate the potentials and limitations of chip calorimetry. Finally, the future of chip calorimetry is addressed in an outlook.

  7. Nanobiocatalyst advancements and bioprocessing applications.

    Science.gov (United States)

    Misson, Mailin; Zhang, Hu; Jin, Bo

    2015-01-06

    The nanobiocatalyst (NBC) is an emerging innovation that synergistically integrates advanced nanotechnology with biotechnology and promises exciting advantages for improving enzyme activity, stability, capability and engineering performances in bioprocessing applications. NBCs are fabricated by immobilizing enzymes with functional nanomaterials as enzyme carriers or containers. In this paper, we review the recent developments of novel nanocarriers/nanocontainers with advanced hierarchical porous structures for retaining enzymes, such as nanofibres (NFs), mesoporous nanocarriers and nanocages. Strategies for immobilizing enzymes onto nanocarriers made from polymers, silicas, carbons and metals by physical adsorption, covalent binding, cross-linking or specific ligand spacers are discussed. The resulting NBCs are critically evaluated in terms of their bioprocessing performances. Excellent performances are demonstrated through enhanced NBC catalytic activity and stability due to conformational changes upon immobilization and localized nanoenvironments, and NBC reutilization by assembling magnetic nanoparticles into NBCs to defray the high operational costs associated with enzyme production and nanocarrier synthesis. We also highlight several challenges associated with the NBC-driven bioprocess applications, including the maturation of large-scale nanocarrier synthesis, design and development of bioreactors to accommodate NBCs, and long-term operations of NBCs. We suggest these challenges are to be addressed through joint collaboration of chemists, engineers and material scientists. Finally, we have demonstrated the great potential of NBCs in manufacturing bioprocesses in the near future through successful laboratory trials of NBCs in carbohydrate hydrolysis, biofuel production and biotransformation. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  8. Guiding bioprocess design by microbial ecology.

    Science.gov (United States)

    Volmer, Jan; Schmid, Andreas; Bühler, Bruno

    2015-06-01

    Industrial bioprocess development is driven by profitability and eco-efficiency. It profits from an early stage definition of process and biocatalyst design objectives. Microbial bioprocess environments can be considered as synthetic technical microbial ecosystems. Natural systems follow Darwinian evolution principles aiming at survival and reproduction. Technical systems objectives are eco-efficiency, productivity, and profitable production. Deciphering technical microbial ecology reveals differences and similarities of natural and technical systems objectives, which are discussed in this review in view of biocatalyst and process design and engineering strategies. Strategies for handling opposing objectives of natural and technical systems and for exploiting and engineering natural properties of microorganisms for technical systems are reviewed based on examples. This illustrates the relevance of considering microbial ecology for bioprocess design and the potential for exploitation by synthetic biology strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. On-line bioprocess monitoring - an academic discipline or an industrial tool?

    DEFF Research Database (Denmark)

    Olsson, Lisbeth; Schulze, Ulrik; Nielsen, Jens Bredal

    1998-01-01

    Bioprocess monitoring capabilities are gaining increasing Importance bath in physiological studies and in bioprocess development, The present article focuses on on-line analytical systems since these represent the backbone of most bioprocess monitoring systems, both in academia and in industry. W...

  10. Aspects of modelling and control of bioprocesses

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiachang

    1995-12-31

    The modelling and control of bioprocesses are the main subjects in this thesis. Different modelling approaches are proposed for different purposes in various bioprocesses. A conventional global model was constructed for a very complex mammalian cell culture process. A new concept of functional state and a multiple model (local models) approach were used for modelling the fed-batch baker`s yeast process for monitoring and control purposes. Finally, a combination of conventional electrical and biological models was used to simulate and to control a microbial fuel cell process. In the thesis, a yeast growth process was taken as an example to demonstrate the usefulness of the functional state concept and local models. The functional states were first defined according to the yeast metabolism. The process was then described by a set of simple local models. In different functional states, different local models were used. On the other hand, the on-line estimation of functional state and biomass of the process was discussed for process control purpose. As a consequence, both the functional state concept and the multiple model approach were applied for fuzzy logic control of yeast growth process. A fuzzy factor was calculated on the basis of a knowledge-based expert system and fuzzy logic rules. The factor was used to correct an ideal substrate feed rate. In the last part of the thesis, microbial fuel cell processes were studied. A microbial fuel cell is a device for direct conversion of chemical energy to electrical energy by using micro-organisms as catalysts. A combined model including conventional electrical and biological models was constructed for the process based on the biological and electrochemical phenomena

  11. Aspects of modelling and control of bioprocesses

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiachang

    1996-12-31

    The modelling and control of bioprocesses are the main subjects in this thesis. Different modelling approaches are proposed for different purposes in various bioprocesses. A conventional global model was constructed for a very complex mammalian cell culture process. A new concept of functional state and a multiple model (local models) approach were used for modelling the fed-batch baker`s yeast process for monitoring and control purposes. Finally, a combination of conventional electrical and biological models was used to simulate and to control a microbial fuel cell process. In the thesis, a yeast growth process was taken as an example to demonstrate the usefulness of the functional state concept and local models. The functional states were first defined according to the yeast metabolism. The process was then described by a set of simple local models. In different functional states, different local models were used. On the other hand, the on-line estimation of functional state and biomass of the process was discussed for process control purpose. As a consequence, both the functional state concept and the multiple model approach were applied for fuzzy logic control of yeast growth process. A fuzzy factor was calculated on the basis of a knowledge-based expert system and fuzzy logic rules. The factor was used to correct an ideal substrate feed rate. In the last part of the thesis, microbial fuel cell processes were studied. A microbial fuel cell is a device for direct conversion of chemical energy to electrical energy by using micro-organisms as catalysts. A combined model including conventional electrical and biological models was constructed for the process based on the biological and electrochemical phenomena

  12. On-line soft sensing in upstream bioprocessing.

    Science.gov (United States)

    Randek, Judit; Mandenius, Carl-Fredrik

    2018-02-01

    This review provides an overview and a critical discussion of novel possibilities of applying soft sensors for on-line monitoring and control of industrial bioprocesses. Focus is on bio-product formation in the upstream process but also the integration with other parts of the process is addressed. The term soft sensor is used for the combination of analytical hardware data (from sensors, analytical devices, instruments and actuators) with mathematical models that create new real-time information about the process. In particular, the review assesses these possibilities from an industrial perspective, including sensor performance, information value and production economy. The capabilities of existing analytical on-line techniques are scrutinized in view of their usefulness in soft sensor setups and in relation to typical needs in bioprocessing in general. The review concludes with specific recommendations for further development of soft sensors for the monitoring and control of upstream bioprocessing.

  13. Dynamic single-cell analysis of Saccharomyces cerevisiae under process perturbation: Comparison of different methods for monitoring the intensity of population heterogeneity

    DEFF Research Database (Denmark)

    Delvigne, Frank; Baert, Jonathan; Gofflot, Sébastien

    2015-01-01

    BACKGROUND: Single cell biology has attracted a lot of attention in recent years and has led to numerous fundamental results pointing out the heterogeneity of clonal cell populations. In this context, microbial phenotypic heterogeneity under bioprocessing conditions needs to be further investigat...

  14. Incorporating unnatural amino acids to engineer biocatalysts for industrial bioprocess applications.

    Science.gov (United States)

    Ravikumar, Yuvaraj; Nadarajan, Saravanan Prabhu; Hyeon Yoo, Tae; Lee, Chong-Soon; Yun, Hyungdon

    2015-12-01

    The bioprocess engineering with biocatalysts broadly spans its development and actual application of enzymes in an industrial context. Recently, both the use of bioprocess engineering and the development and employment of enzyme engineering techniques have been increasing rapidly. Importantly, engineering techniques that incorporate unnatural amino acids (UAAs) in vivo has begun to produce enzymes with greater stability and altered catalytic properties. Despite the growth of this technique, its potential value in bioprocess applications remains to be fully exploited. In this review, we explore the methodologies involved in UAA incorporation as well as ways to synthesize these UAAs. In addition, we summarize recent efforts to increase the yield of UAA engineered proteins in Escherichia coli and also the application of this tool in enzyme engineering. Furthermore, this protein engineering tool based on the incorporation of UAA can be used to develop immobilized enzymes that are ideal for bioprocess applications. Considering the potential of this tool and by exploiting these engineered enzymes, we expect the field of bioprocess engineering to open up new opportunities for biocatalysis in the near future. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Turmeric Bioprocessed with Mycelia from the Shiitake Culinary-Medicinal Mushroom Lentinus edodes (Agaricomycetes) Protects Mice Against Salmonellosis.

    Science.gov (United States)

    Kim, Sung Phil; Lee, Sang Jong; Nam, Seok Hyun; Friedman, Mendel

    2017-01-01

    This study investigated the suppressive mechanisms of an extract from bioprocessed Lentinus edodes mycelial liquid culture supplemented with turmeric (bioprocessed Curcuma longa extract [BPCLE]) against murine salmonellosis. The BPLCE extract from the bioprocessed mycelia of the Salmonella Typhimurium into murine RAW 264.7 macrophage cells, elimination of intracellular bacteria, and elevation of inducible nitric oxide synthase expression. Dietary administration of BPCLE activated leukocytes from the mice infected with Salmonella through the intraperitoneal route. The enzyme-linked immunosorbent assay of the cytokines produced by splenocytes from infected mice showed significant increases in the levels of Th1 cytokines, including interleukin (IL)-1β, IL-2, IL-6, and IL-12. Histology showed that dietary administration of BPCLE protected against necrosis of the liver resulting from a sublethal dose of Salmonella. In addition, the treatment (1) extended the lifespan of lethally infected mice, (2) suppressed the invasion of Salmonella into human Caco-2 colorectal adenocarcinoma cells, (3) increased excretion of the bacterium in the feces, (4) suppressed the translocation of the Salmonella to internal organs, and (5) increased total immunoglobulin A in both serum and intestinal fluids. BPCLE protected the mice against salmonellosis via cooperative effects that include the upregulation of the Th1 immune reaction, prevention of translocation of bacteria across the intestinal epithelial cells, and increased immunoglobulin A production in serum and intestinal fluids.

  16. Quality by control: Towards model predictive control of mammalian cell culture bioprocesses.

    Science.gov (United States)

    Sommeregger, Wolfgang; Sissolak, Bernhard; Kandra, Kulwant; von Stosch, Moritz; Mayer, Martin; Striedner, Gerald

    2017-07-01

    The industrial production of complex biopharmaceuticals using recombinant mammalian cell lines is still mainly built on a quality by testing approach, which is represented by fixed process conditions and extensive testing of the end-product. In 2004 the FDA launched the process analytical technology initiative, aiming to guide the industry towards advanced process monitoring and better understanding of how critical process parameters affect the critical quality attributes. Implementation of process analytical technology into the bio-production process enables moving from the quality by testing to a more flexible quality by design approach. The application of advanced sensor systems in combination with mathematical modelling techniques offers enhanced process understanding, allows on-line prediction of critical quality attributes and subsequently real-time product quality control. In this review opportunities and unsolved issues on the road to a successful quality by design and dynamic control implementation are discussed. A major focus is directed on the preconditions for the application of model predictive control for mammalian cell culture bioprocesses. Design of experiments providing information about the process dynamics upon parameter change, dynamic process models, on-line process state predictions and powerful software environments seem to be a prerequisite for quality by control realization. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Mannheimia haemolytica growth and leukotoxin production for vaccine manufacturing — A bioprocess review

    Directory of Open Access Journals (Sweden)

    Tobias Oppermann

    2017-07-01

    Full Text Available Mannheimia haemolytica leukotoxin (LKT is a known cause of bovine respiratory disease (BRD which results in severe economic losses in the cattle industry (up to USD 1 billion per year in the USA. Vaccines based on LKT offer the most promising measure to contain BRD outbreaks and are already commercially available. However, insufficient LKT yields, predominantly reflecting a lack of knowledge about the LKT expression process, remain a significant engineering problem and further bioprocess optimization is required to increase process efficiency. Most previous investigations have focused on LKT activity and cell growth, but neither of these parameters defines reliable criteria for the improvement of LKT yields. In this article, we review the most important process conditions and operational parameters (temperature, pH, substrate concentration, dissolved oxygen level, medium composition and the presence of metabolites from a bioprocess engineering perspective, in order to maximize LKT yields.

  18. Metabolite profiling of CHO cells: Molecular reflections of bioprocessing effectiveness

    NARCIS (Netherlands)

    Sellick, C.A.; Croxford, A.S.; Maqsood, A.R.; Stephens, G.M.; Westerhoff, H.V.; Goodacre, R.; Dickson, A.J.

    2015-01-01

    Whilst development of medium and feeds has provided major advances in recombinant protein production in CHO cells, the fundamental understanding is limited. We have applied metabolite profiling with established robust (GC-MS) analytics to define the molecular loci by which two yield-enhancing feeds

  19. Fundamentals of affinity cell separations.

    Science.gov (United States)

    Zhang, Ye; Lyons, Veronica; Pappas, Dimitri

    2018-03-01

    Cell separations using affinity methods continue to be an enabling science for a wide variety of applications. In this review, we discuss the fundamental aspects of affinity separation, including the competing forces for cell capture and elution, cell-surface interactions, and models for cell adhesion. Factors affecting separation performance such as bond affinity, contact area, and temperature are presented. We also discuss and demonstrate the effects of nonspecific binding on separation performance. Metrics for evaluating cell separations are presented, along with methods of comparing separation techniques for cell isolation using affinity capture. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing.

    Science.gov (United States)

    Esmonde-White, Karen A; Cuellar, Maryann; Uerpmann, Carsten; Lenain, Bruno; Lewis, Ian R

    2017-01-01

    Adoption of Quality by Design (QbD) principles, regulatory support of QbD, process analytical technology (PAT), and continuous manufacturing are major factors effecting new approaches to pharmaceutical manufacturing and bioprocessing. In this review, we highlight new technology developments, data analysis models, and applications of Raman spectroscopy, which have expanded the scope of Raman spectroscopy as a process analytical technology. Emerging technologies such as transmission and enhanced reflection Raman, and new approaches to using available technologies, expand the scope of Raman spectroscopy in pharmaceutical manufacturing, and now Raman spectroscopy is successfully integrated into real-time release testing, continuous manufacturing, and statistical process control. Since the last major review of Raman as a pharmaceutical PAT in 2010, many new Raman applications in bioprocessing have emerged. Exciting reports of in situ Raman spectroscopy in bioprocesses complement a growing scientific field of biological and biomedical Raman spectroscopy. Raman spectroscopy has made a positive impact as a process analytical and control tool for pharmaceutical manufacturing and bioprocessing, with demonstrated scientific and financial benefits throughout a product's lifecycle.

  1. Multiple reaction monitoring targeted LC-MS analysis of potential cell death marker proteins for increased bioprocess control.

    Science.gov (United States)

    Albrecht, Simone; Kaisermayer, Christian; Reinhart, David; Ambrose, Monica; Kunert, Renate; Lindeberg, Anna; Bones, Jonathan

    2018-05-01

    The monitoring of protein biomarkers for the early prediction of cell stress and death is a valuable tool for process characterization and efficient biomanufacturing control. A representative set of six proteins, namely GPDH, PRDX1, LGALS1, CFL1, TAGLN2 and MDH, which were identified in a previous CHO-K1 cell death model using discovery LC-MS E was translated into a targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM-MS) platform and verified. The universality of the markers was confirmed in a cell growth model for which three Chinese hamster ovary host cell lines (CHO-K1, CHO-S, CHO-DG44) were grown in batch culture in two different types of basal media. LC-MRM-MS was also applied to spent media (n = 39) from four perfusion biomanufacturing series. Stable isotope-labelled peptide analogues and a stable isotope-labelled monoclonal antibody were used for improved protein quantitation and simultaneous monitoring of the workflow reproducibility. Significant increases in protein concentrations were observed for all viability marker proteins upon increased dead cell numbers and allowed for discrimination of spent media with dead cell densities below and above 1 × 10 6  dead cells/mL which highlights the potential of the selected viability marker proteins in bioprocess control. Graphical abstract Overview of the LC-MRM-MS workflow for the determination of proteomic markers in conditioned media from the bioreactor that correlate with CHO cell death.

  2. The art of CHO cell engineering: A comprehensive retrospect and future perspectives.

    Science.gov (United States)

    Fischer, Simon; Handrick, René; Otte, Kerstin

    2015-12-01

    Chinese hamster ovary (CHO) cells represent the most frequently applied host cell system for industrial manufacturing of recombinant protein therapeutics. CHO cells are capable of producing high quality biologics exhibiting human-like post-translational modifications in gram quantities. However, production processes for biopharmaceuticals using mammalian cells still suffer from cellular limitations such as limited growth, low productivity and stress resistance as well as higher expenses compared to bacterial or yeast based expression systems. Besides bioprocess, media and vector optimizations, advances in host cell engineering technologies comprising introduction, knock-out or post-transcriptional silencing of engineering genes have paved the way for remarkable achievements in CHO cell line development. Furthermore, thorough analysis of cellular pathways and mechanisms important for bioprocessing steadily unravels novel target molecules which might be addressed by functional genomic tools in order to establish superior production cell factories. This review provides a comprehensive summary of the most fundamental achievements in CHO cell engineering over the past three decades. Finally, the authors discuss the potential of novel and innovative methodologies that might contribute to further enhancement of existing CHO based production platforms for biopharmaceutical manufacturing in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Design and analysis of heat recovery system in bioprocess plant

    International Nuclear Information System (INIS)

    Anastasovski, Aleksandar; Rašković, Predrag; Guzović, Zvonimir

    2015-01-01

    Highlights: • Heat integration of a bioprocess plant is studied. • Bioprocess plant produces yeast and ethyl-alcohol. • The design of a heat recovery system is performed by batch pinch analysis. • Direct and indirect heat integration approaches are used in process design. • The heat recovery system without a heat storage opportunity is more profitable. - Abstract: The paper deals with the heat integration of a bioprocess plant which produces yeast and ethyl-alcohol. The referent plant is considered to be a multiproduct batch plant which operates in a semi-continuous mode. The design of a heat recovery system is performed by batch pinch analysis and by the use of the Time slice model. The results obtained by direct and indirect heat integration approaches are presented in the form of cost-optimal heat exchanger networks and evaluated by different thermodynamic and economic indicators. They signify that the heat recovery system without a heat storage opportunity can be considered to be a more profitable solution for the energy efficiency increase in a plant

  4. Development of a high-throughput microscale cell disruption platform for Pichia pastoris in rapid bioprocess design.

    Science.gov (United States)

    Bláha, Benjamin A F; Morris, Stephen A; Ogonah, Olotu W; Maucourant, Sophie; Crescente, Vincenzo; Rosenberg, William; Mukhopadhyay, Tarit K

    2018-01-01

    The time and cost benefits of miniaturized fermentation platforms can only be gained by employing complementary techniques facilitating high-throughput at small sample volumes. Microbial cell disruption is a major bottleneck in experimental throughput and is often restricted to large processing volumes. Moreover, for rigid yeast species, such as Pichia pastoris, no effective high-throughput disruption methods exist. The development of an automated, miniaturized, high-throughput, noncontact, scalable platform based on adaptive focused acoustics (AFA) to disrupt P. pastoris and recover intracellular heterologous protein is described. Augmented modes of AFA were established by investigating vessel designs and a novel enzymatic pretreatment step. Three different modes of AFA were studied and compared to the performance high-pressure homogenization. For each of these modes of cell disruption, response models were developed to account for five different performance criteria. Using multiple responses not only demonstrated that different operating parameters are required for different response optima, with highest product purity requiring suboptimal values for other criteria, but also allowed for AFA-based methods to mimic large-scale homogenization processes. These results demonstrate that AFA-mediated cell disruption can be used for a wide range of applications including buffer development, strain selection, fermentation process development, and whole bioprocess integration. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:130-140, 2018. © 2017 American Institute of Chemical Engineers.

  5. Hybrid elementary flux analysis/nonparametric modeling: application for bioprocess control

    Directory of Open Access Journals (Sweden)

    Alves Paula M

    2007-01-01

    Full Text Available Abstract Background The progress in the "-omic" sciences has allowed a deeper knowledge on many biological systems with industrial interest. This knowledge is still rarely used for advanced bioprocess monitoring and control at the bioreactor level. In this work, a bioprocess control method is presented, which is designed on the basis of the metabolic network of the organism under consideration. The bioprocess dynamics are formulated using hybrid rigorous/data driven systems and its inherent structure is defined by the metabolism elementary modes. Results The metabolic network of the system under study is decomposed into elementary modes (EMs, which are the simplest paths able to operate coherently in steady-state. A reduced reaction mechanism in the form of simplified reactions connecting substrates with end-products is obtained. A dynamical hybrid system integrating material balance equations, EMs reactions stoichiometry and kinetics was formulated. EMs kinetics were defined as the product of two terms: a mechanistic/empirical known term and an unknown term that must be identified from data, in a process optimisation perspective. This approach allows the quantification of fluxes carried by individual elementary modes which is of great help to identify dominant pathways as a function of environmental conditions. The methodology was employed to analyse experimental data of recombinant Baby Hamster Kidney (BHK-21A cultures producing a recombinant fusion glycoprotein. The identified EMs kinetics demonstrated typical glucose and glutamine metabolic responses during cell growth and IgG1-IL2 synthesis. Finally, an online optimisation study was conducted in which the optimal feeding strategies of glucose and glutamine were calculated after re-estimation of model parameters at each sampling time. An improvement in the final product concentration was obtained as a result of this online optimisation. Conclusion The main contribution of this work is a

  6. Application of Hydrodynamic Cavitation for Food and Bioprocessing

    Science.gov (United States)

    Gogate, Parag R.

    Hydrodynamic cavitation can be simply generated by the alterations in the flow field in high speed/high pressure devices and also by passage of the liquid through a constriction such as orifice plate, venturi, or throttling valve. Hydrodynamic cavitation results in the formation of local hot spots, release of highly reactive free radicals, and enhanced mass transfer rates due to turbulence generated as a result of liquid circulation currents. These conditions can be suitably applied for intensification of different bioprocessing applications in an energy-efficient manner as compared to conventionally used ultrasound-based reactors. The current chapter aims at highlighting different aspects related to hydrodynamic cavitation, including the theoretical aspects for optimization of operating parameters, reactor designs, and overview of applications relevant to food and bioprocessing. Some case studies highlighting the comparison of hydrodynamic cavitation and acoustic cavitation reactors will also be discussed.

  7. Soft sensors in bioprocessing: A status report and recommendations

    DEFF Research Database (Denmark)

    Luttmann, Reiner; Bracewell, Daniel G.; Cornelissen, Gesine

    2012-01-01

    The following report with recommendations is the result of an expert panel meeting on soft sensor applications in bioprocess engineering that was organized by the Measurement, Monitoring, Modelling and Control (M3C) Working Group of the European Federation of Biotechnology - Section of Biochemical...... Engineering Science (ESBES). The aim of the panel was to provide an update on the present status of the subject and to identify critical needs and issues for the furthering of the successful development of soft sensor methods in bioprocess engineering research and for industrial applications, in particular...... with focus on biopharmaceutical applications. It concludes with a set of recommendations, which highlight current prospects for the extended use of soft sensors and those areas requiring development....

  8. Development of bioprocess for high density cultivation yield of the probiotic Bacillus coagulans and its spores

    Directory of Open Access Journals (Sweden)

    Kavita R. Pandey

    2016-09-01

    Full Text Available Bacillus coagulans is a spore forming lactic acid bacterium. Spore forming bacteria, have been extensively studied and commercialized as probiotics. Probiotics are produced by fermentation technology. There is a limitation to biomass produced by conventional modes of fermentation. With the great demand generated by range of probiotic products, biomass is becoming very valuable for several pharmaceutical, dairy and probiotic companies. Thus, there is a need to develop high cell density cultivation processes for enhanced biomass accumulation. The bioprocess development was carried out in 6.6 L bench top lab scale fermentor. Four different cultivation strategies were employed to develop a bioprocess for higher growth and sporulation efficiencies of probiotic B. coagulans. Batch fermentation of B. coagulans yielded 18 g L-1 biomass (as against 8.0 g L-1 productivity in shake flask with 60% spore efficiency. Fed-batch cultivation was carried out for glucose, which yielded 25 g L-1 of biomass. C/N ratio was very crucial in achieving higher spore titres. Maximum biomass yield recorded was 30 g L-1, corresponding to 3.8 × 1011 cells mL-1 with 81% of cells in sporulated stage. The yield represents increment of 85 times the productivity and 158 times the spore titres relative to the highest reported values for high density cultivation of B. coagulans.

  9. White paper on continuous bioprocessing. May 20-21, 2014 Continuous Manufacturing Symposium.

    Science.gov (United States)

    Konstantinov, Konstantin B; Cooney, Charles L

    2015-03-01

    There is a growing interest in realizing the benefits of continuous processing in biologics manufacturing, which is reflected by the significant number of industrial and academic researchers who are actively involved in the development of continuous bioprocessing systems. These efforts are further encouraged by guidance expressed in recent US FDA conference presentations. The advantages of continuous manufacturing include sustained operation with consistent product quality, reduced equipment size, high-volumetric productivity, streamlined process flow, low-process cycle times, and reduced capital and operating cost. This technology, however, poses challenges, which need to be addressed before routine implementation is considered. This paper, which is based on the available literature and input from a large number of reviewers, is intended to provide a consensus of the opportunities, technical needs, and strategic directions for continuous bioprocessing. The discussion is supported by several examples illustrating various architectures of continuous bioprocessing systems. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Comparative analysis of solid-state bioprocessing and enzymatic treatment of finger millet for mobilization of bound phenolics.

    Science.gov (United States)

    Yadav, Geetanjali; Singh, Anshu; Bhattacharya, Patrali; Yuvraj, Jude; Banerjee, Rintu

    2013-11-01

    The present work investigates the probable bioprocessing technique to mobilize the bound phenolics naturally found in finger millet cell wall for enriching it with dietary antioxidants. Comparative study was performed between the exogenous enzymatic treatment and solid-state fermentation of grain (SSF) with a food grade organism Rhizopus oryzae. SSF results indicated that at the 6th day of incubation, total phenolic content (18.64 mg gallic acid equivalent/gds) and antioxidant property (DPPH radical scavenging activity of 39.03 %, metal chelating ability of 54 % and better reducing power) of finger millet were drastically enhanced when fermented with GRAS filamentous fungi. During the enzymatic bioprocessing, most of the phenolics released during the hydrolysis, leached out into the liquid portion rather than retaining them within the millet grain, resulting in overall loss of dietary antioxidant. The present study establishes the most effective strategy to enrich the finger millet with phenolic antioxidants.

  11. Bioprocess intensification for the effective production of chemical products

    DEFF Research Database (Denmark)

    Woodley, John

    2017-01-01

    The further implementation of new bioprocesses, using biocatalysts in various formats, for the synthesis of chemicals is highly dependent upon effective process intensification. The need for process intensification reflects the fact that the conditions under which a biocatalyst carries out...... a reaction in nature are far from those which are optimal for industrial processes. In this paper the rationale for intensification will be discussed, as well as the four complementary approaches used today to achieve bioprocess intensification. Two of these four approaches are based on alteration...... of the biocatalyst (either by protein engineering or metabolic engineering), resulting in an extra degree of freedom in the process design. To date, biocatalyst engineering has been developed independently from the conventional process engineering methodology to intensification. Although the integration of these two...

  12. Bioprocesses: Modelling needs for process evaluation and sustainability assessment

    DEFF Research Database (Denmark)

    Jiménez-Gonzaléz, Concepcion; Woodley, John

    2010-01-01

    development such that they can also be used to evaluate processes against sustainability metrics, as well as economics as an integral part of assessments. Finally, property models will also be required based on compounds not currently present in existing databases. It is clear that many new opportunities......The next generation of process engineers will face a new set of challenges, with the need to devise new bioprocesses, with high selectivity for pharmaceutical manufacture, and for lower value chemicals manufacture based on renewable feedstocks. In this paper the current and predicted future roles...... of process system engineering and life cycle inventory and assessment in the design, development and improvement of sustainable bioprocesses are explored. The existing process systems engineering software tools will prove essential to assist this work. However, the existing tools will also require further...

  13. Membrane Bioprocesses for Pharmaceutical Micropollutant Removal from Waters

    Directory of Open Access Journals (Sweden)

    Matthias de Cazes

    2014-10-01

    Full Text Available The purpose of this review work is to give an overview of the research reported on bioprocesses for the treatment of domestic or industrial wastewaters (WW containing pharmaceuticals. Conventional WW treatment technologies are not efficient enough to completely remove all pharmaceuticals from water. Indeed, these compounds are becoming an actual public health problem, because they are more and more present in underground and even in potable waters. Different types of bioprocesses are described in this work: from classical activated sludge systems, which allow the depletion of pharmaceuticals by bio-degradation and adsorption, to enzymatic reactions, which are more focused on the treatment of WW containing a relatively high content of pharmaceuticals and less organic carbon pollution than classical WW. Different aspects concerning the advantages of membrane bioreactors for pharmaceuticals removal are discussed, as well as the more recent studies on enzymatic membrane reactors to the depletion of these recalcitrant compounds.

  14. Synthesis and characterization of robust magnetic carriers for bioprocess applications

    Energy Technology Data Exchange (ETDEWEB)

    Kopp, Willian, E-mail: willkopp@gmail.com [Federal University of São Carlos-UFSCar, Graduate Program in Chemical Engineering, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); Silva, Felipe A., E-mail: eq.felipe.silva@gmail.com [Federal University of São Carlos-UFSCar, Graduate Program in Chemical Engineering, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); Lima, Lionete N., E-mail: lionetenunes@yahoo.com.br [Federal University of São Carlos-UFSCar, Graduate Program in Chemical Engineering, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); Masunaga, Sueli H., E-mail: sueli.masunaga@gmail.com [Department of Physics, Montana State University-MSU, 173840, Bozeman, MT 59717-3840 (United States); Tardioli, Paulo W., E-mail: pwtardioli@ufscar.br [Department of Chemical Engineering, Federal University of São Carlos-UFSCar, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); Giordano, Roberto C., E-mail: roberto@ufscar.br [Department of Chemical Engineering, Federal University of São Carlos-UFSCar, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); Araújo-Moreira, Fernando M., E-mail: faraujo@df.ufscar.br [Department of Physics, Federal University of São Carlos-UFSCar, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); and others

    2015-03-15

    Highlights: • Silica magnetic microparticles were synthesized for applications in bioprocesses. • The process to produce magnetic microparticles is inexpensive and easily scalable. • Microparticles with very high saturation magnetization were obtained. • The structure of the silica magnetic microparticles could be controlled. - Abstract: Magnetic carriers are an effective option to withdraw selected target molecules from complex mixtures or to immobilize enzymes. This paper describes the synthesis of robust silica magnetic microparticles (SMMps), particularly designed for applications in bioprocesses. SMMps were synthesized in a micro-emulsion, using sodium silicate as the silica source and superparamagnetic iron oxide nanoparticles as the magnetic core. Thermally resistant particles, with high and accessible surface area, narrow particle size distribution, high saturation magnetization, and with superparamagnetic properties were obtained. Several reaction conditions were tested, yielding materials with saturation magnetization between 45 and 63 emu g{sup −1}, particle size between 2 and 200 μm and average diameter between 11.2 and 15.9 μm, surface area between 49 and 103 m{sup 2} g{sup −1} and pore diameter between 2 and 60 nm. The performance of SMMps in a bioprocess was evaluated by the immobilization of Pseudomonas fluorescens lipase on to octyl modified SMMp, the biocatalyst obtained was used in the production of butyl butyrate with good results.

  15. Bioprocessing of sewage sludge for safe recycling on agricultural land - BIOWASTE

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Jens Ejbye; Angelidaki, Irini; Christensen, Nina; Batstone, Damien John; Lyberatos, Gerasimos; Stamatelatou, Katerina; Lichtfouse, Eric; Elbisser, Brigitte; Rogers, Kayne; Sappin-Didier, Valerie; Dernaix, Laurence; Caria; Giovanni; Metzger, Laure; Borghi, Veronica; Montcada, Eloi

    2003-07-01

    Disposal and handling of sewage sludge are increasing problems in Europe due to the increasing quantities of the sewage sludge produced. A large amount of the sewage sludge contains small fractions of toxic chemicals, which results in problems with safe use of the sewage sludge on agricultural land. From an ecological and economical point of view, it would be essential to establish methodologies, which could allow sewage sludge to be reused as fertilizers on agricultural land. Energy efficient biotreatment processes of organic waste are, therefore, of crucial importance. BIOWASTE will offer an integrated study of this area. The typical composition of sewage sludge will be characterized with regard to key contaminating compounds. The following compounds will be in focus: Emulsifying agents such as nonylphenols and nonylphenol ethoxylates (NPE), polycyclic aromatic hydrocarbons (PAHs) derived from incomplete combustion processes and phthalates, which are used as additives in plastics and surfactants such as linear alkyl benzene sulfonate (LAS). Analytical techniques suitable for qualitative and quantitative evaluation of the chemical species involved in the processes under investigation will be determined. Bacteria that are able to degrade selected contaminating compounds under anaerobic and aerobic conditions will be isolated, characterized and bioaugmented for decontamination of sewage sludge through bioprocessing. Aerobic, anaerobic and combination of aerobic/anaerobic bioprocessing of sewage sludge will be applied. A mathematical model will be developed to describe the biodegradation processes of the contaminating compounds after establishing the kinetic parameters for degradation of contaminating compounds. The bioprocessed sewage sludge will be used in eco- and plant- toxicology tests to evaluate the impact of the xenobiotics on the environment. Methodologies will be developed and applied to assess the cleanliness of the bioprocessing as a safe method for waste

  16. Sense and sensitivity in bioprocessing-detecting cellular metabolites with biosensors.

    Science.gov (United States)

    Dekker, Linda; Polizzi, Karen M

    2017-10-01

    Biosensors use biological elements to detect or quantify an analyte of interest. In bioprocessing, biosensors are employed to monitor key metabolites. There are two main types: fully biological systems or biological recognition coupled with physical/chemical detection. New developments in chemical biosensors include multiplexed detection using microfluidics. Synthetic biology can be used to engineer new biological biosensors with improved characteristics. Although there have been few biosensors developed for bioprocessing thus far, emerging trends can be applied in the future. A range of new platform technologies will enable rapid engineering of new biosensors based on transcriptional activation, riboswitches, and Förster Resonance Energy Transfer. However, translation to industry remains a challenge and more research into the robustness biosensors at scale is needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Design of digital learning material for bioprocess-engineering-education

    NARCIS (Netherlands)

    Schaaf, van der H.

    2007-01-01

    With the advance of computers and the internet, new types of learning material can be developed: web-based digital learning material. Because many complex learning objectives in the food- and bioprocess technology domain are difficult to achieve in a traditional learning environment, a project was

  18. Therapeutic antibodies: market considerations, disease targets and bioprocessing.

    Science.gov (United States)

    Elvin, John G; Couston, Ruairidh G; van der Walle, Christopher F

    2013-01-02

    Antibodies are well established in mainstream clinical practice and present an exciting area for collaborative research and development in industry and academia alike. In this review, we will provide an overview of the current market and an outlook to 2015, focussing on whole antibody molecules while acknowledging the next generation scaffolds containing variable fragments. The market will be discussed in the context of disease targets, particularly in the areas of oncology and immune disorders which generate the greatest revenue by a wide margin. Emerging targets include central nervous system disorders which will also stimulate new delivery strategies. It is becoming increasingly apparent that a better understanding of bioprocessing is required in order to optimize the steps involved in the preparation of a protein prior to formulation. The latter is outside the scope of this review and nor is it our intention to discuss protein delivery and pharmacokinetics. The challenges that lie ahead include the discovery of new disease targets and the development of robust bioprocessing operations. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  19. Application of agent-based system for bioprocess description and process improvement.

    Science.gov (United States)

    Gao, Ying; Kipling, Katie; Glassey, Jarka; Willis, Mark; Montague, Gary; Zhou, Yuhong; Titchener-Hooker, Nigel J

    2010-01-01

    Modeling plays an important role in bioprocess development for design and scale-up. Predictive models can also be used in biopharmaceutical manufacturing to assist decision-making either to maintain process consistency or to identify optimal operating conditions. To predict the whole bioprocess performance, the strong interactions present in a processing sequence must be adequately modeled. Traditionally, bioprocess modeling considers process units separately, which makes it difficult to capture the interactions between units. In this work, a systematic framework is developed to analyze the bioprocesses based on a whole process understanding and considering the interactions between process operations. An agent-based approach is adopted to provide a flexible infrastructure for the necessary integration of process models. This enables the prediction of overall process behavior, which can then be applied during process development or once manufacturing has commenced, in both cases leading to the capacity for fast evaluation of process improvement options. The multi-agent system comprises a process knowledge base, process models, and a group of functional agents. In this system, agent components co-operate with each other in performing their tasks. These include the description of the whole process behavior, evaluating process operating conditions, monitoring of the operating processes, predicting critical process performance, and providing guidance to decision-making when coping with process deviations. During process development, the system can be used to evaluate the design space for process operation. During manufacture, the system can be applied to identify abnormal process operation events and then to provide suggestions as to how best to cope with the deviations. In all cases, the function of the system is to ensure an efficient manufacturing process. The implementation of the agent-based approach is illustrated via selected application scenarios, which

  20. Systematic Development of Miniaturized (Bio)Processes using Process Systems Engineering (PSE) Methods and Tools

    DEFF Research Database (Denmark)

    Krühne, Ulrich; Larsson, Hilde; Heintz, Søren

    2014-01-01

    The focus of this work is on process systems engineering (PSE) methods and tools, and especially on how such PSE methods and tools can be used to accelerate and support systematic bioprocess development at a miniature scale. After a short presentation of the PSE methods and the bioprocess...... development drivers, three case studies are presented. In the first example it is demonstrated how experimental investigations of the bi-enzymatic production of lactobionic acid can be modeled with help of a new mechanistic mathematical model. The reaction was performed at lab scale and the prediction quality...

  1. Monoliths in Bioprocess Technology

    Directory of Open Access Journals (Sweden)

    Vignesh Rajamanickam

    2015-04-01

    Full Text Available Monolithic columns are a special type of chromatography column, which can be used for the purification of different biomolecules. They have become popular due to their high mass transfer properties and short purification times. Several articles have already discussed monolith manufacturing, as well as monolith characteristics. In contrast, this review focuses on the applied aspect of monoliths and discusses the most relevant biomolecules that can be successfully purified by them. We describe success stories for viruses, nucleic acids and proteins and compare them to conventional purification methods. Furthermore, the advantages of monolithic columns over particle-based resins, as well as the limitations of monoliths are discussed. With a compilation of commercially available monolithic columns, this review aims at serving as a ‘yellow pages’ for bioprocess engineers who face the challenge of purifying a certain biomolecule using monoliths.

  2. Production-process optimization algorithm: Application to fed-batch bioprocess

    Czech Academy of Sciences Publication Activity Database

    Pčolka, M.; Čelikovský, Sergej

    2017-01-01

    Roč. 354, č. 18 (2017), s. 8529-8551 ISSN 0016-0032 R&D Projects: GA ČR(CZ) GA17-04682S Institutional support: RVO:67985556 Keywords : Optimal control * Bioprocess * Optimization Subject RIV: BC - Control Systems Theory OBOR OECD: Automation and control systems Impact factor: 3.139, year: 2016 https://doi.org/10.1016/j.jfranklin.2017.10.012

  3. Advances in Consolidated Bioprocessing Using Clostridium thermocellum and Thermoanaerobacter saccharolyticum

    Energy Technology Data Exchange (ETDEWEB)

    Lynd, Lee R. [Dartmouth College, Thayer School of Engineering; Guss, Adam M. [ORNL; Himmel, Mike [National Renewable Energy Laboratory (NREL); Beri, Dhananjay [Dartmouth College, Thayer School of Engineering; Herring, Christopher [Mascoma Corporation; Holwerda, Evert [Dartmouth College, Thayer School of Engineering; Murphy, Sean J. [Dartmouth College, Thayer School of Engineering; Olson, Daniel G. [Dartmouth College, Thayer School of Engineering; Paye, Julie [Dartmouth College, Thayer School of Engineering; Rydzak, Thomas [ORNL; Shao, Xiongjun [Dartmouth College, Thayer School of Engineering; Tian, Liang [Dartmouth College, Thayer School of Engineering; Worthen, Robert [Dartmouth College, Thayer School of Engineering

    2016-11-01

    Recent advances are addressed pertaining to consolidated bioprocessing (CBP) of plant cell walls to ethanol using two thermophilic, saccharolytic bacteria: the cellulose-fermenting Clostridium thermocellum and the hemicellulose- fermenting ermoanaerobacterium saccharolyticum. On the basis of the largest comparative dataset assembled to date, it appears that C. thermocellum is substantially more effective at solubilizing unpretreated plant cell walls than industry-standard fungal cellulase, and that this is particularly the case for more recalcitrant feedstocks. e distinctive central metabolism of C. thermocellum appears to involve more extensive energy coupling (e.g., on the order of 5 ATP per glucosyl moiety) than most fermentative anaerobes. Ethanol yields and titers realized by engineered strains of T. saccharolyticum meet standards for industrial feasibility and provide an important proof of concept as well as a model that may be emulated in other organisms. Progress has also been made with C. thermocellum, although not yet to this extent. e current state of strain development is summarized and outstanding challenges for commercial application are discussed. We speculate that CBP organism development is more promising starting with naturally occurring cellulolytic microbes as compared to starting with noncellulolytic hosts.

  4. Fundamental Principles of Stem Cell Banking.

    Science.gov (United States)

    Sun, Changbin; Yue, Jianhui; He, Na; Liu, Yaqiong; Zhang, Xi; Zhang, Yong

    2016-01-01

    Stem cells are highly promising resources for application in cell therapy, regenerative medicine, drug discovery, toxicology and developmental biology research. Stem cell banks have been increasingly established all over the world in order to preserve their cellular characteristics, prevent contamination and deterioration, and facilitate their effective use in basic and translational research, as well as current and future clinical application. Standardization and quality control during banking procedures are essential to allow researchers from different labs to compare their results and to develop safe and effective new therapies. Furthermore, many stem cells come from once-in-a-life time tissues. Cord blood for example, thrown away in the past, can be used to treat many diseases such as blood cancers nowadays. Meanwhile, these cells stored and often banked for long periods can be immediately available for treatment when needed and early treatment can minimize disease progression. This paper provides an overview of the fundamental principles of stem cell banking, including: (i) a general introduction of the construction and architecture commonly used for stem cell banks; (ii) a detailed section on current quality management practices; (iii) a summary of questions we should consider for long-term storage, such as how long stem cells can be stored stably, how to prevent contamination during long term storage, etc.; (iv) the prospects for stem cell banking.

  5. Fundamentals and Application of Magnetic Particles in Cell Isolation and Enrichment

    Science.gov (United States)

    Plouffe, Brian D.; Murthy, Shashi K.; Lewis, Laura H.

    2014-01-01

    Magnetic sorting using magnetic beads has become a routine methodology for the separation of key cell populations from biological suspensions. Due to the inherent ability of magnets to provide forces at a distance, magnetic cell manipulation is now a standardized process step in numerous processes in tissue engineering, medicine, and in fundamental biological research. Herein we review the current status of magnetic particles to enable isolation and separation of cells, with a strong focus on the fundamental governing physical phenomena, properties and syntheses of magnetic particles and on current applications of magnet-based cell separation in laboratory and clinical settings. We highlight the contribution of cell separation to biomedical research and medicine and detail modern cell separation methods (both magnetic and non-magnetic). In addition to a review of the current state-of-the-art in magnet-based cell sorting, we discuss current challenges and available opportunities for further research, development and commercialization of magnetic particle-based cell separation systems. PMID:25471081

  6. miRNA engineering of CHO cells facilitates production of difficult-to-express proteins and increases success in cell line development.

    Science.gov (United States)

    Fischer, Simon; Marquart, Kim F; Pieper, Lisa A; Fieder, Juergen; Gamer, Martin; Gorr, Ingo; Schulz, Patrick; Bradl, Harald

    2017-07-01

    In recent years, coherent with growing biologics portfolios also the number of complex and thus difficult-to-express (DTE) therapeutic proteins has increased considerably. DTE proteins challenge bioprocess development and can include various therapeutic protein formats such as monoclonal antibodies (mAbs), multi-specific affinity scaffolds (e.g., bispecific antibodies), cytokines, or fusion proteins. Hence, the availability of robust and versatile Chinese hamster ovary (CHO) host cell factories is fundamental for high-yielding bioprocesses. MicroRNAs (miRNAs) have emerged as potent cell engineering tools to improve process performance of CHO manufacturing cell lines. However, there has not been any report demonstrating the impact of beneficial miRNAs on industrial cell line development (CLD) yet. To address this question, we established novel CHO host cells constitutively expressing a pro-productive miRNA: miR-557. Novel host cells were tested in two independent CLD campaigns using two different mAb candidates including a normal as well as a DTE antibody. Presence of miR-557 significantly enhanced each process step during CLD in a product independent manner. Stable expression of miR-557 increased the probability to identify high-producing cell clones. Furthermore, production cell lines derived from miR-557 expressing host cells exhibited significantly increased final product yields in fed-batch cultivation processes without compromising product quality. Strikingly, cells co-expressing miR-557 and a DTE antibody achieved a twofold increase in product titer compared to clones co-expressing a negative control miRNA. Thus, host cell engineering using miRNAs represents a promising tool to overcome limitations in industrial CLD especially with regard to DTE proteins. Biotechnol. Bioeng. 2017;114: 1495-1510. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Gas cell neutralizers (Fundamental principles)

    International Nuclear Information System (INIS)

    Fuehrer, B.

    1985-06-01

    Neutralizing an ion-beam of the size and energy levels involved in the neutral-particle-beam program represents a considerable extension of the state-of-the-art of neutralizer technology. Many different mediums (e.g., solid, liquid, gas, plasma, photons) can be used to strip the hydrogen ion of its extra electron. A large, multidisciplinary R and D effort will no doubt be required to sort out all of the ''pros and cons'' of these various techniques. The purpose of this particular presentation is to discuss some basic configurations and fundamental principles of the gas type of neutralizer cell. Particular emphasis is placed on the ''Gasdynamic Free-Jet'' neutralizer since this configuration has the potential of being much shorter than other type of gas cells (in the beam direction) and it could operate in nearly a continuous mode (CW) if necessary. These were important considerations in the ATSU design which is discussed in some detail in the second presentation entitled ''ATSU Point Design''

  8. Bioprocessing of ores: Application to space resources

    Science.gov (United States)

    Johansson, Karl R.

    1992-01-01

    The role of microorganisms in the oxidation and leaching of various ores (especially those of copper, iron, and uranium) is well known. This role is increasingly being applied by the mining, metallurgy, and sewage industries in the bioconcentration of metal ions from natural receiving waters and from waste waters. It is concluded that bioprocessing using bacteria in closed reactors may be a variable option for the recovery of metals from the lunar regolith. Obviously, considerable research must be done to define the process, specify the appropriate bacteria, determine the necessary conditions and limitations, and evaluate the overall feasibility.

  9. Bioprocessing of wheat bran in whole wheat bread increases the bioavailability of phenolic acids in men and exerts antiinflammatory effects ex vivo.

    Science.gov (United States)

    Mateo Anson, Nuria; Aura, Anna-Marja; Selinheimo, Emilia; Mattila, Ismo; Poutanen, Kaisa; van den Berg, Robin; Havenaar, Robert; Bast, Aalt; Haenen, Guido R M M

    2011-01-01

    Whole grain consumption has been linked to a lower risk of metabolic syndrome, which is normally associated with a low-grade chronic inflammation. The benefits of whole grain are in part related to the inclusion of the bran, rich in phenolic acids and fiber. However, the phenols are poorly bioaccessible from the cereal matrix. The aim of the present study was to investigate the effect of bioprocessing of the bran in whole wheat bread on the bioavailability of phenolic acids, the postprandial plasma antioxidant capacity, and ex vivo antiinflammatory properties. After consumption of a low phenolic acid diet for 3 d and overnight fasting, 8 healthy men consumed 300 g of whole wheat bread containing native bran (control bread) or bioprocessed bran (bioprocessed bread) in a cross-over design. Urine and blood samples were collected for 24 h to analyze the phenolic acids and metabolites. Trolox equivalent antioxidant capacity was measured in plasma. Cytokines were measured in blood after ex vivo stimulation with LPS. The bioavailabilities of ferulic acid, vanillic acid, sinapic acid, and 3,4-dimethoxybenzoic acid from the bioprocessed bread were 2- to 3-fold those from the control bread. Phenylpropionic acid and 3-hydroxyphenylpropionic acid were the main colonic metabolites of the nonbioaccessible phenols. The ratios of pro-:antiinflammatory cytokines were significantly lower in LPS-stimulated blood after the consumption of the bioprocessed bread. In conclusion, bioprocessing can remarkably increase the bioavailability of phenolic acids and their circulating metabolites, compounds which have immunomodulatory effects ex vivo.

  10. A one-step bioprocess for production of high-content fructo-oligosaccharides from inulin by yeast.

    Science.gov (United States)

    Wang, Da; Li, Fu-Li; Wang, Shi-An

    2016-10-20

    Commercial fructo-oligosaccharides (FOS) are predominantly produced from sucrose by transfructosylation process that presents a maximum theoretical yield below 0.60gFOSgSucrose(-1). To obtain high-content FOS, costly purification is generally employed. Additionally, high-content FOS can be produced from inulin by using endo-inulinases. However, commercial endo-inulinases have not been extensively used in scale-up production of FOS. In the present study, a one-step bioprocess that integrated endo-inulinase production, FOS fermentation, and non-FOS sugars removal into one reactor was proposed to produce high-content FOS from inulin. The bioprocess was implemented by a recombinant yeast strain JZHΔS-TSC, in which a heterologous endo-inulinase gene was expressed and the inherent invertase gene SUC2 was disrupted. FOS fermentation at 40°C from 200g/L chicory inulin presented the maximun titer, yield, and productivity of 180.2±0.8g/L, 0.9gFOSgInulin(-1), and 7.51±0.03g/L/h, respectively. This study demonstrated that the one-step bioprocess was simple and highly efficient. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Elm Tree (Ulmus parvifolia) Bark Bioprocessed with Mycelia of Shiitake (Lentinus edodes) Mushrooms in Liquid Culture: Composition and Mechanism of Protection against Allergic Asthma in Mice.

    Science.gov (United States)

    Kim, Sung Phil; Lee, Sang Jong; Nam, Seok Hyun; Friedman, Mendel

    2016-02-03

    Mushrooms can break down complex plant materials into smaller, more digestible and bioactive compounds. The present study investigated the antiasthma effect of an Ulmus parvifolia bark extract bioprocessed in Lentinus edodes liquid mycelium culture (BPUBE) against allergic asthma in chicken egg ovalbumin (OVA)-sensitized/challenged mice. BPUBE suppressed total IgE release from U266B1 cells in a dose-dependent manner without cytotoxicity. Inhibitory activity of BPUBE against OVA-specific IgE secretion in bronchoalveolar lavage fluid (BALF) was observed in OVA-sensitized/challenged asthmatic mice. BPUBE also inhibited OVA-specific IgG and IgG1 secretion into serum from the allergic mice, suggesting the restoration of a Th2-biased immune reaction to a Th1/Th2-balanced status, as indicated by the Th1/Th2 as well as regulatory T cell (Treg) cytokine profile changes caused by BPUBE in serum or BALF. Inflammatory cell counts in BALF and lung histology showed that leukocytosis and eosinophilia induced by OVA-sensitization/challenge were inhibited by the oral administration of BPUBE. Amelioration of eosinophil infiltration near the trachea was associated with reduced eotaxin and vascular cell adhesion molecule-1 (VCAM-1) levels. Changes in proinflammatory mediator levels in BALF suggest that BPUBE decreased OVA-sensitization-induced elevation of leukotriene C4 (LTC4) and prostaglandin D2 (PGD2). The finding that asthma-associated biomarker levels of OVA-sensitized/challenged mice were much more inhibited with BPUBE treatment than NPUBE (not-bioprocessed Ulmus parvifolia extract) treatment suggested the production of new bioactive compounds by the mushroom mycelia that may be involved in enhancing the observed antiasthmatic properties. The possible relation of the composition determined by proximate analysis and GC/MS to observed bioactivity is discussed. The results suggest that the elm tree (Ulmus parvifolia) bark bioprocessed with mycelia of shiitake (Lentinus edodes

  12. A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

    KAUST Repository

    Hefzi, Hooman

    2016-11-23

    Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in CHO and associated them with >1,700 genes in the Cricetulus griseus genome. The genome-scale metabolic model based on this reconstruction, iCHO1766, and cell-line-specific models for CHO-K1, CHO-S, and CHO-DG44 cells provide the biochemical basis of growth and recombinant protein production. The models accurately predict growth phenotypes and known auxotrophies in CHO cells. With the models, we quantify the protein synthesis capacity of CHO cells and demonstrate that common bioprocess treatments, such as histone deacetylase inhibitors, inefficiently increase product yield. However, our simulations show that the metabolic resources in CHO are more than three times more efficiently utilized for growth or recombinant protein synthesis following targeted efforts to engineer the CHO secretory pathway. This model will further accelerate CHO cell engineering and help optimize bioprocesses.

  13. Bioprocessing of lignite coals using reductive microorganisms

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, D.L.

    1992-03-29

    In order to convert lignite coals into liquid fuels, gases or chemical feedstock, the macromolecular structure of the coal must be broken down into low molecular weight fractions prior to further modification. Our research focused on this aspect of coal bioprocessing. We isolated, characterized and studied the lignite coal-depolymerizing organisms Streptomyces viridosporus T7A, Pseudomonas sp. DLC-62, unidentified bacterial strain DLC-BB2 and Gram-positive Bacillus megaterium strain DLC-21. In this research we showed that these bacteria are able to solubilize and depolymerize lignite coals using a combination of biological mechanisms including the excretion of coal solublizing basic chemical metabolites and extracellular coal depolymerizing enzymes.

  14. Consolidated bioprocessing for production of polyhydroxyalkanotes from red algae Gelidium amansii.

    Science.gov (United States)

    Sawant, Shailesh S; Salunke, Bipinchandra K; Kim, Beom Soo

    2018-04-01

    Noncompetitive carbon sources such as algae are unconventional and promising raw material for sustainable biofuel production. The capability of one marine bacterium, Saccharophagus degradans 2-40 to degrade red seaweed Gelidium amansii for production of polyhydroxyalkanoates (PHA) was evaluated in this study. S. degradans can readily attach to algae, degrade algal carbohydrates, and utilize that material as main carbon source. Minimal media containing 8g/L G. amansii were used for the growth of S. degradans. The PHA content obtained was 17-27% of dry cell weight by pure culture of S. degradans and co-culture of S. degradans and Bacillus cereus, a contaminant found with S. degradans cultures. The PHA type was found to be poly(3-hydroxybutyrate) by gas chromatography and Fourier transform-infrared spectroscopy. This work demonstrates PHA production through consolidated bioprocessing of insoluble, untreated red algae by bacterial pure culture and co-culture. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Biogas production from organic wastes in suspended cell cultures and in biofilms

    International Nuclear Information System (INIS)

    Simenonov, I.; Chorukova, E.; Mamatarkova, V.; Nikolov, L.

    2010-01-01

    The results of a comparative study of two biogas production bioprocess systems are presented. The systems submitted to comparison are based on the suspended cells cultures and the biofilm formed on solid inert support. A comprehensive research concept is formulated and discussed. It includes the main considerations regarding the choice of substrate, bioagent as mixed microbial society, type of bioreactors, regimes of functioning, analytical determinations and method of comparison. The main requirements for efficient experimental activity in comparative investigations are formulated. Their satisfaction can grant correctness of the experimental design and data acquisition. On this basis the key parameter of comparison of the two systems is defined as the specific productivity of the bioprocess systems. Under these conditions series of preliminary experiments are carried out for testing the readiness of experimental set ups for long time stable functioning and monitoring devices capabilities to maintain the bioprocess parameters at the determined intervals. These tests grant continuous incessant experimentation with the investigated bioprocess systems. The results obtained show that biofilm bioprocess systems possess up to two and half time higher specific productivity in comparison with the bioprocess systems with the suspended cells. Some visions about the future developments of comparative research on the influence of additional parameters like the mixer rotation steed, organic loads, and higher values of dilution rates are outlined.

  16. Design-for-Six-Sigma To Develop a Bioprocess Knowledge Management Framework.

    Science.gov (United States)

    Junker, Beth; Maheshwari, Gargi; Ranheim, Todd; Altaras, Nedim; Stankevicz, Michael; Harmon, Lori; Rios, Sandra; D'anjou, Marc

    2011-01-01

    Owing to the high costs associated with biopharmaceutical development, considerable pressure has developed for the biopharmaceutical industry to increase productivity by becoming more lean and flexible. The ability to reuse knowledge was identified as one key advantage to streamline productivity, efficiently use resources, and ultimately perform better than the competition. A knowledge management (KM) strategy was assembled for bioprocess-related information using the technique of Design-for-Six-Sigma (DFSS). This strategy supported quality-by-design and process validation efforts for pipeline as well as licensed products. The DFSS technique was selected because it was both streamlined and efficient. These characteristics permitted development of a KM strategy with minimized team leader and team member resources. DFSS also placed a high emphasis on the voice of the customer, information considered crucial to the selection of solutions most appropriate for the current knowledge-based challenges of the organization. The KM strategy developed was comprised of nine workstreams, constructed from related solution buckets which in turn were assembled from the individual solution tasks that were identified. Each workstream's detailed design was evaluated against published and established best practices, as well as the KM strategy project charter and design inputs. Gaps and risks were identified and mitigated as necessary to improve the robustness of the proposed strategy. Aggregated resources (specifically expense/capital funds and staff) and timing were estimated to obtain vital management sponsorship for implementation. Where possible, existing governance and divisional/corporate information technology efforts were leveraged to minimize the additional bioprocess resources required for implementation. Finally, leading and lagging indicator metrics were selected to track the success of pilots and eventual implementation. A knowledge management framework was assembled for

  17. Fundamental Limit of Nanophotonic Light-trapping in Solar Cells

    OpenAIRE

    Yu, Zongfu; Raman, Aaswath; Fan, Shanhui

    2010-01-01

    Establishing the fundamental limit of nanophotonic light-trapping schemes is of paramount importance and is becoming increasingly urgent for current solar cell research. The standard theory of light trapping demonstrated that absorption enhancement in a medium cannot exceed a factor of 4n^2/ sin^2(\\theta), where n is the refractive index of the active layer, and \\theta is the angle of the emission cone in the medium surrounding the cell. This theory, however, is not applicable in the nanophot...

  18. ADAPTIVE HIGH GAIN OBSERVER EXTENSION AND ITS APPLICATION TO BIOPROCESS MONITORING

    Czech Academy of Sciences Publication Activity Database

    Čelikovský, Sergej; Torres-Munoz, J. A.; Dominguez-Bocanegra, A. R.

    2018-01-01

    Roč. 54, č. 1 (2018), s. 155-174 ISSN 0023-5954 Institutional support: RVO:67985556 Keywords : Adaptive observers * nonlinear systems * bioprocess Subject RIV: BC - Control Systems Theory OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.379, year: 2016 http://doi.org/10.14736/kyb-2018-1-0155

  19. Effect of Bioprocessing on the In Vitro Colonic Microbial Metabolism of Phenolic Acids from Rye Bran Fortified Breads

    DEFF Research Database (Denmark)

    Koistinen, Ville M; Nordlund, Emilia; Katina, Kati

    2017-01-01

    in an in vitro colon model, the metabolites were analyzed using two different methods applying mass spectrometry. While phenolic acids were released more extensively from the bioprocessed bran bread and ferulic acid had consistently higher concentrations in the bread type during fermentation, there were only......Cereal bran is an important source of dietary fiber and bioactive compounds, such as phenolic acids. We aimed to study the phenolic acid metabolism of native and bioprocessed rye bran fortified refined wheat bread and to elucidate the microbial metabolic route of phenolic acids. After incubation...

  20. PEM fuel cells thermal and water management fundamentals

    CERN Document Server

    Wang, Yun; Cho, Sung Chan

    2014-01-01

    Polymer Electrolyte Membrane (PEM) fuel cells convert chemical energy in hydrogen into electrical energy with water as the only by-product. Thus, PEM fuel cells hold great promise to reduce both pollutant emissions and dependency on fossil fuels, especially for transportation-passenger cars, utility vehicles, and buses-and small-scale stationary and portable power generators. But one of the greatest challenges to realizing the high efficiency and zero emissions potential of PEM fuel cells technology is heat and water management. This book provides an introduction to the essential concepts for effective thermal and water management in PEM fuel cells and an assessment on the current status of fundamental research in this field. The book offers you: An overview of current energy and environmental challenges and their imperatives for the development of renewable energy resources, including discussion of the role of PEM fuel cells in addressing these issues; Reviews of basic principles pertaining to PEM fuel cel...

  1. Catalysis in electrochemistry: from fundamentals to strategies for fuel cell development

    National Research Council Canada - National Science Library

    Santos, Elizabeth; Schmickler, Wolfgang

    2011-01-01

    "Catalysis in Electrochemistry: From Fundamentals to Strategies for Fuel Cell Development is a modern, comprehensive reference work on catalysis in electrochemistry, including principles, methods, strategies, and applications...

  2. Fundamentals and application of magnetic particles in cell isolation and enrichment: a review

    International Nuclear Information System (INIS)

    Plouffe, Brian D; Murthy, Shashi K; Lewis, Laura H

    2015-01-01

    Magnetic sorting using magnetic beads has become a routine methodology for the separation of key cell populations from biological suspensions. Due to the inherent ability of magnets to provide forces at a distance, magnetic cell manipulation is now a standardized process step in numerous processes in tissue engineering, medicine, and in fundamental biological research. Herein we review the current status of magnetic particles to enable isolation and separation of cells, with a strong focus on the fundamental governing physical phenomena, properties and syntheses of magnetic particles and on current applications of magnet-based cell separation in laboratory and clinical settings. We highlight the contribution of cell separation to biomedical research and medicine and detail modern cell-separation methods (both magnetic and non-magnetic). In addition to a review of the current state-of-the-art in magnet-based cell sorting, we discuss current challenges and available opportunities for further research, development and commercialization of magnetic particle-based cell-separation systems. (review article)

  3. Teaching bioprocess engineering to undergraduates: Multidisciplinary hands-on training in a one-week practical course.

    Science.gov (United States)

    Henkel, Marius; Zwick, Michaela; Beuker, Janina; Willenbacher, Judit; Baumann, Sandra; Oswald, Florian; Neumann, Anke; Siemann-Herzberg, Martin; Syldatk, Christoph; Hausmann, Rudolf

    2015-01-01

    Bioprocess engineering is a highly interdisciplinary field of study which is strongly benefited by practical courses where students can actively experience the interconnection between biology, engineering, and physical sciences. This work describes a lab course developed for 2nd year undergraduate students of bioprocess engineering and related disciplines, where students are challenged with a real-life bioprocess-engineering application, the production of recombinant protein in a fed-batch process. The lab course was designed to introduce students to the subject of operating and supervising an experiment in a bioreactor, along with the analysis of collected data and a final critical evaluation of the experiment. To provide visual feedback of the experimental outcome, the organism used during class was Escherichia coli which carried a plasmid to recombinantly produce enhanced green fluorescent protein (eGFP) upon induction. This can easily be visualized in both the bioreactor and samples by using ultraviolet light. The lab course is performed with bioreactors of the simplest design, and is therefore highly flexible, robust and easy to reproduce. As part of this work the implementation and framework, the results, the evaluation and assessment of student learning combined with opinion surveys are presented, which provides a basis for instructors intending to implement a similar lab course at their respective institution. © 2015 by the International Union of Biochemistry and Molecular Biology.

  4. BIOPROCESS DEVELOPMENTS FOR CELLULASE PRODUCTION BY Aspergillus oryzae CULTIVATED UNDER SOLID-STATE FERMENTATION

    Directory of Open Access Journals (Sweden)

    R. D. P. B. Pirota

    Full Text Available Abstract Bioprocess development studies concerning the production of cellulases are of crucial importance due to the significant impact of these enzymes on the economics of biomass conversion into fuels and chemicals. This work evaluates the effects of solid-state fermentation (SSF operational conditions on cellulase production by a novel strain of Aspergillus oryzae using an instrumented lab-scale bioreactor equipped with an on-line automated monitoring and control system. The use of SSF cultivation under controlled conditions substantially improved cellulase production. Highest production of FPase (0.40 IU g-1, endoglucanase (123.64 IU g-1, and β-glucosidase (18.32 IU g-1 was achieved at 28 °C, using an initial substrate moisture content of 70%, with an inlet air humidity of 80% and an airflow rate of 20 mL min-1. Further studies of kinetic profiles and respirometric analyses were performed. The results showed that these data could be very useful for bioprocess development of cellulase production and scale-up.

  5. Integrated continuous bioprocessing: Economic, operational, and environmental feasibility for clinical and commercial antibody manufacture

    Science.gov (United States)

    Pollock, James; Coffman, Jon; Ho, Sa V.

    2017-01-01

    This paper presents a systems approach to evaluating the potential of integrated continuous bioprocessing for monoclonal antibody (mAb) manufacture across a product's lifecycle from preclinical to commercial manufacture. The economic, operational, and environmental feasibility of alternative continuous manufacturing strategies were evaluated holistically using a prototype UCL decisional tool that integrated process economics, discrete‐event simulation, environmental impact analysis, operational risk analysis, and multiattribute decision‐making. The case study focused on comparing whole bioprocesses that used either batch, continuous or a hybrid combination of batch and continuous technologies for cell culture, capture chromatography, and polishing chromatography steps. The cost of goods per gram (COG/g), E‐factor, and operational risk scores of each strategy were established across a matrix of scenarios with differing combinations of clinical development phase and company portfolio size. The tool outputs predict that the optimal strategy for early phase production and small/medium‐sized companies is the integrated continuous strategy (alternating tangential flow filtration (ATF) perfusion, continuous capture, continuous polishing). However, the top ranking strategy changes for commercial production and companies with large portfolios to the hybrid strategy with fed‐batch culture, continuous capture and batch polishing from a COG/g perspective. The multiattribute decision‐making analysis highlighted that if the operational feasibility was considered more important than the economic benefits, the hybrid strategy would be preferred for all company scales. Further considerations outside the scope of this work include the process development costs required to adopt continuous processing. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:854–866, 2017

  6. Capacity Planning for Batch and Perfusion Bioprocesses Across Multiple Biopharmaceutical Facilities

    OpenAIRE

    Siganporia, Cyrus C; Ghosh, Soumitra; Daszkowski, Thomas; Papageorgiou, Lazaros G; Farid, Suzanne S

    2014-01-01

    Production planning for biopharmaceutical portfolios becomes more complex when products switch between fed-batch and continuous perfusion culture processes. This article describes the development of a discrete-time mixed integer linear programming (MILP) model to optimize capacity plans for multiple biopharmaceutical products, with either batch or perfusion bioprocesses, across multiple facilities to meet quarterly demands. The model comprised specific features to account for products with fe...

  7. Bioprocessing of wheat bran improves in vitro bioaccessibility and colonic metabolism of phenolic compounds

    NARCIS (Netherlands)

    Mateo Anson, N.; Selinheimo, E.; Havenaar, R.; Aura, A.-M.; Mattila, I.; Lehtinen, P.; Bast, A.; Poutanen, K.; Haenen, G.R.M.M.

    2009-01-01

    Ferulic acid (FA) is the most abundant phenolic compound in wheat grain, mainly located in the bran. However, its bioaccessibility from the bran matrix is extremely low. Different bioprocessing techniques involving fermentation or enzymatic and fermentation treatments of wheat bran were developed

  8. Automated measurement and monitoring of bioprocesses: key elements of the M(3)C strategy.

    Science.gov (United States)

    Sonnleitner, Bernhard

    2013-01-01

    The state-of-routine monitoring items established in the bioprocess industry as well as some important state-of-the-art methods are briefly described and the potential pitfalls discussed. Among those are physical and chemical variables such as temperature, pressure, weight, volume, mass and volumetric flow rates, pH, redox potential, gas partial pressures in the liquid and molar fractions in the gas phase, infrared spectral analysis of the liquid phase, and calorimetry over an entire reactor. Classical as well as new optical versions are addressed. Biomass and bio-activity monitoring (as opposed to "measurement") via turbidity, permittivity, in situ microscopy, and fluorescence are critically analyzed. Some new(er) instrumental analytical tools, interfaced to bioprocesses, are explained. Among those are chromatographic methods, mass spectrometry, flow and sequential injection analyses, field flow fractionation, capillary electrophoresis, and flow cytometry. This chapter surveys the principles of monitoring rather than compiling instruments.

  9. Human pluripotent stem cell-derived products: advances towards robust, scalable and cost-effective manufacturing strategies.

    Science.gov (United States)

    Jenkins, Michael J; Farid, Suzanne S

    2015-01-01

    The ability to develop cost-effective, scalable and robust bioprocesses for human pluripotent stem cells (hPSCs) will be key to their commercial success as cell therapies and tools for use in drug screening and disease modelling studies. This review outlines key process economic drivers for hPSCs and progress made on improving the economic and operational feasibility of hPSC bioprocesses. Factors influencing key cost metrics, namely capital investment and cost of goods, for hPSCs are discussed. Step efficiencies particularly for differentiation, media requirements and technology choice are amongst the key process economic drivers identified for hPSCs. Progress made to address these cost drivers in hPSC bioprocessing strategies is discussed. These include improving expansion and differentiation yields in planar and bioreactor technologies, the development of xeno-free media and microcarrier coatings, identification of optimal bioprocess operating conditions to control cell fate and the development of directed differentiation protocols that reduce reliance on expensive morphogens such as growth factors and small molecules. These approaches offer methods to further optimise hPSC bioprocessing in terms of its commercial feasibility. © 2014 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  10. Program for fundamental and applied research of fuel cells in VNIIEF

    Energy Technology Data Exchange (ETDEWEB)

    Anisin, A.V.; Borisseonock, V.A.; Novitskii, Y.Z.; Potyomckin, G.A.

    1996-04-01

    According to VNIIEF the integral part of development of fuel cell power plants is fundamental and applied research. This paper describes areas of research on molten carbonate fuel cells. Topics include the development of mathematical models for porous electrodes, thin film electrolytes, the possibility of solid nickel anodes, model of activation polarization of anode, electrolyte with high solubility of oxygen. Other areas include research on a stationary mode of stack operation, anticorrosion coatings, impedance diagnostic methods, ultrasound diagnostics, radiation treatments, an air aluminium cell, and alternative catalysts for low temperature fuel cells.

  11. Scale-up bioprocess development for production of the antibiotic valinomycin in Escherichia coli based on consistent fed-batch cultivations.

    Science.gov (United States)

    Li, Jian; Jaitzig, Jennifer; Lu, Ping; Süssmuth, Roderich D; Neubauer, Peter

    2015-06-12

    Heterologous production of natural products in Escherichia coli has emerged as an attractive strategy to obtain molecules of interest. Although technically feasible most of them are still constrained to laboratory scale production. Therefore, it is necessary to develop reasonable scale-up strategies for bioprocesses aiming at the overproduction of targeted natural products under industrial scale conditions. To this end, we used the production of the antibiotic valinomycin in E. coli as a model system for scalable bioprocess development based on consistent fed-batch cultivations. In this work, the glucose limited fed-batch strategy based on pure mineral salt medium was used throughout all scales for valinomycin production. The optimal glucose feed rate was initially detected by the use of a biocatalytically controlled glucose release (EnBase® technology) in parallel cultivations in 24-well plates with continuous monitoring of pH and dissolved oxygen. These results were confirmed in shake flasks, where the accumulation of valinomycin was highest when the specific growth rate decreased below 0.1 h(-1). This correlation was also observed for high cell density fed-batch cultivations in a lab-scale bioreactor. The bioreactor fermentation produced valinomycin with titers of more than 2 mg L(-1) based on the feeding of a concentrated glucose solution. Valinomycin production was not affected by oscillating conditions (i.e. glucose and oxygen) in a scale-down two-compartment reactor, which could mimic similar situations in industrial bioreactors, suggesting that the process is very robust and a scaling of the process to a larger industrial scale appears a realistic scenario. Valinomycin production was scaled up from mL volumes to 10 L with consistent use of the fed-batch technology. This work presents a robust and reliable approach for scalable bioprocess development and represents an example for the consistent development of a process for a heterologously expressed natural

  12. Integrated continuous bioprocessing: Economic, operational, and environmental feasibility for clinical and commercial antibody manufacture.

    Science.gov (United States)

    Pollock, James; Coffman, Jon; Ho, Sa V; Farid, Suzanne S

    2017-07-01

    This paper presents a systems approach to evaluating the potential of integrated continuous bioprocessing for monoclonal antibody (mAb) manufacture across a product's lifecycle from preclinical to commercial manufacture. The economic, operational, and environmental feasibility of alternative continuous manufacturing strategies were evaluated holistically using a prototype UCL decisional tool that integrated process economics, discrete-event simulation, environmental impact analysis, operational risk analysis, and multiattribute decision-making. The case study focused on comparing whole bioprocesses that used either batch, continuous or a hybrid combination of batch and continuous technologies for cell culture, capture chromatography, and polishing chromatography steps. The cost of goods per gram (COG/g), E-factor, and operational risk scores of each strategy were established across a matrix of scenarios with differing combinations of clinical development phase and company portfolio size. The tool outputs predict that the optimal strategy for early phase production and small/medium-sized companies is the integrated continuous strategy (alternating tangential flow filtration (ATF) perfusion, continuous capture, continuous polishing). However, the top ranking strategy changes for commercial production and companies with large portfolios to the hybrid strategy with fed-batch culture, continuous capture and batch polishing from a COG/g perspective. The multiattribute decision-making analysis highlighted that if the operational feasibility was considered more important than the economic benefits, the hybrid strategy would be preferred for all company scales. Further considerations outside the scope of this work include the process development costs required to adopt continuous processing. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:854-866, 2017. © 2017 The

  13. Bioprocessing of concentrated mixed hazardous industrial waste

    International Nuclear Information System (INIS)

    Wolfram, J.H.; Rogers, R.D.; Silver, G.; Attalla, A.; Prisc, M.

    1994-01-01

    The use of selected microorganisms for the degradation and/or the detoxification of hazardous organic compounds is gaining wide acceptance as an alternative waste treatment technology. This work describes the unique capabilities of an isolated strain of Pseudomonas for metabolizing methylated aromatic compounds. This strain of Pseudomonas putida Idaho is unique in that it can tolerate and grow under a layer of neat p-xylene. A bioprocess has been developed to degrade LLW and mixed wastes containing methylated aromatic compounds, i.e., pseudocumene, toluene and p-xylene. The process is now in the demonstration phase at a DOE facility and has been running for one year. Feed concentrations of 21200 ppm of the toxic organic substrate have been fed to the bioreactor. This report describes the results obtained thus far

  14. Cleaner bioprocesses for promoting zero-emission biofuels production in Vojvodina

    Energy Technology Data Exchange (ETDEWEB)

    Dodic, Sinisa N.; Vucurovic, Damjan G.; Popov, Stevan D.; Dodic, Jelena M.; Rankovic, Jovana A. [Department of Biotechnology and Pharmaceutical Engineering, Faculty of Technology, University of Novi Sad, Bul. cara Lazara 1, Novi Sad 21000, Vojvodina (RS)

    2010-12-15

    In this study, the policy, market conditions and food security of biomass energy sources are assessed for supplying the future needs of Vojvodina. The Autonomous Province of Vojvodina is an autonomous province in Serbia, containing about 27% of its total population according to the 2002 Census. It is located in the northern part of the country, in the Pannonia plain, in southeastern Europe. Vojvodina is an energy-deficient province. The incentives to invest human and financial resources in the research and development of cleaner bioprocesses are high, considering the benefits which might be achieved in terms of environment protection and manufacturing costs. In the near and medium tenu, the development of bioprocesses for waste recycling and resource recovery might be one of the most viable options, considering much research work has already been done. In Vojvodina, there are technological solutions that biofuels produced in a closed cycle, so that the quantity of waste reduced to a minimum. These solutions include the stillage (remainder after distillation) used for fattening cattle, and cattle excrement to produce biogas and manure as fertilizer. The energy required for the production of bioethanol is obtained combustion lignocelullose residual waste from the production of basic raw materials starch, or biogas. Ash from the burned biomass returned to soil as a source of minerals for plants and replacement of mineral fertilizer. Such a closed cycle is economical for small farms in Vojvodina. (author)

  15. Cleaner bioprocesses for promoting zero-emission biofuels production in Vojvodina

    International Nuclear Information System (INIS)

    Dodic, Sinisa N.; Vucurovic, Damjan G.; Popov, Stevan D.; Dodic, Jelena M.; Rankovic, Jovana A.

    2010-01-01

    In this study, the policy, market conditions and food security of biomass energy sources are assessed for supplying the future needs of Vojvodina. The Autonomous Province of Vojvodina is an autonomous province in Serbia, containing about 27% of its total population according to the 2002 Census. It is located in the northern part of the country, in the Pannonia plain, in southeastern Europe. Vojvodina is an energy-deficient province. The incentives to invest human and financial resources in the research and development of cleaner bioprocesses are high, considering the benefits which might be achieved in terms of environment protection and manufacturing costs. In the near and medium tenu, the development of bioprocesses for waste recycling and resource recovery might be one of the most viable options, considering much research work has already been done. In Vojvodina, there are technological solutions that biofuels produced in a closed cycle, so that the quantity of waste reduced to a minimum. These solutions include the stillage (remainder after distillation) used for fattening cattle, and cattle excrement to produce biogas and manure as fertilizer. The energy required for the production of bioethanol is obtained combustion lignocelullose residual waste from the production of basic raw materials starch, or biogas. Ash from the burned biomass returned to soil as a source of minerals for plants and replacement of mineral fertilizer. Such a closed cycle is economical for small farms in Vojvodina. (author)

  16. Fundamental limit of nanophotonic light trapping in solar cells.

    Science.gov (United States)

    Yu, Zongfu; Raman, Aaswath; Fan, Shanhui

    2010-10-12

    Establishing the fundamental limit of nanophotonic light-trapping schemes is of paramount importance and is becoming increasingly urgent for current solar cell research. The standard theory of light trapping demonstrated that absorption enhancement in a medium cannot exceed a factor of 4n(2)/sin(2)θ, where n is the refractive index of the active layer, and θ is the angle of the emission cone in the medium surrounding the cell. This theory, however, is not applicable in the nanophotonic regime. Here we develop a statistical temporal coupled-mode theory of light trapping based on a rigorous electromagnetic approach. Our theory reveals that the conventional limit can be substantially surpassed when optical modes exhibit deep-subwavelength-scale field confinement, opening new avenues for highly efficient next-generation solar cells.

  17. A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

    KAUST Repository

    Hefzi, Hooman; Ang, Kok  Siong; Hanscho, Michael; Bordbar, Aarash; Ruckerbauer, David; Lakshmanan, Meiyappan; Orellana, Camila  A.; Baycin-Hizal, Deniz; Huang, Yingxiang; Ley, Daniel; Martinez, Veronica  S.; Kyriakopoulos, Sarantos; Jimé nez, Natalia  E.; Zielinski, Daniel  C.; Quek, Lake-Ee; Wulff, Tune; Arnsdorf, Johnny; Li, Shangzhong; Lee, Jae  Seong; Paglia, Giuseppe; Loira, Nicolas; Spahn, Philipp  N.; Pedersen, Lasse  E.; Gutierrez, Jahir  M.; King, Zachary  A.; Lund, Anne  Mathilde; Nagarajan, Harish; Thomas, Alex; Abdel-Haleem, Alyaa M.; Zanghellini, Juergen; Kildegaard, Helene  F.; Voldborg, Bjø rn  G.; Gerdtzen, Ziomara  P.; Betenbaugh, Michael  J.; Palsson, Bernhard  O.; Andersen, Mikael  R.; Nielsen, Lars  K.; Borth, Nicole; Lee, Dong-Yup; Lewis, Nathan  E.

    2016-01-01

    Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess

  18. Bioprocess iterative batch-to-batch optimization based on hybrid parametric/nonparametric models.

    Science.gov (United States)

    Teixeira, Ana P; Clemente, João J; Cunha, António E; Carrondo, Manuel J T; Oliveira, Rui

    2006-01-01

    This paper presents a novel method for iterative batch-to-batch dynamic optimization of bioprocesses. The relationship between process performance and control inputs is established by means of hybrid grey-box models combining parametric and nonparametric structures. The bioreactor dynamics are defined by material balance equations, whereas the cell population subsystem is represented by an adjustable mixture of nonparametric and parametric models. Thus optimizations are possible without detailed mechanistic knowledge concerning the biological system. A clustering technique is used to supervise the reliability of the nonparametric subsystem during the optimization. Whenever the nonparametric outputs are unreliable, the objective function is penalized. The technique was evaluated with three simulation case studies. The overall results suggest that the convergence to the optimal process performance may be achieved after a small number of batches. The model unreliability risk constraint along with sampling scheduling are crucial to minimize the experimental effort required to attain a given process performance. In general terms, it may be concluded that the proposed method broadens the application of the hybrid parametric/nonparametric modeling technique to "newer" processes with higher potential for optimization.

  19. A framework for model-based optimization of bioprocesses under uncertainty: Identifying critical parameters and operating variables

    DEFF Research Database (Denmark)

    Morales Rodriguez, Ricardo; Meyer, Anne S.; Gernaey, Krist

    2011-01-01

    This study presents the development and application of a systematic model-based framework for bioprocess optimization, evaluated on a cellulosic ethanol production case study. The implementation of the framework involves the use of dynamic simulations, sophisticated uncertainty analysis (Monte...

  20. Photonic Design: From Fundamental Solar Cell Physics to Computational Inverse Design

    Science.gov (United States)

    Miller, Owen Dennis

    Photonic innovation is becoming ever more important in the modern world. Optical systems are dominating shorter and shorter communications distances, LED's are rapidly emerging for a variety of applications, and solar cells show potential to be a mainstream technology in the energy space. The need for novel, energy-efficient photonic and optoelectronic devices will only increase. This work unites fundamental physics and a novel computational inverse design approach towards such innovation. The first half of the dissertation is devoted to the physics of high-efficiency solar cells. As solar cells approach fundamental efficiency limits, their internal physics transforms. Photonic considerations, instead of electronic ones, are the key to reaching the highest voltages and efficiencies. Proper photon management led to Alta Device's recent dramatic increase of the solar cell efficiency record to 28.3%. Moreover, approaching the Shockley-Queisser limit for any solar cell technology will require light extraction to become a part of all future designs. The second half of the dissertation introduces inverse design as a new computational paradigm in photonics. An assortment of techniques (FDTD, FEM, etc.) have enabled quick and accurate simulation of the "forward problem" of finding fields for a given geometry. However, scientists and engineers are typically more interested in the inverse problem: for a desired functionality, what geometry is needed? Answering this question breaks from the emphasis on the forward problem and forges a new path in computational photonics. The framework of shape calculus enables one to quickly find superior, non-intuitive designs. Novel designs for optical cloaking and sub-wavelength solar cell applications are presented.

  1. Consolidated bioprocessing for butyric acid production from rice straw with undefined mixed culture

    Directory of Open Access Journals (Sweden)

    Binling Ai

    2016-10-01

    Full Text Available Lignocellulosic biomass is a renewable source with great potential for biofuels and bioproducts. However, the cost of cellulolytic enzymes limits the utilization of the low-cost bioresource. This study aimed to develop a consolidated bioprocessing without the need of supplementary cellulase for butyric acid production from lignocellulosic biomass. A stirred-tank reactor with a working volume of 21 L was constructed and operated in batch and semi-continuous fermentation modes with a cellulolytic butyrate-producing microbial community. The semi-continuous fermentation with intermittent discharging of the culture broth and replenishment with fresh medium achieved the highest butyric acid productivity of 2.69 g/(L•d. In semi-continuous operation mode, the butyric acid and total carboxylic acid concentrations of 16.2 and 28.9 g/L, respectively, were achieved. Over the 21-day fermentation period, their cumulative yields reached 1189 and 2048 g, respectively, corresponding to 41% and 74% of the maximum theoretical yields based on the amount of NaOH pretreated rice straw fed in. This study demonstrated that an undefined mixed culture-based consolidated bioprocessing for butyric acid production can completely eliminate the cost of supplementary cellulolytic enzymes.

  2. Consolidated Bioprocessing for Butyric Acid Production from Rice Straw with Undefined Mixed Culture.

    Science.gov (United States)

    Ai, Binling; Chi, Xue; Meng, Jia; Sheng, Zhanwu; Zheng, Lili; Zheng, Xiaoyan; Li, Jianzheng

    2016-01-01

    Lignocellulosic biomass is a renewable source with great potential for biofuels and bioproducts. However, the cost of cellulolytic enzymes limits the utilization of the low-cost bioresource. This study aimed to develop a consolidated bioprocessing without the need of supplementary cellulase for butyric acid production from lignocellulosic biomass. A stirred-tank reactor with a working volume of 21 L was constructed and operated in batch and semi-continuous fermentation modes with a cellulolytic butyrate-producing microbial community. The semi-continuous fermentation with intermittent discharging of the culture broth and replenishment with fresh medium achieved the highest butyric acid productivity of 2.69 g/(L· d). In semi-continuous operation mode, the butyric acid and total carboxylic acid concentrations of 16.2 and 28.9 g/L, respectively, were achieved. Over the 21-day fermentation period, their cumulative yields reached 1189 and 2048 g, respectively, corresponding to 41 and 74% of the maximum theoretical yields based on the amount of NaOH pretreated rice straw fed in. This study demonstrated that an undefined mixed culture-based consolidated bioprocessing for butyric acid production can completely eliminate the cost of supplementary cellulolytic enzymes.

  3. Production of polyol oils from soybean oil by bioprocess and Philippines edible medicinal wild mushrooms

    Science.gov (United States)

    We have been trying to develop a bioprocess for the production of polyol oils directly from soybean oil. We reported earlier the polyol products produced from soybean oil by Acinetobacter haemolyticus A01-35 (NRRL B-59985) (Hou and Lin, 2013). The objective of this study is to identify the chemical ...

  4. Trends in Process Analytical Technology: Present State in Bioprocessing.

    Science.gov (United States)

    Jenzsch, Marco; Bell, Christian; Buziol, Stefan; Kepert, Felix; Wegele, Harald; Hakemeyer, Christian

    2017-08-04

    Process analytical technology (PAT), the regulatory initiative for incorporating quality in pharmaceutical manufacturing, is an area of intense research and interest. If PAT is effectively applied to bioprocesses, this can increase process understanding and control, and mitigate the risk from substandard drug products to both manufacturer and patient. To optimize the benefits of PAT, the entire PAT framework must be considered and each elements of PAT must be carefully selected, including sensor and analytical technology, data analysis techniques, control strategies and algorithms, and process optimization routines. This chapter discusses the current state of PAT in the biopharmaceutical industry, including several case studies demonstrating the degree of maturity of various PAT tools. Graphical Abstract Hierarchy of QbD components.

  5. The Solubility of Cr-Organic Produced by Hydrolysis, Bioprocess and Bioremediation and its Effect on Fermented Rate, Digestibility and Rumen Microbe Population (in vitro

    Directory of Open Access Journals (Sweden)

    UH Tanuwiria

    2010-09-01

    Full Text Available The research was conducted to study the production of organic chromium from the leather tanning waste and its effect on in vitro rumen fermentation activities. The research was divided into two phases. The first phase was production of organic chromium by alkali hydrolysis, S cereviceae bioprocess, and duckweed bioremediation that perceived solubility in neutral and acid solution. The second phase was the supplementation of organic-Cr in ration seen from in-vitro fermented rate, digestibility and microbe rumen population. Research was conducted experimentally using 4x4 factorial patterns, on the basis of Completely Randomized Design (CRD with three replications in each experimental unit. The first factor was the type of organic-Cr and the second factor was the supplement in ration at four levels, 1, 2, 3 and 4 ppm. The results of this research indicated that organic chromium can be synthesized by alkali hydrolysis, S cereviseae bioprocess and the activity of duckweed bioremediation. Among the three of processes referred, the highest level of Cr was obtained from S cereviseae bioprocess that was originated from leather-tanning waste. The levels of organic-Cr that was resulted from alkali hydrolysis, bioprocess from Cl3Cr.6H2O, bioprocess from Cr leather-tanning waste, and from duckweed bioremediation were 354, 1011, 3833 and 310 mg/kg, respectively. Organic-Cr characteristic of each product has relatively similar in ferment ability, dry matter and organic matter digestibility and rumen ecosystem. There is an indication that dry matter and organic matter digestibility and rumen microbe population in ration that was added with organic Cr from alkali hydrolysis was higher than other supplements. (Animal Production 12(3: 175-183 (2010Key Words: organic-Cr, rumen fermentation activities, rumen microbe population

  6. Upgrading protein products using bioprocessing on agricultural crops

    DEFF Research Database (Denmark)

    Sulewska, Anna Maria; Sørensen, Jens Christian; Markedal, Keld Ejdrup

    to sustainability leads to a demand for plant protein products made from locally grown crops. Novel bioprocessing methods have been developed to generate protein products which are nutritious, readily available and do not generate hazardous waste. The processing focus has therefore been on developing protein......Due to increasing world population, higher average income, and changes in food preferences, there is a growing demand for proteins, especially novel plant-based protein sources, that can substitute animal proteins and supplement currently used soya proteins. Increased customer awareness......-enriched products with minimized content of antinutritional compounds. For every crop it is a challenge to obtain protein fractions with sufficient added value to make processing economically feasible. In this work we present the characterization of protein products developed in pilot scale using the novel...

  7. A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

    DEFF Research Database (Denmark)

    Hefzi, Hooman; Ang, Kok Siong; Hanscho, Michael

    2016-01-01

    Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways...

  8. Turmeric bioprocessed with mycelia from the shiitake culinary-medicinal mushroom lentinus edodes (agaricomycetes) protects mice against salmonellosis

    Science.gov (United States)

    Extracts of the shiitake mushroom Lentinus edodes and the spice tumeric (Curcuma longa) have both been reported to have health-promoting properties. The present study investigated the suppressive mechanisms of a bioprocessed Lentinus edodes liquid mushroom mycelia culture supplemented with turmeric ...

  9. Development and application of an excitation ratiometric optical pH sensor for bioprocess monitoring.

    Science.gov (United States)

    Badugu, Ramachandram; Kostov, Yordan; Rao, Govind; Tolosa, Leah

    2008-01-01

    The development of a fluorescent excitation ratiometric pH sensor (AHQ-PEG) using a novel allylhydroxyquinolinium (AHQ) derivative copolymerized with polyethylene glycol dimethacrylate (PEG) is described. The AHQ-PEG sensor film is shown to be suitable for real-time, noninvasive, continuous, online pH monitoring of bioprocesses. Optical ratiometric measurements are generally more reliable, robust, inexpensive, and insensitive to experimental errors such as fluctuations in the source intensity and fluorophore photobleaching. The sensor AHQ-PEG in deionized water was shown to exhibit two excitation maxima at 375 and 425 nm with a single emission peak at 520 nm. Excitation spectra of AHQ-PEG show a decrease in emission at the 360 nm excitation and an increase at the 420 nm excitation with increasing pH. Accordingly, the ratio of emission at 420:360 nm excitation showed a maximum change between pH 5 and 8 with an apparent pK(a) of 6.40. The low pK(a) value is suitable for monitoring the fermentation of most industrially important microorganisms. Additionally, the AHQ-PEG sensor was shown to have minimal sensitivity to ionic strength and temperature. Because AHQ is covalently attached to PEG, the film shows no probe leaching and is sterilizable by steam and alcohol. It shows rapid (approximately 2 min) and reversible response to pH over many cycles without any photobleaching. Subsequently, the AHQ-PEG sensor film was tested for its suitability in monitoring the pH of S. cereviseae (yeast) fermentation. The observed pH using AHQ-PEG film is in agreement with a conventional glass pH electrode. However, unlike the glass electrode, the present sensor is easily adaptable to noninvasive monitoring of sterilized, closed bioprocess environments without the awkward wire connections that electrodes require. In addition, the AHQ-PEG sensor is easily miniaturized to fit in microwell plates and microbioreactors for high-throughput cell culture applications.

  10. Studies on generalized kinetic model and Pareto optimization of a product-driven self-cycling bioprocess.

    Science.gov (United States)

    Sun, Kaibiao; Kasperski, Andrzej; Tian, Yuan

    2014-10-01

    The aim of this study is the optimization of a product-driven self-cycling bioprocess and presentation of a way to determine the best possible decision variables out of a set of alternatives based on the designed model. Initially, a product-driven generalized kinetic model, which allows a flexible choice of the most appropriate kinetics is designed and analysed. The optimization problem is given as the bi-objective one, where maximization of biomass productivity and minimization of unproductive loss of substrate are the objective functions. Then, the Pareto fronts are calculated for exemplary kinetics. It is found that in the designed bioprocess, a decrease of emptying/refilling fraction and an increase of substrate feeding concentration cause an increase of the biomass productivity. An increase of emptying/refilling fraction and a decrease of substrate feeding concentration cause a decrease of unproductive loss of substrate. The preferred solutions are calculated using the minimum distance from an ideal solution method, while giving proposals of their modifications derived from a decision maker's reactions to the generated solutions.

  11. Technical Aspects of Use of Ultrasound for Intensification of Enzymatic Bio-Processing: New Path to "Green Chemistry"

    Science.gov (United States)

    Use of enzymatic processing in the food, textile, and bio-fuel applications is becoming increasingly popular, primarily because of rapid introduction of a new variety of highly efficient enzymes. In general, an enzymatic bio-processing generates less toxic and readily biodegradable wastewater efflue...

  12. Nano-tubular cellulose for bioprocess technology development.

    Science.gov (United States)

    Koutinas, Athanasios A; Sypsas, Vasilios; Kandylis, Panagiotis; Michelis, Andreas; Bekatorou, Argyro; Kourkoutas, Yiannis; Kordulis, Christos; Lycourghiotis, Alexis; Banat, Ibrahim M; Nigam, Poonam; Marchant, Roger; Giannouli, Myrsini; Yianoulis, Panagiotis

    2012-01-01

    Delignified cellulosic material has shown a significant promotional effect on the alcoholic fermentation as yeast immobilization support. However, its potential for further biotechnological development is unexploited. This study reports the characterization of this tubular/porous cellulosic material, which was done by SEM, porosimetry and X-ray powder diffractometry. The results showed that the structure of nano-tubular cellulose (NC) justifies its suitability for use in "cold pasteurization" processes and its promoting activity in bioprocessing (fermentation). The last was explained by a glucose pump theory. Also, it was demonstrated that crystallization of viscous invert sugar solutions during freeze drying could not be otherwise achieved unless NC was present. This effect as well as the feasibility of extremely low temperature fermentation are due to reduction of the activation energy, and have facilitated the development of technologies such as wine fermentations at home scale (in a domestic refrigerator). Moreover, NC may lead to new perspectives in research such as the development of new composites, templates for cylindrical nano-particles, etc.

  13. Use of focused acoustics for cell disruption to provide ultra scale-down insights of microbial homogenization and its bioprocess impact--recovery of antibody fragments from rec E. coli.

    Science.gov (United States)

    Li, Qiang; Aucamp, Jean P; Tang, Alison; Chatel, Alex; Hoare, Mike

    2012-08-01

    An ultra scale-down (USD) device that provides insight of how industrial homogenization impacts bioprocess performance is desirable in the biopharmaceutical industry, especially at the early stage of process development where only a small quantity of material is available. In this work, we assess the effectiveness of focused acoustics as the basis of an USD cell disruption method to mimic and study high-pressure, step-wise homogenization of rec Escherichia coli cells for the recovery of an intracellular protein, antibody fragment (Fab'). The release of both Fab' and of overall protein follows first-order reaction kinetics with respect to time of exposure to focused acoustics. The rate constant is directly proportional to applied electrical power input per unit volume. For nearly total protein or Fab' release (>99%), the key physical properties of the disruptate produced by focused acoustics, such as cell debris particle size distribution and apparent viscosity show good agreement with those for homogenates produced by high-pressure homogenization operated to give the same fractional release. The only key difference is observed for partial disruption of cells where focused acoustics yields a disruptate of lower viscosity than homogenization, evidently due to a greater extent of polynucleic acids degradation. Verification of this USD approach to cell disruption by high-pressure homogenization is achieved using USD centrifugation to demonstrate the same sedimentation characteristics of disruptates prepared using both the scaled-down focused acoustic and the pilot-scale homogenization methods for the same fraction of protein release. Copyright © 2012 Wiley Periodicals, Inc.

  14. An industrial perspective on bioreactor scale-down: what we can learn from combined large-scale bioprocess and model fluid studies.

    Science.gov (United States)

    Noorman, Henk

    2011-08-01

    For industrial bioreactor design, operation, control and optimization, the scale-down approach is often advocated to efficiently generate data on a small scale, and effectively apply suggested improvements to the industrial scale. In all cases it is important to ensure that the scale-down conditions are representative of the real large-scale bioprocess. Progress is hampered by limited detailed and local information from large-scale bioprocesses. Complementary to real fermentation studies, physical aspects of model fluids such as air-water in large bioreactors provide useful information with limited effort and cost. Still, in industrial practice, investments of time, capital and resources often prohibit systematic work, although, in the end, savings obtained in this way are trivial compared to the expenses that result from real process disturbances, batch failures, and non-flyers with loss of business opportunity. Here we try to highlight what can be learned from real large-scale bioprocess in combination with model fluid studies, and to provide suitable computation tools to overcome data restrictions. Focus is on a specific well-documented case for a 30-m(3) bioreactor. Areas for further research from an industrial perspective are also indicated. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Fundamental understanding and development of low-cost, high-efficiency silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    ROHATGI,A.; NARASIMHA,S.; MOSCHER,J.; EBONG,A.; KAMRA,S.; KRYGOWSKI,T.; DOSHI,P.; RISTOW,A.; YELUNDUR,V.; RUBY,DOUGLAS S.

    2000-05-01

    The overall objectives of this program are (1) to develop rapid and low-cost processes for manufacturing that can improve yield, throughput, and performance of silicon photovoltaic devices, (2) to design and fabricate high-efficiency solar cells on promising low-cost materials, and (3) to improve the fundamental understanding of advanced photovoltaic devices. Several rapid and potentially low-cost technologies are described in this report that were developed and applied toward the fabrication of high-efficiency silicon solar cells.

  16. The fundamental unit of pain is the cell.

    Science.gov (United States)

    Reichling, David B; Green, Paul G; Levine, Jon D

    2013-12-01

    The molecular/genetic era has seen the discovery of a staggering number of molecules implicated in pain mechanisms [18,35,61,69,96,133,150,202,224]. This has stimulated pharmaceutical and biotechnology companies to invest billions of dollars to develop drugs that enhance or inhibit the function of many these molecules. Unfortunately this effort has provided a remarkably small return on this investment. Inevitably, transformative progress in this field will require a better understanding of the functional links among the ever-growing ranks of "pain molecules," as well as their links with an even larger number of molecules with which they interact. Importantly, all of these molecules exist side-by-side, within a functional unit, the cell, and its adjacent matrix of extracellular molecules. To paraphrase a recent editorial in Science magazine [223], although we live in the Golden age of Genetics, the fundamental unit of biology is still arguably the cell, and the cell is the critical structural and functional setting in which the function of pain-related molecules must be understood. This review summarizes our current understanding of the nociceptor as a cell-biological unit that responds to a variety of extracellular inputs with a complex and highly organized interaction of signaling molecules. We also discuss the insights that this approach is providing into peripheral mechanisms of chronic pain and sex dependence in pain.

  17. Intelligent control of mixed-culture bioprocesses

    International Nuclear Information System (INIS)

    Stoner, D.L.; Larsen, E.D.; Miller, K.S.

    1995-01-01

    A hierarchical control system is being developed and applied to a mixed culture bioprocess in a continuous stirred tank reactor. A bioreactor, with its inherent complexity and non-linear behavior was an interesting, yet, difficult application for control theory. The bottom level of the hierarchy was implemented as a number of integrated set point controls and data acquisition modules. Within the second level was a diagnostic system that used expert knowledge to determine the operational status of the sensors, actuators, and control modules. A diagnostic program was successfully implemented for the detection of stirrer malfunctions, and to monitor liquid delivery rates and recalibrate the pumps when deviations from desired flow rates occurred. The highest control level was a supervisory shell that was developed using expert knowledge and the history of the reactor operation to determine the set points required to meet a set of production criteria. At this stage the supervisory shell analyzed the data to determine the state of the system. In future implementations, this shell will determine the set points required to optimize a cost function using expert knowledge and adaptive learning techniques

  18. Intelligent control of mixed-culture bioprocesses

    Energy Technology Data Exchange (ETDEWEB)

    Stoner, D.L.; Larsen, E.D.; Miller, K.S. [Idaho National Engineering Lab., Idaho Falls, ID (United States)] [and others

    1995-12-31

    A hierarchical control system is being developed and applied to a mixed culture bioprocess in a continuous stirred tank reactor. A bioreactor, with its inherent complexity and non-linear behavior was an interesting, yet, difficult application for control theory. The bottom level of the hierarchy was implemented as a number of integrated set point controls and data acquisition modules. Within the second level was a diagnostic system that used expert knowledge to determine the operational status of the sensors, actuators, and control modules. A diagnostic program was successfully implemented for the detection of stirrer malfunctions, and to monitor liquid delivery rates and recalibrate the pumps when deviations from desired flow rates occurred. The highest control level was a supervisory shell that was developed using expert knowledge and the history of the reactor operation to determine the set points required to meet a set of production criteria. At this stage the supervisory shell analyzed the data to determine the state of the system. In future implementations, this shell will determine the set points required to optimize a cost function using expert knowledge and adaptive learning techniques.

  19. Cell culture experiments planned for the space bioreactor

    Science.gov (United States)

    Morrison, Dennis R.; Cross, John H.

    1987-01-01

    Culturing of cells in a pilot-scale bioreactor remains to be done in microgravity. An approach is presented based on several studies of cell culture systems. Previous and current cell culture research in microgravity which is specifically directed towards development of a space bioprocess is described. Cell culture experiments planned for a microgravity sciences mission are described in abstract form.

  20. Stem Cell Microencapsulation for Phenotypic Control, Bioprocessing, and Transplantation

    Science.gov (United States)

    Wilson, Jenna L.

    2014-01-01

    Cell microencapsulation has been utilized for decades as a means to shield cells from the external environment while simultaneously permitting transport of oxygen, nutrients, and secretory molecules. In designing cell therapies, donor primary cells are often difficult to obtain and expand to appropriate numbers, rendering stem cells an attractive alternative due to their capacities for self-renewal, differentiation, and trophic factor secretion. Microencapsulation of stem cells offers several benefits, namely the creation of a defined microenvironment which can be designed to modulate stem cell phenotype, protection from hydrodynamic forces and prevention of agglomeration during expansion in suspension bioreactors, and a means to transplant cells behind a semi-permeable barrier, allowing for molecular secretion while avoiding immune reaction. This review will provide an overview of relevant microencapsulation processes and characterization in the context of maintaining stem cell potency, directing differentiation, investigating scalable production methods, and transplanting stem cells for clinically relevant disorders. PMID:23239279

  1. Photonic Design: From Fundamental Solar Cell Physics to Computational Inverse Design

    OpenAIRE

    Miller, Owen Dennis

    2012-01-01

    Photonic innovation is becoming ever more important in the modern world. Optical systems are dominating shorter and shorter communications distances, LED's are rapidly emerging for a variety of applications, and solar cells show potential to be a mainstream technology in the energy space. The need for novel, energy-efficient photonic and optoelectronic devices will only increase. This work unites fundamental physics and a novel computational inverse design approach towards such innovation....

  2. Nano-tubular cellulose for bioprocess technology development.

    Directory of Open Access Journals (Sweden)

    Athanasios A Koutinas

    Full Text Available Delignified cellulosic material has shown a significant promotional effect on the alcoholic fermentation as yeast immobilization support. However, its potential for further biotechnological development is unexploited. This study reports the characterization of this tubular/porous cellulosic material, which was done by SEM, porosimetry and X-ray powder diffractometry. The results showed that the structure of nano-tubular cellulose (NC justifies its suitability for use in "cold pasteurization" processes and its promoting activity in bioprocessing (fermentation. The last was explained by a glucose pump theory. Also, it was demonstrated that crystallization of viscous invert sugar solutions during freeze drying could not be otherwise achieved unless NC was present. This effect as well as the feasibility of extremely low temperature fermentation are due to reduction of the activation energy, and have facilitated the development of technologies such as wine fermentations at home scale (in a domestic refrigerator. Moreover, NC may lead to new perspectives in research such as the development of new composites, templates for cylindrical nano-particles, etc.

  3. Selection of controlled variables in bioprocesses. Application to a SHARON-Anammox process for autotrophic nitrogen removal

    DEFF Research Database (Denmark)

    Mauricio Iglesias, Miguel; Valverde Perez, Borja; Sin, Gürkan

    Selecting the right controlled variables in a bioprocess is challenging since the objectives of the process (yields, product or substrate concentration) are difficult to relate with a given actuator. We apply here process control tools that can be used to assist in the selection of controlled var...... variables to the case of the SHARON-Anammox process for autotrophic nitrogen removal....

  4. Bioprocess design guided by in situ substrate supply and product removal: process intensification for synthesis of (S)-1-(2-chlorophenyl)ethanol.

    Science.gov (United States)

    Schmölzer, Katharina; Mädje, Katharina; Nidetzky, Bernd; Kratzer, Regina

    2012-03-01

    We report herein on bioprocess development guided by the hydrophobicities of substrate and product. Bioreductions of o-chloroacetophenone are severely limited by instability of the catalyst in the presence of aromatic substrate and (S)-1-(2-chlorophenyl)ethanol. In situ substrate supply and product removal was used to protect the utilized Escherichia coli whole cell catalyst based on Candida tenuis xylose reductase during the reaction. Further engineering at the levels of the catalyst and the reaction media was matched to low substrate concentrations in the aqueous phase. Productivities obtained in aqueous batch reductions were 21-fold improved by addition of 20% (v/v) hexane, NAD(+), expression engineering, cell permeabilization and pH optimization. Reduction of 300 mM substrate was accomplished in 97% yield and use of the co-solvent hexane in subsequent extraction steps led to 88% recovery. Product loss due to high catalyst loading was minimized by using the same extractant in bioreduction and product isolation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Bio-processing of solid wastes and secondary resources for metal extraction – A review

    International Nuclear Information System (INIS)

    Lee, Jae-chun; Pandey, Banshi Dhar

    2012-01-01

    Highlights: ► Review focuses on bio-extraction of metals from solid wastes of industries and consumer goods. ► Bio-processing of certain effluents/wastewaters with metals is also included in brief. ► Quantity/composition of wastes are assessed, and microbes used and leaching conditions included. ► Bio-recovery using bacteria, fungi and archaea is highlighted for resource recycling. ► Process methodology/mechanism, R and D direction and scope of large scale use are briefly included. - Abstract: Metal containing wastes/byproducts of various industries, used consumer goods, and municipal waste are potential pollutants, if not treated properly. They may also be important secondary resources if processed in eco-friendly manner for secured supply of contained metals/materials. Bio-extraction of metals from such resources with microbes such as bacteria, fungi and archaea is being increasingly explored to meet the twin objectives of resource recycling and pollution mitigation. This review focuses on the bio-processing of solid wastes/byproducts of metallurgical and manufacturing industries, chemical/petrochemical plants, electroplating and tanning units, besides sewage sludge and fly ash of municipal incinerators, electronic wastes (e-wastes/PCBs), used batteries, etc. An assessment has been made to quantify the wastes generated and its compositions, microbes used, metal leaching efficiency etc. Processing of certain effluents and wastewaters comprising of metals is also included in brief. Future directions of research are highlighted.

  6. Bioprocessing applications in the management of nuclear and chemical wastes

    International Nuclear Information System (INIS)

    Genung, R.K.

    1988-01-01

    The projected requirements for waste management and environmental restoration activities within the United States will probably cost tens of billions of dollars annually during the next two decades. Expenditures of this magnitude clearly have the potential to affect the international competitiveness of many US industries and the continued operation of many federal facilities. It is argued that the costs of implementing current technology will be too high unless the standards and schedules for compliance are relaxed. Since this is socially unacceptable, efforts to improve the efficiency of existing technologies and to develop new technologies should be pursued. A sizable research, development, and demonstration effort can be easily justified if the potential for reducing costs can be shown. Bioprocessing systems for the treatment of nuclear and chemically hazardous wastes offer such promise. 11 refs

  7. Fluorescence Spectroscopy and Chemometric Modeling for Bioprocess Monitoring

    Directory of Open Access Journals (Sweden)

    Saskia M. Faassen

    2015-04-01

    Full Text Available On-line sensors for the detection of crucial process parameters are desirable for the monitoring, control and automation of processes in the biotechnology, food and pharma industry. Fluorescence spectroscopy as a highly developed and non-invasive technique that enables the on-line measurements of substrate and product concentrations or the identification of characteristic process states. During a cultivation process significant changes occur in the fluorescence spectra. By means of chemometric modeling, prediction models can be calculated and applied for process supervision and control to provide increased quality and the productivity of bioprocesses. A range of applications for different microorganisms and analytes has been proposed during the last years. This contribution provides an overview of different analysis methods for the measured fluorescence spectra and the model-building chemometric methods used for various microbial cultivations. Most of these processes are observed using the BioView® Sensor, thanks to its robustness and insensitivity to adverse process conditions. Beyond that, the PLS-method is the most frequently used chemometric method for the calculation of process models and prediction of process variables.

  8. Fluorescence Spectroscopy and Chemometric Modeling for Bioprocess Monitoring

    Science.gov (United States)

    Faassen, Saskia M.; Hitzmann, Bernd

    2015-01-01

    On-line sensors for the detection of crucial process parameters are desirable for the monitoring, control and automation of processes in the biotechnology, food and pharma industry. Fluorescence spectroscopy as a highly developed and non-invasive technique that enables the on-line measurements of substrate and product concentrations or the identification of characteristic process states. During a cultivation process significant changes occur in the fluorescence spectra. By means of chemometric modeling, prediction models can be calculated and applied for process supervision and control to provide increased quality and the productivity of bioprocesses. A range of applications for different microorganisms and analytes has been proposed during the last years. This contribution provides an overview of different analysis methods for the measured fluorescence spectra and the model-building chemometric methods used for various microbial cultivations. Most of these processes are observed using the BioView® Sensor, thanks to its robustness and insensitivity to adverse process conditions. Beyond that, the PLS-method is the most frequently used chemometric method for the calculation of process models and prediction of process variables. PMID:25942644

  9. Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

    DEFF Research Database (Denmark)

    Hansen, Henning Gram; Pristovsek, Nusa; Kildegaard, Helene Faustrup

    2017-01-01

    Chinese hamster ovary (CHO) cells are the preferred cell factory for the production of therapeutic glycoproteins. Although efforts primarily within bioprocess optimization have led to increased product titers of recombinant proteins (r-proteins) expressed in CHO cells, post-transcriptional bottle...

  10. Atomic force microscopy: Unraveling the fundamental principles governing secretion and membrane fusion in cells

    International Nuclear Information System (INIS)

    Jena, Bhanu P.

    2009-01-01

    The story of cell secretion and membrane fusion is as old as life itself. Without these fundamental cellular processes known to occur in yeast to humans, life would cease to exist. In the last 15 years, primarily using the atomic force microscope, a detailed understanding of the molecular process and of the molecular machinery and mechanism of secretion and membrane fusion in cells has come to light. This has led to a paradigm shift in our understanding of the underlying mechanism of cell secretion. The journey leading to the discovery of a new cellular structure the 'porosome',-the universal secretory machinery in cells, and the contributions of the AFM in our understanding of the general molecular machinery and mechanism of cell secretion and membrane fusion, is briefly discussed in this article.

  11. Toward genome-scale models of the Chinese hamster ovary cells: incentives, status and perspectives

    DEFF Research Database (Denmark)

    Kaas, Christian Schrøder; Fan, Yuzhou; Weilguny, Dietmar

    2014-01-01

    Bioprocessing of the important Chinese hamster ovary (CHO) cell lines used for the production of biopharmaceuticals stands at the brink of several redefining events. In 2011, the field entered the genomics era, which has accelerated omics-based phenotyping of the cell lines. In this review we...

  12. Microsystems for enhanced control of cell behavior fundamentals, design and manufacturing strategies, applications and challenges

    CERN Document Server

    2016-01-01

    This handbook focuses on the entire development process of biomedical microsystems that promote special interactions with cells. Fundamentals of cell biology and mechanobiology are described as necessary preparatory input for design tasks. Advanced design, simulation, and micro/nanomanufacturing resources, whose combined use enables the development of biomedical microsystems capable of interacting at a cellular level, are covered in depth. A detailed series of chapters is then devoted to applications based on microsystems that offer enhanced cellular control, including microfluidic devices for diagnosis and therapy, cell-based sensors and actuators (smart biodevices), microstructured prostheses for improvement of biocompatibility, microstructured and microtextured cell culture matrices for promotion of cell growth and differentiation, electrophoretic microsystems for study of cell mechanics, microstructured and microtextured biodevices for study of cell adhesion and dynamics, and biomimetic microsystems (incl...

  13. Bioprocessing applications in the management of nuclear and chemical wastes

    International Nuclear Information System (INIS)

    Genung, R.K.

    1989-01-01

    The US Department of Energy (DOE), the US Department of Defense (DOD), and other federal agencies already face profound challenges in finding strategies that manage budgets and priorities while bringing their sites and facilities into compliance with current statues and regulations and with agency policies and orders. While it is often agreed that current technology can be used to address most waste management and environmental restoration needs, it is also argued by many that the costs of implementing current technology will be too high unless the standards and schedules for compliance are relaxed. Since this is socially unacceptable, efforts to improve the efficiency of existing technologies and to develop new technologies should be pursued. A sizable research, development, and demonstration effort can be easily justified if the potential for reducing costs can be shown. Bioprocessing systems for the treatment of nuclear and chemically hazardous wastes offer such promise

  14. Fundamental research in the area of high temperature fuel cells in Russia

    Energy Technology Data Exchange (ETDEWEB)

    Dyomin, A.K.

    1996-04-01

    Research in the area of molten carbonate and solid oxide fuel cells has been conducted in Russia since the late 60`s. Institute of High Temperature Electrochemistry is the lead organisation in this area. Research in the area of materials used in fuel cells has allowed us to identify compositions of electrolytes, electrodes, current paths and transmitting, sealing and structural materials appropriate for long-term fuel cell applications. Studies of electrode processes resulted in better understanding of basic patterns of electrode reactions and in the development of a foundation for electrode structure optimization. We have developed methods to increase electrode activity levels that allowed us to reach current density levels of up to 1 amper/cm{sup 2}. Development of mathematical models of processes in high temperature fuel cells has allowed us to optimize their structure. The results of fundamental studies have been tested on laboratory mockups. MCFC mockups with up to 100 W capacity and SOFC mockups with up to 1 kW capacity have been manufactured and tested at IHTE. There are three SOFC structural options: tube, plate and modular.

  15. Advances in consolidated bioprocessing systems for bioethanol and butanol production from biomass: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Gholamreza Salehi Jouzani

    2015-03-01

    Full Text Available Recently, lignocellulosic biomass as the most abundant renewable resource has been widely considered for bioalcohols production. However, the complex structure of lignocelluloses requires a multi-step process which is costly and time consuming. Although, several bioprocessing approaches have been developed for pretreatment, saccharification and fermentation, bioalcohols production from lignocelluloses is still limited because of the economic infeasibility of these technologies. This cost constraint could be overcome by designing and constructing robust cellulolytic and bioalcohols producing microbes and by using them in a consolidated bioprocessing (CBP system. This paper comprehensively reviews potentials, recent advances and challenges faced in CBP systems for efficient bioalcohols (ethanol and butanol production from lignocellulosic and starchy biomass. The CBP strategies include using native single strains with cellulytic and alcohol production activities, microbial co-cultures containing both cellulytic and ethanologenic microorganisms, and genetic engineering of cellulytic microorganisms to be alcohol-producing or alcohol producing microorganisms to be cellulytic. Moreover, high-throughput techniques, such as metagenomics, metatranscriptomics, next generation sequencing and synthetic biology developed to explore novel microorganisms and powerful enzymes with high activity, thermostability and pH stability are also discussed. Currently, the CBP technology is in its infant stage, and ideal microorganisms and/or conditions at industrial scale are yet to be introduced. So, it is essential to bring into attention all barriers faced and take advantage of all the experiences gained to achieve a high-yield and low-cost CBP process.

  16. Implementation and use of cloud-based electronic lab notebook in a bioprocess engineering teaching laboratory.

    Science.gov (United States)

    Riley, Erin M; Hattaway, Holly Z; Felse, P Arthur

    2017-01-01

    Electronic lab notebooks (ELNs) are better equipped than paper lab notebooks (PLNs) to handle present-day life science and engineering experiments that generate large data sets and require high levels of data integrity. But limited training and a lack of workforce with ELN knowledge have restricted the use of ELN in academic and industry research laboratories which still rely on cumbersome PLNs for recordkeeping. We used LabArchives, a cloud-based ELN in our bioprocess engineering lab course to train students in electronic record keeping, good documentation practices (GDPs), and data integrity. Implementation of ELN in the bioprocess engineering lab course, an analysis of user experiences, and our development actions to improve ELN training are presented here. ELN improved pedagogy and learning outcomes of the lab course through stream lined workflow, quick data recording and archiving, and enhanced data sharing and collaboration. It also enabled superior data integrity, simplified information exchange, and allowed real-time and remote monitoring of experiments. Several attributes related to positive user experiences of ELN improved between the two subsequent years in which ELN was offered. Student responses also indicate that ELN is better than PLN for compliance. We demonstrated that ELN can be successfully implemented in a lab course with significant benefits to pedagogy, GDP training, and data integrity. The methods and processes presented here for ELN implementation can be adapted to many types of laboratory experiments.

  17. Selection of bioprocess simulation software for industrial applications.

    Science.gov (United States)

    Shanklin, T; Roper, K; Yegneswaran, P K; Marten, M R

    2001-02-20

    Two commercially available, process-simulation software packages (Aspen Batch Plus v1.2, Aspen Technology, Inc., Cambridge, Massachusetts, and Intelligen SuperPro v3.0, INTELLIGEN, INC., Scotch Plains, Ner Jersey) are evaluated for use in modeling industrial, biotechnology processes. Software is quantitatively evaluated by Kepner-Tregoe Decision Analysis (Kepner and Tregoe, 1981). This evaluation shows that Aspen Batch Plus v1.2 (ABP) and Intelligen SuperPro v3.0 (ISP) can successfully perform specific simulation tasks but do not provide a complete model of all phenomena occurring within a biotechnology process. Software is best suited to provide a format for process management, using material and energy balances to answer scheduling questions, explore equipment change-outs, and calculate cost data. The ability of simulation software to accurately predict unit operation scale-up and optimize bioprocesses is limited. To realistically evaluate the software, a vaccine manufacturing process under development at Merck & Company is simulated. Case studies from the vaccine process are presented as examples of how ABP and ISP can be used to shed light on real-world processing issues. Copyright 2001 John Wiley & Sons, Inc.

  18. Universal Capacitance Model for Real-Time Biomass in Cell Culture

    Directory of Open Access Journals (Sweden)

    Viktor Konakovsky

    2015-09-01

    Full Text Available Capacitance probes have the potential to revolutionize bioprocess control due to their safe and robust use and ability to detect even the smallest capacitors in the form of biological cells. Several techniques have evolved to model biomass statistically, however, there are problems with model transfer between cell lines and process conditions. Errors of transferred models in the declining phase of the culture range for linear models around +100% or worse, causing unnecessary delays with test runs during bioprocess development. The goal of this work was to develop one single universal model which can be adapted by considering a potentially mechanistic factor to estimate biomass in yet untested clones and scales. The novelty of this work is a methodology to select sensitive frequencies to build a statistical model which can be shared among fermentations with an error between 9% and 38% (mean error around 20% for the whole process, including the declining phase. A simple linear factor was found to be responsible for the transferability of biomass models between cell lines, indicating a link to their phenotype or physiology.

  19. [Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects].

    Science.gov (United States)

    Aleksandrova, M A; Marey, M V

    2015-01-01

    Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs.

  20. Dynamics of complex interconnected systems: Networks and bioprocesses[A NATO study seminary

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelmsen, Line K

    2005-07-01

    Rapid detection of chemical and biological agents and weapons, and rapid diagnosis of their effects on people will require molecular recognition as well as signal discrimination, i.e. avoiding false positives and negatives, and signal transduction. It will be important to have reagentless, cheap, easily manufactured sensors that can be field deployed in large numbers. While this problem is urgent it is not yet solved. This ASI brought together researchers with various interests and background including theoretical physicists, soft condensed matter experimentalists, biological physicists, and molecular biologists to identify and discuss areas where synergism between modem physics and biology may be most fruitfully applied to the study of bioprocesses for molecular recognition and of networks for converting molecular reactions into usable signals and appropriate responses. (Author)

  1. Manufacturing recombinant proteins in kg-ton quantities using animal cells in bioreactors.

    Science.gov (United States)

    De Jesus, Maria; Wurm, Florian M

    2011-06-01

    Mammalian cells in bioreactors as production host are the focus of this review. We wish to briefly describe today's technical status and to highlight emerging trends in the manufacture of recombinant therapeutic proteins, focusing on Chinese hamster ovary (CHO) cells. CHO cells are the manufacturing host system of choice for more than 70% of protein pharmaceuticals on the market [21]. The current global capacity to grow mammalian cells in bioreactors stands at about 0.5 million liters, whereby the largest vessels can have a working volume of about 20,000l. We are focusing in this article on the upstream part of protein manufacturing. Over the past 25 years, volumetric yields for recombinant cell lines have increased about 20-fold mainly as the result of improvements in media and bioprocess design. Future yield increases are expected to come from improved gene delivery methods, from improved, possibly genetically modified host systems, and from further improved bioprocesses in bioreactors. Other emerging trends in protein manufacturing that are discussed include the use of disposal bioreactors and transient gene expression. We specifically highlight here current research in our own laboratories. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. 20050411 NATO Advanced Study Institute on Dynamics of Complex Interconnected Biosensor Systems: Networks and Bioprocesses Geilo, Norway 11 - 21 Apr 2005 2005 geilo20050411 NO 20050421

    CERN Document Server

    Skjeltorp, Arne T

    2006-01-01

    The book reviews the synergism between various fields of research that are confronted with networks, such as genetic and metabolic networks, social networks, the Internet and ecological systems. In many cases, the interacting networks manifest so-called emergent properties that are not possessed by any of the individual components. This means that the detailed knowledge of the components is insufficient to describe the whole system. Recent work has indicated that networks in nature have so-called scale-free characteristics, and the associated dynamic network modelling shows unexpected results such as an amazing robustness against accidental failures. Modelling the signal transduction networks in bioprocesses as in living cells is a challenging interdisciplinary research area. It is now realized that the many features of molecular interaction networks within a cell are shared to a large degree by the other complex systems mentioned above, such as the Internet, computer chips and society. Thus knowledge gained ...

  3. New perspectives for the petroleum industry. Bioprocesses for the selective removal of sulphur, nitrogen and metals

    International Nuclear Information System (INIS)

    Zerlia, T.

    2000-01-01

    Fuel biocatalytic conversion is a process that removes, through selective enzyme-catalyzed reactions, sulphur, nitrogen and metals. The mild operating conditions, the specificity of reactions and the quality of coproducts (particularly the organo sulphur compounds, a source for the petrochemical industry) are just a few of the attractive aspects of this new technology which could open a new world of possibilities in the technology and in the environmental impact of fuels. The paper shows the state-of-the-art of the research and applications of bioprocesses to the petroleum field [it

  4. An Intelligent Automation Platform for Rapid Bioprocess Design.

    Science.gov (United States)

    Wu, Tianyi; Zhou, Yuhong

    2014-08-01

    Bioprocess development is very labor intensive, requiring many experiments to characterize each unit operation in the process sequence to achieve product safety and process efficiency. Recent advances in microscale biochemical engineering have led to automated experimentation. A process design workflow is implemented sequentially in which (1) a liquid-handling system performs high-throughput wet lab experiments, (2) standalone analysis devices detect the data, and (3) specific software is used for data analysis and experiment design given the user's inputs. We report an intelligent automation platform that integrates these three activities to enhance the efficiency of such a workflow. A multiagent intelligent architecture has been developed incorporating agent communication to perform the tasks automatically. The key contribution of this work is the automation of data analysis and experiment design and also the ability to generate scripts to run the experiments automatically, allowing the elimination of human involvement. A first-generation prototype has been established and demonstrated through lysozyme precipitation process design. All procedures in the case study have been fully automated through an intelligent automation platform. The realization of automated data analysis and experiment design, and automated script programming for experimental procedures has the potential to increase lab productivity. © 2013 Society for Laboratory Automation and Screening.

  5. An Intelligent Automation Platform for Rapid Bioprocess Design

    Science.gov (United States)

    Wu, Tianyi

    2014-01-01

    Bioprocess development is very labor intensive, requiring many experiments to characterize each unit operation in the process sequence to achieve product safety and process efficiency. Recent advances in microscale biochemical engineering have led to automated experimentation. A process design workflow is implemented sequentially in which (1) a liquid-handling system performs high-throughput wet lab experiments, (2) standalone analysis devices detect the data, and (3) specific software is used for data analysis and experiment design given the user’s inputs. We report an intelligent automation platform that integrates these three activities to enhance the efficiency of such a workflow. A multiagent intelligent architecture has been developed incorporating agent communication to perform the tasks automatically. The key contribution of this work is the automation of data analysis and experiment design and also the ability to generate scripts to run the experiments automatically, allowing the elimination of human involvement. A first-generation prototype has been established and demonstrated through lysozyme precipitation process design. All procedures in the case study have been fully automated through an intelligent automation platform. The realization of automated data analysis and experiment design, and automated script programming for experimental procedures has the potential to increase lab productivity. PMID:24088579

  6. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy

    Science.gov (United States)

    Hollyman, Daniel; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Taylor, Clare; Yeh, Raymond; Capacio, Vanessa; Olszewska, Malgorzata; Hosey, James; Sadelain, Michel; Brentjens, Renier J.; Rivière, Isabelle

    2009-01-01

    Summary Based on promising pre-clinical data demonstrating the eradication of systemic B cell malignancies by CD19-targeted T lymphocytes in vivo in SCID beige mouse models, we are launching Phase 1 clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). We present here the validation of the bioprocess we developed for the production and expansion of clinical grade autologous T cells derived from patients with CLL. We demonstrate that T cells genetically modified with a replication-defective gammaretroviral vector derived from the Moloney murine leukemia virus encoding a chimeric antigen receptor (CAR) targeted to CD19 (1928z) can be expanded with Dynabeads® CD3/CD28. This bioprocess allows us to generate clinical doses of 1928z+ T cells in approximately 2 to 3 weeks in a large-scale semi-closed culture system using the Wave bioreactor. These 1928z+ T cells remain biologically functional not only in vitro but also in SCID beige mice bearing disseminated tumors. The validation requirements in terms of T cell expansion, T cell transduction with the 1928z CAR, biological activity, quality control testing and release criteria were met for all four validation runs using apheresis products from patients with CLL. Additionally, following expansion of the T cells, the diversity of the skewed Vβ T cell receptor repertoire was significantly restored. This validated process will be used in phase I clinical trials in patients with chemo-refractory CLL and in patients with relapsed ALL. It can also be adapted for other clinical trials involving the expansion and transduction of patient or donor T cells using any chimeric antigen receptor or T cell receptor. PMID:19238016

  7. CHO On A Detox: Removing By-Product Formation Through Cell Engineering

    DEFF Research Database (Denmark)

    Pereira, Sara; Kildegaard, Helene Faustrup; Andersen, Mikael Rørdam

    Chinese Hamster Ovary (CHO) cells are the preferred hosts for the production of therapeutic glycoproteins. However, there is a need for improvement of the bioprocesses towards increased cell growth and higher productivities without compromising the product quality. Efforts to obtain tailor-made p......-made products with the desired properties that meet the requirements of regulatory authorities are continuously being made. Of equal relevance is to develop methods to engineer cell lines with improved by-product metabolism....

  8. On Earth, there would be a number of fundamental kinds of primary cells - cellular domains - greater than or equal to four.

    Science.gov (United States)

    Di Giulio, Massimo

    2018-04-14

    In the studies regarding the deep nodes of the tree of life, there is an assumption that might be false. Usually, it is assumed that these nodes - that is to say, those for example regarding the ancestors of bacteria and archaea - are believed to be completely evolved cells and not protocells. In other words, in these studies, it is rarely stressed that, on the contrary, these nodes might correspond to evolutionary stages of premature cells, namely, progenotes. This observation has extremely relevant consequences. Indeed, if the nodes, for example, of the ancestors of bacteria and archaea would correspond to progenotic evolutionary stages, then this should imply that the number of fundamental kinds of primary cells (cellular domains), present on Earth, would be at least four and not two or three as it is currently believed. As a matter of fact, if these two nodes would correspond to two progenotes then, evidently, the fully evolved cells (genotes) - to which we should refer to be able to establish how many fundamental kinds of primary cells are present on Earth - would characterize less deep nodes of these two. Thus, since there is a strong evidence that the ancestors of archaea and bacteria have been of progenotes, these reasonings would assume a particular importance. For instance, it is maintained that one of these fundamental primary cells might be represented by the typical cell of superphylum of the DPANN. In other words, the DPANN superphylum might be a so far non-recognized cellular domain of life. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Bioprocess systems engineering: transferring traditional process engineering principles to industrial biotechnology.

    Science.gov (United States)

    Koutinas, Michalis; Kiparissides, Alexandros; Pistikopoulos, Efstratios N; Mantalaris, Athanasios

    2012-01-01

    The complexity of the regulatory network and the interactions that occur in the intracellular environment of microorganisms highlight the importance in developing tractable mechanistic models of cellular functions and systematic approaches for modelling biological systems. To this end, the existing process systems engineering approaches can serve as a vehicle for understanding, integrating and designing biological systems and processes. Here, we review the application of a holistic approach for the development of mathematical models of biological systems, from the initial conception of the model to its final application in model-based control and optimisation. We also discuss the use of mechanistic models that account for gene regulation, in an attempt to advance the empirical expressions traditionally used to describe micro-organism growth kinetics, and we highlight current and future challenges in mathematical biology. The modelling research framework discussed herein could prove beneficial for the design of optimal bioprocesses, employing rational and feasible approaches towards the efficient production of chemicals and pharmaceuticals.

  10. Bioprocess systems engineering: transferring traditional process engineering principles to industrial biotechnology

    Directory of Open Access Journals (Sweden)

    Michalis Koutinas

    2012-10-01

    Full Text Available The complexity of the regulatory network and the interactions that occur in the intracellular environment of microorganisms highlight the importance in developing tractable mechanistic models of cellular functions and systematic approaches for modelling biological systems. To this end, the existing process systems engineering approaches can serve as a vehicle for understanding, integrating and designing biological systems and processes. Here, we review the application of a holistic approach for the development of mathematical models of biological systems, from the initial conception of the model to its final application in model-based control & optimisation. We also discuss the use of mechanistic models that account for gene regulation, in an attempt to advance the empirical expressions traditionally used to describe micro-organism growth kinetics, and we highlight current and future challenges in mathematical biology. The modelling research framework discussed herein could prove beneficial for the design of optimal bioprocesses, employing rational and feasible approaches towards the efficient production of chemicals and pharmaceuticals.

  11. BIOPROCESS SYSTEMS ENGINEERING: TRANSFERRING TRADITIONAL PROCESS ENGINEERING PRINCIPLES TO INDUSTRIAL BIOTECHNOLOGY

    Directory of Open Access Journals (Sweden)

    Michalis Koutinas

    2012-10-01

    Full Text Available The complexity of the regulatory network and the interactions that occur in the intracellular environment of microorganisms highlight the importance in developing tractable mechanistic models of cellular functions and systematic approaches for modelling biological systems. To this end, the existing process systems engineering approaches can serve as a vehicle for understanding, integrating and designing biological systems and processes. Here, we review the application of a holistic approach for the development of mathematical models of biological systems, from the initial conception of the model to its final application in model-based control and optimisation. We also discuss the use of mechanistic models that account for gene regulation, in an attempt to advance the empirical expressions traditionally used to describe micro-organism growth kinetics, and we highlight current and future challenges in mathematical biology. The modelling research framework discussed herein could prove beneficial for the design of optimal bioprocesses, employing rational and feasible approaches towards the efficient production of chemicals and pharmaceuticals.

  12. Postprandial glucose metabolism and SCFA after consuming wholegrain rye bread and wheat bread enriched with bioprocessed rye bran in individuals with mild gastrointestinal symptoms

    DEFF Research Database (Denmark)

    Lappi, J; Mykkänen, H; Knudsen, Knud Erik Bach

    2014-01-01

    BackgroundRye bread benefits glucose metabolism. It is unknown whether the same effect is achieved by rye bran-enriched wheat bread. We tested whether white wheat bread enriched with bioprocessed rye bran (BRB + WW) and sourdough wholegrain rye bread (WGR) have similar effects on glucose metabolism...... and plasma level of short chain fatty acids (SCFAs).  MethodsTwenty-one (12 women) of 23 recruited subjects completed an intervention with a four-week run-in and two four-week test periods in cross-over design. White wheat bread (WW; 3% fibre) was consumed during the run-in, and WGR and BRB + WW (10% fibre.......05) and propionate (p = 0.009) at 30 min increased during both rye bread periods.ConclusionsBeneficial effects of WGR over white wheat bread on glucose and SCFA production were confirmed. The enrichment of the white wheat bread with bioprocessed rye bran (BRB + WW) yielded similar but not as pronounced effects than...

  13. Novel and improved yeast cell factories for biosustainable processes

    DEFF Research Database (Denmark)

    Workman, Mhairi

    2014-01-01

    The utilization of an increasingly diverse range of cheap waste substrates will be an ongoing challenge for the bio-based economy, where the mobilization of nutrients from a variety of waste products will be necessary for realization of biosustainability on an industrial scale. Bioprocesses....... In addition to plant biomass hydrolysates, glycerol is of interest here, being available in amounts relevant for industrial scale bioprocesses due to increased production of biodiesel. The well characterised cell factory Saccharomyces cerevisiae exhibits a clear preference for glucose as a carbon source......, and is highly adapted to its utilisation. Although there have been several studies on glycerol metabolism in S. cerevisiae, many industrially used strains grow poorly on glycerol (μmax = 0.01h-1). On the other hand, several non-conventional yeast species are efficient in utilization of glycerol, some...

  14. Resveratrol production in bioreactor: Assessment of cell physiological states and plasmid segregational stability

    Directory of Open Access Journals (Sweden)

    Margarida S. Afonso

    2015-03-01

    Full Text Available Resveratrol is a plant secondary metabolite commonly found in peanuts and grapevines with significant health benefits. Recombinant organisms can produce large amounts of resveratrol and, in this work, Escherichia coli BW27784 was used to produce resveratrol in bioreactors while monitoring cell physiology and plasmid stability through flow cytometry and real-time qPCR, respectively. Initially, the influence of culture conditions and precursor addition was evaluated in screening assays and the data gathered was used to perform the bioreactor assays, allowing the production of 160 μg/mL of resveratrol. Cellular physiology and plasmid instability affected the final resveratrol production, with lower viability and plasmid copy numbers associated with lower yields. In sum, this study describes new tools to monitor the bioprocess, evaluating the effect of culture conditions, and its correlation with cell physiology and plasmid segregational stability, in order to define a viable and scalable bioprocess to fulfill the need for larger quantities of resveratrol.

  15. PERM Hypothesis: The Fundamental Machinery Able to Elucidate the Role of Xenobiotics and Hormesis in Cell Survival and Homeostasis

    Directory of Open Access Journals (Sweden)

    Salvatore Chirumbolo

    2017-01-01

    Full Text Available In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P, endoplasmic reticulum (ER and mitochondria (M is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy and stress response. The “PERM hypothesis” suggests that xenobiotics can modulate this central signaling and the regulatory engine made fundamentally by the ER, mitochondria and proteasome, together with other ancillary components such as peroxisomes, by acting on the energetic balance, redox system and macromolecule turnover. In this context, reactive species and stressors are fundamentally signalling molecules that could act as negative-modulating signals if PERM-mediated control is offline, impaired or dysregulated, as occurs in metabolic syndrome, degenerative disorders, chronic inflammation and cancer. Calcium is an important oscillatory input of this regulation and, in this hypothesis, it might play a role in maintaining the correct rhythm of this PERM modulation, probably chaotic in its nature, and guiding cells to a more drastic decision, such as apoptosis. The commonest effort sustained by cells is to maintain their survival balance and the proterome has the fundamental task of supporting this mechanism. Mild stress is probably the main stimulus in this sense. Hormesis is therefore re-interpreted in the light of this hypothetical model and that experimental evidence arising from flavonoid and hormesis reasearch.

  16. Microencapsulation Technology: A Powerful Tool for Integrating Expansion and Cryopreservation of Human Embryonic Stem Cells

    Science.gov (United States)

    Malpique, Rita; Brito, Catarina; Jensen, Janne; Bjorquist, Petter; Carrondo, Manuel J. T.; Alves, Paula M.

    2011-01-01

    The successful implementation of human embryonic stem cells (hESCs)-based technologies requires the production of relevant numbers of well-characterized cells and their efficient long-term storage. In this study, cells were microencapsulated in alginate to develop an integrated bioprocess for expansion and cryopreservation of pluripotent hESCs. Different three-dimensional (3D) culture strategies were evaluated and compared, specifically, microencapsulation of hESCs as: i) single cells, ii) aggregates and iii) immobilized on microcarriers. In order to establish a scalable bioprocess, hESC-microcapsules were cultured in stirred tank bioreactors. The combination of microencapsulation and microcarrier technology resulted in a highly efficient protocol for the production and storage of pluripotent hESCs. This strategy ensured high expansion ratios (an approximately twenty-fold increase in cell concentration) and high cell recovery yields (>70%) after cryopreservation. When compared with non-encapsulated cells, cell survival post-thawing demonstrated a three-fold improvement without compromising hESC characteristics. Microencapsulation also improved the culture of hESC aggregates by protecting cells from hydrodynamic shear stress, controlling aggregate size and maintaining cell pluripotency for two weeks. This work establishes that microencapsulation technology may prove a powerful tool for integrating the expansion and cryopreservation of pluripotent hESCs. The 3D culture strategy developed herein represents a significant breakthrough towards the implementation of hESCs in clinical and industrial applications. PMID:21850261

  17. Fundamentals of radiological protection

    International Nuclear Information System (INIS)

    Wells, J.; Mill, A.J.; Charles, M.W.

    1978-05-01

    The basic processes of living cells which are relevant to an understanding of the interaction of ionizing radiation with man are described. Particular reference is made to cell death, cancer induction and genetic effects. This is the second of a series of reports which present the fundamentals necessary for an understanding of the bases of regulatory criteria such as those recommended by the International Commision on Radiological Protection (ICRP). Others consider basic radiation physics and the biological effects of ionizing radiation. (author)

  18. Production of a generic microbial feedstock for lignocellulose biorefineries through sequential bioprocessing.

    Science.gov (United States)

    Chang, Chen-Wei; Webb, Colin

    2017-03-01

    Lignocellulosic materials, mostly from agricultural and forestry residues, provide a potential renewable resource for sustainable biorefineries. Reducing sugars can be produced only after a pre-treatment stage, which normally involves chemicals but can be biological. In this case, two steps are usually necessary: solid-state cultivation of fungi for deconstruction, followed by enzymatic hydrolysis using cellulolytic enzymes. In this research, the utilisation of solid-state bioprocessing using the fungus Trichoderma longibrachiatum was implemented as a simultaneous microbial pretreatment and in-situ enzyme production method for fungal autolysis and further enzyme hydrolysis of fermented solids. Suspending the fermented solids in water at 50°C led to the highest hydrolysis yields of 226mg/g reducing sugar and 7.7mg/g free amino nitrogen (FAN). The resultant feedstock was shown to be suitable for the production of various products including ethanol. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Grouping annotations on the subcellular layered interactome demonstrates enhanced autophagy activity in a recurrent experimental autoimmune uveitis T cell line.

    Directory of Open Access Journals (Sweden)

    Xiuzhi Jia

    Full Text Available Human uveitis is a type of T cell-mediated autoimmune disease that often shows relapse-remitting courses affecting multiple biological processes. As a cytoplasmic process, autophagy has been seen as an adaptive response to cell death and survival, yet the link between autophagy and T cell-mediated autoimmunity is not certain. In this study, based on the differentially expressed genes (GSE19652 between the recurrent versus monophasic T cell lines, whose adoptive transfer to susceptible animals may result in respective recurrent or monophasic uveitis, we proposed grouping annotations on a subcellular layered interactome framework to analyze the specific bioprocesses that are linked to the recurrence of T cell autoimmunity. That is, the subcellular layered interactome was established by the Cytoscape and Cerebral plugin based on differential expression, global interactome, and subcellular localization information. Then, the layered interactomes were grouping annotated by the ClueGO plugin based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis showed that significant bioprocesses with autophagy were orchestrated in the cytoplasmic layered interactome and that mTOR may have a regulatory role in it. Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we confirmed by transmission electron microscopy that, in comparison to the monophasic disease, recurrent uveitis in vivo showed significantly increased autophagy activity and extended lymphocyte infiltration to the affected retina. In summary, our framework methodology is a useful tool to disclose specific bioprocesses and molecular targets that can be attributed to a certain disease. Our results indicated that targeted inhibition of autophagy pathways may perturb the recurrence of uveitis.

  20. Bioprocessing of lignite coals using reductive microorganisms. Final technical report, September 30, 1988--March 29, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, D.L.

    1992-03-29

    In order to convert lignite coals into liquid fuels, gases or chemical feedstock, the macromolecular structure of the coal must be broken down into low molecular weight fractions prior to further modification. Our research focused on this aspect of coal bioprocessing. We isolated, characterized and studied the lignite coal-depolymerizing organisms Streptomyces viridosporus T7A, Pseudomonas sp. DLC-62, unidentified bacterial strain DLC-BB2 and Gram-positive Bacillus megaterium strain DLC-21. In this research we showed that these bacteria are able to solubilize and depolymerize lignite coals using a combination of biological mechanisms including the excretion of coal solublizing basic chemical metabolites and extracellular coal depolymerizing enzymes.

  1. Development of the Fibulin-3 protein therapeutics of non small cell lung cancer stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Gyu; Kim, Kugchan; Jung, Il Lae; Kim, Seo Yeon; Choi, Su Im; Lee, Jae Ha

    2013-09-15

    This study focuses on developing an efficient bioprocess for large-scale production of fibulin-3 using Chinese Hamster Ovary cell expression system and evaluating its therapeutic potential for the treatment of cancer. The specific aims are as follows: Isolation and establishment of CSCs using FACS based on cell surface markers and high ALDH1 activity. Identification and characterization of lung cancer stem cells that acquire features of CSC upon exposure to ionizing radiation. Evaluation of the fibulin-3 effects on the stem traits and signaling pathways required for the generation and maintenance of CSCs. In vivo validation of fivulin-3 for tumor prognosis and therapeutic efficacy against lung cancer using animal model.

  2. Process integration in bioprocess indystry: waste heat recovery in yeast and ethyl alcohol plant

    International Nuclear Information System (INIS)

    Raskovic, P.; Anastasovski, A.; Markovska, Lj.; Mesko, V.

    2010-01-01

    The process integration of the bioprocess plant for production of yeast and alcohol was studied. Preliminary energy audit of the plant identified the huge amount of thermal losses, caused by waste heat in exhausted process streams, and reviled the great potential for energy efficiency improvement by heat recovery system. Research roadmap, based on process integration approach, is divided on six phases, and the primary tool used for the design of heat recovery network was Pinch Analysis. Performance of preliminary design are obtained by targeting procedure, for three process stream sets, and evaluated by the economic criteria. The results of process integration study are presented in the form of heat exchanger networks which fulfilled the utilization of waste heat and enable considerable savings of energy in short payback period.

  3. Progress in emerging techniques for characterization of immobilized viable whole-cell biocatalysts

    Czech Academy of Sciences Publication Activity Database

    Bučko, M.; Vikartovská, A.; Schenkmayerová, A.; Tkáč, J.; Filip, J.; Chorvát Jr., D.; Neděla, Vilém; Ansorge-Schumacher, M.B.; Gemeiner, P.

    2017-01-01

    Roč. 71, č. 11 (2017), s. 2309-2324 ISSN 0366-6352 Institutional support: RVO:68081731 Keywords : bioelectrocatalysis * imaging techniques * immobilized whole-cell biocatalyst * multienzyme cascade reactions * online kinetics Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering OBOR OECD: Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation Impact factor: 1.258, year: 2016

  4. Induction of fungal laccase production under solid state bioprocessing of new agroindustrial waste and its application on dye decolorization.

    Science.gov (United States)

    Akpinar, Merve; Ozturk Urek, Raziye

    2017-06-01

    Lignocellulosic wastes are generally produced in huge amounts worldwide. Peach waste of these obtained from fruit juice industry was utilized as the substrate for laccase production by Pleurotus eryngii under solid state bioprocessing (SSB). Its chemical composition was determined and this bioprocess was carried out under stationary conditions at 28 °C. The effects of different compounds; copper, iron, Tween 80, ammonium nitrate and manganese, and their variable concentrations on laccase production were investigated in detail. The optimum production of laccase (43,761.33 ± 3845 U L -1 ) was achieved on the day of 20 by employing peach waste of 5.0 g and 70 µM Cu 2+ , 18 µM Fe 2+ , 0.025% (v/v) Tween 80, 4.0 g L -1 ammonium nitrate, 750 µM Mn 2+ as the inducers. The dye decolorization also researched to determine the degrading capability of laccase produced from peach culture under the above-mentioned conditions. Within this scope of the study, methyl orange, tartrazine, reactive red 2 and reactive black dyes were treated with this enzyme. The highest decolorization was performed with methyl orange as 43 ± 2.8% after 5 min of treatment when compared to other dyes. Up to now, this is the first report on the induction of laccase production by P. eryngii under SSB using peach waste as the substrate.

  5. Rapid Analysis of Carbohydrates in Bioprocess Samples: An Evaluation of the CarboPac SA10 for HPAE-PAD Analysis by Interlaboratory Comparison

    Energy Technology Data Exchange (ETDEWEB)

    Sevcik, R. S.; Hyman, D. A.; Basumallich, L.; Scarlata, C. J.; Rohrer, J.; Chambliss, C. K.

    2013-01-01

    A technique for carbohydrate analysis for bioprocess samples has been developed, providing reduced analysis time compared to current practice in the biofuels R&D community. The Thermofisher CarboPac SA10 anion-exchange column enables isocratic separation of monosaccharides, sucrose and cellobiose in approximately 7 minutes. Additionally, use of a low-volume (0.2 mL) injection valve in combination with a high-volume detection cell minimizes the extent of sample dilution required to bring sugar concentrations into the linear range of the pulsed amperometric detector (PAD). Three laboratories, representing academia, industry, and government, participated in an interlaboratory study which analyzed twenty-one opportunistic samples representing biomass pretreatment, enzymatic saccharification, and fermentation samples. The technique's robustness, linearity, and interlaboratory reproducibility were evaluated and showed excellent-to-acceptable characteristics. Additionally, quantitation by the CarboPac SA10/PAD was compared with the current practice method utilizing a HPX-87P/RID. While these two methods showed good agreement a statistical comparison found significant quantitation difference between them, highlighting the difference between selective and universal detection modes.

  6. Microscale technologies for cell engineering

    CERN Document Server

    Gaharwar, Akhilesh

    2016-01-01

    This book offers readers cutting-edge research at the interface of polymer science and engineering, biomedical engineering, materials science, and biology. State-of-the-art developments in microscale technologies for cell engineering applications are covered, including technologies relevant to both pluripotent and adult stem cells, the immune system, and somatic cells of the animal and human origin. This book bridges the gap in the understanding of engineering biology at multiple length scale, including microenvironmental control, bioprocessing, and tissue engineering in the areas of cardiac, cartilage, skeletal, and vascular tissues, among others. This book also discusses unique, emerging areas of micropatterning and three-dimensional printing models of cellular engineering, and contributes to the better understanding of the role of biophysical factors in determining the cell fate. Microscale Technologies for Cell Engineering is valuable for bioengineers, biomaterial scientists, tissue engineers, clinicians,...

  7. A fluorescence anisotropy method for measuring protein concentration in complex cell culture media.

    Science.gov (United States)

    Groza, Radu Constantin; Calvet, Amandine; Ryder, Alan G

    2014-04-22

    The rapid, quantitative analysis of the complex cell culture media used in biopharmaceutical manufacturing is of critical importance. Requirements for cell culture media composition profiling, or changes in specific analyte concentrations (e.g. amino acids in the media or product protein in the bioprocess broth) often necessitate the use of complicated analytical methods and extensive sample handling. Rapid spectroscopic methods like multi-dimensional fluorescence (MDF) spectroscopy have been successfully applied for the routine determination of compositional changes in cell culture media and bioprocess broths. Quantifying macromolecules in cell culture media is a specific challenge as there is a need to implement measurements rapidly on the prepared media. However, the use of standard fluorescence spectroscopy is complicated by the emission overlap from many media components. Here, we demonstrate how combining anisotropy measurements with standard total synchronous fluorescence spectroscopy (TSFS) provides a rapid, accurate quantitation method for cell culture media. Anisotropy provides emission resolution between large and small fluorophores while TSFS provides a robust measurement space. Model cell culture media was prepared using yeastolate (2.5 mg mL(-1)) spiked with bovine serum albumin (0 to 5 mg mL(-1)). Using this method, protein emission is clearly discriminated from background yeastolate emission, allowing for accurate bovine serum albumin (BSA) quantification over a 0.1 to 4.0 mg mL(-1) range with a limit of detection (LOD) of 13.8 μg mL(-1). Copyright © 2014. Published by Elsevier B.V.

  8. Bioprocess Intensification of Beer Fermentation Using Immobilised Cells

    Science.gov (United States)

    Verbelen, Pieter J.; Nedović, Viktor A.; Manojlović, Verica; Delvaux, Freddy R.; Laskošek-Čukalović, Ida; Bugarski, Branko; Willaert, Ronnie

    Beer production with immobilised yeast has been the subject of research for approximately 30 years but has so far found limited application in the brewing industry, due to engineering problems, unrealised cost advantages, microbial contaminations and an unbalanced beer flavor (Linko et al. 1998; Brányik et al. 2005; Willaert and Nedović 2006). The ultimate aim of this research is the production of beer of desired quality within 1-3 days. Traditional beer fermentation systems use freely suspended yeast cells to ferment wort in an unstirred batch reactor. The primary fermentation takes approximately 7 days with a subsequent secondary fermentation (maturation) of several weeks. A batch culture system employing immobilization could benefit from an increased rate of fermentation. However, it appears that in terms of increasing productivity, a continuous fermentation system with immobilization would be the best method (Verbelen et al. 2006). An important issue of the research area is whether beer can be produced by immobilised yeast in continuous culture with the same characteristic as the traditional method.

  9. Homogenizing bacterial cell factories: Analysis and engineering of phenotypic heterogeneity.

    Science.gov (United States)

    Binder, Dennis; Drepper, Thomas; Jaeger, Karl-Erich; Delvigne, Frank; Wiechert, Wolfgang; Kohlheyer, Dietrich; Grünberger, Alexander

    2017-07-01

    In natural habitats, microbes form multispecies communities that commonly face rapidly changing and highly competitive environments. Thus, phenotypic heterogeneity has evolved as an innate and important survival strategy to gain an overall fitness advantage over cohabiting competitors. However, in defined artificial environments such as monocultures in small- to large-scale bioreactors, cell-to-cell variations are presumed to cause reduced production yields as well as process instability. Hence, engineering microbial production toward phenotypic homogeneity is a highly promising approach for synthetic biology and bioprocess optimization. In this review, we discuss recent studies that have unraveled the cell-to-cell heterogeneity observed during bacterial gene expression and metabolite production as well as the molecular mechanisms involved. In addition, current single-cell technologies are briefly reviewed with respect to their applicability in exploring cell-to-cell variations. We highlight emerging strategies and tools to reduce phenotypic heterogeneity in biotechnological expression setups. Here, strain or inducer modifications are combined with cell physiology manipulations to achieve the ultimate goal of equalizing bacterial populations. In this way, the majority of cells can be forced into high productivity, thus reducing less productive subpopulations that tend to consume valuable resources during production. Modifications in uptake systems, inducer molecules or nutrients represent valuable tools for diminishing heterogeneity. Finally, we address the challenge of transferring homogeneously responding cells into large-scale bioprocesses. Environmental heterogeneity originating from extrinsic factors such as stirring speed and pH, oxygen, temperature or nutrient distribution can significantly influence cellular physiology. We conclude that engineering microbial populations toward phenotypic homogeneity is an increasingly important task to take biotechnological

  10. FUNDAMENTAL TUNNELING PROCESSES IN MOSa SOLAR CELLS

    OpenAIRE

    Balberg , I.; Hanak , J.; Weakliem , H.; Gal , E.

    1981-01-01

    In previous studies of tunneling through a MOSa tunnel junction, where Sa was a-Si : H, it was shown that their characteristics resemble those of MOSc devices where Sc was crystalline silicon. In the present work we would like to report a demonstration of fundamental tunneling processes in such tunnel junctions. In particular, the transition from semiconductor controlled regime to tunneling controlled regime can be clearly distinguished. The present results represent one of the rare cases whe...

  11. Fundamental studies of leukemic cell labeling with 111 In-oxine and their applications to cell kinetics in patients with acute leukemia

    International Nuclear Information System (INIS)

    Takagi, Yuhkoh; Matsuda, Shin; Uchida, Tatsumi; Kariyone, Shigeo

    1984-01-01

    Fundamental studies of leukemic cell labeling with 111 In-oxine and their applications to leukemic cell kinetics in five patients with acute myeloblastic leukemia (AML) were examined. Labeling efficiency of leukemic cells was 80.3 +- 3.6% for more than 1 x 10 8 cells at room temperature for 20 minutes of incubation followed by two times washes. Cell viability determined by means of trypanblue exclusion test was 95.3 +- 2.6%. In vitro elution rate of 111 In from the labeled cells during 12 hours was 10.0 +- 1.2%. The disappearance curves of labeled leukemic cells in AMLs followed a single exponential fashion, and the half time of disappearance (T 1/2) ranged from 9.6 to 31.8 hours. Total blood leukemic cell pool (TBLCP) calculated with the dilution principles of radioisotopes correlated significantly with the leukemic cell counts (LC) in the peripheral blood (Y = 0.32 + 1.94X, r = 0.99). In the studies of organ distribution which were observed and analized with gamma camera and computer, labeled leukemic cells passed through lungs within 15 minutes. Radioactivity in the spleen increased rapidly for 30 - 60 minutes, then reached a plateau. Hepatic radioactivity showed a temporary decrease during 10 - 60 minutes following the moderate accumulation in initial 10 minutes. In two cases, bone marrow was visualized 24 hours after the injection. Radioactivity of the leukemic cells isolated from the bone marrow at 22 hours after the injection in one case was one third of the radioactivity in leukemic cells obtained from the peripheral blood at the same time. (author)

  12. Mid Year Meetings

    Indian Academy of Sciences (India)

    10.30, M. KRISHNAMURTHY, Tata Institute of Fundamental Research, Mumbai Making a ... Averaging operations on matrices, View PDF file (220 kbytes) ... Food and bio-process engineering - research contributions, View presentation.

  13. Bio-processing of solid wastes and secondary resources for metal extraction - A review.

    Science.gov (United States)

    Lee, Jae-Chun; Pandey, Banshi Dhar

    2012-01-01

    Metal containing wastes/byproducts of various industries, used consumer goods, and municipal waste are potential pollutants, if not treated properly. They may also be important secondary resources if processed in eco-friendly manner for secured supply of contained metals/materials. Bio-extraction of metals from such resources with microbes such as bacteria, fungi and archaea is being increasingly explored to meet the twin objectives of resource recycling and pollution mitigation. This review focuses on the bio-processing of solid wastes/byproducts of metallurgical and manufacturing industries, chemical/petrochemical plants, electroplating and tanning units, besides sewage sludge and fly ash of municipal incinerators, electronic wastes (e-wastes/PCBs), used batteries, etc. An assessment has been made to quantify the wastes generated and its compositions, microbes used, metal leaching efficiency etc. Processing of certain effluents and wastewaters comprising of metals is also included in brief. Future directions of research are highlighted. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Invitro Study on the Fluid From Banana Stem Bioprocess as Direct Fed Microbial

    Science.gov (United States)

    Mutaqin, B. K.; Tanuwiria, U. H.; Hernawan, E.

    2018-02-01

    The purpose of this research was to study the liquid produced by the bioprocess of banana stem as a Direct Fed Microbial (DFM) in order to enhance local sheep productivity invitro. Studying was the use of DFM in two invitro feeds. The object observed in this research was fermentability and digestibility value. The method was experimental with the experimental design, i.e. factorial experimental design with two factors. The first factor was DFM, the levels of which were 0, 0,2, 0,4 and 0,6%, while the second factor was two feed types (complete feed and Pennisetum purpureum only) with the treatment of threefold repetition. This research showed that fermentability and digestibility value were influenced by the DFM in the invitro complete feed. The research result analyzed using MANOVA with further testing using Duncan Test. The conclusion of the research result were shows the interaction DFM in the complete feed improve fermentability and digestibility values and DFM 0,6% shows the highest value.

  15. Simultaneous production of lipases and biosurfactants by submerged and solid-state bioprocesses.

    Science.gov (United States)

    Colla, Luciane Maria; Rizzardi, Juliana; Pinto, Marta Heidtmann; Reinehr, Christian Oliveira; Bertolin, Telma Elita; Costa, Jorge Alberto Vieira

    2010-11-01

    Lipases and biosurfactants are compounds produced by microorganisms generally involved in the metabolization of oil substrates. However, the relationship between the production of lipases and biosurfactants has not been established yet. Therefore, this study aimed to evaluate the correlation between production of lipases and biosurfactants by submerged (SmgB) and solid-state bioprocess (SSB) using Aspergillus spp., which were isolated from a soil contaminated by diesel oil. SSB had the highest production of lipases, with lipolytic activities of 25.22U, while SmgB had 4.52U. The production of biosurfactants was not observed in the SSB. In the SmgB, correlation coefficients of 91% and 87% were obtained between lipolytic activity and oil in water and water in oil emulsifying activities, respectively. A correlation of 84% was obtained between lipolytic activity and reduction of surface tension in the culture medium. The surface tension decreased from 50 to 28mNm(-1) indicating that biosurfactants were produced in the culture medium. Copyright 2010 Elsevier Ltd. All rights reserved.

  16. Development of serum-free media for lepidopteran insect cell lines.

    Science.gov (United States)

    Agathos, Spiros N

    2007-01-01

    Lepidopteran insect cell culture technology has progressed to the point of becoming an essential part of one of the most successful eukaryotic expression systems and is increasingly used industrially on a large scale. Therefore, there is a constant need for convenient and low-cost culture media capable of supporting good insect cell growth and ensuring high yield of baculovirus as well as the strong expression of recombinant proteins. Vertebrate sera or invertebrate hemolymph were essential supplements in first-generation insect cell media. These supplements, however, are cumbersome and expensive for routine large-scale culture; thus, their use is now circumvented by substituting the essential growth factors present in these supplements with serum-free substances. Such non-serum supplements are typically of non-animal origin and include protein hydrolysates, lipid emulsions, and specialized substances (e.g., surfactants and shear damage protecting chemicals). These supplements need to complement the defined, synthetic basal medium to ensure that the fundamental nutritional needs of the cells are satisfied. Although there is a significant number of proprietary serum-free and low-protein or protein-free media on the market, the lack of information concerning their detailed composition is a drawback in their adoption for different applications, including their adaptation to the metabolic and kinetic analysis and monitoring of a given insect cell based bioprocess. Hence, there is wide appeal for formulating serum-free media based on a rational assessment of the metabolic requirements of the lepidopteran cells during both the growth and the production phases. Techniques such as statistical experimental design and genetic algorithms adapted to the cellular behavior and the bioreactor operation mode (batch, fed-batch, or perfusion) permit the formulation of versatile serum- and protein-free media. These techniques are illustrated with recent developments of serum

  17. Simplex-based optimization of numerical and categorical inputs in early bioprocess development: Case studies in HT chromatography.

    Science.gov (United States)

    Konstantinidis, Spyridon; Titchener-Hooker, Nigel; Velayudhan, Ajoy

    2017-08-01

    Bioprocess development studies often involve the investigation of numerical and categorical inputs via the adoption of Design of Experiments (DoE) techniques. An attractive alternative is the deployment of a grid compatible Simplex variant which has been shown to yield optima rapidly and consistently. In this work, the method is combined with dummy variables and it is deployed in three case studies wherein spaces are comprised of both categorical and numerical inputs, a situation intractable by traditional Simplex methods. The first study employs in silico data and lays out the dummy variable methodology. The latter two employ experimental data from chromatography based studies performed with the filter-plate and miniature column High Throughput (HT) techniques. The solute of interest in the former case study was a monoclonal antibody whereas the latter dealt with the separation of a binary system of model proteins. The implemented approach prevented the stranding of the Simplex method at local optima, due to the arbitrary handling of the categorical inputs, and allowed for the concurrent optimization of numerical and categorical, multilevel and/or dichotomous, inputs. The deployment of the Simplex method, combined with dummy variables, was therefore entirely successful in identifying and characterizing global optima in all three case studies. The Simplex-based method was further shown to be of equivalent efficiency to a DoE-based approach, represented here by D-Optimal designs. Such an approach failed, however, to both capture trends and identify optima, and led to poor operating conditions. It is suggested that the Simplex-variant is suited to development activities involving numerical and categorical inputs in early bioprocess development. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Application of the wavelet image analysis technique to monitor cell concentration in bioprocesses

    Directory of Open Access Journals (Sweden)

    G. J. R. Garófano

    2005-12-01

    Full Text Available The growth of cells of great practical interest, such as, the filamentous cells of bacterium Streptomyces clavuligerus, the yeast Saccharomyces cerevisiae and the insect Spodoptera frugiperda (Sf9 cell, cultivated in shaking flasks with complex media at appropriate temperatures and pHs, was quantified by the new wavelet transform technique. This image analysis tool was implemented using Matlab 5.2 software to process digital images acquired of samples taken of these three types of cells throughoot their cultivation. The values of the average wavelet coefficients (AWCs of simplified images were compared with experimental measurements of cell concentration and with computer-based densitometric measurements. AWCs were shown to be directly proportional to measurements of cell concentration and to densitometric measurements, making evident the great potential of the wavelet transform technique to quantitatively estimate the growth of several types of cells.

  19. Fundamental ecology is fundamental.

    Science.gov (United States)

    Courchamp, Franck; Dunne, Jennifer A; Le Maho, Yvon; May, Robert M; Thébaud, Christophe; Hochberg, Michael E

    2015-01-01

    The primary reasons for conducting fundamental research are satisfying curiosity, acquiring knowledge, and achieving understanding. Here we develop why we believe it is essential to promote basic ecological research, despite increased impetus for ecologists to conduct and present their research in the light of potential applications. This includes the understanding of our environment, for intellectual, economical, social, and political reasons, and as a major source of innovation. We contend that we should focus less on short-term, objective-driven research and more on creativity and exploratory analyses, quantitatively estimate the benefits of fundamental research for society, and better explain the nature and importance of fundamental ecology to students, politicians, decision makers, and the general public. Our perspective and underlying arguments should also apply to evolutionary biology and to many of the other biological and physical sciences. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Fast Filtration of Bacterial or Mammalian Suspension Cell Cultures for Optimal Metabolomics Results.

    Directory of Open Access Journals (Sweden)

    Natalie Bordag

    Full Text Available The metabolome offers real time detection of the adaptive, multi-parametric response of the organisms to environmental changes, pathophysiological stimuli or genetic modifications and thus rationalizes the optimization of cell cultures in bioprocessing. In bioprocessing the measurement of physiological intracellular metabolite levels is imperative for successful applications. However, a sampling method applicable to all cell types with little to no validation effort which simultaneously offers high recovery rates, high metabolite coverage and sufficient removal of extracellular contaminations is still missing. Here, quenching, centrifugation and fast filtration were compared and fast filtration in combination with a stabilizing washing solution was identified as the most promising sampling method. Different influencing factors such as filter type, vacuum pressure, washing solutions were comprehensively tested. The improved fast filtration method (MxP® FastQuench followed by routine lipid/polar extraction delivers a broad metabolite coverage and recovery reflecting well physiological intracellular metabolite levels for different cell types, such as bacteria (Escherichia coli as well as mammalian cells chinese hamster ovary (CHO and mouse myeloma cells (NS0.The proposed MxP® FastQuench allows sampling, i.e. separation of cells from medium with washing and quenching, in less than 30 seconds and is robustly designed to be applicable to all cell types. The washing solution contains the carbon source respectively the 13C-labeled carbon source to avoid nutritional stress during sampling. This method is also compatible with automation which would further reduce sampling times and the variability of metabolite profiling data.

  1. Influence of multiple bioprocess parameters on production of lipase from Pseudomonas sp. BWS-5

    Directory of Open Access Journals (Sweden)

    Balwinder Singh Sooch

    2013-10-01

    Full Text Available The aim of the present work was to study the influence of multiple bioprocess parameters for the maximum production of lipase from Pseudomonas sp. BWS-5. The culture reached the stationary phase of growth after 36h of incubation when the maximum lipase production was obtained at flask level. The different media components such as carbon sources, nitrogen sources, trace elements and process parameters such as the pH of the medium, temperature and time of incubation, agitation/stationary conditions, etc. were optimized at flask level and at bioreactor level. The maximum enzyme production of 298 IU/mL was obtained with the use of simple medium with pH 6.5 containing glucose (1 %, w/v, peptone (3 %, w/v and KCl (0.05 %, w/v after 30h of incubation at 37°C under agitation (200 rpm conditions with 0.75 vvm of air supply.

  2. Fundamental Research and Development for Improved Crystalline Silicon Solar Cells: Final Subcontract Report, March 2002 - July 2006

    Energy Technology Data Exchange (ETDEWEB)

    Rohatgi, A.

    2007-11-01

    This report summarizes the progress made by Georgia Tech in the 2002-2006 period toward high-efficiency, low-cost crystalline silicon solar cells. This program emphasize fundamental and applied research on commercial substrates and manufacturable technologies. A combination of material characterization, device modeling, technology development, and complete cell fabrication were used to accomplish the goals of this program. This report is divided into five sections that summarize our work on i) PECVD SiN-induced defect passivation (Sections 1 and 2); ii) the effect of material inhomogeneity on the performance of mc-Si solar cells (Section 3); iii) a comparison of light-induced degradation in commercially grown Ga- and B-doped Czochralski Si ingots (Section 4); and iv) the understanding of the formation of high-quality thick-film Ag contacts on high sheet-resistance emitters (Section 5).

  3. The Draft Genome Sequence of Clostridium sp. Strain NJ4, a Bacterium Capable of Producing Butanol from Inulin Through Consolidated Bioprocessing.

    Science.gov (United States)

    Jiang, Yujia; Lu, Jiasheng; Chen, Tianpeng; Yan, Wei; Dong, Weiliang; Zhou, Jie; Zhang, Wenming; Ma, Jiangfeng; Jiang, Min; Xin, Fengxue

    2018-05-23

    A novel butanogenic Clostridium sp. NJ4 was successfully isolated and characterized, which could directly produce relatively high titer of butanol from inulin through consolidated bioprocessing (CBP). The assembled draft genome of strain NJ4 is 4.09 Mp, containing 3891 encoded protein sequences with G+C content of 30.73%. Among these annotated genes, a levanase, a hypothetical inulinase, and two bifunctional alcohol/aldehyde dehydrogenases (AdhE) were found to play key roles in the achievement of ABE production from inulin through CBP.

  4. Progress in biocatalysis with immobilized viable whole cells: systems development, reaction engineering and applications

    Czech Academy of Sciences Publication Activity Database

    Polakovič, M.; Švitel, J.; Bučko, M.; Filip, J.; Neděla, Vilém; Ansorge-Schumacher, M.B.; Gemeiner, P.

    2017-01-01

    Roč. 39, č. 5 (2017), s. 667-683 ISSN 0141-5492 Institutional support: RVO:68081731 Keywords : biocatalysis * immobilization methods * immobilized whole-cell biocatalyst * multienzyme cascade reactions * process economics * reaction engineering Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering OBOR OECD: Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation Impact factor: 1.730, year: 2016

  5. Fundamentals of bladder tissue engineering | Mahfouz | African ...

    African Journals Online (AJOL)

    Fundamentals of bladder tissue engineering. ... could affect the bladder and lead to eventual loss of its integrity, with the need for replacement or repair. ... Tissue engineering relies upon three essential pillars; the scaffold, the cells seeded on ...

  6. A fast and systematic procedure to develop dynamic models of bioprocesses: application to microalgae cultures

    Directory of Open Access Journals (Sweden)

    J. Mailier

    2010-09-01

    Full Text Available The purpose of this paper is to report on the development of a procedure for inferring black-box, yet biologically interpretable, dynamic models of bioprocesses based on sets of measurements of a few external components (biomass, substrates, and products of interest. The procedure has three main steps: (a the determination of the number of macroscopic biological reactions linking the measured components; (b the estimation of a first reaction scheme, which has interesting mathematical properties, but might lack a biological interpretation; and (c the "projection" (or transformation of this reaction scheme onto a biologically-consistent scheme. The advantage of the method is that it allows the fast prototyping of models for the culture of microorganisms that are not well documented. The good performance of the third step of the method is demonstrated by application to an example of microalgal culture.

  7. Contributions of depth filter components to protein adsorption in bioprocessing.

    Science.gov (United States)

    Khanal, Ohnmar; Singh, Nripen; Traylor, Steven J; Xu, Xuankuo; Ghose, Sanchayita; Li, Zheng J; Lenhoff, Abraham M

    2018-04-16

    Depth filtration is widely used in downstream bioprocessing to remove particulate contaminants via depth straining and is therefore applied to harvest clarification and other processing steps. However, depth filtration also removes proteins via adsorption, which can contribute variously to impurity clearance and to reduction in product yield. The adsorption may occur on the different components of the depth filter, that is, filter aid, binder, and cellulose filter. We measured adsorption of several model proteins and therapeutic proteins onto filter aids, cellulose, and commercial depth filters at pH 5-8 and ionic strengths filter component in the adsorption of proteins with different net charges, using confocal microscopy. Our findings show that a complete depth filter's maximum adsorptive capacity for proteins can be estimated by its protein monolayer coverage values, which are of order mg/m 2 , depending on the protein size. Furthermore, the extent of adsorption of different proteins appears to depend on the nature of the resin binder and its extent of coating over the depth filter surface, particularly in masking the cation-exchanger-like capacity of the siliceous filter aids. In addition to guiding improved depth filter selection, the findings can be leveraged in inspiring a more intentional selection of components and design of depth filter construction for particular impurity removal targets. © 2018 Wiley Periodicals, Inc.

  8. Suspension culture of pluripotent stem cells: effect of shear on stem cell fate.

    Science.gov (United States)

    Keller, Kevin C; Rodrigues, Beatriz; zur Nieden, Nicole I

    2014-01-01

    Despite significant promise, the routine usage of suspension cell culture to manufacture stem cell-derived differentiated cells has progressed slowly. Suspension culture is an innovative way of either expanding or differentiating cells and sometimes both are combined into a single bioprocess. Its advantages over static 2D culturing include a homogeneous and controllable culture environment and producing a large quantity of cells in a fraction of time. This feature makes suspension cell culture ideal for use in stem cell research and eventually ideal in the large-scale production of differentiated cells for regenerative medicine. Because of their tremendous differentiation capacities and unlimited growth properties, pluripotent stem cells (PSCs) in particular are considered potential sources for future cell-replacement therapies. Currently, expansion of PSCs is accomplished in 2D, which only permits a limited amount of cell growth per culture flask before cells need to be passaged. However, before stem cells can be applied clinically, several aspects of their expansion, such as directed growth, but also differentiation, need to be better controlled. This review will summarize recent advantages in suspension culture of PSCs, while at the same time highlighting current challenges.

  9. Insights to the effects of free cells on community structure of attached cells and chalcopyrite bioleaching during different stages.

    Science.gov (United States)

    Feng, Shoushuai; Yang, Hailin; Wang, Wu

    2016-01-01

    The effects of free cells on community structure of attached cells and chalcopyrite bioleaching by Acidithiobacillus sp. during different stages were investigated. The attached cells of Acidithiobacillus thiooxidans owned the community advantage from 14thd to the end of bioprocess in the normal system. The community structure of attached cells was greatly influenced in the free cells-deficient systems. Compared to A. thiooxidans, the attached cells community of Acidithiobacillus ferrooxidans had a higher dependence on its free cells. Meanwhile, the analysis of key biochemical parameters revealed that the effects of free cells on chalcopyrite bioleaching in different stages were diverse, ranging from 32.8% to 64.3%. The bioleaching contribution of free cells of A. ferrooxidans in the stationary stage (8-14thd) was higher than those of A. thiooxidans, while the situation was gradually reversed in the jarosite passivation inhibited stage (26-40thd). These results may be useful in guiding chalcopyrite bioleaching. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Fundamental studies of leukemic cell labeling with /sup 111/In-oxine and their applications to cell kinetics in patients with acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Takagi, Yuhkoh; Matsuda, Shin; Uchida, Tatsumi; Kariyone, Shigeo [Fukushima Medical Coll. (Japan)

    1984-04-01

    Fundamental studies of leukemic cell labeling with /sup 111/In-oxine and their applications to leukemic cell kinetics in five patients with acute myeloblastic leukemia (AML) were examined. Labeling efficiency of leukemic cells was 80.3 +- 3.6% for more than 1 x 10/sup 8/ cells at room temperature for 20 minutes of incubation followed by two times washes. Cell viability determined by means of trypanblue exclusion test was 95.3 +- 2.6%. In vitro elution rate of /sup 111/In from the labeled cells during 12 hours was 10.0 +- 1.2%. The disappearance curves of labeled leukemic cells in AMLs followed a single exponential fashion, and the half time of disappearance (T 1/2) ranged from 9.6 to 31.8 hours. Total blood leukemic cell pool (TBLCP) calculated with the dilution principles of radioisotopes correlated significantly with the leukemic cell counts (LC) in the peripheral blood (Y = 0.32 + 1.94X, r = 0.99). In the studies of organ distribution which were observed and analyzed with gamma camera and computer, labeled leukemic cells passed through lungs within 15 minutes. Radioactivity in the spleen increased rapidly for 30 - 60 minutes, then reached a plateau. Hepatic radioactivity showed a temporary decrease during 10 - 60 minutes following the moderate accumulation in initial 10 minutes. In two cases, bone marrow was visualized 24 hours after the injection. Radioactivity of the leukemic cells isolated from the bone marrow at 22 hours after the injection in one case was one third of the radioactivity in leukemic cells obtained from the peripheral blood at the same time.

  11. Treatment of supermarket vegetable wastes to be used as alternative substrates in bioprocesses.

    Science.gov (United States)

    Díaz, Ana Isabel; Laca, Amanda; Laca, Adriana; Díaz, Mario

    2017-09-01

    Fruits and vegetables have the highest wastage rates at retail and consumer levels. These wastes have promising potential for being used as substrates in bioprocesses. However, an effective hydrolysis of carbohydrates that form these residues has to be developed before the biotransformation. In this work, vegetable wastes from supermarket (tomatoes, green peppers and potatoes) have been separately treated by acid, thermal and enzymatic hydrolysis processes in order to maximise the concentration of fermentable sugars in the final broth. For all substrates, thermal and enzymatic processes have shown to be the most effective. A new combined hydrolysis procedure including these both treatments was also assayed and the enzymatic step was successfully modelled. With this combined hydrolysis, the percentage of reducing sugars extracted was increased, in comparison with the amount extracted from non-hydrolysed samples, approximately by 30% in the case of tomato and green peeper wastes. For potato wastes this percentage increased from values lower than 1% to 77%. In addition, very low values of fermentation inhibitors were found in the final broth. Copyright © 2017. Published by Elsevier Ltd.

  12. Developing a mesophilic co-culture for direct conversion of cellulose to butanol in consolidated bioprocess.

    Science.gov (United States)

    Wang, Zhenyu; Cao, Guangli; Zheng, Ju; Fu, Defeng; Song, Jinzhu; Zhang, Junzheng; Zhao, Lei; Yang, Qian

    2015-01-01

    Consolidated bioprocessing (CBP) of butanol production from cellulosic biomass is a promising strategy for cost saving compared to other processes featuring dedicated cellulase production. CBP requires microbial strains capable of hydrolyzing biomass with enzymes produced on its own with high rate and high conversion and simultaneously produce a desired product at high yield. However, current reported butanol-producing candidates are unable to utilize cellulose as a sole carbon source and energy source. Consequently, developing a co-culture system using different microorganisms by taking advantage of their specific metabolic capacities to produce butanol directly from cellulose in consolidated bioprocess is of great interest. This study was mainly undertaken to find complementary organisms to the butanol producer that allow simultaneous saccharification and fermentation of cellulose to butanol in their co-culture under mesophilic condition. Accordingly, a highly efficient and stable consortium N3 on cellulose degradation was first developed by multiple subcultures. Subsequently, the functional microorganisms with 16S rRNA sequences identical to the denaturing gradient gel electrophoresis (DGGE) profile were isolated from consortium N3. The isolate Clostridium celevecrescens N3-2 exhibited higher cellulose-degrading capability was thus chosen as the partner strain for butanol production with Clostridium acetobutylicum ATCC824. Meanwhile, the established stable consortium N3 was also investigated to produce butanol by co-culturing with C. acetobutylicum ATCC824. Butanol was produced from cellulose when C. acetobutylicum ATCC824 was co-cultured with either consortium N3 or C. celevecrescens N3-2. Co-culturing C. acetobutylicum ATCC824 with the stable consortium N3 resulted in a relatively higher butanol concentration, 3.73 g/L, and higher production yield, 0.145 g/g of glucose equivalent. The newly isolated microbial consortium N3 and strain C. celevecrescens N3

  13. Fundamental and clinical evaluation of ''SCC RIABEAD'' kit for immunoradiometric assay of squamous cell carcinoma related antigen

    International Nuclear Information System (INIS)

    Koizumi, Mitsuru; Endo, Keigo; Nakajima, Kotoko

    1987-01-01

    A commercial ''SCC RIABEAD'' kit for immunoradiometric assay of squamous cell carcinoma related antigen (SCC antigen) was fundamentally and clinically evaluated. Laboratory performance was satisfactory for intra-assay and inter-assay reproducibility, recovery, and dilution, with rapid and simple measurement techniques. Seropositivity for SCC antigen was significantly higher for squamous cell carcinoma of the liver and uterine cervix than the other histology types. In the case of cervical squamous cell carcinoma, it increased with progressing disease. Post-treatment serum levels of SCC antigen returned to negative. SCC antigen is considered to be a useful tumor marker for these diseases. There was a good correlation between the measurement values obtained from the present and conventional (SCC RIAKIT) assays. The present assay remarkably decreased false-positive cases of pulmonary benign diseases. The results showed a ''SCC RIABEAD'' to be a favorable kit for immunoradiometric assay of SSC antigen, as compared with conventional assay kit. (Namekawa, K.)

  14. Large Scale Production of Stem Cells and Their Derivatives

    Science.gov (United States)

    Zweigerdt, Robert

    Stem cells have been envisioned to become an unlimited cell source for regenerative medicine. Notably, the interest in stem cells lies beyond direct therapeutic applications. They might also provide a previously unavailable source of valuable human cell types for screening platforms, which might facilitate the development of more efficient and safer drugs. The heterogeneity of stem cell types as well as the numerous areas of application suggests that differential processes are mandatory for their in vitro culture. Many of the envisioned applications would require the production of a high number of stem cells and their derivatives in scalable, well-defined and potentially clinical compliant manner under current good manufacturing practice (cGMP). In this review we provide an overview on recent strategies to develop bioprocesses for the expansion, differentiation and enrichment of stem cells and their progenies, presenting examples for adult and embryonic stem cells alike.

  15. Fundamental criteria for the design of high-performance Josephson nondestructive readout random access memory cells and experimental confirmation

    International Nuclear Information System (INIS)

    Henkels, W.H.

    1979-01-01

    Fundamental design criteria for Josephson nondestructive readout random access memory (NDRO RAM) cells are presented, within the context of an LSI array environment. Emphasis is placed upon principles which are relevant to high performance. The criteria are elucidated via a specific design which is simulated and then experimentally evaluated in a technology with a smallest critical dimension of 5 μm. The specific cell differs from previously tested Josephson NDRO cells in several respects; namely, the cell stores only approx.8Phi 0 , employs interferometer gates and an external damping resistor, allows switching into device resonances, and eliminates the need for a special initialization cycle. The cell-selection scheme, employing triple coincidence, results in larger operating margins and smaller operating currents than have previously been achieved. The large operating margins and all basic cell design criteria were experimentally verified. The experimental interferometer gate characteristics were analyzed in detail and found to be describable by simple models. In addition, it was discovered that single flux quantum transitions in the interferometer gates could be exploited beneficially in order to enhance the insensitivity of operating margins to fabrication tolerances

  16. Cell Culturing of Cytoskeleton

    Science.gov (United States)

    2004-01-01

    Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc., has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc., is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

  17. Photoelectrochemistry, photocatalysis and photoreactors. Fundamentals and developments

    Energy Technology Data Exchange (ETDEWEB)

    Schiavello, M [ed.

    1985-01-01

    During this conference 29 lectures were read on following subjects: materials for electrodes and photochemical cells, fundamentals of photochemistry and photocatalysis, design and modelling of photochemical reactors and reactions. The aim was to define the state of the art and of outlining perspectives, developments and practical utilization. (A.V.)

  18. Design and validation of a consistent and reproducible manufacture process for the production of clinical-grade bone marrow-derived multipotent mesenchymal stromal cells.

    Science.gov (United States)

    Codinach, Margarita; Blanco, Margarita; Ortega, Isabel; Lloret, Mireia; Reales, Laura; Coca, Maria Isabel; Torrents, Sílvia; Doral, Manel; Oliver-Vila, Irene; Requena-Montero, Miriam; Vives, Joaquim; Garcia-López, Joan

    2016-09-01

    Multipotent mesenchymal stromal cells (MSC) have achieved a notable prominence in the field of regenerative medicine, despite the lack of common standards in the production processes and suitable quality controls compatible with Good Manufacturing Practice (GMP). Herein we describe the design of a bioprocess for bone marrow (BM)-derived MSC isolation and expansion, its validation and production of 48 consecutive batches for clinical use. BM samples were collected from the iliac crest of patients for autologous therapy. Manufacturing procedures included: (i) isolation of nucleated cells (NC) by automated density-gradient centrifugation and plating; (ii) trypsinization and expansion of secondary cultures; and (iii) harvest and formulation of a suspension containing 40 ± 10 × 10(6) viable cells. Quality controls were defined as: (i) cell count and viability assessment; (ii) immunophenotype; and (iii) sterility tests, Mycoplasma detection, endotoxin test and Gram staining. A 3-week manufacturing bioprocess was first designed and then validated in 3 consecutive mock productions, prior to producing 48 batches of BM-MSC for clinical use. Validation included the assessment of MSC identity and genetic stability. Regarding production, 139.0 ± 17.8 mL of BM containing 2.53 ± 0.92 × 10(9) viable NC were used as starting material, yielding 38.8 ± 5.3 × 10(6) viable cells in the final product. Surface antigen expression was consistent with the expected phenotype for MSC, displaying high levels of CD73, CD90 and CD105, lack of expression of CD31 and CD45 and low levels of HLA-DR. Tests for sterility, Mycoplasma, Gram staining and endotoxin had negative results in all cases. Herein we demonstrated the establishment of a feasible, consistent and reproducible bioprocess for the production of safe BM-derived MSC for clinical use. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  19. Fundamentals of radiological protection

    International Nuclear Information System (INIS)

    Charles, M.W.; Wells, J.; Mill, A.J.

    1978-04-01

    A brief review is presented of the early and late effects of ionising radiation on man, with particular emphasis on those aspects of importance in radiological protection. The terminology and dose response curves, are explained. Early effects on cells, tissues and whole organs are discussed. Late somatic effects considered include cancer and life-span shortening. Genetic effects are examined. The review is the third of a series of reports which present the fundamentals necessary for an understanding of the basis of regulatory criteria, such as those of the ICRP. (u.K.)

  20. Sustained productivity in recombinant Chinese Hamster Ovary (CHO) cell lines: proteome analysis of the molecular basis for a process-related phenotype

    LENUS (Irish Health Repository)

    Meleady, Paula

    2011-07-24

    Abstract Background The ability of mammalian cell lines to sustain cell specific productivity (Qp) over the full duration of bioprocess culture is a highly desirable phenotype, but the molecular basis for sustainable productivity has not been previously investigated in detail. In order to identify proteins that may be associated with a sustained productivity phenotype, we have conducted a proteomic profiling analysis of two matched pairs of monoclonal antibody-producing Chinese hamster ovary (CHO) cell lines that differ in their ability to sustain productivity over a 10 day fed-batch culture. Results Proteomic profiling of inherent differences between the two sets of comparators using 2D-DIGE (Difference Gel Electrophoresis) and LC-MS\\/MS resulted in the identification of 89 distinct differentially expressed proteins. Overlap comparisons between the two sets of cell line pairs identified 12 proteins (AKRIB8, ANXA1, ANXA4, EIF3I, G6PD, HSPA8, HSP90B1, HSPD1, NUDC, PGAM1, RUVBL1 and CNN3) that were differentially expressed in the same direction. Conclusion These proteins may have an important role in sustaining high productivity of recombinant protein over the duration of a fed-batch bioprocess culture. It is possible that many of these proteins could be useful for future approaches to successfully manipulate or engineer CHO cells in order to sustain productivity of recombinant protein.

  1. Bioprocessing of low-level radioactive and mixed hazard wastes

    International Nuclear Information System (INIS)

    Stoner, D.L.

    1990-01-01

    Biologically-based treatment technologies are currently being developed at the Idaho National Engineering Laboratory (INEL) to aid in volume reduction and/or reclassification of low-level radioactive and mixed hazardous wastes prior to processing for disposal. The approaches taken to treat low-level radioactive and mixed wastes will reflect the physical (e.g., liquid, solid, slurry) and chemical (inorganic and/or organic) nature of the waste material being processed. Bioprocessing utilizes the diverse metabolic and biochemical characteristics of microorganisms. The application of bioadsorption and bioflocculation to reduce the volume of low-level radioactive waste are strategies comparable to the use of ion-exchange resins and coagulants that are currently used in waste reduction processes. Mixed hazardous waste would require organic as well as radionuclide treatment processes. Biodegradation of organic wastes or bioemulsification could be used in conjunction with radioisotope bioadsorption methods to treat mixed hazardous radioactive wastes. The degradation of the organic constituents of mixed wastes can be considered an alternative to incineration, while the use of bioemulsification may simply be used as a means to separate inorganic and organics to enable reclassification of wastes. The proposed technology base for the biological treatment of low-level radioactive and mixed hazardous waste has been established. Biodegradation of a variety of organic compounds that are typically found in mixed hazardous wastes has been demonstrated, degradative pathways determined and the nutritional requirements of the microorganisms are understood. Accumulation, adsorption and concentration of heavy and transition metal species and transuranics by microorganisms is widely recognized. Work at the INEL focuses on the application of demonstrated microbial transformations to process development

  2. A carbon dioxide stripping model for mammalian cell culture in manufacturing scale bioreactors.

    Science.gov (United States)

    Xing, Zizhuo; Lewis, Amanda M; Borys, Michael C; Li, Zheng Jian

    2017-06-01

    Control of carbon dioxide within the optimum range is important in mammalian bioprocesses at the manufacturing scale in order to ensure robust cell growth, high protein yields, and consistent quality attributes. The majority of bioprocess development work is done in laboratory bioreactors, in which carbon dioxide levels are more easily controlled. Some challenges in carbon dioxide control can present themselves when cell culture processes are scaled up, because carbon dioxide accumulation is a common feature due to longer gas-residence time of mammalian cell culture in large scale bioreactors. A carbon dioxide stripping model can be used to better understand and optimize parameters that are critical to cell culture processes at the manufacturing scale. The prevailing carbon dioxide stripping models in literature depend on mass transfer coefficients and were applicable to cell culture processes with low cell density or at stationary/cell death phase. However, it was reported that gas bubbles are saturated with carbon dioxide before leaving the culture, which makes carbon dioxide stripping no longer depend on a mass transfer coefficient in the new generation cell culture processes characterized by longer exponential growth phase, higher peak viable cell densities, and higher specific production rate. Here, we present a new carbon dioxide stripping model for manufacturing scale bioreactors, which is independent of carbon dioxide mass transfer coefficient, but takes into account the gas-residence time and gas CO 2 saturation time. The model was verified by CHO cell culture processes with different peak viable cell densities (7 to 12 × 10 6  cells mL -1 ) for two products in 5,000-L and 25,000-L bioreactors. The model was also applied to a next generation cell culture process to optimize cell culture conditions and reduce carbon dioxide levels at manufacturing scale. The model provides a useful tool to understand and better control cell culture carbon dioxide

  3. A two-stage bioprocess for hydrogen and methane production from rice straw bioethanol residues.

    Science.gov (United States)

    Cheng, Hai-Hsuan; Whang, Liang-Ming; Wu, Chao-Wei; Chung, Man-Chien

    2012-06-01

    This study evaluates a two-stage bioprocess for recovering hydrogen and methane while treating organic residues of fermentative bioethanol from rice straw. The obtained results indicate that controlling a proper volumetric loading rate, substrate-to-biomass ratio, or F/M ratio is important to maximizing biohydrogen production from rice straw bioethanol residues. Clostridium tyrobutyricum, the identified major hydrogen-producing bacteria enriched in the hydrogen bioreactor, is likely utilizing lactate and acetate for biohydrogen production. The occurrence of acetogenesis during biohydrogen fermentation may reduce the B/A ratio and lead to a lower hydrogen production. Organic residues remained in the effluent of hydrogen bioreactor can be effectively converted to methane with a rate of 2.8 mmol CH(4)/gVSS/h at VLR of 4.6 kg COD/m(3)/d. Finally, approximately 75% of COD in rice straw bioethanol residues can be removed and among that 1.3% and 66.1% of COD can be recovered in the forms of hydrogen and methane, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. 1991 Second international symposium on the biological processing of coal: Proceedings

    International Nuclear Information System (INIS)

    1991-09-01

    This symposium was held to aid in the advancement of science and technology in the area of coal bioprocessing by facilitating the exchange of technical information and offering a forum for open discussion and review. The symposium was complemented by four workshops which introduced the attendees to the fundamentals of genetic, mass ampersand energy balances, process ampersand economic analysis, and advanced analytical techniques as they pertain to bioprocessing of coal. Eleven countries were represented, as were numerous universities, national laboratories, federal agencies and corporations. Topics discussed include desulfurization, coal dissolution, gene cloning, and enzyme activity. Individual projects are processed separately on the databases

  5. Integrating Cellular and Bioprocess Engineering in the Non-Conventional Yeast Yarrowia lipolytica for Biodiesel Production: A Review

    Directory of Open Access Journals (Sweden)

    Dongming Xie

    2017-10-01

    Full Text Available As one of the major biofuels to replace fossil fuel, biodiesel has now attracted more and more attention due to its advantages in higher energy density and overall less greenhouse gas generation. Biodiesel (fatty acid alkyl esters is produced by chemically or enzymatically catalyzed transesterification of lipids from microbial cells, microalgae, oil crops, or animal fats. Currently, plant oils or waste cooking oils/fats remain the major source for biodiesel production via enzymatic route, but the production capacity is limited either by the uncertain supplement of plant oils or by the low or inconsistent quality of waste oils/fats. In the past decades, significant progresses have been made on synthesis of microalgae oils directly from CO2via a photosynthesis process, but the production cost from any current technologies is still too high to be commercialized due to microalgae’s slow growth rate on CO2, inefficiency in photo-bioreactors, lack of efficient contamination control methods, and high cost in downstream recovery. At the same time, many oleaginous microorganisms have been studied to produce lipids via the fatty acid synthesis pathway under aerobic fermentation conditions, among them one of the most studied is the non-conventional yeast, Yarrowia lipolytica, which is able to produce fatty acids at very high titer, rate, and yield from various economical substrates. This review summarizes the recent research progresses in both cellular and bioprocess engineering in Y. lipolytica to produce lipids at a low cost that may lead to commercial-scale biodiesel production. Specific technologies include the strain engineering for using various substrates, metabolic engineering in high-yield lipid synthesis, cell morphology study for efficient substrate uptake and product formation, free fatty acid formation and secretion for improved downstream recovery, and fermentation engineering for higher productivities and less operating cost. To further

  6. Relativities of fundamentality

    Science.gov (United States)

    McKenzie, Kerry

    2017-08-01

    S-dualities have been held to have radical implications for our metaphysics of fundamentality. In particular, it has been claimed that they make the fundamentality status of a physical object theory-relative in an important new way. But what physicists have had to say on the issue has not been clear or consistent, and in particular seems to be ambiguous between whether S-dualities demand an anti-realist interpretation of fundamentality talk or merely a revised realism. This paper is an attempt to bring some clarity to the matter. After showing that even antecedently familiar fundamentality claims are true only relative to a raft of metaphysical, physical, and mathematical assumptions, I argue that the relativity of fundamentality inherent in S-duality nevertheless represents something new, and that part of the reason for this is that it has both realist and anti-realist implications for fundamentality talk. I close by discussing the broader significance that S-dualities have for structuralist metaphysics and for fundamentality metaphysics more generally.

  7. Cell phone-induced ostracism threatens fundamental needs.

    Science.gov (United States)

    Hales, Andrew H; Dvir, Maayan; Wesselmann, Eric D; Kruger, Daniel J; Finkenauer, Catrin

    2018-01-01

    Cell phones are useful tools with both practical and social benefits. However, using them in the context of face-to-face conversations may be problematic. We consider this behavior a form of ostracism and test its effects on the satisfaction of basic psychological needs for belonging, self-esteem, control, and meaningful existence. In Study 1 participants who recalled a time in which a friend was checking a cell phone during a serious conversation reported feeling more ostracized (ignored and excluded), greater pain, and threat to basic needs than participants recalling a conversation without a cell phone interruption or a control event. Study 2 replicated and extended this effect: Cell phone-induced ostracism's effects were partially mediated by decreased feelings of relational evaluation, and threatened basic needs both in serious and casual conversation contexts. Findings from both studies also indicated that cell phone-induced ostracism hurts women more so than men.

  8. Community dynamics of attached and free cells and the effects of attached cells on chalcopyrite bioleaching by Acidithiobacillus sp.

    Science.gov (United States)

    Yang, Hailin; Feng, Shoushuai; Xin, Yu; Wang, Wu

    2014-02-01

    The community dynamics of attached and free cells of Acidithiobacillus sp. were investigated and compared during chalcopyrite bioleaching process. In the mixed strains system, Acidithiobacillus ferrooxidans was the dominant species at the early stage while Acidithiobacillus thiooxidans owned competitive advantage from the middle stage to the end of bioprocess. Meanwhile, compared to A. ferrooxidans, more significant effects of attached cells on free biomass with A. thiooxidans were shown in either the pure or mixed strains systems. Moreover, the effects of attached cells on key chemical parameters were also studied in different adsorption-deficient systems. Consistently, the greatest reduction of key chemical ion was shown with A. thiooxidans and the loss of bioleaching efficiency was high to 50.5%. These results all demonstrated the bioleaching function of attached cells was more efficient than the free cells, especially with A. thiooxidans. These notable results would help us to further understand the chalcopyrite bioleaching. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Photovoltaics fundamentals, technology and practice

    CERN Document Server

    Mertens, Konrad

    2013-01-01

    Concise introduction to the basic principles of solar energy, photovoltaic systems, photovoltaic cells, photovoltaic measurement techniques, and grid connected systems, overviewing the potential of photovoltaic electricity for students and engineers new to the topic After a brief introduction to the topic of photovoltaics' history and the most important facts, Chapter 1 presents the subject of radiation, covering properties of solar radiation, radiation offer, and world energy consumption. Chapter 2 looks at the fundamentals of semiconductor physics. It discusses the build-up of semiconducto

  10. New-found fundamentals of bacterial persistence.

    Science.gov (United States)

    Kint, Cyrielle I; Verstraeten, Natalie; Fauvart, Maarten; Michiels, Jan

    2012-12-01

    Persister cells display tolerance to high doses of bactericidal antibiotics and typically comprise a small fraction of a bacterial population. Recently, evidence was provided for a causal link between therapy failure and the presence of persister cells in chronic infections, underscoring the need for research on bacterial persistence. A series of recent breakthroughs have shed light on the multiplicity of persister genes, the contribution of gene expression noise to persister formation, the importance of active responses to antibiotic tolerance and heterogeneity among persister cells. Moreover, the development of in vivo model systems has highlighted the clinical relevance of persistence. This review discusses these recent advances and how this knowledge fundamentally changes the way in which we will perceive the problem of antibiotic tolerance in years to come. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Organic solar cells fundamentals, devices, and upscaling

    CERN Document Server

    Rand, Barry P

    2014-01-01

    Solution-Processed DonorsB. Burkhart, B. C. ThompsonSmall-Molecule and Vapor-Deposited Organic Photovoltaics R. R. Lunt, R. J. HolmesAcceptor Materials for Solution-Processed Solar Cells Y. HeInterfacial Layers R. Po, C. Carbonera, A. BernardiElectrodes in Organic Photovoltaic Cells S. Yoo, J.-Y. Lee, H. Kim, J. LeeTandem and Multi-Junction Organic Solar Cells J. Gilot, R. A. J. JanssenBulk Heterojunction Morphology Control and Characterization T. Wang, D. G. LidzeyOptical Modeling and Light Management

  12. Development of microorganisms for cellulose-biofuel consolidated bioprocessings: metabolic engineers’ tricks

    Directory of Open Access Journals (Sweden)

    Roberto Mazzoli

    2012-10-01

    Full Text Available Cellulose waste biomass is the most abundant and attractive substrate for "biorefinery strategies" that are aimed to produce high-value products (e.g. solvents, fuels, building blocks by economically and environmentally sustainable fermentation processes. However, cellulose is highly recalcitrant to biodegradation and its conversion by biotechnological strategies currently requires economically inefficient multistep industrial processes. The need for dedicated cellulase production continues to be a major constraint to cost-effective processing of cellulosic biomass.Research efforts have been aimed at developing recombinant microorganisms with suitable characteristics for single step biomass fermentation (consolidated bioprocessing, CBP. Two paradigms have been applied for such, so far unsuccessful, attempts: a “native cellulolytic strategies”, aimed at conferring high-value product properties to natural cellulolytic microorganisms; b “recombinant cellulolytic strategies”, aimed to confer cellulolytic ability to microorganisms exhibiting high product yields and titers.By starting from the description of natural enzyme systems for plant biomass degradation and natural metabolic pathways for some of the most valuable product (i.e. butanol, ethanol, and hydrogen biosynthesis, this review describes state-of-the-art bottlenecks and solutions for the development of recombinant microbial strains for cellulosic biofuel CBP by metabolic engineering. Complexed cellulases (i.e. cellulosomes benefit from stronger proximity effects and show enhanced synergy on insoluble substrates (i.e. crystalline cellulose with respect to free enzymes. For this reason, special attention was held on strategies involving cellulosome/designer cellulosome-bearing recombinant microorganisms.

  13. Deconstructing stem cell population heterogeneity: Single-cell analysis and modeling approaches

    Science.gov (United States)

    Wu, Jincheng; Tzanakakis, Emmanuel S.

    2014-01-01

    Isogenic stem cell populations display cell-to-cell variations in a multitude of attributes including gene or protein expression, epigenetic state, morphology, proliferation and proclivity for differentiation. The origins of the observed heterogeneity and its roles in the maintenance of pluripotency and the lineage specification of stem cells remain unclear. Addressing pertinent questions will require the employment of single-cell analysis methods as traditional cell biochemical and biomolecular assays yield mostly population-average data. In addition to time-lapse microscopy and flow cytometry, recent advances in single-cell genomic, transcriptomic and proteomic profiling are reviewed. The application of multiple displacement amplification, next generation sequencing, mass cytometry and spectrometry to stem cell systems is expected to provide a wealth of information affording unprecedented levels of multiparametric characterization of cell ensembles under defined conditions promoting pluripotency or commitment. Establishing connections between single-cell analysis information and the observed phenotypes will also require suitable mathematical models. Stem cell self-renewal and differentiation are orchestrated by the coordinated regulation of subcellular, intercellular and niche-wide processes spanning multiple time scales. Here, we discuss different modeling approaches and challenges arising from their application to stem cell populations. Integrating single-cell analysis with computational methods will fill gaps in our knowledge about the functions of heterogeneity in stem cell physiology. This combination will also aid the rational design of efficient differentiation and reprogramming strategies as well as bioprocesses for the production of clinically valuable stem cell derivatives. PMID:24035899

  14. Micro-Electromechanical Affinity Sensor for the Monitoring of Glucose in Bioprocess Media

    Directory of Open Access Journals (Sweden)

    Lorenz Theuer

    2017-06-01

    Full Text Available An affinity-viscometry-based micro-sensor probe for continuous glucose monitoring was investigated with respect to its suitability for bioprocesses. The sensor operates with glucose and dextran competing as binding partner for concanavalin A, while the viscosity of the assay scales with glucose concentration. Changes in viscosity are determined with a micro-electromechanical system (MEMS in the measurement cavity of the sensor probe. The study aimed to elucidate the interactions between the assay and a typical phosphate buffered bacterial cultivation medium. It turned out that contact with the medium resulted in a significant long-lasting drift of the assay’s viscosity at zero glucose concentration. Adding glucose to the medium lowers the drift by a factor of eight. The cglc values measured off-line with the glucose sensor for monitoring of a bacterial cultivation were similar to the measurements with an enzymatic assay with a difference of less than ±0.15 g·L−1. We propose that lectin agglomeration, the electro-viscous effect, and constitutional changes of concanavalin A due to exchanges of the incorporated metal ions may account for the observed viscosity increase. The study has demonstrated the potential of the MEMS sensor to determine sensitive viscosity changes within very small sample volumes, which could be of interest for various biotechnological applications.

  15. Comparison of solid-state and submerged-state fermentation for the bioprocessing of switchgrass to ethanol and acetate by Clostridium phytofermentans.

    Science.gov (United States)

    Jain, Abhiney; Morlok, Charles K; Henson, J Michael

    2013-01-01

    The conversion of sustainable energy crops using microbiological fermentation to biofuels and bioproducts typically uses submerged-state processes. Alternatively, solid-state fermentation processes have several advantages when compared to the typical submerged-state processes. This study compares the use of solid-state versus submerged-state fermentation using the mesophilic anaerobic bacterium Clostridium phytofermentans in the conversion of switchgrass to the end products of ethanol, acetate, and hydrogen. A shift in the ratio of metabolic products towards more acetate and hydrogen production than ethanol production was observed when C. phytofermentans was grown under solid-state conditions as compared to submerged-state conditions. Results indicated that the end product concentrations (in millimolar) obtained using solid-state fermentation were higher than using submerged-state fermentation. In contrast, the total fermentation products (in weight of product per weight of carbohydrates consumed) and switchgrass conversion were higher for submerged-state fermentation. The conversion of xylan was greater than glucan conversion under both fermentation conditions. An initial pH of 7 and moisture content of 80 % resulted in maximum end products formation. Scanning electron microscopy study showed the presence of biofilm formed by C. phytofermentans growing on switchgrass under submerged-state fermentation whereas bacterial cells attached to surface and no apparent biofilm was observed when grown under solid-state fermentation. To our knowledge, this is the first study reporting consolidated bioprocessing of a lignocellulosic substrate by a mesophilic anaerobic bacterium under solid-state fermentation conditions.

  16. Fundamentalism and science

    Directory of Open Access Journals (Sweden)

    Massimo Pigliucci

    2006-06-01

    Full Text Available The many facets of fundamentalism. There has been much talk about fundamentalism of late. While most people's thought on the topic go to the 9/11 attacks against the United States, or to the ongoing war in Iraq, fundamentalism is affecting science and its relationship to society in a way that may have dire long-term consequences. Of course, religious fundamentalism has always had a history of antagonism with science, and – before the birth of modern science – with philosophy, the age-old vehicle of the human attempt to exercise critical thinking and rationality to solve problems and pursue knowledge. “Fundamentalism” is defined by the Oxford Dictionary of the Social Sciences1 as “A movement that asserts the primacy of religious values in social and political life and calls for a return to a 'fundamental' or pure form of religion.” In its broadest sense, however, fundamentalism is a form of ideological intransigence which is not limited to religion, but includes political positions as well (for example, in the case of some extreme forms of “environmentalism”.

  17. Fundamental safety principles. Safety fundamentals

    International Nuclear Information System (INIS)

    2007-01-01

    This publication states the fundamental safety objective and ten associated safety principles, and briefly describes their intent and purpose. The fundamental safety objective - to protect people and the environment from harmful effects of ionizing radiation - applies to all circumstances that give rise to radiation risks. The safety principles are applicable, as relevant, throughout the entire lifetime of all facilities and activities - existing and new - utilized for peaceful purposes, and to protective actions to reduce existing radiation risks. They provide the basis for requirements and measures for the protection of people and the environment against radiation risks and for the safety of facilities and activities that give rise to radiation risks, including, in particular, nuclear installations and uses of radiation and radioactive sources, the transport of radioactive material and the management of radioactive waste

  18. Fundamental safety principles. Safety fundamentals

    International Nuclear Information System (INIS)

    2006-01-01

    This publication states the fundamental safety objective and ten associated safety principles, and briefly describes their intent and purpose. The fundamental safety objective - to protect people and the environment from harmful effects of ionizing radiation - applies to all circumstances that give rise to radiation risks. The safety principles are applicable, as relevant, throughout the entire lifetime of all facilities and activities - existing and new - utilized for peaceful purposes, and to protective actions to reduce existing radiation risks. They provide the basis for requirements and measures for the protection of people and the environment against radiation risks and for the safety of facilities and activities that give rise to radiation risks, including, in particular, nuclear installations and uses of radiation and radioactive sources, the transport of radioactive material and the management of radioactive waste

  19. A Bioprocessed Polysaccharide from Lentinus edodes Mycelia Cultures with Turmeric Protects Chicks from a Lethal Challenge of Salmonella Gallinarum.

    Science.gov (United States)

    Han, Dalmuri; Lee, Hyung Tae; Lee, June Bong; Kim, Yongbaek; Lee, Sang Jong; Yoon, Jang Won

    2017-02-01

    Our previous studies demonstrated that a bioprocessed polysaccharide (BPP) isolated from Lentinus edodes mushroom mycelia cultures supplemented with black rice bran can protect mice against Salmonella lipopolysaccharide-induced endotoxemia and reduce the mortality from Salmonella Typhimurium infection through upregulated T-helper 1 immunity. Here, we report that a BPP from L. edodes mushroom mycelia liquid cultures supplemented with turmeric (referred to as BPP-turmeric) alters chicken macrophage responses against avian-adapted Salmonella Gallinarum and protects chicks against a lethal challenge from Salmonella Gallinarum. In vitro analyses revealed that the water extract of BPP-turmeric (i) changed the protein expression or secretion profile of Salmonella Gallinarum, although it was not bactericidal, (ii) reduced the phagocytic activity of the chicken-derived macrophage cell line HD-11 when infected with Salmonella Gallinarum, and (iii) significantly activated the transcription expression of interleukin (IL)-1β, IL-10, tumor necrosis factor α, and inducible nitric oxide synthase in response to various Salmonella infections, whereas it repressed that of IL-4, IL-6, interferon-β, and interferon-γ. We also found that BPP-turmeric (0.1 g/kg of feed) as a feed additive provided significant protection to 1-day-old chicks infected with a lethal dose of Salmonella Gallinarum. Collectively, these results imply that BPP-turmeric contains biologically active component(s) that protect chicks against Salmonella Gallinarum infection, possibly by regulating macrophage immune responses. Further studies are needed to evaluate the potential efficacy of BPP-turmeric as a livestock feed additive for the preharvest control of fowl typhoid or foodborne salmonellosis.

  20. Dynamics of immature mAb glycoform secretion during CHO cell culture

    DEFF Research Database (Denmark)

    Jimenez del Val, Ioscani; Fan, Yuzhou; Weilguny, Dietmar

    2016-01-01

    Ensuring consistent glycosylation-associated quality of therapeutic monoclonal antibodies (mAbs) has become a priority in pharmaceutical bioprocessing given that the distribution and composition of the carbohydrates (glycans) bound to these molecules determines their therapeutic efficacy and immu......Ensuring consistent glycosylation-associated quality of therapeutic monoclonal antibodies (mAbs) has become a priority in pharmaceutical bioprocessing given that the distribution and composition of the carbohydrates (glycans) bound to these molecules determines their therapeutic efficacy...

  1. Escola de ensino fundamental(s em movimento – movimento na escola de ensino fundamental

    Directory of Open Access Journals (Sweden)

    Reiner Hildebrandt-Stramann

    2007-12-01

    Full Text Available A escola de ensino fundamental na Alemanha sofreu movimento nos últimos 15 anos, porque, entre outros motivos, entrou movimento nessas escolas. Esse jogo de palavras chama atenção a duas linhas de trabalho que determinam a discussão na atual pedagogia escolar. O presente trabalho revela essas duas perspectivas. Uma das linhas está relacionada ao atual processo de mudança na pedagogia escolar. Essa prediz que a escola de ensino fundamental deve ser um lugar de aprendizagem e de vivência para as crianças. A outra linha tem a ver com o jogo de palavras ancorado a esses processos da pedagogia do movimento, a qual ganha cada vez maiores dimensões. A escola de ensino fundamental deve ser vista sob a perspectiva do movimento e transformada em um lugar de movimento.

  2. Fundamental volatility and stock returns : does fundamental volatility explain stock returns?

    OpenAIRE

    Selboe, Guner K.; Virdee, Jaspal Singh

    2017-01-01

    In this thesis, we investigate whether the fundamental uncertainty can explain the crosssection of stock returns. To measure the fundamental uncertainty, we estimate rolling standard deviations and accounting betas of four different fundamentals: revenues, gross profit, earnings and cash flows. The standard deviation and the beta of revenues significantly explain returns in the Fama-Macbeth procedure, but only appears significant among smaller stocks in the portfolio formation ...

  3. The emergence of Clostridium thermocellum as a high utility candidate for consolidated bioprocessing applications

    Directory of Open Access Journals (Sweden)

    Arthur eRagauskas

    2014-08-01

    Full Text Available First isolated in 1926, Clostridium thermocellum has recently received increased attention as a high utility candidate for use in consolidated bioprocessing applications. These applications, which seek to process lignocellulosic biomass directly into useful products such as ethanol, are gaining traction as economically feasible routes towards the production of fuel and other high value chemical compounds as the shortcomings of fossil fuels become evident. This review evaluates C. thermocellum’s role in this transitory process by highlighting recent discoveries relating to its genomic, transcriptomic, proteomic, and metabolomic responses to varying biomass sources, with a special emphasis placed on providing an overview of its unique, multivariate enzyme cellulosome complex and the role that this structure performs during biomass degradation. Both naturally evolved and genetically engineered strains are examined in light of their unique attributes and responses to various biomass treatment conditions, and the genetic tools that have been employed for their creation are presented. Several future routes for potential industrial usage are presented, and it is concluded that, although there have been many advances to significantly improve C. thermocellum’s amenability to industrial use, several hurdles still remain to be overcome as this unique organism enjoys increased attention within the scientific community.

  4. Fundamental aspects affecting the return on investment from solar power plants

    International Nuclear Information System (INIS)

    Cintula, B.; Viglas, D.

    2012-01-01

    The article deals with fundamental parameters of solar cells-conversion efficiency of solar radiation into electricity and price of solar cells. These two aspects affect each other, so it is important to deal with both at once. In introduction are described the theoretical solutions about efficiency analysis. Furthermore the article is focused on a description of materials used in the photovoltaic cells. In addition, the article shows the price trend of photovoltaic cells for the last year. Finally, these two aspects are evaluated for return on investment in photovoltaic power plants. (Authors)

  5. Capacity planning for batch and perfusion bioprocesses across multiple biopharmaceutical facilities.

    Science.gov (United States)

    Siganporia, Cyrus C; Ghosh, Soumitra; Daszkowski, Thomas; Papageorgiou, Lazaros G; Farid, Suzanne S

    2014-01-01

    Production planning for biopharmaceutical portfolios becomes more complex when products switch between fed-batch and continuous perfusion culture processes. This article describes the development of a discrete-time mixed integer linear programming (MILP) model to optimize capacity plans for multiple biopharmaceutical products, with either batch or perfusion bioprocesses, across multiple facilities to meet quarterly demands. The model comprised specific features to account for products with fed-batch or perfusion culture processes such as sequence-dependent changeover times, continuous culture constraints, and decoupled upstream and downstream operations that permit independent scheduling of each. Strategic inventory levels were accounted for by applying cost penalties when they were not met. A rolling time horizon methodology was utilized in conjunction with the MILP model and was shown to obtain solutions with greater optimality in less computational time than the full-scale model. The model was applied to an industrial case study to illustrate how the framework aids decisions regarding outsourcing capacity to third party manufacturers or building new facilities. The impact of variations on key parameters such as demand or titres on the optimal production plans and costs was captured. The analysis identified the critical ratio of in-house to contract manufacturing organization (CMO) manufacturing costs that led the optimization results to favor building a future facility over using a CMO. The tool predicted that if titres were higher than expected then the optimal solution would allocate more production to in-house facilities, where manufacturing costs were lower. Utilization graphs indicated when capacity expansion should be considered. © 2014 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers.

  6. Fundamentals of electronics

    CERN Document Server

    Schubert, Thomas F

    2015-01-01

    This book, Electronic Devices and Circuit Application, is the first of four books of a larger work, Fundamentals of Electronics. It is comprised of four chapters describing the basic operation of each of the four fundamental building blocks of modern electronics: operational amplifiers, semiconductor diodes, bipolar junction transistors, and field effect transistors. Attention is focused on the reader obtaining a clear understanding of each of the devices when it is operated in equilibrium. Ideas fundamental to the study of electronic circuits are also developed in the book at a basic level to

  7. Fundamentals of gas dynamics

    CERN Document Server

    Babu, V

    2014-01-01

    Fundamentals of Gas Dynamics, Second Edition isa comprehensively updated new edition and now includes a chapter on the gas dynamics of steam. It covers the fundamental concepts and governing equations of different flows, and includes end of chapter exercises based on the practical applications. A number of useful tables on the thermodynamic properties of steam are also included.Fundamentals of Gas Dynamics, Second Edition begins with an introduction to compressible and incompressible flows before covering the fundamentals of one dimensional flows and normal shock wav

  8. Radiotherapy and antitumoral immunity. Fundamentals of immunooncology

    International Nuclear Information System (INIS)

    Klimovich, V.B.

    1982-01-01

    The fundamental states of immunooncology are described briefly: conception of immunologic inspection, antiblastomic immunologic factors, antigeny of tumor cells and mechanisms of slipping out of immune inspection, problastomic immunologic factors. The conclusion is made that tumor formation and extenstion go on under the action of opposite directed but not mutually exclusive factors of immunologic nature. Growth rate and regression of neoplasm are determined by balance between antiblastomic mechanism activity and activity of problastomic factors and factors of immunoresistant neoplasms

  9. Ectopic expression of human mTOR increases viability, robustness, cell size, proliferation, and antibody production of chinese hamster ovary cells.

    Science.gov (United States)

    Dreesen, Imke A J; Fussenegger, Martin

    2011-04-01

    Engineering of mammalian production cell lines to improve titer and quality of biopharmaceuticals is a top priority of the biopharmaceutical manufacturing industry providing protein therapeutics to patients worldwide. While many engineering strategies have been successful in the past decade they were often based on the over-expression of a single transgene and therefore limited to addressing a single bottleneck in the cell's production capacity. We provide evidence that ectopic expression of the global metabolic sensor and processing protein mammalian target of rapamycin (mTOR), simultaneously improves key bioprocess-relevant characteristics of Chinese hamster ovary (CHO) cell-derived production cell lines such as cell growth (increased cell size and protein content), proliferation (increased cell-cycle progression), viability (decreased apoptosis), robustness (decreased sensitivity to sub-optimal growth factor and oxygen supplies) and specific productivity of secreted human glycoproteins. Cultivation of mTOR-transgenic CHO-derived cell lines engineered for secretion of a therapeutic IgG resulted in antibody titers of up to 50 pg/cell/day, which represents a four-fold increase compared to the parental production cell line. mTOR-based engineering of mammalian production cell lines may therefore have a promising future in biopharmaceutical manufacturing of human therapeutic proteins. Copyright © 2010 Wiley Periodicals, Inc.

  10. Improved ethanol production at high temperature by consolidated bioprocessing using Saccharomyces cerevisiae strain engineered with artificial zinc finger protein.

    Science.gov (United States)

    Khatun, M Mahfuza; Yu, Xinshui; Kondo, Akihiko; Bai, Fengwu; Zhao, Xinqing

    2017-12-01

    In this work, the consolidated bioprocessing (CBP) yeast Saccharomyces cerevisiae MNII/cocδBEC3 was transformed by an artificial zinc finger protein (AZFP) library to improve its thermal tolerance, and the strain MNII-AZFP with superior growth at 42°C was selected. Improved degradation of acid swollen cellulose by 45.9% led to an increase in ethanol production, when compared to the control strain. Moreover, the fermentation of Jerusalem artichoke stalk (JAS) by MNII-AZFP was shortened by 12h at 42°C with a concomitant improvement in ethanol production. Comparative transcriptomics analysis suggested that the AZFP in the mutant exerted beneficial effect by modulating the expression of multiple functional genes. These results provide a feasible strategy for efficient ethanol production from JAS and other cellulosic biomass through CBP based-fermentation at elevated temperatures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Exchange Rates and Fundamentals.

    Science.gov (United States)

    Engel, Charles; West, Kenneth D.

    2005-01-01

    We show analytically that in a rational expectations present-value model, an asset price manifests near-random walk behavior if fundamentals are I (1) and the factor for discounting future fundamentals is near one. We argue that this result helps explain the well-known puzzle that fundamental variables such as relative money supplies, outputs,…

  12. Bio-Refineries Bioprocess Technologies for Waste-Water Treatment, Energy and Product Valorization

    Science.gov (United States)

    Keith Cowan, A.

    2010-04-01

    Increasing pressure is being exerted on communities and nations to source energy from forms other than fossil fuels. Also, potable water is becoming a scarce resource in many parts of the world, and there remains a large divide in the demand and utilization of plant products derived from genetically modified organisms (GMOs) and non-GMOs. The most extensive user and manager of terrestrial ecosystems is agriculture which is also the de facto steward of natural resources. As stated by Miller (2008) no other industry or institution comes close to the comparative advantage held for this vital responsibility while simultaneously providing food, fiber, and other biology-based products, including energy. Since modern commercial agriculture is transitioning from the production of bulk commodities to the provision of standardized products and specific-attribute raw materials for differentiated markets, we can argue that processes such as mass cultivation of microalgae and the concept of bio-refineries be seen as part of a `new' agronomy. EBRU is currently exploring the integration of bioprocess technologies using microalgae as biocatalysts to achieve waste-water treatment, water polishing and endocrine disruptor (EDC) removal, sustainable energy production, and exploitation of the resultant biomass in agriculture as foliar fertilizer and seed coatings, and for commercial extraction of bulk commodities such as bio-oils and lecithin. This presentation will address efforts to establish a fully operational solar-driven microalgae bio-refinery for use not only in waste remediation but to transform waste and biomass to energy, fuels, and other useful materials (valorisation), with particular focus on environmental quality and sustainability goals.

  13. In situ microscopy for online monitoring of cell concentration in Pichia pastoris cultivations.

    Science.gov (United States)

    Marquard, D; Enders, A; Roth, G; Rinas, U; Scheper, T; Lindner, P

    2016-09-20

    In situ Microscopy (ISM) is an optical non-invasive technique to monitor cells in bioprocesses in real-time. Pichia pastoris is one of the most promising protein expression systems. This yeast combines fast growth on simple media and important eukaryotic features such as glycosylation. In this work, the ISM technology was applied to Pichia pastoris cultivations for online monitoring of the cell concentration during cultivation. Different ISM settings were tested. The acquired images were analyzed with two image processing algorithms. In seven cultivations the cell concentration was monitored by the applied algorithms and offline samples were taken to determine optical density (OD) and dry cell mass (DCM). Cell concentrations up to 74g/L dry cell mass could be analyzed via the ISM. Depending on the algorithm and the ISM settings, an accuracy between 0.3 % and 12 % was achieved. The overall results show that for a robust measurement a combination of the two described algorithms is required. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Stem cell biobanks.

    Science.gov (United States)

    Bardelli, Silvana

    2010-04-01

    Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment.

  15. Radiology fundamentals

    CERN Document Server

    Singh, Harjit

    2011-01-01

    ""Radiology Fundamentals"" is a concise introduction to the dynamic field of radiology for medical students, non-radiology house staff, physician assistants, nurse practitioners, radiology assistants, and other allied health professionals. The goal of the book is to provide readers with general examples and brief discussions of basic radiographic principles and to serve as a curriculum guide, supplementing a radiology education and providing a solid foundation for further learning. Introductory chapters provide readers with the fundamental scientific concepts underlying the medical use of imag

  16. Bioprocessing papaya processing waste for potential aquaculture feed supplement--economic and nutrient analysis with shrimp feeding trial.

    Science.gov (United States)

    Kang, H Y; Yang, P Y; Dominy, W G; Lee, C S

    2010-10-01

    Papaya processing waste (PPW), a major fruit processing waste in the Hawaii islands, served as substrate for yeast (Saccharomyces cerevisiae) growth. The fermented PPW products containing nutrients of 45% crude protein and various fat, fiber, lignin, cellulose, and minerals were advantages to nutrients of yeast alone. Three experimental diets controlled at 35% protein formulation containing different levels of inclusion of PPW products and a commercial control diet were fed to shrimps for 8 weeks. The 50% inclusion of PPW diets were comparable to commercial feed in weight, growth, feed conversion ratio (FCR) and survival rate. Such bioprocess treatment system would be economically feasible with the control of annual cost and increase of the amount of PPW treated. The selling price of PPW products and annual operation and maintenance cost were the most influential factors to additional profits. This study presented a promising alternative for environmental-friendly treatment of organic wastes as well as the sustainability of local agriculture and aquaculture industries. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Arguing against fundamentality

    Science.gov (United States)

    McKenzie, Kerry

    This paper aims to open up discussion on the relationship between fundamentality and naturalism, and in particular on the question of whether fundamentality may be denied on naturalistic grounds. A historico-inductive argument for an anti-fundamentalist conclusion, prominent within the contemporary metaphysical literature, is examined; finding it wanting, an alternative 'internal' strategy is proposed. By means of an example from the history of modern physics - namely S-matrix theory - it is demonstrated that (1) this strategy can generate similar (though not identical) anti-fundamentalist conclusions on more defensible naturalistic grounds, and (2) that fundamentality questions can be empirical questions. Some implications and limitations of the proposed approach are discussed.

  18. The Supercontinuum Laser Source Fundamentals with Updated References

    CERN Document Server

    Alfano, Robert R

    2006-01-01

    Photonics and nonlinear optics are important areas of science, engineering and technology. One of the most important ultrafast nonlinear optical processes is the supercontinuum (SC) – the production of intense white light pulses covering: uv, visible, NIR, MIR, and IR. It is produced using ultrashort laser pulses (ps/fs) to produce the ultrabroad band of frequencies. This book covers the fundamental principles and surveys research of current thinkers and experts in the field with updated references of the key breakthroughs over the past decade and a half. The application of SC are time-resolved pump-SC probe absorption and excitation spectroscopy for chemistry, biology and physics fundamental processes; optical coherence tomography; ultrashort pulse generation in femtosecond and attosecond regions; frequency clocks; phase stabilization; optical communication; atmospheric science; lightning control; optical medical imaging; biological cell imaging; and metrology standards.

  19. Polyelectrolyte Complex Beads by Novel Two-Step Process for Improved Performance of Viable Whole-Cell Baeyer-Villiger Monoxygenase by Immobilization

    Czech Academy of Sciences Publication Activity Database

    Krajčovič, T.; Bučko, M.; Vikartovská, A.; Lacík, I.; Uhelská, L.; Chorvát, D.; Neděla, Vilém; Tihlaříková, Eva; Gericke, M.; Heinze, T.; Gemeiner, P.

    2017-01-01

    Roč. 7, č. 11 (2017), s. 353-364 ISSN 2073-4344 Institutional support: RVO:68081731 Keywords : polyelectrolyte complex beads * environmental scanning electron microscopy * confocal laser scanning microscopy * Baeyer-Villiger biooxidation * cyclohexanone monoxygenase * immobilization * viable whole-cell biocatalyst Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering OBOR OECD: Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation Impact factor: 3.082, year: 2016 http://www.mdpi.com/2073-4344/7/11/353

  20. Recent advances in yeast cell-surface display technologies for waste biorefineries.

    Science.gov (United States)

    Liu, Zhuo; Ho, Shih-Hsin; Hasunuma, Tomohisa; Chang, Jo-Shu; Ren, Nan-Qi; Kondo, Akihiko

    2016-09-01

    Waste biorefinery aims to maximize the output of value-added products from various artificial/agricultural wastes by using integrated bioprocesses. To make waste biorefinery economically feasible, it is thus necessary to develop a low-cost, environment-friendly technique to perform simultaneous biodegradation and bioconversion of waste materials. Cell-surface display engineering is a novel, cost-effective technique that can auto-immobilize proteins on the cell exterior of microorganisms, and has been applied for use with waste biofinery. Through tethering different enzymes (e.g., cellulase, lipase, and protease) or metal-binding peptides on cell surfaces, various yeast strains can effectively produce biofuels and biochemicals from sugar/protein-rich waste materials, catalyze waste oils into biodiesels, or retrieve heavy metals from wastewater. This review critically summarizes recent applications of yeast cell-surface display on various types of waste biorefineries, highlighting its potential and future challenges with regard to commercializing this technology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Quantitative proteomics of Spodoptera frugiperda cells during growth and baculovirus infection.

    Directory of Open Access Journals (Sweden)

    Nuno Carinhas

    Full Text Available Baculovirus infection of Spodoptera frugiperda cells is a system of choice to produce a range of recombinant proteins, vaccines and, potentially, gene therapy vectors. While baculovirus genomes are well characterized, the genome of S. frugiperda is not sequenced and the virus-host molecular interplay is sparsely known. Herein, we describe the application of stable isotope labeling by amino acids in cell culture (SILAC to obtain the first comparative proteome quantitation of S. frugiperda cells during growth and early baculovirus infection. The proteome coverage was maximized by compiling a search database with protein annotations from insect species. Of interest were differentially proteins related to energy metabolism, endoplasmic reticulum and oxidative stress, yet not investigated in the scope of baculovirus infection. Further, the reduced expression of key viral-encoded proteins early in the infection cycle is suggested to be related with decreased viral replication at high cell density culture. These findings have implications for virological research and improvement of baculovirus-based bioprocesses.

  2. Process relevant screening of cellulolytic organisms for consolidated bioprocessing.

    Science.gov (United States)

    Antonov, Elena; Schlembach, Ivan; Regestein, Lars; Rosenbaum, Miriam A; Büchs, Jochen

    2017-01-01

    Although the biocatalytic conversion of cellulosic biomass could replace fossil oil for the production of various compounds, it is often not economically viable due to the high costs of cellulolytic enzymes. One possibility to reduce costs is consolidated bioprocessing (CBP), integrating cellulase production, hydrolysis of cellulose, and the fermentation of the released sugars to the desired product into one process step. To establish such a process, the most suitable cellulase-producing organism has to be identified. Thereby, it is crucial to evaluate the candidates under target process conditions. In this work, the chosen model process was the conversion of cellulose to the platform chemical itaconic acid by a mixed culture of a cellulolytic fungus with Aspergillus terreus as itaconic acid producer. Various cellulase producers were analyzed by the introduced freeze assay that measures the initial carbon release rate, quantifying initial cellulase activity under target process conditions. Promising candidates were then characterized online by monitoring their respiration activity metabolizing cellulose to assess the growth and enzyme production dynamics. The screening of five different cellulase producers with the freeze assay identified Trichoderma   reesei and Penicillium   verruculosum as most promising. The measurement of the respiration activity revealed a retarded induction of cellulase production for P.   verruculosum but a similar cellulase production rate afterwards, compared to T.   reesei . The freeze assay measurement depicted that P.   verruculosum reaches the highest initial carbon release rate among all investigated cellulase producers. After a modification of the cultivation procedure, these results were confirmed by the respiration activity measurement. To compare both methods, a correlation between the measured respiration activity and the initial carbon release rate of the freeze assay was introduced. The analysis revealed that the

  3. Capacity Planning for Batch and Perfusion Bioprocesses Across Multiple Biopharmaceutical Facilities

    Science.gov (United States)

    Siganporia, Cyrus C; Ghosh, Soumitra; Daszkowski, Thomas; Papageorgiou, Lazaros G; Farid, Suzanne S

    2014-01-01

    Production planning for biopharmaceutical portfolios becomes more complex when products switch between fed-batch and continuous perfusion culture processes. This article describes the development of a discrete-time mixed integer linear programming (MILP) model to optimize capacity plans for multiple biopharmaceutical products, with either batch or perfusion bioprocesses, across multiple facilities to meet quarterly demands. The model comprised specific features to account for products with fed-batch or perfusion culture processes such as sequence-dependent changeover times, continuous culture constraints, and decoupled upstream and downstream operations that permit independent scheduling of each. Strategic inventory levels were accounted for by applying cost penalties when they were not met. A rolling time horizon methodology was utilized in conjunction with the MILP model and was shown to obtain solutions with greater optimality in less computational time than the full-scale model. The model was applied to an industrial case study to illustrate how the framework aids decisions regarding outsourcing capacity to third party manufacturers or building new facilities. The impact of variations on key parameters such as demand or titres on the optimal production plans and costs was captured. The analysis identified the critical ratio of in-house to contract manufacturing organization (CMO) manufacturing costs that led the optimization results to favor building a future facility over using a CMO. The tool predicted that if titres were higher than expected then the optimal solution would allocate more production to in-house facilities, where manufacturing costs were lower. Utilization graphs indicated when capacity expansion should be considered. © 2013 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 30:594–606, 2014 PMID:24376262

  4. Extracellular Electron Uptake: Among Autotrophs and Mediated by Surfaces

    DEFF Research Database (Denmark)

    Tremblay, Pier-Luc; Angenent, Largus T.; Zhang, Tian

    2017-01-01

    Autotrophic microbes can acquire electrons from solid donors such as steel, other microbial cells, or electrodes. Based on this feature, bioprocesses are being developed for the microbial electrosynthesis (MES) of useful products from the greenhouse gas CO2. Extracellular electron-transfer mechan......Autotrophic microbes can acquire electrons from solid donors such as steel, other microbial cells, or electrodes. Based on this feature, bioprocesses are being developed for the microbial electrosynthesis (MES) of useful products from the greenhouse gas CO2. Extracellular electron......; or (iii) mediator-generating enzymes detached from cells. This review explores the interactions of autotrophs with solid electron donors and their importance in nature and for biosustainable technologies....

  5. Fundamentals of 5G mobile networks

    CERN Document Server

    Rodriguez, Jonathan

    2015-01-01

    Fundamentals of 5G Mobile Networks provides an overview of the key features of the 5th Generation (5G) mobile networks,  discussing the motivation for 5G and the main challenges in developing this new technology. This book provides an insight into the key areas of research that will define this new system technology paving the path towards future research and development.  The book is multi-disciplinary in nature, and aims to cover a whole host of intertwined subjects that will predominantly influence the 5G landscape, including the future Internet, cloud computing, small cells and self-organ

  6. Quantitative intracellular flux modeling and applications in biotherapeutic development and production using CHO cell cultures.

    Science.gov (United States)

    Huang, Zhuangrong; Lee, Dong-Yup; Yoon, Seongkyu

    2017-12-01

    Chinese hamster ovary (CHO) cells have been widely used for producing many recombinant therapeutic proteins. Constraint-based modeling, such as flux balance analysis (FBA) and metabolic flux analysis (MFA), has been developing rapidly for the quantification of intracellular metabolic flux distribution at a systematic level. Such methods would produce detailed maps of flows through metabolic networks, which contribute significantly to better understanding of metabolism in cells. Although these approaches have been extensively established in microbial systems, their application to mammalian cells is sparse. This review brings together the recent development of constraint-based models and their applications in CHO cells. The further development of constraint-based modeling approaches driven by multi-omics datasets is discussed, and a framework of potential modeling application in cell culture engineering is proposed. Improved cell culture system understanding will enable robust developments in cell line and bioprocess engineering thus accelerating consistent process quality control in biopharmaceutical manufacturing. © 2017 Wiley Periodicals, Inc.

  7. Microbial ecology of fermentative hydrogen producing bioprocesses: useful insights for driving the ecosystem function.

    Science.gov (United States)

    Cabrol, Lea; Marone, Antonella; Tapia-Venegas, Estela; Steyer, Jean-Philippe; Ruiz-Filippi, Gonzalo; Trably, Eric

    2017-03-01

    One of the most important biotechnological challenges is to develop environment friendly technologies to produce new sources of energy. Microbial production of biohydrogen through dark fermentation, by conversion of residual biomass, is an attractive solution for short-term development of bioH2 producing processes. Efficient biohydrogen production relies on complex mixed communities working in tight interaction. Species composition and functional traits are of crucial importance to maintain the ecosystem service. The analysis of microbial community revealed a wide phylogenetic diversity that contributes in different-and still mostly unclear-ways to hydrogen production. Bridging this gap of knowledge between microbial ecology features and ecosystem functionality is essential to optimize the bioprocess and develop strategies toward a maximization of the efficiency and stability of substrate conversion. The aim of this review is to provide a comprehensive overview of the most up-to-date biodata available and discuss the main microbial community features of biohydrogen engineered ecosystems, with a special emphasis on the crucial role of interactions and the relationships between species composition and ecosystem service. The elucidation of intricate relationships between community structure and ecosystem function would make possible to drive ecosystems toward an improved functionality on the basis of microbial ecology principles. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Enhanced Bioethanol Production from Potato Peel Waste Via Consolidated Bioprocessing with Statistically Optimized Medium.

    Science.gov (United States)

    Hossain, Tahmina; Miah, Abdul Bathen; Mahmud, Siraje Arif; Mahin, Abdullah-Al-

    2018-04-12

    In this study, an extensive screening was undertaken to isolate some amylolytic microorganisms capable of producing bioethanol from starchy biomass through Consolidated Bioprocessing (CBP). A total of 28 amylolytic microorganisms were isolated, from which 5 isolates were selected based on high α-amylase and glucoamylase activities and identified as Candida wangnamkhiaoensis, Hyphopichia pseudoburtonii (2 isolates), Wickerhamia sp., and Streptomyces drozdowiczii based on 26S rDNA and 16S rDNA sequencing. Wickerhamia sp. showed the highest ethanol production (30.4 g/L) with fermentation yield of 0.3 g ethanol/g starch. Then, a low cost starchy waste, potato peel waste (PPW) was used as a carbon source to produce ethanol by Wickerhamia sp. Finally, in order to obtain maximum ethanol production from PPW, a fermentation medium was statistically designed. The effect of various medium ingredients was evaluated initially by Plackett-Burman design (PBD), where malt extracts, tryptone, and KH 2 PO 4 showed significantly positive effect (p value < 0.05). Using Response Surface Modeling (RSM), 40 g/L (dry basis) PPW and 25 g/L malt extract were found optimum and yielded 21.7 g/L ethanol. This study strongly suggests Wickerhamia sp. as a promising candidate for bioethanol production from starchy biomass, in particular, PPW through CBP.

  9. Fundamental neutron physics

    International Nuclear Information System (INIS)

    Deslattes, R.; Dombeck, T.; Greene, G.; Ramsey, N.; Rauch, H.; Werner, S.

    1984-01-01

    Fundamental physics experiments of merit can be conducted at the proposed intense neutron sources. Areas of interest include: neutron particle properties, neutron wave properties, and fundamental physics utilizing reactor produced γ-rays. Such experiments require intense, full-time utilization of a beam station for periods ranging from several months to a year or more

  10. Examining the sources of variability in cell culture media used for biopharmaceutical production.

    Science.gov (United States)

    McGillicuddy, Nicola; Floris, Patrick; Albrecht, Simone; Bones, Jonathan

    2018-01-01

    Raw materials, in particular cell culture media, represent a significant source of variability to biopharmaceutical manufacturing processes that can detrimentally affect cellular growth, viability and specific productivity or alter the quality profile of the expressed therapeutic protein. The continual expansion of the biopharmaceutical industry is creating an increasing demand on the production and supply chain consistency for cell culture media, especially as companies embrace intensive continuous processing. Here, we provide a historical perspective regarding the transition from serum containing to serum-free media, the development of chemically-defined cell culture media for biopharmaceutical production using industrial scale bioprocesses and review production mechanisms for liquid and powder culture media. An overview and critique of analytical approaches used for the characterisation of cell culture media and the identification of root causes of variability are also provided, including in-depth liquid phase separations, mass spectrometry and spectroscopic methods.

  11. An SEU tolerant memory cell derived from fundamental studies of SEU mechanisms in SRAM

    International Nuclear Information System (INIS)

    Weaver, H.T.; Axness, C.L.; McBrayer, J.D.; Browning, J.S.; Fu, J.S.; Ochoa, A. Jr.; Koga, R.

    1987-01-01

    A new single event upset (SEU) hardening concept, an LRAM cell, is demonstrated theoretically and experimentally. Decoupling resistors in the LRAM are used only to protect against the short n-channel transient; longer persisting pulses are reduced in magnitude by a voltage divider, a basically new concept for SEU protection. In such a design, smaller resistors provide SEU tolerance, allowing higher performance, hardened memories. As basis for the LRAM idea, techniques were developed to measure time constants for ion induced voltage transients in conventional static random access memories, SRAM. Time constants of 0.8 and 6.3 nsec were measured for transients following strikes at the n- and p-channel drains, respectively - primary areas of SEU sensitivity. These data are the first transient time measurements on full memory chips and the large difference is fundamental to the LRAM concept. Test structures of the new design exhibit equivalent SEU tolerance with resistors 5-to-10 times smaller than currently used in SRAM. Our advanced transport-plus-circuit numerical simulations of the SEU process predicted this result and account for the LRAM experiments, as well as a variety of experiments on conventional SRAM

  12. Islamic fundamentalism in Indonesia

    OpenAIRE

    Nagy, Sandra L.

    1996-01-01

    This is a study of Islamic fundamentalism in Indonesia. Islamic fundamentalism is defined as the return to the foundations and principles of Islam including all movements based on the desire to create a more Islamic society. After describing the practices and beliefs of Islam, this thesis examines the three aspects of universal Islamic fundamentalism: revivalism, resurgence, and radicalism. It analyzes the role of Islam in Indonesia under Dutch colonial rule, an alien Christian imperialist po...

  13. Recycling and Energy Recovery Pilot Project: Project Report and Future Efforts

    Energy Technology Data Exchange (ETDEWEB)

    Rivard, C.

    1999-05-19

    A novel bioprocessing technology was developed that efficiently converts negative-value organic waste, including domestic refuse, animal manures, industrial wastes, food processing wastes, and municipal sewage sludge into saleable products, including fuel gas and compost. This technology is known as high solids anaerobic digestion and was developed at NREL from fundamental research to laboratory- and intermediate-scale system evaluations.

  14. Consolidated bioprocessing of microalgal biomass to carboxylates by a mixed culture of cow rumen bacteria using anaerobic sequencing batch reactor (ASBR).

    Science.gov (United States)

    Zhao, Baisuo; Liu, Jie; Frear, Craig; Holtzapple, Mark; Chen, Shulin

    2016-12-01

    This study employed mixed-culture consolidated bioprocessing (CBP) to digest microalgal biomass in an anaerobic sequencing batch reactor (ASBR). The primary objectives are to evaluate the impact of hydraulic residence time (HRT) on the productivity of carboxylic acids and to characterize the bacterial community. HRT affects the production rate and patterns of carboxylic acids. For the 5-L laboratory-scale fermentation, a 12-day HRT was selected because it offered the highest productivity of carboxylic acids and it synthesized longer chains. The variability of the bacterial community increased with longer HRT (R 2 =0.85). In the 5-L laboratory-scale fermentor, the most common phyla were Firmicutes (58.3%), Bacteroidetes (27.4%), and Proteobacteria (11.9%). The dominant bacterial classes were Clostridia (29.8%), Bacteroidia (27.4%), Tissierella (26.2%), and Betaproteobacteria (8.9%). Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. HSC-explorer: a curated database for hematopoietic stem cells.

    Science.gov (United States)

    Montrone, Corinna; Kokkaliaris, Konstantinos D; Loeffler, Dirk; Lechner, Martin; Kastenmüller, Gabi; Schroeder, Timm; Ruepp, Andreas

    2013-01-01

    HSC-Explorer (http://mips.helmholtz-muenchen.de/HSC/) is a publicly available, integrative database containing detailed information about the early steps of hematopoiesis. The resource aims at providing fast and easy access to relevant information, in particular to the complex network of interacting cell types and molecules, from the wealth of publications in the field through visualization interfaces. It provides structured information on more than 7000 experimentally validated interactions between molecules, bioprocesses and environmental factors. Information is manually derived by critical reading of the scientific literature from expert annotators. Hematopoiesis-relevant interactions are accompanied with context information such as model organisms and experimental methods for enabling assessment of reliability and relevance of experimental results. Usage of established vocabularies facilitates downstream bioinformatics applications and to convert the results into complex networks. Several predefined datasets (Selected topics) offer insights into stem cell behavior, the stem cell niche and signaling processes supporting hematopoietic stem cell maintenance. HSC-Explorer provides a versatile web-based resource for scientists entering the field of hematopoiesis enabling users to inspect the associated biological processes through interactive graphical presentation.

  16. HSC-explorer: a curated database for hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Corinna Montrone

    Full Text Available HSC-Explorer (http://mips.helmholtz-muenchen.de/HSC/ is a publicly available, integrative database containing detailed information about the early steps of hematopoiesis. The resource aims at providing fast and easy access to relevant information, in particular to the complex network of interacting cell types and molecules, from the wealth of publications in the field through visualization interfaces. It provides structured information on more than 7000 experimentally validated interactions between molecules, bioprocesses and environmental factors. Information is manually derived by critical reading of the scientific literature from expert annotators. Hematopoiesis-relevant interactions are accompanied with context information such as model organisms and experimental methods for enabling assessment of reliability and relevance of experimental results. Usage of established vocabularies facilitates downstream bioinformatics applications and to convert the results into complex networks. Several predefined datasets (Selected topics offer insights into stem cell behavior, the stem cell niche and signaling processes supporting hematopoietic stem cell maintenance. HSC-Explorer provides a versatile web-based resource for scientists entering the field of hematopoiesis enabling users to inspect the associated biological processes through interactive graphical presentation.

  17. The Ovonic regenerative fuel cell, a fundamentally new approach

    International Nuclear Information System (INIS)

    Ovshinsky, S.R.; Venkatesan, S.; Corrigan, D.A.

    2004-01-01

    The Ovonic Regenerative Fuel Cell utilizes Ovonic metal hydride materials in place of traditional noble metal catalysts in the hydrogen fuel electrode. This provides unique features including the ability to capture and utilize regenerative braking energy at high efficiency and the ability to operate for a significant period upon interruption of the hydrogen fuel supply. Additionally, this novel fuel cell does not use high price components, such as platinum catalysts, microporous membranes, and graphite bipolar plates, used in PEM fuel cells. Proof of concept has been demonstrated in full-size multicell prototypes delivering about 100 W power. The Ovonic Regenerative Fuel Cell is yet another component of ECD Ovonic technology contributing to the emerging hydrogen economy which already includes Uni-Solar PV solar cells, Ovonic solid-state hydrogen storage devices, and Ovonic nickel-metal hydride batteries from Cobasys, a joint venture between ECD Ovonics and ChevronTexaco. (author)

  18. Fundamentals and applications of organic electrochemistry synthesis, materials, devices

    CERN Document Server

    Fuchigami, Toshio; Inagi, Shinsuke

    2014-01-01

    This textbook is an accessible overview of the broad field of organic electrochemistry, covering the fundamentals and applications of contemporary organic electrochemistry.  The book begins with an introduction to the fundamental aspects of electrode electron transfer and methods for the electrochemical measurement of organic molecules. It then goes on to discuss organic electrosynthesis of molecules and macromolecules, including detailed experimental information for the electrochemical synthesis of organic compounds and conducting polymers. Later chapters highlight new methodology for organic electrochemical synthesis, for example electrolysis in ionic liquids, the application to organic electronic devices such as solar cells and LEDs, and examples of commercialized organic electrode processes. Appendices present useful supplementary information including experimental examples of organic electrosynthesis, and tables of physical data (redox potentials of various organic solvents and organic compounds and phy...

  19. Consolidated bioprocessing strategy for ethanol production from Jerusalem artichoke tubers by Kluyveromyces marxianus under high gravity conditions.

    Science.gov (United States)

    Yuan, W J; Chang, B L; Ren, J G; Liu, J P; Bai, F W; Li, Y Y

    2012-01-01

    Developing an innovative process for ethanol fermentation from Jerusalem artichoke tubers under very high gravity (VHG) conditions. A consolidated bioprocessing (CBP) strategy that integrated inulinase production, saccharification of inulin contained in Jerusalem artichoke tubers and ethanol production from sugars released from inulin by the enzyme was developed with the inulinase-producing yeast Kluyveromyces marxianus Y179 and fed-batch operation. The impact of inoculum age, aeration, the supplementation of pectinase and nutrients on the ethanol fermentation performance of the CBP system was studied. Although inulinase activities increased with the extension of the seed incubation time, its contribution to ethanol production was negligible because vigorously growing yeast cells harvested earlier carried out ethanol fermentation more efficiently. Thus, the overnight incubation that has been practised in ethanol production from starch-based feedstocks is recommended. Aeration facilitated the fermentation process, but compromised ethanol yield because of the negative Crabtree effect of the species, and increases the risk of contamination under industrial conditions. Therefore, nonaeration conditions are preferred for the CBP system. Pectinase supplementation reduced viscosity of the fermentation broth and improved ethanol production performance, particularly under high gravity conditions, but the enzyme cost should be carefully balanced. Medium optimization was performed, and ethanol concentration as high as 94·2 g l(-1) was achieved when 0·15 g l(-1) K(2) HPO(4) was supplemented, which presents a significant progress in ethanol production from Jerusalem artichoke tubers. A CBP system using K. marxianus is suitable for efficient ethanol production from Jerusalem artichoke tubers under VHG conditions. Jerusalem artichoke tubers are an alternative to grain-based feedstocks for ethanol production. The high ethanol concentration achieved using K. marxianus with the

  20. Fundamentals of ergonomic exoskeleton robots

    NARCIS (Netherlands)

    Schiele, A.

    2008-01-01

    This thesis is the first to provide the fundamentals of ergonomic exoskeleton design. The fundamental theory as well as technology necessary to analyze and develop ergonomic wearable robots interacting with humans is established and validated by experiments and prototypes. The fundamentals are (1) a

  1. Fundamentals of thinking, patterns

    Science.gov (United States)

    Gafurov, O. M.; Gafurov, D. O.; Syryamkin, V. I.

    2018-05-01

    The authors analyze the fundamentals of thinking and propose to consider a model of the brain based on the presence of magnetic properties of gliacytes (Schwann cells) because of their oxygen saturation (oxygen has paramagnetic properties). The authors also propose to take into account the motion of electrical discharges through synapses causing electric and magnetic fields as well as additional effects such as paramagnetic resonance, which allows combining multisensory object-related information located in different parts of the brain. Therefore, the events of the surrounding world are reflected and remembered in the cortex columns, thus, creating isolated subnets with altered magnetic properties (patterns) and subsequently participate in recognition of objects, form a memory, and so on. The possibilities for the pattern-based thinking are based on the practical experience of applying methods and technologies of artificial neural networks in the form of a neuroemulator and neuromorphic computing devices.

  2. Scalable microcarrier-based manufacturing of mesenchymal stem/stromal cells.

    Science.gov (United States)

    de Soure, António M; Fernandes-Platzgummer, Ana; da Silva, Cláudia L; Cabral, Joaquim M S

    2016-10-20

    Due to their unique features, mesenchymal stem/stromal cells (MSC) have been exploited in clinical settings as therapeutic candidates for the treatment of a variety of diseases. However, the success in obtaining clinically-relevant MSC numbers for cell-based therapies is dependent on efficient isolation and ex vivo expansion protocols, able to comply with good manufacturing practices (GMP). In this context, the 2-dimensional static culture systems typically used for the expansion of these cells present several limitations that may lead to reduced cell numbers and compromise cell functions. Furthermore, many studies in the literature report the expansion of MSC using fetal bovine serum (FBS)-supplemented medium, which has been critically rated by regulatory agencies. Alternative platforms for the scalable manufacturing of MSC have been developed, namely using microcarriers in bioreactors, with also a considerable number of studies now reporting the production of MSC using xenogeneic/serum-free medium formulations. In this review we provide a comprehensive overview on the scalable manufacturing of human mesenchymal stem/stromal cells, depicting the various steps involved in the process from cell isolation to ex vivo expansion, using different cell tissue sources and culture medium formulations and exploiting bioprocess engineering tools namely microcarrier technology and bioreactors. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. A novel ionic liquid-tolerant Fusarium oxysporum BN secreting ionic liquid-stable cellulase: consolidated bioprocessing of pretreated lignocellulose containing residual ionic liquid.

    Science.gov (United States)

    Xu, Jiaxing; Wang, Xinfeng; Hu, Lei; Xia, Jun; Wu, Zhen; Xu, Ning; Dai, Benlin; Wu, Bin

    2015-04-01

    In this study, microbial communities from chemicals polluted microhabitats were cultured with the addition of imidazolium-based ionic liquid (IL) to enrich for IL-tolerant microbes. A strain of Fusarium oxysporum BN producing cellulase from these enrichments was capable of growing in 10% (w/v) 1-ethyl-3-methylimidazolium phosphinate, much higher than the normal IL concentrations in the lignocellulose regenerated from ILs. Cellulase secreted by the strain showed high resistance to ILs based on phosphate and sulfate radicals, evidencing of a high conformational stability in relevant media. Gratifyingly, F. oxysporum BN can directly convert IL-pretreated rice straw to bioethanol via consolidated bioprocessing (I-CBP). At optimum fermentation condition, a maximum ethanol yield of 0.125 g ethanol g(-1) of rice straw was finally obtained, corresponding to 64.2% of the theoretical yield. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Bio-processing of Agro-industrial Wastes for Production of Food-grade Enzymes: Progress and Prospects

    Directory of Open Access Journals (Sweden)

    Parmjit S Panesar

    2016-10-01

    Full Text Available Background and Objectives: In the era of global industrialization, enzymes are being used extensively in the various sectors including food processing. Owing to the high price of enzymes, various initiatives have been undertaken by the R&D sector for the development of new processes or improvement in the existing processes for production of cost effective enzymes. With the advancement in the field of biotechnology, different bioprocesses are being used for utilization of different agro-industrial residues for the production of various enzymes. This review focuses on different types of agro-industrial wastes and their utilization in the production of enzymes. The present scenario as well as the future scope of utilization of enzymes in the food industry has also been discussed.Results and Conclusion: The regulations from the various governmental as well as environmental agencies for the demand of cleaner environment have led to the advancement in various technologies for utilization of the wastes for the production of value-added products such as enzymes. Among the different types of fermentation, maximum work has been carried under solid state conditions by batch fermentation. The research has indicated the significant potential of agro-industrial wastes for production of food-grade enzymes in order to improve the economics of the process.Conflict of interests: The authors declare no conflict of interest.

  5. Fundamentals of turbomachines

    CERN Document Server

    Dick, Erik

    2015-01-01

    This book explores the working principles of all kinds of turbomachines. The same theoretical framework is used to analyse the different machine types. Fundamentals are first presented and theoretical concepts are then elaborated for particular machine types, starting with the simplest ones.For each machine type, the author strikes a balance between building basic understanding and exploring knowledge of practical aspects. Readers are invited through challenging exercises to consider how the theory applies to particular cases and how it can be generalised.   The book is primarily meant as a course book. It teaches fundamentals and explores applications. It will appeal to senior undergraduate and graduate students in mechanical engineering and to professional engineers seeking to understand the operation of turbomachines. Readers will gain a fundamental understanding of turbomachines. They will also be able to make a reasoned choice of turbomachine for a particular application and to understand its operation...

  6. Information security fundamentals

    CERN Document Server

    Peltier, Thomas R

    2013-01-01

    Developing an information security program that adheres to the principle of security as a business enabler must be the first step in an enterprise's effort to build an effective security program. Following in the footsteps of its bestselling predecessor, Information Security Fundamentals, Second Edition provides information security professionals with a clear understanding of the fundamentals of security required to address the range of issues they will experience in the field.The book examines the elements of computer security, employee roles and r

  7. Fundamentals of statistics

    CERN Document Server

    Mulholland, Henry

    1968-01-01

    Fundamentals of Statistics covers topics on the introduction, fundamentals, and science of statistics. The book discusses the collection, organization and representation of numerical data; elementary probability; the binomial Poisson distributions; and the measures of central tendency. The text describes measures of dispersion for measuring the spread of a distribution; continuous distributions for measuring on a continuous scale; the properties and use of normal distribution; and tests involving the normal or student's 't' distributions. The use of control charts for sample means; the ranges

  8. Fundamental investigations on periodic nano- and microstructured organic solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Niggemann, M.

    2005-03-15

    Using organic semiconducting materials in solar cells is a new approach with promising possibilities. The great potential of low cost production combined with mechanical flexibility gives rise to new applications. Due to the relatively simple fabrication process from solution and the mechanical flexibility, the production of organic solar cells by the cost effective roll-to-roll process appears promising. However, the preconditions for commercialization are not fulfilled as yet. The demands on organic solar cells strongly depend on the type of application. The highest demands on solar cell technologies are set by the energy market. Organic solar cells are only expected to be competitive on the energy market when the requirements on efficiency, lifetime and costs are fulfilled at the same time. Regarding this as a long term goal, a less demanding but still challenging medium term goal would be the application of relatively small organic solar cell modules for i.e. portable electronic devices. The integration of Organic Field Effect Transistors (OFET) and Organic Light Emitting Diodes (OLED) to all-polymer electronic devices is still under development. Nevertheless, the integration of organic solar cells as one functional component appears promising as the production technologies are expected to be compatible. The innovative contribution of this thesis to the development of organic solar cells is as follows: Motivated by the desire to fabricate efficient and cost effective organic solar cells, the approach of developing novel solar cell architectures based on periodic nano- and microstructures is followed. At present, planar organic solar cells with indium tin oxide (ITO) as a transparent electrode are intensively studied. One decisive cost factor would, however, be the indium price, which is the key component of the ITO electrode. The planar cell architecture can be conceived as a one-dimensional photonic device, however the presented work widens the investigations

  9. A CORN STEM AS BIOMATERIAL FOR SACCHAROMYCES CEREVISIAE CELLS IMMOBILIZATION FOR THE ETHANOL PRODUCTION

    Directory of Open Access Journals (Sweden)

    Vesna Vučurović

    2008-11-01

    Full Text Available This study provides a preliminary contribution to the development of a bioprocess for the production of ethanol using Saccharomyces cerevisiae cells immobilized onto a corn stem. For this purpose, the yeast cells were submitted to the batch tests in situ adsorption onto 0.5 cm long corn stem. Cells immobilization was analyzed by optical microscopy. The number of the yeast cells, fermentation kinetics, the ethanol yield in the presence or the absence of the support in the fermentation medium was investigated. It was determined that the addition of the corn stem led to the abrupt increase of the yeast cells number in substrate, ethanol yield, pH value, a total dissolved salts content and substrate conductivity. The addition of 5 and 10g of the corn stem pith per liter of the medium decreased the amount of residual sugar. The results indicate that a corn stem might be a good carrier for the yeast cell immobilization, and also a cheap alternative recourse of mineral components with the possibility of application for improving ethanol productivities.

  10. Infosec management fundamentals

    CERN Document Server

    Dalziel, Henry

    2015-01-01

    Infosec Management Fundamentals is a concise overview of the Information Security management concepts and techniques, providing a foundational template for both experienced professionals and those new to the industry. This brief volume will also appeal to business executives and managers outside of infosec who want to understand the fundamental concepts of Information Security and how it impacts their business decisions and daily activities. Teaches ISO/IEC 27000 best practices on information security management Discusses risks and controls within the context of an overall information securi

  11. Fundamental limits to position determination by concentration gradients.

    Directory of Open Access Journals (Sweden)

    Filipe Tostevin

    2007-04-01

    Full Text Available Position determination in biological systems is often achieved through protein concentration gradients. Measuring the local concentration of such a protein with a spatially varying distribution allows the measurement of position within the system. For these systems to work effectively, position determination must be robust to noise. Here, we calculate fundamental limits to the precision of position determination by concentration gradients due to unavoidable biochemical noise perturbing the gradients. We focus on gradient proteins with first-order reaction kinetics. Systems of this type have been experimentally characterised in both developmental and cell biology settings. For a single gradient we show that, through time-averaging, great precision potentially can be achieved even with very low protein copy numbers. As a second example, we investigate the ability of a system with oppositely directed gradients to find its centre. With this mechanism, positional precision close to the centre improves more slowly with increasing averaging time, and so longer averaging times or higher copy numbers are required for high precision. For both single and double gradients, we demonstrate the existence of optimal length scales for the gradients for which precision is maximized, as well as analyze how precision depends on the size of the concentration-measuring apparatus. These results provide fundamental constraints on the positional precision supplied by concentration gradients in various contexts, including both in developmental biology and also within a single cell.

  12. Fundamental length

    International Nuclear Information System (INIS)

    Pradhan, T.

    1975-01-01

    The concept of fundamental length was first put forward by Heisenberg from purely dimensional reasons. From a study of the observed masses of the elementary particles known at that time, it is sumrised that this length should be of the order of magnitude 1 approximately 10 -13 cm. It was Heisenberg's belief that introduction of such a fundamental length would eliminate the divergence difficulties from relativistic quantum field theory by cutting off the high energy regions of the 'proper fields'. Since the divergence difficulties arise primarily due to infinite number of degrees of freedom, one simple remedy would be the introduction of a principle that limits these degrees of freedom by removing the effectiveness of the waves with a frequency exceeding a certain limit without destroying the relativistic invariance of the theory. The principle can be stated as follows: It is in principle impossible to invent an experiment of any kind that will permit a distintion between the positions of two particles at rest, the distance between which is below a certain limit. A more elegant way of introducing fundamental length into quantum theory is through commutation relations between two position operators. In quantum field theory such as quantum electrodynamics, it can be introduced through the commutation relation between two interpolating photon fields (vector potentials). (K.B.)

  13. Fundamentals of ergonomic exoskeleton robots

    OpenAIRE

    Schiele, A.

    2008-01-01

    This thesis is the first to provide the fundamentals of ergonomic exoskeleton design. The fundamental theory as well as technology necessary to analyze and develop ergonomic wearable robots interacting with humans is established and validated by experiments and prototypes. The fundamentals are (1) a new theoretical framework for analyzing physical human robot interaction (pHRI) with exoskeletons, and (2) a clear set of design rules of how to build wearable, portable exoskeletons to easily and...

  14. Fundamental limit of light trapping in grating structures

    KAUST Repository

    Yu, Zongfu

    2010-08-11

    We use a rigorous electromagnetic approach to analyze the fundamental limit of light-trapping enhancement in grating structures. This limit can exceed the bulk limit of 4n 2, but has significant angular dependency. We explicitly show that 2D gratings provide more enhancement than 1D gratings. We also show the effects of the grating profile’s symmetry on the absorption enhancement limit. Numerical simulations are applied to support the theory. Our findings provide general guidance for the design of grating structures for light-trapping solar cells.

  15. Optical code division multiple access fundamentals and applications

    CERN Document Server

    Prucnal, Paul R

    2005-01-01

    Code-division multiple access (CDMA) technology has been widely adopted in cell phones. Its astonishing success has led many to evaluate the promise of this technology for optical networks. This field has come to be known as Optical CDMA (OCDMA). Surveying the field from its infancy to the current state, Optical Code Division Multiple Access: Fundamentals and Applications offers the first comprehensive treatment of OCDMA from technology to systems.The book opens with a historical perspective, demonstrating the growth and development of the technologies that would eventually evolve into today's

  16. Dynamic cell culture system (7-IML-1)

    Science.gov (United States)

    Cogoli, Augusto

    1992-01-01

    This experiment is one of the Biorack experiments being flown on the International Microgravity Laboratory 1 (MIL-1) mission as part of an investigation studying cell proliferation and performance in space. One of the objectives of this investigation is to assess the potential benefits of bioprocessing in space with the ultimate goal of developing a bioreactor for continuous cell cultures in space. This experiment will test the operation of an automated culture chamber that was designed for use in a Bioreactor in space. The device to be tested is called the Dynamic Cell Culture System (DCCS). It is a simple device in which media are renewed or chemicals are injected automatically, by means of osmotic pumps. This experiment uses four Type I/O experiment containers. One DCCS unit, which contains a culture chamber with renewal of medium and a second chamber without a medium supply fits in each container. Two DCCS units are maintained under zero gravity conditions during the on-orbit period. The other two units are maintained under 1 gh conditions in a 1 g centrifuge. The schedule for incubator transfer is given.

  17. Communication technology update and fundamentals

    CERN Document Server

    Grant, August E

    2010-01-01

    New communication technologies are being introduced at an astonishing rate. Making sense of these technologies is increasingly difficult. Communication Technology Update and Fundamentals is the single best source for the latest developments, trends, and issues in communication technology. Featuring the fundamental framework along with the history and background of communication technologies, Communication Technology Update and Fundamentals, 12th edition helps you stay ahead of these ever-changing and emerging technologies.As always, every chapter ha

  18. SYSTEMS BIOLOGY AND METABOLIC ENGINEERING OF ARTHROSPIRA CELL FACTORIES

    Directory of Open Access Journals (Sweden)

    Amornpan Klanchui

    2012-10-01

    Full Text Available Arthrospira are attractive candidates to serve as cell factories for production of many valuable compounds useful for food, feed, fuel and pharmaceutical industries. In connection with the development of sustainable bioprocessing, it is a challenge to design and develop efficient Arthrospira cell factories which can certify effective conversion from the raw materials (i.e. CO2 and sun light into desired products. With the current availability of the genome sequences and metabolic models of Arthrospira, the development of Arthrospira factories can now be accelerated by means of systems biology and the metabolic engineering approach. Here, we review recent research involving the use of Arthrospira cell factories for industrial applications, as well as the exploitation of systems biology and the metabolic engineering approach for studying Arthrospira. The current status of genomics and proteomics through the development of the genome-scale metabolic model of Arthrospira, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies are discussed. At the end, the perspective and future direction on Arthrospira cell factories for industrial biotechnology are presented.

  19. Individual differences in fundamental social motives.

    Science.gov (United States)

    Neel, Rebecca; Kenrick, Douglas T; White, Andrew Edward; Neuberg, Steven L

    2016-06-01

    Motivation has long been recognized as an important component of how people both differ from, and are similar to, each other. The current research applies the biologically grounded fundamental social motives framework, which assumes that human motivational systems are functionally shaped to manage the major costs and benefits of social life, to understand individual differences in social motives. Using the Fundamental Social Motives Inventory, we explore the relations among the different fundamental social motives of Self-Protection, Disease Avoidance, Affiliation, Status, Mate Seeking, Mate Retention, and Kin Care; the relationships of the fundamental social motives to other individual difference and personality measures including the Big Five personality traits; the extent to which fundamental social motives are linked to recent life experiences; and the extent to which life history variables (e.g., age, sex, childhood environment) predict individual differences in the fundamental social motives. Results suggest that the fundamental social motives are a powerful lens through which to examine individual differences: They are grounded in theory, have explanatory value beyond that of the Big Five personality traits, and vary meaningfully with a number of life history variables. A fundamental social motives approach provides a generative framework for considering the meaning and implications of individual differences in social motivation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  20. Teaching the Politics of Islamic Fundamentalism.

    Science.gov (United States)

    Kazemzadeh, Masoud

    1998-01-01

    Argues that the rise of Islamic fundamentalism since the Iranian Revolution has generated a number of issues of analytical significance for political science. Describes three main models in teaching and research on Islamic fundamentalism: Islamic exceptionalism, comparative fundamentalisms, and class analysis. Discusses the construction of a…

  1. Fundamental principles of heat transfer

    CERN Document Server

    Whitaker, Stephen

    1977-01-01

    Fundamental Principles of Heat Transfer introduces the fundamental concepts of heat transfer: conduction, convection, and radiation. It presents theoretical developments and example and design problems and illustrates the practical applications of fundamental principles. The chapters in this book cover various topics such as one-dimensional and transient heat conduction, energy and turbulent transport, forced convection, thermal radiation, and radiant energy exchange. There are example problems and solutions at the end of every chapter dealing with design problems. This book is a valuable int

  2. A wearable multichannel tactile display of voice fundamental frequency.

    Science.gov (United States)

    Yeung, E; Boothroyd, A; Redmond, C

    1988-12-01

    This paper describes a wearable sensory aid that provides the deaf with tactually encoded information about intonation. Fundamental frequency is represented as both place and rate of vibration in a linear array of solenoids. Pitch extraction is accomplished through low-pass filtering and peak detection. A microcomputer is used to measure pitch period, which in turn determines which of the solenoids is actuated. By comparing consecutive periods, the system discriminates against random, noise-related inputs. The device is switchable between 1-, 8-, and 16-channel operation. The electronics package is contained in a case that may be worn on a belt. The solenoid array is worn on the forearm. The system is powered by five, rechargeable lithium cells and runs for at least 6 hours between charges. Proposed developments include the incorporation of digital pitch extraction methods and the option to use the spatial output dimension to encode speech parameters other than fundamental frequency.

  3. Fundamental Astronomy

    CERN Document Server

    Karttunen, Hannu; Oja, Heikki; Poutanen, Markku; Donner, Karl Johan

    2007-01-01

    Fundamental Astronomy gives a well-balanced and comprehensive introduction to the topics of classical and modern astronomy. While emphasizing both the astronomical concepts and the underlying physical principles, the text provides a sound basis for more profound studies in the astronomical sciences. The fifth edition of this successful undergraduate textbook has been extensively modernized and extended in the parts dealing with the Milky Way, extragalactic astronomy and cosmology as well as with extrasolar planets and the solar system (as a consequence of recent results from satellite missions and the new definition by the International Astronomical Union of planets, dwarf planets and small solar-system bodies). Furthermore a new chapter on astrobiology has been added. Long considered a standard text for physical science majors, Fundamental Astronomy is also an excellent reference and entrée for dedicated amateur astronomers.

  4. Glycolysis is governed by growth regime and simple enzyme regulation in adherent MDCK cells.

    Science.gov (United States)

    Rehberg, Markus; Ritter, Joachim B; Reichl, Udo

    2014-10-01

    Due to its vital importance in the supply of cellular pathways with energy and precursors, glycolysis has been studied for several decades regarding its capacity and regulation. For a systems-level understanding of the Madin-Darby canine kidney (MDCK) cell metabolism, we couple a segregated cell growth model published earlier with a structured model of glycolysis, which is based on relatively simple kinetics for enzymatic reactions of glycolysis, to explain the pathway dynamics under various cultivation conditions. The structured model takes into account in vitro enzyme activities, and links glycolysis with pentose phosphate pathway and glycogenesis. Using a single parameterization, metabolite pool dynamics during cell cultivation, glucose limitation and glucose pulse experiments can be consistently reproduced by considering the cultivation history of the cells. Growth phase-dependent glucose uptake together with cell-specific volume changes generate high intracellular metabolite pools and flux rates to satisfy the cellular demand during growth. Under glucose limitation, the coordinated control of glycolytic enzymes re-adjusts the glycolytic flux to prevent the depletion of glycolytic intermediates. Finally, the model's predictive power supports the design of more efficient bioprocesses.

  5. Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors

    Directory of Open Access Journals (Sweden)

    Tyler DiStefano

    2018-01-01

    Full Text Available Pluripotent stem cells can be differentiated into 3D retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioprocess using rotating-wall vessel (RWV bioreactors to culture retinal organoids derived from mouse pluripotent stem cells. Organoids in RWV demonstrate enhanced proliferation, with well-defined morphology and improved differentiation of neurons including ganglion cells and S-cone photoreceptors. Furthermore, RWV organoids at day 25 (D25 reveal similar maturation and transcriptome profile as those at D32 in static culture, closely recapitulating spatiotemporal development of postnatal day 6 mouse retina in vivo. Interestingly, however, retinal organoids do not differentiate further under any in vitro condition tested here, suggesting additional requirements for functional maturation. Our studies demonstrate that bioreactors can accelerate and improve organoid growth and differentiation for modeling retinal disease and evaluation of therapies.

  6. Country Fundamentals and Currency Excess Returns

    Directory of Open Access Journals (Sweden)

    Daehwan Kim

    2014-06-01

    Full Text Available We examine whether country fundamentals help explain the cross-section of currency excess returns. For this purpose, we consider fundamental variables such as default risk, foreign exchange rate regime, capital control as well as interest rate in the multi-factor model framework. Our empirical results show that fundamental factors explain a large part of the cross-section of currency excess returns. The zero-intercept restriction of the factor model is not rejected for most currencies. They also reveal that our factor model with country fundamentals performs better than a factor model with usual investment-style factors. Our main empirical results are based on 2001-2010 balanced panel data of 19 major currencies. This paper may fill the gap between country fundamentals and practitioners' strategies on currency investment.

  7. The use of 'Omics technology to rationally improve industrial mammalian cell line performance.

    Science.gov (United States)

    Lewis, Amanda M; Abu-Absi, Nicholas R; Borys, Michael C; Li, Zheng Jian

    2016-01-01

    Biologics represent an increasingly important class of therapeutics, with 7 of the 10 top selling drugs from 2013 being in this class. Furthermore, health authority approval of biologics in the immuno-oncology space is expected to transform treatment of patients with debilitating and deadly diseases. The growing importance of biologics in the healthcare field has also resulted in the recent approvals of several biosimilars. These recent developments, combined with pressure to provide treatments at lower costs to payers, are resulting in increasing need for the industry to quickly and efficiently develop high yielding, robust processes for the manufacture of biologics with the ability to control quality attributes within narrow distributions. Achieving this level of manufacturing efficiency and the ability to design processes capable of regulating growth, death and other cellular pathways through manipulation of media, feeding strategies, and other process parameters will undoubtedly be facilitated through systems biology tools generated in academic and public research communities. Here we discuss the intersection of systems biology, 'Omics technologies, and mammalian bioprocess sciences. Specifically, we address how these methods in conjunction with traditional monitoring techniques represent a unique opportunity to better characterize and understand host cell culture state, shift from an empirical to rational approach to process development and optimization of bioreactor cultivation processes. We summarize the following six key areas: (i) research applied to parental, non-recombinant cell lines; (ii) systems level datasets generated with recombinant cell lines; (iii) datasets linking phenotypic traits to relevant biomarkers; (iv) data depositories and bioinformatics tools; (v) in silico model development, and (vi) examples where these approaches have been used to rationally improve cellular processes. We critically assess relevant and state of the art research

  8. Application of CFD in Bioprocessing: Separation of mammalian cells using disc stack centrifuge during production of biotherapeutics.

    Science.gov (United States)

    Shekhawat, Lalita Kanwar; Sarkar, Jayati; Gupta, Rachit; Hadpe, Sandeep; Rathore, Anurag S

    2018-02-10

    Centrifugation continues to be one of the most commonly used unit operations for achieving efficient harvest of the product from the mammalian cell culture broth during production of therapeutic monoclonal antibodies (mAbs). Since the mammalian cells are known to be shear sensitive, optimal performance of the centrifuge requires a balance between productivity and shear. In this study, Computational Fluid Dynamics (CFD) has been successfully used as a tool to facilitate efficient optimization. Multiphase Eulerian-Eulerian model coupled with Gidaspow drag model along with Eulerian-Eulerian k-ε mixture turbulence model have been used to quantify the complex hydrodynamics of the centrifuge and thus evaluate the turbulent stresses generated by the centrifugal forces. An empirical model has been developed by statistical analysis of experimentally observed cell lysis data as a function of turbulent stresses. An operating window that offers the optimal balance between high productivity, high separation efficiency, and low cell damage has been identified by use of CFD modeling. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Religious fundamentalism and conflict

    OpenAIRE

    Muzaffer Ercan Yılmaz

    2006-01-01

    This study provides an analytical discussion for the issue of religious fundamentalism and itsrelevance to conflict, in its broader sense. It is stressed that religious fundamentalism manifests itself in twoways: nonviolent intolerance and violent intolerance. The sources of both types of intolerance and theirconnection to conflict are addressed and discussed in detail. Further research is also suggested on conditionsconnecting religion to nonviolent intolerance so as to cope with the problem...

  10. A novel cell autolysis system for cost-competitive downstream processing.

    Science.gov (United States)

    Hajnal, Ivan; Chen, Xiangbin; Chen, Guo-Qiang

    2016-11-01

    The industrial production of low value-added biological products poses significant challenges due to cost pressures. In recent years, it has been argued that synthetic biology approaches will lead to breakthroughs that eliminate price bottlenecks for the production of a wide range of biological products including bioplastics and biofuels. One significant bottleneck lies in the necessity to break the tough cell walls of microbes in order to release intracellular products. We here report the implementation of the first synthetic biology standard part based on the lambda phage SRRz genes and a synthetic ribosome binding site (RBS) that works in Escherichia coli and Halomonas campaniensis, which enables the producer strains to induce lysis after the addition of small amounts (1-5 %) of solvents or to spontaneously lyse during the stresses of downstream processing, and thus has the potential to eliminate the mechanical cell disruption step as both an efficiency bottleneck and a significant capex barrier when implementing downstream bioprocesses.

  11. Microbial population heterogeneity versus bioreactor heterogeneity: evaluation of Redox Sensor Green as an exogenous metabolic biosensor

    DEFF Research Database (Denmark)

    Baert, Jonathan; Delepierre, Anissa; Telek, Samuel

    2016-01-01

    Microbial heterogeneity in metabolic performances has attracted a lot of attention, considering its potential impact on industrial bioprocesses. However, little is known about the impact of extracellular perturbations (i.e. bioreactor heterogeneity) on cell-to-cell variability in metabolic...

  12. Impact of CHO Metabolism on Cell Growth and Protein Production: An Overview of Toxic and Inhibiting Metabolites and Nutrients

    DEFF Research Database (Denmark)

    Pereira, Sara; Kildegaard, Helene F.; Andersen, Mikael R.

    2018-01-01

    and process optimization and monitoring to perform efficiently. One of the main reasons for this is the production and accumulation of toxic and growth-inhibiting metabolites during culture. Lactate and ammonium are the most known, but many more have been identified. In this review, we present an overview...... of metabolites that deplete and accumulate throughout the course of cultivations with toxic and growth inhibitory effects to the cells. We further provide an overview of the CHO metabolism with emphasis to metabolic pathways of amino acids, glutathione (GSH), and related compounds which have growth...... of resources that describe the cellular mechanisms of CHO and are available on-line. Finally, we discuss the application of this knowledge for bioprocess and medium development and cell line engineering....

  13. Yeast cell surface display: An efficient strategy for improvement of bioethanol fermentation performance.

    Science.gov (United States)

    Chen, Xianzhong

    2017-03-04

    The cell surface serves as a functional interface between the inside and the outside of the cell. Within the past 20 y the ability of yeast (Saccharomyces cerevisiae) to display heterologous proteins on the cell surface has been demonstrated. Furthermore, S. cerevisiae has been both developed and applied in expression of various proteins on the cell surface. Using this novel and useful strategy, proteins and peptides of various kinds can be displayed on the yeast cell surface by fusing the protein of interest with the glycosylphosphatidylinositol (GPI)-anchoring system. Consolidated bioprocessing (CBP) using S. cerevisiae represents a promising technology for bioethanol production. However, further work is needed to improve the fermentation performance. There is some excellent previous research regarding construction of yeast biocatalyst using the surface display system to decrease cost, increase efficiency of ethanol production and directly utilize starch or biomass for fuel production. In this commentary, we reviewed the yeast surface display system and highlighted recent work. Additionally, the strategy for decrease of phytate phosphate content in dried distillers grains with solubles (DDGS) by display of phytase on the yeast cell surface is discussed.

  14. Applications of cell-free protein synthesis in synthetic biology: Interfacing bio-machinery with synthetic environments.

    Science.gov (United States)

    Lee, Kyung-Ho; Kim, Dong-Myung

    2013-11-01

    Synthetic biology is built on the synthesis, engineering, and assembly of biological parts. Proteins are the first components considered for the construction of systems with designed biological functions because proteins carry out most of the biological functions and chemical reactions inside cells. Protein synthesis is considered to comprise the most basic levels of the hierarchical structure of synthetic biology. Cell-free protein synthesis has emerged as a powerful technology that can potentially transform the concept of bioprocesses. With the ability to harness the synthetic power of biology without many of the constraints of cell-based systems, cell-free protein synthesis enables the rapid creation of protein molecules from diverse sources of genetic information. Cell-free protein synthesis is virtually free from the intrinsic constraints of cell-based methods and offers greater flexibility in system design and manipulability of biological synthetic machinery. Among its potential applications, cell-free protein synthesis can be combined with various man-made devices for rapid functional analysis of genomic sequences. This review covers recent efforts to integrate cell-free protein synthesis with various reaction devices and analytical platforms. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Land Prices and Fundamentals

    OpenAIRE

    Koji Nakamura; Yumi Saita

    2007-01-01

    This paper examines the long-term relationship between macro economic fundamentals and the weighted-average land price indicators, which are supposed to be more appropriate than the official land price indicators when analyzing their impacts on the macro economy. In many cases, we find the cointegrating relationships between the weighted-average land price indicators and the discounted present value of land calculated based on the macro economic fundamentals indicators. We also find that the ...

  16. Fundamental volatility is regime specific

    NARCIS (Netherlands)

    Arnold, I.J.M.; MacDonald, R.; Vries, de C.G.

    2006-01-01

    A widely held notion holds that freely floating exchange rates are excessively volatile when judged against fundamentals and when moving from fixed to floating exchange rates. We re-examine the data and conclude that the disparity between the fundamentals and exchange rate volatility is more

  17. [From fundamental research to clinical development: a review of orthodontics].

    Science.gov (United States)

    Zhao, Zhi-he; Bai, Ding

    2011-11-01

    In recent years, new approaches to the diagnosis and treatment of malocclusion have emerged. The diagnostic and therapeutic techniques of orthodontics have evolved from two dimensions to five dimensions with the development of computer technology, auto-machining and imaging. Furthermore, interdisciplinary study has become the driving force for the advancement of fundamental research in orthodontics. The mechanisms of malocclusion and orthodontic tooth movement have been extensively studied to the details at the level of cells and molecules.

  18. The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies).

    OpenAIRE

    Amaral David G; Scharfman Helen E; Lavenex Pierre

    2007-01-01

    The dentate gyrus is a simple cortical region that is an integral portion of the larger functional brain system called the hippocampal formation. In this review, the fundamental neuroanatomical organization of the dentate gyrus is described, including principal cell types and their connectivity, and a summary of the major extrinsic inputs of the dentate gyrus is provided. Together, this information provides essential information that can serve as an introduction to the dentate gyrus — a “dent...

  19. Fundamental principles in bacterial physiology—history, recent progress, and the future with focus on cell size control: a review

    Science.gov (United States)

    Jun, Suckjoon; Si, Fangwei; Pugatch, Rami; Scott, Matthew

    2018-05-01

    Bacterial physiology is a branch of biology that aims to understand overarching principles of cellular reproduction. Many important issues in bacterial physiology are inherently quantitative, and major contributors to the field have often brought together tools and ways of thinking from multiple disciplines. This article presents a comprehensive overview of major ideas and approaches developed since the early 20th century for anyone who is interested in the fundamental problems in bacterial physiology. This article is divided into two parts. In the first part (sections 1–3), we review the first ‘golden era’ of bacterial physiology from the 1940s to early 1970s and provide a complete list of major references from that period. In the second part (sections 4–7), we explain how the pioneering work from the first golden era has influenced various rediscoveries of general quantitative principles and significant further development in modern bacterial physiology. Specifically, section 4 presents the history and current progress of the ‘adder’ principle of cell size homeostasis. Section 5 discusses the implications of coarse-graining the cellular protein composition, and how the coarse-grained proteome ‘sectors’ re-balance under different growth conditions. Section 6 focuses on physiological invariants, and explains how they are the key to understanding the coordination between growth and the cell cycle underlying cell size control in steady-state growth. Section 7 overviews how the temporal organization of all the internal processes enables balanced growth. In the final section 8, we conclude by discussing the remaining challenges for the future in the field.

  20. Copper-induced adaptation, oxidative stress and its tolerance in Aspergillus niger UCP1261

    Directory of Open Access Journals (Sweden)

    Marcos A. Cavalcanti Luna

    2015-11-01

    Conclusions: The results indicate that the isolate was able to grow in high concentrations of copper, activates mechanisms for adaptation and tolerance in the presence of metal, and is highly efficient at removing the agent. Such data are fundamental if a better understanding is to be reached of the cellular and molecular abilities of native isolates, which can be used to develop bioprocesses in environmental and industrial areas.

  1. Fundamental number theory with applications

    CERN Document Server

    Mollin, Richard A

    2008-01-01

    An update of the most accessible introductory number theory text available, Fundamental Number Theory with Applications, Second Edition presents a mathematically rigorous yet easy-to-follow treatment of the fundamentals and applications of the subject. The substantial amount of reorganizing makes this edition clearer and more elementary in its coverage. New to the Second Edition           Removal of all advanced material to be even more accessible in scope           New fundamental material, including partition theory, generating functions, and combinatorial number theory           Expa

  2. Polysome profiling of mAb producing CHO cell lines links translational control of cell proliferation and recombinant mRNA loading onto ribosomes with global and recombinant protein synthesis.

    Science.gov (United States)

    Godfrey, Charlotte L; Mead, Emma J; Daramola, Olalekan; Dunn, Sarah; Hatton, Diane; Field, Ray; Pettman, Gary; Smales, C Mark

    2017-08-01

    mRNA translation is a key process determining growth, proliferation and duration of a Chinese hamster ovary (CHO) cell culture and influences recombinant protein synthesis rate. During bioprocessing, CHO cells can experience stresses leading to reprogramming of translation and decreased global protein synthesis. Here we apply polysome profiling to determine reprogramming and translational capabilities in host and recombinant monoclonal antibody-producing (mAb) CHO cell lines during batch culture. Recombinant cell lines with the fastest cell specific growth rates were those with the highest global translational efficiency. However, total ribosomal capacity, determined from polysome profiles, did not relate to the fastest growing or highest producing mAb cell line, suggesting it is the ability to utilise available machinery that determines protein synthetic capacity. Cell lines with higher cell specific productivities tended to have elevated recombinant heavy chain transcript copy numbers, localised to the translationally active heavy polysomes. The highest titre cell line was that which sustained recombinant protein synthesis and maintained high recombinant transcript copy numbers in polysomes. Investigation of specific endogenous transcripts revealed a number that maintained or reprogrammed into heavy polysomes, identifying targets for potential cell engineering or those with 5' untranslated regions that might be utilised to enhance recombinant transcript translation. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Cell Motility

    CERN Document Server

    Lenz, Peter

    2008-01-01

    Cell motility is a fascinating example of cell behavior which is fundamentally important to a number of biological and pathological processes. It is based on a complex self-organized mechano-chemical machine consisting of cytoskeletal filaments and molecular motors. In general, the cytoskeleton is responsible for the movement of the entire cell and for movements within the cell. The main challenge in the field of cell motility is to develop a complete physical description on how and why cells move. For this purpose new ways of modeling the properties of biological cells have to be found. This long term goal can only be achieved if new experimental techniques are developed to extract physical information from these living systems and if theoretical models are found which bridge the gap between molecular and mesoscopic length scales. Cell Motility gives an authoritative overview of the fundamental biological facts, theoretical models, and current experimental developments in this fascinating area.

  4. Fundamentals of structural dynamics

    CERN Document Server

    Craig, Roy R

    2006-01-01

    From theory and fundamentals to the latest advances in computational and experimental modal analysis, this is the definitive, updated reference on structural dynamics.This edition updates Professor Craig's classic introduction to structural dynamics, which has been an invaluable resource for practicing engineers and a textbook for undergraduate and graduate courses in vibrations and/or structural dynamics. Along with comprehensive coverage of structural dynamics fundamentals, finite-element-based computational methods, and dynamic testing methods, this Second Edition includes new and e

  5. Transcriptomics as a tool for assessing the scalability of mammalian cell perfusion systems.

    Science.gov (United States)

    Jayapal, Karthik P; Goudar, Chetan T

    2014-01-01

    DNA microarray-based transcriptomics have been used to determine the time course of laboratory and manufacturing-scale perfusion bioreactors in an attempt to characterize cell physiological state at these two bioreactor scales. Given the limited availability of genomic data for baby hamster kidney (BHK) cells, a Chinese hamster ovary (CHO)-based microarray was used following a feasibility assessment of cross-species hybridization. A heat shock experiment was performed using both BHK and CHO cells and resulting DNA microarray data were analyzed using a filtering criteria of perfect match (PM)/single base mismatch (MM) > 1.5 and PM-MM > 50 to exclude probes with low specificity or sensitivity for cross-species hybridizations. For BHK cells, 8910 probe sets (39 %) passed the cutoff criteria, whereas 12,961 probe sets (56 %) passed the cutoff criteria for CHO cells. Yet, the data from BHK cells allowed distinct clustering of heat shock and control samples as well as identification of biologically relevant genes as being differentially expressed, indicating the utility of cross-species hybridization. Subsequently, DNA microarray analysis was performed on time course samples from laboratory- and manufacturing-scale perfusion bioreactors that were operated under the same conditions. A majority of the variability (37 %) was associated with the first principal component (PC-1). Although PC-1 changed monotonically with culture duration, the trends were very similar in both the laboratory and manufacturing-scale bioreactors. Therefore, despite time-related changes to the cell physiological state, transcriptomic fingerprints were similar across the two bioreactor scales at any given instance in culture. Multiple genes were identified with time-course expression profiles that were very highly correlated (> 0.9) with bioprocess variables of interest. Although the current incomplete annotation limits the biological interpretation of these observations, their full potential may be

  6. Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

    Science.gov (United States)

    Abbasalizadeh, Saeed; Baharvand, Hossein

    2013-12-01

    Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing. © 2013.

  7. MDL, Collineations and the Fundamental Matrix

    OpenAIRE

    Maybank , Steve; Sturm , Peter

    1999-01-01

    International audience; Scene geometry can be inferred from point correspondences between two images. The inference process includes the selection of a model. Four models are considered: background (or null), collineation, affine fundamental matrix and fundamental matrix. It is shown how Minimum Description Length (MDL) can be used to compare the different models. The main result is that there is little reason for preferring the fundamental matrix model over the collineation model, even when ...

  8. Heat pipes and solid sorption transformations fundamentals and practical applications

    CERN Document Server

    Vasiliev, LL

    2013-01-01

    Developing clean energy and utilizing waste energy has become increasingly vital. Research targeting the advancement of thermally powered adsorption cooling technologies has progressed in the past few decades, and the awareness of fuel cells and thermally activated (heat pipe heat exchangers) adsorption systems using natural refrigerants and/or alternatives to hydrofluorocarbon-based refrigerants is becoming ever more important. Heat Pipes and Solid Sorption Transformations: Fundamentals and Practical Applications concentrates on state-of-the-art adsorption research and technologies for releva

  9. Virtual and composite fundamentals in the ERM

    NARCIS (Netherlands)

    Knot, KHW; Sturm, JE

    1999-01-01

    A latent-variable approach is applied to identify the appropriate driving process for fundamental exchange rates in the ERM. From the time-series characteristics of so-called "virtual fundamentals" and "composite fundamentals", a significant degree of mean reversion can be asserted. The relative

  10. Fundamentals of Geophysics

    Science.gov (United States)

    Frohlich, Cliff

    Choosing an intermediate-level geophysics text is always problematic: What should we teach students after they have had introductory courses in geology, math, and physics, but little else? Fundamentals of Geophysics is aimed specifically at these intermediate-level students, and the author's stated approach is to construct a text “using abundant diagrams, a simplified mathematical treatment, and equations in which the student can follow each derivation step-by-step.” Moreover, for Lowrie, the Earth is round, not flat—the “fundamentals of geophysics” here are the essential properties of our Earth the planet, rather than useful techniques for finding oil and minerals. Thus this book is comparable in both level and approach to C. M. R. Fowler's The Solid Earth (Cambridge University Press, 1990).

  11. Fundamentals of continuum mechanics

    CERN Document Server

    Rudnicki, John W

    2014-01-01

    A concise introductory course text on continuum mechanics Fundamentals of Continuum Mechanics focuses on the fundamentals of the subject and provides the background for formulation of numerical methods for large deformations and a wide range of material behaviours. It aims to provide the foundations for further study, not just of these subjects, but also the formulations for much more complex material behaviour and their implementation computationally.  This book is divided into 5 parts, covering mathematical preliminaries, stress, motion and deformation, balance of mass, momentum and energ

  12. Pragmatic electrical engineering fundamentals

    CERN Document Server

    Eccles, William

    2011-01-01

    Pragmatic Electrical Engineering: Fundamentals introduces the fundamentals of the energy-delivery part of electrical systems. It begins with a study of basic electrical circuits and then focuses on electrical power. Three-phase power systems, transformers, induction motors, and magnetics are the major topics.All of the material in the text is illustrated with completely-worked examples to guide the student to a better understanding of the topics. This short lecture book will be of use at any level of engineering, not just electrical. Its goal is to provide the practicing engineer with a practi

  13. Fundamental investigations in the barite flotation using the radionuclide technique

    International Nuclear Information System (INIS)

    Schmitz, J.; Wiese, K.; Hunsinger, H.

    1977-01-01

    The application of radioactive tracers in flotation is described taking the example of barite/silicate separation in a mechanically improved laboratory cell. The particular suitability of the radionuclide technique is not only brought out in the field of fundamental investigations, but also in the determination of dynamic systems data. The labelling of the liquid phase was done with Na 24 whereas useful mineral and gangue were traced by means of neutron-induced double-labelling. The necessary labelling, measuring and evaluating technique is described. (orig.) [de

  14. Arithmetic fundamental groups and moduli of curves

    International Nuclear Information System (INIS)

    Makoto Matsumoto

    2000-01-01

    This is a short note on the algebraic (or sometimes called arithmetic) fundamental groups of an algebraic variety, which connects classical fundamental groups with Galois groups of fields. A large part of this note describes the algebraic fundamental groups in a concrete manner. This note gives only a sketch of the fundamental groups of the algebraic stack of moduli of curves. Some application to a purely topological statement, i.e., an obstruction to the subjectivity of Johnson homomorphisms in the mapping class groups, which comes from Galois group of Q, is explained. (author)

  15. Constant physics and characteristics of fundamental constant

    International Nuclear Information System (INIS)

    Tarrach, R.

    1998-01-01

    We present some evidence which supports a surprising physical interpretation of the fundamental constants. First, we relate two of them through the renormalization group. This leaves as many fundamental constants as base units. Second, we introduce and a dimensional system of units without fundamental constants. Third, and most important, we find, while interpreting the units of the a dimensional system, that is all cases accessible to experimentation the fundamental constants indicate either discretization at small values or boundedness at large values of the corresponding physical quantity. (Author) 12 refs

  16. Continuous volatile fatty acid production from lignocellulosic biomass by a novel rumen-mimetic bioprocess.

    Science.gov (United States)

    Agematu, Hitosi; Takahashi, Takehiko; Hamano, Yoshio

    2017-11-01

    Lignocellulosic biomass is an attractive source of biofuels and biochemicals, being abundant in various plant sources. However, processing this type of biomass requires hydrolysis of cellulose. The proposed rumen-mimetic bioprocess consists of dry-pulverization of lignocellulosic biomass and pH-controlled continuous cultivation of ruminal bacteria using ammonium as a nitrogen source. In this study, ruminal bacteria were continuously cultivated for over 60 days and used to digest microcrystalline cellulose, rice straw, and Japanese cedar to produce volatile fatty acids (VFAs). The ruminal bacteria grew well in the chemically defined medium. The amounts of VFAs produced from 20 g of cellulose, rice straw, and Japanese cedar were 183 ± 29.7, 69.6 ± 12.2, and 21.8 ± 12.9 mmol, respectively. Each digestion completed within 24 h. The carbon yield was 60.6% when 180 mmol of VFAs was produced from 20 g of cellulose. During the cultivation, the bacteria were observed to form flocs that enfolded the feed particles. These flocs likely contain all of the bacterial species necessary to convert lignocellulosic biomass to VFAs and microbial protein symbiotically. Denaturing gradient gel electrophoresis (DGGE) analysis of PCR-amplified 16S rDNA fragments revealed that the bacterial community was relatively stable after 1 week in cultivation, though it was different from the original community structure. Furthermore, sequence analysis of the DGGE bands indicates that the microbial community includes a cellulolytic bacterium, a bacterium acting synergistically with cellulolytic bacteria, and a propionate-producing bacterium, as well as other anaerobic bacteria. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Ion beam analysis fundamentals and applications

    CERN Document Server

    Nastasi, Michael; Wang, Yongqiang

    2015-01-01

    Ion Beam Analysis: Fundamentals and Applications explains the basic characteristics of ion beams as applied to the analysis of materials, as well as ion beam analysis (IBA) of art/archaeological objects. It focuses on the fundamentals and applications of ion beam methods of materials characterization.The book explains how ions interact with solids and describes what information can be gained. It starts by covering the fundamentals of ion beam analysis, including kinematics, ion stopping, Rutherford backscattering, channeling, elastic recoil detection, particle induced x-ray emission, and nucle

  18. Elastin-like polypeptides: the power of design for smart cell encapsulation.

    Science.gov (United States)

    Bandiera, Antonella

    2017-01-01

    Cell encapsulation technology is still a challenging issue. Innovative methodologies such as additive manufacturing, and alternative bioprocesses, such as cell therapeutic delivery, where cell encapsulation is a key tool are rapidly gaining importance for their potential in regenerative medicine. Responsive materials such as elastin-based recombinant expression products have features that are particularly attractive for cell encapsulation. They can be designed and tailored to meet desired requirements. Thus, they represent promising candidates for the development of new concept-based materials that can be employed in this field. Areas covered: An overview of the design and employment of elastin-like polypeptides for cell encapsulation is given to outline the state of the art. Special attention is paid to the design of the macromolecule employed as well as to the method of matrix formation and the biological system involved. Expert opinion: As a result of recent progress in regenerative medicine there is a compelling need for materials that provide specific properties and demonstrate defined functional features. Rationally designed materials that may adapt according to applied external stimuli and that are responsive to biological systems, such as elastin-like polypeptides, belong to this class of smart material. A run through the components described to date represents a good starting point for further advancement in this area. Employment of these components in cell encapsulation application will promote its advance toward 'smart cell encapsulation technology'.

  19. Different Variants of Fundamental Portfolio

    Directory of Open Access Journals (Sweden)

    Tarczyński Waldemar

    2014-06-01

    Full Text Available The paper proposes the fundamental portfolio of securities. This portfolio is an alternative for the classic Markowitz model, which combines fundamental analysis with portfolio analysis. The method’s main idea is based on the use of the TMAI1 synthetic measure and, in limiting conditions, the use of risk and the portfolio’s rate of return in the objective function. Different variants of fundamental portfolio have been considered under an empirical study. The effectiveness of the proposed solutions has been related to the classic portfolio constructed with the help of the Markowitz model and the WIG20 market index’s rate of return. All portfolios were constructed with data on rates of return for 2005. Their effectiveness in 2006- 2013 was then evaluated. The studied period comprises the end of the bull market, the 2007-2009 crisis, the 2010 bull market and the 2011 crisis. This allows for the evaluation of the solutions’ flexibility in various extreme situations. For the construction of the fundamental portfolio’s objective function and the TMAI, the study made use of financial and economic data on selected indicators retrieved from Notoria Serwis for 2005.

  20. An integrated bio-process for production of functional biomolecules utilizing raw and by-products from dairy and sugarcane industries.

    Science.gov (United States)

    Lata, Kusum; Sharma, Manisha; Patel, Satya Narayan; Sangwan, Rajender S; Singh, Sudhir P

    2018-04-21

    The study investigated an integrated bioprocessing of raw and by-products from sugarcane and dairy industries for production of non-digestible prebiotic and functional ingredients. The low-priced feedstock, whey, molasses, table sugar, jaggery, etc., were subjected to transglucosylation reactions catalyzed by dextransucrase from Leuconostoc mesenteroides MTCC 10508. HPLC analysis approximated production of about 11-14 g L -1 trisaccharide i.e. 2-α-D-glucopyranosyl-lactose (4-galactosyl-kojibiose) from the feedstock prepared from table sugar, jaggery, cane molasses and liquid whey, containing about 30 g L -1 sucrose and lactose each. The trisaccharide was hydrolysed into the prebiotic disaccharide, kojibiose, by employing recombinant β-galactosidase from Escherichia coli. The enzyme β-galactosidase achieved about 90% conversion of 2-α-D-glucopyranosyl-lactose into kojibiose. The D-fructose generated by catalytic reactions of dextransucrase was targeted for catalytic transformation into rare sugar, D-allulose (or D-psicose), by treating the samples with Smt3-D-psicose 3-epimerase. The catalytic reactions resulted in the conversion of ~ 25% D-fructose to D-allulose. These bioactive compounds are known to exert a plethora of benefits to human health, and therefore, are preferred ingredients for making functional foods.

  1. Fundamentals of piping design

    CERN Document Server

    Smith, Peter

    2013-01-01

    Written for the piping engineer and designer in the field, this two-part series helps to fill a void in piping literature,since the Rip Weaver books of the '90s were taken out of print at the advent of the Computer Aid Design(CAD) era. Technology may have changed, however the fundamentals of piping rules still apply in the digitalrepresentation of process piping systems. The Fundamentals of Piping Design is an introduction to the designof piping systems, various processes and the layout of pipe work connecting the major items of equipment forthe new hire, the engineering student and the vetera

  2. Automated Cell Enrichment of Cytomegalovirus-specific T cells for Clinical Applications using the Cytokine-capture System.

    Science.gov (United States)

    Kumaresan, Pappanaicken; Figliola, Mathew; Moyes, Judy S; Huls, M Helen; Tewari, Priti; Shpall, Elizabeth J; Champlin, Richard; Cooper, Laurence J N

    2015-10-05

    The adoptive transfer of pathogen-specific T cells can be used to prevent and treat opportunistic infections such as cytomegalovirus (CMV) infection occurring after allogeneic hematopoietic stem-cell transplantation. Viral-specific T cells from allogeneic donors, including third party donors, can be propagated ex vivo in compliance with current good manufacturing practice (cGMP), employing repeated rounds of antigen-driven stimulation to selectively propagate desired T cells. The identification and isolation of antigen-specific T cells can also be undertaken based upon the cytokine capture system of T cells that have been activated to secrete gamma-interferon (IFN-γ). However, widespread human application of the cytokine capture system (CCS) to help restore immunity has been limited as the production process is time-consuming and requires a skilled operator. The development of a second-generation cell enrichment device such as CliniMACS Prodigy now enables investigators to generate viral-specific T cells using an automated, less labor-intensive system. This device separates magnetically labeled cells from unlabeled cells using magnetic activated cell sorting technology to generate clinical-grade products, is engineered as a closed system and can be accessed and operated on the benchtop. We demonstrate the operation of this new automated cell enrichment device to manufacture CMV pp65-specific T cells obtained from a steady-state apheresis product obtained from a CMV seropositive donor. These isolated T cells can then be directly infused into a patient under institutional and federal regulatory supervision. All the bio-processing steps including removal of red blood cells, stimulation of T cells, separation of antigen-specific T cells, purification, and washing are fully automated. Devices such as this raise the possibility that T cells for human application can be manufactured outside of dedicated good manufacturing practice (GMP) facilities and instead be produced

  3. Transporter engineering in biomass utilization by yeast.

    Science.gov (United States)

    Hara, Kiyotaka Y; Kobayashi, Jyumpei; Yamada, Ryosuke; Sasaki, Daisuke; Kuriya, Yuki; Hirono-Hara, Yoko; Ishii, Jun; Araki, Michihiro; Kondo, Akihiko

    2017-11-01

    Biomass resources are attractive carbon sources for bioproduction because of their sustainability. Many studies have been performed using biomass resources to produce sugars as carbon sources for cell factories. Expression of biomass hydrolyzing enzymes in cell factories is an important approach for constructing biomass-utilizing bioprocesses because external addition of these enzymes is expensive. In particular, yeasts have been extensively engineered to be cell factories that directly utilize biomass because of their manageable responses to many genetic engineering tools, such as gene expression, deletion and editing. Biomass utilizing bioprocesses have also been developed using these genetic engineering tools to construct metabolic pathways. However, sugar input and product output from these cells are critical factors for improving bioproduction along with biomass utilization and metabolic pathways. Transporters are key components for efficient input and output activities. In this review, we focus on transporter engineering in yeast to enhance bioproduction from biomass resources. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Concise Review: Microfluidic Technology Platforms: Poised to Accelerate Development and Translation of Stem Cell-Derived Therapies

    Science.gov (United States)

    Titmarsh, Drew M.; Chen, Huaying; Glass, Nick R.; Cooper-White, Justin J.

    2014-01-01

    Stem cells are a powerful resource for producing a variety of cell types with utility in clinically associated applications, including preclinical drug screening and development, disease and developmental modeling, and regenerative medicine. Regardless of the type of stem cell, substantial barriers to clinical translation still exist and must be overcome to realize full clinical potential. These barriers span processes including cell isolation, expansion, and differentiation; purification, quality control, and therapeutic efficacy and safety; and the economic viability of bioprocesses for production of functional cell products. Microfluidic systems have been developed for a myriad of biological applications and have the intrinsic capability of controlling and interrogating the cellular microenvironment with unrivalled precision; therefore, they have particular relevance to overcoming such barriers to translation. Development of microfluidic technologies increasingly utilizes stem cells, addresses stem cell-relevant biological phenomena, and aligns capabilities with translational challenges and goals. In this concise review, we describe how microfluidic technologies can contribute to the translation of stem cell research outcomes, and we provide an update on innovative research efforts in this area. This timely convergence of stem cell translational challenges and microfluidic capabilities means that there is now an opportunity for both disciplines to benefit from increased interaction. PMID:24311699

  5. Thermotolerant Kluyveromyces marxianus and Saccharomyces cerevisiae strains representing potentials for bioethanol production from Jerusalem artichoke by consolidated bioprocessing.

    Science.gov (United States)

    Hu, Nan; Yuan, Bo; Sun, Juan; Wang, Shi-An; Li, Fu-Li

    2012-09-01

    Thermotolerant inulin-utilizing yeast strains are desirable for ethanol production from Jerusalem artichoke tubers by consolidated bioprocessing (CBP). To obtain such strains, 21 naturally occurring yeast strains isolated by using an enrichment method and 65 previously isolated Saccharomyces cerevisiae strains were investigated in inulin utilization, extracellular inulinase activity, and ethanol fermentation from inulin and Jerusalem artichoke tuber flour at 40 °C. The strains Kluyveromyces marxianus PT-1 (CGMCC AS2.4515) and S. cerevisiae JZ1C (CGMCC AS2.3878) presented the highest extracellular inulinase activity and ethanol yield in this study. The highest ethanol concentration in Jerusalem artichoke tuber flour fermentation (200 g L(-1)) at 40 °C achieved by K. marxianus PT-1 and S. cerevisiae JZ1C was 73.6 and 65.2 g L(-1), which corresponded to the theoretical ethanol yield of 90.0 and 79.7 %, respectively. In the range of 30 to 40 °C, temperature did not have a significant effect on ethanol production for both strains. This study displayed the distinctive superiority of K. marxianus PT-1 and S. cerevisiae JZ1C in the thermotolerance and utilization of inulin-type oligosaccharides reserved in Jerusalem artichoke tubers. It is proposed that both K. marxianus and S. cerevisiae have considerable potential in ethanol production from Jerusalem artichoke tubers by a high temperature CBP.

  6. Thermotolerant Kluyveromyces marxianus and Saccharomyces cerevisiae strains representing potentials for bioethanol production from Jerusalem artichoke by consolidated bioprocessing

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Nan [Agricultural Univ., Qingdao, SD (China). College of Animal Science and Technology; Chinese Academy of Sciences, Qingdao, SD (China). Key Lab. of Biofuels; Yuan, Bo; Wang, Shi-An; Li, Fu-Li [Chinese Academy of Sciences, Qingdao, SD (China). Key Lab. of Biofuels; Sun, Juan [Agricultural Univ., Qingdao, SD (China). College of Animal Science and Technology

    2012-09-15

    Thermotolerant inulin-utilizing yeast strains are desirable for ethanol production from Jerusalem artichoke tubers by consolidated bioprocessing (CBP). To obtain such strains, 21 naturally occurring yeast strains isolated by using an enrichment method and 65 previously isolated Saccharomyces cerevisiae strains were investigated in inulin utilization, extracellular inulinase activity, and ethanol fermentation from inulin and Jerusalem artichoke tuber flour at 40 C. The strains Kluyveromyces marxianus PT-1 (CGMCC AS2.4515) and S. cerevisiae JZ1C (CGMCC AS2.3878) presented the highest extracellular inulinase activity and ethanol yield in this study. The highest ethanol concentration in Jerusalem artichoke tuber flour fermentation (200 g L{sup -1}) at 40 C achieved by K. marxianus PT-1 and S. cerevisiae JZ1C was 73.6 and 65.2 g L{sup -1}, which corresponded to the theoretical ethanol yield of 90.0 and 79.7 %, respectively. In the range of 30 to 40 C, temperature did not have a significant effect on ethanol production for both strains. This study displayed the distinctive superiority of K. marxianus PT-1 and S. cerevisiae JZ1C in the thermotolerance and utilization of inulin-type oligosaccharides reserved in Jerusalem artichoke tubers. It is proposed that both K. marxianus and S. cerevisiae have considerable potential in ethanol production from Jerusalem artichoke tubers by a high temperature CBP. (orig.)

  7. Proposed experiment to test fundamentally binary theories

    Science.gov (United States)

    Kleinmann, Matthias; Vértesi, Tamás; Cabello, Adán

    2017-09-01

    Fundamentally binary theories are nonsignaling theories in which measurements of many outcomes are constructed by selecting from binary measurements. They constitute a sensible alternative to quantum theory and have never been directly falsified by any experiment. Here we show that fundamentally binary theories are experimentally testable with current technology. For that, we identify a feasible Bell-type experiment on pairs of entangled qutrits. In addition, we prove that, for any n , quantum n -ary correlations are not fundamentally (n -1 ) -ary. For that, we introduce a family of inequalities that hold for fundamentally (n -1 ) -ary theories but are violated by quantum n -ary correlations.

  8. Fundamentals of electronic image processing

    CERN Document Server

    Weeks, Arthur R

    1996-01-01

    This book is directed to practicing engineers and scientists who need to understand the fundamentals of image processing theory and algorithms to perform their technical tasks. It is intended to fill the gap between existing high-level texts dedicated to specialists in the field and the need for a more practical, fundamental text on image processing. A variety of example images are used to enhance reader understanding of how particular image processing algorithms work.

  9. Qualitative insights on fundamental mechanics

    OpenAIRE

    Mardari, G. N.

    2002-01-01

    The gap between classical mechanics and quantum mechanics has an important interpretive implication: the Universe must have an irreducible fundamental level, which determines the properties of matter at higher levels of organization. We show that the main parameters of any fundamental model must be theory-independent. They cannot be predicted, because they cannot have internal causes. However, it is possible to describe them in the language of classical mechanics. We invoke philosophical reas...

  10. Homeschooling and religious fundamentalism

    Directory of Open Access Journals (Sweden)

    Robert Kunzman

    2010-10-01

    Full Text Available This article considers the relationship between homeschooling and religious fundamentalism by focusing on their intersection in the philosophies and practices of conservative Christian homeschoolers in the United States. Homeschooling provides an ideal educational setting to support several core fundamentalist principles: resistance to contemporary culture; suspicion of institutional authority and professional expertise; parental control and centrality of the family; and interweaving of faith and academics. It is important to recognize, however, that fundamentalism exists on a continuum; conservative religious homeschoolers resist liberal democratic values to varying degrees, and efforts to foster dialogue and accommodation with religious homeschoolers can ultimately help strengthen the broader civic fabric.

  11. Fundamental Perspectives on Supply Chain Management

    NARCIS (Netherlands)

    Omta, S.W.F.; Hoenen, S.J.

    2012-01-01

    The aim of the present literature study is to find the fundamental perspectives/models in the realm of supply chain management and to investigate whether they can be extended based on recent literature findings. The fundamental perspectives were found using a two-tier snowball collection method,

  12. EU criminal law and fundamental rights

    NARCIS (Netherlands)

    de Hert, Paul; Mitsilegas, V.; Bergström, M.; Konstadinides, Th.

    2016-01-01

    The chapter first offers a background analysis to EU fundamental rights law, recalling the historical affirmation of the protection of fundamental rights as a EU concern, and the important innovation brought about by the Lisbon Treaty (section 2) and the multiplicity of actors involved in the system

  13. Fundamental symmetries and interactions-selected topics

    NARCIS (Netherlands)

    Jungmann, Klaus P.

    2015-01-01

    In the field of fundamental interactions and symmetries numerous experiments are underway or planned in order to verify the standard model in particle physics, to search for possible extensions to it or to exploit the standard model for extracting most precise values for fundamental constants. We

  14. Fundamental partial compositeness

    DEFF Research Database (Denmark)

    Sannino, Francesco; Strumia, Alessandro; Tesi, Andrea

    2016-01-01

    We construct renormalizable Standard Model extensions, valid up to the Planck scale, that give a composite Higgs from a new fundamental strong force acting on fermions and scalars. Yukawa interactions of these particles with Standard Model fermions realize the partial compositeness scenario. Unde...

  15. Plasmon assisted optical trapping: fundamentals and biomedical applications

    Science.gov (United States)

    Serafetinides, Alexandros A.; Makropoulou, Mersini; Tsigaridas, Georgios N.; Gousetis, Anastasios

    2015-01-01

    The field of optical trapping has dramatically grown due to implementation in various arenas including physics, biology, medicine and nanotechnology. Certainly, optical tweezers are an invaluable tool to manipulate a variation of particles, such as small dielectric spheres, cells, bacteria, chromosomes and even genes, by highly focused laser beams through microscope. As the main disadvantage of the conventional optical trapping systems is the diffraction limit of the incident light, plasmon assisted nanotrapping is reported as a suitable technique for trapping sub-wavelength metallic or dielectric particles. In this work, firstly, we report briefly on the basic theory of plasmon excitation, focusing on the interaction of nanoscale metallic structures with laser light. Secondly, experimental and numerical simulation results are also presented, demonstrating enhancement of the trapping efficiency of glass or SiO2 substrates, coated with Au and Ag nanostructures, with or without nanoparticles. The optical forces were calculated by measuring the particle's escape velocity calibration method. Finally, representative applications of plasmon assisted optical trapping are reviewed, from cancer therapeutics to fundamental biology and cell nanosurgery.

  16. Exploring continuous and integrated strategies for the up- and downstream processing of human mesenchymal stem cells.

    Science.gov (United States)

    Cunha, Bárbara; Aguiar, Tiago; Silva, Marta M; Silva, Ricardo J S; Sousa, Marcos F Q; Pineda, Earl; Peixoto, Cristina; Carrondo, Manuel J T; Serra, Margarida; Alves, Paula M

    2015-11-10

    The integration of up- and downstream unit operations can result in the elimination of hold steps, thus decreasing the footprint, and ultimately can create robust closed system operations. This type of design is desirable for the bioprocess of human mesenchymal stem cells (hMSC), where high numbers of pure cells, at low volumes, need to be delivered for therapy applications. This study reports a proof of concept of the integration of a continuous perfusion culture in bioreactors with a tangential flow filtration (TFF) system for the concentration and washing of hMSC. Moreover, we have also explored a continuous alternative for concentrating hMSC. Results show that expanding cells in a continuous perfusion operation mode provided a higher expansion ratio, and led to a shift in cells' metabolism. TFF operated either in continuous or discontinuous allowed to concentrate cells, with high cell recovery (>80%) and viability (>95%); furthermore, continuous TFF permitted to operate longer with higher cell concentrations. Continuous diafiltration led to higher protein clearance (98%) with lower cell death, when comparing to discontinuous diafiltration. Overall, an integrated process allowed for a shorter process time, recovering 70% of viable hMSC (>95%), with no changes in terms of morphology, immunophenotype, proliferation capacity and multipotent differentiation potential. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Heterologous Expression of Plant Cell Wall Degrading Enzymes for Effective Production of Cellulosic Biofuels

    Science.gov (United States)

    Jung, Sang-Kyu; Parisutham, Vinuselvi; Jeong, Seong Hun; Lee, Sung Kuk

    2012-01-01

    A major technical challenge in the cost-effective production of cellulosic biofuel is the need to lower the cost of plant cell wall degrading enzymes (PCDE), which is required for the production of sugars from biomass. Several competitive, low-cost technologies have been developed to produce PCDE in different host organisms such as Escherichia coli, Zymomonas mobilis, and plant. Selection of an ideal host organism is very important, because each host organism has its own unique features. Synthetic biology-aided tools enable heterologous expression of PCDE in recombinant E. coli or Z. mobilis and allow successful consolidated bioprocessing (CBP) in these microorganisms. In-planta expression provides an opportunity to simplify the process of enzyme production and plant biomass processing and leads to self-deconstruction of plant cell walls. Although the future of currently available technologies is difficult to predict, a complete and viable platform will most likely be available through the integration of the existing approaches with the development of breakthrough technologies. PMID:22911272

  18. NMR methods for the investigation of structure and transport

    CERN Document Server

    Hardy, Edme H

    2011-01-01

    Methods of nuclear magnetic resonance (NMR) are increasingly applied in engineering sciences. The book summarizes research in the field of chemical and process engineering performed at the Karlsruhe Institute of Technology (KIT). Fundamentals of the methods are exposed for readers with an engineering background. Applications cover the fields of mechanical process engineering (filtration, solid-liquid separation, powder mixing, rheometry), chemical process engineering (trickle-bed reactor, ceramic sponges), bioprocess engineering (biofilm growth), and food process engineering (microwave heating

  19. Fundamental physics in particle traps

    International Nuclear Information System (INIS)

    Quint, Wolfgang; Vogel, Manuel

    2014-01-01

    The individual topics are covered by leading experts in the respective fields of research. Provides readers with present theory and experiments in this field. A useful reference for researchers. This volume provides detailed insight into the field of precision spectroscopy and fundamental physics with particles confined in traps. It comprises experiments with electrons and positrons, protons and antiprotons, antimatter and highly charged ions, together with corresponding theoretical background. Such investigations represent stringent tests of quantum electrodynamics and the Standard model, antiparticle and antimatter research, test of fundamental symmetries, constants, and their possible variations with time and space. They are key to various aspects within metrology such as mass measurements and time standards, as well as promising to further developments in quantum information processing. The reader obtains a valuable source of information suited for beginners and experts with an interest in fundamental studies using particle traps.

  20. 33 CFR 86.03 - Limits of fundamental frequencies.

    Science.gov (United States)

    2010-07-01

    ... of fundamental frequencies. To ensure a wide variety of whistle characteristics, the fundamental... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Limits of fundamental frequencies. 86.03 Section 86.03 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY...

  1. Continuous downstream processing for high value biological products: A Review.

    Science.gov (United States)

    Zydney, Andrew L

    2016-03-01

    There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations. © 2015 Wiley Periodicals, Inc.

  2. What is Fundamental?

    CERN Multimedia

    2004-01-01

    Discussing what is fundamental in a variety of fields, biologist Richard Dawkins, physicist Gerardus 't Hooft, and mathematician Alain Connes spoke to a packed Main Auditorium at CERN 15 October. Dawkins, Professor of the Public Understanding of Science at Oxford University, explained simply the logic behind Darwinian natural selection, and how it would seem to apply anywhere in the universe that had the right conditions. 't Hooft, winner of the 1999 Physics Nobel Prize, outlined some of the main problems in physics today, and said he thinks physics is so fundamental that even alien scientists from another planet would likely come up with the same basic principles, such as relativity and quantum mechanics. Connes, winner of the 1982 Fields Medal (often called the Nobel Prize of Mathematics), explained how physics is different from mathematics, which he described as a "factory for concepts," unfettered by connection to the physical world. On 16 October, anthropologist Sharon Traweek shared anecdotes from her ...

  3. Fundamentals of reactor chemistry

    International Nuclear Information System (INIS)

    Akatsu, Eiko

    1981-12-01

    In the Nuclear Engineering School of JAERI, many courses are presented for the people working in and around the nuclear reactors. The curricula of the courses contain also the subject material of chemistry. With reference to the foreign curricula, a plan of educational subject material of chemistry in the Nuclear Engineering School of JAERI was considered, and the fundamental part of reactor chemistry was reviewed in this report. Since the students of the Nuclear Engineering School are not chemists, the knowledge necessary in and around the nuclear reactors was emphasized in order to familiarize the students with the reactor chemistry. The teaching experience of the fundamentals of reactor chemistry is also given. (author)

  4. Fundamentals of electro-engineering I

    International Nuclear Information System (INIS)

    Rapsik, M.; Smola, M.; Bohac, M.; Mucha, M.

    2004-01-01

    This is the text-book of the fundamentals of electro-engineering. It contains the following chapters: (1) Selected terms in electro-engineering; (2) Fundamental electric values; (3) Energy and their transformations; (4) Water, hydro-energy and hydro-energetic potential of the Slovak Republic; (5) Nuclear power engineering; (6) Conventional thermal power plants; (7) Heating and cogeneration of electric power and heat production; (8) Equipment of electricity supply system; (9) Measurements in electro-engineering ; (10) Regulation of frequency and voltage, electric power quality

  5. Value of Fundamental Science

    Science.gov (United States)

    Burov, Alexey

    Fundamental science is a hard, long-term human adventure that has required high devotion and social support, especially significant in our epoch of Mega-science. The measure of this devotion and this support expresses the real value of the fundamental science in public opinion. Why does fundamental science have value? What determines its strength and what endangers it? The dominant answer is that the value of science arises out of curiosity and is supported by the technological progress. Is this really a good, astute answer? When trying to attract public support, we talk about the ``mystery of the universe''. Why do these words sound so attractive? What is implied by and what is incompatible with them? More than two centuries ago, Immanuel Kant asserted an inseparable entanglement between ethics and metaphysics. Thus, we may ask: which metaphysics supports the value of scientific cognition, and which does not? Should we continue to neglect the dependence of value of pure science on metaphysics? If not, how can this issue be addressed in the public outreach? Is the public alienated by one or another message coming from the face of science? What does it mean to be politically correct in this sort of discussion?

  6. Temperature dependence of the hydrogen-broadening coefficient for the nu 9 fundamental of ethane

    Science.gov (United States)

    Halsey, G. W.; Hillman, J. J.; Nadler, Shacher; Jennings, D. E.

    1988-01-01

    Experimental results for the temperature dependence of the H2-broadening coefficient for the nu 9 fundamental of ethane are reported. Measurements were made over the temperature range 95-300 K using a novel low-temperature absorption cell. These spectra were recorded with the Doppler-limited diode laser spectrometer at NASA Goddard. The results are compared with recent measurements and model predictions.

  7. Introduction and fundamentals

    International Nuclear Information System (INIS)

    Thomas, R.H.

    1980-01-01

    This introduction discusses advances in the fundamental sciences which underlie the applied science of health physics and radiation protection. Risk assessments in nuclear medicine are made by defining the conditions of exposure, identification of adverse effects, relating exposure with effect, and estimation of the overall risk for ionizing radiations

  8. Fundamentals of astrodynamics

    NARCIS (Netherlands)

    Wakker, K.F.

    2015-01-01

    This book deals with the motion of the center of mass of a spacecraft; this discipline is generally called astrodynamics. The book focuses on an analytical treatment of the motion of spacecraft and provides insight into the fundamentals of spacecraft orbit dynamics. A large number of topics are

  9. FUNDAMENTALS OF BIOMECHANICS

    Directory of Open Access Journals (Sweden)

    Duane Knudson

    2007-09-01

    Full Text Available DESCRIPTION This book provides a broad and in-depth theoretical and practical description of the fundamental concepts in understanding biomechanics in the qualitative analysis of human movement. PURPOSE The aim is to bring together up-to-date biomechanical knowledge with expert application knowledge. Extensive referencing for students is also provided. FEATURES This textbook is divided into 12 chapters within four parts, including a lab activities section at the end. The division is as follows: Part 1 Introduction: 1.Introduction to biomechanics of human movement; 2.Fundamentals of biomechanics and qualitative analysis; Part 2 Biological/Structural Bases: 3.Anatomical description and its limitations; 4.Mechanics of the musculoskeletal system; Part 3 Mechanical Bases: 5.Linear and angular kinematics; 6.Linear kinetics; 7.Angular kinetics; 8.Fluid mechanics; Part 4 Application of Biomechanics in Qualitative Analysis :9.Applying biomechanics in physical education; 10.Applying biomechanics in coaching; 11.Applying biomechanics in strength and conditioning; 12.Applying biomechanics in sports medicine and rehabilitation. AUDIENCE This is an important reading for both student and educators in the medicine, sport and exercise-related fields. For the researcher and lecturer it would be a helpful guide to plan and prepare more detailed experimental designs or lecture and/or laboratory classes in exercise and sport biomechanics. ASSESSMENT The text provides a constructive fundamental resource for biomechanics, exercise and sport-related students, teachers and researchers as well as anyone interested in understanding motion. It is also very useful since being clearly written and presenting several ways of examples of the application of biomechanics to help teach and apply biomechanical variables and concepts, including sport-related ones

  10. Femtosecond UV-laser pulses to unveil protein-protein interactions in living cells.

    Science.gov (United States)

    Itri, Francesco; Monti, Daria M; Della Ventura, Bartolomeo; Vinciguerra, Roberto; Chino, Marco; Gesuele, Felice; Lombardi, Angelina; Velotta, Raffaele; Altucci, Carlo; Birolo, Leila; Piccoli, Renata; Arciello, Angela

    2016-02-01

    A hallmark to decipher bioprocesses is to characterize protein-protein interactions in living cells. To do this, the development of innovative methodologies, which do not alter proteins and their natural environment, is particularly needed. Here, we report a method (LUCK, Laser UV Cross-linKing) to in vivo cross-link proteins by UV-laser irradiation of living cells. Upon irradiation of HeLa cells under controlled conditions, cross-linked products of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were detected, whose yield was found to be a linear function of the total irradiation energy. We demonstrated that stable dimers of GAPDH were formed through intersubunit cross-linking, as also observed when the pure protein was irradiated by UV-laser in vitro. We proposed a defined patch of aromatic residues located at the enzyme subunit interface as the cross-linking sites involved in dimer formation. Hence, by this technique, UV-laser is able to photofix protein surfaces that come in direct contact. Due to the ultra-short time scale of UV-laser-induced cross-linking, this technique could be extended to weld even transient protein interactions in their native context.

  11. Fundamentals of multicore software development

    CERN Document Server

    Pankratius, Victor; Tichy, Walter F

    2011-01-01

    With multicore processors now in every computer, server, and embedded device, the need for cost-effective, reliable parallel software has never been greater. By explaining key aspects of multicore programming, Fundamentals of Multicore Software Development helps software engineers understand parallel programming and master the multicore challenge. Accessible to newcomers to the field, the book captures the state of the art of multicore programming in computer science. It covers the fundamentals of multicore hardware, parallel design patterns, and parallel programming in C++, .NET, and Java. It

  12. The fundamental interactions of matter

    International Nuclear Information System (INIS)

    Falla, D.F.

    1977-01-01

    Elementary particles are here discussed, in the context of the extent to which the fundamental interactions are related to the elementary constituents of matter. The field quanta related to the four fundamental interactions (electromagnetic, strong,weak and gravitational) are discussed within an historical context beginning with the conception of the photon. The discovery of the mesons and discoveries relevant to the nature of the heavy vector boson are considered. Finally a few recent speculations on the properties of the graviton are examined. (U.K.)

  13. Fundamental Issues in Manufacturing Photovoltaic Modules Beyond the Current Generation of Materials

    Directory of Open Access Journals (Sweden)

    G. F. Alapatt

    2012-01-01

    Full Text Available Many methods to improve the solar cell’s efficiency beyond current generation of bulk and thin film of photovoltaic (PV devices have been reported during the last five decades. Concepts such as multiple exciton generations (MEG, carrier multiplication (CM, hot carrier extraction, and intermediate band solar cells have fundamental flaws, and there is no experimental evidence of fabricating practical higher efficiency solar cells based on the proposed concepts. To take advantages of quantum features of nanostructures for higher performance PV devices, self-assembly-based bottom-up processing techniques are not suitable for manufacturing due to inherent problems of variability, defects, reliability, and yield. For processing nanostructures, new techniques need to be invented with the features of critical dimensional control, structural homogeneity, and lower cost of ownership as compared to the processing tools used in current generations of bulk and thin-film solar cells.

  14. O DIREITO FUNDAMENTAL AO DESENVOLVIMENTO SUSTENTÁVEL

    OpenAIRE

    Fernandes, Jeferson Nogueira

    2012-01-01

    Este artigo jurídico trata do direito fundamental do ser humano ter um desenvolvimento sustentável, e tem como objetivo identificar o desenvolvimento sustentável como sendo um direito fundamental consagrado universalmente. Em sua elaboração foi utilizado o seguinte material: textos doutrinários, legislação nacional pertinente e documentos internacionais. A conclusão indica que: o desenvolvimento sustentável é um direito fundamental do homem e que devemos manter equilibrada a relação ambiente ...

  15. RFID design fundamentals and applications

    CERN Document Server

    Lozano-Nieto, Albert

    2010-01-01

    RFID is an increasingly pervasive tool that is now used in a wide range of fields. It is employed to substantiate adherence to food preservation and safety standards, combat the circulation of counterfeit pharmaceuticals, and verify authenticity and history of critical parts used in aircraft and other machinery-and these are just a few of its uses. Goes beyond deployment, focusing on exactly how RFID actually worksRFID Design Fundamentals and Applications systematically explores the fundamental principles involved in the design and characterization of RFID technologies. The RFID market is expl

  16. Astrophysical probes of fundamental physics

    International Nuclear Information System (INIS)

    Martins, C.J.A.P.

    2009-01-01

    I review the motivation for varying fundamental couplings and discuss how these measurements can be used to constrain fundamental physics scenarios that would otherwise be inaccessible to experiment. I highlight the current controversial evidence for varying couplings and present some new results. Finally I focus on the relation between varying couplings and dark energy, and explain how varying coupling measurements might be used to probe the nature of dark energy, with some advantages over standard methods. In particular I discuss what can be achieved with future spectrographs such as ESPRESSO and CODEX.

  17. Astrophysical probes of fundamental physics

    Energy Technology Data Exchange (ETDEWEB)

    Martins, C.J.A.P. [Centro de Astrofisica, Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); DAMTP, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom)

    2009-10-15

    I review the motivation for varying fundamental couplings and discuss how these measurements can be used to constrain fundamental physics scenarios that would otherwise be inaccessible to experiment. I highlight the current controversial evidence for varying couplings and present some new results. Finally I focus on the relation between varying couplings and dark energy, and explain how varying coupling measurements might be used to probe the nature of dark energy, with some advantages over standard methods. In particular I discuss what can be achieved with future spectrographs such as ESPRESSO and CODEX.

  18. Qualitative insights on fundamental mechanics

    International Nuclear Information System (INIS)

    Mardari, Ghenadie N

    2007-01-01

    The gap between classical mechanics and quantum mechanics has an important interpretive implication: the Universe must have an irreducible fundamental level, which determines the properties of matter at higher levels of organization. We show that the main parameters of any fundamental model must be theory-independent. Moreover, such models must also contain discrete identical entities with constant properties. These conclusions appear to support the work of Kaniadakis on subquantum mechanics. A qualitative analysis is offered to suggest compatibility with relevant phenomena, as well as to propose new means for verification

  19. The fundamentals of mathematical analysis

    CERN Document Server

    Fikhtengol'ts, G M

    1965-01-01

    The Fundamentals of Mathematical Analysis, Volume 1 is a textbook that provides a systematic and rigorous treatment of the fundamentals of mathematical analysis. Emphasis is placed on the concept of limit which plays a principal role in mathematical analysis. Examples of the application of mathematical analysis to geometry, mechanics, physics, and engineering are given. This volume is comprised of 14 chapters and begins with a discussion on real numbers, their properties and applications, and arithmetical operations over real numbers. The reader is then introduced to the concept of function, i

  20. Shareholders' Fundamental Rights in Listed Companies

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2017-01-01

    There can be no reasonable doubt that the EU’s initiatives in the field of shareholders’ fundamental rights in listed companies are among the successful, relevant and necessary provisions under EU corporate and stock exchange law. This also holds true for the main Directive 2007/36. When consider......There can be no reasonable doubt that the EU’s initiatives in the field of shareholders’ fundamental rights in listed companies are among the successful, relevant and necessary provisions under EU corporate and stock exchange law. This also holds true for the main Directive 2007/36. When...... considering the whole spirit and idea of the EU and its competences, the field of basic shareholders’ rights, including cross-border shareholding, is to be regarded as a welcome initiative that has facilitated the exercise of fundamental rights also in cross-border shareholding. The success is further...... emphasized by the fact that some countries, including Denmark, have regarded a number of the fundamental rights vested in the directive as being so well formulated that the countries have chosen to gold-plate their own legislation by introducing rights which are similar to those in the directive also for non...

  1. Default Bayesian Estimation of the Fundamental Frequency

    DEFF Research Database (Denmark)

    Nielsen, Jesper Kjær; Christensen, Mads Græsbøll; Jensen, Søren Holdt

    2013-01-01

    Joint fundamental frequency and model order esti- mation is an important problem in several applications. In this paper, a default estimation algorithm based on a minimum of prior information is presented. The algorithm is developed in a Bayesian framework, and it can be applied to both real....... Moreover, several approximations of the posterior distributions on the fundamental frequency and the model order are derived, and one of the state-of-the-art joint fundamental frequency and model order estimators is demonstrated to be a special case of one of these approximations. The performance...

  2. On the importance of identifying, characterizing, and predicting fundamental phenomena towards microbial electrochemistry applications.

    Science.gov (United States)

    Torres, César Iván

    2014-06-01

    The development of microbial electrochemistry research toward technological applications has increased significantly in the past years, leading to many process configurations. This short review focuses on the need to identify and characterize the fundamental phenomena that control the performance of microbial electrochemical cells (MXCs). Specifically, it discusses the importance of recent efforts to discover and characterize novel microorganisms for MXC applications, as well as recent developments to understand transport limitations in MXCs. As we increase our understanding of how MXCs operate, it is imperative to continue modeling efforts in order to effectively predict their performance, design efficient MXC technologies, and implement them commercially. Thus, the success of MXC technologies largely depends on the path of identifying, understanding, and predicting fundamental phenomena that determine MXC performance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Mining manufacturing data for discovery of high productivity process characteristics.

    Science.gov (United States)

    Charaniya, Salim; Le, Huong; Rangwala, Huzefa; Mills, Keri; Johnson, Kevin; Karypis, George; Hu, Wei-Shou

    2010-06-01

    Modern manufacturing facilities for bioproducts are highly automated with advanced process monitoring and data archiving systems. The time dynamics of hundreds of process parameters and outcome variables over a large number of production runs are archived in the data warehouse. This vast amount of data is a vital resource to comprehend the complex characteristics of bioprocesses and enhance production robustness. Cell culture process data from 108 'trains' comprising production as well as inoculum bioreactors from Genentech's manufacturing facility were investigated. Each run constitutes over one-hundred on-line and off-line temporal parameters. A kernel-based approach combined with a maximum margin-based support vector regression algorithm was used to integrate all the process parameters and develop predictive models for a key cell culture performance parameter. The model was also used to identify and rank process parameters according to their relevance in predicting process outcome. Evaluation of cell culture stage-specific models indicates that production performance can be reliably predicted days prior to harvest. Strong associations between several temporal parameters at various manufacturing stages and final process outcome were uncovered. This model-based data mining represents an important step forward in establishing a process data-driven knowledge discovery in bioprocesses. Implementation of this methodology on the manufacturing floor can facilitate a real-time decision making process and thereby improve the robustness of large scale bioprocesses. 2010 Elsevier B.V. All rights reserved.

  4. Unified composite model of all fundamental particles and forces

    International Nuclear Information System (INIS)

    Terazawa, H.

    2000-01-01

    The unified supersymmetric composite model of all fundamental particles (and forces) including not only the fundamental fermions (quarks and leptons) but also the fundamental bosons (gauge bosons and Higgs scalars) is reviewed in detail

  5. The Fundamental Principle of Human Dignity and the Right to Life : Collision Any of These Fundamental Principles The Perspective of Abortion

    Directory of Open Access Journals (Sweden)

    Érika do Amaral Véras

    2016-12-01

    Full Text Available This legal article works the theme of the collision of the fundamental principles, especially the principle of human dignity and the right to life, abortion perspective. First, we discuss of fundamental rights, bringing its definition, observed the distinction between human rights and fundamental rights. Then the super principle of human dignity is covered and, soon after, the right to life is highlighted through its relevant elements. Finally, talks on a possible collision beween the fundamental right to life and the principle of human dignity, with a special focus on the issue of abortion.

  6. 48 CFR 9904.416-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement..., OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.416-40 Fundamental requirement. (a) The amount of...

  7. 48 CFR 9904.413-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement..., OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.413-40 Fundamental requirement. (a) Assignment of...

  8. 48 CFR 9904.417-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.417-40 Fundamental requirement. The cost of money applicable to the investment in tangible and intangible capital assets being constructed, fabricated, or...

  9. 48 CFR 9905.501-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.501-40 Fundamental... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9905.501-40 Section 9905.501-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  10. 48 CFR 9905.502-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.502-40 Fundamental... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9905.502-40 Section 9905.502-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  11. 48 CFR 9905.506-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS FOR EDUCATIONAL INSTITUTIONS 9905.506-40 Fundamental... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9905.506-40 Section 9905.506-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  12. Mapping the Fundamental Niches of Two Freshwater Microalgae, Chlorella vulgaris (Trebouxiophyceae and Peridinium cinctum (Dinophyceae, in 5-Dimensional Ion Space

    Directory of Open Access Journals (Sweden)

    Terence J. Evens

    2011-01-01

    Full Text Available The fundamental niche defined by five ions, NO3 −, PO4 3−, K+, Na+, and Cl−, was mapped for Chlorella vulgaris (Trebouxiophyceae and Peridinium cinctum (Dinophyceae growth rates and maximum cell densities in batch cultures. A five dimensional ion-mixture experimental design was projected across a total ion concentration gradient of 1 to 30 mM to delineate the ion-based, “potential” niche space, defined as the entire n-dimensional hypervolume demarcated by the feasible ranges of the independent factors under consideration. The growth rate-based, fundamental niche volumes overlapped for ca. 94% of the ion mixtures, although the regions of maximal growth rates and cell densities were different for each alga. Both C. vulgaris and P. cinctum exhibited similar positive responses to cations and negative responses to anions. It was determined that total ion concentration for these five ions, from 1 to 30 mM, did not directly affect either growth rate or maximal cell density for either alga, although it did play an interactive role with several ions. This study is the first that we are aware of to attempt the mapping of a multivariate, ion-based, fundamental niche volume. The implications of the experimental design utilized and the potential utility of this type of approach are discussed.

  13. A Kalman-based Fundamental Frequency Estimation Algorithm

    DEFF Research Database (Denmark)

    Shi, Liming; Nielsen, Jesper Kjær; Jensen, Jesper Rindom

    2017-01-01

    Fundamental frequency estimation is an important task in speech and audio analysis. Harmonic model-based methods typically have superior estimation accuracy. However, such methods usually as- sume that the fundamental frequency and amplitudes are station- ary over a short time frame. In this pape...

  14. 48 CFR 9904.420-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement..., OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.420-40 Fundamental requirement. (a) The basic unit for...

  15. 48 CFR 9904.411-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.411-40 Fundamental requirement. (a) The contractor shall... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9904.411-40 Section 9904.411-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  16. 48 CFR 9904.402-40 - Fundamental requirement.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.402-40 Fundamental requirement. All costs incurred for... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirement. 9904.402-40 Section 9904.402-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  17. 48 CFR 9904.418-40 - Fundamental requirements.

    Science.gov (United States)

    2010-10-01

    ... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.418-40 Fundamental requirements. (a) A business unit... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Fundamental requirements. 9904.418-40 Section 9904.418-40 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD...

  18. Fundamental understanding and rational design of high energy structural microbatteries

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel; Li, Huidong; Mendoza, Sarah; Zhang, Ji-Guang; Deng, Zhiqun Daniel; Xiao, Jie

    2018-01-01

    Microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices and medical applications, etc. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Multiple design features adopted to accommodate large mechanical stress during the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.

  19. Overview of the fundamental safety principles

    International Nuclear Information System (INIS)

    Chishinga, Milton Mulenga

    2015-02-01

    The primary objective of this work was to provide an overview of the International Atomic Energy (IAEA) document; 'Fundamental Safety principles, SF.1'. The document outlines ten (10) fundamental principles which provide the basis for an effective the radiation protection framework. The document is the topmost in the hierarchy of the IAEA Safety Standards Series. These principles are the foundation of the nuclear safety put stringent obligations on Parties under the Convention on Nuclear Safety. The fundamental safety objective is to protect people and the environment from harmful effects of ionizing radiation. The fundamental Safety objective of protecting people individually and collectively and the environment has to be achieved without unduly limiting the operation of facilities or the conduct of activities that give rise to risks. The thematic areas covered are; responsibility for safety, role of government, leadership and management for safety, justification of facilities and activities, optimization of protection, limitation of risks to individuals, protection of present and future generations, prevention of accidents, emergency preparedness and response and protective actions to reduce existing or unregulated radiation risks. Appropriate recommendations have been provided for effective application of the principles by Governments, Regulatory Bodies and Operating Organizations of facilities and Nuclear Installations the give rise to radiation risks. (au)

  20. Fundamentals of electrochemical science

    CERN Document Server

    Oldham, Keith

    1993-01-01

    Key Features* Deals comprehensively with the basic science of electrochemistry* Treats electrochemistry as a discipline in its own right and not as a branch of physical or analytical chemistry* Provides a thorough and quantitative description of electrochemical fundamentals

  1. Fundamentals of ion exchange

    International Nuclear Information System (INIS)

    Townsend, R.P.

    1993-01-01

    In this paper the fundamentals of ion exchange mechanisms and their thermodynamics are described. A range of ion exchange materials is considered and problems of communication and technology transfer between scientists working in the field are discussed. (UK)

  2. Fundamental Concepts in Biophysics Volume 1

    CERN Document Server

    Jue, Thomas

    2009-01-01

    HANDBOOK OF MODERN BIOPHYSICS Series Editor Thomas Jue, PhD Handbook of Modern Biophysics brings current biophysics topics into focus, so that biology, medical, engineering, mathematics, and physical-science students or researchers can learn fundamental concepts and the application of new techniques in addressing biomedical challenges. Chapters explicate the conceptual framework of the physics formalism and illustrate the biomedical applications. With the addition of problem sets, guides to further study, and references, the interested reader can continue to explore independently the ideas presented. Volume I: Fundamental Concepts in Biophysics Editor Thomas Jue, PhD In Fundamental Concepts in Biophysics, prominent professors have established a foundation for the study of biophysics related to the following topics: Mathematical Methods in Biophysics Quantum Mechanics Basic to Biophysical Methods Computational Modeling of Receptor–Ligand Binding and Cellular Signaling Processes Fluorescence Spectroscopy Elec...

  3. Safety analysis fundamentals

    International Nuclear Information System (INIS)

    Wright, A.C.D.

    2002-01-01

    This paper discusses the safety analysis fundamentals in reactor design. This study includes safety analysis done to show consequences of postulated accidents are acceptable. Safety analysis is also used to set design of special safety systems and includes design assist analysis to support conceptual design. safety analysis is necessary for licensing a reactor, to maintain an operating license, support changes in plant operations

  4. The Impact of Systems Biology on Bioprocessing

    DEFF Research Database (Denmark)

    Campbell, Kate; Xia, Jianye; Nielsen, Jens

    2017-01-01

    alongside mathematical modeling to characterize and predict cellular physiology. This approach can drive cycles of design, build, test, and learn implemented by metabolic engineers to optimize the cell factory performance. Streamlining of the design phase requires a clearer understanding of metabolism...

  5. Development of Synechocystis sp. PCC 6803 as a Phototrophic Cell Factory

    Directory of Open Access Journals (Sweden)

    Fuzhong Zhang

    2013-08-01

    Full Text Available Cyanobacteria (blue-green algae play profound roles in ecology and biogeochemistry. One model cyanobacterial species is the unicellular cyanobacterium Synechocystis sp. PCC 6803. This species is highly amenable to genetic modification. Its genome has been sequenced and many systems biology and molecular biology tools are available to study this bacterium. Recently, researchers have put significant efforts into understanding and engineering this bacterium to produce chemicals and biofuels from sunlight and CO2. To demonstrate our perspective on the application of this cyanobacterium as a photosynthesis-based chassis, we summarize the recent research on Synechocystis 6803 by focusing on five topics: rate-limiting factors for cell cultivation; molecular tools for genetic modifications; high-throughput system biology for genome wide analysis; metabolic modeling for physiological prediction and rational metabolic engineering; and applications in producing diverse chemicals. We also discuss the particular challenges for systems analysis and engineering applications of this microorganism, including precise characterization of versatile cell metabolism, improvement of product rates and titers, bioprocess scale-up, and product recovery. Although much progress has been achieved in the development of Synechocystis 6803 as a phototrophic cell factory, the biotechnology for “Compounds from Synechocystis” is still significantly lagging behind those for heterotrophic microbes (e.g., Escherichia coli.

  6. The fundamental role of endothelial cells in hantavirus pathogenesis

    Directory of Open Access Journals (Sweden)

    Jussi eHepojoki

    2014-12-01

    Full Text Available Hantavirus, a genus of rodent- and insectivore-borne viruses in the family Bunyaviridae, is a group of emerging zoonotic pathogens. Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS and hantavirus cardiopulmonary syndrome (HCPS in man, often with severe consequences. Vascular leakage is evident in severe hantavirus infections, and increased permeability contributes to the pathogenesis. This review summarizes the current knowledge on hantavirus interactions with endothelial cells, and their effects on the increased vascular permeability.

  7. Fundamentals of Fire Phenomena

    DEFF Research Database (Denmark)

    Quintiere, James

    analyses. Fire phenomena encompass everything about the scientific principles behind fire behaviour. Combining the principles of chemistry, physics, heat and mass transfer, and fluid dynamics necessary to understand the fundamentals of fire phenomena, this book integrates the subject into a clear...

  8. Industrial separation processes : fundamentals

    NARCIS (Netherlands)

    Haan, de A.B.; Bosch, Hans

    2013-01-01

    Separation processes on an industrial scale comprise well over half of the capital and operating costs. They are basic knowledge in every chemical engineering and process engineering study. This book provides comprehensive and fundamental knowledge of university teaching in this discipline,

  9. Fundamentals of plasma physics

    CERN Document Server

    Bittencourt, J A

    1986-01-01

    A general introduction designed to present a comprehensive, logical and unified treatment of the fundamentals of plasma physics based on statistical kinetic theory. Its clarity and completeness make it suitable for self-learning and self-paced courses. Problems are included.

  10. Latent Fundamentals Arbitrage with a Mixed Effects Factor Model

    Directory of Open Access Journals (Sweden)

    Andrei Salem Gonçalves

    2012-09-01

    Full Text Available We propose a single-factor mixed effects panel data model to create an arbitrage portfolio that identifies differences in firm-level latent fundamentals. Furthermore, we show that even though the characteristics that affect returns are unknown variables, it is possible to identify the strength of the combination of these latent fundamentals for each stock by following a simple approach using historical data. As a result, a trading strategy that bought the stocks with the best fundamentals (strong fundamentals portfolio and sold the stocks with the worst ones (weak fundamentals portfolio realized significant risk-adjusted returns in the U.S. market for the period between July 1986 and June 2008. To ensure robustness, we performed sub period and seasonal analyses and adjusted for trading costs and we found further empirical evidence that using a simple investment rule, that identified these latent fundamentals from the structure of past returns, can lead to profit.

  11. Production and purification of a soluble hydrogenase from Ralstonia eutropha H16 for potential hydrogen fuel cell applications.

    Science.gov (United States)

    Jugder, Bat-Erdene; Lebhar, Helene; Aguey-Zinsou, Kondo-Francois; Marquis, Christopher P

    2016-01-01

    The soluble hydrogenase (SH) from Ralstonia eutropha H16 is a promising candidate enzyme for H2-based biofuel application as it favours H2 oxidation and is relatively oxygen-tolerant. In this report, bioprocess development studies undertaken to produce and purify an active SH are described, based on the methods previously reported [1], [2], [3], [4]. Our modifications are: •Upstream method optimizations were undertaken on heterotrophic growth media and cell lysis involving ultrasonication.•Two anion exchangers (Q Sepharose and RESOURCE Q) and size exclusion chromatographic (Superdex 200) matrices were successfully employed for purification of a hexameric SH from R. eutropha.•The H2 oxidizing activity of the SH was demonstrated spectrophotometrically in solution and also immobilized on an EPG electrode using cyclic voltammetry.

  12. Fundamentals and Applications of Semiconductor Nanocrystals : A study on the synthesis, optical properties, and interactions of quantum dots

    NARCIS (Netherlands)

    Koole, R.

    2008-01-01

    This thesis focuses on both the fundamental aspects as well as applications of colloidal semiconductor nanocrystals, also called quantum dots (QDs). Due to the unique size-dependent optical and electronic properties of QDs, they hold great promise for a wide range of applications like solar cells,

  13. Grenoble Fundamental Research Department

    International Nuclear Information System (INIS)

    1979-01-01

    A summary of the various activities of the Fundamental Research Institute, Grenoble, France is given. The following fields are covered: Nuclear physics, solid state physics, physical chemistry, biology and advanced techniques. Fore more detailed descriptions readers are referred to scientific literature [fr

  14. Fundamentals and Optimal Institutions

    DEFF Research Database (Denmark)

    Gonzalez-Eiras, Martin; Harmon, Nikolaj Arpe; Rossi, Martín

    2016-01-01

    of regulatory institutions such as revenue sharing, salary caps or luxury taxes. We show, theoretically and empirically, that these large differences in adopted institutions can be rationalized as optimal responses to differences in the fundamental characteristics of the sports being played. This provides...

  15. Fundamental superstrings as holograms

    International Nuclear Information System (INIS)

    Dabholkar, A.; Murthy, S.

    2007-06-01

    The worldsheet of a macroscopic fundamental superstring in the Green-Schwarz light-cone gauge is viewed as a possible boundary hologram of the near horizon region of a small black string. For toroidally compactified strings, the hologram has global symmetries of AdS 3 x S d-1 x T 8-d ( d = 3, . . . , 8), only some of which extend to local conformal symmetries. We construct the bulk string theory in detail for the particular case of d = 3. The symmetries of the hologram are correctly reproduced from this exact worldsheet description in the bulk. Moreover, the central charge of the boundary Virasoro algebra obtained from the bulk agrees with the Wald entropy of the associated small black holes. This construction provides an exact CFT description of the near horizon region of small black holes both in Type-II and heterotic string theory arising from multiply wound fundamental superstrings. (author)

  16. Fundamental superstrings as holograms

    International Nuclear Information System (INIS)

    Dabholkar, Atish; Murthy, Sameer

    2008-01-01

    The worldsheet of a macroscopic fundamental superstring in the Green-Schwarz light-cone gauge is viewed as a possible boundary hologram of the near horizon region of a small black string. For toroidally compactified strings, the hologram has global symmetries of AdS 3 x S d-1 x T 8-d (d = 3, ..., 8), only some of which extend to local conformal symmetries. We construct the bulk string theory in detail for the particular case of d = 3. The symmetries of the hologram are correctly reproduced from this exact worldsheet description in the bulk. Moreover, the central charge of the boundary Virasoro algebra obtained from the bulk agrees with the Wald entropy of the associated small black holes. This construction provides an exact CFT description of the near horizon region of small black holes both in Type-II and heterotic string theory arising from multiply wound fundamental superstrings

  17. Single-cell sequencing in stem cell biology.

    Science.gov (United States)

    Wen, Lu; Tang, Fuchou

    2016-04-15

    Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.

  18. Fundamentals of Structural Geology

    Science.gov (United States)

    Pollard, David D.; Fletcher, Raymond C.

    2005-09-01

    Fundamentals of Structural Geology provides a new framework for the investigation of geological structures by integrating field mapping and mechanical analysis. Assuming a basic knowledge of physical geology, introductory calculus and physics, it emphasizes the observational data, modern mapping technology, principles of continuum mechanics, and the mathematical and computational skills, necessary to quantitatively map, describe, model, and explain deformation in Earth's lithosphere. By starting from the fundamental conservation laws of mass and momentum, the constitutive laws of material behavior, and the kinematic relationships for strain and rate of deformation, the authors demonstrate the relevance of solid and fluid mechanics to structural geology. This book offers a modern quantitative approach to structural geology for advanced students and researchers in structural geology and tectonics. It is supported by a website hosting images from the book, additional colour images, student exercises and MATLAB scripts. Solutions to the exercises are available to instructors. The book integrates field mapping using modern technology with the analysis of structures based on a complete mechanics MATLAB is used to visualize physical fields and analytical results and MATLAB scripts can be downloaded from the website to recreate textbook graphics and enable students to explore their choice of parameters and boundary conditions The supplementary website hosts color images of outcrop photographs used in the text, supplementary color images, and images of textbook figures for classroom presentations The textbook website also includes student exercises designed to instill the fundamental relationships, and to encourage the visualization of the evolution of geological structures; solutions are available to instructors

  19. Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors

    Science.gov (United States)

    Rafiq, Qasim A.; Coopman, Karen; Nienow, Alvin W.

    2016-01-01

    Abstract Production of human mesenchymal stem cells for allogeneic cell therapies requires scalable, cost‐effective manufacturing processes. Microcarriers enable the culture of anchorage‐dependent cells in stirred‐tank bioreactors. However, no robust, transferable methodology for microcarrier selection exists, with studies providing little or no reason explaining why a microcarrier was employed. We systematically evaluated 13 microcarriers for human bone marrow‐derived MSC (hBM‐MSCs) expansion from three donors to establish a reproducible and transferable methodology for microcarrier selection. Monolayer studies demonstrated input cell line variability with respect to growth kinetics and metabolite flux. HBM‐MSC1 underwent more cumulative population doublings over three passages in comparison to hBM‐MSC2 and hBM‐MSC3. In 100 mL spinner flasks, agitated conditions were significantly better than static conditions, irrespective of donor, and relative microcarrier performance was identical where the same microcarriers outperformed others with respect to growth kinetics and metabolite flux. Relative growth kinetics between donor cells on the microcarriers were the same as the monolayer study. Plastic microcarriers were selected as the optimal microcarrier for hBM‐MSC expansion. HBM‐MSCs were successfully harvested and characterised, demonstrating hBM‐MSC immunophenotype and differentiation capacity. This approach provides a systematic method for microcarrier selection, and the findings identify potentially significant bioprocessing implications for microcarrier‐based allogeneic cell therapy manufacture. PMID:26632496

  20. Variation of nonlinearity parameter at low fundamental amplitudes

    Science.gov (United States)

    Barnard, Daniel J.

    1999-04-01

    Recent harmonic generation measurements of the nonlinearity parameter β in polycrystalline Cu-Al alloys have shown a transition to lower values at low fundamental amplitude levels. Values for β at high (>10 Å) fundamental levels are in the range predicted by single-crystal second- and third-order elastic constants while lower fundamental levels (alloy by others. The source of the effect is unclear but initial results may require a reexamination of current methods for measurement of third-order elastic constants.

  1. Skin appendage-derived stem cells: cell biology and potential for wound repair

    OpenAIRE

    Xie, Jiangfan; Yao, Bin; Han, Yutong; Huang, Sha; Fu, Xiaobing

    2016-01-01

    Stem cells residing in the epidermis and skin appendages are imperative for skin homeostasis and regeneration. These stem cells also participate in the repair of the epidermis after injuries, inducing restoration of tissue integrity and function of damaged tissue. Unlike epidermis-derived stem cells, comprehensive knowledge about skin appendage-derived stem cells remains limited. In this review, we summarize the current knowledge of skin appendage-derived stem cells, including their fundament...

  2. THE FUNDAMENTS OF EXPLANATORY CAUSES

    Directory of Open Access Journals (Sweden)

    Lavinia Mihaela VLĂDILĂ

    2015-07-01

    Full Text Available The new Criminal Code in the specter of the legal life the division of causes removing the criminal feature of the offence in explanatory causes and non-attributable causes. This dichotomy is not without legal and factual fundaments and has been subjected to doctrinaire debates even since the period when the Criminal Code of 1969 was still in force. From our perspective, one of the possible legal fundaments of the explanatory causes results from that the offence committed is based on the protection of a right at least equal with the one prejudiced by the action of aggression, salvation, by the legal obligation imposed or by the victim’s consent.

  3. Biophotonics sensor acclimatization to stem cells environment

    Science.gov (United States)

    Mohamad Shahimin, Mukhzeer

    2017-11-01

    The ability to discriminate, characterise and purify biological cells from heterogeneous population of cells is fundamental to numerous prognosis and diagnosis applications; often forming the basis for current and emerging clinical protocols in stem cell therapy. Current sorting approaches exploit differences in cell density, specific immunologic targets, or receptor-ligand interactions to isolate particular cells. Identification of novel properties by which different cell types may be discerned and of new ways for their selective manipulation are clearly fundamental components for improving sorting methodologies. Biophotonics sensor developed by our team are potentially capable of discriminating cells according to their refractive index (which is highly dependable on the organelles inside the cell), size (indicator to cell stage) and shape (in certain cases as an indicator to cell type). The sensor, which already discriminate particles efficiently, is modified to acclimatize into biological environment, especially for stem cell applications.

  4. O sofrimento psíquico na perspectiva da psicopatologia fundamental Psychic suffering from the fundamental psychopathology perspective

    Directory of Open Access Journals (Sweden)

    Paulo Ceccarelli

    2005-12-01

    Full Text Available Partindo da palavra PSICOPATOLOGIA, o autor mostra, de forma resumida, como cada contexto histórico tentou "decompor" o sofrimento psíquico em seus elementos de base para classificá-lo, estudá-lo e tratá-lo. Após uma breve apresentação da psicopatologia na contemporaneidade, o autor introduz os pressupostos da Psicopatologia Fundamental e suas contribuições na compreensão do sofrimento psíquico. Ainda que não seja objetivo do texto participar do debate atual sobre as diretrizes curriculares que norteiam a formação do psicólogo, o autor toma o estudo do conhecimento (logos da alma (psyché - a psicologia - como exemplo de um dos campos de aplicação da Psicopatologia Fundamental.From the word PSYCHOPATHOLOGY the author briefly shows how each historical context had its own way to decompose psychic suffering in order to classify, study and search for its cure. After a short discussion about psychopathology in contemporaneity the author introduces the theoretical bases of Fundamental Psychopathology and its contributions to understanding psychic suffering. Although this text does not claim to participate in the debate about psychology students training, the author exemplifies through the study of the soul (psyche knowledge (logos one of the applications of Fundamental Psychopathology.

  5. Fundamental understanding and rational design of high energy structural microbatteries

    International Nuclear Information System (INIS)

    Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel; Li, Huidong; Mendoza, Sarah

    2017-01-01

    We present that microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices, medical applications, and animal acoustic telemetry transmitters among others. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Finally, multiple design features adopted to accommodate large mechanical stress during the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.

  6. Is G a conversion factor or a fundamental unit?

    OpenAIRE

    Fiorentini, G.; Okun, L.; Vysotsky, M.

    2001-01-01

    By using fundamental units c, h, G as conversion factors one can easily transform the dimensions of all observables. In particular one can make them all ``geometrical'', or dimensionless. However this has no impact on the fact that there are three fundamental units, G being one of them. Only experiment can tell us whether G is basically fundamental.

  7. Fundamental Metallurgy of Solidification

    DEFF Research Database (Denmark)

    Tiedje, Niels

    2004-01-01

    The text takes the reader through some fundamental aspects of solidification, with focus on understanding the basic physics that govern solidification in casting and welding. It is described how the first solid is formed and which factors affect nucleation. It is described how crystals grow from...

  8. Fast fundamental frequency estimation

    DEFF Research Database (Denmark)

    Nielsen, Jesper Kjær; Jensen, Tobias Lindstrøm; Jensen, Jesper Rindom

    2017-01-01

    Modelling signals as being periodic is common in many applications. Such periodic signals can be represented by a weighted sum of sinusoids with frequencies being an integer multiple of the fundamental frequency. Due to its widespread use, numerous methods have been proposed to estimate the funda...

  9. Fundamentals and applications of ultrasonic waves

    CERN Document Server

    Cheeke, J David N

    2002-01-01

    Ultrasonics. A subject with applications across all the basic sciences, engineering, medicine, and oceanography, yet even the broader topic of acoustics is now rarely offered at undergraduate levels. Ultrasonics is addressed primarily at the doctoral level, and texts appropriate for beginning graduate students or newcomers to the field are virtually nonexistent.Fundamentals and Applications of Ultrasonic Waves fills that void. Designed specifically for senior undergraduates, beginning graduate students, and those just entering the field, it begins with the fundamentals, but goes well beyond th

  10. STEP and fundamental physics

    Science.gov (United States)

    Overduin, James; Everitt, Francis; Worden, Paul; Mester, John

    2012-09-01

    The Satellite Test of the Equivalence Principle (STEP) will advance experimental limits on violations of Einstein's equivalence principle from their present sensitivity of two parts in 1013 to one part in 1018 through multiple comparison of the motions of four pairs of test masses of different compositions in a drag-free earth-orbiting satellite. We describe the experiment, its current status and its potential implications for fundamental physics. Equivalence is at the heart of general relativity, our governing theory of gravity and violations are expected in most attempts to unify this theory with the other fundamental interactions of physics, as well as in many theoretical explanations for the phenomenon of dark energy in cosmology. Detection of such a violation would be equivalent to the discovery of a new force of nature. A null result would be almost as profound, pushing upper limits on any coupling between standard-model fields and the new light degrees of freedom generically predicted by these theories down to unnaturally small levels.

  11. Fundamentals of differential beamforming

    CERN Document Server

    Benesty, Jacob; Pan, Chao

    2016-01-01

    This book provides a systematic study of the fundamental theory and methods of beamforming with differential microphone arrays (DMAs), or differential beamforming in short. It begins with a brief overview of differential beamforming and some popularly used DMA beampatterns such as the dipole, cardioid, hypercardioid, and supercardioid, before providing essential background knowledge on orthogonal functions and orthogonal polynomials, which form the basis of differential beamforming. From a physical perspective, a DMA of a given order is defined as an array that measures the differential acoustic pressure field of that order; such an array has a beampattern in the form of a polynomial whose degree is equal to the DMA order. Therefore, the fundamental and core problem of differential beamforming boils down to the design of beampatterns with orthogonal polynomials. But certain constraints also have to be considered so that the resulting beamformer does not seriously amplify the sensors’ self noise and the mism...

  12. Monitoring cell culture media degradation using surface enhanced Raman scattering (SERS) spectroscopy.

    Science.gov (United States)

    Calvet, Amandine; Ryder, Alan G

    2014-08-20

    The quality of the cell culture media used in biopharmaceutical manufacturing is a crucial factor affecting bioprocess performance and the quality of the final product. Due to their complex composition these media are inherently unstable, and significant compositional variations can occur particularly when in the prepared liquid state. For example photo-degradation of cell culture media can have adverse effects on cell viability and thus process performance. There is therefore, from quality control, quality assurance and process management view points, an urgent demand for the development of rapid and inexpensive tools for the stability monitoring of these complex mixtures. Spectroscopic methods, based on fluorescence or Raman measurements, have now become viable alternatives to more time-consuming and expensive (on a unit analysis cost) chromatographic and/or mass spectrometry based methods for routine analysis of media. Here we demonstrate the application of surface enhanced Raman scattering (SERS) spectroscopy for the simple, fast, analysis of cell culture media degradation. Once stringent reproducibility controls are implemented, chemometric data analysis methods can then be used to rapidly monitor the compositional changes in chemically defined media. SERS shows clearly that even when media are stored at low temperature (2-8°C) and in the dark, significant chemical changes occur, particularly with regard to cysteine/cystine concentration. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Testing Our Fundamental Assumptions

    Science.gov (United States)

    Kohler, Susanna

    2016-06-01

    Science is all about testing the things we take for granted including some of the most fundamental aspects of how we understand our universe. Is the speed of light in a vacuum the same for all photons regardless of their energy? Is the rest mass of a photon actually zero? A series of recent studies explore the possibility of using transient astrophysical sources for tests!Explaining Different Arrival TimesArtists illustration of a gamma-ray burst, another extragalactic transient, in a star-forming region. [NASA/Swift/Mary Pat Hrybyk-Keith and John Jones]Suppose you observe a distant transient astrophysical source like a gamma-ray burst, or a flare from an active nucleus and two photons of different energies arrive at your telescope at different times. This difference in arrival times could be due to several different factors, depending on how deeply you want to question some of our fundamental assumptions about physics:Intrinsic delayThe photons may simply have been emitted at two different times by the astrophysical source.Delay due to Lorentz invariance violationPerhaps the assumption that all massless particles (even two photons with different energies) move at the exact same velocity in a vacuum is incorrect.Special-relativistic delayMaybe there is a universal speed for massless particles, but the assumption that photons have zero rest mass is wrong. This, too, would cause photon velocities to be energy-dependent.Delay due to gravitational potentialPerhaps our understanding of the gravitational potential that the photons experience as they travel is incorrect, also causing different flight times for photons of different energies. This would mean that Einsteins equivalence principle, a fundamental tenet of general relativity (GR), is incorrect.If we now turn this problem around, then by measuring the arrival time delay between photons of different energies from various astrophysical sources the further away, the better we can provide constraints on these

  14. Major advances in fundamental dairy cattle nutrition.

    Science.gov (United States)

    Drackley, J K; Donkin, S S; Reynolds, C K

    2006-04-01

    Fundamental nutrition seeks to describe the complex biochemical reactions involved in assimilation and processing of nutrients by various tissues and organs, and to quantify nutrient movement (flux) through those processes. Over the last 25 yr, considerable progress has been made in increasing our understanding of metabolism in dairy cattle. Major advances have been made at all levels of biological organization, including the whole animal, organ systems, tissues, cells, and molecules. At the whole-animal level, progress has been made in delineating metabolism during late pregnancy and the transition to lactation, as well as in whole-body use of energy-yielding substrates and amino acids for growth in young calves. An explosion of research using multicatheterization techniques has led to better quantitative descriptions of nutrient use by tissues of the portal-drained viscera (digestive tract, pancreas, and associated adipose tissues) and liver. Isolated tissue preparations have provided important information on the interrelationships among glucose, fatty acid, and amino acid metabolism in liver, adipose tissue, and mammary gland, as well as the regulation of these pathways during different physiological states. Finally, the last 25 yr has witnessed the birth of "molecular biology" approaches to understanding fundamental nutrition. Although measurements of mRNA abundance for proteins of interest already have provided new insights into regulation of metabolism, the next 25 yr will likely see remarkable advances as these techniques continue to be applied to problems of dairy cattle biology. Integration of the "omics" technologies (functional genomics, proteomics, and metabolomics) with measurements of tissue metabolism obtained by other methods is a particularly exciting prospect for the future. The result should be improved animal health and well being, more efficient dairy production, and better models to predict nutritional requirements and provide rations to meet

  15. Biotechnology and genetic engineering in the new drug development. Part I. DNA technology and recombinant proteins.

    Science.gov (United States)

    Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

    2013-01-01

    Pharmaceutical biotechnology has a long tradition and is rooted in the last century, first exemplified by penicillin and streptomycin as low molecular weight biosynthetic compounds. Today, pharmaceutical biotechnology still has its fundamentals in fermentation and bioprocessing, but the paradigmatic change affected by biotechnology and pharmaceutical sciences has led to an updated definition. The biotechnology revolution redrew the research, development, production and even marketing processes of drugs. Powerful new instruments and biotechnology related scientific disciplines (genomics, proteomics) make it possible to examine and exploit the behavior of proteins and molecules. Recombinant DNA (rDNA) technologies (genetic, protein, and metabolic engineering) allow the production of a wide range of peptides, proteins, and biochemicals from naturally nonproducing cells. This technology, now approximately 25 years old, is becoming one of the most important technologies developed in the 20(th) century. Pharmaceutical products and industrial enzymes were the first biotech products on the world market made by means of rDNA. Despite important advances regarding rDNA applications in mammalian cells, yeasts still represent attractive hosts for the production of heterologous proteins. In this review we describe these processes.

  16. Are fundamental constants really constant

    International Nuclear Information System (INIS)

    Norman, E.B.

    1986-01-01

    Reasons for suspecting that fundamental constants might change with time are reviewed. Possible consequences of such variations are examined. The present status of experimental tests of these ideas is discussed

  17. Religious Fundamentalism/Religious Modernism: Conceptual Adversaries or Ambivalent Phenomena?

    Directory of Open Access Journals (Sweden)

    D. GOLOVUSHKIN

    2015-02-01

    Full Text Available Both religious modernism and religious fundamentalism appeared as problems in academic and theological literature at the beginning of the 20th century. They came about as the result of the dynamic development of modernistic ideology in Russia, the United States, Western Europe and the Islamic world. Today, the concepts of religious modernism and religious fundamentalism are widely used to describe religious processes and phenomena which are the result of interaction between religion (as a dynamic spiritual and social subsystem and society - as a social system experiencing evolution. The concept of religious modernism is traditionally associated with religious renewal, the contemporary world, and innovation. Fundamentalism, on the contrary, is an ideological commitment to the “roots and origins” of religion. Under the aegis of fundamentalism, any religious idea, value or concept has a right to exist. Religious Studies, during the course of time and the production of ever new material, encountered a serious theoretic-methodological problem: How can various religious movements and religious traditions be organized into groups since some of them combine elements of religious modernism and of religious fundamentalism? Already at the end of the nineteen-eighties, the well-established view defining “fundamentalism-modernism” as contrary positions had to be rethought. Studies dating from the nineteen-nineties and the beginning of the new millennium concentrated on noting the social origins and the political character of these phenomena. They demonstrated that neither fundamentalism nor modernism present the whole picture. The lines dividing them are so blurred, that they become confl uent. Consequently, the author concludes that religious fundamentalism and religious modernism are ambivalent phenomena, which can, on occasion, interact with each other.

  18. Oxygen transport enhancement by functionalized magnetic nanoparticles (FMP) in bioprocesses

    Science.gov (United States)

    Ataide, Filipe Andre Prata

    The enhancement of fluid properties, namely thermal conductivity and mass diffusivity for a wide range of applications, through the use of nanosized particles' suspensions has been gathering increasing interest in the scientific community. In previous studies, Olle et al. (2006) showed an enhancement in oxygen absorption to aqueous solutions of up to 6-fold through the use of functionalized nanosized magnetic particles with oleic acid coating. Krishnamurthy et al. (2006) showed a remarkable 26-fold enhancement in dye diffusion in water. These two publications are landmarks in mass transfer enhancement in chemical systems through the use of nanoparticles. The central goal of this Ph.D. thesis was to develop functionalized magnetic nanoparticles to enhance oxygen transport in bioprocesses. The experimental protocol for magnetic nanoparticles synthesis and purification adopted in this thesis is a modification of that reported by Olle et al. (2006). This is facilitated by employing twice the quantity of ammonia, added at a slower rate, and by filtering the final nanoparticle solution in a cross-flow filtration modulus against 55 volumes of distilled water. This modification in the protocol resulted in improved magnetic nanoparticles with measurably higher mass transfer enhancement. Magnetic nanoparticles with oleic acid and Hitenol-BC coating were screened for oxygen transfer enhancement, since these particles are relatively inexpensive and easy to synthesize. A glass 0.5-liter reactor was custom manufactured specifically for oxygen transport studies in magnetic nanoparticles suspensions. The reactor geometry, baffles and Rushton impeller are of standard dimensions. Mass transfer tests were conducted through the use of the sulphite oxidation method, applying iodometric back-titration. A 3-factor central composite circumscribed design (CCD) was adopted for design of experiments in order to generate sufficiently informative data to model the effect of magnetic

  19. The industrial applicability of purified cellulase complex indigenously produced by Trichoderma viride through solid-state bio-processing of agro-industrial and municipal paper wastes

    Directory of Open Access Journals (Sweden)

    Muhammad Irshad

    2013-02-01

    Full Text Available An indigenous strain of Trichoderma viride produced high titers of cellulase complex in solid-state bio-processing of agro-industrial orange peel waste, which was used as the growth-supporting substrate. When the conditions of the SSF medium containing 15 g orange peel (50% w/w moisture inoculated with 5 mL of inoculum were optimal, the maximum productions of endoglucanase (655 ± 5.5 U/mL, exoglucanase (412 ± 4.3 U/mL, and β-glucosidase (515 ± 3.7 U/mL were recorded after 4 days of incubation at pH 5 and 35 °C. The enzyme with maximum activity (endoglucanase was purified by ammonium sulfate fractionation and Sephadex G-100 column gel filtration chromatographic technique. Endoglucanase was 5.5-fold purified with specific activity of 498 U/mg in comparison to the crude enzyme. The enzyme was shown to have a molecular weight of 58 kDa by sodium dodecyl sulphate poly-acrylamide gel electrophoresis (SDS-PAGE. The shelf life profile revealed that the enzyme could be stored at room temperature (30 °C for up to 45 days without losing much of its activity.

  20. Fundamental characteristics of droplet direct injection ICPMS for nano liter analysis

    International Nuclear Information System (INIS)

    Nakashima, N.; Miyahara, H.; Meguro, T.; Hotta, E.; Okino, A.

    2009-01-01

    Full text: Recently, target of the elemental analysis has been shifted to smaller amount samples such as bio cells or nano-particles. However, a conventional ICP system consumes large amount sample solutions, so it was not suitable for these samples. To realize much smaller sample introduction, a droplet direct injection nebulizer (D-DIN) system has been developed. In this study, we applied the D-DIN system to an ICPMS device. As a result, using a single 5 nL sample solution contains 1 mg/L of Na, Mg, Sr and Ba, mass signal of these elements were successfully obtained. Fundamental characteristics of D-DIN ICPMS will be presented. (author)

  1. DOE Fundamentals Handbook: Classical Physics

    International Nuclear Information System (INIS)

    1992-06-01

    The Classical Physics Fundamentals Handbook was developed to assist nuclear facility operating contractors provide operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of physical forces and their properties. The handbook includes information on the units used to measure physical properties; vectors, and how they are used to show the net effect of various forces; Newton's Laws of motion, and how to use these laws in force and motion applications; and the concepts of energy, work, and power, and how to measure and calculate the energy involved in various applications. This information will provide personnel with a foundation for understanding the basic operation of various types of DOE nuclear facility systems and equipment

  2. Fundamentals of electronic systems design

    CERN Document Server

    Lienig, Jens

    2017-01-01

    This textbook covers the design of electronic systems from the ground up, from drawing and CAD essentials to recycling requirements. Chapter by chapter, it deals with the challenges any modern system designer faces: the design process and its fundamentals, such as technical drawings and CAD, electronic system levels, assembly and packaging issues and appliance protection classes, reliability analysis, thermal management and cooling, electromagnetic compatibility (EMC), all the way to recycling requirements and environmental-friendly design principles. Enables readers to face various challenges of designing electronic systems, including coverage from various engineering disciplines; Written to be accessible to readers of varying backgrounds; Uses illustrations extensively to reinforce fundamental concepts; Organized to follow essential design process, although chapters are self-contained and can be read in any order.

  3. Fundamental measure theory for hard-sphere mixtures: a review

    International Nuclear Information System (INIS)

    Roth, Roland

    2010-01-01

    Hard-sphere systems are one of the fundamental model systems of statistical physics and represent an important reference system for molecular or colloidal systems with soft repulsive or attractive interactions in addition to hard-core repulsion at short distances. Density functional theory for classical systems, as one of the core theoretical approaches of statistical physics of fluids and solids, has to be able to treat such an important system successfully and accurately. Fundamental measure theory is up to date the most successful and most accurate density functional theory for hard-sphere mixtures. Since its introduction fundamental measure theory has been applied to many problems, tested against computer simulations, and further developed in many respects. The literature on fundamental measure theory is already large and is growing fast. This review aims to provide a starting point for readers new to fundamental measure theory and an overview of important developments. (topical review)

  4. Marketing fundamentals.

    Science.gov (United States)

    Redmond, W H

    2001-01-01

    This chapter outlines current marketing practice from a managerial perspective. The role of marketing within an organization is discussed in relation to efficiency and adaptation to changing environments. Fundamental terms and concepts are presented in an applied context. The implementation of marketing plans is organized around the four P's of marketing: product (or service), promotion (including advertising), place of delivery, and pricing. These are the tools with which marketers seek to better serve their clients and form the basis for competing with other organizations. Basic concepts of strategic relationship management are outlined. Lastly, alternate viewpoints on the role of advertising in healthcare markets are examined.

  5. Review of nonconventional bioreactor technology

    Energy Technology Data Exchange (ETDEWEB)

    Turick, C.E.; Mcllwain, M.E.

    1993-09-01

    Biotechnology will significantly affect many industrial sectors in the future. Industrial sectors that will be affected include pharmaceutical, chemical, fuel, agricultural, and environmental remediation. Future research is needed to improve bioprocessing efficiency and cost-effectiveness in order to compete with traditional technologies. This report describes recent advances in bioprocess technologies and bioreactor designs and relates them to problems encountered in many industrial bioprocessing operations. The primary focus is directed towards increasing gas and vapor transfer for enhanced bioprocess kinetics as well as unproved by-product separation and removal. The advantages and disadvantages of various conceptual designs such as hollow-fiber, gas-phase, hyperbaric/hypobaric, and electrochemical bioreactors are also discussed. Specific applications that are intended for improved bioprocesses include coal desulfurization, coal liquefaction, soil bioremediation, biomass conversion to marketable chemicals, biomining, and biohydrometallurgy as well as bioprocessing of gases and vapors.

  6. Appa Rao Podile | Speakers | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    In the past decade, domain shuf- fling/swapping of recombinant bacterial chitinases, bioprocess development for production of chitooligosaccharides by enzymatic methods, mechanism of elicitor (harpin) induced cell death, nanotechnology for crop protection, and non-host resistance have been his major areas of research ...

  7. Measurements of the fundamental thermodynamic parameters of Li/BCX and Li/SOCl2 cells

    Science.gov (United States)

    Kalu, E. E.; White, R. E.; Darcy, E. C.

    1992-01-01

    Two experimental techniques - equilibrium or reversible cell discharge and measurement of open circuit potential as a function of temperature - are used to determine the thermodynamic data needed to estimate the heat generation characteristics of Li/BCX and Li/SOCl2 cells. The results obtained showed that the reversible cell potential, the temperature dependence of the reversible cell potential, and the thermoneutral potential of the BCX cell were 3.74 V, -0.857 +/- 0.198 mV/K, and 3.994 +/- 0.0603 V, respectively. The respective values obtained for the Li/SOCl2 cell were 3.67 V, -0.776 +/- 0.255 mV/K, and 3.893 +/- 0.0776 V. The difference between the thermoneutral potential of Li/BCX and Li/SCl2 cells is attributable to the difference in their electroactive components.

  8. SU (2) with fundamental fermions and scalars

    DEFF Research Database (Denmark)

    Hansen, Martin; Janowski, Tadeusz; Pica, Claudio

    2018-01-01

    We present preliminary results on the lattice simulation of an SU(2) gauge theory with two fermion flavors and one strongly interacting scalar field, all in the fundamental representation of SU(2). The motivation for this study comes from the recent proposal of "fundamental" partial compositeness...... the properties of light meson resonances previously obtained for the SU(2) model. Preprint: CP3-Origins-2017-047 DNRF90...

  9. From marine bio-corrosion to new bio-processes

    International Nuclear Information System (INIS)

    Bergel, A.; Dasilva, S.; Basseguy, R.; Feron, D.; Mollica, A.

    2004-01-01

    Full text of publication follows: From the middle of the last century it has been observed that the development of marine bio-films on the surface of stainless steels and different metallic materials induces the ennoblement of their free corrosion potential. A main step in deciphering the mechanisms of aerobic marine bio-corrosion has been achieved around 1976 with the demonstration that the potential ennoblement was due to the modification of the cathodic process. Since this date, the catalysis of oxygen reduction by marine bio-films has been the topic of numerous controversies, but it is now commonly agreed as a basic phenomena in aerobic corrosion. Several hypotheses have been proposed to explain the fine mechanisms of the bio-film-catalysed reduction of oxygen: intermediate formation of hydrogen peroxide, modification of the oxide layer on the stainless steel surface, involvement of manganese species and manganese oxidising bacteria, catalysis by proteins produced by the micro-organisms... Recent results may confirm the possible involvement of hemic enzymes or proteins. Whatever the mechanisms, very promising results have been obtained with the possible application of bio-film-catalysed oxygen reduction to conceive innovative biofuel cells with stainless steel electrodes. Actually, the catalysis of oxygen reduction is a key step that still drastically hinders the development of economically efficient hydrogen/oxygen fuel cells. The current technology requires high amounts of platinum or platinum-based materials to catalyze oxygen reduction on the cathode of these cells. The prohibitive cost of platinum is a main obstacle to the commercialization of low-cost fuel cells. Unpublished results recently showed that adapting the enzyme-catalysed reaction that was assumed for bio-corrosion on the cathode of hydrogen/oxygen fuel cells may lead to a significant decrease in the charge of platinum. Moreover, it was demonstrated on a laboratory-scale fuel cell pilot that

  10. Accounting Fundamentals for Non-Accountants

    Science.gov (United States)

    The purpose of this module is to provide an introduction and overview of accounting fundamentals for non-accountants. The module also covers important topics such as communication, internal controls, documentation and recordkeeping.

  11. The Quantitative and Qualitative Status of Fundamental Movement ...

    African Journals Online (AJOL)

    South African Journal for Research in Sport, Physical Education and Recreation ... The Bruininks-Oseretsky Test of Motor Proficiency 2 (BOT-2), was used to assess six fundamental movement skills quantitatively, and the Fundamental Movement Pattern Assessment Instrument (FMPAI), was applied to analyse the same ...

  12. Fundamentals of Diesel Engines.

    Science.gov (United States)

    Marine Corps Inst., Washington, DC.

    This student guide, one of a series of correspondence training courses designed to improve the job performance of members of the Marine Corps, deals with the fundamentals of diesel engine mechanics. Addressed in the three individual units of the course are the following topics: basic principles of diesel mechanics; principles, mechanics, and…

  13. Mammalian Cell Culture Process for Monoclonal Antibody Production: Nonlinear Modelling and Parameter Estimation

    Directory of Open Access Journals (Sweden)

    Dan Selişteanu

    2015-01-01

    Full Text Available Monoclonal antibodies (mAbs are at present one of the fastest growing products of pharmaceutical industry, with widespread applications in biochemistry, biology, and medicine. The operation of mAbs production processes is predominantly based on empirical knowledge, the improvements being achieved by using trial-and-error experiments and precedent practices. The nonlinearity of these processes and the absence of suitable instrumentation require an enhanced modelling effort and modern kinetic parameter estimation strategies. The present work is dedicated to nonlinear dynamic modelling and parameter estimation for a mammalian cell culture process used for mAb production. By using a dynamical model of such kind of processes, an optimization-based technique for estimation of kinetic parameters in the model of mammalian cell culture process is developed. The estimation is achieved as a result of minimizing an error function by a particle swarm optimization (PSO algorithm. The proposed estimation approach is analyzed in this work by using a particular model of mammalian cell culture, as a case study, but is generic for this class of bioprocesses. The presented case study shows that the proposed parameter estimation technique provides a more accurate simulation of the experimentally observed process behaviour than reported in previous studies.

  14. The polarization and the fundamental sensitivity of 39K (133Cs)-85Rb-4He hybrid optical pumping spin exchange relaxation free atomic magnetometers.

    Science.gov (United States)

    Liu, Jian-Hua; Jing, Dong-Yang; Wang, Liang-Liang; Li, Yang; Quan, Wei; Fang, Jian-Cheng; Liu, Wu-Ming

    2017-07-28

    The hybrid optical pumping spin exchange relaxation free (SERF) atomic magnetometers can realize ultrahigh sensitivity measurement of magnetic field and inertia. We have studied the 85 Rb polarization of two types of hybrid optical pumping SERF magnetometers based on 39 K- 85 Rb- 4 He and 133 Cs- 85 Rb- 4 He respectively. Then we found that 85 Rb polarization varies with the number density of buffer gas 4 He and quench gas N 2 , pumping rate of pump beam and cell temperature respectively, which will provide an experimental guide for the design of the magnetometer. We obtain a general formula on the fundamental sensitivity of the hybrid optical pumping SERF magnetometer due to shot-noise. The formula describes that the fundamental sensitivity of the magnetometer varies with the number density of buffer gas and quench gas, the pumping rate of pump beam, external magnetic field, cell effective radius, measurement volume, cell temperature and measurement time. We obtain a highest fundamental sensitivity of 1.5073 aT/Hz 1/2 (1 aT = 10 -18 T) with 39 K- 85 Rb- 4 He magnetometer between above two types of magnetometers when 85 Rb polarization is 0.1116. We estimate the fundamental sensitivity limit of the hybrid optical pumping SERF magnetometer to be superior to 1.8359 × 10 -2 aT/Hz 1/2 , which is higher than the shot-noise-limited sensitivity of 1 aT/Hz 1/2 of K SERF atomic magnetometer.

  15. Parallel steady state studies on a milliliter scale accelerate fed-batch bioprocess design for recombinant protein production with Escherichia coli.

    Science.gov (United States)

    Schmideder, Andreas; Cremer, Johannes H; Weuster-Botz, Dirk

    2016-11-01

    In general, fed-batch processes are applied for recombinant protein production with Escherichia coli (E. coli). However, state of the art methods for identifying suitable reaction conditions suffer from severe drawbacks, i.e. direct transfer of process information from parallel batch studies is often defective and sequential fed-batch studies are time-consuming and cost-intensive. In this study, continuously operated stirred-tank reactors on a milliliter scale were applied to identify suitable reaction conditions for fed-batch processes. Isopropyl β-d-1-thiogalactopyranoside (IPTG) induction strategies were varied in parallel-operated stirred-tank bioreactors to study the effects on the continuous production of the recombinant protein photoactivatable mCherry (PAmCherry) with E. coli. Best-performing induction strategies were transferred from the continuous processes on a milliliter scale to liter scale fed-batch processes. Inducing recombinant protein expression by dynamically increasing the IPTG concentration to 100 µM led to an increase in the product concentration of 21% (8.4 g L -1 ) compared to an implemented high-performance production process with the most frequently applied induction strategy by a single addition of 1000 µM IPGT. Thus, identifying feasible reaction conditions for fed-batch processes in parallel continuous studies on a milliliter scale was shown to be a powerful, novel method to accelerate bioprocess design in a cost-reducing manner. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1426-1435, 2016. © 2016 American Institute of Chemical Engineers.

  16. Immune modules shared by innate lymphoid cells and T cells.

    Science.gov (United States)

    Robinette, Michelle L; Colonna, Marco

    2016-11-01

    In recent years, innate lymphoid cells (ILCs) have emerged as innate correlates to T cells. The similarities between ILCs and T cells indicate that lymphocytes of fundamentally distinct lineages can share core "immune modules" that encompass transcriptional circuitry and effector functions while using nonredundant complementary mechanisms of pattern recognition to enact these functions. We review modules currently recognized to be shared between ILCs and T cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Calpain-Mediated positional information directs cell wall orientation to sustain plant stem cell activity, growth and development

    Science.gov (United States)

    Eukaryotic development and stem cell control depend on the integration of cell positional sensing with cell cycle control and cell wall positioning, yet few factors that directly link these events are known. The DEFECTIVE KERNEL1 (DEK1) gene encoding the unique plant calpain protein is fundamental f...

  18. Fundamental physics possibilities at the European Spallation Source

    DEFF Research Database (Denmark)

    Klinkby, Esben Bryndt; Soldner, Torsten

    2016-01-01

    The construction of the European Spallation Source ESS is ongoing in Lund, Sweden. This new high power spallation source with its long-pulse structure opens up new possibilities for fundamental physics experiments. This paper focusses on two proposals for fundamental physics at the ESS: The ANNI...

  19. Asymmetries in Cell Division, Cell Size, and Furrowing in the Xenopus laevis Embryo.

    Science.gov (United States)

    Tassan, Jean-Pierre; Wühr, Martin; Hatte, Guillaume; Kubiak, Jacek

    2017-01-01

    Asymmetric cell divisions produce two daughter cells with distinct fate. During embryogenesis, this mechanism is fundamental to build tissues and organs because it generates cell diversity. In adults, it remains crucial to maintain stem cells. The enthusiasm for asymmetric cell division is not only motivated by the beauty of the mechanism and the fundamental questions it raises, but has also very pragmatic reasons. Indeed, misregulation of asymmetric cell divisions is believed to have dramatic consequences potentially leading to pathogenesis such as cancers. In diverse model organisms, asymmetric cell divisions result in two daughter cells, which differ not only by their fate but also in size. This is the case for the early Xenopus laevis embryo, in which the two first embryonic divisions are perpendicular to each other and generate two pairs of blastomeres, which usually differ in size: one pair of blastomeres is smaller than the other. Small blastomeres will produce embryonic dorsal structures, whereas the larger pair will evolve into ventral structures. Here, we present a speculative model on the origin of the asymmetry of this cell division in the Xenopus embryo. We also discuss the apparently coincident asymmetric distribution of cell fate determinants and cell-size asymmetry of the 4-cell stage embryo. Finally, we discuss the asymmetric furrowing during epithelial cell cytokinesis occurring later during Xenopus laevis embryo development.

  20. Lattice Symmetry and Identification-The Fundamental Role of Reduced Cells in Materials Characterization.

    Science.gov (United States)

    Mighell, A D

    2001-01-01

    In theory, physical crystals can be represented by idealized mathematical lattices. Under appropriate conditions, these representations can be used for a variety of purposes such as identifying, classifying, and understanding the physical properties of materials. Critical to these applications is the ability to construct a unique representation of the lattice. The vital link that enabled this theory to be realized in practice was provided by the 1970 paper on the determination of reduced cells. This seminal paper led to a mathematical approach to lattice analysis initially based on systematic reduction procedures and the use of standard cells. Subsequently, the process evolved to a matrix approach based on group theory and linear algebra that offered a more abstract and powerful way to look at lattices and their properties. Application of the reduced cell to both database work and laboratory research at NIST was immediately successful. Currently, this cell and/or procedures based on reduction are widely and routinely used by the general scientific community: (i) for calculating standard cells for the reporting of crystalline materials, (ii) for classifying materials, (iii) in crystallographic database work (iv) in routine x-ray and neutron diffractometry, and (v) in general crystallographic research. Especially important is its use in symmetry determination and in identification. The focus herein is on the role of the reduced cell in lattice symmetry determination.

  1. DOE Fundamentals Handbook: Mathematics, Volume 1

    International Nuclear Information System (INIS)

    1992-06-01

    The Mathematics Fundamentals Handbook was developed to assist nuclear facility operating contractors provide operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of mathematics and its application to facility operation. The handbook includes a review of introductory mathematics and the concepts and functional use of algebra, geometry, trigonometry, and calculus. Word problems, equations, calculations, and practical exercises that require the use of each of the mathematical concepts are also presented. This information will provide personnel with a foundation for understanding and performing basic mathematical calculations that are associated with various DOE nuclear facility operations

  2. DOE Fundamentals Handbook: Mathematics, Volume 2

    International Nuclear Information System (INIS)

    1992-06-01

    The Mathematics Fundamentals Handbook was developed to assist nuclear facility operating contractors provide operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of mathematics and its application to facility operation. The handbook includes a review of introductory mathematics and the concepts and functional use of algebra, geometry, trigonometry, and calculus. Word problems, equations, calculations, and practical exercises that require the use of each of the mathematical concepts are also presented. This information will provide personnel with a foundation for understanding and performing basic mathematical calculations that are associated with various DOE nuclear facility operations

  3. STEP and fundamental physics

    International Nuclear Information System (INIS)

    Overduin, James; Everitt, Francis; Worden, Paul; Mester, John

    2012-01-01

    The Satellite Test of the Equivalence Principle (STEP) will advance experimental limits on violations of Einstein's equivalence principle from their present sensitivity of two parts in 10 13 to one part in 10 18 through multiple comparison of the motions of four pairs of test masses of different compositions in a drag-free earth-orbiting satellite. We describe the experiment, its current status and its potential implications for fundamental physics. Equivalence is at the heart of general relativity, our governing theory of gravity and violations are expected in most attempts to unify this theory with the other fundamental interactions of physics, as well as in many theoretical explanations for the phenomenon of dark energy in cosmology. Detection of such a violation would be equivalent to the discovery of a new force of nature. A null result would be almost as profound, pushing upper limits on any coupling between standard-model fields and the new light degrees of freedom generically predicted by these theories down to unnaturally small levels. (paper)

  4. Quivers, words and fundamentals

    International Nuclear Information System (INIS)

    Mattioli, Paolo; Ramgoolam, Sanjaye

    2015-01-01

    A systematic study of holomorphic gauge invariant operators in general N=1 quiver gauge theories, with unitary gauge groups and bifundamental matter fields, was recently presented in http://dx.doi.org/10.1007/JHEP04(2013)094. For large ranks a simple counting formula in terms of an infinite product was given. We extend this study to quiver gauge theories with fundamental matter fields, deriving an infinite product form for the refined counting in these cases. The infinite products are found to be obtained from substitutions in a simple building block expressed in terms of the weighted adjacency matrix of the quiver. In the case without fundamentals, it is a determinant which itself is found to have a counting interpretation in terms of words formed from partially commuting letters associated with simple closed loops in the quiver. This is a new relation between counting problems in gauge theory and the Cartier-Foata monoid. For finite ranks of the unitary gauge groups, the refined counting is given in terms of expressions involving Littlewood-Richardson coefficients.

  5. FUNDAMENTALIZATION OF ICT LEARNING IN MODERN HIGH TECH ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    M. P. Shyshkina

    2013-03-01

    Full Text Available The article outlines the features of the process of fundamentalization of ICT learning, educational background to ensure it in high school. The concept of fundamental knowledge and its role in training of a specialist is described. The problems of access to qualitative education, particularly to electronic learning resources in modern high-tech environment are revealed. The role of computer mathematics as a tool of ICT learning fundamentalization is emphasized.

  6. Sensors, Volume 1, Fundamentals and General Aspects

    Science.gov (United States)

    Grandke, Thomas; Ko, Wen H.

    1996-12-01

    'Sensors' is the first self-contained series to deal with the whole area of sensors. It describes general aspects, technical and physical fundamentals, construction, function, applications and developments of the various types of sensors. This volume deals with the fundamentals and common principles of sensors and covers the wide areas of principles, technologies, signal processing, and applications. Contents include: Sensor Fundamentals, e.g. Sensor Parameters, Modeling, Design and Packaging; Basic Sensor Technologies, e.g. Thin and Thick Films, Integrated Magnetic Sensors, Optical Fibres and Intergrated Optics, Ceramics and Oxides; Sensor Interfaces, e.g. Signal Processing, Multisensor Signal Processing, Smart Sensors, Interface Systems; Sensor Applications, e.g. Automotive: On-board Sensors, Traffic Surveillance and Control, Home Appliances, Environmental Monitoring, etc. This volume is an indispensable reference work and text book for both specialits and newcomers, researchers and developers.

  7. Consolidated ethanol production from Jerusalem artichoke tubers at elevated temperature by Saccharomyces cerevisiae engineered with inulinase expression through cell surface display.

    Science.gov (United States)

    Khatun, M Mahfuza; Liu, Chen-Guang; Zhao, Xin-Qing; Yuan, Wen-Jie; Bai, Feng-Wu

    2017-02-01

    Ethanol fermentation from Jerusalem artichoke tubers was performed at elevated temperatures by the consolidated bioprocessing strategy using Saccharomyces cerevisiae MK01 expressing inulinase through cell surface display. No significant difference was observed in yeast growth when temperature was controlled at 38 and 40 °C, respectively, but inulinase activity with yeast cells was substantially enhanced at 40 °C. As a result, enzymatic hydrolysis of inulin was facilitated and ethanol production was improved with 89.3 g/L ethanol produced within 72 h from 198.2 g/L total inulin sugars consumed. Similar results were also observed in ethanol production from Jerusalem artichoke tubers with 85.2 g/L ethanol produced within 72 h from 185.7 g/L total sugars consumed. On the other hand, capital investment on cooling facilities and energy consumption for running the facilities would be saved, since regular cooling water instead of chill water could be used to cool down the fermentation system.

  8. Fundamentals of calculus

    CERN Document Server

    Morris, Carla C

    2015-01-01

    Fundamentals of Calculus encourages students to use power, quotient, and product rules for solutions as well as stresses the importance of modeling skills.  In addition to core integral and differential calculus coverage, the book features finite calculus, which lends itself to modeling and spreadsheets.  Specifically, finite calculus is applied to marginal economic analysis, finance, growth, and decay.  Includes: Linear Equations and FunctionsThe DerivativeUsing the Derivative Exponential and Logarithmic Functions Techniques of DifferentiationIntegral CalculusIntegration TechniquesFunctions

  9. Biomedical engineering fundamentals

    CERN Document Server

    Bronzino, Joseph D

    2014-01-01

    Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering.Biomedical Engineering Fundamentals, the first volume of the handbook, presents material from respected scientists with diverse backgrounds in physiological systems, biomechanics, biomaterials, bioelectric phenomena, and neuroengineering. More than three dozen specific topics are examined, including cardia

  10. Peaks and Valleys : Experimental Asset Markets With Non-Monotonic Fundamentals

    NARCIS (Netherlands)

    Noussair, C.N.; Powell, O.R.

    2008-01-01

    We report the results of an experiment designed to measure how well asset market prices track fundamentals when the latter experience peaks and troughs. We observe greater price efficiency in markets in which fundamentals rise to a peak and then decline, than in markets in which fundamentals decline

  11. Fundamentals, Misvaluation, and Investment: The Real Story

    OpenAIRE

    Chirinko, Robert S.; Schaller, Huntley

    2006-01-01

    Abstract: Is real investment fully determined by fundamentals or is it sometimes affected by stockmarket misvaluation? We introduce three new tests that: measure the reaction of investment to sales shocks for firms that may be overvalued; use Fama-MacBeth regressions to determine whether "overinvestment" affects subsequent returns; and analyze the time path of the marginal product of capital in reaction to fundamental and misvaluation shocks. Besides these qualitative tests, we introduce a me...

  12. Fundamental Rights, European Private Law, and Financial Services

    NARCIS (Netherlands)

    Cherednychenko, O.O.; Micklitz, H.-W.

    2014-01-01

    Although it seems to be undisputed today that the harmonisation of private law in the EU cannot take place without due regard for fundamental rights, many questions still exist as to how and to what extent European private law can and should be influenced by fundamental rights. This chapter aims to

  13. Thermostability of biological systems: fundamentals, challenges, and quantification.

    Science.gov (United States)

    He, Xiaoming

    2011-01-01

    This review examines the fundamentals and challenges in engineering/understanding the thermostability of biological systems over a wide temperature range (from the cryogenic to hyperthermic regimen). Applications of the bio-thermostability engineering to either destroy unwanted or stabilize useful biologicals for the treatment of diseases in modern medicine are first introduced. Studies on the biological responses to cryogenic and hyperthermic temperatures for the various applications are reviewed to understand the mechanism of thermal (both cryo and hyperthermic) injury and its quantification at the molecular, cellular and tissue/organ levels. Methods for quantifying the thermophysical processes of the various applications are then summarized accounting for the effect of blood perfusion, metabolism, water transport across cell plasma membrane, and phase transition (both equilibrium and non-equilibrium such as ice formation and glass transition) of water. The review concludes with a summary of the status quo and future perspectives in engineering the thermostability of biological systems.

  14. Cascades of bioreactors

    NARCIS (Netherlands)

    Gooijer, de C.D.

    1995-01-01

    In this thesis a common phenomenon in bioprocess engineering is described : the execution of a certain bioprocess in more than one bioreactor. Chapter 1, a review, classifies bioprocesses by means of a number of characteristics :
    i) processes with a variable

  15. Fundamental requirements for petrochemical development

    International Nuclear Information System (INIS)

    Flint, G. B.

    1999-01-01

    The development of NOVA Chemicals over the past 20 years is described as an illustration of how the petrochemical industry provides markets for natural gas, natural gas liquids and the products of crude oil distillation, and functions as a conduit for upgrading products which would otherwise be sold into the fuel market. Some fundamental characteristics of the business which are foundations for competitiveness are reviewed in the process. These fundamentals help to understand why the industry locates in certain geographic regions of the world, which are often remote from end-use markets. Chief among these fundamentals is access to an adequate supply of appropriately priced feedstock; this is the single most important reason why chemical companies continue to emphasize developments in areas of the world where feedstock are advantageously priced. The cost of operations is equally significant. Cost depends not so much on location but on the scale of operations, hence the tendency towards large scale plants. Plant and product rationalization, technology and product development synergies and leverage with suppliers are all opportunities for cost reduction throughout the product supply chain. The combination of lower natural gas cost in Alberta, the lower fixed cost of extraction and the economies of scale achieved by large scale operation (five billion pounds per year of polyethylene production capacity) are the crucial factors that will enable NOVA Chemicals to maintain its competitive position and to weather the highs and lows in industry price fluctuations

  16. Quantum mechanics I the fundamentals

    CERN Document Server

    Rajasekar, S

    2015-01-01

    Quantum Mechanics I: The Fundamentals provides a graduate-level account of the behavior of matter and energy at the molecular, atomic, nuclear, and sub-nuclear levels. It covers basic concepts, mathematical formalism, and applications to physically important systems.

  17. Predicting Achievable Fundamental Frequency Ranges in Vocalization Across Species.

    Directory of Open Access Journals (Sweden)

    Ingo Titze

    2016-06-01

    Full Text Available Vocal folds are used as sound sources in various species, but it is unknown how vocal fold morphologies are optimized for different acoustic objectives. Here we identify two main variables affecting range of vocal fold vibration frequency, namely vocal fold elongation and tissue fiber stress. A simple vibrating string model is used to predict fundamental frequency ranges across species of different vocal fold sizes. While average fundamental frequency is predominantly determined by vocal fold length (larynx size, range of fundamental frequency is facilitated by (1 laryngeal muscles that control elongation and by (2 nonlinearity in tissue fiber tension. One adaptation that would increase fundamental frequency range is greater freedom in joint rotation or gliding of two cartilages (thyroid and cricoid, so that vocal fold length change is maximized. Alternatively, tissue layers can develop to bear a disproportionate fiber tension (i.e., a ligament with high density collagen fibers, increasing the fundamental frequency range and thereby vocal versatility. The range of fundamental frequency across species is thus not simply one-dimensional, but can be conceptualized as the dependent variable in a multi-dimensional morphospace. In humans, this could allow for variations that could be clinically important for voice therapy and vocal fold repair. Alternative solutions could also have importance in vocal training for singing and other highly-skilled vocalizations.

  18. Fundamental Processes in Plasmas. Final report

    International Nuclear Information System (INIS)

    O'Neil, Thomas M.; Driscoll, C. Fred

    2009-01-01

    This research focuses on fundamental processes in plasmas, and emphasizes problems for which precise experimental tests of theory can be obtained. Experiments are performed on non-neutral plasmas, utilizing three electron traps and one ion trap with a broad range of operating regimes and diagnostics. Theory is focused on fundamental plasma and fluid processes underlying collisional transport and fluid turbulence, using both analytic techniques and medium-scale numerical simulations. The simplicity of these systems allows a depth of understanding and a precision of comparison between theory and experiment which is rarely possible for neutral plasmas in complex geometry. The recent work has focused on three areas in basic plasma physics. First, experiments and theory have probed fundamental characteristics of plasma waves: from the low-amplitude thermal regime, to inviscid damping and fluid echoes, to cold fluid waves in cryogenic ion plasmas. Second, the wide-ranging effects of dissipative separatrices have been studied experimentally and theoretically, finding novel wave damping and coupling effects and important plasma transport effects. Finally, correlated systems have been investigated experimentally and theoretically: UCSD experients have now measured the Salpeter correlation enhancement, and theory work has characterized the 'guiding center atoms of antihydrogen created at CERN

  19. Fundamentals of estuarine physical oceanography

    CERN Document Server

    Bruner de Miranda, Luiz; Kjerfve, Björn; Castro Filho, Belmiro Mendes de

    2017-01-01

    This book provides an introduction to the complex system functions, variability and human interference in ecosystem between the continent and the ocean. It focuses on circulation, transport and mixing of estuarine and coastal water masses, which is ultimately related to an understanding of the hydrographic and hydrodynamic characteristics (salinity, temperature, density and circulation), mixing processes (advection and diffusion), transport timescales such as the residence time and the exposure time. In the area of physical oceanography, experiments using these water bodies as a natural laboratory and interpreting their circulation and mixing processes using theoretical and semi-theoretical knowledge are of fundamental importance. Small-scale physical models may also be used together with analytical and numerical models. The book highlights the fact that research and theory are interactive, and the results provide the fundamentals for the development of the estuarine research.

  20. Fundamental investigations of catalyst nanoparticles

    DEFF Research Database (Denmark)

    Elkjær, Christian Fink

    and economic development in the 20th century. There is however a downside to this development and we are seeing significant pollution and pressure on resources. Catalysis therefore has an increasingly important role in limiting pollution and optimizing the use of resources. This development will depend on our...... fundamental understanding of catalytic processes and our ability to make use of that understanding. This thesis presents fundamental studies of catalyst nanoparticles with particular focus on dynamic processes. Such studies often require atomic-scale characterization, because the catalytic conversion takes...... important that we only study intrinsic structures and phenomena and not those that may be induced by the high energy electrons used to image the specimen. This requires careful consideration of the influence of the electron beam in order to understand, control and minimize that influence. I present four...

  1. Fundamental research in developing countries

    International Nuclear Information System (INIS)

    Moravesik, M.J.

    1964-01-01

    Technical assistance is today a widespread activity. Large numbers of persons with special qualifications in the applied sciences go to the developing countries to work on specific research and development projects, as do educationists on Fulbright or other programmes - usually to teach elementary or intermediate courses. But I believe that until now it has been rare for a person primarily interested in fundamental research to go to one of these countries to help build up advanced education and pure research work. Having recently returned from such an assignment, and having found it a most stimulating and enlightening experience, I feel moved to urge strongly upon others who may be in a position to do so that they should seek similar experience themselves. The first step is to show that advanced education and fundamental research are badly needed in the under-developed countries.

  2. Lasers and optoelectronics fundamentals, devices and applications

    CERN Document Server

    Maini, Anil K

    2013-01-01

    With emphasis on the physical and engineering principles, this book provides a comprehensive and highly accessible treatment of modern lasers and optoelectronics. Divided into four parts, it explains laser fundamentals, types of lasers, laser electronics & optoelectronics, and laser applications, covering each of the topics in their entirety, from basic fundamentals to advanced concepts. Key features include: exploration of technological and application-related aspects of lasers and optoelectronics, detailing both existing and emerging applications in industry, medical diag

  3. Fundamentals of photonics

    CERN Document Server

    Saleh, Bahaa E A

    2007-01-01

    Now in a new full-color edition, Fundamentals of Photonics, Second Edition is a self-contained and up-to-date introductory-level textbook that thoroughly surveys this rapidly expanding area of engineering and applied physics. Featuring a logical blend of theory and applications, coverage includes detailed accounts of the primary theories of light, including ray optics, wave optics, electromagnetic optics, and photon optics, as well as the interaction of photons and atoms, and semiconductor optics. Presented at increasing levels of complexity, preliminary sections build toward more advan

  4. Fundamental understanding of matter: an engineering viewpoint

    International Nuclear Information System (INIS)

    Cullingford, H.S.; Cort, G.E.

    1980-01-01

    Fundamental understanding of matter is a continuous process that should produce physical data for use by engineers and scientists in their work. Lack of fundamental property data in any engineering endeavor cannot be mitigated by theoretical work that is not confirmed by physical experiments. An engineering viewpoint will be presented to justify the need for understanding of matter. Examples will be given in the energy engineering field to outline the importance of further understanding of material and fluid properties and behavior. Cases will be cited to show the effects of various data bases in energy, mass, and momentum transfer. The status of fundamental data sources will be discussed in terms of data centers, new areas of engineering, and the progress in measurement techniques. Conclusions and recommendations will be outlined to improve the current situation faced by engineers in carrying out their work. 4 figures

  5. Fundamental Elements and Interactions of Nature: A Classical Unification Theory

    Directory of Open Access Journals (Sweden)

    Tianxi Zhang

    2010-04-01

    Full Text Available A classical unification theory that completely unifies all the fundamental interactions of nature is developed. First, the nature is suggested to be composed of the following four fundamental elements: mass, radiation, electric charge, and color charge. All known types of matter or particles are a combination of one or more of the four fundamental elements. Photons are radiation; neutrons have only mass; protons have both mass and electric charge; and quarks contain mass, electric charge, and color charge. The nature fundamental interactions are interactions among these nature fundamental elements. Mass and radiation are two forms of real energy. Electric and color charges are considered as two forms of imaginary energy. All the fundamental interactions of nature are therefore unified as a single interaction between complex energies. The interaction between real energies is the gravitational force, which has three types: mass-mass, mass-radiation, and radiation-radiation interactions. Calculating the work done by the mass-radiation interaction on a photon derives the Einsteinian gravitational redshift. Calculating the work done on a photon by the radiation-radiation interaction derives a radiation redshift, which is much smaller than the gravitational redshift. The interaction between imaginary energies is the electromagnetic (between electric charges, weak (between electric and color charges, and strong (between color charges interactions. In addition, we have four imaginary forces between real and imaginary energies, which are mass-electric charge, radiation-electric charge, mass-color charge, and radiation-color charge interactions. Among the four fundamental elements, there are ten (six real and four imaginary fundamental interactions. This classical unification theory deepens our understanding of the nature fundamental elements and interactions, develops a new concept of imaginary energy for electric and color charges, and provides a

  6. Fundamental Elements and Interactions of Nature: A Classical Unification Theory

    Directory of Open Access Journals (Sweden)

    Zhang T. X.

    2010-04-01

    Full Text Available A classical unification theory that completely unifies all the fundamental interactions of nature is developed. First, the nature is suggested to be composed of the following four fundamental elements: mass, radiation, electric charge, and color charge. All known types of matter or particles are a combination of one or more of the four fundamental elements. Photons are radiation; neutrons have only mass; protons have both mass and electric charge; and quarks contain mass, electric charge, and color charge. The nature fundamental interactions are interactions among these nature fundamental elements. Mass and radiation are two forms of real energy. Electric and color charges are con- sidered as two forms of imaginary energy. All the fundamental interactions of nature are therefore unified as a single interaction between complex energies. The interac- tion between real energies is the gravitational force, which has three types: mass-mass, mass-radiation, and radiation-radiation interactions. Calculating the work done by the mass-radiation interaction on a photon derives the Einsteinian gravitational redshift. Calculating the work done on a photon by the radiation-radiation interaction derives a radiation redshift, which is much smaller than the gravitational redshift. The interaction between imaginary energies is the electromagnetic (between electric charges, weak (between electric and color charges, and strong (between color charges interactions. In addition, we have four imaginary forces between real and imaginary energies, which are mass-electric charge, radiation-electric charge, mass-color charge, and radiation- color charge interactions. Among the four fundamental elements, there are ten (six real and four imaginary fundamental interactions. This classical unification theory deep- ens our understanding of the nature fundamental elements and interactions, develops a new concept of imaginary energy for electric and color charges, and provides a

  7. The implications of fundamental cause theory for priority setting.

    Science.gov (United States)

    Goldberg, Daniel S

    2014-10-01

    Application of fundamental cause theory to Powers and Faden's model of social justice highlights the ethical superiority of upstream public health interventions. In this article, I assess the ramifications of fundamental cause theory specifically in context of public health priority setting. Ethically optimal public health policy simultaneously maximizes overall population health and compresses health inequalities. The fundamental cause theory is an important framework in helping to identify which categories of public health interventions are most likely to advance these twin goals.

  8. Fundamental-mode sources in approach to critical experiments

    International Nuclear Information System (INIS)

    Goda, J.; Busch, R.

    2000-01-01

    An equivalent fundamental-mode source is an imaginary source that is distributed identically in space, energy, and angle to the fundamental-mode fission source. Therefore, it produces the same neutron multiplication as the fundamental-mode fission source. Even if two source distributions produce the same number of spontaneous fission neutrons, they will not necessarily contribute equally toward the multiplication of a given system. A method of comparing the relative importance of source distributions is needed. A factor, denoted as g* and defined as the ratio of the fixed-source multiplication to the fundamental-mode multiplication, is used to convert a given source strength to its equivalent fundamental-mode source strength. This factor is of interest to criticality safety as it relates to the 1/M method of approach to critical. Ideally, a plot of 1/M versus κ eff is linear. However, since 1/M = (1 minus κ eff )/g*, the plot will be linear only if g* is constant with κ eff . When g* increases with κ eff , the 1/M plot is said to be conservative because the critical mass is underestimated. However, it is possible for g* to decrease with κ eff yielding a nonconservative 1/M plot. A better understanding of g* would help predict whether a given approach to critical will be conservative or nonconservative. The equivalent fundamental-mode source strength g*S can be predicted by experiment. The experimental method was tested on the XIX-1 core on the Fast Critical Assembly at the Japan Atomic Energy Research Institute. The results showed a 30% difference between measured and calculated values. However, the XIX-1 reactor had significant intermediate-energy neutrons. The presence of intermediate-energy neutrons may have made the cross-section set used for predicted values less than ideal for the system

  9. Fundamental Rights and the EU Internal Market: Just how Fundamental are the EU Treaty Freedoms?
    A Normative Enquiry Based on John Rawls’ Political Philosophy

    Directory of Open Access Journals (Sweden)

    Nik J. de Boer

    2013-01-01

    Full Text Available This article assesses whether the EU Treaty freedoms - the free movement of goods, persons, services and capital - should be considered as fundamental rights which are hierarchically equal to other fundamental rights. It uses the political philosophy of John Rawls to assess why we should attach priority to certain rights and which rights should therefore be considered fundamental rights. On this basis it is argued that we should recognise two main types of fundamental rights, namely basic rights and liberties associated with Rawls' first principle of justice and the rights associated with the principle of fair equality of opportunity. This is followed by an analysis of the interpretation that the European Court of Justice (CJEU gives to the Treaty freedoms. On the basis of the normative framework, it is argued that the Treaty freedoms can be seen as fundamental rights insofar as they embody the value of equality of opportunity. Nonetheless, the CJEU increasingly seems to rely on a broader market access approach rather than an equal treatment approach in interpreting the Treaty freedoms. It is argued that where equal treatment is not at stake, the Treaty freedoms should not be seen as fundamental rights. Therefore, in cases where there is a conflict between a fundamental right and a Treaty freedom the CJEU should carefully distinguish between these two different interpretations of the Treaty freedoms. In cases where it is merely market access that is at stake, the CJEU should regard the protection of fundamental rights as more important, and be very careful in allowing a restriction of fundamental rights in order to protect the exercise of the Treaty freedom. On the other hand, in cases where the Treaty freedoms can be seen as protecting equality of opportunity and where they conflict with other fundamental rights, the Court is justified in construing the conflict as a right-right conflict in which a fair balance has to be sought.

  10. Fundamentals of convolutional coding

    CERN Document Server

    Johannesson, Rolf

    2015-01-01

    Fundamentals of Convolutional Coding, Second Edition, regarded as a bible of convolutional coding brings you a clear and comprehensive discussion of the basic principles of this field * Two new chapters on low-density parity-check (LDPC) convolutional codes and iterative coding * Viterbi, BCJR, BEAST, list, and sequential decoding of convolutional codes * Distance properties of convolutional codes * Includes a downloadable solutions manual

  11. Bioreactor-Based Online Recovery of Human Progenitor Cells with Uncompromised Regenerative Potential: A Bone Tissue Engineering Perspective.

    Directory of Open Access Journals (Sweden)

    Maarten Sonnaert

    Full Text Available The use of a 3D perfusion culture environment for stem cell expansion has been shown to be beneficial for maintenance of the original cell functionality but due to several system inherent characteristics such as the presence of extracellular matrix, the continued development and implementation of 3D perfusion bioreactor technologies is hampered. Therefore, this study developed a methodology for harvesting a progenitor cell population from a 3D open porous culture surface after expansion in a perfusion bioreactor and performed a functional characterization of the expanded cells. An initial screening showed collagenase to be the most interesting reagent to release the cells from the 3D culture surface as it resulted in high yields without compromising cell viability. Subsequently a Design of Experiment approach was used to obtain optimized 3D harvest conditions by assessing the interplay of flow rate, collagenase concentration and incubation time on the harvest efficiency, viability and single cell fraction. Cells that were recovered with the optimized harvest protocol, by perfusing a 880 U/ml collagenase solution for 7 hours at a flow rate of 4 ml/min, were thereafter functionally analyzed for their characteristics as expanded progenitor cell population. As both the in vitro tri-lineage differentiation capacity and the in vivo bone forming potential were maintained after 3D perfusion bioreactor expansion we concluded that the developed seeding, culture and harvest processes did not significantly compromise the viability and potency of the cells and can contribute to the future development of integrated bioprocesses for stem cell expansion.

  12. Fundamentals of modern unsteady aerodynamics

    CERN Document Server

    Gülçat, Ülgen

    2010-01-01

    This introduction to the principles of unsteady aerodynamics covers all the core concepts, provides readers with a review of the fundamental physics, terminology and basic equations, and covers hot new topics such as the use of flapping wings for propulsion.

  13. Downstream bioprocess characterisation within microfluidic devices

    DEFF Research Database (Denmark)

    Marques, Marco; Krühne, Ulrich; Szita, Nicolas

    2016-01-01

    developed which has, to some extent, hindered their implementation as early process development tools. Microfluidic devices are particularly attractive for using fewer resources, for having the possibility of parallelisation and for requiring fewer mechanical manipulations. The expectation...... is that these devices will facilitate the rapid definition of critical process parameters, and thus ultimately reduce production costs. We have developed several microfluidic mDUOs and combined them with advanced and novel analytical approaches, resulting in devices that can potentially be employed for both analytical...... for the liquid–liquid extraction of pharmaceuticals, for the purification and concentration of drug delivery vehicles, and for the flocculation of yeast cells in microfluidic devices. For the latter, we will present for the first time the capability to study flocculation-growth independent from the floc breakage...

  14. Fundamentals of Turbulent and Multi-Phase Combustion

    CERN Document Server

    Kuo, Kenneth Kuan-yun

    2012-01-01

    Detailed coverage of advanced combustion topics from the author of Principles of Combustion, Second Edition Turbulence, turbulent combustion, and multiphase reacting flows have become major research topics in recent decades due to their application across diverse fields, including energy, environment, propulsion, transportation, industrial safety, and nanotechnology. Most of the knowledge accumulated from this research has never been published in book form-until now. Fundamentals of Turbulent and Multiphase Combustion presents up-to-date, integrated coverage of the fundamentals of turbulence

  15. Fundamental absorption edge of NiO nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Sokolov, V.I., E-mail: visokolov@imp.uran.ru [Institute of Metal Physics, Ural Branch of RAS, S. Kovalevskaya Street 18, 620990 Yekaterinburg (Russian Federation); Druzhinin, A.V. [Institute of Metal Physics, Ural Branch of RAS, S. Kovalevskaya Street 18, 620990 Yekaterinburg (Russian Federation); Kim, G.A. [Institute of Organic Synthesis Ural Branch of RAS, S. Kovalevskaya Street 20, 620990 Yekaterinburg (Russian Federation); Gruzdev, N.B.; Yermakov, A.Ye.; Uimin, M.A.; Byzov, I.V.; Shchegoleva, N.N.; Vykhodets, V.B.; Kurennykh, T.E. [Institute of Metal Physics, Ural Branch of RAS, S. Kovalevskaya Street 18, 620990 Yekaterinburg (Russian Federation)

    2013-12-01

    NiO nanocrystals with the average size of 5, 10 and 25 nm were synthesized by gas-condensation method. The well-defined increase of the optical density D near the fundamental absorption edge of NiO nanocrystals in the range of 3.5–4.0 eV observed after the annealing in air is caused by the oxygen content growth. It is the direct experimental evidence of the fact that p—d charge transfer transitions form the fundamental absorption edge.

  16. Fundamental absorption edge of NiO nanocrystals

    International Nuclear Information System (INIS)

    Sokolov, V.I.; Druzhinin, A.V.; Kim, G.A.; Gruzdev, N.B.; Yermakov, A.Ye.; Uimin, M.A.; Byzov, I.V.; Shchegoleva, N.N.; Vykhodets, V.B.; Kurennykh, T.E.

    2013-01-01

    NiO nanocrystals with the average size of 5, 10 and 25 nm were synthesized by gas-condensation method. The well-defined increase of the optical density D near the fundamental absorption edge of NiO nanocrystals in the range of 3.5–4.0 eV observed after the annealing in air is caused by the oxygen content growth. It is the direct experimental evidence of the fact that p—d charge transfer transitions form the fundamental absorption edge

  17. Mathematical analysis fundamentals

    CERN Document Server

    Bashirov, Agamirza

    2014-01-01

    The author's goal is a rigorous presentation of the fundamentals of analysis, starting from elementary level and moving to the advanced coursework. The curriculum of all mathematics (pure or applied) and physics programs include a compulsory course in mathematical analysis. This book will serve as can serve a main textbook of such (one semester) courses. The book can also serve as additional reading for such courses as real analysis, functional analysis, harmonic analysis etc. For non-math major students requiring math beyond calculus, this is a more friendly approach than many math-centric o

  18. Fundamentals of magnetism

    CERN Document Server

    Getzlaff, Mathias

    2007-01-01

    In the last decade a tremendous progress has taken place in understanding the basis of magnetism, especially in reduced dimensions. In the first part, the fundamentals of magnetism are conveyed for atoms and bulk-like solid-state systems providing a basis for the understanding of new phenomena which exclusively occur in low-dimensional systems as the giant magneto resistance. This wide field is discussed in the second part and illustrated by copious examples. This textbook is particularly suitable for graduate students in physical and materials sciences. It includes numerous examples, exercises, and references.

  19. A plant U-box protein, PUB4, regulates asymmetric cell division and cell proliferation in the root meristem

    NARCIS (Netherlands)

    Kinoshita, A.; Hove, ten C.A.; Tabata, R.; Yamada, M.; Shimizu, N.; Ishida, T.; Yamaguchi, K.; Shigenobu, S.; Takebayashi, Y.; Luchies, J.; Kobayashi, M.; Kurata, T.; Wada, T.; Seo, M.; Hasebe, M.; Blilou, I.; Fukuda, H.; Scheres, B.; Heidstra, R.; Kamiya, Y.; Sawa, S.

    2015-01-01

    The root meristem (RM) is a fundamental structure that is responsible for postembryonic root growth. The RM contains the quiescent center (QC), stem cells and frequently dividing meristematic cells, in which the timing and the frequency of cell division are tightly regulated. In Arabidopsis

  20. Process analytical technology (PAT) in insect and mammalian cell culture processes: dielectric spectroscopy and focused beam reflectance measurement (FBRM).

    Science.gov (United States)

    Druzinec, Damir; Weiss, Katja; Elseberg, Christiane; Salzig, Denise; Kraume, Matthias; Pörtner, Ralf; Czermak, Peter

    2014-01-01

    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 to allow for early interventions in order to prevent losses of production batches due to quality issues. Process analytical technologies such as the dielectric spectroscopy or focused beam reflectance measurement (FBRM) are possible online monitoring tools, which can be applied to monitor cell growth as well as morphological changes. Since the dielectric spectroscopy only captures cells with intact cell membranes, even information about dead cells with ruptured or leaking cell membranes can be derived. The following chapter describes the application of dielectric spectroscopy on various virus-infected and non-infected cell lines with respect to adherent as well as suspension cultures in common stirred tank reactors. The adherent mammalian cell lines Vero (African green monkey kidney cells) and hMSC-TERT (telomerase-immortalized human mesenchymal stem cells) are thereby cultured on microcarrier, which provide the required growth surface and allow the cultivation of these cells even in dynamic culture systems. In turn, the insect-derived cell lines S2 and Sf21 are used as examples for cells typically cultured in suspension. Moreover, the FBRM technology as a further monitoring tool for cell culture applications has been included in this chapter using the example of Drosophila S2 insect cells.

  1. Fundamental length and relativistic length

    International Nuclear Information System (INIS)

    Strel'tsov, V.N.

    1988-01-01

    It si noted that the introduction of fundamental length contradicts the conventional representations concerning the contraction of the longitudinal size of fast-moving objects. The use of the concept of relativistic length and the following ''elongation formula'' permits one to solve this problem

  2. High-accuracy mass spectrometry for fundamental studies.

    Science.gov (United States)

    Kluge, H-Jürgen

    2010-01-01

    Mass spectrometry for fundamental studies in metrology and atomic, nuclear and particle physics requires extreme sensitivity and efficiency as well as ultimate resolving power and accuracy. An overview will be given on the global status of high-accuracy mass spectrometry for fundamental physics and metrology. Three quite different examples of modern mass spectrometric experiments in physics are presented: (i) the retardation spectrometer KATRIN at the Forschungszentrum Karlsruhe, employing electrostatic filtering in combination with magnetic-adiabatic collimation-the biggest mass spectrometer for determining the smallest mass, i.e. the mass of the electron anti-neutrino, (ii) the Experimental Cooler-Storage Ring at GSI-a mass spectrometer of medium size, relative to other accelerators, for determining medium-heavy masses and (iii) the Penning trap facility, SHIPTRAP, at GSI-the smallest mass spectrometer for determining the heaviest masses, those of super-heavy elements. Finally, a short view into the future will address the GSI project HITRAP at GSI for fundamental studies with highly-charged ions.

  3. A new fundamental type of conformational isomerism

    Science.gov (United States)

    Canfield, Peter J.; Blake, Iain M.; Cai, Zheng-Li; Luck, Ian J.; Krausz, Elmars; Kobayashi, Rika; Reimers, Jeffrey R.; Crossley, Maxwell J.

    2018-06-01

    Isomerism is a fundamental chemical concept, reflecting the fact that the arrangement of atoms in a molecular entity has a profound influence on its chemical and physical properties. Here we describe a previously unclassified fundamental form of conformational isomerism through four resolved stereoisomers of a transoid (BF)O(BF)-quinoxalinoporphyrin. These comprise two pairs of enantiomers that manifest structural relationships not describable within existing IUPAC nomenclature and terminology. They undergo thermal diastereomeric interconversion over a barrier of 104 ± 2 kJ mol-1, which we term `akamptisomerization'. Feasible interconversion processes between conceivable synthesis products and reaction intermediates were mapped out by density functional theory calculations, identifying bond-angle inversion (BAI) at a singly bonded atom as the reaction mechanism. We also introduce the necessary BAI stereodescriptors parvo and amplo. Based on an extended polytope formalism of molecular structure and stereoisomerization, BAI-driven akamptisomerization is shown to be the final fundamental type of conformational isomerization.

  4. Integrating fundamental movement skills in late childhood.

    Science.gov (United States)

    Gimenez, Roberto; Manoel, Edison de J; de Oliveira, Dalton Lustosa; Dantas, Luiz; Marques, Inara

    2012-04-01

    The study examined how children of different ages integrate fundamental movement skills, such as running and throwing, and whether their developmental status was related to the combination of these skills. Thirty children were divided into three groups (G1 = 6-year-olds, G2 = 9-year-olds, and G3 = 12-year-olds) and filmed performing three tasks: running, overarm throwing, and the combined task. Patterns were identified and described, and the efficiency of integration was calculated (distance differences of the ball thrown in two tasks, overarm throwing and combined task). Differences in integration were related to age: the 6-year-olds were less efficient in combining the two skills than the 9- and 12-year-olds. These differences may be indicative of a phase of integrating fundamental movement skills in the developmental sequence. This developmental status, particularly throwing, seems to be related to the competence to integrate skills, which suggests that fundamental movement skills may be developmental modules.

  5. Baking Arithmetic and Error Analyses for PEFP Fundamental Power Couplers

    International Nuclear Information System (INIS)

    Zhang, Liping; An, Sun; Tang, Yazhe; Cho, Yong Sub

    2009-01-01

    The Proton Engineering Frontier Project (PEFP) is considering developing and using SRF technology to accelerate a proton beam at 700 MHz in its present project and its extended project (PEP). The first section of the PEFP SRF linac (SCL) is composed of low-beta cryomodules. Each cryomodule has three 5-cell cavities and each cavity has one fundamental power coupler (FPC). Before the high power RF processing, each FPC needs to be baked out for 24 hours at 200 degrees Celsius ( .deg. C). The whole control system is described in reference, in this system, the temperature in the baking-box need to be changed according to three straight lines with different slope. This paper described how we can make the temperature of the baking-box changed according to the required values

  6. Baking Arithmetic and Error Analyses for PEFP Fundamental Power Couplers

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liping; An, Sun; Tang, Yazhe; Cho, Yong Sub [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-05-15

    The Proton Engineering Frontier Project (PEFP) is considering developing and using SRF technology to accelerate a proton beam at 700 MHz in its present project and its extended project (PEP). The first section of the PEFP SRF linac (SCL) is composed of low-beta cryomodules. Each cryomodule has three 5-cell cavities and each cavity has one fundamental power coupler (FPC). Before the high power RF processing, each FPC needs to be baked out for 24 hours at 200 degrees Celsius ( .deg. C). The whole control system is described in reference, in this system, the temperature in the baking-box need to be changed according to three straight lines with different slope. This paper described how we can make the temperature of the baking-box changed according to the required values.

  7. Fundamentals of condensed matter physics

    CERN Document Server

    Cohen, Marvin L

    2016-01-01

    Based on an established course and covering the fundamentals, central areas, and contemporary topics of this diverse field, Fundamentals of Condensed Matter Physics is a much-needed textbook for graduate students. The book begins with an introduction to the modern conceptual models of a solid from the points of view of interacting atoms and elementary excitations. It then provides students with a thorough grounding in electronic structure as a starting point to understand many properties of condensed matter systems - electronic, structural, vibrational, thermal, optical, transport, magnetic and superconductivity - and methods to calculate them. Taking readers through the concepts and techniques, the text gives both theoretically and experimentally inclined students the knowledge needed for research and teaching careers in this field. It features 200 illustrations, 40 worked examples and 150 homework problems for students to test their understanding. Solutions to the problems for instructors are available at w...

  8. Protection of fundamental rights today

    International Nuclear Information System (INIS)

    Meyer-Abich, K.M.

    1984-01-01

    Technical developments can both change the methods of dealing with existing conflicts, and cause new conflicts. Meyer-Abich analyzes five conflicts caused by the technological development in the solution of which the constitutional, liberal, and democratic protection of fundamental rights is not at all guaranteed. Meyer-Abich thinks that these new conflicts can be solved in the framework of the liberal constitutional state, if legal and political consequences are taken in order to guarantee the uncharged protection of fundamental rights under changing conditions. The necessary reforms can, however, only be realized if the way how state and science see themselves changes. Both have to give up their one-sidedness into which have been pushed by conflict which havbe been caused by the scientific and technical development. Only then it will be possible to solve the jemerging conflicts without eopardizing the integritiy of the society. (orig.) [de

  9. Fundamental solutions of singular SPDEs

    International Nuclear Information System (INIS)

    Selesi, Dora

    2011-01-01

    Highlights: → Fundamental solutions of linear SPDEs are constructed. → Wick-convolution product is introduced for the first time. → Fourier transformation maps Wick-convolution into Wick product. → Solutions of linear SPDEs are expressed via Wick-convolution with fundamental solutions. → Stochastic Helmholtz equation is solved. - Abstract: This paper deals with some models of mathematical physics, where random fluctuations are modeled by white noise or other singular Gaussian generalized processes. White noise, as the distributional derivative od Brownian motion, which is the most important case of a Levy process, is defined in the framework of Hida distribution spaces. The Fourier transformation in the framework of singular generalized stochastic processes is introduced and its applications to solving stochastic differential equations involving Wick products and singularities such as the Dirac delta distribution are presented. Explicit solutions are obtained in form of a chaos expansion in the Kondratiev white noise space, while the coefficients of the expansion are tempered distributions. Stochastic differential equations of the form P(ω, D) ◊ u(x, ω) = A(x, ω) are considered, where A is a singular generalized stochastic process and P(ω, D) is a partial differential operator with random coefficients. We introduce the Wick-convolution operator * which enables us to express the solution as u = s*A ◊ I ◊(-1) , where s denotes the fundamental solution and I is the unit random variable. In particular, the stochastic Helmholtz equation is solved, which in physical interpretation describes waves propagating with a random speed from randomly appearing point sources.

  10. Fundamental gravitational limitations to quantum computing

    International Nuclear Information System (INIS)

    Gambini, R.; Porto, A.; Pullin, J.

    2006-01-01

    Lloyd has considered the ultimate limitations the fundamental laws of physics place on quantum computers. He concludes in particular that for an 'ultimate laptop' (a computer of one liter of volume and one kilogram of mass) the maximum number of operations per second is bounded by 10 51 . The limit is derived considering ordinary quantum mechanics. Here we consider additional limits that are placed by quantum gravity ideas, namely the use of a relational notion of time and fundamental gravitational limits that exist on time measurements. We then particularize for the case of an ultimate laptop and show that the maximum number of operations is further constrained to 10 47 per second. (authors)

  11. Fundamental problems in fault detection and identification

    DEFF Research Database (Denmark)

    Saberi, Ali; Stoorvogel, Anton A.; Sannuti, Peddapullaiah

    1999-01-01

    For certain fundamental problems in fault detection and identification, the necessary and sufficient conditions for their solvability are derived. These conditions are weaker than the ones found in the literature, since we do not assume any particular structure for the residual generator......For certain fundamental problems in fault detection and identification, the necessary and sufficient conditions for their solvability are derived. These conditions are weaker than the ones found in the literature, since we do not assume any particular structure for the residual generator...

  12. Philosophy of Information and Fundamental Problems of Modern Informatics

    Directory of Open Access Journals (Sweden)

    Konstantin Kolin

    2011-10-01

    Full Text Available Actual philosophical and scientifically methodological problems of modern Informatics as fundamental science and a complex scientific direction are considered. Communication of these problems with prospects of development of Informatics and fundamental science as a whole is shown.

  13. Summary: fundamental interactions and processes

    International Nuclear Information System (INIS)

    Koltun, D.S.

    1982-01-01

    The subjects of the talks of the first day of the workshop are discussed in terms of fundamental interactions, dynamical theory, and relevant degrees of freedom. Some general considerations are introduced and are used to confront the various approaches taken in the earlier talks

  14. Fundamentals of Welding. Teacher Edition.

    Science.gov (United States)

    Fortney, Clarence; And Others

    These instructional materials assist teachers in improving instruction on the fundamentals of welding. The following introductory information is included: use of this publication; competency profile; instructional/task analysis; related academic and workplace skills list; tools, materials, and equipment list; and 27 references. Seven units of…

  15. Fundamentals of Biomass pellet production

    DEFF Research Database (Denmark)

    Holm, Jens Kai; Henriksen, Ulrik Birk; Hustad, Johan Einar

    2005-01-01

    Pelletizing experiments along with modelling of the pelletizing process have been carried out with the aim of understanding the fundamental physico-chemical mechanisms that control the quality and durability of biomass pellets. A small-scale California pellet mill (25 kg/h) located with the Biomass...

  16. Fundamentals: IVC and Computer Science

    NARCIS (Netherlands)

    Gozalvez, Javier; Haerri, Jerome; Hartenstein, Hannes; Heijenk, Geert; Kargl, Frank; Petit, Jonathan; Scheuermann, Björn; Tieler, Tessa; Altintas, O.; Dressler, F.; Hartenstein, H.; Tonguz, O.K.

    The working group on “Fundamentals: IVC and Computer Science‿ discussed the lasting value of achieved research results as well as potential future directions in the field of inter- vehicular communication. Two major themes ‘with variations’ were the dependence on a specific technology (particularly

  17. Good Administration as a Fundamental Right

    Directory of Open Access Journals (Sweden)

    Margrét Vala Kristjánsdóttir

    2013-06-01

    Full Text Available The EU Charter of Fundamental Rights lists good administration as a fundamental right. The scope of this right, as defined in Article 41 of the EU Charter, is limited to situations in which persons are dealing with the institutions and bodies of the European Union; this gives it a narrower scope than that of the Charter as a whole. This paper discusses the status of this right as a subjective, fundamental right and a codified principle of EU law. The focus is on the question of applicability of the right to situations in which persons are dealing with the institutions and bodies of Member States and questions are raised regarding the implications of Article 41 in this respect. The paper concludes that Article 41 of the Charter in fact limits the applicability of good administration to the institutions and bodies of the EU. This does not however, preclude the applicability of a general principle of good administration, as established by the European Court of Justice, to Member States and the formal recognition of this principle in the EU Charter seems to affect legal reasoning and contribute to some extent to the protection of administrative rules in the implementation of EU law.

  18. Lessons from single-cell transcriptome analysis of oxygen-sensing cells.

    Science.gov (United States)

    Zhou, Ting; Matsunami, Hiroaki

    2018-05-01

    The advent of single-cell RNA-sequencing (RNA-Seq) technology has enabled transcriptome profiling of individual cells. Comprehensive gene expression analysis at the single-cell level has proven to be effective in characterizing the most fundamental aspects of cellular function and identity. This unbiased approach is revolutionary for small and/or heterogeneous tissues like oxygen-sensing cells in identifying key molecules. Here, we review the major methods of current single-cell RNA-Seq technology. We discuss how this technology has advanced the understanding of oxygen-sensing glomus cells in the carotid body and helped uncover novel oxygen-sensing cells and mechanisms in the mice olfactory system. We conclude by providing our perspective on future single-cell RNA-Seq research directed at oxygen-sensing cells.

  19. Treatment strategies for high resveratrol induction in Vitis vinifera L. cell suspension culture

    Directory of Open Access Journals (Sweden)

    Thu V. Vuong

    2014-06-01

    Full Text Available Bioprocesses capable of producing large scales of resveratrol at nutraceutical grade are in demand. This study herein investigated treatment strategies to induce the production of resveratrol in Vitis vinifera L. cell suspension cultures. Among seven investigated elicitors, jasmonic acid (JA, salicylic acid, β-glucan (GLU, and chitosan enhanced the production of intracellular resveratrol manyfold. The combined treatment of JA and GLU increased extracellular resveratrol production by up to tenfold. The application of Amberlite XAD-7 resin for in situ removal and artificial storage of secreted resveratrol further increased resveratrol production by up to four orders of magnitude. The level of resveratrol produced in response to the combined treatment with 200 g/L XAD-7, 10 μM JA and 1 mg/mL GLU was approximately 2400 mg/L, allowing the production of resveratrol at an industrial scale. The high yield of resveratrol is due to the involvement of a number of mechanisms working in concert.

  20. Switching the mode of sucrose utilization by Saccharomyces cerevisiae

    OpenAIRE

    Badotti, Fernanda; Dário, Marcelo G; Alves, Sergio L; Cordioli, Maria Luiza A; Miletti, Luiz C; de Araujo, Pedro S; Stambuk, Boris U

    2008-01-01

    Abstract Background Overflow metabolism is an undesirable characteristic of aerobic cultures of Saccharomyces cerevisiae during biomass-directed processes. It results from elevated sugar consumption rates that cause a high substrate conversion to ethanol and other bi-products, severely affecting cell physiology, bioprocess performance, and biomass yields. Fed-batch culture, where sucro...