SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool

PubMed Central

Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

2008-01-01

Background It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models. Results This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface. Conclusion SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes. PMID:18706080

SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool.

PubMed

Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

2008-08-15

It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models. This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface. SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes.

Lessons from (patho)physiological tissue stiffness and their implications for drug screening, drug delivery and regenerative medicine.

PubMed

Chen, Wen Li Kelly; Simmons, Craig A

2011-04-30

Diseased tissues are noted for their compromised mechanical properties, which contribute to organ failure; regeneration entails restoration of tissue structure and thereby functions. Thus, the physical signature of a tissue is closely associated with its biological function. In this review, we consider a mechanics-centric view of disease and regeneration by drawing parallels between in vivo tissue-level observations and corroborative cellular evidence in vitro to demonstrate the importance of the mechanical stiffness of the extracellular matrix in these processes. This is not intended to devalue the importance of biochemical signaling; in fact, as we discuss, many mechanical stiffness-driven processes not only require cooperation with biochemical cues, but they ultimately converge at common signaling cascades to influence cell and tissue function in an integrative manner. The study of how physical and biochemical signals collectively modulate cell function not only brings forth a more holistic understanding of cell (patho)biology, but it also creates opportunities to control material properties to improve culture platforms for research and drug screening and aid in the rationale design of biomaterials for molecular therapy and tissue engineering applications. Copyright © 2011 Elsevier B.V. All rights reserved.

Time-resolved SERS for characterizing extracellular vesicles

NASA Astrophysics Data System (ADS)

Rojalin, Tatu; Saari, Heikki; Somersalo, Petter; Laitinen, Saara; Turunen, Mikko; Viitala, Tapani; Wachsmann-Hogiu, Sebastian; Smith, Zachary J.; Yliperttula, Marjo

2017-02-01

The aim of this work is to develop a platform for characterizing extracellular vesicles (EV) by using gold-polymer nanopillar SERS arrays simultaneously circumventing the photoluminescence-related disadvantages of Raman with a time-resolved approach. EVs are rich of biochemical information reporting of, for example, diseased state of the biological system. Currently, straightforward, label-free and fast EV characterization methods with low sample consumption are warranted. In this study, SERS spectra of red blood cell and platelet derived EVs were successfully measured and their biochemical contents analyzed using multivariate data analysis techniques. The developed platform could be conveniently used for EV analytics in general.

Optofluidic lasers with a single molecular layer of gain

PubMed Central

Chen, Qiushu; Ritt, Michael; Sivaramakrishnan, Sivaraj; Sun, Yuze; Fan, Xudong

2014-01-01

We achieve optofluidic lasers with a single molecular layer of gain, in which green fluorescent protein, dye-labeled bovine serum albumin, and dye-labeled DNA are respectively used as the gain medium and attached to the surface of a ring resonator via surface immobilization biochemical methods. It is estimated that the surface density of the gain molecules is on the order of 1012/cm2, sufficient for lasing under pulsed optical excitation. It is further shown that the optofluidic laser can be tuned by energy transfer mechanisms through biomolecular interactions. This work not only opens a door to novel photonic devices that can be controlled at the level of a single molecular layer, but also provides a promising sensing platform to analyze biochemical processes at the solid-liquid interface. PMID:25312306

Integrated microfluidic platforms for investigating neuronal networks

NASA Astrophysics Data System (ADS)

Kim, Hyung Joon

This dissertation describes the development and application of integrated microfluidics-based assay platforms to study neuronal activities in the nervous system in-vitro. The assay platforms were fabricated using soft lithography and micro/nano fabrication including microfluidics, surface patterning, and nanomaterial synthesis. The use of integrated microfluidics-based assay platform allows culturing and manipulating many types of neuronal tissues in precisely controlled microenvironment. Furthermore, they provide organized multi-cellular in-vitro model, long-term monitoring with live cell imaging, and compatibility with molecular biology techniques and electrophysiology experiment. In this dissertation, the integrated microfluidics-based assay platforms are developed for investigation of neuronal activities such as local protein synthesis, impairment of axonal transport by chemical/physical variants, growth cone path finding under chemical/physical cues, and synaptic transmission in neuronal circuit. Chapter 1 describes the motivation, objectives, and scope for developing in-vitro platform to study various neuronal activities. Chapter 2 introduces microfluidic culture platform for biochemical assay with large-scale neuronal tissues that are utilized as model system in neuroscience research. Chapter 3 focuses on the investigation of impaired axonal transport by beta-Amyloid and oxidative stress. The platform allows to control neuronal processes and to quantify mitochondrial movement in various regions of axons away from applied drugs. Chapter 4 demonstrates the development of microfluidics-based growth cone turning assay to elucidate the mechanism underlying axon guidance under soluble factors and shear flow. Using this platform, the behaviors of growth cone of mammalian neurons are verified under the gradient of inhibitory molecules and also shear flow in well-controlled manner. In Chapter 5, I combine in-vitro multicellular model with microfabricated MEA (multielectrode array) or nanowire electrode array to study electrophysiology in neuronal network. Also, "diode-like" microgrooves to control the number of neuronal processes is embedded in this platform. Chapter 6 concludes with a possible future direction of this work. Interfacing micro/nanotechnology with primary neuron culture would open many doors in fundamental neuroscience research and also biomedical innovation.

Biochemical Characterization of β-Amino Acid Incorporation in Fluvirucin B 2 Biosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barajas, Jesus F.; Zargar, Amin; Pang, Bo

Naturally occurring lactams, such as the polyketide-derived macrolactams, provide a diverse class of natural products that could enhance existing chemically produced lactams. While β-amino acid loading in the fluvirucin B 2 polyketide pathway has been proposed by a previously identified putative biosynthetic gene cluster, biochemical characterization of the complete loading enzymes has not been described. In this paper, we elucidate the complete biosynthetic pathway of the β-amino acid loading pathway in fluvirucin B 2 biosynthesis. We demonstrate the promiscuity of the loading pathway to utilize a range of amino acids and further illustrate the ability to introduce non-native acyl transferasesmore » to selectively transfer β-amino acids onto a PKS loading platform. The results presented here provide a detailed biochemical description of β-amino acid selection and will further aid in future efforts to develop engineered lactam-producing PKS platforms.« less

Biochemical Characterization of β-Amino Acid Incorporation in Fluvirucin B 2 Biosynthesis

DOE PAGES

Barajas, Jesus F.; Zargar, Amin; Pang, Bo; ...

2018-03-30

Naturally occurring lactams, such as the polyketide-derived macrolactams, provide a diverse class of natural products that could enhance existing chemically produced lactams. While β-amino acid loading in the fluvirucin B 2 polyketide pathway has been proposed by a previously identified putative biosynthetic gene cluster, biochemical characterization of the complete loading enzymes has not been described. In this paper, we elucidate the complete biosynthetic pathway of the β-amino acid loading pathway in fluvirucin B 2 biosynthesis. We demonstrate the promiscuity of the loading pathway to utilize a range of amino acids and further illustrate the ability to introduce non-native acyl transferasesmore » to selectively transfer β-amino acids onto a PKS loading platform. The results presented here provide a detailed biochemical description of β-amino acid selection and will further aid in future efforts to develop engineered lactam-producing PKS platforms.« less

Payao: a community platform for SBML pathway model curation

PubMed Central

Matsuoka, Yukiko; Ghosh, Samik; Kikuchi, Norihiro; Kitano, Hiroaki

2010-01-01

Summary: Payao is a community-based, collaborative web service platform for gene-regulatory and biochemical pathway model curation. The system combines Web 2.0 technologies and online model visualization functions to enable a collaborative community to annotate and curate biological models. Payao reads the models in Systems Biology Markup Language format, displays them with CellDesigner, a process diagram editor, which complies with the Systems Biology Graphical Notation, and provides an interface for model enrichment (adding tags and comments to the models) for the access-controlled community members. Availability and implementation: Freely available for model curation service at http://www.payaologue.org. Web site implemented in Seaser Framework 2.0 with S2Flex2, MySQL 5.0 and Tomcat 5.5, with all major browsers supported. Contact: kitano@sbi.jp PMID:20371497

Understanding sequence similarity and framework analysis between centromere proteins using computational biology.

PubMed

Doss, C George Priya; Chakrabarty, Chiranjib; Debajyoti, C; Debottam, S

2014-11-01

Certain mysteries pointing toward their recruitment pathways, cell cycle regulation mechanisms, spindle checkpoint assembly, and chromosome segregation process are considered the centre of attraction in cancer research. In modern times, with the established databases, ranges of computational platforms have provided a platform to examine almost all the physiological and biochemical evidences in disease-associated phenotypes. Using existing computational methods, we have utilized the amino acid residues to understand the similarity within the evolutionary variance of different associated centromere proteins. This study related to sequence similarity, protein-protein networking, co-expression analysis, and evolutionary trajectory of centromere proteins will speed up the understanding about centromere biology and will create a road map for upcoming researchers who are initiating their work of clinical sequencing using centromere proteins.

Biochemical component identification by plasmonic improved whispering gallery mode optical resonance based sensor

NASA Astrophysics Data System (ADS)

Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Saetchnikov, Anton V.; Schweiger, Gustav; Ostendorf, Andreas

2014-05-01

Experimental data on detection and identification of variety of biochemical agents, such as proteins, microelements, antibiotic of different generation etc. in both single and multi component solutions under varied in wide range concentration analyzed on the light scattering parameters of whispering gallery mode optical resonance based sensor are represented. Multiplexing on parameters and components has been realized using developed fluidic sensor cell with fixed in adhesive layer dielectric microspheres and data processing. Biochemical component identification has been performed by developed network analysis techniques. Developed approach is demonstrated to be applicable both for single agent and for multi component biochemical analysis. Novel technique based on optical resonance on microring structures, plasmon resonance and identification tools has been developed. To improve a sensitivity of microring structures microspheres fixed by adhesive had been treated previously by gold nanoparticle solution. Another technique used thin film gold layers deposited on the substrate below adhesive. Both biomolecule and nanoparticle injections caused considerable changes of optical resonance spectra. Plasmonic gold layers under optimized thickness also improve parameters of optical resonance spectra. Biochemical component identification has been also performed by developed network analysis techniques both for single and for multi component solution. So advantages of plasmon enhancing optical microcavity resonance with multiparameter identification tools is used for development of a new platform for ultra sensitive label-free biomedical sensor.

Modular microfluidics for point-of-care protein purifications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Millet, L. J.; Lucheon, J. D.; Standaert, R. F.

Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured tomore » suit a variety of fluidic operations or biochemical processes. In conclusion, we demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.« less

Modular microfluidics for point-of-care protein purifications.

PubMed

Millet, L J; Lucheon, J D; Standaert, R F; Retterer, S T; Doktycz, M J

2015-04-21

Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured to suit a variety of fluidic operations or biochemical processes. We demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.

Modular microfluidics for point-of-care protein purifications

DOE PAGES

Millet, L. J.; Lucheon, J. D.; Standaert, R. F.; ...

2015-01-01

Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured tomore » suit a variety of fluidic operations or biochemical processes. In conclusion, we demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.« less

The Molecular Basis of Wound Healing Processes Induced by Lithospermi Radix: A Proteomics and Biochemical Analysis

PubMed Central

Hsiao, Chia-Yen; Tsai, Tung-Hu; Chak, Kin-Fu

2012-01-01

Lithospermi Radix (LR) is an effective traditional Chinese herb in various types of wound healing; however, its mechanism of action remains unknown. A biochemical and proteomic platform was generated to explore the biological phenomena associated with LR and its active component shikonin. We found that both LR ethanol extracts and shikonin are able to promote cell proliferation by up to 25%. The results of proteomic analysis revealed that twenty-two differentially expressed proteins could be identified when fibroblast cells were treated with LR or shikonin. The functions of those proteins are associated with antioxidant activity, antiapoptosis activity, the regulation of cell mobility, the secretion of collagen, the removal of abnormal proteins, and the promotion of cell proliferation, indicating that the efficacy of LR in wound healing may be derived from a synergistic effect on a number of factors induced by the herbal medicine. Furthermore, an animal model confirmed that LR is able to accelerate wound healing on the flank back of the SD rats. Together these findings help to pinpoint the molecular basis of wound healing process induced by LR. PMID:23024692

Synthetic in vitro transcriptional oscillators

PubMed Central

Kim, Jongmin; Winfree, Erik

2011-01-01

The construction of synthetic biochemical circuits from simple components illuminates how complex behaviors can arise in chemistry and builds a foundation for future biological technologies. A simplified analog of genetic regulatory networks, in vitro transcriptional circuits, provides a modular platform for the systematic construction of arbitrary circuits and requires only two essential enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H, to produce and degrade RNA signals. In this study, we design and experimentally demonstrate three transcriptional oscillators in vitro. First, a negative feedback oscillator comprising two switches, regulated by excitatory and inhibitory RNA signals, showed up to five complete cycles. To demonstrate modularity and to explore the design space further, a positive-feedback loop was added that modulates and extends the oscillatory regime. Finally, a three-switch ring oscillator was constructed and analyzed. Mathematical modeling guided the design process, identified experimental conditions likely to yield oscillations, and explained the system's robust response to interference by short degradation products. Synthetic transcriptional oscillators could prove valuable for systematic exploration of biochemical circuit design principles and for controlling nanoscale devices and orchestrating processes within artificial cells. PMID:21283141

Metabolic engineering in chemolithoautotrophic hosts for the production of fuels and chemicals.

PubMed

Nybo, S Eric; Khan, Nymul E; Woolston, Benjamin M; Curtis, Wayne R

2015-07-01

The ability of autotrophic organisms to fix CO2 presents an opportunity to utilize this 'greenhouse gas' as an inexpensive substrate for biochemical production. Unlike conventional heterotrophic microorganisms that consume carbohydrates and amino acids, prokaryotic chemolithoautotrophs have evolved the capacity to utilize reduced chemical compounds to fix CO2 and drive metabolic processes. The use of chemolithoautotrophic hosts as production platforms has been renewed by the prospect of metabolically engineered commodity chemicals and fuels. Efforts such as the ARPA-E electrofuels program highlight both the potential and obstacles that chemolithoautotrophic biosynthetic platforms provide. This review surveys the numerous advances that have been made in chemolithoautotrophic metabolic engineering with a focus on hydrogen oxidizing bacteria such as the model chemolithoautotrophic organism (Ralstonia), the purple photosynthetic bacteria (Rhodobacter), and anaerobic acetogens. Two alternative strategies of microbial chassis development are considered: (1) introducing or enhancing autotrophic capabilities (carbon fixation, hydrogen utilization) in model heterotrophic organisms, or (2) improving tools for pathway engineering (transformation methods, promoters, vectors etc.) in native autotrophic organisms. Unique characteristics of autotrophic growth as they relate to bioreactor design and process development are also discussed in the context of challenges and opportunities for genetic manipulation of organisms as production platforms. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Combinatorial screening of 3D biomaterial properties that promote myofibrogenesis for mesenchymal stromal cell-based heart valve tissue engineering.

PubMed

Usprech, Jenna; Romero, David A; Amon, Cristina H; Simmons, Craig A

2017-08-01

The physical and chemical properties of a biomaterial integrate with soluble cues in the cell microenvironment to direct cell fate and function. Predictable biomaterial-based control of integrated cell responses has been investigated with two-dimensional (2D) screening platforms, but integrated responses in 3D have largely not been explored systematically. To address this need, we developed a screening platform using polyethylene glycol norbornene (PEG-NB) as a model biomaterial with which the polymer wt% (to control elastic modulus) and adhesion peptide types (RGD, DGEA, YIGSR) and densities could be controlled independently and combinatorially in arrays of 3D hydrogels. We applied this platform and regression modeling to identify combinations of biomaterial and soluble biochemical (TGF-β1) factors that best promoted myofibrogenesis of human mesenchymal stromal cells (hMSCs) in order to inform our understanding of regenerative processes for heart valve tissue engineering. In contrast to 2D culture, our screens revealed that soft hydrogels (low PEG-NB wt%) best promoted spread myofibroblastic cells that expressed high levels of α-smooth muscle actin (α-SMA) and collagen type I. High concentrations of RGD enhanced α-SMA expression in the presence of TGF-β1 and cell spreading regardless of whether TGF-β1 was in the culture medium. Strikingly, combinations of peptides that maximized collagen expression depended on the presence or absence of TGF-β1, indicating that biomaterial properties can modulate MSC response to soluble signals. This combination of a 3D biomaterial array screening platform with statistical modeling is broadly applicable to systematically identify combinations of biomaterial and microenvironmental conditions that optimally guide cell responses. We present a novel screening platform and methodology to model and identify how combinations of biomaterial and microenvironmental conditions guide cell phenotypes in 3D. Our approach to systematically identify complex relationships between microenvironmental cues and cell responses enables greater predictive power over cell fate in conditions with interacting material design factors. We demonstrate that this approach not only predicts that mesenchymal stromal cell (MSC) myofibrogenesis is promoted by soft, porous 3D biomaterials, but also generated new insights which demonstrate how biomaterial properties can differentially modulate MSC response to soluble signals. An additional benefit of the process includes utilizing both parametric and non parametric analyses which can demonstrate dominant significant trends as well as subtle interactions between biochemical and biomaterial cues. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Optical devices for biochemical sensing in flame hydrolysis deposited glass

NASA Astrophysics Data System (ADS)

Ruano-Lopez, Jesus M.

Previous research in the field of Flame Hydrolysis Deposition (FHD) of glasses has focused on the production of low cost optical devices for the field of telecommunications. The originality of this doctoral research resides in the exploration of this technology in the fabrication of optical bio-chemical sensors, with integrated "Lab-on-a-chip" devices. To achieve this goal, we have combined and applied different microfabrication processes for the manufacture of sensor platforms using FHD. These structures are unique in that they take advantage of the intrinsic benefits of the microfabrication process, such as, miniaturisation and mass production, and combine them with the properties of FHD glass, namely: low loss optical transducing mechanisms, planar technologies and monolithic integration. This thesis demonstrates that FHD is a suitable technology for biosensing and Lab- on-a-Chip applications. The objective is to provide future researchers with the necessary tools to accomplish an integrated analytical system based on FHD. We have designed, fabricated, and successfully tested a FHD miniaturised sensor, which comprised optical and microfluidic circuitry, in the framework of low volume fluorescence assays. For the first time, volumes as low as 570 pL were analysed with a Cyanine-5 fluorophore with a detection limit of 20 pM, or ca. 6000 molecules (+/-3sigma) for this platform. The fabrication of the sensor generated a compilation of processes that were then utilised to produce other possible optical platforms for bio-chemical sensors in FHD, e.g. arrays and microfluidics. The "catalogue" of methods used included new recipes for reactive ion etching, glass deposition and bonding techniques that enabled the development of the microfluidic circuitry, integrated with an optical circuitry. Furthermore, we developed techniques to implement new tasks such as optical signal treatment using integrated optical structures, planar arraying of sensors, a separating element for liquid chromatography, and finally a pumping system for delivering small amounts of liquid along the microfluidic channels. This thesis comprises six chapters. In Chapter 1, an overview of the topic was presented, offering a review of the various fields addressed, as well as a description of the motivation and originality of this work. Chapter 2 describes the processes developed to fabricate an optical sensor, and Chapter 3 assesses its performance. In Chapter 4, integrated optical circuit designs and their fabrication methods, as well as developing and testing of an array of sensors, are presented. The description of a separating element involved in a liquid chromatography system, and the pumping of liquids in a FHD optical device, were addressed in Chapter 5. Finally, Chapter 6 summarised the conclusions and suggested possible future work. Last but not least, the appendix, contains techniques for hybrid integration; recipes for etching of rare earth glasses; as well as instrumentation designs. This research has taken Flame Hydrolysis Deposition technique into the world of optical bio-chemical sensors, creating a bridge between analytical assays and FHD glass. In this respect, the demonstrated flexibility of the technology will enable a variety of configurations to be created and implemented, with the prospect of using the techniques for laboratory-on-a-chip technologies. The work has been patented by the University of Glasgow, for future exploitation in analytical biotechnology and Lab-on-a-Chip.

Metabolic engineering of Escherichia coli: a sustainable industrial platform for bio-based chemical production.

PubMed

Chen, Xianzhong; Zhou, Li; Tian, Kangming; Kumar, Ashwani; Singh, Suren; Prior, Bernard A; Wang, Zhengxiang

2013-12-01

In order to decrease carbon emissions and negative environmental impacts of various pollutants, more bulk and/or fine chemicals are produced by bioprocesses, replacing the traditional energy and fossil based intensive route. The Gram-negative rod-shaped bacterium, Escherichia coli has been studied extensively on a fundamental and applied level and has become a predominant host microorganism for industrial applications. Furthermore, metabolic engineering of E. coli for the enhanced biochemical production has been significantly promoted by the integrated use of recent developments in systems biology, synthetic biology and evolutionary engineering. In this review, we focus on recent efforts devoted to the use of genetically engineered E. coli as a sustainable platform for the production of industrially important biochemicals such as biofuels, organic acids, amino acids, sugar alcohols and biopolymers. In addition, representative secondary metabolites produced by E. coli will be systematically discussed and the successful strategies for strain improvements will be highlighted. Moreover, this review presents guidelines for future developments in the bio-based chemical production using E. coli as an industrial platform. Copyright © 2013 Elsevier Inc. All rights reserved.

Structural Basis of Multifunctionality in a Vitamin B[subscript 12]-processing Enzyme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koutmos, Markos; Gherasim, Carmen; Smith, Janet L.

An early step in the intracellular processing of vitamin B{sub 12} involves CblC, which exhibits dual reactivity, catalyzing the reductive decyanation of cyanocobalamin (vitamin B{sub 12}), and the dealkylation of alkylcobalamins (e.g. methylcobalamin; MeCbl). Insights into how the CblC scaffold supports this chemical dichotomy have been unavailable despite it being the most common locus of patient mutations associated with inherited cobalamin disorders that manifest in both severe homocystinuria and methylmalonic aciduria. Herein, we report structures of human CblC, with and without bound MeCbl, which provide novel biochemical insights into its mechanism of action. Our results reveal that CblC is themore » most divergent member of the NADPH-dependent flavin reductase family and can use FMN or FAD as a prosthetic group to catalyze reductive decyanation. Furthermore, CblC is the first example of an enzyme with glutathione transferase activity that has a sequence and structure unrelated to the GST superfamily. CblC thus represents an example of evolutionary adaptation of a common structural platform to perform diverse chemistries. The CblC structure allows us to rationalize the biochemical basis of a number of pathological mutations associated with severe clinical phenotypes.« less

Biochemical Conversion Processes of Lignocellulosic Biomass to Fuels and Chemicals - A Review.

PubMed

Brethauer, Simone; Studer, Michael H

2015-01-01

Lignocellulosic biomass - such as wood, agricultural residues or dedicated energy crops - is a promising renewable feedstock for production of fuels and chemicals that is available at large scale at low cost without direct competition for food usage. Its biochemical conversion in a sugar platform biorefinery includes three main unit operations that are illustrated in this review: the physico-chemical pretreatment of the biomass, the enzymatic hydrolysis of the carbohydrates to a fermentable sugar stream by cellulases and finally the fermentation of the sugars by suitable microorganisms to the target molecules. Special emphasis in this review is put on the technology, commercial status and future prospects of the production of second-generation fuel ethanol, as this process has received most research and development efforts so far. Despite significant advances, high enzyme costs are still a hurdle for large scale competitive lignocellulosic ethanol production. This could be overcome by a strategy termed 'consolidated bioprocessing' (CBP), where enzyme production, enzymatic hydrolysis and fermentation is integrated in one step - either by utilizing one genetically engineered superior microorganism or by creating an artificial co-culture. Insight is provided on both CBP strategies for the production of ethanol as well as of advanced fuels and commodity chemicals.

NREL 2012 Achievement of Ethanol Cost Targets: Biochemical Ethanol Fermentation via Dilute-Acid Pretreatment and Enzymatic Hydrolysis of Corn Stover

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tao, L.; Schell, D.; Davis, R.

2014-04-01

For the DOE Bioenergy Technologies Office, the annual State of Technology (SOT) assessment is an essential activity for quantifying the benefits of biochemical platform research. This assessment has historically allowed the impact of research progress achieved through targeted Bioenergy Technologies Office funding to be quantified in terms of economic improvements within the context of a fully integrated cellulosic ethanol production process. As such, progress toward the ultimate 2012 goal of demonstrating cost-competitive cellulosic ethanol technology can be tracked. With an assumed feedstock cost for corn stover of $58.50/ton this target has historically been set at $1.41/gal ethanol for conversion costsmore » only (exclusive of feedstock) and $2.15/gal total production cost (inclusive of feedstock) or minimum ethanol selling price (MESP). This year, fully integrated cellulosic ethanol production data generated by National Renewable Energy Laboratory (NREL) researchers in their Integrated Biorefinery Research Facility (IBRF) successfully demonstrated performance commensurate with both the FY 2012 SOT MESP target of $2.15/gal (2007$, $58.50/ton feedstock cost) and the conversion target of $1.41/gal through core research and process improvements in pretreatment, enzymatic hydrolysis, and fermentation.« less

Process simulation of ethanol production from biomass gasification and syngas fermentation.

PubMed

Pardo-Planas, Oscar; Atiyeh, Hasan K; Phillips, John R; Aichele, Clint P; Mohammad, Sayeed

2017-12-01

The hybrid gasification-syngas fermentation platform can produce more bioethanol utilizing all biomass components compared to the biochemical conversion technology. Syngas fermentation operates at mild temperatures and pressures and avoids using expensive pretreatment processes and enzymes. This study presents a new process simulation model developed with Aspen Plus® of a biorefinery based on a hybrid conversion technology for the production of anhydrous ethanol using 1200tons per day (wb) of switchgrass. The simulation model consists of three modules: gasification, fermentation, and product recovery. The results revealed a potential production of about 36.5million gallons of anhydrous ethanol per year. Sensitivity analyses were also performed to investigate the effects of gasification and fermentation parameters that are keys for the development of an efficient process in terms of energy conservation and ethanol production. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optical Fiber Sensing Using Quantum Dots

PubMed Central

Jorge, Pedro; Martins, Manuel António; Trindade, Tito; Santos, José Luís; Farahi, Faramarz

2007-01-01

Recent advances in the application of semiconductor nanocrystals, or quantum dots, as biochemical sensors are reviewed. Quantum dots have unique optical properties that make them promising alternatives to traditional dyes in many luminescence based bioanalytical techniques. An overview of the more relevant progresses in the application of quantum dots as biochemical probes is addressed. Special focus will be given to configurations where the sensing dots are incorporated in solid membranes and immobilized in optical fibers or planar waveguide platforms. PMID:28903308

Ras plasma membrane signalling platforms

PubMed Central

2005-01-01

The plasma membrane is a complex, dynamic structure that provides platforms for the assembly of many signal transduction pathways. These platforms have the capacity to impose an additional level of regulation on cell signalling networks. In this review, we will consider specifically how Ras proteins interact with the plasma membrane. The focus will be on recent studies that provide novel spatial and dynamic insights into the micro-environments that different Ras proteins utilize for signal transduction. We will correlate these recent studies suggesting Ras proteins might operate within a heterogeneous plasma membrane with earlier biochemical work on Ras signal transduction. PMID:15954863

The Cell Collective: Toward an open and collaborative approach to systems biology

PubMed Central

2012-01-01

Background Despite decades of new discoveries in biomedical research, the overwhelming complexity of cells has been a significant barrier to a fundamental understanding of how cells work as a whole. As such, the holistic study of biochemical pathways requires computer modeling. Due to the complexity of cells, it is not feasible for one person or group to model the cell in its entirety. Results The Cell Collective is a platform that allows the world-wide scientific community to create these models collectively. Its interface enables users to build and use models without specifying any mathematical equations or computer code - addressing one of the major hurdles with computational research. In addition, this platform allows scientists to simulate and analyze the models in real-time on the web, including the ability to simulate loss/gain of function and test what-if scenarios in real time. Conclusions The Cell Collective is a web-based platform that enables laboratory scientists from across the globe to collaboratively build large-scale models of various biological processes, and simulate/analyze them in real time. In this manuscript, we show examples of its application to a large-scale model of signal transduction. PMID:22871178

Earth observing system - Concepts and implementation strategy

NASA Technical Reports Server (NTRS)

Hartle, R. E.

1986-01-01

The concepts of an Earth Observing System (EOS), an information system being developed by the EOS Science and Mission Requirements Working Group for international use and planned to begin in the 1990s, are discussed. The EOS is designed to study the factors that control the earth's hydrologic cycle, biochemical cycles, and climatologic processes by combining the measurements from remote sensing instruments, in situ measurement devices, and a data and information system. Three EOS platforms are planned to be launched into low, polar, sun-synchronous orbits during the Space Station's Initial Operating Configuration, one to be provided by ESA and two by the United States.

Genomic analysis of thermophilic Bacillus coagulans strains: efficient producers for platform bio-chemicals.

PubMed

Su, Fei; Xu, Ping

2014-01-29

Microbial strains with high substrate efficiency and excellent environmental tolerance are urgently needed for the production of platform bio-chemicals. Bacillus coagulans has these merits; however, little genetic information is available about this species. Here, we determined the genome sequences of five B. coagulans strains, and used a comparative genomic approach to reconstruct the central carbon metabolism of this species to explain their fermentation features. A novel xylose isomerase in the xylose utilization pathway was identified in these strains. Based on a genome-wide positive selection scan, the selection pressure on amino acid metabolism may have played a significant role in the thermal adaptation. We also researched the immune systems of B. coagulans strains, which provide them with acquired resistance to phages and mobile genetic elements. Our genomic analysis provides comprehensive insights into the genetic characteristics of B. coagulans and paves the way for improving and extending the uses of this species.

Genomic analysis of thermophilic Bacillus coagulans strains: efficient producers for platform bio-chemicals

PubMed Central

Su, Fei; Xu, Ping

2014-01-01

Microbial strains with high substrate efficiency and excellent environmental tolerance are urgently needed for the production of platform bio-chemicals. Bacillus coagulans has these merits; however, little genetic information is available about this species. Here, we determined the genome sequences of five B. coagulans strains, and used a comparative genomic approach to reconstruct the central carbon metabolism of this species to explain their fermentation features. A novel xylose isomerase in the xylose utilization pathway was identified in these strains. Based on a genome-wide positive selection scan, the selection pressure on amino acid metabolism may have played a significant role in the thermal adaptation. We also researched the immune systems of B. coagulans strains, which provide them with acquired resistance to phages and mobile genetic elements. Our genomic analysis provides comprehensive insights into the genetic characteristics of B. coagulans and paves the way for improving and extending the uses of this species. PMID:24473268

A collaborative visual analytics suite for protein folding research.

PubMed

Harvey, William; Park, In-Hee; Rübel, Oliver; Pascucci, Valerio; Bremer, Peer-Timo; Li, Chenglong; Wang, Yusu

2014-09-01

Molecular dynamics (MD) simulation is a crucial tool for understanding principles behind important biochemical processes such as protein folding and molecular interaction. With the rapidly increasing power of modern computers, large-scale MD simulation experiments can be performed regularly, generating huge amounts of MD data. An important question is how to analyze and interpret such massive and complex data. One of the (many) challenges involved in analyzing MD simulation data computationally is the high-dimensionality of such data. Given a massive collection of molecular conformations, researchers typically need to rely on their expertise and prior domain knowledge in order to retrieve certain conformations of interest. It is not easy to make and test hypotheses as the data set as a whole is somewhat "invisible" due to its high dimensionality. In other words, it is hard to directly access and examine individual conformations from a sea of molecular structures, and to further explore the entire data set. There is also no easy and convenient way to obtain a global view of the data or its various modalities of biochemical information. To this end, we present an interactive, collaborative visual analytics tool for exploring massive, high-dimensional molecular dynamics simulation data sets. The most important utility of our tool is to provide a platform where researchers can easily and effectively navigate through the otherwise "invisible" simulation data sets, exploring and examining molecular conformations both as a whole and at individual levels. The visualization is based on the concept of a topological landscape, which is a 2D terrain metaphor preserving certain topological and geometric properties of the high dimensional protein energy landscape. In addition to facilitating easy exploration of conformations, this 2D terrain metaphor also provides a platform where researchers can visualize and analyze various properties (such as contact density) overlayed on the top of the 2D terrain. Finally, the software provides a collaborative environment where multiple researchers can assemble observations and biochemical events into storyboards and share them in real time over the Internet via a client-server architecture. The software is written in Scala and runs on the cross-platform Java Virtual Machine. Binaries and source code are available at http://www.aylasoftware.org and have been released under the GNU General Public License. Copyright © 2014 Elsevier Inc. All rights reserved.

Dynamically Tunable Cell Culture Platforms for Tissue Engineering and Mechanobiology

PubMed Central

Uto, Koichiro; Tsui, Jonathan H.; DeForest, Cole A.; Kim, Deok-Ho

2016-01-01

Human tissues are sophisticated ensembles of many distinct cell types embedded in the complex, but well-defined, structures of the extracellular matrix (ECM). Dynamic biochemical, physicochemical, and mechano-structural changes in the ECM define and regulate tissue-specific cell behaviors. To recapitulate this complex environment in vitro, dynamic polymer-based biomaterials have emerged as powerful tools to probe and direct active changes in cell function. The rapid evolution of polymerization chemistries, structural modulation, and processing technologies, as well as the incorporation of stimuli-responsiveness, now permit synthetic microenvironments to capture much of the dynamic complexity of native tissue. These platforms are comprised not only of natural polymers chemically and molecularly similar to ECM, but those fully synthetic in origin. Here, we review recent in vitro efforts to mimic the dynamic microenvironment comprising native tissue ECM from the viewpoint of material design. We also discuss how these dynamic polymer-based biomaterials are being used in fundamental cell mechanobiology studies, as well as towards efforts in tissue engineering and regenerative medicine. PMID:28522885

Thin metal bilayer for surface plasmon resonance sensors in a multimode plastic optical fiber: the case of palladium and gold metal films

NASA Astrophysics Data System (ADS)

Cennamo, Nunzio; Zuppella, Paola; Bacco, Davide; Corso, Alain J.; Pelizzo, Maria G.; Pesavento, Maria; Zeni, Luigi

2016-05-01

A novel sensing platform based on thin metal bilayer for surface plasmon resonance (SPR) in a D-shaped plastic optical fiber (POF) has been designed, implemented and tested. The experimental results are congruent with the numerical studies. This platform has been properly optimized to work in the 1.38 -1.42 refractive index range and it exhibits excellent sensitivity. This refractive index range is very interesting for bio-chemical applications, where the polymer layer are used as receptors (e.g. molecularly imprinted polymer) or to immobilize the bio-receptor on the metal surface. The proposed metallic bilayer is based on palladium and gold films and replaces the traditional gold by exhibiting higher performances. Furthermore, the deposition of the thin bilayer is a single process and no further manufacturing step is required. In fact, in this case the photoresist buffer layer between the POF core and the metal layer, usually required to increase the refractive index range, is no longer necessary.

Energy-based culture medium design for biomanufacturing optimization: A case study in monoclonal antibody production by GS-NS0 cells.

PubMed

Quiroga-Campano, Ana L; Panoskaltsis, Nicki; Mantalaris, Athanasios

2018-03-02

Demand for high-value biologics, a rapidly growing pipeline, and pressure from competition, time-to-market and regulators, necessitate novel biomanufacturing approaches, including Quality by Design (QbD) principles and Process Analytical Technologies (PAT), to facilitate accelerated, efficient and effective process development platforms that ensure consistent product quality and reduced lot-to-lot variability. Herein, QbD and PAT principles were incorporated within an innovative in vitro-in silico integrated framework for upstream process development (UPD). The central component of the UPD framework is a mathematical model that predicts dynamic nutrient uptake and average intracellular ATP content, based on biochemical reaction networks, to quantify and characterize energy metabolism and its adaptive response, metabolic shifts, to maintain ATP homeostasis. The accuracy and flexibility of the model depends on critical cell type/product/clone-specific parameters, which are experimentally estimated. The integrated in vitro-in silico platform and the model's predictive capacity reduced burden, time and expense of experimentation resulting in optimal medium design compared to commercially available culture media (80% amino acid reduction) and a fed-batch feeding strategy that increased productivity by 129%. The framework represents a flexible and efficient tool that transforms, improves and accelerates conventional process development in biomanufacturing with wide applications, including stem cell-based therapies. Copyright © 2018. Published by Elsevier Inc.

Data Streaming for Metabolomics: Accelerating Data Processing and Analysis from Days to Minutes

PubMed Central

2016-01-01

The speed and throughput of analytical platforms has been a driving force in recent years in the “omics” technologies and while great strides have been accomplished in both chromatography and mass spectrometry, data analysis times have not benefited at the same pace. Even though personal computers have become more powerful, data transfer times still represent a bottleneck in data processing because of the increasingly complex data files and studies with a greater number of samples. To meet the demand of analyzing hundreds to thousands of samples within a given experiment, we have developed a data streaming platform, XCMS Stream, which capitalizes on the acquisition time to compress and stream recently acquired data files to data processing servers, mimicking just-in-time production strategies from the manufacturing industry. The utility of this XCMS Online-based technology is demonstrated here in the analysis of T cell metabolism and other large-scale metabolomic studies. A large scale example on a 1000 sample data set demonstrated a 10 000-fold time savings, reducing data analysis time from days to minutes. Further, XCMS Stream has the capability to increase the efficiency of downstream biochemical dependent data acquisition (BDDA) analysis by initiating data conversion and data processing on subsets of data acquired, expanding its application beyond data transfer to smart preliminary data decision-making prior to full acquisition. PMID:27983788

Data streaming for metabolomics: Accelerating data processing and analysis from days to minutes

DOE PAGES

Montenegro-Burke, J. Rafael; Aisporna, Aries E.; Benton, H. Paul; ...

2016-12-16

The speed and throughput of analytical platforms has been a driving force in recent years in the “omics” technologies and while great strides have been accomplished in both chromatography and mass spectrometry, data analysis times have not benefited at the same pace. Even though personal computers have become more powerful, data transfer times still represent a bottleneck in data processing because of the increasingly complex data files and studies with a greater number of samples. To meet the demand of analyzing hundreds to thousands of samples within a given experiment, we have developed a data streaming platform, XCMS Stream, whichmore » capitalizes on the acquisition time to compress and stream recently acquired data files to data processing servers, mimicking just-in-time production strategies from the manufacturing industry. The utility of this XCMS Online-based technology is demonstrated here in the analysis of T cell metabolism and other large-scale metabolomic studies. A large scale example on a 1000 sample data set demonstrated a 10 000-fold time savings, reducing data analysis time from days to minutes. Here, XCMS Stream has the capability to increase the efficiency of downstream biochemical dependent data acquisition (BDDA) analysis by initiating data conversion and data processing on subsets of data acquired, expanding its application beyond data transfer to smart preliminary data decision-making prior to full acquisition.« less

Data Streaming for Metabolomics: Accelerating Data Processing and Analysis from Days to Minutes.

PubMed

Montenegro-Burke, J Rafael; Aisporna, Aries E; Benton, H Paul; Rinehart, Duane; Fang, Mingliang; Huan, Tao; Warth, Benedikt; Forsberg, Erica; Abe, Brian T; Ivanisevic, Julijana; Wolan, Dennis W; Teyton, Luc; Lairson, Luke; Siuzdak, Gary

2017-01-17

The speed and throughput of analytical platforms has been a driving force in recent years in the "omics" technologies and while great strides have been accomplished in both chromatography and mass spectrometry, data analysis times have not benefited at the same pace. Even though personal computers have become more powerful, data transfer times still represent a bottleneck in data processing because of the increasingly complex data files and studies with a greater number of samples. To meet the demand of analyzing hundreds to thousands of samples within a given experiment, we have developed a data streaming platform, XCMS Stream, which capitalizes on the acquisition time to compress and stream recently acquired data files to data processing servers, mimicking just-in-time production strategies from the manufacturing industry. The utility of this XCMS Online-based technology is demonstrated here in the analysis of T cell metabolism and other large-scale metabolomic studies. A large scale example on a 1000 sample data set demonstrated a 10 000-fold time savings, reducing data analysis time from days to minutes. Further, XCMS Stream has the capability to increase the efficiency of downstream biochemical dependent data acquisition (BDDA) analysis by initiating data conversion and data processing on subsets of data acquired, expanding its application beyond data transfer to smart preliminary data decision-making prior to full acquisition.

Targeting homeostasis in drug delivery using bioresponsive hydrogel microforms.

PubMed

Wilson, A Nolan; Guiseppi-Elie, Anthony

2014-01-30

A drug delivery platform comprising a biocompatible, bioresponsive hydrogel and possessing a covalently tethered peptide-drug conjugate was engineered to achieve stasis, via a closed control loop, of the external biochemical activity of the actuating protease. The delivery platform contains a peptide-drug conjugate covalently tethered to the hydrogel matrix, which in the presence of the appropriate protease, was cleaved and the drug released into the bathing environment. This platform was developed and investigated in silico using a finite element modeling (FEM) approach. Firstly, the primary governing phenomena guiding drug release profiles were investigated, and it was confirmed that under transport-limited conditions, the diffusion of the enzyme within the hydrogel and the coupled enzyme kinetics accurately model the system and are in agreement with published results. Secondly, the FEM model was used to investigate the release of a competitive protease inhibitor, MAG283, via cleavage of Acetyl-Pro-Leu-Gly|Leu-MAG-283 by MMP9 in order to achieve targeted homeostasis of MMP-9 activity, such as in the pathophysiology of chronic wounds, via closed-loop feedback control. The key engineering parameters for the delivery device are the radii of the hydrogel microspheres and the concentration of the peptide-inhibitor conjugate. Homeostatic drug delivery, where the focus turns away from the drug release rate and turns toward achieving targeted control of biochemical activity within a biochemical pathway, is an emerging approach in drug delivery methodologies for which the potential has not yet been fully realized. Copyright © 2013 Elsevier B.V. All rights reserved.

Prospects for energy recovery during hydrothermal and biological processing of waste biomass.

PubMed

Gerber Van Doren, Léda; Posmanik, Roy; Bicalho, Felipe A; Tester, Jefferson W; Sills, Deborah L

2017-02-01

Thermochemical and biological processes represent promising technologies for converting wet biomasses, such as animal manure, organic waste, or algae, to energy. To convert biomass to energy and bio-chemicals in an economical manner, internal energy recovery should be maximized to reduce the use of external heat and power. In this study, two conversion pathways that couple hydrothermal liquefaction with anaerobic digestion or catalytic hydrothermal gasification were compared. Each of these platforms is followed by two alternative processes for gas utilization: 1) combined heat and power; and 2) combustion in a boiler. Pinch analysis was applied to integrate thermal streams among unit processes and improve the overall system efficiency. A techno-economic analysis was conducted to compare the feasibility of the four modeled scenarios under different market conditions. Our results show that a systems approach designed to recover internal heat and power can reduce external energy demands and increase the overall process sustainability. Copyright © 2016 Elsevier Ltd. All rights reserved.

ISS Biotechnology Facility - Overview of Analytical Tools for Cellular Biotechnology Investigations

NASA Technical Reports Server (NTRS)

Jeevarajan, A. S.; Towe, B. C.; Anderson, M. M.; Gonda, S. R.; Pellis, N. R.

2001-01-01

The ISS Biotechnology Facility (BTF) platform provides scientists with a unique opportunity to carry out diverse experiments in a microgravity environment for an extended period of time. Although considerable progress has been made in preserving cells on the ISS for long periods of time for later return to Earth, future biotechnology experiments would desirably monitor, process, and analyze cells in a timely way on-orbit. One aspect of our work has been directed towards developing biochemical sensors for pH, glucose, oxygen, and carbon dioxide for perfused bioreactor system developed at Johnson Space Center. Another aspect is the examination and identification of new and advanced commercial biotechnologies that may have applications to on-orbit experiments.

Automated Long-Term Monitoring of Parallel Microfluidic Operations Applying a Machine Vision-Assisted Positioning Method

PubMed Central

Yip, Hon Ming; Li, John C. S.; Cui, Xin; Gao, Qiannan; Leung, Chi Chiu

2014-01-01

As microfluidics has been applied extensively in many cell and biochemical applications, monitoring the related processes is an important requirement. In this work, we design and fabricate a high-throughput microfluidic device which contains 32 microchambers to perform automated parallel microfluidic operations and monitoring on an automated stage of a microscope. Images are captured at multiple spots on the device during the operations for monitoring samples in microchambers in parallel; yet the device positions may vary at different time points throughout operations as the device moves back and forth on a motorized microscopic stage. Here, we report an image-based positioning strategy to realign the chamber position before every recording of microscopic image. We fabricate alignment marks at defined locations next to the chambers in the microfluidic device as reference positions. We also develop image processing algorithms to recognize the chamber positions in real-time, followed by realigning the chambers to their preset positions in the captured images. We perform experiments to validate and characterize the device functionality and the automated realignment operation. Together, this microfluidic realignment strategy can be a platform technology to achieve precise positioning of multiple chambers for general microfluidic applications requiring long-term parallel monitoring of cell and biochemical activities. PMID:25133248

Using slaughterhouse waste in a biochemical-based biorefinery - results from pilot scale tests.

PubMed

Schwede, Sebastian; Thorin, Eva; Lindmark, Johan; Klintenberg, Patrik; Jääskeläinen, Ari; Suhonen, Anssi; Laatikainen, Reino; Hakalehto, Elias

2017-05-01

A novel biorefinery concept was piloted using protein-rich slaughterhouse waste, chicken manure and straw as feedstocks. The basic idea was to provide a proof of concept for the production of platform chemicals and biofuels from organic waste materials at non-septic conditions. The desired biochemical routes were 2,3-butanediol and acetone-butanol fermentation. The results showed that hydrolysis resulted only in low amounts of easily degradable carbohydrates. However, amino acids released from the protein-rich slaughterhouse waste were utilized and fermented by the bacteria in the process. Product formation was directed towards acidogenic compounds rather than solventogenic products due to increasing pH-value affected by ammonia release during amino acid fermentation. Hence, the process was not effective for 2,3-butanediol production, whereas butyrate, propionate, γ-aminobutyrate and valerate were predominantly produced. This offered fast means for converting tedious protein-rich waste mixtures into utilizable chemical goods. Furthermore, the residual liquid from the bioreactor showed significantly higher biogas production potential than the corresponding substrates. The combination of the biorefinery approach to produce chemicals and biofuels with anaerobic digestion of the residues to recover energy in form of methane and nutrients that can be utilized for animal feed production could be a feasible concept for organic waste utilization.

Slot-waveguide biochemical sensor.

PubMed

Barrios, Carlos A; Gylfason, Kristinn B; Sánchez, Benito; Griol, Amadeu; Sohlström, H; Holgado, M; Casquel, R

2007-11-01

We report an experimental demonstration of an integrated biochemical sensor based on a slot-waveguide microring resonator. The microresonator is fabricated on a Si3N4-SiO2 platform and operates at a wavelength of 1.3 microm. The transmission spectrum of the sensor is measured with different ambient refractive indices ranging from n=1.33 to 1.42. A linear shift of the resonant wavelength with increasing ambient refractive index of 212 nm/refractive index units (RIU) is observed. The sensor detects a minimal refractive index variation of 2x10(-4) RIU.

Prospect redux

NASA Technical Reports Server (NTRS)

Jacquemoud, S.; Ustin, S. L.; Verdebout, J.; Schmuck, G.; Andreoli, G.; Hosgood, B.

1995-01-01

The remote estimation of leaf biochemical content from spaceborne platforms has been the subject of many studies aimed at better understanding of terrestrial ecosystem functioning. The major ecological processes involved in exchange of matter and energy, like photosynthesis, primary production, evaportranspiration, respiration, and decomposition can be related to plant properties e.g., chlorophyll, water, protein, cellulose and lignin contents. As leaves represent the most important plant surfaces interacting with solar energy, a top priority has been to relate optical properties to biochemical constituents. Two different approaches have been considered: first, statistical correlations between the leaf reflectance (or transmittance) and biochemical content, and second, physically based models of leaf scattering and absorption developed using the laws of optics. Recently reviewed by Verdebout et al., the development of models of leaf optical properties has resulted in better understanding of the interaction of light with plant leaves. Present radiative transfer models mainly use chlorophyll and/or water contents as input parameters to calculate leaf reflectance. Inversion of these models allows to retrieve these constituents from spectrophotometric measurements. Conel et al. recently proposed a two-stream Kubelka-Munk model to analyze the influence of protein, cellulose, lignin, and starch on leaf reflectance, but in fact, the estimation of leaf biochemistry from remote sensing is still an open question. In order to clarify it, a laboratory experiment associating visible/infrared spectra of plan leaves both with physical measurements and biochemical analyses was conducted at the Joint Research Center during the summer of 1993. This unique data set has been used to upgrade the PROSPECT model, by including leaf biochemistry.

Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering.

PubMed

Shamloo, Amir; Mohammadaliha, Negar; Mohseni, Mina

2015-10-20

This review aims to propose the integrative implementation of microfluidic devices, biomaterials, and computational methods that can lead to a significant progress in tissue engineering and regenerative medicine researches. Simultaneous implementation of multiple techniques can be very helpful in addressing biological processes. Providing controllable biochemical and biomechanical cues within artificial extracellular matrix similar to in vivo conditions is crucial in tissue engineering and regenerative medicine researches. Microfluidic devices provide precise spatial and temporal control over cell microenvironment. Moreover, generation of accurate and controllable spatial and temporal gradients of biochemical factors is attainable inside microdevices. Since biomaterials with tunable properties are a worthwhile option to construct artificial extracellular matrix, in vitro platforms that simultaneously utilize natural, synthetic, or engineered biomaterials inside microfluidic devices are phenomenally advantageous to experimental studies in the field of tissue engineering. Additionally, collaboration between experimental and computational methods is a useful way to predict and understand mechanisms responsible for complex biological phenomena. Computational results can be verified by using experimental platforms. Computational methods can also broaden the understanding of the mechanisms behind the biological phenomena observed during experiments. Furthermore, computational methods are powerful tools to optimize the fabrication of microfluidic devices and biomaterials with specific features. Here we present a succinct review of the benefits of microfluidic devices, biomaterial, and computational methods in the case of tissue engineering and regeneration medicine. Furthermore, some breakthroughs in biological phenomena including the neuronal axon development, cancerous cell migration and blood vessel formation via angiogenesis by virtue of the aforementioned approaches are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Bridging the gap between modules in isolation and as part of networks: A systems framework for elucidating interaction and regulation of signalling modules

NASA Astrophysics Data System (ADS)

Menon, Govind; Krishnan, J.

2016-07-01

While signalling and biochemical modules have been the focus of numerous studies, they are typically studied in isolation, with no examination of the effects of the ambient network. In this paper we formulate and develop a systems framework, rooted in dynamical systems, to understand such effects, by studying the interaction of signalling modules. The modules we consider are (i) basic covalent modification, (ii) monostable switches, (iii) bistable switches, (iv) adaptive modules, and (v) oscillatory modules. We systematically examine the interaction of these modules by analyzing (a) sequential interaction without shared components, (b) sequential interaction with shared components, and (c) oblique interactions. Our studies reveal that the behaviour of a module in isolation may be substantially different from that in a network, and explicitly demonstrate how the behaviour of a given module, the characteristics of the ambient network, and the possibility of shared components can result in new effects. Our global approach illuminates different aspects of the structure and functioning of modules, revealing the importance of dynamical characteristics as well as biochemical features; this provides a methodological platform for investigating the complexity of natural modules shaped by evolution, elucidating the effects of ambient networks on a module in multiple cellular contexts, and highlighting the capabilities and constraints for engineering robust synthetic modules. Overall, such a systems framework provides a platform for bridging the gap between non-linear information processing modules, in isolation and as parts of networks, and a basis for understanding new aspects of natural and engineered cellular networks.

Bridging the gap between modules in isolation and as part of networks: A systems framework for elucidating interaction and regulation of signalling modules.

PubMed

Menon, Govind; Krishnan, J

2016-07-21

While signalling and biochemical modules have been the focus of numerous studies, they are typically studied in isolation, with no examination of the effects of the ambient network. In this paper we formulate and develop a systems framework, rooted in dynamical systems, to understand such effects, by studying the interaction of signalling modules. The modules we consider are (i) basic covalent modification, (ii) monostable switches, (iii) bistable switches, (iv) adaptive modules, and (v) oscillatory modules. We systematically examine the interaction of these modules by analyzing (a) sequential interaction without shared components, (b) sequential interaction with shared components, and (c) oblique interactions. Our studies reveal that the behaviour of a module in isolation may be substantially different from that in a network, and explicitly demonstrate how the behaviour of a given module, the characteristics of the ambient network, and the possibility of shared components can result in new effects. Our global approach illuminates different aspects of the structure and functioning of modules, revealing the importance of dynamical characteristics as well as biochemical features; this provides a methodological platform for investigating the complexity of natural modules shaped by evolution, elucidating the effects of ambient networks on a module in multiple cellular contexts, and highlighting the capabilities and constraints for engineering robust synthetic modules. Overall, such a systems framework provides a platform for bridging the gap between non-linear information processing modules, in isolation and as parts of networks, and a basis for understanding new aspects of natural and engineered cellular networks.

Microfluidic technology platforms for synthesizing, labeling and measuring the kinetics of transport and biochemical reactions for developing molecular imaging probes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phelps, Michael E.

2009-09-01

Radiotracer techniques are used in environmental sciences, geology, biology and medicine. Radiotracers with Positron Emission Tomography (PET) provided biological examinations of ~3 million patients 2008. Despite the success of positron labeled tracers in many sciences, there is limited access in an affordable and convenient manner to develop and use new tracers. Integrated microfluidic chips are a new technology well matched to the concentrations of tracers. Our goal is to develop microfluidic chips and new synthesis approaches to enable wide dissemination of diverse types of tracers at low cost, and to produce new generations of radiochemists for which there are manymore » unfilled jobs. The program objectives are to: 1. Develop an integrated microfluidic platform technology for synthesizing and 18F-labeling diverse arrays of different classes of molecules. 2. Incorporate microfluidic chips into small PC controlled devices (“Synthesizer”) with a platform interfaced to PC for electronic and fluid input/out control. 3. Establish a de-centralized model with Synthesizers for discovering and producing molecular imaging probes, only requiring delivery of inexpensive [18F]fluoride ion from commercial PET radiopharmacies vs the centralized approach of cyclotron facilities synthesizing and shipping a few different types of 18F-probes. 4. Develop a position sensitive avalanche photo diode (PSAPD) camera for beta particles embedded in a microfluidic chip for imaging and measuring transport and biochemical reaction rates to valid new 18F-labeled probes in an array of cell cultures. These objectives are met within a research and educational program integrating radio-chemistry, synthetic chemistry, biochemistry, engineering and biology in the Crump Institute for Molecular Imaging. The Radiochemistry Training Program exposes PhD and post doctoral students to molecular imaging in vitro in cells and microorganisms in microfluidic chips and in vivo with PET, from new technologies for radiochemistry (macro to micro levels), biochemistry and biology to imaging principles, tracer kinetics, pharmacokinetics and biochemical assays. New generations of radiochemists will be immersed in the biochemistry and biology for which their labeled probes are being developed for assays of these processes. In this program engineers and radio-chemists integrate the principles of microfluidics and radiolabeling along with proper system design and chemistry rule sets to yield Synthesizers enabling biological and pharmaceutical scientists to develop diverse arrays of probes to pursue their interests. This progression would allow also radiochemists to focus on the further evolution of rapid, high yield synthetic reactions with new enabling technologies, rather than everyday production of radiotracers that should be done by technologists. The invention of integrated circuits in electronics established a platform technology that allowed an evolution of ideas and applications far beyond what could have been imagined at the beginning. Rather than provide a technology for the solution to a single problem, it is hoped that microfluidic radiochemistry will be an enabling platform technology for others to solve many problems. As part of this objective, another program goal is to commercialize the technologies that come from this work so that they can be provided to others who wish to use it.« less

Label-free optical resonant sensors for biochemical applications

NASA Astrophysics Data System (ADS)

Ciminelli, Caterina; Campanella, Clarissa Martina; Dell'Olio, Francesco; Campanella, Carlo Edoardo; Armenise, Mario Nicola

2013-03-01

For a number of years, the scientific community has been paying growing attention to the monitoring and enhancement of public health and the quality of life through the detection of all dangerous agents for the human body, including gases, proteins, virus, and bacterial agents. When these agents are detected through label-free biochemical sensors, the molecules are not modified structurally or functionally by adding fluorescent or radioactive dyes. This work focuses on label-free optical ring resonator-based configurations suited for bio-chemical sensing, highlighting their physical aspects and specific applications. Resonant wavelength shift and the modal splitting occurring when the analyte interacts with microresonant structures are the two major physical aspects analyzed in this paper. Competitive optical platforms proposed in the literature are also illustrated together with their properties and performance.

Covering Chemical Diversity of Genetically-Modified Tomatoes Using Metabolomics for Objective Substantial Equivalence Assessment

PubMed Central

Hirai, Tadayoshi; Oikawa, Akira; Matsuda, Fumio; Fukushima, Atsushi; Arita, Masanori; Watanabe, Shin; Yano, Megumu; Hiwasa-Tanase, Kyoko; Ezura, Hiroshi; Saito, Kazuki

2011-01-01

As metabolomics can provide a biochemical snapshot of an organism's phenotype it is a promising approach for charting the unintended effects of genetic modification. A critical obstacle for this application is the inherently limited metabolomic coverage of any single analytical platform. We propose using multiple analytical platforms for the direct acquisition of an interpretable data set of estimable chemical diversity. As an example, we report an application of our multi-platform approach that assesses the substantial equivalence of tomatoes over-expressing the taste-modifying protein miraculin. In combination, the chosen platforms detected compounds that represent 86% of the estimated chemical diversity of the metabolites listed in the LycoCyc database. Following a proof-of-safety approach, we show that % had an acceptable range of variation while simultaneously indicating a reproducible transformation-related metabolic signature. We conclude that multi-platform metabolomics is an approach that is both sensitive and robust and that it constitutes a good starting point for characterizing genetically modified organisms. PMID:21359231

Single Molecule Enzymology via Nanoelectronic Circuits

NASA Astrophysics Data System (ADS)

Collins, Philip

Traditional single-molecule techniques rely on fluorescence or force transduction to monitor conformational changes and biochemical activity. Recent demonstrations of single-molecule monitoring with electronic transistors are poised to add to the single-molecule research toolkit. The transistor-based technique is sensitive to the motion of single charged side chain residues and can transduce those motions with microsecond resolution, opening the doors to single-molecule enzymology with unprecedented resolution. Furthermore, the solid-state platform provides opportunities for parallelization in arrays and long-duration monitoring of one molecule's activity or processivity, all without the limitations caused by photo-oxidation or mutagenic fluorophore incorporation. This presentation will review some of these advantages and their particular application to DNA polymerase I processing single-stranded DNA templates. This research was supported financially by the NIH NCI (R01 CA133592-01), the NIH NIGMS (1R01GM106957-01) and the NSF (DMR-1104629 and ECCS-1231910).

Seamless integration of dose-response screening and flow chemistry: efficient generation of structure-activity relationship data of β-secretase (BACE1) inhibitors.

PubMed

Werner, Michael; Kuratli, Christoph; Martin, Rainer E; Hochstrasser, Remo; Wechsler, David; Enderle, Thilo; Alanine, Alexander I; Vogel, Horst

2014-02-03

Drug discovery is a multifaceted endeavor encompassing as its core element the generation of structure-activity relationship (SAR) data by repeated chemical synthesis and biological testing of tailored molecules. Herein, we report on the development of a flow-based biochemical assay and its seamless integration into a fully automated system comprising flow chemical synthesis, purification and in-line quantification of compound concentration. This novel synthesis-screening platform enables to obtain SAR data on b-secretase (BACE1) inhibitors at an unprecedented cycle time of only 1 h instead of several days. Full integration and automation of industrial processes have always led to productivity gains and cost reductions, and this work demonstrates how applying these concepts to SAR generation may lead to a more efficient drug discovery process. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The structure and function of cell membranes studied by atomic force microscopy.

PubMed

Shi, Yan; Cai, Mingjun; Zhou, Lulu; Wang, Hongda

2018-01-01

The cell membrane, involved in almost all communications of cells and surrounding matrix, is one of the most complicated components of cells. Lack of suitable methods for the detection of cell membranes in vivo has sparked debates on the biochemical composition and structure of cell membranes over half a century. The development of single molecule techniques, such as AFM, SMFS, and TREC, provides a versatile platform for imaging and manipulating cell membranes in biological relevant environments. Here, we discuss the latest developments in AFM and the progress made in cell membrane research. In particular, we highlight novel structure models and dynamic processes, including the mechanical properties of the cell membranes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors

PubMed Central

Zhang, Yu Shrike; Aleman, Julio; Shin, Su Ryon; Kim, Duckjin; Mousavi Shaegh, Seyed Ali; Massa, Solange; Riahi, Reza; Chae, Sukyoung; Hu, Ning; Avci, Huseyin; Zhang, Weijia; Silvestri, Antonia; Sanati Nezhad, Amir; Manbohi, Ahmad; De Ferrari, Fabio; Polini, Alessandro; Calzone, Giovanni; Shaikh, Noor; Alerasool, Parissa; Budina, Erica; Kang, Jian; Bhise, Nupura; Pourmand, Adel; Skardal, Aleksander; Shupe, Thomas; Bishop, Colin E.; Dokmeci, Mehmet Remzi; Atala, Anthony; Khademhosseini, Ali

2017-01-01

Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner. We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters. PMID:28265064

Reducing the Anaerobic Digestion Model No. 1 for its application to an industrial wastewater treatment plant treating winery effluent wastewater.

PubMed

García-Diéguez, Carlos; Bernard, Olivier; Roca, Enrique

2013-03-01

The Anaerobic Digestion Model No. 1 (ADM1) is a complex model which is widely accepted as a common platform for anaerobic process modeling and simulation. However, it has a large number of parameters and states that hinder its calibration and use in control applications. A principal component analysis (PCA) technique was extended and applied to simplify the ADM1 using data of an industrial wastewater treatment plant processing winery effluent. The method shows that the main model features could be obtained with a minimum of two reactions. A reduced stoichiometric matrix was identified and the kinetic parameters were estimated on the basis of representative known biochemical kinetics (Monod and Haldane). The obtained reduced model takes into account the measured states in the anaerobic wastewater treatment (AWT) plant and reproduces the dynamics of the process fairly accurately. The reduced model can support on-line control, optimization and supervision strategies for AWT plants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cognitive and hippocampus biochemical changes following sleep deprivation in the adult male rat.

PubMed

Nabaee, Ebrahim; Kesmati, Mahnaz; Shahriari, Ali; Khajehpour, Lotfollah; Torabi, Mozhgan

2018-05-14

Sleep deprivation (SD) influences physiological processes such as cognitive function. The balance of oxidant and antioxidant markers, neurotrophic factors and magnesium are affected by sleep deprivation but there is no difference between pre and post training sleep deprivation. This study was designed to investigate memory retrieval and biochemical factors such as oxidant and antioxidant enzyme, brain-derived neurotrophic factor (BDNF) and magnesium levels in the hippocampus following pre and post-training sleep deprivation. Male Wistar rats (weighing 200 ± 20 g) in below groups were used: control 1, 24, 48 and 72 h SD before training groups, control2, 24 h SD1 after training (being evaluated 24 h after training) and SD2 24 after training (being evaluated 48 h after training). Memory was evaluated 90 min, 24 h or 48 h after training by step-through passive avoidance apparatus. Multiple platforms method was used to induce SD. Oxidant and antioxidant markers including glutathione (GSH), glutathione reductase (GPx), malonedialdehyde (MDA), Total antioxidant concentration, catalase, superoxide dismutase (SOD), magnesium and BDNF were assessed in the hippocampus or/and brain. 72 h pre-training SD impaired short and long-term memory significantly. There was no significant difference in hippocampus oxidant and antioxidant markers compared to control. Hippocampal BDNF and magnesium did not show any changes in all SD groups. Lack of correlation between memory impairment and levels of BDNF, magnesium and/or oxidant and antioxidant balance in the hippocampus is likely to be related to animal locomotor activity in the multiple platforms method. More research is needed to clarify the role of neurochemical systems. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Catalytic Conversion of Carbohydrates to Initial Platform Chemicals: Chemistry and Sustainability.

PubMed

Mika, László T; Cséfalvay, Edit; Németh, Áron

2018-01-24

The replacement of fossil resources that currently provide more than 90% of our energy needs and feedstocks of the chemical industry in combination with reduced emission of carbon dioxide is one of the most pressing challenges of mankind. Biomass as a globally available resource has been proposed as an alternative feedstock for production of basic building blocks, which could partially or even fully replace the currently utilized fossil-based ones in well-established chemical processes. The destruction of lignocellulosic feed followed by oxygen removal from its cellulose and hemicellulose content by catalytic processes results in the formation of initial platform chemicals (IPCs). However, their sustainable production strongly depends on the availability of resources, their efficient or even industrially viable conversion processes, and replenishment time of feedstocks. Herein, we overview recent advances and developments in catalytic transformations of the carbohydrate content of lignocellulosic biomass to IPCs (i.e., ethanol, 3-hydroxypropionic acid, isoprene, succinic and levulinic acids, furfural, and 5-hydroxymethylfurfural). The mechanistic aspects, development of new catalysts, different efficiency indicators (yield and selectivity), and conversion conditions of their production are presented and compared. The potential biochemical production routes utilizing recently engineered microorganisms are reviewed, as well. The sustainability metrics that could be applied to the chemical industry (individual set of sustainability indicators, composite indices methods, material and energy flow analysis-based metrics, and ethanol equivalents) are also overviewed as well as an outlook is provided to highlight challenges and opportunities associated with this huge research area.

Targeted metabolomics and medication classification data from participants in the ADNI1 cohort.

PubMed

St John-Williams, Lisa; Blach, Colette; Toledo, Jon B; Rotroff, Daniel M; Kim, Sungeun; Klavins, Kristaps; Baillie, Rebecca; Han, Xianlin; Mahmoudiandehkordi, Siamak; Jack, John; Massaro, Tyler J; Lucas, Joseph E; Louie, Gregory; Motsinger-Reif, Alison A; Risacher, Shannon L; Saykin, Andrew J; Kastenmüller, Gabi; Arnold, Matthias; Koal, Therese; Moseley, M Arthur; Mangravite, Lara M; Peters, Mette A; Tenenbaum, Jessica D; Thompson, J Will; Kaddurah-Daouk, Rima

2017-10-17

Alzheimer's disease (AD) is the most common neurodegenerative disease presenting major health and economic challenges that continue to grow. Mechanisms of disease are poorly understood but significant data point to metabolic defects that might contribute to disease pathogenesis. The Alzheimer Disease Metabolomics Consortium (ADMC) in partnership with Alzheimer Disease Neuroimaging Initiative (ADNI) is creating a comprehensive biochemical database for AD. Using targeted and non- targeted metabolomics and lipidomics platforms we are mapping metabolic pathway and network failures across the trajectory of disease. In this report we present quantitative metabolomics data generated on serum from 199 control, 356 mild cognitive impairment and 175 AD subjects enrolled in ADNI1 using AbsoluteIDQ-p180 platform, along with the pipeline for data preprocessing and medication classification for confound correction. The dataset presented here is the first of eight metabolomics datasets being generated for broad biochemical investigation of the AD metabolome. We expect that these collective metabolomics datasets will provide valuable resources for researchers to identify novel molecular mechanisms contributing to AD pathogenesis and disease phenotypes.

Co-fabrication of chitosan and epoxy photoresist to form microwell arrays with permeable hydrogel bottoms

PubMed Central

Ornoff, Douglas M.; Wang, Yuli; Proctor, Angela; Shah, Akash S.; Allbritton, Nancy L.

2015-01-01

Microfabrication technology offers the potential to create biological platforms with customizable patterns and surface chemistries, allowing precise control over the biochemical microenvironment to which a cell or group of cells is exposed. However, most microfabricated platforms grow cells on impermeable surfaces. This report describes the co-fabrication of a micropatterned epoxy photoresist film with a chitosan film to create a freestanding array of permeable, hydrogel-bottomed microwells. These films possess optical properties ideal for microscopy applications, and the chitosan layers are semi-permeable with a molecular exclusion of 9.9 ± 2.1 kDa. By seeding cells into the microwells, overlaying inert mineral oil, and supplying media via the bottom surface, this hybrid film permits cells to be physically isolated from one another but maintained in culture for at least 4 days. Arrays co-fabricated using these materials reduce both large-molecular-weight biochemical crosstalk between cells and mixing of different clonal populations, and will enable high-throughput studies of cellular heterogeneity with increased ability to customize dynamic interrogations compared to materials in currently available technologies. PMID:26447557

Electrochemical Fabrication of Nanostructures on Porous Silicon for Biochemical Sensing Platforms.

PubMed

Ko, Euna; Hwang, Joonki; Kim, Ji Hye; Lee, Joo Heon; Lee, Sung Hwan; Tran, Van-Khue; Chung, Woo Sung; Park, Chan Ho; Choo, Jaebum; Seong, Gi Hun

2016-01-01

We present a method for the electrochemical patterning of gold nanoparticles (AuNPs) or silver nanoparticles (AgNPs) on porous silicon, and explore their applications in: (1) the quantitative analysis of hydroxylamine as a chemical sensing electrode and (2) as a highly sensitive surface-enhanced Raman spectroscopy (SERS) substrate for Rhodamine 6G. For hydroxylamine detection, AuNPs-porous silicon can enhance the electrochemical oxidation of hydroxylamine. The current changed linearly for concentrations ranging from 100 μM to 1.32 mM (R(2) = 0.995), and the detection limit was determined to be as low as 55 μM. When used as SERS substrates, these materials also showed that nanoparticles decorated on porous silicon substrates have more SERS hot spots than those decorated on crystalline silicon substrates, resulting in a larger SERS signal. Moreover, AgNPs-porous silicon provided five-times higher signal compared to AuNPs-porous silicon. From these results, we expect that nanoparticles decorated on porous silicon substrates can be used in various types of biochemical sensing platforms.

Targeted metabolomics and medication classification data from participants in the ADNI1 cohort

PubMed Central

St John-Williams, Lisa; Blach, Colette; Toledo, Jon B.; Rotroff, Daniel M.; Kim, Sungeun; Klavins, Kristaps; Baillie, Rebecca; Han, Xianlin; Mahmoudiandehkordi, Siamak; Jack, John; Massaro, Tyler J.; Lucas, Joseph E.; Louie, Gregory; Motsinger-Reif, Alison A.; Risacher, Shannon L.; Saykin, Andrew J.; Kastenmüller, Gabi; Arnold, Matthias; Koal, Therese; Moseley, M. Arthur; Mangravite, Lara M.; Peters, Mette A.; Tenenbaum, Jessica D.; Thompson, J. Will; Kaddurah-Daouk, Rima

2017-01-01

Alzheimer’s disease (AD) is the most common neurodegenerative disease presenting major health and economic challenges that continue to grow. Mechanisms of disease are poorly understood but significant data point to metabolic defects that might contribute to disease pathogenesis. The Alzheimer Disease Metabolomics Consortium (ADMC) in partnership with Alzheimer Disease Neuroimaging Initiative (ADNI) is creating a comprehensive biochemical database for AD. Using targeted and non- targeted metabolomics and lipidomics platforms we are mapping metabolic pathway and network failures across the trajectory of disease. In this report we present quantitative metabolomics data generated on serum from 199 control, 356 mild cognitive impairment and 175 AD subjects enrolled in ADNI1 using AbsoluteIDQ-p180 platform, along with the pipeline for data preprocessing and medication classification for confound correction. The dataset presented here is the first of eight metabolomics datasets being generated for broad biochemical investigation of the AD metabolome. We expect that these collective metabolomics datasets will provide valuable resources for researchers to identify novel molecular mechanisms contributing to AD pathogenesis and disease phenotypes. PMID:29039849

Activity-based protein profiling for biochemical pathway discovery in cancer

PubMed Central

Nomura, Daniel K.; Dix, Melissa M.; Cravatt, Benjamin F.

2011-01-01

Large-scale profiling methods have uncovered numerous gene and protein expression changes that correlate with tumorigenesis. However, determining the relevance of these expression changes and which biochemical pathways they affect has been hindered by our incomplete understanding of the proteome and its myriad functions and modes of regulation. Activity-based profiling platforms enable both the discovery of cancer-relevant enzymes and selective pharmacological probes to perturb and characterize these proteins in tumour cells. When integrated with other large-scale profiling methods, activity-based proteomics can provide insight into the metabolic and signalling pathways that support cancer pathogenesis and illuminate new strategies for disease diagnosis and treatment. PMID:20703252

[Analysis and research on the degradation and migration of organic pollutants in textile wastewater treatment process by GC-MS].

PubMed

Liu, Wei-jing; Zhang, Long; Wu, Wei; Tu, Yong

2010-04-01

In order to analyze the advantages/disadvantages of the combined treatment process between "physicochemical + biochemical" and "biochemical + physicochemical" in treatment of textile wastewater, gas chromatography-mass spectrometry (GC-MS) was used to determine the degradation process of organic pollutants in this two totally different treatment processes. The same analysis was also conducted to the sludge and discharged water. The results showed that the "physicochemical + biochemical" process displayed a poorer effect than "biochemical + physicochemical" in degrading the organic pollutants. The latter was 6.2% higher than the former in removing the organic pollutants averagely. The difference was mainly manifested in the efficiency of anaerobic hydrolysis in the two coupled processes. Moreover, the implement of "physicochemical + biochemical" process resulted in the migration of plenty of typical organic pollutants to sludge from primary coagulation sedimentation process and to the discharged water, which would cause secondary pollution easily.

Automated, high-throughput platform for protein solubility screening using a split-GFP system

PubMed Central

Listwan, Pawel; Terwilliger, Thomas C.

2010-01-01

Overproduction of soluble and stable proteins for functional and structural studies is a major bottleneck for structural genomics programs and traditional biochemistry laboratories. Many high-payoff proteins that are important in various biological processes are “difficult to handle” as protein reagents in their native form. We have recently made several advances in enabling biochemical technologies for improving protein stability (http://www.lanl.gov/projects/gfp/), allowing stratagems for efficient protein domain trapping, solubility-improving mutations, and finding protein folding partners. In particular split-GFP protein tags are a very powerful tool for detection of stable protein domains. Soluble, stable proteins tagged with the 15 amino acid GFP fragment (amino acids 216–228) can be detected in vivo and in vitro using the engineered GFP 1–10 “detector” fragment (amino acids 1–215). If the small tag is accessible, the detector fragment spontaneously binds resulting in fluorescence. Here, we describe our current and on-going efforts to move this process from the bench (manual sample manipulation) to an automated, high-throughput, liquid-handling platform. We discuss optimization and validation of bacterial culture growth, lysis protocols, protein extraction, and assays of soluble and insoluble protein in multiple 96 well plate format. The optimized liquid-handling protocol can be used for rapid determination of the optimal, compact domains from single ORFS, collections of ORFS, or cDNA libraries. PMID:19039681

2D materials integrated in Si3N4 photonics platform

NASA Astrophysics Data System (ADS)

Faneca, Joaquin; Hogan, Benjamin T.; Torres Alonso, E.; Craciun, Monica; Baldycheva, Anna

2018-02-01

In this paper, we discuss a back-end CMOS fabrication process for the large-scale integration of 2D materials on SOI (siliconon-insulator) platform and present a complete theoretical study of the change in the effective refractive index of 2D materialsenabled silicon nitride waveguide structures. The chemical vapour deposition (CVD) and liquid exfoliation fabrication methods are described for the fabrication of graphene, WS2 and MoS2 thin films. Finite-difference frequency-domain (FDFD) approach and the Transfer Matrix Method were used in order to mathematically describe these structures. The introduction of thin films of 2D material onto Si3N4 waveguide structures allows manipulation of the optical characteristics to a high degree of precision by varying the Fermi-level through the engineering of the number of atomically thin layers or by electrical tuning, for example. Based on the proposed tuning approach, designs of graphene, WS2 and MoS2 enabled Si3N4 micro-ring structures are presented for the visible and NIR range, which demonstrate versatility and desirable properties for a wide range of applications, such as bio-chemical sensing and optical communications.

Integrated Platform for Expedited Synthesis–Purification–Testing of Small Molecule Libraries

PubMed Central

2017-01-01

The productivity of medicinal chemistry programs can be significantly increased through the introduction of automation, leading to shortened discovery cycle times. Herein, we describe a platform that consolidates synthesis, purification, quantitation, dissolution, and testing of small molecule libraries. The system was validated through the synthesis and testing of two libraries of binders of polycomb protein EED, and excellent correlation of obtained data with results generated through conventional approaches was observed. The fully automated and integrated platform enables batch-supported compound synthesis based on a broad array of chemical transformations with testing in a variety of biochemical assay formats. A library turnaround time of between 24 and 36 h was achieved, and notably, each library synthesis produces sufficient amounts of compounds for further evaluation in secondary assays thereby contributing significantly to the shortening of medicinal chemistry discovery cycles. PMID:28435537

Deep subwavelength fourfold rotationally symmetric split-ring-resonator metamaterials for highly sensitive and robust biosensing platform

PubMed Central

Tobing, Landobasa Y. M.; Tjahjana, Liliana; Zhang, Dao Hua; Zhang, Qing; Xiong, Qihua

2013-01-01

Metamaterials provide a good platform for biochemical sensing due to its strong field localization at nanoscale. In this work, we show that electric and magnetic resonant modes in split-ring-resonator (SRR) can be efficiently excited under unpolarized light illumination when the SRRs are arranged in fourfold rotationally symmetric lattice configuration. The fabrication and characterization of deep subwavelength (~λ/15) gold-based SRR structures with resonator size as small as ~ 60 nm are reported with magnetic resonances in Vis-NIR spectrum range. The feasibility for sensing is demonstrated with refractive index sensitivity as high as ~ 636 nm/RIU. PMID:23942416

A robust robotic high-throughput antibody purification platform.

PubMed

Schmidt, Peter M; Abdo, Michael; Butcher, Rebecca E; Yap, Min-Yin; Scotney, Pierre D; Ramunno, Melanie L; Martin-Roussety, Genevieve; Owczarek, Catherine; Hardy, Matthew P; Chen, Chao-Guang; Fabri, Louis J

2016-07-15

Monoclonal antibodies (mAbs) have become the fastest growing segment in the drug market with annual sales of more than 40 billion US$ in 2013. The selection of lead candidate molecules involves the generation of large repertoires of antibodies from which to choose a final therapeutic candidate. Improvements in the ability to rapidly produce and purify many antibodies in sufficient quantities reduces the lead time for selection which ultimately impacts on the speed with which an antibody may transition through the research stage and into product development. Miniaturization and automation of chromatography using micro columns (RoboColumns(®) from Atoll GmbH) coupled to an automated liquid handling instrument (ALH; Freedom EVO(®) from Tecan) has been a successful approach to establish high throughput process development platforms. Recent advances in transient gene expression (TGE) using the high-titre Expi293F™ system have enabled recombinant mAb titres of greater than 500mg/L. These relatively high protein titres reduce the volume required to generate several milligrams of individual antibodies for initial biochemical and biological downstream assays, making TGE in the Expi293F™ system ideally suited to high throughput chromatography on an ALH. The present publication describes a novel platform for purifying Expi293F™-expressed recombinant mAbs directly from cell-free culture supernatant on a Perkin Elmer JANUS-VariSpan ALH equipped with a plate shuttle device. The purification platform allows automated 2-step purification (Protein A-desalting/size exclusion chromatography) of several hundred mAbs per week. The new robotic method can purify mAbs with high recovery (>90%) at sub-milligram level with yields of up to 2mg from 4mL of cell-free culture supernatant. Copyright © 2016 Elsevier B.V. All rights reserved.

Förster resonance energy transfer as a tool to study photoreceptor biology

PubMed Central

Hovan, Stephanie C.; Howell, Scott; Park, Paul S.-H.

2010-01-01

Vision is initiated in photoreceptor cells of the retina by a set of biochemical events called phototransduction. These events occur via coordinated dynamic processes that include changes in secondary messenger concentrations, conformational changes and post-translational modifications of signaling proteins, and protein-protein interactions between signaling partners. A complete description of the orchestration of these dynamic processes is still unavailable. Described in this work is the first step in the development of tools combining fluorescent protein technology, Förster resonance energy transfer (FRET), and transgenic animals that have the potential to reveal important molecular insights about the dynamic processes occurring in photoreceptor cells. We characterize the fluorescent proteins SCFP3A and SYFP2 for use as a donor-acceptor pair in FRET assays, which will facilitate the visualization of dynamic processes in living cells. We also demonstrate the targeted expression of these fluorescent proteins to the rod photoreceptor cells of Xenopus laevis, and describe a general method for detecting FRET in these cells. The general approaches described here can address numerous types of questions related to phototransduction and photoreceptor biology by providing a platform to visualize dynamic processes in molecular detail within a native context. PMID:21198205

Effective inactivation of Saccharomyces cerevisiae in minimally processed Makgeolli using low-pressure homogenization-based pasteurization.

PubMed

Bak, Jin Seop

2015-01-01

In order to address the limitations associated with the inefficient pasteurization platform used to make Makgeolli, such as the presence of turbid colloidal dispersions in suspension, commercially available Makgeolli was minimally processed using a low-pressure homogenization-based pasteurization (LHBP) process. This continuous process demonstrates that promptly reducing the exposure time to excessive heat using either large molecules or insoluble particles can dramatically improve internal quality and decrease irreversible damage. Specifically, optimal homogenization increased concomitantly with physical parameters such as colloidal stability (65.0% of maximum and below 25-μm particles) following two repetitions at 25.0 MPa. However, biochemical parameters such as microbial population, acidity, and the presence of fermentable sugars rarely affected Makgeolli quality. Remarkably, there was a 4.5-log reduction in the number of Saccharomyces cerevisiae target cells at 53.5°C for 70 sec in optimally homogenized Makgeolli. This value was higher than the 37.7% measured from traditionally pasteurized Makgeolli. In contrast to the analytical similarity among homogenized Makgeollis, our objective quality evaluation demonstrated significant differences between pasteurized (or unpasteurized) Makgeolli and LHBP-treated Makgeolli. Low-pressure homogenization-based pasteurization, Makgeolli, minimal processing-preservation, Saccharomyces cerevisiae, suspension stability.

Peptide-MHC-based nanomedicines for autoimmunity function as T-cell receptor microclustering devices

NASA Astrophysics Data System (ADS)

Singha, Santiswarup; Shao, Kun; Yang, Yang; Clemente-Casares, Xavier; Solé, Patricia; Clemente, Antonio; Blanco, Jesús; Dai, Qin; Song, Fayi; Liu, Shang Wan; Yamanouchi, Jun; Umeshappa, Channakeshava Sokke; Nanjundappa, Roopa Hebbandi; Detampel, Pascal; Amrein, Matthias; Fandos, César; Tanguay, Robert; Newbigging, Susan; Serra, Pau; Khadra, Anmar; Chan, Warren C. W.; Santamaria, Pere

2017-07-01

We have shown that nanoparticles (NPs) can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo. Nanoparticles coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHC) blunted autoimmune responses by triggering the differentiation and expansion of antigen-specific regulatory T cells in vivo. Here, we define the engineering principles impacting biological activity, detail a synthesis process yielding safe and stable compounds, and visualize how these nanomedicines interact with cognate T cells. We find that the triggering properties of pMHC-NPs are a function of pMHC intermolecular distance and involve the sustained assembly of large antigen receptor microclusters on murine and human cognate T cells. These compounds show no off-target toxicity in zebrafish embryos, do not cause haematological, biochemical or histological abnormalities, and are rapidly captured by phagocytes or processed by the hepatobiliary system. This work lays the groundwork for the design of ligand-based NP formulations to re-program in vivo cellular responses using nanotechnology.

3D plasmonic nanobowl platform for the study of exosomes in solution

NASA Astrophysics Data System (ADS)

Lee, Changwon; Carney, Randy P.; Hazari, Sidhartha; Smith, Zachary J.; Knudson, Alisha; Robertson, Christopher S.; Lam, Kit S.; Wachsmann-Hogiu, Sebastian

2015-05-01

Thin silver film coated nanobowl Surface Enhanced Raman Spectroscopy (SERS) substrates are used to capture exosomes in solution for SERS measurements that can provide biochemical analysis of intact and ruptured exosomes. Exosomes derived via Total Exosome Isolation Reagent (TEIR) as well as ultracentrifugation (UC) from the SKOV3 cell line were analyzed. Spectra of exosomes derived via TEIR are dominated by a signal characteristic for the TEIR kit that needs to be subtracted for all measurements. Differences in SERS spectra recorded at different times during the drying of the exosome solution are statistically analyzed with Principal Component Analysis (PCA). At the beginning of the drying process, SERS spectra of exosomes exhibit peaks characteristic for both lipids and proteins. Later on during the drying process, new SERS peaks develop, suggesting that the initially intact exosome ruptures over time. This time-dependent evolution of SERS peaks enables analysis of exosomal membrane contents and the contents inside the exosomes.

A novel biochemical route for fuels and chemicals production from cellulosic biomass.

PubMed

Fan, Zhiliang; Wu, Weihua; Hildebrand, Amanda; Kasuga, Takao; Zhang, Ruifu; Xiong, Xiaochao

2012-01-01

The conventional biochemical platform featuring enzymatic hydrolysis involves five key steps: pretreatment, cellulase production, enzymatic hydrolysis, fermentation, and product recovery. Sugars are produced as reactive intermediates for subsequent fermentation to fuels and chemicals. Herein, an alternative biochemical route is proposed. Pretreatment, enzymatic hydrolysis and cellulase production is consolidated into one single step, referred to as consolidated aerobic processing, and sugar aldonates are produced as the reactive intermediates for biofuels production by fermentation. In this study, we demonstrate the viability of consolidation of the enzymatic hydrolysis and cellulase production steps in the new route using Neurospora crassa as the model microorganism and the conversion of cellulose to ethanol as the model system. We intended to prove the two hypotheses: 1) cellulose can be directed to produce cellobionate by reducing β-glucosidase production and by enhancing cellobiose dehydrogenase production; and 2) both of the two hydrolysis products of cellobionate--glucose and gluconate--can be used as carbon sources for ethanol and other chemical production. Our results showed that knocking out multiple copies of β-glucosidase genes led to cellobionate production from cellulose, without jeopardizing the cellulose hydrolysis rate. Simulating cellobiose dehydrogenase over-expression by addition of exogenous cellobiose dehydrogenase led to more cellobionate production. Both of the two hydrolysis products of cellobionate: glucose and gluconate can be used by Escherichia coli KO 11 for efficient ethanol production. They were utilized simultaneously in glucose and gluconate co-fermentation. Gluconate was used even faster than glucose. The results support the viability of the two hypotheses that lay the foundation for the proposed new route.

A Novel Biochemical Route for Fuels and Chemicals Production from Cellulosic Biomass

PubMed Central

Fan, Zhiliang; Wu, Weihua; Hildebrand, Amanda; Kasuga, Takao; Zhang, Ruifu; Xiong, Xiaochao

2012-01-01

The conventional biochemical platform featuring enzymatic hydrolysis involves five key steps: pretreatment, cellulase production, enzymatic hydrolysis, fermentation, and product recovery. Sugars are produced as reactive intermediates for subsequent fermentation to fuels and chemicals. Herein, an alternative biochemical route is proposed. Pretreatment, enzymatic hydrolysis and cellulase production is consolidated into one single step, referred to as consolidated aerobic processing, and sugar aldonates are produced as the reactive intermediates for biofuels production by fermentation. In this study, we demonstrate the viability of consolidation of the enzymatic hydrolysis and cellulase production steps in the new route using Neurospora crassa as the model microorganism and the conversion of cellulose to ethanol as the model system. We intended to prove the two hypotheses: 1) cellulose can be directed to produce cellobionate by reducing β-glucosidase production and by enhancing cellobiose dehydrogenase production; and 2) both of the two hydrolysis products of cellobionate—glucose and gluconate—can be used as carbon sources for ethanol and other chemical production. Our results showed that knocking out multiple copies of β-glucosidase genes led to cellobionate production from cellulose, without jeopardizing the cellulose hydrolysis rate. Simulating cellobiose dehydrogenase over-expression by addition of exogenous cellobiose dehydrogenase led to more cellobionate production. Both of the two hydrolysis products of cellobionate: glucose and gluconate can be used by Escherichia coli KO 11 for efficient ethanol production. They were utilized simultaneously in glucose and gluconate co-fermentation. Gluconate was used even faster than glucose. The results support the viability of the two hypotheses that lay the foundation for the proposed new route. PMID:22384058

Studying the rapid bioconversion of lignocellulosic sugars into ethanol using high cell density fermentations with cell recycle

PubMed Central

2014-01-01

Background The Rapid Bioconversion with Integrated recycle Technology (RaBIT) process reduces capital costs, processing times, and biocatalyst cost for biochemical conversion of cellulosic biomass to biofuels by reducing total bioprocessing time (enzymatic hydrolysis plus fermentation) to 48 h, increasing biofuel productivity (g/L/h) twofold, and recycling biocatalysts (enzymes and microbes) to the next cycle. To achieve these results, RaBIT utilizes 24-h high cell density fermentations along with cell recycling to solve the slow/incomplete xylose fermentation issue, which is critical for lignocellulosic biofuel fermentations. Previous studies utilizing similar fermentation conditions showed a decrease in xylose consumption when recycling cells into the next fermentation cycle. Eliminating this decrease is critical for RaBIT process effectiveness for high cycle counts. Results Nine different engineered microbial strains (including Saccharomyces cerevisiae strains, Scheffersomyces (Pichia) stipitis strains, Zymomonas mobilis 8b, and Escherichia coli KO11) were tested under RaBIT platform fermentations to determine their suitability for this platform. Fermentation conditions were then optimized for S. cerevisiae GLBRCY128. Three different nutrient sources (corn steep liquor, yeast extract, and wheat germ) were evaluated to improve xylose consumption by recycled cells. Capacitance readings were used to accurately measure viable cell mass profiles over five cycles. Conclusion The results showed that not all strains are capable of effectively performing the RaBIT process. Acceptable performance is largely correlated to the specific xylose consumption rate. Corn steep liquor was found to reduce the deleterious impacts of cell recycle and improve specific xylose consumption rates. The viable cell mass profiles indicated that reduction in specific xylose consumption rate, not a drop in viable cell mass, was the main cause for decreasing xylose consumption. PMID:24847379

Towards an Understanding of How Protein Hydrolysates Stimulate More Efficient Biosynthesis in Cultured Cells

NASA Astrophysics Data System (ADS)

Siemensma, André; Babcock, James; Wilcox, Chris; Huttinga, Hans

In the light of the growing demand for high quality plant-derived hydrolysates (i.e., HyPep™ and UltraPep™ series), Sheffield Bio-Science has developed a new hydrolysate platform that addresses the need for animal-free cell culture medium supplements while also minimizing variability concerns. The platform is based upon a novel approach to enzymatic digestion and more refined processing. At the heart of the platform is a rationally designed animal component-free (ACF) enzyme cocktail that includes both proteases and non-proteolytic enzymes (hydrolases) whose activities can also liberate primary components of the polymerized non-protein portion of the raw material. This enzyme system is added during a highly optimized process step that targets specific enzyme-substrate reactions to expand the range of beneficial nutritional factors made available to cells in culture. Such factors are fundamental to improving the bio-performance of the culture system, as they provide not merely growth-promoting peptides and amino acids, but also key carbohydrates, lipids, minerals, and vitamins that improve both rate and quality of protein expression, and serve to improve culture life due to osmo-protectant and anti-apoptotic properties. Also of significant note is that, compared to typical hydrolysates, the production process is greatly reduced and requires fewer steps, intrinsically yielding a better-controlled and therefore more reproducible product. Finally, the more sophisticated approach to enzymatic digestion renders hydrolysates more amenable to sterile filtration, allowing hydrolysate end users to experience streamlined media preparation and bioreactor supplementation activities. Current and future development activities will evolve from a better understanding of the complex interactions within a handful of key biochemical pathways that impact the growth and productivity of industrially relevant organisms. Presented in this chapter are some examples of the efforts that have been made so far to elucidate the mechanisms for the often dramatic benefits that hydrolysates can impart on cell culture processes. Given the variety of roles that hydrolysates likely play in each cell type, close collaboration between protein hydrolysate manufacturers and biopharmaceutical developers will continue to be critical to expanding the industry's knowledge and retaining hydrolysates as a tool for enhancing media formulations.

A systematic petri net approach for multiple-scale modeling and simulation of biochemical processes.

PubMed

Chen, Ming; Hu, Minjie; Hofestädt, Ralf

2011-06-01

A method to exploit hybrid Petri nets for modeling and simulating biochemical processes in a systematic way was introduced. Both molecular biology and biochemical engineering aspects are manipulated. With discrete and continuous elements, the hybrid Petri nets can easily handle biochemical factors such as metabolites concentration and kinetic behaviors. It is possible to translate both molecular biological behavior and biochemical processes workflow into hybrid Petri nets in a natural manner. As an example, penicillin production bioprocess is modeled to illustrate the concepts of the methodology. Results of the dynamic of production parameters in the bioprocess were simulated and observed diagrammatically. Current problems and post-genomic perspectives were also discussed.

Responds of Bone Cells to Microgravity: Ground-Based Research

NASA Astrophysics Data System (ADS)

Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

2015-11-01

Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

New technology for early detection of health threats

NASA Astrophysics Data System (ADS)

Southern, Šárka O.; Lilienthal, Gerald W.

2008-04-01

Governmental agencies charged with protecting the health of the population and agriculture have several main strategic objectives including the detection of harmful agents, the identification of vulnerable biological targets, the prediction of health outcomes and the development of countermeasures. New technologies are urgently needed in several critical areas of bio-chemical defense: economical and minimally invasive biosensors for field use in humans and other species important for agriculture and infrastructure, universal analytical platforms for broad-based, early warnings of threats and technologies guiding the development of countermeasures. A new technology called Stress Response Profiling (SRP) was recently developed by the Gaia Medical Institute. SRP provides a universal analytical platform for monitoring health status based on measurements of physiological stress. The platform is implemented through handheld devices that can be used for noninvasive detection of early-stage health problems. This paper summarizes SRP features, advantages and potential benefits for critical areas of homeland defense.

Strategies to Maximize the Potential of Marine Biomaterials as a Platform for Cell Therapy

PubMed Central

Kim, Hyeongmin; Lee, Jaehwi

2016-01-01

Marine biopolymers have been explored as a promising cell therapy system for efficient cell delivery and tissue engineering. However, the marine biomaterial-based systems themselves have exhibited limited performance in terms of maintenance of cell viability and functions, promotion of cell proliferation and differentiation as well as cell delivery efficiency. Thus, numerous novel strategies have been devised to improve cell therapy outcomes. The strategies include optimization of physical and biochemical properties, provision of stimuli-responsive functions, and design of platforms for efficient cell delivery and tissue engineering. These approaches have demonstrated substantial improvement of therapeutic outcomes in a variety of research settings. In this review, therefore, research progress made with marine biomaterials as a platform for cell therapy is reported along with current research directions to further advance cell therapies as a tool to cure incurable diseases. PMID:26821034

A cobalt oxyhydroxide-modified upconversion nanosystem for sensitive fluorescence sensing of ascorbic acid in human plasma

NASA Astrophysics Data System (ADS)

Cen, Yao; Tang, Jun; Kong, Xiang-Juan; Wu, Shuang; Yuan, Jing; Yu, Ru-Qin; Chu, Xia

2015-08-01

Ascorbic acid (AA), a potent antioxidant readily scavenging reactive species, is a crucial micronutrient involved in many biochemical processes. Here, we have developed a cobalt oxyhydroxide (CoOOH)-modified upconversion nanosystem for fluorescence sensing of AA activity in human plasma. The nanosystem consists of upconversion nanoparticles (UCNPs) NaYF4:30% Yb,0.5% Tm@NaYF4, which serve as energy donors, and CoOOH nanoflakes formed on the surface of UCNPs, which act as efficient energy acceptors. The fluorescence resonance energy transfer (FRET) process from the UCNPs to the absorbance of the CoOOH nanoflakes occurs in the nanosystem. The AA-mediated specific redox reaction reduces CoOOH into Co2+, leading to the inhibition of FRET, and resulting in the recovery of upconversion emission spectra. On the basis of these features, the nanosystem can be used for sensing AA activity with sensitivity and selectivity. Moreover, due to the minimizing background interference provided by UCNPs, the nanosystem has been applied to monitoring AA levels in human plasma sample with satisfactory results. The proposed approach may potentially provide an analytical platform for research and clinical diagnosis of AA related diseases.Ascorbic acid (AA), a potent antioxidant readily scavenging reactive species, is a crucial micronutrient involved in many biochemical processes. Here, we have developed a cobalt oxyhydroxide (CoOOH)-modified upconversion nanosystem for fluorescence sensing of AA activity in human plasma. The nanosystem consists of upconversion nanoparticles (UCNPs) NaYF4:30% Yb,0.5% Tm@NaYF4, which serve as energy donors, and CoOOH nanoflakes formed on the surface of UCNPs, which act as efficient energy acceptors. The fluorescence resonance energy transfer (FRET) process from the UCNPs to the absorbance of the CoOOH nanoflakes occurs in the nanosystem. The AA-mediated specific redox reaction reduces CoOOH into Co2+, leading to the inhibition of FRET, and resulting in the recovery of upconversion emission spectra. On the basis of these features, the nanosystem can be used for sensing AA activity with sensitivity and selectivity. Moreover, due to the minimizing background interference provided by UCNPs, the nanosystem has been applied to monitoring AA levels in human plasma sample with satisfactory results. The proposed approach may potentially provide an analytical platform for research and clinical diagnosis of AA related diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03588k

Isotopic studies of metabolic systems by mass spectrometry: using Pascal's triangle to produce biological standards with fully controlled labeling patterns.

PubMed

Millard, Pierre; Massou, Stéphane; Portais, Jean-Charles; Létisse, Fabien

2014-10-21

Mass spectrometry (MS) is widely used for isotopic studies of metabolism in which detailed information about biochemical processes is obtained from the analysis of isotope incorporation into metabolites. The biological value of such experiments is dependent on the accuracy of the isotopic measurements. Using MS, isotopologue distributions are measured from the quantitative analysis of isotopic clusters. These measurements are prone to various biases, which can occur during the experimental workflow and/or MS analysis. The lack of relevant standards limits investigations of the quality of the measured isotopologue distributions. To meet that need, we developed a complete theoretical and experimental framework for the biological production of metabolites with fully controlled and predictable labeling patterns. This strategy is valid for different isotopes and different types of metabolisms and organisms, and was applied to two model microorganisms, Pichia augusta and Escherichia coli, cultivated on (13)C-labeled methanol and acetate as sole carbon source, respectively. The isotopic composition of the substrates was designed to obtain samples in which the isotopologue distribution of all the metabolites should give the binomial coefficients found in Pascal's triangle. The strategy was validated on a liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform by quantifying the complete isotopologue distributions of different intracellular metabolites, which were in close agreement with predictions. This strategy can be used to evaluate entire experimental workflows (from sampling to data processing) or different analytical platforms in the context of isotope labeling experiments.

DEAD-box Helicases as Integrators of RNA, Nucleotide and Protein Binding

PubMed Central

Putnam, Andrea A.

2013-01-01

DEAD-box helicases perform diverse cellular functions in virtually all steps of RNA metabolism from Bacteria to Humans. Although DEAD-box helicases share a highly conserved core domain, the enzymes catalyze a wide range of biochemical reactions. In addition to the well established RNA unwinding and corresponding ATPase activities, DEAD-box helicases promote duplex formation and displace proteins from RNA. They can also function as assembly platforms for larger ribonucleoprotein complexes, and as metabolite sensors. This review aims to provide a perspective on the diverse biochemical features of DEAD-box helicases and connections to structural information. We discuss these data in the context of a model that views the enzymes as integrators of RNA, nucleotide, and protein binding. PMID:23416748

System-Level and Granger Network Analysis of Integrated Proteomic and Metabolomic Dynamics Identifies Key Points of Grape Berry Development at the Interface of Primary and Secondary Metabolism.

PubMed

Wang, Lei; Sun, Xiaoliang; Weiszmann, Jakob; Weckwerth, Wolfram

2017-01-01

Grapevine is a fruit crop with worldwide economic importance. The grape berry undergoes complex biochemical changes from fruit set until ripening. This ripening process and production processes define the wine quality. Thus, a thorough understanding of berry ripening is crucial for the prediction of wine quality. For a systemic analysis of grape berry development we applied mass spectrometry based platforms to analyse the metabolome and proteome of Early Campbell at 12 stages covering major developmental phases. Primary metabolites involved in central carbon metabolism, such as sugars, organic acids and amino acids together with various bioactive secondary metabolites like flavonols, flavan-3-ols and anthocyanins were annotated and quantified. At the same time, the proteomic analysis revealed the protein dynamics of the developing grape berries. Multivariate statistical analysis of the integrated metabolomic and proteomic dataset revealed the growth trajectory and corresponding metabolites and proteins contributing most to the specific developmental process. K-means clustering analysis revealed 12 highly specific clusters of co-regulated metabolites and proteins. Granger causality network analysis allowed for the identification of time-shift correlations between metabolite-metabolite, protein- protein and protein-metabolite pairs which is especially interesting for the understanding of developmental processes. The integration of metabolite and protein dynamics with their corresponding biochemical pathways revealed an energy-linked metabolism before veraison with high abundances of amino acids and accumulation of organic acids, followed by protein and secondary metabolite synthesis. Anthocyanins were strongly accumulated after veraison whereas other flavonoids were in higher abundance at early developmental stages and decreased during the grape berry developmental processes. A comparison of the anthocyanin profile of Early Campbell to other cultivars revealed similarities to Concord grape and indicates the strong effect of genetic background on metabolic partitioning in primary and secondary metabolism.

System-Level and Granger Network Analysis of Integrated Proteomic and Metabolomic Dynamics Identifies Key Points of Grape Berry Development at the Interface of Primary and Secondary Metabolism

PubMed Central

Wang, Lei; Sun, Xiaoliang; Weiszmann, Jakob; Weckwerth, Wolfram

2017-01-01

Grapevine is a fruit crop with worldwide economic importance. The grape berry undergoes complex biochemical changes from fruit set until ripening. This ripening process and production processes define the wine quality. Thus, a thorough understanding of berry ripening is crucial for the prediction of wine quality. For a systemic analysis of grape berry development we applied mass spectrometry based platforms to analyse the metabolome and proteome of Early Campbell at 12 stages covering major developmental phases. Primary metabolites involved in central carbon metabolism, such as sugars, organic acids and amino acids together with various bioactive secondary metabolites like flavonols, flavan-3-ols and anthocyanins were annotated and quantified. At the same time, the proteomic analysis revealed the protein dynamics of the developing grape berries. Multivariate statistical analysis of the integrated metabolomic and proteomic dataset revealed the growth trajectory and corresponding metabolites and proteins contributing most to the specific developmental process. K-means clustering analysis revealed 12 highly specific clusters of co-regulated metabolites and proteins. Granger causality network analysis allowed for the identification of time-shift correlations between metabolite-metabolite, protein- protein and protein-metabolite pairs which is especially interesting for the understanding of developmental processes. The integration of metabolite and protein dynamics with their corresponding biochemical pathways revealed an energy-linked metabolism before veraison with high abundances of amino acids and accumulation of organic acids, followed by protein and secondary metabolite synthesis. Anthocyanins were strongly accumulated after veraison whereas other flavonoids were in higher abundance at early developmental stages and decreased during the grape berry developmental processes. A comparison of the anthocyanin profile of Early Campbell to other cultivars revealed similarities to Concord grape and indicates the strong effect of genetic background on metabolic partitioning in primary and secondary metabolism. PMID:28713396

Life Science Research in Outer Space: New Platform Technologies for Low-Cost, Autonomous Small Satellite Missions

NASA Technical Reports Server (NTRS)

Ricco, Antonio J.; Parra, Macarena P.; Niesel, David; McGinnis, Michael; Ehrenfreund, Pascale; Nicholson, Wayne; Mancinelli, Rocco; Piccini, Matthew E.; Beasley, Christopher C.; Timucin, Linda R.;

CHRONIOUS: a wearable platform for monitoring and management of patients with chronic disease.

PubMed

Bellos, Christos; Papadopoulos, Athanassios; Rosso, Roberto; Fotiadis, Dimitrios I

2011-01-01

The CHRONIOUS system has been developed based on an open architecture design that consists of a set of subsystems which interact in order to provide all the needed services to the chronic disease patients. An advanced multi-parametric expert system is being implemented that fuses information effectively from various sources using intelligent techniques. Data are collected by sensors of a body network controlling vital signals while additional tools record dietary habits and plans, drug intake, environmental and biochemical parameters and activity data. The CHRONIOUS platform provides guidelines and standards for the future generations of "chronic disease management systems" and facilitates sophisticated monitoring tools. In addition, an ontological information retrieval system is being delivered satisfying the necessities for up-to-date clinical information of Chronic Obstructive pulmonary disease (COPD) and Chronic Kidney Disease (CKD). Moreover, support tools are being embedded in the system, such as the Mental Tools for the monitoring of patient mental health status. The integrated platform provides real-time patient monitoring and supervision, both indoors and outdoors and represents a generic platform for the management of various chronic diseases.

Glyco-Immune Diagnostic Signatures and Therapeutic Targets of Mesothelioma

DTIC Science & Technology

2015-09-01

Immunoprofiles; Robotic Arrayer 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACT: UU 18. NUMBER OF PAGES 19 19a. NAME OF RESPONSIBLE...General Comments: This project involved novel technology in which biochemically synthesized glycans were robotically printed on glass slides...glycans and the platform was known as the PGA-400. (Figure 1) A standard robotic technology for printing a large range of aminefunctionalized

Glyco-Immune Diagnostic Signatures and Therapeutic Targets of Mesothelioma

DTIC Science & Technology

2015-09-01

Mesothelioma; Glycan Array; Immunoprofiles; Robotic Arrayer 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACT: UU 18. NUMBER OF PAGES 19 19a...PROJECT SUMMARY: General Comments: This project involved novel technology in which biochemically synthesized glycans were robotically printed on glass...include 386 glycans and the platform was known as the PGA-400. (Figure 1) A standard robotic technology for printing a large range of

Flexible, secure agent development framework

DOEpatents

Goldsmith,; Steven, Y [Rochester, MN

2009-04-07

While an agent generator is generating an intelligent agent, it can also evaluate the data processing platform on which it is executing, in order to assess a risk factor associated with operation of the agent generator on the data processing platform. The agent generator can retrieve from a location external to the data processing platform an open site that is configurable by the user, and load the open site into an agent substrate, thereby creating a development agent with code development capabilities. While an intelligent agent is executing a functional program on a data processing platform, it can also evaluate the data processing platform to assess a risk factor associated with performing the data processing function on the data processing platform.

Analytical considerations and dimensionless analysis for a description of particle interactions in high pressure processes

NASA Astrophysics Data System (ADS)

Rauh, Cornelia; Delgado, Antonio

2010-12-01

High pressures of up to several hundreds of MPa are utilized in a wide range of applications in chemical, bio-, and food engineering, aiming at selective control of (bio-)chemical reactions. Non-uniformity of process conditions may threaten the safety and quality of the resulting products because processing conditions such as pressure, temperature, and treatment history are crucial for the course of (bio-)chemical reactions. Therefore, thermofluid-dynamical phenomena during the high pressure process have to be examined, and numerical tools to predict process uniformity and to optimize the processes have to be developed. Recently applied mathematical models and numerical simulations of laboratory and industrial scale high pressure processes investigating the mentioned crucial phenomena are based on continuum balancing models of thermofluid dynamics. Nevertheless, biological systems are complex fluids containing the relevant (bio-)chemical compounds (enzymes and microorganisms). These compounds are particles that interact with the surrounding medium and between each other. This contribution deals with thermofluid-dynamical interactions of the relevant particulate (bio-)chemical compounds (enzymes and microorganisms) with the surrounding fluid. By consideration of characteristic time and length scales and particle forces, the motion of the (bio-)chemical compounds is characterized.

Evaluation of peristaltic micromixers for highly integrated microfluidic systems

PubMed Central

Kim, Duckjong; Rho, Hoon Suk; Jambovane, Sachin; Shin, Soojeong; Hong, Jong Wook

2016-01-01

Microfluidic devices based on the multilayer soft lithography allow accurate manipulation of liquids, handling reagents at the sub-nanoliter level, and performing multiple reactions in parallel processors by adapting micromixers. Here, we have experimentally evaluated and compared several designs of micromixers and operating conditions to find design guidelines for the micromixers. We tested circular, triangular, and rectangular mixing loops and measured mixing performance according to the position and the width of the valves that drive nanoliters of fluids in the micrometer scale mixing loop. We found that the rectangular mixer is best for the applications of highly integrated microfluidic platforms in terms of the mixing performance and the space utilization. This study provides an improved understanding of the flow behaviors inside micromixers and design guidelines for micromixers that are critical to build higher order fluidic systems for the complicated parallel bio/chemical processes on a chip. PMID:27036809

Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry.

PubMed

Ejsing, Christer S; Sampaio, Julio L; Surendranath, Vineeth; Duchoslav, Eva; Ekroos, Kim; Klemm, Robin W; Simons, Kai; Shevchenko, Andrej

2009-02-17

Although the transcriptome, proteome, and interactome of several eukaryotic model organisms have been described in detail, lipidomes remain relatively uncharacterized. Using Saccharomyces cerevisiae as an example, we demonstrate that automated shotgun lipidomics analysis enabled lipidome-wide absolute quantification of individual molecular lipid species by streamlined processing of a single sample of only 2 million yeast cells. By comparative lipidomics, we achieved the absolute quantification of 250 molecular lipid species covering 21 major lipid classes. This analysis provided approximately 95% coverage of the yeast lipidome achieved with 125-fold improvement in sensitivity compared with previous approaches. Comparative lipidomics demonstrated that growth temperature and defects in lipid biosynthesis induce ripple effects throughout the molecular composition of the yeast lipidome. This work serves as a resource for molecular characterization of eukaryotic lipidomes, and establishes shotgun lipidomics as a powerful platform for complementing biochemical studies and other systems-level approaches.

Evaluation of peristaltic micromixers for highly integrated microfluidic systems

NASA Astrophysics Data System (ADS)

Kim, Duckjong; Rho, Hoon Suk; Jambovane, Sachin; Shin, Soojeong; Hong, Jong Wook

2016-03-01

Microfluidic devices based on the multilayer soft lithography allow accurate manipulation of liquids, handling reagents at the sub-nanoliter level, and performing multiple reactions in parallel processors by adapting micromixers. Here, we have experimentally evaluated and compared several designs of micromixers and operating conditions to find design guidelines for the micromixers. We tested circular, triangular, and rectangular mixing loops and measured mixing performance according to the position and the width of the valves that drive nanoliters of fluids in the micrometer scale mixing loop. We found that the rectangular mixer is best for the applications of highly integrated microfluidic platforms in terms of the mixing performance and the space utilization. This study provides an improved understanding of the flow behaviors inside micromixers and design guidelines for micromixers that are critical to build higher order fluidic systems for the complicated parallel bio/chemical processes on a chip.

Microfluidics-based integrated airborne pathogen detection systems

NASA Astrophysics Data System (ADS)

Northrup, M. Allen; Alleman-Sposito, Jennifer; Austin, Todd; Devitt, Amy; Fong, Donna; Lin, Phil; Nakao, Brian; Pourahmadi, Farzad; Vinas, Mary; Yuan, Bob

2006-09-01

Microfluidic Systems is focused on building microfluidic platforms that interface front-end mesofluidics to handle real world sample volumes for optimal sensitivity coupled to microfluidic circuitry to process small liquid volumes for complex reagent metering, mixing, and biochemical analysis, particularly for pathogens. MFSI is the prime contractor on two programs for the US Department of Homeland Security: BAND (Bioagent Autonomous Networked Detector) and IBADS (Instantaneous Bio-Aerosol Detection System). The goal of BAND is to develop an autonomous system for monitoring the air for known biological agents. This consists of air collection, sample lysis, sample purification, detection of DNA, RNA, and toxins, and a networked interface to report the results. For IBADS, MFSI is developing the confirmatory device which must verify the presence of a pathogen with 5 minutes of an air collector/trigger sounding an alarm. Instrument designs and biological assay results from both BAND and IBADS will be presented.

Direct assembling methodologies for high-throughput bioscreening

PubMed Central

Rodríguez-Dévora, Jorge I.; Shi, Zhi-dong; Xu, Tao

2012-01-01

Over the last few decades, high-throughput (HT) bioscreening, a technique that allows rapid screening of biochemical compound libraries against biological targets, has been widely used in drug discovery, stem cell research, development of new biomaterials, and genomics research. To achieve these ambitions, scaffold-free (or direct) assembly of biological entities of interest has become critical. Appropriate assembling methodologies are required to build an efficient HT bioscreening platform. The development of contact and non-contact assembling systems as a practical solution has been driven by a variety of essential attributes of the bioscreening system, such as miniaturization, high throughput, and high precision. The present article reviews recent progress on these assembling technologies utilized for the construction of HT bioscreening platforms. PMID:22021162

The Paris-Sud yeast structural genomics pilot-project: from structure to function.

PubMed

Quevillon-Cheruel, Sophie; Liger, Dominique; Leulliot, Nicolas; Graille, Marc; Poupon, Anne; Li de La Sierra-Gallay, Inès; Zhou, Cong-Zhao; Collinet, Bruno; Janin, Joël; Van Tilbeurgh, Herman

2004-01-01

We present here the outlines and results from our yeast structural genomics (YSG) pilot-project. A lab-scale platform for the systematic production and structure determination is presented. In order to validate this approach, 250 non-membrane proteins of unknown structure were targeted. Strategies and final statistics are evaluated. We finally discuss the opportunity of structural genomics programs to contribute to functional biochemical annotation.

Integration of biochemical sensors into wearable biomaterial platforms

NASA Astrophysics Data System (ADS)

Jandhyala, Sidhartha; Walper, Scott A.; Cargill, Allison A.; Ozual, Abigail; Daniele, Michael A.

2016-05-01

With rapidly inflating healthcare costs, a limited supply of physicians and an alarming surge in lifestyle diseases, radical changes must be made to improve preventative medicine and ensure a sustainable healthcare system. A compelling solution is to equip the population with wearable health monitors to continuously record representative and actionable physiological data. Herein, we present a preliminary design and evaluation of a biochemical sensor node enabled by a substrate comprised of a nanocellulose thin-film that conforms to the skin and carries a printed sensor element. The nanocellulose layer ensures conformal and biocompatible contact with the skin, while a printed layer provides a high surface-area electrode. While the recognition/transduction element can be exchanged for many different sensing motifs, we utilize the general structure of an electrochemical glucose sensor.

Modeling Molecular and Cellular Aspects of Human Disease using the Nematode Caenorhabditis elegans

PubMed Central

Silverman, Gary A.; Luke, Cliff J.; Bhatia, Sangeeta R.; Long, Olivia S.; Vetica, Anne C.; Perlmutter, David H.; Pak, Stephen C.

2009-01-01

As an experimental system, Caenorhabditis elegans, offers a unique opportunity to interrogate in vivo the genetic and molecular functions of human disease-related genes. For example, C. elegans has provided crucial insights into fundamental biological processes such as cell death and cell fate determinations, as well as pathological processes such as neurodegeneration and microbial susceptibility. The C. elegans model has several distinct advantages including a completely sequenced genome that shares extensive homology with that of mammals, ease of cultivation and storage, a relatively short lifespan and techniques for generating null and transgenic animals. However, the ability to conduct unbiased forward and reverse genetic screens in C. elegans remains one of the most powerful experimental paradigms for discovering the biochemical pathways underlying human disease phenotypes. The identification of these pathways leads to a better understanding of the molecular interactions that perturb cellular physiology, and forms the foundation for designing mechanism-based therapies. To this end, the ability to process large numbers of isogenic animals through automated work stations suggests that C. elegans, manifesting different aspects of human disease phenotypes, will become the platform of choice for in vivo drug discovery and target validation using high-throughput/content screening technologies. PMID:18852689

Current and Developing Technologies for Monitoring Agents of Bioterrorism and Biowarfare

PubMed Central

Lim, Daniel V.; Simpson, Joyce M.; Kearns, Elizabeth A.; Kramer, Marianne F.

2005-01-01

Recent events have made public health officials acutely aware of the importance of rapidly and accurately detecting acts of bioterrorism. Because bioterrorism is difficult to predict or prevent, reliable platforms to rapidly detect and identify biothreat agents are important to minimize the spread of these agents and to protect the public health. These platforms must not only be sensitive and specific, but must also be able to accurately detect a variety of pathogens, including modified or previously uncharacterized agents, directly from complex sample matrices. Various commercial tests utilizing biochemical, immunological, nucleic acid, and bioluminescence procedures are currently available to identify biological threat agents. Newer tests have also been developed to identify such agents using aptamers, biochips, evanescent wave biosensors, cantilevers, living cells, and other innovative technologies. This review describes these current and developing technologies and considers challenges to rapid, accurate detection of biothreat agents. Although there is no ideal platform, many of these technologies have proved invaluable for the detection and identification of biothreat agents. PMID:16223949

Label-Free Discovery Array Platform for the Characterization of Glycan Binding Proteins and Glycoproteins.

PubMed

Gray, Christopher J; Sánchez-Ruíz, Antonio; Šardzíková, Ivana; Ahmed, Yassir A; Miller, Rebecca L; Reyes Martinez, Juana E; Pallister, Edward; Huang, Kun; Both, Peter; Hartmann, Mirja; Roberts, Hannah N; Šardzík, Robert; Mandal, Santanu; Turnbull, Jerry E; Eyers, Claire E; Flitsch, Sabine L

2017-04-18

The identification of carbohydrate-protein interactions is central to our understanding of the roles of cell-surface carbohydrates (the glycocalyx), fundamental for cell-recognition events. Therefore, there is a need for fast high-throughput biochemical tools to capture the complexity of these biological interactions. Here, we describe a rapid method for qualitative label-free detection of carbohydrate-protein interactions on arrays of simple synthetic glycans, more complex natural glycosaminoglycans (GAG), and lectins/carbohydrate binding proteins using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The platform can unequivocally identify proteins that are captured from either purified or complex sample mixtures, including biofluids. Identification of proteins bound to the functionalized array is achieved by analyzing either the intact protein mass or, after on-chip proteolytic digestion, the peptide mass fingerprint and/or tandem mass spectrometry of selected peptides, which can yield highly diagnostic sequence information. The platform described here should be a valuable addition to the limited analytical toolbox that is currently available for glycomics.

On-Site Production of Cellulolytic Enzymes by the Sequential Cultivation Method.

PubMed

Farinas, Cristiane S; Florencio, Camila; Badino, Alberto C

2018-01-01

The conversion of renewable lignocellulosic biomass into fuels, chemicals, and high-value materials using the biochemical platform has been considered the most sustainable alternative for the implementation of future biorefineries. However, the high cost of the cellulolytic enzymatic cocktails used in the saccharification step significantly affects the economics of industrial large-scale conversion processes. The on-site production of enzymes, integrated to the biorefinery plant, is being considered as a potential strategy that could be used to reduce costs. In such approach, the microbial production of enzymes can be carried out using the same lignocellulosic biomass as feedstock for fungal development and biofuels production. Most of the microbial cultivation processes for the production of industrial enzymes have been developed using the conventional submerged fermentation. Recently, a sequential solid-state followed by submerged fermentation has been described as a potential alternative cultivation method for cellulolytic enzymes production. This chapter presents the detailed procedure of the sequential cultivation method, which could be employed for the on-site production of the cellulolytic enzymes required to convert lignocellulosic biomass into simple sugars.

Creating knowledge structures in the pharmaceutical industry: the increasing significance of virtual organisation.

PubMed

Salazar, A; Howells, J

2000-01-01

This paper explores the specific trend and challenges facing the pharmaceutical industry regarding the exploitation of Internet e-commerce technology and virtual organisation to develop and maintain competitive advantage. There are two important facets of the current trend. One is the rapid development of a complex network of alliances between the established pharmaceutical companies and the specialised biotechnology company start-ups. The other is the rapid growth of internet e-commerce companies dedicated to developing specialised technological platforms for acquiring and selling genetic and biochemical knowledge. The underlying challenge is how big pharmaceutical companies can emulate some of the innovation processes of smaller biotechnology company start-ups, and how they can appropriate and applied new technological knowledge on the development of new drugs. Pharmaceutical companies in order to retain competitive advantage need to continuously monitor all aspects of knowledge management with regard to the R&D and manufacturing process (as well as customer management and marketing). Technological change and organisational restructuring should be aimed at boosting the capacity of large firms to innovate rapidly.

Structure of the dimerization domain of DiGeorge Critical Region 8

PubMed Central

Senturia, Rachel; Faller, Michael; Yin, Sheng; Loo, Joseph A; Cascio, Duilio; Sawaya, Michael R; Hwang, Daniel; Clubb, Robert T; Guo, Feng

2010-01-01

Maturation of microRNAs (miRNAs, ∼22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298–352) at 1.7 Å resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis. PMID:20506313

Point-of-Care Quantitative Measure of Glucose-6-Phosphate Dehydrogenase Enzyme Deficiency.

PubMed

Bhutani, Vinod K; Kaplan, Michael; Glader, Bertil; Cotten, Michael; Kleinert, Jairus; Pamula, Vamsee

2015-11-01

Widespread newborn screening on a point-of-care basis could prevent bilirubin neurotoxicity in newborns with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We evaluated a quantitative G6PD assay on a digital microfluidic platform by comparing its performance with standard clinical methods. G6PD activity was measured quantitatively by using digital microfluidic fluorescence and the gold standard fluorescence biochemical test on a convenience sample of 98 discarded blood samples. Twenty-four samples were designated as G6PD deficient. Mean ± SD G6PD activity for normal samples using the digital microfluidic method and the standard method, respectively, was 9.7 ± 2.8 and 11.1 ± 3.0 U/g hemoglobin (Hb), respectively; for G6PD-deficient samples, it was 0.8 ± 0.7 and 1.4 ± 0.9 U/g Hb. Bland-Altman analysis determined a mean difference of -0.96 ± 1.8 U/g Hb between the digital microfluidic fluorescence results and the standard biochemical test results. The lower and upper limits for the digital microfluidic platform were 4.5 to 19.5 U/g Hb for normal samples and 0.2 to 3.7 U/g Hb for G6PD-deficient samples. The lower and upper limits for the Stanford method were 5.5 to 20.7 U/g Hb for normal samples and 0.1 to 2.8 U/g Hb for G6PD-deficient samples. The measured activity discriminated between G6PD-deficient samples and normal samples with no overlap. Pending further validation, a digital microfluidics platform could be an accurate point-of-care screening tool for rapid newborn G6PD screening. Copyright © 2015 by the American Academy of Pediatrics.

3D extracellular matrix interactions modulate tumour cell growth, invasion and angiogenesis in engineered tumour microenvironments.

PubMed

Taubenberger, Anna V; Bray, Laura J; Haller, Barbara; Shaposhnykov, Artem; Binner, Marcus; Freudenberg, Uwe; Guck, Jochen; Werner, Carsten

2016-05-01

Interactions between tumour cells and extracellular matrix proteins of the tumour microenvironment play crucial roles in cancer progression. So far, however, there are only a few experimental platforms available that allow us to study these interactions systematically in a mechanically defined three-dimensional (3D) context. Here, we have studied the effect of integrin binding motifs found within common extracellular matrix (ECM) proteins on 3D breast (MCF-7) and prostate (PC-3, LNCaP) cancer cell cultures, and co-cultures with endothelial and mesenchymal stromal cells. For this purpose, matrix metalloproteinase-degradable biohybrid poly(ethylene) glycol-heparin hydrogels were decorated with the peptide motifs RGD, GFOGER (collagen I), or IKVAV (laminin-111). Over 14days, cancer spheroids of 100-200μm formed. While the morphology of poorly invasive MCF-7 and LNCaP cells was not modulated by any of the peptide motifs, the aggressive PC-3 cells exhibited an invasive morphology when cultured in hydrogels comprising IKVAV and GFOGER motifs compared to RGD motifs or nonfunctionalised controls. PC-3 (but not MCF-7 and LNCaP) cell growth and endothelial cell infiltration were also significantly enhanced in IKVAV and GFOGER presenting gels. Taken together, we have established a 3D culture model that allows for dissecting the effect of biochemical cues on processes relevant to early cancer progression. These findings provide a basis for more mechanistic studies that may further advance our understanding of how ECM modulates cancer cell invasion and how to ultimately interfere with this process. Threedimensional in vitro cancer models have generated great interest over the past decade. However, most models are not suitable to systematically study the effects of environmental cues on cancer development and progression. To overcome this limitation, we have developed an innovative hydrogel platform to study the interactions between breast and prostate cancer cells and extracellular matrix ligands relevant to the tumour microenvironment. Our results show that hydrogels with laminin- and collagen-derived adhesive peptides induce a malignant phenotype in a cell-line specific manner. Thus, we have identified a method to control the incorporation of biochemical cues within a three dimensional culture model and anticipate that it will help us in better understanding the effects of the tumour microenvironment on cancer progression. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated saccharification assay for determination of digestibility in plant materials.

PubMed

Gomez, Leonardo D; Whitehead, Caragh; Barakate, Abdellah; Halpin, Claire; McQueen-Mason, Simon J

2010-10-27

Cell wall resistance represents the main barrier for the production of second generation biofuels. The deconstruction of lignocellulose can provide sugars for the production of fuels or other industrial products through fermentation. Understanding the biochemical basis of the recalcitrance of cell walls to digestion will allow development of more effective and cost efficient ways to produce sugars from biomass. One approach is to identify plant genes that play a role in biomass recalcitrance, using association genetics. Such an approach requires a robust and reliable high throughput (HT) assay for biomass digestibility, which can be used to screen the large numbers of samples involved in such studies. We developed a HT saccharification assay based on a robotic platform that can carry out in a 96-well plate format the enzymatic digestion and quantification of the released sugars. The handling of the biomass powder for weighing and formatting into 96 wells is performed by a robotic station, where the plant material is ground, delivered to the desired well in the plates and weighed with a precision of 0.1 mg. Once the plates are loaded, an automated liquid handling platform delivers an optional mild pretreatment (< 100°C) followed by enzymatic hydrolysis of the biomass. Aliquots from the hydrolysis are then analyzed for the release of reducing sugar equivalents. The same platform can be used for the comparative evaluation of different enzymes and enzyme cocktails. The sensitivity and reliability of the platform was evaluated by measuring the saccharification of stems from lignin modified tobacco plants, and the results of automated and manual analyses compared. The automated assay systems are sensitive, robust and reliable. The system can reliably detect differences in the saccharification of plant tissues, and is able to process large number of samples with a minimum amount of human intervention. The automated system uncovered significant increases in the digestibility of certain lignin modified lines in a manner compatible with known effects of lignin modification on cell wall properties. We conclude that this automated assay platform is of sufficient sensitivity and reliability to undertake the screening of the large populations of plants necessary for mutant identification and genetic association studies.

Ryan Davis | NREL

Science.gov Websites

design TEA LCA Biochemical conversion process pathways Algal biomass production and conversion pathways Production," Green Chemistry (2015) Process Design and Economics for the Conversion of Lignocellulosic Production," Applied Energy (2011) Process Design and Economics for Biochemical Conversion of

Precursor uptake assays and metabolic analyses in isolated tomato fruit chromoplasts

PubMed Central

2012-01-01

Background Carotenoids are the most widespread group of pigments found in nature. In addition to their role in the physiology of the plant, carotenoids also have nutritional relevance as their incorporation in the human diet provides health benefits. In non-photosynthetic tissues, carotenoids are synthesized and stored in specialized plastids called chromoplasts. At present very little is known about the origin of the metabolic precursors and cofactors required to sustain the high rate of carotenoid biosynthesis in these plastids. Recent proteomic data have revealed a number of biochemical and metabolic processes potentially operating in fruit chromoplasts. However, considering that chloroplast to chromoplast differentiation is a very rapid process during fruit ripening, there is the possibility that some of the proteins identified in the proteomic analysis could represent remnants no longer having a functional role in chromoplasts. Therefore, experimental validation is necessary to prove whether these predicted processes are actually operative in chromoplasts. Results A method has been established for high-yield purification of tomato fruit chromoplasts suitable for metabolic studies. Radiolabeled precursors were efficiently incorporated and further metabolized in isolated chromoplast. Analysis of labeled lipophilic compounds has revealed that lipid biosynthesis is a very efficient process in chromoplasts, while the relatively low incorporation levels found in carotenoids suggest that lipid production may represent a competing pathway for carotenoid biosynthesis. Malate and pyruvate are efficiently converted into acetyl-CoA, in agreement with the active operation of the malic enzyme and the pyruvate dehydrogenase complex in the chromoplast. Our results have also shown that isolated chromoplasts can actively sustain anabolic processes without the exogenous supply of ATP, thus suggesting that these organelles may generate this energetic cofactor in an autonomous way. Conclusions We have set up a method for high yield purification of intact tomato fruit chromoplasts suitable for precursor uptake assays and metabolic analyses. Using targeted radiolabeled precursors we have been able to unravel novel biochemical and metabolic aspects related with carotenoid and lipid biosynthesis in tomato fruit chromoplasts. The reported chromoplast system could represent a valuable platform to address the validation and characterization of functional processes predicted from recent transcriptomic and proteomic data. PMID:22243738

Precursor uptake assays and metabolic analyses in isolated tomato fruit chromoplasts.

PubMed

Angaman, Djédoux Maxime; Petrizzo, Rocco; Hernández-Gras, Francesc; Romero-Segura, Carmen; Pateraki, Irene; Busquets, Montserrat; Boronat, Albert

2012-01-13

Carotenoids are the most widespread group of pigments found in nature. In addition to their role in the physiology of the plant, carotenoids also have nutritional relevance as their incorporation in the human diet provides health benefits. In non-photosynthetic tissues, carotenoids are synthesized and stored in specialized plastids called chromoplasts. At present very little is known about the origin of the metabolic precursors and cofactors required to sustain the high rate of carotenoid biosynthesis in these plastids. Recent proteomic data have revealed a number of biochemical and metabolic processes potentially operating in fruit chromoplasts. However, considering that chloroplast to chromoplast differentiation is a very rapid process during fruit ripening, there is the possibility that some of the proteins identified in the proteomic analysis could represent remnants no longer having a functional role in chromoplasts. Therefore, experimental validation is necessary to prove whether these predicted processes are actually operative in chromoplasts. A method has been established for high-yield purification of tomato fruit chromoplasts suitable for metabolic studies. Radiolabeled precursors were efficiently incorporated and further metabolized in isolated chromoplast. Analysis of labeled lipophilic compounds has revealed that lipid biosynthesis is a very efficient process in chromoplasts, while the relatively low incorporation levels found in carotenoids suggest that lipid production may represent a competing pathway for carotenoid biosynthesis. Malate and pyruvate are efficiently converted into acetyl-CoA, in agreement with the active operation of the malic enzyme and the pyruvate dehydrogenase complex in the chromoplast. Our results have also shown that isolated chromoplasts can actively sustain anabolic processes without the exogenous supply of ATP, thus suggesting that these organelles may generate this energetic cofactor in an autonomous way. We have set up a method for high yield purification of intact tomato fruit chromoplasts suitable for precursor uptake assays and metabolic analyses. Using targeted radiolabeled precursors we have been able to unravel novel biochemical and metabolic aspects related with carotenoid and lipid biosynthesis in tomato fruit chromoplasts. The reported chromoplast system could represent a valuable platform to address the validation and characterization of functional processes predicted from recent transcriptomic and proteomic data.

A Multicenter Study To Evaluate the Performance of High-Throughput Sequencing for Virus Detection

PubMed Central

Ng, Siemon H. S.; Vandeputte, Olivier; Aljanahi, Aisha; Deyati, Avisek; Cassart, Jean-Pol; Charlebois, Robert L.; Taliaferro, Lanyn P.

2017-01-01

ABSTRACT The capability of high-throughput sequencing (HTS) for detection of known and unknown viruses makes it a powerful tool for broad microbial investigations, such as evaluation of novel cell substrates that may be used for the development of new biological products. However, like any new assay, regulatory applications of HTS need method standardization. Therefore, our three laboratories initiated a study to evaluate performance of HTS for potential detection of viral adventitious agents by spiking model viruses in different cellular matrices to mimic putative materials for manufacturing of biologics. Four model viruses were selected based upon different physical and biochemical properties and commercial availability: human respiratory syncytial virus (RSV), Epstein-Barr virus (EBV), feline leukemia virus (FeLV), and human reovirus (REO). Additionally, porcine circovirus (PCV) was tested by one laboratory. Independent samples were prepared for HTS by spiking intact viruses or extracted viral nucleic acids, singly or mixed, into different HeLa cell matrices (resuspended whole cells, cell lysate, or total cellular RNA). Data were obtained using different sequencing platforms (Roche 454, Illumina HiSeq1500 or HiSeq2500). Bioinformatic analyses were performed independently by each laboratory using available tools, pipelines, and databases. The results showed that comparable virus detection was obtained in the three laboratories regardless of sample processing, library preparation, sequencing platform, and bioinformatic analysis: between 0.1 and 3 viral genome copies per cell were detected for all of the model viruses used. This study highlights the potential for using HTS for sensitive detection of adventitious viruses in complex biological samples containing cellular background. IMPORTANCE Recent high-throughput sequencing (HTS) investigations have resulted in unexpected discoveries of known and novel viruses in a variety of sample types, including research materials, clinical materials, and biological products. Therefore, HTS can be a powerful tool for supplementing current methods for demonstrating the absence of adventitious or unwanted viruses in biological products, particularly when using a new cell line. However, HTS is a complex technology with different platforms, which needs standardization for evaluation of biologics. This collaborative study was undertaken to investigate detection of different virus types using two different HTS platforms. The results of the independently performed studies demonstrated a similar sensitivity of virus detection, regardless of the different sample preparation and processing procedures and bioinformatic analyses done in the three laboratories. Comparable HTS detection of different virus types supports future development of reference virus materials for standardization and validation of different HTS platforms. PMID:28932815

Flexible Sensory Platform Based on Oxide-based Neuromorphic Transistors

NASA Astrophysics Data System (ADS)

Liu, Ning; Zhu, Li Qiang; Feng, Ping; Wan, Chang Jin; Liu, Yang Hui; Shi, Yi; Wan, Qing

2015-12-01

Inspired by the dendritic integration and spiking operation of a biological neuron, flexible oxide-based neuromorphic transistors with multiple input gates are fabricated on flexible plastic substrates for pH sensor applications. When such device is operated in a quasi-static dual-gate synergic sensing mode, it shows a high pH sensitivity of ~105 mV/pH. Our results also demonstrate that single-spike dynamic mode can remarkably improve pH sensitivity and reduce response/recover time and power consumption. Moreover, we find that an appropriate negative bias applied on the sensing gate electrode can further enhance the pH sensitivity and reduce the power consumption. Our flexible neuromorphic transistors provide a new-concept sensory platform for biochemical detection with high sensitivity, rapid response and ultralow power consumption.

Microfluidic in-channel multi-electrode platform for neurotransmitter sensing

NASA Astrophysics Data System (ADS)

Kara, A.; Mathault, J.; Reitz, A.; Boisvert, M.; Tessier, F.; Greener, J.; Miled, A.

2016-03-01

In this project we present a microfluidic platform with in-channel micro-electrodes for in situ screening of bio/chemical samples through a lab-on-chip system. We used a novel method to incorporate electrochemical sensors array (16x20) connected to a PCB, which opens the way for imaging applications. A 200 μm height microfluidic channel was bonded to electrochemical sensors. The micro-channel contains 3 inlets used to introduce phosphate buffer saline (PBS), ferrocynide and neurotransmitters. The flow rate was controlled through automated micro-pumps. A multiplexer was used to scan electrodes and perform individual cyclic voltammograms by a custom potentiostat. The behavior of the system was linear in terms of variation of current versus concentration. It was used to detect the neurotransmitters serotonin, dopamine and glutamate.

Flexible Sensory Platform Based on Oxide-based Neuromorphic Transistors

PubMed Central

Liu, Ning; Zhu, Li Qiang; Feng, Ping; Wan, Chang Jin; Liu, Yang Hui; Shi, Yi; Wan, Qing

2015-01-01

Inspired by the dendritic integration and spiking operation of a biological neuron, flexible oxide-based neuromorphic transistors with multiple input gates are fabricated on flexible plastic substrates for pH sensor applications. When such device is operated in a quasi-static dual-gate synergic sensing mode, it shows a high pH sensitivity of ~105 mV/pH. Our results also demonstrate that single-spike dynamic mode can remarkably improve pH sensitivity and reduce response/recover time and power consumption. Moreover, we find that an appropriate negative bias applied on the sensing gate electrode can further enhance the pH sensitivity and reduce the power consumption. Our flexible neuromorphic transistors provide a new-concept sensory platform for biochemical detection with high sensitivity, rapid response and ultralow power consumption. PMID:26656113

Biotechnologies as a Context for Enhancing Junior High-School Students' Ability to Ask Meaningful Questions about Abstract Biological Processes.

ERIC Educational Resources Information Center

Olsher, G.; Dreyfus, A.

1999-01-01

Suggests a new approach to teaching about biochemical cellular processes by stimulating student interest in those biochemical processes that allowed for the outcomes of modern biotechnologies. Discusses the development of students' ability to ask meaningful questions about intra-cellular processes, and the resulting meaningful learning of relevant…

Electrical conditioning of adipose-derived stem cells in a multi-chamber culture platform.

PubMed

Pavesi, A; Soncini, M; Zamperone, A; Pietronave, S; Medico, E; Redaelli, A; Prat, M; Fiore, G B

2014-07-01

In tissue engineering, several factors play key roles in providing adequate stimuli for cells differentiation, in particular biochemical and physical stimuli, which try to mimic the physiological microenvironments. Since electrical stimuli are important in the developing heart, we have developed an easy-to-use, cost-effective cell culture platform, able to provide controlled electrical stimulation aimed at investigating the influence of the electric field in the stem cell differentiation process. This bioreactor consists of an electrical stimulator and 12 independent, petri-like culture chambers and a 3-D computational model was used to characterize the distribution and the intensity of the electric field generated in the cell culture volume. We explored the effects of monophasic and biphasic square wave pulse stimulation on a mouse adipose-derived stem cell line (m17.ASC) comparing cell viability, proliferation, protein, and gene expression. Both monophasic (8 V, 2 ms, 1 Hz) and biphasic (+4 V, 1 ms and -4 V, 1 ms; 1 Hz) stimulation were compatible with cell survival and proliferation. Biphasic stimulation induced the expression of Connexin 43, which was found to localize also at the cell membrane, which is its recognized functional mediating intercellular electrical coupling. Electrically stimulated cells showed an induced transcriptional profile more closely related to that of neonatal cadiomyocytes, particularly for biphasic stimulation. The developed platform thus allowed to set-up precise conditions to drive adult stem cells toward a myocardial phenotype solely by physical stimuli, in the absence of exogenously added expensive bioactive molecules, and can thus represent a valuable tool for translational applications for heart tissue engineering and regeneration. © 2014 Wiley Periodicals, Inc.

Dramatic nano-fluidic properties of carbon nanotube membranes as a platform for protein channel mimetics

NASA Astrophysics Data System (ADS)

Hinds, Bruce

2013-03-01

Carbon nanotubes have three key attributes that make them of great interest for novel membrane applications: 1) atomically flat graphite surface allows for ideal fluid slip boundary conditions and extremely fast flow rates 2) the cutting process to open CNTs inherently places functional chemistry at CNT core entrance for chemical selectivity and 3) CNT are electrically conductive allowing for electrochemical reactions and application of electric fields gradients at CNT tips. Pressure driven flux of a variety of solvents (H2O, hexane, decane ethanol, methanol) are 4-5 orders of magnitude higher than conventional Newtonian flow [Nature 2005, 438, 44] due to atomically flat graphite planes inducing nearly ideal slip conditions. However this is eliminated with selective chemical functionalization [ACS Nano 2011 5(5) 3867-3877] needed to give chemical selectivity. These unique properties allow us to explore the hypothesis of producing ``Gatekeeper'' membranes that mimic natural protein channels to actively pump through rapid nm-scale channels. With anionic tip functionality strong electroosmotic flow is induced by unimpeded cation flow with similar 10,000 fold enhancements [Nature Nano 2012 7(2) 133-39]. With enhanced power efficiency, carbon nanotube membranes were employed as the active element of a switchable transdermal drug delivery device that can facilitate more effective treatments of drug abuse and addiction. Recently methods to deposit Pt monolayers on CNT surface have been developed making for highly efficient catalytic platforms. Discussed are other applications of CNT protein channel mimetics, for large area robust engineering platforms, including water purification, flow battery energy storage, and biochemical/biomass separations. DOE EPSCoR (DE-FG02-07ER46375) and DARPA, W911NF-09-1-0267

Biochemical Conversion: Using Enzymes, Microbes, and Catalysis to Make Fuels and Chemicals

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2013-07-26

This fact sheet describes the Bioenergy Technologies Office's biochemical conversion work and processes. BETO conducts collaborative research, development, and demonstration projects to improve several processing routes for the conversion of cellulosic biomass.

Risk-based process safety assessment and control measures design for offshore process facilities.

PubMed

Khan, Faisal I; Sadiq, Rehan; Husain, Tahir

2002-09-02

Process operation is the most hazardous activity next to the transportation and drilling operation on an offshore oil and gas (OOG) platform. Past experiences of onshore and offshore oil and gas activities have revealed that a small mis-happening in the process operation might escalate to a catastrophe. This is of especial concern in the OOG platform due to the limited space and compact geometry of the process area, less ventilation, and difficult escape routes. On an OOG platform, each extra control measure, which is implemented, not only occupies space on the platform and increases congestion but also adds extra load to the platform. Eventualities in the OOG platform process operation can be avoided through incorporating the appropriate control measures at the early design stage. In this paper, the authors describe a methodology for risk-based process safety decision making for OOG activities. The methodology is applied to various offshore process units, that is, the compressor, separators, flash drum and driers of an OOG platform. Based on the risk potential, appropriate safety measures are designed for each unit. This paper also illustrates that implementation of the designed safety measures reduces the high Fatal accident rate (FAR) values to an acceptable level.

A novel rotating experimental platform in a superconducting magnet.

PubMed

Chen, Da; Cao, Hui-Ling; Ye, Ya-Jing; Dong, Chen; Liu, Yong-Ming; Shang, Peng; Yin, Da-Chuan

2016-08-01

This paper introduces a novel platform designed to be used in a strong static magnetic field (in a superconducting magnet). The platform is a sample holder that rotates in the strong magnetic field. Any samples placed in the platform will rotate due to the rotation of the sample holder. With this platform, a number of experiments such as material processing, culture of biological systems, chemical reactions, or other processes can be carried out. In this report, we present some preliminary experiments (protein crystallization, cell culture, and seed germination) conducted using this platform. The experimental results showed that the platform can affect the processes, indicating that it provides a novel environment that has not been investigated before and that the effects of such an environment on many different physical, chemical, or biological processes can be potentially useful for applications in many fields.

Surface-Enhanced Raman Spectroscopy for Staphylococcus aureus DNA Detection by Using Surface-Enhanced Raman Scattering Tag on Au Film Over Nanosphere Substrate.

PubMed

Chen, Jian; Wang, Jun-Feng; Wu, Xue-Zhong; Rong, Zhen; Dong, Pei-Tao; Xiao, Rui

2018-06-01

We developed a high-performance surface-enhanced Raman scattering (SERS) sensing platform that can be used for specific and sensitive DNA detection. The SERS platform combines the advantages of Au film over nanosphere (AuFON) substrate and Ag@PATP@SiO2 SERS tag. SERS tag-on-AuFON is a sensing system that operates by the self-assembly of SERS tag onto an AuFON substrate in the presence of target DNAs. The SERS signals can be dramatically enhanced by the formation of "hot spots" in the interstices between the assembled nanostructures, as confirmed by finite-difference time-domain (FDTD) simulation. As a new sensing platform, SERS tag-on-AuFON was utilized to detect Staphylococcus aureus (S. aureus) DNA with a limit of detection at 1 nM. A linear relationship was also observed between the SERS intensity at Raman peak 1439 cm-1 and the logarithm of target DNA concentrations ranging from 1 μM to 1 nM. Besides, the sensing platform showed good homogeneity, with a relative standard deviation of about 1%. The sensitive SERS platform created in this study is a promising tool for detecting trace biochemical molecules because of its relatively simple and effective fabrication procedure, high sensitivity, and high reproducibility of the SERS effect.

Nanostructured optical fibre arrays for high-density biochemical sensing and remote imaging.

PubMed

Deiss, F; Sojic, N; White, D J; Stoddart, P R

2010-01-01

Optical fibre bundles usually comprise a few thousand to tens of thousands of individually clad glass optical fibres. The ordered arrangement of the fibres enables coherent transmission of an image through the bundle and therefore enables analysis and viewing in remote locations. In fused bundles, this architecture has also been used to fabricate arrays of various micro to nano-scale surface structures (micro/nanowells, nanotips, triangles, etc.) over relatively large areas. These surface structures have been used to obtain new optical and analytical capabilities. Indeed, the imaging bundle can be thought of as a "starting material" that can be sculpted by a combination of fibre drawing and selective wet-chemical etching processes. A large variety of bioanalytical applications have thus been developed, ranging from nano-optics to DNA nanoarrays. For instance, nanostructured optical surfaces with intrinsic light-guiding properties have been exploited as surface-enhanced Raman scattering (SERS) platforms and as near-field probe arrays. They have also been productively associated with electrochemistry to fabricate arrays of transparent nanoelectrodes with electrochemiluminescent imaging properties. The confined geometry of the wells has been loaded with biosensing materials and used as femtolitre-sized vessels to detect single molecules. This review describes the fabrication of high-density nanostructured optical fibre arrays and summarizes the large range of optical and bioanalytical applications that have been developed, reflecting the versatility of this ordered light-guiding platform.

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

PubMed

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.

An in vitro synthetic biology platform for the industrial biomanufacturing of myo-inositol from starch.

PubMed

You, Chun; Shi, Ting; Li, Yunjie; Han, Pingping; Zhou, Xigui; Zhang, Yi-Heng Percival

2017-08-01

Myo-Inositol (vitamin B8) is widely used in the drug, cosmetic, and food & feed industries. Here, we present an in vitro non-fermentative enzymatic pathway that converts starch to inositol in one vessel. This in vitro pathway is comprised of four enzymes that operate without ATP or NAD + supplementation. All enzyme BioBricks are carefully selected from hyperthermophilic microorganisms, that is, alpha-glucan phosphorylase from Thermotoga maritima, phosphoglucomutase from Thermococcus kodakarensis, inositol 1-phosphate synthase from Archaeoglobus fulgidus, and inositol monophosphatase from T. maritima. They were expressed efficiently in high-density fermentation of Escherichia coli BL21(DE3) and easily purified by heat treatment. The four-enzyme pathway supplemented with two other hyperthermophilic enzymes (i.e., 4-α-glucanotransferase from Thermococcus litoralis and isoamylase from Sulfolobus tokodaii) converts branched or linear starch to inositol, accomplishing a very high product yield of 98.9 ± 1.8% wt./wt. This in vitro (aeration-free) biomanufacturing has been successfully operated on 20,000-L reactors. Less costly inositol would be widely added in heath food, low-end soft drink, and animal feed, and may be converted to other value-added biochemicals (e.g., glucarate). This biochemical is the first product manufactured by the in vitro synthetic biology platform on an industrial scale. Biotechnol. Bioeng. 2017;114: 1855-1864. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Infrared Microspectroscopy: A Multiple-Screening Platform for Investigating Single-Cell Biochemical Perturbations upon Prion Infection

PubMed Central

2011-01-01

Prion diseases are a group of fatal neurodegenerative disorders characterized by the accumulation of prions in the central nervous system. The pathogenic prion (PrPSc) possesses the capability to convert the host-encoded cellular isoform of the prion protein, PrPC, into nascent PrPSc. The present work aims at providing novel insight into cellular response upon prion infection evidenced by synchrotron radiation infrared microspectroscopy (SR-IRMS). This non-invasive, label-free analytical technique was employed to investigate the biochemical perturbations undergone by prion infected mouse hypothalamic GT1-1 cells at the cellular and subcellular level. A decrement in total cellular protein content upon prion infection was identified by infrared (IR) whole-cell spectra and validated by bicinchoninic acid assay and single-cell volume analysis by atomic force microscopy (AFM). Hierarchical cluster analysis (HCA) of IR data discriminated between infected and uninfected cells and allowed to deduce an increment of lysosomal bodies within the cytoplasm of infected GT1-1 cells, a hypothesis further confirmed by SR-IRMS at subcellular spatial resolution and fluorescent microscopy. The purpose of this work, therefore, consists of proposing IRMS as a powerful multiscreening platform, drawing on the synergy with conventional biological assays and microscopy techniques in order to increase the accuracy of investigations performed at the single-cell level. PMID:22778865

Infrared microspectroscopy: a multiple-screening platform for investigating single-cell biochemical perturbations upon prion infection.

PubMed

Didonna, Alessandro; Vaccari, Lisa; Bek, Alpan; Legname, Giuseppe

2011-03-16

Prion diseases are a group of fatal neurodegenerative disorders characterized by the accumulation of prions in the central nervous system. The pathogenic prion (PrP(Sc)) possesses the capability to convert the host-encoded cellular isoform of the prion protein, PrP(C), into nascent PrP(Sc). The present work aims at providing novel insight into cellular response upon prion infection evidenced by synchrotron radiation infrared microspectroscopy (SR-IRMS). This non-invasive, label-free analytical technique was employed to investigate the biochemical perturbations undergone by prion infected mouse hypothalamic GT1-1 cells at the cellular and subcellular level. A decrement in total cellular protein content upon prion infection was identified by infrared (IR) whole-cell spectra and validated by bicinchoninic acid assay and single-cell volume analysis by atomic force microscopy (AFM). Hierarchical cluster analysis (HCA) of IR data discriminated between infected and uninfected cells and allowed to deduce an increment of lysosomal bodies within the cytoplasm of infected GT1-1 cells, a hypothesis further confirmed by SR-IRMS at subcellular spatial resolution and fluorescent microscopy. The purpose of this work, therefore, consists of proposing IRMS as a powerful multiscreening platform, drawing on the synergy with conventional biological assays and microscopy techniques in order to increase the accuracy of investigations performed at the single-cell level.

Remote sensing of key grassland nutrients using hyperspectral techniques in KwaZulu-Natal, South Africa

NASA Astrophysics Data System (ADS)

Singh, Leeth; Mutanga, Onisimo; Mafongoya, Paramu; Peerbhay, Kabir

2017-07-01

The concentration of forage fiber content is critical in explaining the palatability of forage quality for livestock grazers in tropical grasslands. Traditional methods of determining forage fiber content are usually time consuming, costly, and require specialized laboratory analysis. With the potential of remote sensing technologies, determination of key fiber attributes can be made more accurately. This study aims to determine the effectiveness of known absorption wavelengths for detecting forage fiber biochemicals, neutral detergent fiber, acid detergent fiber, and lignin using hyperspectral data. Hyperspectral reflectance spectral measurements (350 to 2500 nm) of grass were collected and implemented within the random forest (RF) ensemble. Results show successful correlations between the known absorption features and the biochemicals with coefficients of determination (R2) ranging from 0.57 to 0.81 and root mean square errors ranging from 6.97 to 3.03 g/kg. In comparison, using the entire dataset, the study identified additional wavelengths for detecting fiber biochemicals, which contributes to the accurate determination of forage quality in a grassland environment. Overall, the results showed that hyperspectral remote sensing in conjunction with the competent RF ensemble could discriminate each key biochemical evaluated. This study shows the potential to upscale the methodology to a space-borne multispectral platform with similar spectral configurations for an accurate and cost effective mapping analysis of forage quality.

Antioxidant power as biochemical endpoint in bread for screening and early managing quality and toxicant-related safety anomalies in food production.

PubMed

Dragone, Roberto; Ermilov, Laura; Grasso, Gerardo; Maggioni, Silvia; Mantovani, Alberto; Frazzoli, Chiara

2016-08-01

Flaxseeds are both a food ingredient and a natural source of antioxidants (e.g. lignans, PUFAs) and pro-oxidant contaminants (e.g. cadmium): the variable mixture of anti- and pro-oxidant substances may impact on the redox homeostasis of flaxseed-enriched foods. The antioxidant power is studied here as biochemical activity of flaxseeds in white wheat bread and as endpoint for possible screening of anomalous variations of bioactive mixtures (antioxidants vs. prooxidants) in food matrices. A bioprobe assay based on the superoxide dismutase (SOD) enzyme (6 channels of the multiprobe bioelectronic platform BEST) was performed on white wheat bread with and without flaxseeds. Nine BEST channels were simultaneously used for validation and monitoring of measuring conditions (temperature, pH, conductivity). Findings were compared with quantitative analysis of antioxidants and pro-oxidant contaminants. Organic and aqueous extracts of both bread types were examined in parallel. The SOD-probe detected the difference in antioxidant power given by 10% flaxseed, thus supporting the use of antioxidant power detected by bioenzymatic screening as sensitive biochemical endpoint. Mixtures of bioactive molecules in foods generate biochemical activities that can be monitored as time-effective indicators of invariability, which is pivotal in the daily control of anomalies in food production and therefore in the protection of consumers' health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Orbiter processing facility: Access platforms Kennedy Space Center, Florida, from challenge to achievement

NASA Technical Reports Server (NTRS)

Haratunian, M.

1985-01-01

A system of access platforms and equipment within the space shuttle orbiter processing facility at Kennedy Space Center is described. The design challenges of the platforms, including clearance envelopes, load criteria, and movement, are discussed. Various applications of moveable platforms are considered.

"Chemical transformers" from nanoparticle ensembles operated with logic.

PubMed

Motornov, Mikhail; Zhou, Jian; Pita, Marcos; Gopishetty, Venkateshwarlu; Tokarev, Ihor; Katz, Evgeny; Minko, Sergiy

2008-09-01

The pH-responsive nanoparticles were coupled with information-processing enzyme-based systems to yield "smart" signal-responsive hybrid systems with built-in Boolean logic. The enzyme systems performed AND/OR logic operations, transducing biochemical input signals into reversible structural changes (signal-directed self-assembly) of the nanoparticle assemblies, thus resulting in the processing and amplification of the biochemical signals. The hybrid system mimics biological systems in effective processing of complex biochemical information, resulting in reversible changes of the self-assembled structures of the nanoparticles. The bioinspired approach to the nanostructured morphing materials could be used in future self-assembled molecular robotic systems.

Optical tweezers and multiphoton microscopies integrated photonic tool for mechanical and biochemical cell processes studies

NASA Astrophysics Data System (ADS)

de Thomaz, A. A.; Faustino, W. M.; Fontes, A.; Fernandes, H. P.; Barjas-Castro, M. d. L.; Metze, K.; Giorgio, S.; Barbosa, L. C.; Cesar, C. L.

2007-09-01

The research in biomedical photonics is clearly evolving in the direction of the understanding of biological processes at the cell level. The spatial resolution to accomplish this task practically requires photonics tools. However, an integration of different photonic tools and a multimodal and functional approach will be necessary to access the mechanical and biochemical cell processes. This way we can observe mechanicaly triggered biochemical events or biochemicaly triggered mechanical events, or even observe simultaneously mechanical and biochemical events triggered by other means, e.g. electricaly. One great advantage of the photonic tools is its easiness for integration. Therefore, we developed such integrated tool by incorporating single and double Optical Tweezers with Confocal Single and Multiphoton Microscopies. This system can perform 2-photon excited fluorescence and Second Harmonic Generation microscopies together with optical manipulations. It also can acquire Fluorescence and SHG spectra of specific spots. Force, elasticity and viscosity measurements of stretched membranes can be followed by real time confocal microscopies. Also opticaly trapped living protozoas, such as leishmania amazonensis. Integration with CARS microscopy is under way. We will show several examples of the use of such integrated instrument and its potential to observe mechanical and biochemical processes at cell level.

The "Vsoil Platform" : a tool to integrate the various physical, chemical and biological processes contributing to the soil functioning at the local scale.

NASA Astrophysics Data System (ADS)

Lafolie, François; Cousin, Isabelle; Mollier, Alain; Pot, Valérie; Moitrier, Nicolas; Balesdent, Jérome; bruckler, Laurent; Moitrier, Nathalie; Nouguier, Cédric; Richard, Guy

2014-05-01

Models describing the soil functioning are valuable tools for addressing challenging issues related to agricultural production, soil protection or biogeochemical cycles. Coupling models that address different scientific fields is actually required in order to develop numerical tools able to simulate the complex interactions and feed-backs occurring within a soil profile in interaction with climate and human activities. We present here a component-based modelling platform named "VSoil", that aims at designing, developing, implementing and coupling numerical representation of biogeochemical and physical processes in soil, from the aggregate to the profile scales. The platform consists of four softwares, i) Vsoil_Processes dedicated to the conceptual description of processes and of their inputs and outputs, ii) Vsoil_Modules devoted to the development of numerical representation of elementary processes as modules, iii) Vsoil_Models which permits the coupling of modules to create models, iv) Vsoil_Player for the run of the model and the primary analysis of results. The platform is designed to be a collaborative tool, helping scientists to share not only their models, but also the scientific knowledge on which the models are built. The platform is based on the idea that processes of any kind can be described and characterized by their inputs (state variables required) and their outputs. The links between the processes are automatically detected by the platform softwares. For any process, several numerical representations (modules) can be developed and made available to platform users. When developing modules, the platform takes care of many aspects of the development task so that the user can focus on numerical calculations. Fortran2008 and C++ are the supported languages and existing codes can be easily incorporated into platform modules. Building a model from available modules simply requires selecting the processes being accounted for and for each process a module. During this task, the platform displays available modules and checks the compatibility between the modules. The model (main program) is automatically created when compatible modules have been selected for all the processes. A GUI is automatically generated to help the user providing parameters and initial situations. Numerical results can be immediately visualized, archived and exported. The platform also provides facilities to carry out sensitivity analysis. Parameters estimation and links with databases are being developed. The platform can be freely downloaded from the web site (http://www.inra.fr/sol_virtuel/) with a set of processes, variables, modules and models. However, it is designed so that any user can add its own components. Theses adds-on can be shared with co-workers by means of an export/import mechanism using the e-mail. The adds-on can also be made available to the whole community of platform users when developers asked for. A filtering tool is available to explore the content of the platform (processes, variables, modules, models).

Biochemical transformation of coals

DOEpatents

Lin, Mow S.; Premuzic, Eugene T.

1999-03-23

A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed.

Biochemical upgrading of oils

DOEpatents

Premuzic, Eugene T.; Lin, Mow S.

1999-01-12

A process for biochemical conversion of heavy crude oils is provided. The process includes contacting heavy crude oils with adapted biocatalysts. The resulting upgraded oil shows, a relative increase in saturated hydrocarbons, emulsions and oxygenates and a decrease in compounds containing in organic sulfur, organic nitrogen and trace metals. Adapted microorganisms which have been modified under challenged growth processes are also disclosed.

Biochemical upgrading of oils

DOEpatents

Premuzic, E.T.; Lin, M.S.

1999-01-12

A process for biochemical conversion of heavy crude oils is provided. The process includes contacting heavy crude oils with adapted biocatalysts. The resulting upgraded oil shows, a relative increase in saturated hydrocarbons, emulsions and oxygenates and a decrease in compounds containing organic sulfur, organic nitrogen and trace metals. Adapted microorganisms which have been modified under challenged growth processes are also disclosed. 121 figs.

Generation and precise control of dynamic biochemical gradients for cellular assays

NASA Astrophysics Data System (ADS)

Saka, Yasushi; MacPherson, Murray; Giuraniuc, Claudiu V.

2017-03-01

Spatial gradients of diffusible signalling molecules play crucial roles in controlling diverse cellular behaviour such as cell differentiation, tissue patterning and chemotaxis. In this paper, we report the design and testing of a microfluidic device for diffusion-based gradient generation for cellular assays. A unique channel design of the device eliminates cross-flow between the source and sink channels, thereby stabilizing gradients by passive diffusion. The platform also enables quick and flexible control of chemical concentration that makes highly dynamic gradients in diffusion chambers. A model with the first approximation of diffusion and surface adsorption of molecules recapitulates the experimentally observed gradients. Budding yeast cells cultured in a gradient of a chemical inducer expressed a reporter fluorescence protein in a concentration-dependent manner. This microfluidic platform serves as a versatile prototype applicable to a broad range of biomedical investigations.

Canine model of crush syndrome established by a digital crush injury device platform

PubMed Central

Song, Jie; Ding, Hui; Fan, Hao-Jun; Dong, Wen-Long; Sun, Zhen-Xing; Hou, Shi-Ke

2015-01-01

Objective: To establish a canine model of crush syndrome (CS). Methods: A total of 16 healthy adult female Beagle dogs were randomly divided into the control group (n=8) and the experimental group (n=8). The crush injury was created in the left hind leg of each dog in the experimental group. Results: The biochemical indexes in the experimental group changed significantly compared to the values before extrusion. And they were also significantly different from the values of the control group. The glomerular capillary dilation, renal tubular epithelial cell degeneration, and renal interstitial lymphocytic infiltration were found in the kidneys. Conclusion: The canine CS model established by the digital crush injury device platform was successful according with the diagnosis of CS. It is good for the investigation of the CS mechanism and treatment using this model. PMID:26261489

IMGMD: A platform for the integration and standardisation of In silico Microbial Genome-scale Metabolic Models.

PubMed

Ye, Chao; Xu, Nan; Dong, Chuan; Ye, Yuannong; Zou, Xuan; Chen, Xiulai; Guo, Fengbiao; Liu, Liming

2017-04-07

Genome-scale metabolic models (GSMMs) constitute a platform that combines genome sequences and detailed biochemical information to quantify microbial physiology at the system level. To improve the unity, integrity, correctness, and format of data in published GSMMs, a consensus IMGMD database was built in the LAMP (Linux + Apache + MySQL + PHP) system by integrating and standardizing 328 GSMMs constructed for 139 microorganisms. The IMGMD database can help microbial researchers download manually curated GSMMs, rapidly reconstruct standard GSMMs, design pathways, and identify metabolic targets for strategies on strain improvement. Moreover, the IMGMD database facilitates the integration of wet-lab and in silico data to gain an additional insight into microbial physiology. The IMGMD database is freely available, without any registration requirements, at http://imgmd.jiangnan.edu.cn/database.

Energizing eukaryotic cell-free protein synthesis with glucose metabolism.

PubMed

Anderson, Mark J; Stark, Jessica C; Hodgman, C Eric; Jewett, Michael C

2015-07-08

Eukaryotic cell-free protein synthesis (CFPS) is limited by the dependence on costly high-energy phosphate compounds and exogenous enzymes to power protein synthesis (e.g., creatine phosphate and creatine kinase, CrP/CrK). Here, we report the ability to use glucose as a secondary energy substrate to regenerate ATP in a Saccharomyces cerevisiae crude extract CFPS platform. We observed synthesis of 3.64±0.35 μg mL(-1) active luciferase in batch reactions with 16 mM glucose and 25 mM phosphate, resulting in a 16% increase in relative protein yield (μg protein/$ reagents) compared to the CrP/CrK system. Our demonstration provides the foundation for development of cost-effective eukaryotic CFPS platforms. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology.

PubMed

Bache, Michael; Bosco, Filippo G; Brøgger, Anna L; Frøhling, Kasper B; Alstrøm, Tommy Sonne; Hwu, En-Te; Chen, Ching-Hsiu; Eugen-Olsen, Jesper; Hwang, Ing-Shouh; Boisen, Anja

2013-11-08

In this work the use of a high-throughput nanomechanical detection system based on a DVD-ROM optical drive and cantilever sensors is presented for the detection of urokinase plasminogen activator receptor inflammatory biomarker (uPAR). Several large scale studies have linked elevated levels of soluble uPAR (suPAR) to infectious diseases, such as HIV, and certain types of cancer. Using hundreds of cantilevers and a DVD-based platform, cantilever deflection response from antibody-antigen recognition is investigated as a function of suPAR concentration. The goal is to provide a cheap and portable detection platform which can carry valuable prognostic information. In order to optimize the cantilever response the antibody immobilization and unspecific binding are initially characterized using quartz crystal microbalance technology. Also, the choice of antibody is explored in order to generate the largest surface stress on the cantilevers, thus increasing the signal. Using optimized experimental conditions the lowest detectable suPAR concentration is currently around 5 nM. The results reveal promising research strategies for the implementation of specific biochemical assays in a portable and high-throughput microsensor-based detection platform.

Conformational Response of 30S-bound IF3 to A-Site Binders Streptomycin and Kanamycin

PubMed Central

Chulluncuy, Roberto; Espiche, Carlos; Nakamoto, Jose Alberto; Fabbretti, Attilio; Milón, Pohl

2016-01-01

Aminoglycoside antibiotics are widely used to treat infectious diseases. Among them, streptomycin and kanamycin (and derivatives) are of importance to battle multidrug-resistant (MDR) Mycobacterium tuberculosis. Both drugs bind the small ribosomal subunit (30S) and inhibit protein synthesis. Genetic, structural, and biochemical studies indicate that local and long-range conformational rearrangements of the 30S subunit account for this inhibition. Here, we use intramolecular FRET between the C- and N-terminus domains of the flexible IF3 to monitor real-time perturbations of their binding sites on the 30S platform. Steady and pre-steady state binding experiments show that both aminoglycosides bring IF3 domains apart, promoting an elongated state of the factor. Binding of Initiation Factor IF1 triggers closure of IF3 bound to the 30S complex, while both aminoglycosides revert the IF1-dependent conformation. Our results uncover dynamic perturbations across the 30S subunit, from the A-site to the platform, and suggest that both aminoglycosides could interfere with prokaryotic translation initiation by modulating the interaction between IF3 domains with the 30S platform. PMID:27983590

Microfluidic platform for assessing pancreatic islet functionality through dielectric spectroscopy

PubMed Central

Heileman, K.; Daoud, J.; Hasilo, C.; Gasparrini, M.; Paraskevas, S.; Tabrizian, M.

2015-01-01

Human pancreatic islets are seldom assessed for dynamic responses to external stimuli. Thus, the elucidation of human islet functionality would provide insights into the progression of diabetes mellitus, evaluation of preparations for clinical transplantation, as well as for the development of novel therapeutics. The objective of this study was to develop a microfluidic platform for in vitro islet culture, allowing the multi-parametric investigation of islet response to chemical and biochemical stimuli. This was accomplished through the fabrication and implementation of a microfluidic platform that allowed the perifusion of islet culture while integrating real-time monitoring using impedance spectroscopy, through microfabricated, interdigitated electrodes located along the microchamber arrays. Real-time impedance measurements provide important dielectric parameters, such as cell membrane capacitance and cytoplasmic conductivity, representing proliferation, differentiation, viability, and functionality. The perifusion of varying glucose concentrations and monitoring of the resulting impedance of pancreatic islets were performed as proof-of-concept validation of the lab-on-chip platform. This novel technique to elucidate the underlying mechanisms that dictate islet functionality is presented, providing new information regarding islet function that could improve the evaluation of islet preparations for transplantation. In addition, it will lead to a better understanding of fundamental diabetes-related islet dysfunction and the development of therapeutics through evaluation of potential drug effects. PMID:26339324

Digitized molecular diagnostics: reading disk-based bioassays with standard computer drives.

PubMed

Li, Yunchao; Ou, Lily M L; Yu, Hua-Zhong

2008-11-01

We report herein a digital signal readout protocol for screening disk-based bioassays with standard optical drives of ordinary desktop/notebook computers. Three different types of biochemical recognition reactions (biotin-streptavidin binding, DNA hybridization, and protein-protein interaction) were performed directly on a compact disk in a line array format with the help of microfluidic channel plates. Being well-correlated with the optical darkness of the binding sites (after signal enhancement by gold nanoparticle-promoted autometallography), the reading error levels of prerecorded audio files can serve as a quantitative measure of biochemical interaction. This novel readout protocol is about 1 order of magnitude more sensitive than fluorescence labeling/scanning and has the capability of examining multiplex microassays on the same disk. Because no modification to either hardware or software is needed, it promises a platform technology for rapid, low-cost, and high-throughput point-of-care biomedical diagnostics.

In situ modeling of PAH dynamics in agricultural soils amended with composts using the "VSOIL" platform

NASA Astrophysics Data System (ADS)

Brimo, Khaled; Ouvrard, Stéphanie; Houot, Sabine; Lafolie, François; Deschamps, Marjolaine; Benoit, Pierre; Garnier, Patricia

2017-04-01

Numerous studies have shown the presence of organic pollutants (OPs) in composts. Compost application in agricultural soil generates flux of OPs and among them polycyclic aromatic hydrocarbons (PAHs). A potential accumulation of PAHs in soils from successive compost applications could imply risks to environment. To explore and design scenarios that help land managers in their impact evaluations when composts are added in soils, there is a need to a new generation of models built from multi-modules that mimic the whole interactions between the different processes describing OP dynamic in soil. Our work is based on the implementation of an interdisciplinary global model for PAHs in soil by coupling modules describing the major physical, biochemical and biological processes influencing the fate of PAHs in soil, with modules that simulate water transfer, heat transfer, solute transport, and organic matter transformation under climatic conditions. The coupling is being facilitated by the «VSOIL» modeling platform. The steps of our modelling study are the following: 1) calibrate the field model using parameters previously estimated in laboratory completed with field data on a short period, 2) test the simulations using field experimental data, 3) build scenarios to explore the impact of PAHs accumulation in a long term (40 years). Our results show that the model can adequately predict the fate of PAHs in soil and can contribute to clarify some of unexplored aspects regarding the behavior of PAHs in soil like their mineralization and stabilization. Scenarios that predict the dynamic of PAHs in soil at long terms show a low PAH accumulation in soil after 40 years due to a high sequestration of the PAH in soils that is slightly higher for municipal solid waste composts than for green waste sludge composts.

21 CFR 315.5 - Evaluation of effectiveness.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

21 CFR 601.34 - Evaluation of effectiveness.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

21 CFR 315.5 - Evaluation of effectiveness.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

21 CFR 315.5 - Evaluation of effectiveness.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

21 CFR 601.34 - Evaluation of effectiveness.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

21 CFR 601.34 - Evaluation of effectiveness.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

21 CFR 315.5 - Evaluation of effectiveness.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

21 CFR 601.34 - Evaluation of effectiveness.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

21 CFR 601.34 - Evaluation of effectiveness.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

21 CFR 315.5 - Evaluation of effectiveness.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., physiological, or biochemical assessment is established by demonstrating in a defined clinical setting reliable measurement of function(s) or physiological, biochemical, or molecular process(es). (3) The claim of disease... demonstrating in a defined clinical setting that the test is useful in diagnostic or therapeutic patient...

Breast cancer diagnosis: Imaging techniques and biochemical markers.

PubMed

Jafari, Seyed Hamed; Saadatpour, Zahra; Salmaninejad, Arash; Momeni, Fatemeh; Mokhtari, Mojgan; Nahand, Javid Sadri; Rahmati, Majid; Mirzaei, Hamed; Kianmehr, Mojtaba

2018-07-01

Breast cancer is a complex disease which is found as the second cause of cancer-associated death among women. Accumulating of evidence indicated that various factors (i.e., gentical and envirmental factors) could be associated with initiation and progression of breast cancer. Diagnosis of breast cancer patients in early stages is one of important aspects of breast cancer treatment. Among of various diagnosis platforms, imaging techniques are main diagnosis approaches which could provide valuable data on patients with breast cancer. It has been showed that various imaging techniques such as mammography, magnetic resonance imaging (MRI), positron-emission tomography (PET), Computed tomography (CT), and single-photon emission computed tomography (SPECT) could be used for diagnosis and monitoring patients with breast cancer in various stages. Beside, imaging techniques, utilization of biochemical biomarkers such as proteins, DNAs, mRNAs, and microRNAs could be employed as new diagnosis and therapeutic tools for patients with breast cancer. Here, we summarized various imaging techniques and biochemical biomarkers could be utilized as diagnosis of patients with breast cancer. Moreover, we highlighted microRNAs and exosomes as new diagnosis and therapeutic biomarkers for monitoring patients with breast cancer. © 2017 Wiley Periodicals, Inc.

Design and Application of Sensors for Chemical Cytometry.

PubMed

Vickerman, Brianna M; Anttila, Matthew M; Petersen, Brae V; Allbritton, Nancy L; Lawrence, David S

2018-02-08

The bulk cell population response to a stimulus, be it a growth factor or a cytotoxic agent, neglects the cell-to-cell variability that can serve as a friend or as a foe in human biology. Biochemical variations among closely related cells furnish the basis for the adaptability of the immune system but also act as the root cause of resistance to chemotherapy by tumors. Consequently, the ability to probe for the presence of key biochemical variables at the single-cell level is now recognized to be of significant biological and biomedical impact. Chemical cytometry has emerged as an ultrasensitive single-cell platform with the flexibility to measure an array of cellular components, ranging from metabolite concentrations to enzyme activities. We briefly review the various chemical cytometry strategies, including recent advances in reporter design, probe and metabolite separation, and detection instrumentation. We also describe strategies for improving intracellular delivery, biochemical specificity, metabolic stability, and detection sensitivity of probes. Recent applications of these strategies to small molecules, lipids, proteins, and other analytes are discussed. Finally, we assess the current scope and limitations of chemical cytometry and discuss areas for future development to meet the needs of single-cell research.

Strategies for target identification of antimicrobial natural products.

PubMed

Farha, Maya A; Brown, Eric D

2016-05-04

Covering: 2000 to 2015Despite a pervasive decline in natural product research at many pharmaceutical companies over the last two decades, natural products have undeniably been a prolific and unsurpassed source for new lead antibacterial compounds. Due to their inherent complexity, natural extracts face several hurdles in high-throughout discovery programs, including target identification. Target identification and validation is a crucial process for advancing hits through the discovery pipeline, but has remained a major bottleneck. In the case of natural products, extremely low yields and limited compound supply further impede the process. Here, we review the wealth of target identification strategies that have been proposed and implemented for the characterization of novel antibacterials. Traditionally, these have included genomic and biochemical-based approaches, which, in recent years, have been improved with modern-day technology and better honed for natural product discovery. Further, we discuss the more recent innovative approaches for uncovering the target of new antibacterial natural products, which have resulted from modern advances in chemical biology tools. Finally, we present unique screening platforms implemented to streamline the process of target identification. The different innovative methods to respond to the challenge of characterizing the mode of action for antibacterial natural products have cumulatively built useful frameworks that may advocate a renovated interest in natural product drug discovery programs.

Biochemical transformation of solid carbonaceous material

DOEpatents

Lin, Mow S.; Premuzic, Eugene T.

2001-09-25

A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed.

Biochemical transformation of coals

DOEpatents

Lin, M.S.; Premuzic, E.T.

1999-03-23

A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed. 7 figs.

The underlying pathway structure of biochemical reaction networks

PubMed Central

Schilling, Christophe H.; Palsson, Bernhard O.

1998-01-01

Bioinformatics is yielding extensive, and in some cases complete, genetic and biochemical information about individual cell types and cellular processes, providing the composition of living cells and the molecular structure of its components. These components together perform integrated cellular functions that now need to be analyzed. In particular, the functional definition of biochemical pathways and their role in the context of the whole cell is lacking. In this study, we show how the mass balance constraints that govern the function of biochemical reaction networks lead to the translation of this problem into the realm of linear algebra. The functional capabilities of biochemical reaction networks, and thus the choices that cells can make, are reflected in the null space of their stoichiometric matrix. The null space is spanned by a finite number of basis vectors. We present an algorithm for the synthesis of a set of basis vectors for spanning the null space of the stoichiometric matrix, in which these basis vectors represent the underlying biochemical pathways that are fundamental to the corresponding biochemical reaction network. In other words, all possible flux distributions achievable by a defined set of biochemical reactions are represented by a linear combination of these basis pathways. These basis pathways thus represent the underlying pathway structure of the defined biochemical reaction network. This development is significant from a fundamental and conceptual standpoint because it yields a holistic definition of biochemical pathways in contrast to definitions that have arisen from the historical development of our knowledge about biochemical processes. Additionally, this new conceptual framework will be important in defining, characterizing, and studying biochemical pathways from the rapidly growing information on cellular function. PMID:9539712

A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bradshaw, Niels; Levdikov, Vladimir M.; Zimanyi, Christina M.

PP2C phosphatases control biological processes including stress responses, development, and cell division in all kingdoms of life. Diverse regulatory domains adapt PP2C phosphatases to specific functions, but how these domains control phosphatase activity was unknown. We present structures representing active and inactive states of the PP2C phosphatase SpoIIE from Bacillus subtilis. Based on structural analyses and genetic and biochemical experiments, we identify an α-helical switch that shifts a carbonyl oxygen into the active site to coordinate a metal cofactor. Our analysis indicates that this switch is widely conserved among PP2C family members, serving as a platform to control phosphatase activitymore » in response to diverse inputs. Remarkably, the switch is shared with proteasomal proteases, which we identify as evolutionary and structural relatives of PP2C phosphatases. Although these proteases use an unrelated catalytic mechanism, rotation of equivalent helices controls protease activity by movement of the equivalent carbonyl oxygen into the active site.« less

Pretreatment of lignocellulose: Formation of inhibitory by-products and strategies for minimizing their effects.

PubMed

Jönsson, Leif J; Martín, Carlos

2016-01-01

Biochemical conversion of lignocellulosic feedstocks to advanced biofuels and other commodities through a sugar-platform process involves a pretreatment step enhancing the susceptibility of the cellulose to enzymatic hydrolysis. A side effect of pretreatment is formation of lignocellulose-derived by-products that inhibit microbial and enzymatic biocatalysts. This review provides an overview of the formation of inhibitory by-products from lignocellulosic feedstocks as a consequence of using different pretreatment methods and feedstocks as well as an overview of different strategies used to alleviate problems with inhibitors. As technologies for biorefining of lignocellulose become mature and are transferred from laboratory environments to industrial contexts, the importance of management of inhibition problems is envisaged to increase as issues that become increasingly relevant will include the possibility to use recalcitrant feedstocks, obtaining high product yields and high productivity, minimizing the charges of enzymes and microorganisms, and using high solids loadings to obtain high product titers. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Highly-efficient enzymatic conversion of crude algal oils into biodiesel.

PubMed

Wang, Yao; Liu, Jin; Gerken, Henri; Zhang, Chengwu; Hu, Qiang; Li, Yantao

2014-11-01

Energy-intensive chemical conversion of crude algal oils into biodiesel is a major barrier for cost-effective algal biofuel production. To overcome this problem, we developed an enzyme-based platform for conversion of crude algal oils into fatty acid methyl esters. Crude algal oils were extracted from the oleaginous microalga Nannochloropsis oceanica IMET1 and converted by an immobilized lipase from Candida antarctica. The effects of different acyl acceptors, t-butanol as a co-solvent, oil to t-butanol ratio, oil to methanol ratio, temperature and reaction time on biodiesel conversion efficiency were studied. The conversion efficiency reached 99.1% when the conversion conditions were optimized, i.e., an oil to t-butanol weight ratio of 1:1, an oil to methanol molar ratio of 1:12, and a reaction time of 4h at 25°C. The enzymatic conversion process developed in this study may hold a promise for low energy consumption, low wastewater-discharge biochemical conversion of algal feedstocks into biofuels. Published by Elsevier Ltd.

Microfluidic devices for cell cultivation and proliferation

PubMed Central

Tehranirokh, Masoomeh; Kouzani, Abbas Z.; Francis, Paul S.; Kanwar, Jagat R.

2013-01-01

Microfluidic technology provides precise, controlled-environment, cost-effective, compact, integrated, and high-throughput microsystems that are promising substitutes for conventional biological laboratory methods. In recent years, microfluidic cell culture devices have been used for applications such as tissue engineering, diagnostics, drug screening, immunology, cancer studies, stem cell proliferation and differentiation, and neurite guidance. Microfluidic technology allows dynamic cell culture in microperfusion systems to deliver continuous nutrient supplies for long term cell culture. It offers many opportunities to mimic the cell-cell and cell-extracellular matrix interactions of tissues by creating gradient concentrations of biochemical signals such as growth factors, chemokines, and hormones. Other applications of cell cultivation in microfluidic systems include high resolution cell patterning on a modified substrate with adhesive patterns and the reconstruction of complicated tissue architectures. In this review, recent advances in microfluidic platforms for cell culturing and proliferation, for both simple monolayer (2D) cell seeding processes and 3D configurations as accurate models of in vivo conditions, are examined. PMID:24273628

Emergence of a catalytic tetrad during evolution of a highly active artificial aldolase.

PubMed

Obexer, Richard; Godina, Alexei; Garrabou, Xavier; Mittl, Peer R E; Baker, David; Griffiths, Andrew D; Hilvert, Donald

2017-01-01

Designing catalysts that achieve the rates and selectivities of natural enzymes is a long-standing goal in protein chemistry. Here, we show that an ultrahigh-throughput droplet-based microfluidic screening platform can be used to improve a previously optimized artificial aldolase by an additional factor of 30 to give a >10 9 rate enhancement that rivals the efficiency of class I aldolases. The resulting enzyme catalyses a reversible aldol reaction with high stereoselectivity and tolerates a broad range of substrates. Biochemical and structural studies show that catalysis depends on a Lys-Tyr-Asn-Tyr tetrad that emerged adjacent to a computationally designed hydrophobic pocket during directed evolution. This constellation of residues is poised to activate the substrate by Schiff base formation, promote mechanistically important proton transfers and stabilize multiple transition states along a complex reaction coordinate. The emergence of such a sophisticated catalytic centre shows that there is nothing magical about the catalytic activities or mechanisms of naturally occurring enzymes, or the evolutionary process that gave rise to them.

The effect of high hydrostatic pressure on the physiological and biochemical properties of pepper (Capsicum annuum L.) seedlings

NASA Astrophysics Data System (ADS)

İşlek, Cemil; Murat Altuner, Ergin; Alpas, Hami

2015-10-01

High hydrostatic pressure is a non-thermal food processing technology, which also has several successful applications in different areas besides food processing. In this study, Capsicum annuum L. (pepper) seeds are subjected to 50, 100, 200 and 300 MPa pressure for 5 min at 25°C and the seedlings of HHP processed seeds are used to compare percentage of seed germination and biochemical properties such as chlorophyll a, b and a/b, proline content, total protein, carotenoid, malondialdehyde, glucose, fructose and phenolic compounds concentrations. As a result of the study, it was observed that there are remarkable changes in terms of biochemical properties especially for seedlings, whose seeds were pressurized at 200 and 300 MPa. More detailed studies are needed to put forward the mechanism behind the changes in biochemical properties.

Dynamics of biochemical processes and redox conditions in geochemically linked landscapes of oligotrophic bogs

NASA Astrophysics Data System (ADS)

Inisheva, L. I.; Szajdak, L.; Sergeeva, M. A.

2016-04-01

The biological activity in oligotrophic peatlands at the margins of the Vasyugan Mire has been studied. It is shown found that differently directed biochemical processes manifest themselves in the entire peat profile down to the underlying mineral substrate. Their activity is highly variable. It is argued that the notion about active and inert layers in peat soils is only applicable for the description of their water regime. The degree of the biochemical activity is specified by the physical soil properties. As a result of the biochemical processes, a micromosaic aerobic-anaerobic medium is developed under the surface waterlogged layer of peat deposits. This layer contains the gas phase, including oxygen. It is concluded that the organic and mineral parts of peat bogs represent a single functional system of a genetic peat profile with a clear record of the history of its development.

Microstructure change in wood cell wall fracture from mechanical pretreatment and its influence on enzymatic hydrolysis

Treesearch

Jinxue Jiang; Jinwu Wang; Xiao Zhang; Michael Wolcott

2017-01-01

tMechanical pretreatment is an effective process for chemical or biochemical conversion of woodybiomass. The deconstruction features of the wood cell wall play an important role in its chemical or bio-chemical processing. In this work, we evaluated the wood cell wall fracture in the early stage of mechanicalpretreatment process conducted with various initial moisture...

Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering.

PubMed

Menolascina, Filippo; Bellomo, Domenico; Maiwald, Thomas; Bevilacqua, Vitoantonio; Ciminelli, Caterina; Paradiso, Angelo; Tommasi, Stefania

2009-10-15

Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response experiments (SRE) have been used to gain a deeper insight into the details of biochemical mechanisms underlying cell life and functioning. Optimisation of the input time-profile, however, still remains a major area of research due to the complexity of the problem and its relevance for the task of information retrieval in systems biology-related experiments. We have addressed the problem of quantifying the information associated to an experiment using the Fisher Information Matrix and we have proposed an optimal experimental design strategy based on evolutionary algorithm to cope with the problem of information gathering in Systems Biology. On the basis of the theoretical results obtained in the field of control systems theory, we have studied the dynamical properties of the signals to be used in cell stimulation. The results of this study have been used to develop a microfluidic device for the automation of the process of cell stimulation for system identification. We have applied the proposed approach to the Epidermal Growth Factor Receptor pathway and we observed that it minimises the amount of parametric uncertainty associated to the identified model. A statistical framework based on Monte-Carlo estimations of the uncertainty ellipsoid confirmed the superiority of optimally designed experiments over canonical inputs. The proposed approach can be easily extended to multiobjective formulations that can also take advantage of identifiability analysis. Moreover, the availability of fully automated microfluidic platforms explicitly developed for the task of biochemical model identification will hopefully reduce the effects of the 'data rich--data poor' paradox in Systems Biology.

Biochemical characterization of recombinant Enterovirus 71 3C protease with fluorogenic model peptide substrates and development of a biochemical assay.

PubMed

Shang, Luqing; Zhang, Shumei; Yang, Xi; Sun, Jixue; Li, Linfeng; Cui, Zhengjie; He, Qiuhong; Guo, Yu; Sun, Yuna; Yin, Zheng

2015-04-01

Enterovirus 71 (EV71), a primary pathogen of hand, foot, and mouth disease (HFMD), affects primarily infants and children. Currently, there are no effective drugs against HFMD. EV71 3C protease performs multiple tasks in the viral replication, which makes it an ideal antiviral target. We synthesized a small set of fluorogenic model peptides derived from cleavage sites of EV71 polyprotein and examined their efficiencies of cleavage by EV71 3C protease. The novel peptide P08 [(2-(N-methylamino)benzoyl) (NMA)-IEALFQGPPK(DNP)FR] was determined to be the most efficiently cleaved by EV71 3C protease, with a kinetic constant kcat/Km of 11.8 ± 0.82 mM(-1) min(-1). Compared with literature reports, P08 gave significant improvement in the signal/background ratio, which makes it an attractive substrate for assay development. A Molecular dynamics simulation study elaborated the interactions between substrate P08 and EV71 3C protease. Arg39, which is located at the bottom of the S2 pocket of EV71 3C protease, may participate in the proteolysis process of substrates. With an aim to evaluate EV71 3C protease inhibitors, a reliable and robust biochemical assay with a Z' factor of 0.87 ± 0.05 was developed. A novel compound (compound 3) (50% inhibitory concentration [IC50] = 1.89 ± 0.25 μM) was discovered using this assay, which effectively suppressed the proliferation of EV 71 (strain Fuyang) in rhabdomyosarcoma (RD) cells with a highly selective index (50% effective concentration [EC50] = 4.54 ± 0.51 μM; 50% cytotoxic concentration [CC50] > 100 μM). This fast and efficient assay for lead discovery and optimization provides an ideal platform for anti-EV71 drug development targeting 3C protease. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Apparatus and method for materials processing utilizing a rotating magnetic field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muralidharan, Govindarajan; Angelini, Joseph A.; Murphy, Bart L.

An apparatus for materials processing utilizing a rotating magnetic field comprises a platform for supporting a specimen, and a plurality of magnets underlying the platform. The plurality of magnets are configured for rotation about an axis of rotation intersecting the platform. A heat source is disposed above the platform for heating the specimen during the rotation of the plurality of magnets. A method for materials processing utilizing a rotating magnetic field comprises providing a specimen on a platform overlying a plurality of magnets; rotating the plurality of magnets about an axis of rotation intersecting the platform, thereby applying a rotatingmore » magnetic field to the specimen; and, while rotating the plurality of magnets, heating the specimen to a desired temperature.« less

Effect of whole-body vibration training on body composition, exercise performance and biochemical responses in middle-aged mice.

PubMed

Lin, Ching-I; Huang, Wen-Ching; Chen, Wen-Chyuan; Kan, Nai-Wen; Wei, Li; Chiu, Yen-Shuo; Huang, Chi-Chang

2015-09-01

Whole-body vibration (WBV) is a well-known light-resistance exercise by automatic adaptations to rapid and repeated oscillations from a vibrating platform, which is also a simple and convenient exercise for older adults. However, the potential benefits of WBV on aging-associated changes in body composition, exercise performance, and fatigue are currently unclear. The objective of the study is to investigate the beneficial effects of WBV training on body composition, exercise performance, and physical fatigue-related and biochemical responses in middle-aged mice. In total, 24 male C57BL/6 mice aged 15 months old were randomly divided into 3 groups (n=8 per group): sedentary control (SC), relatively low-frequency WBV (5.6 Hz, 2 mm, 0.13 g) (LV), and relatively high-frequency WBV (13 Hz, 2 mm, 0.68 g) (HV). Mice in the LV and HV groups were placed inside a vibration platform and vibrated at different frequencies and fixed amplitude (2 mm) for 15 min, 5 days/week for 4 weeks. Exercise performance, core temperature and anti-fatigue function were evaluated by forelimb grip strength and levels of serum lactate, ammonia, glucose, and creatine kinase (CK) after a 15-min swimming exercise, as were changes in body composition and biochemical variables at the end of the experiment. Relative muscle and brown adipose tissue weight (%) was significantly higher for the HV than SC mice, but relative liver weight (%) was lower. On trend analysis, WBV increased grip strength, aerobic endurance and core temperature in mice. As well, serum lactate, ammonia and CK levels were dose-dependently decreased with vibration frequency after the swimming test. Fasting serum levels of albumin and total protein were increased and serum levels of alkaline phosphatase and creatinine decreased dose-dependently with vibration frequency. Moreover, WBV training improved the age-related abnormal morphology of skeletal muscle, liver and kidney tissues. Therefore, it could improve exercise performance and ameliorate fatigue and prevent senescence-associated biochemical and pathological alterations in middle-aged mice. WBV training may be an effective intervention for health promotion in the aging population. The detailed molecular mechanism of how WBV training regulates anti-aging activity warrants further functional studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical-Scale Cell-Surface-Marker Independent Acoustic Microfluidic Enrichment of Tumor Cells from Blood.

PubMed

Magnusson, Cecilia; Augustsson, Per; Lenshof, Andreas; Ceder, Yvonne; Laurell, Thomas; Lilja, Hans

2017-11-21

Enumeration of circulating tumor cells (CTCs) predicts overall survival and treatment response in metastatic cancer, but as many commercialized assays isolate CTCs positive for epithelial cell markers alone, CTCs with little or no epithelial cell adhesion molecule (EpCAM) expression stay undetected. Therefore, CTC enrichment and isolation by label-free methods based on biophysical rather than biochemical properties could provide a more representative spectrum of CTCs. Here, we report on a clinical-scale automated acoustic microfluidic platform processing 5 mL of erythrocyte-depleted paraformaldehyde (PFA)-fixed blood (diluted 1:2) at a flow rate of 75 μL/min, recovering 43/50 (86 ± 2.3%) breast cancer cell line cells (MCF7), with 0.11% cancer cell purity and 162-fold enrichment in close to 2 h based on intrinsic biophysical cell properties. Adjustments of the voltage settings aimed at higher cancer cell purity in the central outlet provided 0.72% cancer cell purity and 1445-fold enrichment that resulted in 62 ± 8.7% cancer cell recovery. Similar rates of cancer-cell recovery, cancer-cell purity, and fold-enrichment were seen with both prostate cancer (DU145, PC3) and breast cancer (MCF7) cell line cells. We identified eosinophil granulocytes as the predominant white blood cell (WBC) contaminant (85%) in the enriched cancer-cell fraction. Processing of viable cancer cells in erythrocyte-depleted blood provided slightly reduced results as to fixed cells (77% cancer cells in the enriched cancer cell fraction, with 0.2% WBC contamination). We demonstrate feasibility of enriching either PFA-fixed or viable cancer cells with a clinical-scale acoustic microfluidic platform that can be adjusted to meet requirements for either high cancer-cell recovery or higher purity and can process 5 mL blood samples in close to 2 h.

30 CFR 250.909 - What is the Platform Verification Program?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What is the Platform Verification Program? 250... Platforms and Structures Platform Verification Program § 250.909 What is the Platform Verification Program? The Platform Verification Program is the MMS approval process for ensuring that floating platforms...

Matt Wecker | NREL

Science.gov Websites

acetaldehyde from bacteria. The idea was to short-sheet the ethanol fermentation pathway to produce ; Biochem. (1995) "Fermentation strategies: Acetaldehyde or ethanol?," Process Biochem. (1987

Transference of CALIPER pediatric reference intervals to biochemical assays on the Roche cobas 6000 and the Roche Modular P.

PubMed

Higgins, Victoria; Chan, Man Khun; Nieuwesteeg, Michelle; Hoffman, Barry R; Bromberg, Irvin L; Gornall, Doug; Randell, Edward; Adeli, Khosrow

2016-01-01

The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has recently established pediatric age- and sex-specific reference intervals for over 85 biochemical markers on the Abbott Architect system. Previously, CALIPER reference intervals for several biochemical markers were successfully transferred from Abbott assays to Roche, Beckman, Ortho, and Siemens assays. This study further broadens the CALIPER database by performing transference and verification for 52 biochemical assays on the Roche cobas 6000 and the Roche Modular P. Using CLSI C28-A3 and EP9-A2 guidelines, transference of the CALIPER reference intervals was attempted for 16 assays on the Roche cobas 6000 and 36 on the Modular P. Calculated reference intervals were further verified using 100 healthy CALIPER samples. Most assays showed strong correlation between assay systems and were transferable from Abbott to the Roche cobas 6000 (81%) and the Modular P (86%). Bicarbonate and magnesium were not transferable on either system and calcium and prealbumin were not transferable to the Modular P. Of the transferable analytes, 62% and 61% were verified on the cobas 6000 and the Modular P, respectively. This study extends the utility of the CALIPER database to two additional analytical systems, which facilitates the broad application of CALIPER reference intervals at pediatric centers utilizing Roche biochemical assays. Transference studies across different analytical platforms can later be collectively analyzed in an attempt to develop common reference intervals across all clinical chemistry instruments to harmonize laboratory test interpretation in diagnosis and monitoring of pediatric disease. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Exploration of graphene oxide as an intelligent platform for cancer vaccines

NASA Astrophysics Data System (ADS)

Yue, Hua; Wei, Wei; Gu, Zonglin; Ni, Dezhi; Luo, Nana; Yang, Zaixing; Zhao, Lin; Garate, Jose Antonio; Zhou, Ruhong; Su, Zhiguo; Ma, Guanghui

2015-11-01

We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The ``folding GO'' acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a ``One but All'' modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines.We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The ``folding GO'' acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a ``One but All'' modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04986e

Exploring infrared neural stimulation with multimodal nonlinear imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Adams, Wilson R.; Mahadevan-Jansen, Anita

2017-02-01

Infrared neural stimulation (INS) provides optical control of neural excitability using near to mid-infrared (mid-IR) light, which allows for spatially selective, artifact-free excitation without the introduction of exogenous agents or genetic modification. Although neural excitability is mediated by a transient temperature increase due to water absorption of IR energy, the molecular nature of IR excitability in neural tissue remains unknown. Current research suggests that transient changes in local tissue temperature give rise to a myriad of cellular responses that have been individually attributed to IR mediated excitability. To further elucidate the underlying biophysical mechanisms, we have begun work towards employing a novel multimodal nonlinear imaging platform to probe the molecular underpinnings of INS. Our imaging system performs coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS), two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG) and thermal imaging into a single platform that allows for unprecedented co-registration of thermal and biochemical information in real-time. Here, we present our work leveraging CARS and SRS in acute thalamocortical brain slice preparations. We observe the evolution of lipid and protein-specific Raman bands during INS and electrically evoked activity in real-time. Combined with two-photon fluorescence and second harmonic generation, we offer insight to cellular metabolism and membrane dynamics during INS. Thermal imaging allows for the coregistration of acquired biochemical information with temperature information. Our work previews the versatility and capabilities of coherent Raman imaging combined with multiphoton imaging to observe biophysical phenomena for neuroscience applications.

Integrated Experimental Platforms to Study Blast Injuries: a Bottom-Up Approach

NASA Astrophysics Data System (ADS)

Bo, Chiara

2013-06-01

Developing a cellular and molecular understanding of the nature of traumatic and post-traumatic effects of blast events on live biological samples is critical for improving clinical outcomes.1 To investigate the consequences of pressure waves upon cellular structures and the underlying physiological and biochemical changes, we are using an integrated approach to study the material and biological properties of cells, tissues and organs when subjected to extreme conditions. In particular we have developed a confined Split Hopkinson Pressure Bar (SHPB) system, which allows us to subject cells in suspension or in a monolayer to compression waves of the order of few MPa and duration of hundreds of microseconds.2 The chamber design also enables recovery of the biological samples for cellular and molecular analysis. Specifically, cell survivability, viability, proliferation and morphological changes are investigated post compression for different cell populations. The SHPB platform, coupled with Quasi-Static experiments, is also used to determine stress-strain curves of soft biological tissues under compression at low, medium and high strain rates. Samples are also examined using histological techniques to study macro- and microscopical changes induced by compression waves. Finally, a shock tube has been developed to replicate primary blast damage on organs (i.e. mice lungs) and cell monolayers by generating single or multiple air blast of the order of kPa and few milliseconds duration. This platform allows us to visualize post-traumatic morphological changes at the cellular level as a function of the stimulus pressure and duration as well as biomarker signatures of blast injuries. Adapting and integrating a variety of approaches with different experimental platforms allows us to sample a vast pressure-time space in terms of biological and structural damage that mimic blast injuries and also to determine which physical parameters (peak pressure, stimulus duration, impulse) are contributing to the injury process. Moreover, understanding biological damage following blast events is crucial to developing novel clinical approaches to detect and treat traumatic injury pathologies. This work is supported by he Atomic Weapons Establishment, UK and The Royal British Legion Centre for Blast Injury Studies at Imperial College London, UK

In-vitro nanodiagnostic platform through nanoparticles and DNA-RNA nanotechnology.

PubMed

Chan, Ki; Ng, Tzi Bun

2015-04-01

Nanocomposites containing nanoparticles or nanostructured domains exhibit an even higher degree of material complexity that leads to an extremely high variability of nanostructured materials. This review introduces analytical concepts and techniques for nanomaterials and derives recommendations for a qualified selection of characterization techniques for specific types of samples, and focuses the characterization of nanoparticles and their agglomerates or aggregates. In addition, DNA nanotechnology and the more recent newcomer RNA nanotechnology have achieved almost an advanced status among nanotechnology researchers¸ therefore, the core features, potential, and significant challenges of DNA nanotechnology are also highlighted as a new discipline. Moreover, nanobiochips made by nanomaterials are rapidly emerging as a new paradigm in the area of large-scale biochemical analysis. The use of nanoscale components enables higher precision in diagnostics while considerably reducing the cost of the platform that leads this review to explore the use of nanoparticles, nanomaterials, and other bionanotechnologies for its application to nanodiagnostics in-vitro.

Microfluidics for cell-based high throughput screening platforms - A review.

PubMed

Du, Guansheng; Fang, Qun; den Toonder, Jaap M J

2016-01-15

In the last decades, the basic techniques of microfluidics for the study of cells such as cell culture, cell separation, and cell lysis, have been well developed. Based on cell handling techniques, microfluidics has been widely applied in the field of PCR (Polymerase Chain Reaction), immunoassays, organ-on-chip, stem cell research, and analysis and identification of circulating tumor cells. As a major step in drug discovery, high-throughput screening allows rapid analysis of thousands of chemical, biochemical, genetic or pharmacological tests in parallel. In this review, we summarize the application of microfluidics in cell-based high throughput screening. The screening methods mentioned in this paper include approaches using the perfusion flow mode, the droplet mode, and the microarray mode. We also discuss the future development of microfluidic based high throughput screening platform for drug discovery. Copyright © 2015 Elsevier B.V. All rights reserved.

Cell illustrator 4.0: a computational platform for systems biology.

PubMed

Nagasaki, Masao; Saito, Ayumu; Jeong, Euna; Li, Chen; Kojima, Kaname; Ikeda, Emi; Miyano, Satoru

2011-01-01

Cell Illustrator is a software platform for Systems Biology that uses the concept of Petri net for modeling and simulating biopathways. It is intended for biological scientists working at bench. The latest version of Cell Illustrator 4.0 uses Java Web Start technology and is enhanced with new capabilities, including: automatic graph grid layout algorithms using ontology information; tools using Cell System Markup Language (CSML) 3.0 and Cell System Ontology 3.0; parameter search module; high-performance simulation module; CSML database management system; conversion from CSML model to programming languages (FORTRAN, C, C++, Java, Python and Perl); import from SBML, CellML, and BioPAX; and, export to SVG and HTML. Cell Illustrator employs an extension of hybrid Petri net in an object-oriented style so that biopathway models can include objects such as DNA sequence, molecular density, 3D localization information, transcription with frame-shift, translation with codon table, as well as biochemical reactions.

Nucleic acid programmable protein array a just-in-time multiplexed protein expression and purification platform.

PubMed

Qiu, Ji; LaBaer, Joshua

2011-01-01

Systematic study of proteins requires the availability of thousands of proteins in functional format. However, traditional recombinant protein expression and purification methods have many drawbacks for such study at the proteome level. We have developed an innovative in situ protein expression and capture system, namely NAPPA (nucleic acid programmable protein array), where C-terminal tagged proteins are expressed using an in vitro expression system and efficiently captured/purified by antitag antibodies coprinted at each spot. The NAPPA technology presented in this chapter enable researchers to produce and display fresh proteins just in time in a multiplexed high-throughput fashion and utilize them for various downstream biochemical researches of interest. This platform could revolutionize the field of functional proteomics with it ability to produce thousands of spatially separated proteins in high density with narrow dynamic rand of protein concentrations, reproducibly and functionally. Copyright © 2011 Elsevier Inc. All rights reserved.

Cell Illustrator 4.0: a computational platform for systems biology.

PubMed

Nagasaki, Masao; Saito, Ayumu; Jeong, Euna; Li, Chen; Kojima, Kaname; Ikeda, Emi; Miyano, Satoru

2010-01-01

Cell Illustrator is a software platform for Systems Biology that uses the concept of Petri net for modeling and simulating biopathways. It is intended for biological scientists working at bench. The latest version of Cell Illustrator 4.0 uses Java Web Start technology and is enhanced with new capabilities, including: automatic graph grid layout algorithms using ontology information; tools using Cell System Markup Language (CSML) 3.0 and Cell System Ontology 3.0; parameter search module; high-performance simulation module; CSML database management system; conversion from CSML model to programming languages (FORTRAN, C, C++, Java, Python and Perl); import from SBML, CellML, and BioPAX; and, export to SVG and HTML. Cell Illustrator employs an extension of hybrid Petri net in an object-oriented style so that biopathway models can include objects such as DNA sequence, molecular density, 3D localization information, transcription with frame-shift, translation with codon table, as well as biochemical reactions.

The business impact of an integrated continuous biomanufacturing platform for recombinant protein production.

PubMed

Walther, Jason; Godawat, Rahul; Hwang, Chris; Abe, Yuki; Sinclair, Andrew; Konstantinov, Konstantin

2015-11-10

The biotechnology industry primarily uses batch technologies to manufacture recombinant proteins. The natural evolution of other industries has shown that transitioning from batch to continuous processing can yield significant benefits. A quantitative understanding of these benefits is critical to guide the implementation of continuous processing. In this manuscript, we use process economic modeling and Monte Carlo simulations to evaluate an integrated continuous biomanufacturing (ICB) platform and conduct risk-based valuation to generate a probabilistic range of net-present values (NPVs). For a specific ten-year product portfolio, the ICB platform reduces average cost by 55% compared to conventional batch processing, considering both capital and operating expenses. The model predicts that these savings can further increase by an additional 25% in situations with higher-than-expected product demand showing the upward potential of the ICB platform. The ICB platform achieves these savings and corresponding flexibility mainly due to process intensification in both upstream and downstream unit operations. This study demonstrates the promise of continuous bioprocessing while also establishing a novel framework to quantify financial benefits of other platform process technologies. Copyright © 2015 Elsevier B.V. All rights reserved.

Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guarino, Vincenzo, E-mail: vguarino@unina.it; Altobelli, Rosaria; Cirillo, Valentina

A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial’s manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow tomore » produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell–biomaterial and cell– cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues.« less

Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

NASA Astrophysics Data System (ADS)

Guarino, Vincenzo; Altobelli, Rosaria; Cirillo, Valentina; Ambrosio, Luigi

2015-12-01

A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial's manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow to produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell-biomaterial and cell- cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues.

Chromatography process development in the quality by design paradigm I: Establishing a high-throughput process development platform as a tool for estimating "characterization space" for an ion exchange chromatography step.

PubMed

Bhambure, R; Rathore, A S

2013-01-01

This article describes the development of a high-throughput process development (HTPD) platform for developing chromatography steps. An assessment of the platform as a tool for establishing the "characterization space" for an ion exchange chromatography step has been performed by using design of experiments. Case studies involving use of a biotech therapeutic, granulocyte colony-stimulating factor have been used to demonstrate the performance of the platform. We discuss the various challenges that arise when working at such small volumes along with the solutions that we propose to alleviate these challenges to make the HTPD data suitable for empirical modeling. Further, we have also validated the scalability of this platform by comparing the results from the HTPD platform (2 and 6 μL resin volumes) against those obtained at the traditional laboratory scale (resin volume, 0.5 mL). We find that after integration of the proposed correction factors, the HTPD platform is capable of performing the process optimization studies at 170-fold higher productivity. The platform is capable of providing semi-quantitative assessment of the effects of the various input parameters under consideration. We think that platform such as the one presented is an excellent tool for examining the "characterization space" and reducing the extensive experimentation at the traditional lab scale that is otherwise required for establishing the "design space." Thus, this platform will specifically aid in successful implementation of quality by design in biotech process development. This is especially significant in view of the constraints with respect to time and resources that the biopharma industry faces today. Copyright © 2013 American Institute of Chemical Engineers.

Stochastic hybrid systems for studying biochemical processes.

PubMed

Singh, Abhyudai; Hespanha, João P

2010-11-13

Many protein and mRNA species occur at low molecular counts within cells, and hence are subject to large stochastic fluctuations in copy numbers over time. Development of computationally tractable frameworks for modelling stochastic fluctuations in population counts is essential to understand how noise at the cellular level affects biological function and phenotype. We show that stochastic hybrid systems (SHSs) provide a convenient framework for modelling the time evolution of population counts of different chemical species involved in a set of biochemical reactions. We illustrate recently developed techniques that allow fast computations of the statistical moments of the population count, without having to run computationally expensive Monte Carlo simulations of the biochemical reactions. Finally, we review different examples from the literature that illustrate the benefits of using SHSs for modelling biochemical processes.

Integrated microdroplet-based system for enzyme synthesis and sampling

NASA Astrophysics Data System (ADS)

Lapierre, Florian; Best, Michel; Stewart, Robert; Oakeshott, John; Peat, Thomas; Zhu, Yonggang

2013-12-01

Microdroplet-based microfluidic devices are emerging as powerful tools for a wide range of biochemical screenings and analyses. Monodispersed aqueous microdroplets from picoliters to nanoliters in volume are generated inside microfluidic channels within an immiscible oil phase. This results in the formation of emulsions which can contain various reagents for chemical reactions and can be considered as discrete bioreactors. In this paper an integrated microfluidic platform for the synthesis, screening and sorting of libraries of an organophosphate degrading enzyme is presented. The variants of the selected enzyme are synthesized from a DNA source using in-vitro transcription and translation method. The synthesis occurs inside water-in-oil emulsion droplets, acting as bioreactors. Through a fluorescence based detection system, only the most efficient enzymes are selected. All the necessary steps from the enzyme synthesis to selection of the best genes (producing the highest enzyme activity) are thus integrated inside a single and unique device. In the second part of the paper, an innovative design of the microfluidic platform is presented, integrating an electronic prototyping board for ensuring the communication between the various components of the platform (camera, syringe pumps and high voltage power supply), resulting in a future handheld, user-friendly, fully automated device for enzyme synthesis, screening and selection. An overview on the capabilities as well as future perspectives of this new microfluidic platform is provided.

[Biochemical changes in apoptosis and methods for their determination (review)].

PubMed

Sedláková, A; Kohút, A; Kalina, I

1999-08-01

Apoptosis or programmed cell death is a physiological process which occurs at different biological states as well as at disease process. Morphologically it is characterized by the chromatine condensation and other changes with preserved integrity of plasmatic membrane. The major and most frequently studied biochemical characteristic of apoptosis is a DNA fragmentation. In our paper attention is directed to the early biochemical changes in cell membranes, i.g., the externalization of phosphatidylserine, hydrolysis of sphingomyeline on the ceramide and activation of phospholipases especially phospholipase A2. In one part we described the changes of cysteine proteases (caspases), which play a key role in the execution of apoptosis. These biochemical changes are associated with ceramide signalization of apoptosis. Briefly are presented also some dates about apoptosis induction with reactive oxygen radicals and the role of the arachidonic acid metabolites in this process. We consider the investigation and determination of these changes as important parameters of apoptosis at some diseases, e.g., cancer or degenerative diseases, and of their treatment.

Metabolomics and malaria biology

PubMed Central

Lakshmanan, Viswanathan; Rhee, Kyu Y.; Daily, Johanna P.

2010-01-01

Metabolomics has ushered in a novel and multi-disciplinary realm in biological research. It has provided researchers with a platform to combine powerful biochemical, statistical, computational, and bioinformatics techniques to delve into the mysteries of biology and disease. The application of metabolomics to study malaria parasites represents a major advance in our approach towards gaining a more comprehensive perspective on parasite biology and disease etiology. This review attempts to highlight some of the important aspects of the field of metabolomics, and its ongoing and potential future applications to malaria research. PMID:20970461

Recent Advances in Nanobiotechnology and High-Throughput Molecular Techniques for Systems Biomedicine

PubMed Central

Kim, Eung-Sam; Ahn, Eun Hyun; Chung, Euiheon; Kim, Deok-Ho

2013-01-01

Nanotechnology-based tools are beginning to emerge as promising platforms for quantitative high-throughput analysis of live cells and tissues. Despite unprecedented progress made over the last decade, a challenge still lies in integrating emerging nanotechnology-based tools into macroscopic biomedical apparatuses for practical purposes in biomedical sciences. In this review, we discuss the recent advances and limitations in the analysis and control of mechanical, biochemical, fluidic, and optical interactions in the interface areas of nanotechnology-based materials and living cells in both in vitro and in vivo settings. PMID:24258011

Recent advances in nanobiotechnology and high-throughput molecular techniques for systems biomedicine.

PubMed

Kim, Eung-Sam; Ahn, Eun Hyun; Chung, Euiheon; Kim, Deok-Ho

2013-12-01

Nanotechnology-based tools are beginning to emerge as promising platforms for quantitative high-throughput analysis of live cells and tissues. Despite unprecedented progress made over the last decade, a challenge still lies in integrating emerging nanotechnology-based tools into macroscopic biomedical apparatuses for practical purposes in biomedical sciences. In this review, we discuss the recent advances and limitations in the analysis and control of mechanical, biochemical, fluidic, and optical interactions in the interface areas of nanotechnologybased materials and living cells in both in vitro and in vivo settings.

Apparatus and method for converting biomass to feedstock for biofuel and biochemical manufacturing processes

DOEpatents

Kania, John; Qiao, Ming; Woods, Elizabeth M.; Cortright, Randy D.; Myren, Paul

2015-12-15

The present invention includes improved systems and methods for producing biomass-derived feedstocks for biofuel and biochemical manufacturing processes. The systems and methods use components that are capable of transferring relatively high concentrations of solid biomass utilizing pressure variations between vessels, and allows for the recovery and recycling of heterogeneous catalyst materials.

30 CFR 250.909 - What is the Platform Verification Program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What is the Platform Verification Program? 250... Verification Program § 250.909 What is the Platform Verification Program? The Platform Verification Program is the MMS approval process for ensuring that floating platforms; platforms of a new or unique design...

Carbon nanotubes as novel spacer materials on silver thin-films for generating superior fluorescence enhancements via surface plasmon coupled emission

NASA Astrophysics Data System (ADS)

Mulpur, Pradyumna; Podila, Ramakrishna; Rao, Apparao M.; Kamisetti, Venkataramaniah

2016-06-01

In this study, we report the first time implementation of single/multi-walled carbon nanotubes, as novel spacer materials, on a silver (Ag) thin-film based surface plasmon coupled emission (SPCE) platform. The engineered Ag-CNT SPCE substrates enabled the realization of up to ∼10-fold enhancement in fluorescence signal intensity, of the rhodamine b dye. This study addresses the issue that, while many of the biochemical sensing strategies are based on fluorescence, they are all fundamentally limited by the isotropic nature of the phenomenon that results in low signal collection efficiency (<1%). Pursuant to the aim of realizing superior levels of signal sensitivity, we previously reported graphene and C60 as novel spacer materials, and similarly project CNTs in this study as ‘active’ contributors for the amplification of fluorescence signals on the SPCE platform that generates highly directional emission, with very high signal to noise ratios and >50% signal collection efficiency. Considering the easy functionalization of these carbon nano-allotropes, and their high sensitivity; the economical Ag-CNT SPCE platforms can be effectively extended towards sensing applications.

A Binaural CI Research Platform for Oticon Medical SP/XP Implants Enabling ITD/ILD and Variable Rate Processing

PubMed Central

Adiloğlu, K.; Herzke, T.

2015-01-01

We present the first portable, binaural, real-time research platform compatible with Oticon Medical SP and XP generation cochlear implants. The platform consists of (a) a pair of behind-the-ear devices, each containing front and rear calibrated microphones, (b) a four-channel USB analog-to-digital converter, (c) real-time PC-based sound processing software called the Master Hearing Aid, and (d) USB-connected hardware and output coils capable of driving two implants simultaneously. The platform is capable of processing signals from the four microphones simultaneously and producing synchronized binaural cochlear implant outputs that drive two (bilaterally implanted) SP or XP implants. Both audio signal preprocessing algorithms (such as binaural beamforming) and novel binaural stimulation strategies (within the implant limitations) can be programmed by researchers. When the whole research platform is combined with Oticon Medical SP implants, interaural electrode timing can be controlled on individual electrodes to within ±1 µs and interaural electrode energy differences can be controlled to within ±2%. Hence, this new platform is particularly well suited to performing experiments related to interaural time differences in combination with interaural level differences in real-time. The platform also supports instantaneously variable stimulation rates and thereby enables investigations such as the effect of changing the stimulation rate on pitch perception. Because the processing can be changed on the fly, researchers can use this platform to study perceptual changes resulting from different processing strategies acutely. PMID:26721923

A Binaural CI Research Platform for Oticon Medical SP/XP Implants Enabling ITD/ILD and Variable Rate Processing.

PubMed

Backus, B; Adiloğlu, K; Herzke, T

2015-12-30

We present the first portable, binaural, real-time research platform compatible with Oticon Medical SP and XP generation cochlear implants. The platform consists of (a) a pair of behind-the-ear devices, each containing front and rear calibrated microphones, (b) a four-channel USB analog-to-digital converter, (c) real-time PC-based sound processing software called the Master Hearing Aid, and (d) USB-connected hardware and output coils capable of driving two implants simultaneously. The platform is capable of processing signals from the four microphones simultaneously and producing synchronized binaural cochlear implant outputs that drive two (bilaterally implanted) SP or XP implants. Both audio signal preprocessing algorithms (such as binaural beamforming) and novel binaural stimulation strategies (within the implant limitations) can be programmed by researchers. When the whole research platform is combined with Oticon Medical SP implants, interaural electrode timing can be controlled on individual electrodes to within ±1 µs and interaural electrode energy differences can be controlled to within ±2%. Hence, this new platform is particularly well suited to performing experiments related to interaural time differences in combination with interaural level differences in real-time. The platform also supports instantaneously variable stimulation rates and thereby enables investigations such as the effect of changing the stimulation rate on pitch perception. Because the processing can be changed on the fly, researchers can use this platform to study perceptual changes resulting from different processing strategies acutely. © The Author(s) 2015.

Analysis of offshore platforms lifting with fixed pile structure type (fixed platform) based on ASD89

NASA Astrophysics Data System (ADS)

Sugianto, Agus; Indriani, Andi Marini

2017-11-01

Platform construction GTS (Gathering Testing Sattelite) is offshore construction platform with fix pile structure type/fixed platform functioning to support the mining of petroleum exploitation. After construction fabrication process platform was moved to barges, then shipped to the installation site. Moving process is generally done by pull or push based on construction design determined when planning. But at the time of lifting equipment/cranes available in the work area then the moving process can be done by lifting so that moving activity can be implemented more quickly of work. This analysis moving process of GTS platform in a different way that is generally done to GTS platform types by lifting using problem is construction reinforcement required, so the construction can be moved by lifting with analyzing and checking structure working stress that occurs due to construction moving process by lifting AISC code standard and analysis using the SAP2000 structure analysis program. The analysis result showed that existing condition cannot be moved by lifting because stress ratio is above maximum allowable value that is 0.950 (AISC-ASD89). Overstress occurs on the member 295 and 324 with stress ratio value 0.97 and 0.95 so that it is required structural reinforcement. Box plate aplication at both members so that it produces stress ratio values 0.78 at the member 295 and stress ratio of 0.77 at the member 324. These results indicate that the construction have qualified structural reinforcement for being moved by lifting.

Digital microfluidic platform for multiplexing enzyme assays: implications for lysosomal storage disease screening in newborns.

PubMed

Sista, Ramakrishna S; Eckhardt, Allen E; Wang, Tong; Graham, Carrie; Rouse, Jeremy L; Norton, Scott M; Srinivasan, Vijay; Pollack, Michael G; Tolun, Adviye A; Bali, Deeksha; Millington, David S; Pamula, Vamsee K

2011-10-01

Newborn screening for lysosomal storage diseases (LSDs) has been gaining considerable interest owing to the availability of enzyme replacement therapies. We present a digital microfluidic platform to perform rapid, multiplexed enzymatic analysis of acid α-glucosidase (GAA) and acid α-galactosidase to screen for Pompe and Fabry disorders. The results were compared with those obtained using standard fluorometric methods. We performed bench-based, fluorometric enzymatic analysis on 60 deidentified newborn dried blood spots (DBSs), plus 10 Pompe-affected and 11 Fabry-affected samples, at Duke Biochemical Genetics Laboratory using a 3-mm punch for each assay and an incubation time of 20 h. We used a digital microfluidic platform to automate fluorometric enzymatic assays at Advanced Liquid Logic Inc. using extract from a single punch for both assays, with an incubation time of 6 h. Assays were also performed with an incubation time of 1 h. Assay results were generally comparable, although mean enzymatic activity for GAA using microfluidics was approximately 3 times higher than that obtained using bench-based methods, which could be attributed to higher substrate concentration. Clear separation was observed between the normal and affected samples at both 6- and 1-h incubation times using digital microfluidics. A digital microfluidic platform compared favorably with a clinical reference laboratory to perform enzymatic analysis in DBSs for Pompe and Fabry disorders. This platform presents a new technology for a newborn screening laboratory to screen LSDs by fully automating all the liquid-handling operations in an inexpensive system, providing rapid results.

Developing Extracellular Matrix Technology to Treat Retinal or Optic Nerve Injury

PubMed Central

van der Merwe, Yolandi

2015-01-01

Abstract Adult mammalian CNS neurons often degenerate after injury, leading to lost neurologic functions. In the visual system, retinal or optic nerve injury often leads to retinal ganglion cell axon degeneration and irreversible vision loss. CNS axon degeneration is increasingly linked to the innate immune response to injury, which leads to tissue-destructive inflammation and scarring. Extracellular matrix (ECM) technology can reduce inflammation, while increasing functional tissue remodeling, over scarring, in various tissues and organs, including the peripheral nervous system. However, applying ECM technology to CNS injuries has been limited and virtually unstudied in the visual system. Here we discuss advances in deriving fetal CNS-specific ECMs, like fetal porcine brain, retina, and optic nerve, and fetal non-CNS-specific ECMs, like fetal urinary bladder, and the potential for using tissue-specific ECMs to treat retinal or optic nerve injuries in two platforms. The first platform is an ECM hydrogel that can be administered as a retrobulbar, periocular, or even intraocular injection. The second platform is an ECM hydrogel and polymer “biohybrid” sheet that can be readily shaped and wrapped around a nerve. Both platforms can be tuned mechanically and biochemically to deliver factors like neurotrophins, immunotherapeutics, or stem cells. Since clinical CNS therapies often use general anti-inflammatory agents, which can reduce tissue-destructive inflammation but also suppress tissue-reparative immune system functions, tissue-specific, ECM-based devices may fill an important need by providing naturally derived, biocompatible, and highly translatable platforms that can modulate the innate immune response to promote a positive functional outcome. PMID:26478910

Analysis of scalability of high-performance 3D image processing platform for virtual colonoscopy

NASA Astrophysics Data System (ADS)

Yoshida, Hiroyuki; Wu, Yin; Cai, Wenli

2014-03-01

One of the key challenges in three-dimensional (3D) medical imaging is to enable the fast turn-around time, which is often required for interactive or real-time response. This inevitably requires not only high computational power but also high memory bandwidth due to the massive amount of data that need to be processed. For this purpose, we previously developed a software platform for high-performance 3D medical image processing, called HPC 3D-MIP platform, which employs increasingly available and affordable commodity computing systems such as the multicore, cluster, and cloud computing systems. To achieve scalable high-performance computing, the platform employed size-adaptive, distributable block volumes as a core data structure for efficient parallelization of a wide range of 3D-MIP algorithms, supported task scheduling for efficient load distribution and balancing, and consisted of a layered parallel software libraries that allow image processing applications to share the common functionalities. We evaluated the performance of the HPC 3D-MIP platform by applying it to computationally intensive processes in virtual colonoscopy. Experimental results showed a 12-fold performance improvement on a workstation with 12-core CPUs over the original sequential implementation of the processes, indicating the efficiency of the platform. Analysis of performance scalability based on the Amdahl's law for symmetric multicore chips showed the potential of a high performance scalability of the HPC 3DMIP platform when a larger number of cores is available.

Biotechnological advances towards an enhanced peroxidase production in Pichia pastoris.

PubMed

Krainer, Florian W; Gerstmann, Michaela A; Darnhofer, Barbara; Birner-Gruenberger, Ruth; Glieder, Anton

2016-09-10

Horseradish peroxidase (HRP) is a high-demand enzyme for applications in diagnostics, bioremediation, biocatalysis and medicine. Current HRP preparations are isolated from horseradish roots as mixtures of biochemically diverse isoenzymes. Thus, there is a strong need for a recombinant production process enabling a steady supply with enzyme preparations of consistent high quality. However, most current recombinant production systems are limited at titers in the low mg/L range. In this study, we used the well-known yeast Pichia pastoris as host for recombinant HRP production. To enhance recombinant enzyme titers we systematically evaluated engineering approaches on the secretion process, coproduction of helper proteins, and compared expression from the strong methanol-inducible PAOX1 promoter, the strong constitutive PGAP promoter, and a novel bidirectional promoter PHTX1. Ultimately, coproduction of HRP and active Hac1 under PHTX1 control yielded a recombinant HRP titer of 132mg/L after 56h of cultivation in a methanol-independent and easy-to-do bioreactor cultivation process. With regard to the many versatile applications for HRP, the establishment of a microbial host system suitable for efficient recombinant HRP production was highly overdue. The novel HRP production platform in P. pastoris presented in this study sets a new benchmark for this medically relevant enzyme. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

COLDEX-86: Fluid and Electrolyte Changes during Prolonged Cold Water Immersion

DTIC Science & Technology

1990-12-01

4 Urine and blood collections .................. ..................... 5 Sample processing and biochemical analyses...and decaffeinated tea and coffee. Ingestion of fluids was encouraged. After completing the immersion, 16 oz of warm apple or cranberry juice was...day. Sample processing and biochemical analyses. Blood samples (25 ml) were drawn from an antecubital vein with minimum stasis. Each sample was divided

Turbine engine airfoil and platform assembly

DOEpatents

Campbell, Christian X [Oviedo, FL; James, Allister W [Chuluota, FL; Morrison, Jay A [Oviedo, FL

2012-07-31

A turbine airfoil (22A) is formed by a first process using a first material. A platform (30A) is formed by a second process using a second material that may be different from the first material. The platform (30A) is assembled around a shank (23A) of the airfoil. One or more pins (36A) extend from the platform into holes (28) in the shank (23A). The platform may be formed in two portions (32A, 34A) and placed around the shank, enclosing it. The two platform portions may be bonded to each other. Alternately, the platform (30B) may be cast around the shank (23B) using a metal alloy with better castability than that of the blade and shank, which may be specialized for thermal tolerance. The pins (36A-36D) or holes for them do not extend to an outer surface (31) of the platform, avoiding stress concentrations.

Exact Hybrid Particle/Population Simulation of Rule-Based Models of Biochemical Systems

PubMed Central

Stover, Lori J.; Nair, Niketh S.; Faeder, James R.

2014-01-01

Detailed modeling and simulation of biochemical systems is complicated by the problem of combinatorial complexity, an explosion in the number of species and reactions due to myriad protein-protein interactions and post-translational modifications. Rule-based modeling overcomes this problem by representing molecules as structured objects and encoding their interactions as pattern-based rules. This greatly simplifies the process of model specification, avoiding the tedious and error prone task of manually enumerating all species and reactions that can potentially exist in a system. From a simulation perspective, rule-based models can be expanded algorithmically into fully-enumerated reaction networks and simulated using a variety of network-based simulation methods, such as ordinary differential equations or Gillespie's algorithm, provided that the network is not exceedingly large. Alternatively, rule-based models can be simulated directly using particle-based kinetic Monte Carlo methods. This “network-free” approach produces exact stochastic trajectories with a computational cost that is independent of network size. However, memory and run time costs increase with the number of particles, limiting the size of system that can be feasibly simulated. Here, we present a hybrid particle/population simulation method that combines the best attributes of both the network-based and network-free approaches. The method takes as input a rule-based model and a user-specified subset of species to treat as population variables rather than as particles. The model is then transformed by a process of “partial network expansion” into a dynamically equivalent form that can be simulated using a population-adapted network-free simulator. The transformation method has been implemented within the open-source rule-based modeling platform BioNetGen, and resulting hybrid models can be simulated using the particle-based simulator NFsim. Performance tests show that significant memory savings can be achieved using the new approach and a monetary cost analysis provides a practical measure of its utility. PMID:24699269

Exact hybrid particle/population simulation of rule-based models of biochemical systems.

PubMed

Hogg, Justin S; Harris, Leonard A; Stover, Lori J; Nair, Niketh S; Faeder, James R

2014-04-01

Detailed modeling and simulation of biochemical systems is complicated by the problem of combinatorial complexity, an explosion in the number of species and reactions due to myriad protein-protein interactions and post-translational modifications. Rule-based modeling overcomes this problem by representing molecules as structured objects and encoding their interactions as pattern-based rules. This greatly simplifies the process of model specification, avoiding the tedious and error prone task of manually enumerating all species and reactions that can potentially exist in a system. From a simulation perspective, rule-based models can be expanded algorithmically into fully-enumerated reaction networks and simulated using a variety of network-based simulation methods, such as ordinary differential equations or Gillespie's algorithm, provided that the network is not exceedingly large. Alternatively, rule-based models can be simulated directly using particle-based kinetic Monte Carlo methods. This "network-free" approach produces exact stochastic trajectories with a computational cost that is independent of network size. However, memory and run time costs increase with the number of particles, limiting the size of system that can be feasibly simulated. Here, we present a hybrid particle/population simulation method that combines the best attributes of both the network-based and network-free approaches. The method takes as input a rule-based model and a user-specified subset of species to treat as population variables rather than as particles. The model is then transformed by a process of "partial network expansion" into a dynamically equivalent form that can be simulated using a population-adapted network-free simulator. The transformation method has been implemented within the open-source rule-based modeling platform BioNetGen, and resulting hybrid models can be simulated using the particle-based simulator NFsim. Performance tests show that significant memory savings can be achieved using the new approach and a monetary cost analysis provides a practical measure of its utility.

Thermodynamic considerations on Ca2+-induced biochemical reactions in living cells

NASA Astrophysics Data System (ADS)

Lucia, Umberto; Ponzetto, Antonio

2016-02-01

Cells can be regarded as complex engines that execute a series of chemical reactions. Energy transformations, thermo-electro-chemical processes and transport phenomena can occur across cell membranes. Different, related thermo-electro-biochemical behaviour can occur between health and disease states. Analysis of the irreversibility related to ion fluxes can represent a new approach to study and control the biochemical behaviour of living cells.

TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing.

PubMed

Chendrimada, Thimmaiah P; Gregory, Richard I; Kumaraswamy, Easwari; Norman, Jessica; Cooch, Neil; Nishikura, Kazuko; Shiekhattar, Ramin

2005-08-04

MicroRNAs (miRNAs) are generated by a two-step processing pathway to yield RNA molecules of approximately 22 nucleotides that negatively regulate target gene expression at the post-transcriptional level. Primary miRNAs are processed to precursor miRNAs (pre-miRNAs) by the Microprocessor complex. These pre-miRNAs are cleaved by the RNase III Dicer to generate mature miRNAs that direct the RNA-induced silencing complex (RISC) to messenger RNAs with complementary sequence. Here we show that TRBP (the human immunodeficiency virus transactivating response RNA-binding protein), which contains three double-stranded, RNA-binding domains, is an integral component of a Dicer-containing complex. Biochemical analysis of TRBP-containing complexes revealed the association of Dicer-TRBP with Argonaute 2 (Ago2), the catalytic engine of RISC. The physical association of Dicer-TRBP and Ago2 was confirmed after the isolation of the ternary complex using Flag-tagged Ago2 cell lines. In vitro reconstitution assays demonstrated that TRBP is required for the recruitment of Ago2 to the small interfering RNA (siRNA) bound by Dicer. Knockdown of TRBP results in destabilization of Dicer and a consequent loss of miRNA biogenesis. Finally, depletion of the Dicer-TRBP complex via exogenously introduced siRNAs diminished RISC-mediated reporter gene silencing. These results support a role of the Dicer-TRBP complex not only in miRNA processing but also as a platform for RISC assembly.

Novel developments in mobile sensing based on the integration of microfluidic devices and smartphones.

PubMed

Yang, Ke; Peretz-Soroka, Hagit; Liu, Yong; Lin, Francis

2016-03-21

Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS(2)) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS(2) offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS(2) in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS(2) enables applications to remote in-field testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on-chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS(2) by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field.

Novel Developments of Mobile Sensing Based on the Integration of Microfluidic Devices and Smartphone

PubMed Central

Yang, Ke; Peretz-Soroka, Hagit; Liu, Yong; Lin, Francis

2016-01-01

Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS2) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS2 offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS2 in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS2 enables applications to remote infield testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on-chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS2 by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field. PMID:26899264

Mach-Zehnder Interferometer Biochemical Sensor Based on Silicon-on-Insulator Rib Waveguide with Large Cross Section

PubMed Central

Yuan, Dengpeng; Dong, Ying; Liu, Yujin; Li, Tianjian

2015-01-01

A high-sensitivity Mach-Zehnder interferometer (MZI) biochemical sensing platform based on Silicon-in-insulator (SOI) rib waveguide with large cross section is proposed in this paper. Based on the analyses of the evanescent field intensity, the mode polarization and cross section dimensions of the SOI rib waveguide are optimized through finite difference method (FDM) simulation. To realize high-resolution MZI read-out configuration based on the SOI rib waveguide, medium-filled trenches are employed and their performances are simulated through two-dimensional finite-difference-time domain (2D-FDTD) method. With the fundamental EH-polarized mode of the SOI rib waveguide with a total rib height of 10 μm, an outside rib height of 5 μm and a rib width of 2.5 μm at the operating wavelength of 1550 nm, when the length of the sensitive window in the MZI configuration is 10 mm, a homogeneous sensitivity of 7296.6%/refractive index unit (RIU) is obtained. Supposing the resolutions of the photoelectric detectors connected to the output ports are 0.2%, the MZI sensor can achieve a detection limit of 2.74 × 10−6 RIU. Due to high coupling efficiency of SOI rib waveguide with large cross section with standard single-mode glass optical fiber, the proposed MZI sensing platform can be conveniently integrated with optical fiber communication systems and (opto-) electronic systems, and therefore has the potential to realize remote sensing, in situ real-time detecting, and possible applications in the internet of things. PMID:26343678

Deep sequencing of the Mexican avocado transcriptome, an ancient angiosperm with a high content of fatty acids.

PubMed

Ibarra-Laclette, Enrique; Méndez-Bravo, Alfonso; Pérez-Torres, Claudia Anahí; Albert, Victor A; Mockaitis, Keithanne; Kilaru, Aruna; López-Gómez, Rodolfo; Cervantes-Luevano, Jacob Israel; Herrera-Estrella, Luis

2015-08-13

Avocado (Persea americana) is an economically important tropical fruit considered to be a good source of fatty acids. Despite its importance, the molecular and cellular characterization of biochemical and developmental processes in avocado is limited due to the lack of transcriptome and genomic information. The transcriptomes of seeds, roots, stems, leaves, aerial buds and flowers were determined using different sequencing platforms. Additionally, the transcriptomes of three different stages of fruit ripening (pre-climacteric, climacteric and post-climacteric) were also analyzed. The analysis of the RNAseqatlas presented here reveals strong differences in gene expression patterns between different organs, especially between root and flower, but also reveals similarities among the gene expression patterns in other organs, such as stem, leaves and aerial buds (vegetative organs) or seed and fruit (storage organs). Important regulators, functional categories, and differentially expressed genes involved in avocado fruit ripening were identified. Additionally, to demonstrate the utility of the avocado gene expression atlas, we investigated the expression patterns of genes implicated in fatty acid metabolism and fruit ripening. A description of transcriptomic changes occurring during fruit ripening was obtained in Mexican avocado, contributing to a dynamic view of the expression patterns of genes involved in fatty acid biosynthesis and the fruit ripening process.

Handheld 2-channel impedimetric cell counting system with embedded real-time processing

NASA Astrophysics Data System (ADS)

Rottigni, A.; Carminati, M.; Ferrari, G.; Vahey, M. D.; Voldman, J.; Sampietro, M.

2011-05-01

Lab-on-a-chip systems have been attracting a growing attention for the perspective of miniaturization and portability of bio-chemical assays. Here we present a the design and characterization of a miniaturized, USB-powered, self-contained, 2-channel instrument for impedance sensing, suitable for label-free tracking and real-time detection of cells flowing in microfluidic channels. This original circuit features a signal generator based on a direct digital synthesizer, a transimpedance amplifier, an integrated square-wave lock-in coupled to a Σ▵ ADC converter, and a digital processing platform. Real-time automatic peak detection on two channels is implemented in a FPGA. System functionality has been tested with an electronic resistance modulator to simulate 1% impedance variation produced by cells, reaching a time resolution of 50μs (enabling a count rate of 2000 events/s) with an applied voltage as low as 200mV. Biological experiments have been carried out counting yeast cells. Statistical analysis of events is in agreement with the expected amplitude and time distributions. 2-channel yeast counting has been performed with concomitant dielectrophoretic cell separation, showing that this novel and ultra compact sensing system, thanks to the selectivity of the lock-in detector, is compatible with other AC electrical fields applied to the device.

Complete integrability of information processing by biochemical reactions

PubMed Central

Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

2016-01-01

Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling – based on spin systems – has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis–Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy – based on completely integrable hydrodynamic-type systems of PDEs – which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions. PMID:27812018

Complete integrability of information processing by biochemical reactions

NASA Astrophysics Data System (ADS)

Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

2016-11-01

Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling - based on spin systems - has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis-Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy - based on completely integrable hydrodynamic-type systems of PDEs - which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions.

Complete integrability of information processing by biochemical reactions.

PubMed

Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

2016-11-04

Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling - based on spin systems - has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis-Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy - based on completely integrable hydrodynamic-type systems of PDEs - which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions.

Creating A Nationwide Nonpartisan Initiative for Family Caregivers in Political Party Platforms.

PubMed

Scribner, Ben; Lynn, Joanne; Walker, Victoria; Morgan, Les; Montgomery, Anne; Blair, Elizabeth; Baird, Davis; Goldschmidt, Barbara; Kirschenbaum, Naomi

2017-06-01

Policymakers have been slow to support family caregivers, and political agendas mostly fail to address the cost burdens, impact on employment and productivity, and other challenges in taking on long-term care tasks. This project set out to raise policymakers' awareness of family caregivers through proposals to Republican and Democratic party platforms during the 2016 political season. The Family Caregiver Platform Project (FCPP) reviewed the state party platform submission process for Democratic and Republican parties in all 50 states and the District of Columbia. We built a website to make each process understandable by caregiver advocates. We designed model submissions to help volunteers tailor a proposal and recruited caregiver advocates participating in their state process. Finally, we mobilized a ground operation in many states and followed the progress of submissions in each state, as well as the formation of the national platforms. In 39 states, at least one party, Republican or Democrat, hosted a state party platform process. As of September 2016 FCPP volunteers submitted proposals to 29 state parties in 22 states. Family caregiver language was added to eight state party platforms, one state party resolution, two bipartisan legislative resolutions, and one national party platform. The FCPP generated a non-partisan grassroots effort to educate and motivate policymakers to address caregiving issues and solutions. Democratic party leaders provided more opportunities to connect with political leaders, with seven Democratic parties and one Republican party, addressing family caregiver issues in their party platforms. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Mobile magnetic particles as solid-supports for rapid surface-based bioanalysis in continuous flow.

PubMed

Peyman, Sally A; Iles, Alexander; Pamme, Nicole

2009-11-07

An extremely versatile microfluidic device is demonstrated in which multi-step (bio)chemical procedures can be performed in continuous flow. The system operates by generating several co-laminar flow streams, which contain reagents for specific (bio)reactions across a rectangular reaction chamber. Functionalized magnetic microparticles are employed as mobile solid-supports and are pulled from one side of the reaction chamber to the other by use of an external magnetic field. As the particles traverse the co-laminar reagent streams, binding and washing steps are performed on their surface in one operation in continuous flow. The applicability of the platform was first demonstrated by performing a proof-of-principle binding assay between streptavidin coated magnetic particles and biotin in free solution with a limit of detection of 20 ng mL(-1) of free biotin. The system was then applied to a mouse IgG sandwich immunoassay as a first example of a process involving two binding steps and two washing steps, all performed within 60 s, a fraction of the time required for conventional testing.

A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases

PubMed Central

Bradshaw, Niels; Levdikov, Vladimir M; Zimanyi, Christina M; Gaudet, Rachelle; Wilkinson, Anthony J; Losick, Richard

2017-01-01

PP2C phosphatases control biological processes including stress responses, development, and cell division in all kingdoms of life. Diverse regulatory domains adapt PP2C phosphatases to specific functions, but how these domains control phosphatase activity was unknown. We present structures representing active and inactive states of the PP2C phosphatase SpoIIE from Bacillus subtilis. Based on structural analyses and genetic and biochemical experiments, we identify an α-helical switch that shifts a carbonyl oxygen into the active site to coordinate a metal cofactor. Our analysis indicates that this switch is widely conserved among PP2C family members, serving as a platform to control phosphatase activity in response to diverse inputs. Remarkably, the switch is shared with proteasomal proteases, which we identify as evolutionary and structural relatives of PP2C phosphatases. Although these proteases use an unrelated catalytic mechanism, rotation of equivalent helices controls protease activity by movement of the equivalent carbonyl oxygen into the active site. DOI: http://dx.doi.org/10.7554/eLife.26111.001 PMID:28527238

Peptidomics of prolyl endopeptidase in the central nervous system

PubMed Central

Nolte, Whitney M.; Tagore, Debarati M.; Lane, William S.; Saghatelian, Alan

2009-01-01

Prolyl endopeptidase (Prep) is a member of the prolyl peptidase family and is of interest due to its unique biochemistry and connections to cognitive function. Using an unbiased mass spectrometry (MS)-based peptidomics platform, we identified Prep regulated peptides in the central nervous system (CNS) of mice by measuring changes in the peptidome as a function of Prep activity. This approach was validated by the identification of known Prep substrates, such as the neuropeptide substance P and thymosin-β4, the precursor to the bioactive peptide Ac-SDKP. In addition to these known substrates, we also discovered that Prep regulates many additional peptides, including additional bioactive peptides and proline rich peptides (PRPs). Biochemical experiments confirmed that some of these Prep regulated peptides are indeed substrates of the enzyme. Moreover, these experiments also supported the known preference of Prep for shorter peptides, while revealing a previously unknown cleavage site specificity of Prep when processing certain multi-proline containing peptides, including PRPs. The discovery of Prep regulated peptides implicates Prep in new biological pathways and provides insights into the biochemistry of this enzyme. PMID:19911840

Novel Advances in Shotgun Lipidomics for Biology and Medicine

PubMed Central

Wang, Miao; Wang, Chunyan; Han, Rowland H.; Han, Xianlin

2015-01-01

The field of lipidomics, as coined in 2003, has made profound advances and been rapidly expanded. The mass spectrometry-based strategies of this analytical methodology-oriented research discipline for lipid analysis are largely fallen into three categories: direct infusion-based shotgun lipidomics, liquid chromatography-mass spectrometry-based platforms, and matrix-assisted laser desorption/ionization mass spectrometry-based approaches (particularly in imagining lipid distribution in tissues or cells). This review focuses on shotgun lipidomics. After briefly introducing its fundamentals, the major materials of this article cover its recent advances. These include the novel methods of lipid extraction, novel shotgun lipidomics strategies for identification and quantification of previously hardly accessible lipid classes and molecular species including isomers, and novel tools for processing and interpretation of lipidomics data. Representative applications of advanced shotgun lipidomics for biological and biomedical research are also presented in this review. We believe that with these novel advances in shotgun lipidomics, this approach for lipid analysis should become more comprehensive and high throughput, thereby greatly accelerating the lipidomics field to substantiate the aberrant lipid metabolism, signaling, trafficking, and homeostasis under pathological conditions and their underpinning biochemical mechanisms. PMID:26703190

Re-engineering of Bacterial Luciferase; For New Aspects of Bioluminescence.

PubMed

Kim, Da-Som; Choi, Jeong-Ran; Ko, Jeong-Ae; Kim, Kangmin

2018-01-01

Bacterial luminescence is the end-product of biochemical reactions catalyzed by the luciferase enzyme. Nowadays, this fascinating phenomenon has been widely used as reporter and/or sensors to detect a variety of biological and environmental processes. The enhancement or diversification of the luciferase activities will increase the versatility of bacterial luminescence. Here, to establish the strategy for luciferase engineering, we summarized the identity and relevant roles of key amino acid residues modulating luciferase in Vibrio harveyi, a model luminous bacterium. The current opinions on crystal structures and the critical amino acid residues involved in the substrate binding sites and unstructured loop have been delineated. Based on these, the potential target residues and/or parameters for enzyme engineering were also suggested in limited scale. In conclusion, even though the accurate knowledge on the bacterial luciferase is yet to be reported, the structure-guided site-directed mutagenesis approaches targeting the regulatory amino acids will provide a useful platform to re-engineer the bacterial luciferase in the future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Platform C North Arrival

NASA Image and Video Library

2016-08-30

A section of the second half of the C-level platforms, C North, for NASA’s Space Launch System (SLS) rocket, arrives at the agency’s Kennedy Space Center in Florida. The platform was offloaded from a heavy lift transport truck and secured in a staging area in the west parking lot of the Vehicle Assembly Building (VAB). The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft and provide access for testing and processing.

Changes in composition of cuticular biochemicals of the facultatively polygynous ant Petalomyrmex phylax during range expansion in Cameroon with respect to social, spatial and genetic variation.

PubMed

Dalecky, Ambroise; Renucci, Marielle; Tirard, Alain; Debout, Gabriel; Roux, Maurice; Kjellberg, Finn; Provost, Erick

2007-09-01

In social insects, biochemicals found at the surface of the cuticle are involved in the recognition process and in protection against desiccation and pathogens. However, the relative contribution of evolutionary forces in shaping diversity of these biochemicals remains largely unresolved in ants. We determined the composition of epicuticular biochemicals for workers sampled in 12 populations of the ant Petalomyrmex phylax from Cameroon. Genetic variation at 12 microsatellite markers was used to infer population history and to provide null expectations under the neutrality hypothesis. Genetic data suggest a recent southward range expansion of this ant species. Furthermore, there is a decline southward in the numbers of queens present in mature colonies. Here, we contrast the pattern of biochemical variation against genetic, social and spatial parameters. We thus provide the first estimates of the relative contribution of neutral and selective processes on variation of ant cuticular profile. Populations in migration-drift disequilibrium showed reduction of within-population variation for genetic markers as well as for cuticular profiles. In these populations, the cuticular profile became biased towards a limited number of high molecular weight molecules. Within- and among-population biochemical variation was explained by both genetic and social variation and by the spatial distribution of populations. We therefore propose that during range expansion of P. phylax, the composition of epicuticular compounds has been affected by a combination of neutral processes - genetic drift and spatially limited dispersal - and spatially varying selection, social organization and environmental effects.

The Design and Development of Test Platform for Wheat Precision Seeding Based on Image Processing Techniques

NASA Astrophysics Data System (ADS)

Li, Qing; Lin, Haibo; Xiu, Yu-Feng; Wang, Ruixue; Yi, Chuijie

The test platform of wheat precision seeding based on image processing techniques is designed to develop the wheat precision seed metering device with high efficiency and precision. Using image processing techniques, this platform gathers images of seeds (wheat) on the conveyer belt which are falling from seed metering device. Then these data are processed and analyzed to calculate the qualified rate, reseeding rate and leakage sowing rate, etc. This paper introduces the whole structure, design parameters of the platform and hardware & software of the image acquisition system were introduced, as well as the method of seed identification and seed-space measurement using image's threshold and counting the seed's center. By analyzing the experimental result, the measurement error is less than ± 1mm.

Current Challenges in Plant Eco-Metabolomics

PubMed Central

Peters, Kristian; Worrich, Anja; Alka, Oliver; Balcke, Gerd; Bruelheide, Helge; Dietz, Sophie; Dührkop, Kai; Heinig, Uwe; Kücklich, Marlen; Müller, Caroline; Poeschl, Yvonne; Pohnert, Georg; Ruttkies, Christoph; Schweiger, Rabea; Shahaf, Nir; Tortosa, Maria; Ueberschaar, Nico; Velasco, Pablo; Weiß, Brigitte M.; van Dam, Nicole M.

2018-01-01

The relatively new research discipline of Eco-Metabolomics is the application of metabolomics techniques to ecology with the aim to characterise biochemical interactions of organisms across different spatial and temporal scales. Metabolomics is an untargeted biochemical approach to measure many thousands of metabolites in different species, including plants and animals. Changes in metabolite concentrations can provide mechanistic evidence for biochemical processes that are relevant at ecological scales. These include physiological, phenotypic and morphological responses of plants and communities to environmental changes and also interactions with other organisms. Traditionally, research in biochemistry and ecology comes from two different directions and is performed at distinct spatiotemporal scales. Biochemical studies most often focus on intrinsic processes in individuals at physiological and cellular scales. Generally, they take a bottom-up approach scaling up cellular processes from spatiotemporally fine to coarser scales. Ecological studies usually focus on extrinsic processes acting upon organisms at population and community scales and typically study top-down and bottom-up processes in combination. Eco-Metabolomics is a transdisciplinary research discipline that links biochemistry and ecology and connects the distinct spatiotemporal scales. In this review, we focus on approaches to study chemical and biochemical interactions of plants at various ecological levels, mainly plant–organismal interactions, and discuss related examples from other domains. We present recent developments and highlight advancements in Eco-Metabolomics over the last decade from various angles. We further address the five key challenges: (1) complex experimental designs and large variation of metabolite profiles; (2) feature extraction; (3) metabolite identification; (4) statistical analyses; and (5) bioinformatics software tools and workflows. The presented solutions to these challenges will advance connecting the distinct spatiotemporal scales and bridging biochemistry and ecology. PMID:29734799

Observational and numerical evidence for ocean frontogenesis inducing submesoscale processes and impacting biochemistry

NASA Astrophysics Data System (ADS)

Claret, M.; Ruiz, S.; Pascual, A.; Olita, A.; Mahadevan, A.; Tovar, A.; Troupin, C.; Tintore, J.; Capet, A.

2016-02-01

We present the results of ALBOREX, a multi-platform and multi-disciplinary experiment completed in May 2014 as a part of PERSEUS EU funded project. This unique process-oriented experiment in the eastern Alboran Sea (Western Mediterranean) examined mesoscale and submesoscale dynamics at an intense front. The field campaign, conducted during 8 days, included 25 drifters, 2 gliders, 3 Argo floats and one ship (66 CTDs and 500 biochemical samples). The drifters followed coherently an anticyclonic gyre. ADCP data showed consistent patterns with currents up to 1 m/s in the southern part of the domain and Rossby numbers up to 1.5 suggesting significant ageostrophic motion. We show observational evidence for mesoscale frontogenesis produced by the confluence of (fresh) Atlantic Water and the resident (more saline) Mediterranean Water. This confluence resulted in lateral density gradients of the order of 1 kg/m3 in 10 km and associated vertical velocities of about ±20 m/day, diagnosed using the QG Omega equation. However, the vertical velocity is likely underestimated due to unresolved submesoscale processes (<10 km), which are induced by intense mesoscale frontogenesis. In order to assess the role of these submesoscale processes in the frontal vertical transport, a high-resolution Process Ocean Model Study is initialized with hydrographic data (0.5-1 km resolution) from underwater gliders. Numerical results show that observed lateral buoyancy gradients are large enough to trigger submesoscale mixed layer instabilities. The coupling between mesoscale and submesoscale phenomena can explain remarkable subduction events of chlorophyll and oxygen captured by ocean gliders, as well as local increases of primary production.

The research and realization of digital management platform for ultra-precision optical elements within life-cycle

NASA Astrophysics Data System (ADS)

Wang, Juan; Wang, Jian; Li, Lijuan; Zhou, Kun

2014-08-01

In order to solve the information fusion, process integration, collaborative design and manufacturing for ultra-precision optical elements within life-cycle management, this paper presents a digital management platform which is based on product data and business processes by adopting the modern manufacturing technique, information technique and modern management technique. The architecture and system integration of the digital management platform are discussed in this paper. The digital management platform can realize information sharing and interaction for information-flow, control-flow and value-stream from user's needs to offline in life-cycle, and it can also enhance process control, collaborative research and service ability of ultra-precision optical elements.

Evaluation of Algal Biofilms on Indium Tin Oxide (ITO) for Use in Biophotovoltaic Platforms Based on Photosynthetic Performance

PubMed Central

Ng, Fong-Lee; Phang, Siew-Moi; Periasamy, Vengadesh; Yunus, Kamran; Fisher, Adrian C.

2014-01-01

In photosynthesis, a very small amount of the solar energy absorbed is transformed into chemical energy, while the rest is wasted as heat and fluorescence. This excess energy can be harvested through biophotovoltaic platforms to generate electrical energy. In this study, algal biofilms formed on ITO anodes were investigated for use in the algal biophotovoltaic platforms. Sixteen algal strains, comprising local isolates and two diatoms obtained from the Culture Collection of Marine Phytoplankton (CCMP), USA, were screened and eight were selected based on the growth rate, biochemical composition and photosynthesis performance using suspension cultures. Differences in biofilm formation between the eight algal strains as well as their rapid light curve (RLC) generated using a pulse amplitude modulation (PAM) fluorometer, were examined. The RLC provides detailed information on the saturation characteristics of electron transport and overall photosynthetic performance of the algae. Four algal strains, belonging to the Cyanophyta (Cyanobacteria) Synechococcus elongatus (UMACC 105), Spirulina platensis. (UMACC 159) and the Chlorophyta Chlorella vulgaris (UMACC 051), and Chlorella sp. (UMACC 313) were finally selected for investigation using biophotovoltaic platforms. Based on power output per Chl-a content, the algae can be ranked as follows: Synechococcus elongatus (UMACC 105) (6.38×10−5 Wm−2/µgChl-a)>Chlorella vulgaris UMACC 051 (2.24×10−5 Wm−2/µgChl-a)>Chlorella sp.(UMACC 313) (1.43×10−5 Wm−2/µgChl-a)>Spirulina platensis (UMACC 159) (4.90×10−6 Wm−2/µgChl-a). Our study showed that local algal strains have potential for use in biophotovoltaic platforms due to their high photosynthetic performance, ability to produce biofilm and generation of electrical power. PMID:24874081

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

A 250-ton crane is used to lift the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket high above the transfer aisle inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform is being lifted up for transfer into High Bay 3 for installation. The platform will be secured about 86 feet above the VAB floor, on tower E of the high bay. The K work platforms will provide access to the SLS core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

Biochemistry of homologous recombination in Escherichia coli.

PubMed Central

Kowalczykowski, S C; Dixon, D A; Eggleston, A K; Lauder, S D; Rehrauer, W M

1994-01-01

Homologous recombination is a fundamental biological process. Biochemical understanding of this process is most advanced for Escherichia coli. At least 25 gene products are involved in promoting genetic exchange. At present, this includes the RecA, RecBCD (exonuclease V), RecE (exonuclease VIII), RecF, RecG, RecJ, RecN, RecOR, RecQ, RecT, RuvAB, RuvC, SbcCD, and SSB proteins, as well as DNA polymerase I, DNA gyrase, DNA topoisomerase I, DNA ligase, and DNA helicases. The activities displayed by these enzymes include homologous DNA pairing and strand exchange, helicase, branch migration, Holliday junction binding and cleavage, nuclease, ATPase, topoisomerase, DNA binding, ATP binding, polymerase, and ligase, and, collectively, they define biochemical events that are essential for efficient recombination. In addition to these needed proteins, a cis-acting recombination hot spot known as Chi (chi: 5'-GCTGGTGG-3') plays a crucial regulatory function. The biochemical steps that comprise homologous recombination can be formally divided into four parts: (i) processing of DNA molecules into suitable recombination substrates, (ii) homologous pairing of the DNA partners and the exchange of DNA strands, (iii) extension of the nascent DNA heteroduplex; and (iv) resolution of the resulting crossover structure. This review focuses on the biochemical mechanisms underlying these steps, with particular emphases on the activities of the proteins involved and on the integration of these activities into likely biochemical pathways for recombination. Images PMID:7968921

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

Work is underway to secure the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket in High Bay 3 inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform is being secured into position on tower E, about 86 feet above the floor. The K work platforms will provide access to NASA's Space Launch System (SLS) core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

A 250-ton crane is used to lower the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket into High Bay 3 inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform will be secured about 86 feet above the VAB floor, on tower E of the high bay. The K work platforms will provide access to the SLS core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

Integrating the glioblastoma microenvironment into engineered experimental models

PubMed Central

Xiao, Weikun; Sohrabi, Alireza; Seidlits, Stephanie K

2017-01-01

Glioblastoma (GBM) is the most lethal cancer originating in the brain. Its high mortality rate has been attributed to therapeutic resistance and rapid, diffuse invasion – both of which are strongly influenced by the unique microenvironment. Thus, there is a need to develop new models that mimic individual microenvironmental features and are able to provide clinically relevant data. Current understanding of the effects of the microenvironment on GBM progression, established experimental models of GBM and recent developments using bioengineered microenvironments as ex vivo experimental platforms that mimic the biochemical and physical properties of GBM tumors are discussed. PMID:28883992

Calcium and Bone Metabolism During Spaceflight

NASA Technical Reports Server (NTRS)

Smith, Scott M.

2002-01-01

The ability to understand and counteract weightlessness-induced bone loss will be critical for crew health and safety during and after space station or exploration missions lasting months or years, respectively. Until its deorbit in 2001 , the Mir Space Station provided a valuable platform for long-duration space missions and life sciences research. Long-duration flights are critical for studying bone loss, as the 2- to 3-week Space Shuttle flights are not long enough to detect changes in bone mass. This review will describe human spaceflight data, focusing on biochemical surrogates of bone and calcium metabolism. This subject has been reviewed previously. 1-

A Nimbus G pre-launch field experiment in the Gulf of Mexico, October 1977

NASA Technical Reports Server (NTRS)

Vanderpiepen, H.

1977-01-01

A large scale field experiment, which was arranged in support of the Nimbus G - Coastal Zone Color Scanner (CZCS) project was studied. The experiment was to provide three air and two shipborne platforms simultaneously to members of the Nimbus G Experiment Team (NET) and to other scientists in order to collect data from common test sites. Besides establishing fundamental relations between the light in the sea and the biochemical properties of water, the data will be used mainly for the development of algorithms during the prelaunch phase of Nimbus G.

Activity-Based Protein Profiling of Organophosphorus and Thiocarbamate Pesticides Reveals Multiple Serine Hydrolase Targets in Mouse Brain

PubMed Central

NOMURA, DANIEL K.; CASIDA, JOHN E.

2010-01-01

Organophosphorus (OP) and thiocarbamate (TC) agrochemicals are used worldwide as insecticides, herbicides, and fungicides, but their safety assessment in terms of potential off-targets remains incomplete. In this study, we used a chemoproteomic platform, termed activity-based protein profiling, to broadly define serine hydrolase targets in mouse brain of a panel of 29 OP and TC pesticides. Among the secondary targets identified, enzymes involved in degradation of endocannabinoid signaling lipids, monoacylglycerol lipase and fatty acid amide hydrolase, were inhibited by several OP and TC pesticides. Blockade of these two enzymes led to elevations in brain endocannabinoid levels and dysregulated brain arachidonate metabolism. Other secondary targets include enzymes thought to also play important roles in the nervous system and unannotated proteins. This study reveals a multitude of secondary targets for OP and TC pesticides and underscores the utility of chemoproteomic platforms in gaining insights into biochemical pathways that are perturbed by these toxicants. PMID:21341672

Benchmarking a Visual-Basic based multi-component one-dimensional reactive transport modeling tool

NASA Astrophysics Data System (ADS)

Torlapati, Jagadish; Prabhakar Clement, T.

2013-01-01

We present the details of a comprehensive numerical modeling tool, RT1D, which can be used for simulating biochemical and geochemical reactive transport problems. The code can be run within the standard Microsoft EXCEL Visual Basic platform, and it does not require any additional software tools. The code can be easily adapted by others for simulating different types of laboratory-scale reactive transport experiments. We illustrate the capabilities of the tool by solving five benchmark problems with varying levels of reaction complexity. These literature-derived benchmarks are used to highlight the versatility of the code for solving a variety of practical reactive transport problems. The benchmarks are described in detail to provide a comprehensive database, which can be used by model developers to test other numerical codes. The VBA code presented in the study is a practical tool that can be used by laboratory researchers for analyzing both batch and column datasets within an EXCEL platform.

Construction of a Near-Infrared-Activatable Enzyme Platform To Remotely Trigger Intracellular Signal Transduction Using an Upconversion Nanoparticle.

PubMed

Gao, Hua-De; Thanasekaran, Pounraj; Chiang, Chao-Wei; Hong, Jia-Lin; Liu, Yen-Chun; Chang, Yu-Hsu; Lee, Hsien-Ming

2015-07-28

Photoactivatable (caged) bioeffectors provide a way to remotely trigger or disable biochemical pathways in living organisms at a desired time and location with a pulse of light (uncaging), but the phototoxicity of ultraviolet (UV) often limits its application. In this study, we have demonstrated the near-infrared (NIR) photoactivatable enzyme platform using protein kinase A (PKA), an important enzyme in cell biology. We successfully photoactivated PKA using NIR to phosphorylate its substrate, and this induced a downstream cellular response in living cells with high spatiotemporal resolution. In addition, this system allows NIR to selectively activate the caged enzyme immobilized on the nanoparticle surface without activating other caged proteins in the cytosol. This NIR-responsive enzyme-nanoparticle system provides an innovative approach to remote-control proteins and enzymes, which can be used by researchers who need to avoid direct UV irradiation or use UV as a secondary channel to turn on a bioeffector.

Insertion of scFv into the hinge domain of full-length IgG1 monoclonal antibody results in tetravalent bispecific molecule with robust properties.

PubMed

Bezabeh, Binyam; Fleming, Ryan; Fazenbaker, Christine; Zhong, Haihong; Coffman, Karen; Yu, Xiang-Qing; Leow, Ching Ching; Gibson, Nerea; Wilson, Susan; Stover, C Kendall; Wu, Herren; Gao, Changshou; Dimasi, Nazzareno

By simultaneous binding two disease mediators, bispecific antibodies offer the opportunity to broaden the utility of antibody-based therapies. Herein, we describe the design and characterization of Bs4Ab, an innovative and generic bispecific tetravalent antibody platform. The Bs4Ab format comprises a full-length IgG1 monoclonal antibody with a scFv inserted into the hinge domain. The Bs4Ab design demonstrates robust manufacturability as evidenced by MEDI3902, which is currently in clinical development. To further demonstrate the applicability of the Bs4Ab technology, we describe the molecular engineering, biochemical, biophysical, and in vivo characterization of a bispecific tetravalent Bs4Ab that, by simultaneously binding vascular endothelial growth factor and angiopoietin-2, inhibits their function. We also demonstrate that the Bs4Ab platform allows Fc-engineering similar to that achieved with IgG1 antibodies, such as mutations to extend half-life or modulate effector functions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hornemann, Andrea, E-mail: andrea.hornemann@ptb.de; Hoehl, Arne, E-mail: arne.hoehl@ptb.de; Ulm, Gerhard, E-mail: gerhard.ulm@ptb.de

Bio-diagnostic assays of high complexity rely on nanoscaled assay recognition elements that can provide unique selectivity and design-enhanced sensitivity features. High throughput performance requires the simultaneous detection of various analytes combined with appropriate bioassay components. Nanoparticle induced sensitivity enhancement, and subsequent multiplexed capability Surface-Enhanced InfraRed Absorption (SEIRA) assay formats are fitting well these purposes. SEIRA constitutes an ideal platform to isolate the vibrational signatures of targeted bioassay and active molecules. The potential of several targeted biolabels, here fluorophore-labeled antibody conjugates, chemisorbed onto low-cost biocompatible gold nano-aggregates substrates have been explored for their use in assay platforms. Dried films were analyzedmore » by synchrotron radiation based FTIR/SEIRA spectro-microscopy and the resulting complex hyperspectral datasets were submitted to automated statistical analysis, namely Principal Components Analysis (PCA). The relationships between molecular fingerprints were put in evidence to highlight their spectral discrimination capabilities. We demonstrate that robust spectral encoding via SEIRA fingerprints opens up new opportunities for fast, reliable and multiplexed high-end screening not only in biodiagnostics but also in vitro biochemical imaging.« less

Multiple wavelength silicon photonic 200 mm R+D platform for 25Gb/s and above applications

NASA Astrophysics Data System (ADS)

Szelag, B.; Blampey, B.; Ferrotti, T.; Reboud, V.; Hassan, K.; Malhouitre, S.; Grand, G.; Fowler, D.; Brision, S.; Bria, T.; Rabillé, G.; Brianceau, P.; Hartmann, J. M.; Hugues, V.; Myko, A.; Elleboode, F.; Gays, F.; Fédéli, J. M.; Kopp, C.

2016-05-01

A silicon photonics platform that uses a CMOS foundry line is described. Fabrication process is following a modular integration scheme which leads to a flexible platform, allowing different device combinations. A complete device library is demonstrated for 1310 nm applications with state of the art performances. A PDK which includes specific photonic features and which is compatible with commercial EDA tools has been developed allowing an MPW shuttle service. Finally platform evolutions such as device offer extension to 1550 nm or new process modules introduction are presented.

On the Supply Chain Management Supported by E-Commerce Service Platform for Agreement based Circulation of Fruits and Vegetables

NASA Astrophysics Data System (ADS)

Bao, Liwei; Huang, Yuchi; Ma, Zengjun; Zhang, Jie; Lv, Qingchu

According to analysis of the supply chain process of agricultural products, the IT application requirements of the market entities participating in the agreement based circulation of fruits and vegetables have been discussed. The strategy of supply chain management basing on E-commerce service platform for fruits and vegetables has been proposed in this paper. The architecture and function composing of the service platform have been designed and implemented. The platform is constructed on a set of application service modules User can choose some of the application service modules and define them according to the business process. The application service modules chosen and defined by user are integrated as an application service package and applied as management information system of business process. With the E-commerce service platform, the supply chain management for agreement based circulation of agricultural products of vegetables and fruits can be implemented.

Hardware design and implementation of fast DOA estimation method based on multicore DSP

NASA Astrophysics Data System (ADS)

Guo, Rui; Zhao, Yingxiao; Zhang, Yue; Lin, Qianqiang; Chen, Zengping

2016-10-01

In this paper, we present a high-speed real-time signal processing hardware platform based on multicore digital signal processor (DSP). The real-time signal processing platform shows several excellent characteristics including high performance computing, low power consumption, large-capacity data storage and high speed data transmission, which make it able to meet the constraint of real-time direction of arrival (DOA) estimation. To reduce the high computational complexity of DOA estimation algorithm, a novel real-valued MUSIC estimator is used. The algorithm is decomposed into several independent steps and the time consumption of each step is counted. Based on the statistics of the time consumption, we present a new parallel processing strategy to distribute the task of DOA estimation to different cores of the real-time signal processing hardware platform. Experimental results demonstrate that the high processing capability of the signal processing platform meets the constraint of real-time direction of arrival (DOA) estimation.

Platform C South Arrival

NASA Image and Video Library

2016-08-05

A heavy load transport truck from Tillett Heavy Hauling in Titusville, Florida, arrives at the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida, carrying the second section of the first half of the C-level work platforms, C South, for the agency’s Space Launch System (SLS) rocket. The platform will be offloaded in the VAB staging area in the west parking lot. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft and provide access for testing and processing.

Platform C South Arrival

NASA Image and Video Library

2016-08-04

A heavy load transport truck from Tillett Heavy Hauling in Titusville, Florida, arrives at the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida, carrying a section of the first half of the C-level work platforms, C south, for the agency’s Space Launch System (SLS) rocket. The platform will be delivered to the VAB staging area in the west parking lot. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft and provide access for testing and processing.

Mechanical Characterization of Microengineered Epithelial Cysts by Using Atomic Force Microscopy.

PubMed

Shen, Yusheng; Guan, Dongshi; Serien, Daniela; Takeuchi, Shoji; Tong, Penger; Yobas, Levent; Huang, Pingbo

2017-01-24

Most organs contain interconnected tubular tissues that are one-cell-thick, polarized epithelial monolayers enclosing a fluid-filled lumen. Such tissue organization plays crucial roles in developmental and normal physiology, and the proper functioning of these tissues depends on their regulation by complex biochemical perturbations and equally important, but poorly understood, mechanical perturbations. In this study, by combining micropatterning techniques and atomic force microscopy, we developed a simple in vitro experimental platform for characterizing the mechanical properties of the MDCK II cyst, the simplest model of lumen-enclosing epithelial monolayers. By using this platform, we estimated the elasticity of the cyst monolayer and showed that the presence of a luminal space influences cyst mechanics substantially, which could be attributed to polarization and tissue-level coordination. More interestingly, the results from force-relaxation experiments showed that the cysts also displayed tissue-level poroelastic characteristics that differed slightly from those of single cells. Our study provides the first quantitative findings, to our knowledge, on the tissue-level mechanics of well-polarized epithelial cysts and offers new insights into the interplay between cyst mechanics and cyst physiology. Moreover, our simple platform is a potentially useful tool for enhancing the current understanding of cyst mechanics in health and disease. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

A simple and low-cost platform technology for producing pexiganan antimicrobial peptide in E. coli.

PubMed

Zhao, Chun-Xia; Dwyer, Mirjana Dimitrijev; Yu, Alice Lei; Wu, Yang; Fang, Sheng; Middelberg, Anton P J

2015-05-01

Antimicrobial peptides, as a new class of antibiotics, have generated tremendous interest as potential alternatives to classical antibiotics. However, the large-scale production of antimicrobial peptides remains a significant challenge. This paper reports a simple and low-cost chromatography-free platform technology for producing antimicrobial peptides in Escherichia coli (E. coli). A fusion protein comprising a variant of the helical biosurfactant protein DAMP4 and the known antimicrobial peptide pexiganan is designed by joining the two polypeptides, at the DNA level, via an acid-sensitive cleavage site. The resulting DAMP4(var)-pexiganan fusion protein expresses at high level and solubility in recombinant E. coli, and a simple heat-purification method was applied to disrupt cells and deliver high-purity DAMP4(var)-pexiganan protein. Simple acid cleavage successfully separated the DAMP4 variant protein and the antimicrobial peptide. Antimicrobial activity tests confirmed that the bio-produced antimicrobial peptide has the same antimicrobial activity as the equivalent product made by conventional chemical peptide synthesis. This simple and low-cost platform technology can be easily adapted to produce other valuable peptide products, and opens a new manufacturing approach for producing antimicrobial peptides at large scale using the tools and approaches of biochemical engineering. © 2014 Wiley Periodicals, Inc.

Clinical validation of the CHRONIOUS wearable system in patients with chronic disease.

PubMed

Bellos, Christos; Papadopoulos, Athanassios; Rosso, Roberto; Fotiadis, Dimitrios I

2013-01-01

The CHRONIOUS system defines a powerful and easy to use framework which has been designed to provide services to clinicians and their patients suffering from chronic diseases. The system is composed of a wearable shirt that integrate several body sensors, a portable smart device and a central sub-system that is responsible for the long term storage of the collected patient's data. A multi-parametric expert system is developed for the analysis of the collected data using intelligent algorithms and complex techniques. Apart for the vital signals, dietary habits, drug intake, activity data, environmental and biochemical parameters are recorded. The CHRONIOUS platform is validated through clinical trials in several medical centers and patient's home environments recruiting patients suffering from Chronic Obstructive pulmonary disease (COPD) and Chronic Kidney Disease (CKD) diseases. The clinical trials contribute in improving the system's accuracy, while Pulmonologists and Nephrologists experts utilized the CHRONIOUS platform to evaluate its efficiency and performance. The results of the utilization of the system were very encouraging. The CHRONIOUS system has been proven to be a well-validated real-time patient monitoring and supervision platform, providing a useful tool for the clinician and the patient that would contribute to the more effective management of chronic diseases.

Microfabrication of a platform to measure and manipulate the mechanics of engineered microtissues.

PubMed

Ramade, Alexandre; Legant, Wesley R; Picart, Catherine; Chen, Christopher S; Boudou, Thomas

2014-01-01

Engineered tissues can be used to understand fundamental features of biology, develop organotypic in vitro model systems, and as engineered tissue constructs for replacing damaged tissue in vivo. However, a key limitation is an inability to test the wide range of parameters that might impact the engineered tissue in a high-throughput manner and in an environment that mimics the three-dimensional (3D) native architecture. We developed a microfabricated platform to generate arrays of microtissues embedded within 3D micropatterned matrices. Microcantilevers simultaneously constrain microtissue formation and report forces generated by the microtissues in real time, opening the possibility to use high-throughput, low-volume screening for studies on engineered tissues. Thanks to the micrometer scale of the microtissues, this platform is also suitable for high-throughput monitoring of drug-induced effect on architecture and contractility in engineered tissues. Moreover, independent variations of the mechanical stiffness of the cantilevers and collagen matrix allow the measurement and manipulation of the mechanics of the microtissues. Thus, our approach will likely provide valuable opportunities to elucidate how biomechanical, electrical, biochemical, and genetic/epigenetic cues modulate the formation and maturation of 3D engineered tissues. In this chapter, we describe the microfabrication, preparation, and experimental use of such microfabricated tissue gauges. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative immune responses of corals to stressors associated with offshore reef-based tourist platforms

PubMed Central

Lamb, Joleah B; van Oppen, Madeleine J H; Willis, Bette L; Bourne, David G

2015-01-01

Abstract Unravelling the contributions of local anthropogenic and seasonal environmental factors in suppressing the coral immune system is important for prioritizing management actions at reefs exposed to high levels of human activities. Here, we monitor health of the model coral Acropora millepora adjacent to a high-use and an unused reef-based tourist platform, plus a nearby control site without a platform, over 7 months spanning a typical austral summer. Comparisons of temporal patterns in a range of biochemical and genetic immune parameters (Toll-like receptor signalling pathway, lectin–complement system, prophenoloxidase-activating system and green fluorescent protein-like proteins) among healthy, injured and diseased corals revealed that corals exhibit a diverse array of immune responses to environmental and anthropogenic stressors. In healthy corals at the control site, expression of genes involved in the Toll-like receptor signalling pathway (MAPK p38, MEKK1, cFos and ATF4/5) and complement system (C3 and Bf) was modulated by seasonal environmental factors in summer months. Corals at reef platform sites experienced additional stressors over the summer, as evidenced by increased expression of various immune genes, including MAPK p38 and MEKK1. Despite increased expression of immune genes, signs of white syndromes were detected in 31% of study corals near tourist platforms in the warmest summer month. Evidence that colonies developing disease showed reduced expression of genes involved in the complement pathway prior to disease onset suggests that their immune systems may have been compromised. Responses to disease and physical damage primarily involved the melanization cascade and GFP-like proteins, and appeared to be sufficient for recovery when summer heat stress subsided. Overall, seasonal and anthropogenic factors may have interacted synergistically to overwhelm the immune systems of corals near reef platforms, leading to increased disease prevalence in summer at these sites. PMID:27293717

Metal Removal Efficiency And Ecotoxicological Assessment Of Field-Scale Passive Treatment Biochemical Reactors

EPA Science Inventory

Anaerobic biochemical reactors (BCRs) are useful for removing metals from mining-impacted water at remote sites. Removal processes include sorption and precipitation of metal sulfides, carbonates, and hydroxides. A question of interest is whether BCRs remove aquatic toxicity. ...

Production of biofuels and biochemicals by in vitro synthetic biosystems: Opportunities and challenges.

PubMed

Zhang, Yi-Heng Percival

2015-11-15

The largest obstacle to the cost-competitive production of low-value and high-impact biofuels and biochemicals (called biocommodities) is high production costs catalyzed by microbes due to their inherent weaknesses, such as low product yield, slow reaction rate, high separation cost, intolerance to toxic products, and so on. This predominant whole-cell platform suffers from a mismatch between the primary goal of living microbes - cell proliferation and the desired biomanufacturing goal - desired products (not cell mass most times). In vitro synthetic biosystems consist of numerous enzymes as building bricks, enzyme complexes as building modules, and/or (biomimetic) coenzymes, which are assembled into synthetic enzymatic pathways for implementing complicated bioreactions. They emerge as an alternative solution for accomplishing a desired biotransformation without concerns of cell proliferation, complicated cellular regulation, and side-product formation. In addition to the most important advantage - high product yield, in vitro synthetic biosystems feature several other biomanufacturing advantages, such as fast reaction rate, easy product separation, open process control, broad reaction condition, tolerance to toxic substrates or products, and so on. In this perspective review, the general design rules of in vitro synthetic pathways are presented with eight supporting examples: hydrogen, n-butanol, isobutanol, electricity, starch, lactate,1,3-propanediol, and poly-3-hydroxylbutyrate. Also, a detailed economic analysis for enzymatic hydrogen production from carbohydrates is presented to illustrate some advantages of this system and the remaining challenges. Great market potentials will motivate worldwide efforts from multiple disciplines (i.e., chemistry, biology and engineering) to address the remaining obstacles pertaining to cost and stability of enzymes and coenzymes, standardized building parts and modules, biomimetic coenzymes, biosystem optimization, and scale-up, soon. Copyright © 2014 Elsevier Inc. All rights reserved.

Characteristics of produced water discharged to the Gulf of Mexico hypoxiczone.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veil, J. A.; Kimmell, T. A.; Rechner, A. C.

2005-08-24

Each summer, an area of low dissolved oxygen (the hypoxic zone) forms in the shallow nearshore Gulf of Mexico waters from the Mississippi River Delta westward to near the Texas/Louisiana border. Most scientists believe that the leading contributor to the hypoxic zone is input of nutrients (primarily nitrogen and phosphorus compounds) from the Mississippi and Atchafalaya Rivers. The nutrients stimulate growth of phytoplankton. As the phytoplankton subsequently die, they fall to the bottom waters where they are decomposed by microorganisms. The decomposition process consumes oxygen in the bottom waters to create hypoxic conditions. Sources other than the two rivers mentionedmore » above may also contribute significant quantities of oxygen-demanding pollutants. One very visible potential source is the hundreds of offshore oil and gas platforms located within or near the hypoxic zone. Many of these platforms discharge varying volumes of produced water. However, only limited data characterizing oxygen demand and nutrient concentration and loading from offshore produced water discharges have been collected. No comprehensive and coordinated oxygen demand data exist for produced water discharges in the Gulf of Mexico. This report describes the results of a program to sample 50 offshore oil and gas platforms located within the Gulf of Mexico hypoxic zone. The program was conducted in response to a requirement in the U.S. Environmental Protection Agency (EPA) general National Pollutant Discharge Elimination System (NPDES) permit for offshore oil and gas discharges. EPA requested information on the amount of oxygen-demanding substances contained in the produced water discharges. This information is needed as inputs to several water quality models that EPA intends to run to estimate the relative contributions of the produced water discharges to the occurrence of the hypoxic zone. Sixteen platforms were sampled 3 times each at approximately one-month intervals to give an estimate of temporal variability. An additional 34 platforms were sampled one time. The 50 sampled platforms were scattered throughout the hypoxic zone to give an estimate of spatial variability. Each platform was sampled for biochemical oxygen demand (BOD), total organic carbon (TOC), nitrogen (ammonia, nitrate, nitrite, and total Kjeldahl nitrogen [TKN]), and phosphorus (total phosphorus and orthophosphate). In addition to these parameters, each sample was monitored for pH, conductivity, salinity, and temperature. The sampling provided average platform concentrations for each parameter. Table ES-1 shows the mean, median, maximum, and minimum for the sampled parameters. For some of the parameters, the mean is considerably larger than the median, suggesting that one or a few data points are much higher than the rest of the points (outliers). Chapter 4 contains an extensive discussion of outliers and shows how the sample results change if outliers are deleted from consideration. A primary goal of this study is to estimate the mass loading (lb/day) of each of the oxygen-demanding pollutants from the 50 platforms sampled in the study. Loading is calculated by multiplying concentrations by the discharge volume and then by a conversion factor to allow units to match. The loadings calculated in this study of 50 platforms represent a produced water discharge volume of about 176,000 bbl/day. The total amount of produced water generated in the hypoxic zone during the year 2003 was estimated as 508,000 bbl/day. This volume is based on reports by operators to the Minerals Management Service each year. It reflects the volume of produced water that is generated from each lease, not the volume that is discharged from each platform. The mass loadings from offshore oil and gas discharges to the entire hypoxic zone were estimated by multiplying the 50-platform loadings by the ratio of total water generated to 50-platform discharge volume. The loadings estimated for the 50 platforms and for the entire hypoxic zone are shown in Table ES-2. These estimates and the sampling data from 50 platforms represent the most complete and comprehensive effort ever undertaken to characterize the amount and potential sources of the oxygen demand in offshore oil and gas produced water discharges.« less

Distributed Processing of Sentinel-2 Products using the BIGEARTH Platform

NASA Astrophysics Data System (ADS)

Bacu, Victor; Stefanut, Teodor; Nandra, Constantin; Mihon, Danut; Gorgan, Dorian

2017-04-01

The constellation of observational satellites orbiting around Earth is constantly increasing, providing more data that need to be processed in order to extract meaningful information and knowledge from it. Sentinel-2 satellites, part of the Copernicus Earth Observation program, aim to be used in agriculture, forestry and many other land management applications. ESA's SNAP toolbox can be used to process data gathered by Sentinel-2 satellites but is limited to the resources provided by a stand-alone computer. In this paper we present a cloud based software platform that makes use of this toolbox together with other remote sensing software applications to process Sentinel-2 products. The BIGEARTH software platform [1] offers an integrated solution for processing Earth Observation data coming from different sources (such as satellites or on-site sensors). The flow of processing is defined as a chain of tasks based on the WorDeL description language [2]. Each task could rely on a different software technology (such as Grass GIS and ESA's SNAP) in order to process the input data. One important feature of the BIGEARTH platform comes from this possibility of interconnection and integration, throughout the same flow of processing, of the various well known software technologies. All this integration is transparent from the user perspective. The proposed platform extends the SNAP capabilities by enabling specialists to easily scale the processing over distributed architectures, according to their specific needs and resources. The software platform [3] can be used in multiple configurations. In the basic one the software platform runs as a standalone application inside a virtual machine. Obviously in this case the computational resources are limited but it will give an overview of the functionalities of the software platform, and also the possibility to define the flow of processing and later on to execute it on a more complex infrastructure. The most complex and robust configuration is based on cloud computing and allows the installation on a private or public cloud infrastructure. In this configuration, the processing resources can be dynamically allocated and the execution time can be considerably improved by the available virtual resources and the number of parallelizable sequences in the processing flow. The presentation highlights the benefits and issues of the proposed solution by analyzing some significant experimental use cases. Main references for further information: [1] BigEarth project, http://cgis.utcluj.ro/projects/bigearth [2] Constantin Nandra, Dorian Gorgan: "Defining Earth data batch processing tasks by means of a flexible workflow description language", ISPRS Ann. Photogramm. Remote Sens. Spatial Inf. Sci., III-4, 59-66, (2016). [3] Victor Bacu, Teodor Stefanut, Dorian Gorgan, "Adaptive Processing of Earth Observation Data on Cloud Infrastructures Based on Workflow Description", Proceedings of the Intelligent Computer Communication and Processing (ICCP), IEEE-Press, pp.444-454, (2015).

Scalable Parameter Estimation for Genome-Scale Biochemical Reaction Networks

PubMed Central

Kaltenbacher, Barbara; Hasenauer, Jan

2017-01-01

Mechanistic mathematical modeling of biochemical reaction networks using ordinary differential equation (ODE) models has improved our understanding of small- and medium-scale biological processes. While the same should in principle hold for large- and genome-scale processes, the computational methods for the analysis of ODE models which describe hundreds or thousands of biochemical species and reactions are missing so far. While individual simulations are feasible, the inference of the model parameters from experimental data is computationally too intensive. In this manuscript, we evaluate adjoint sensitivity analysis for parameter estimation in large scale biochemical reaction networks. We present the approach for time-discrete measurement and compare it to state-of-the-art methods used in systems and computational biology. Our comparison reveals a significantly improved computational efficiency and a superior scalability of adjoint sensitivity analysis. The computational complexity is effectively independent of the number of parameters, enabling the analysis of large- and genome-scale models. Our study of a comprehensive kinetic model of ErbB signaling shows that parameter estimation using adjoint sensitivity analysis requires a fraction of the computation time of established methods. The proposed method will facilitate mechanistic modeling of genome-scale cellular processes, as required in the age of omics. PMID:28114351

A Review: Some biological effects of high LET radiations

NASA Technical Reports Server (NTRS)

Wiley, A., Jr.

1972-01-01

There are qualitative and quantitative differences in the biological damage observed after exposure to high LET radiation as compared to that caused by low LET radiations. This review is concerned with these differences, which are ultimately reflected at the biochemical, cellular and even whole animal levels. In general, high LET radiations seem to produce biochemical damage which is more severe and possibly less repairable. Experimental data for those effects are presented in terms of biochemical RBE's with consideration of both early and late manifestations. An LET independent process by which significant biochemical damage may result from protons, neutrons and negative pion mesons is discussed.

Graph processing platforms at scale: practices and experiences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Seung-Hwan; Lee, Sangkeun; Brown, Tyler C

2015-01-01

Graph analysis unveils hidden associations of data in many phenomena and artifacts, such as road network, social networks, genomic information, and scientific collaboration. Unfortunately, a wide diversity in the characteristics of graphs and graph operations make it challenging to find a right combination of tools and implementation of algorithms to discover desired knowledge from the target data set. This study presents an extensive empirical study of three representative graph processing platforms: Pegasus, GraphX, and Urika. Each system represents a combination of options in data model, processing paradigm, and infrastructure. We benchmarked each platform using three popular graph operations, degree distribution,more » connected components, and PageRank over a variety of real-world graphs. Our experiments show that each graph processing platform shows different strength, depending the type of graph operations. While Urika performs the best in non-iterative operations like degree distribution, GraphX outputforms iterative operations like connected components and PageRank. In addition, we discuss challenges to optimize the performance of each platform over large scale real world graphs.« less

Infrared and Raman Microscopy in Cell Biology

PubMed Central

Matthäus, Christian; Bird, Benjamin; Miljković, Miloš; Chernenko, Tatyana; Romeo, Melissa; Diem, Max

2009-01-01

This chapter presents novel microscopic methods to monitor cell biological processes of live or fixed cells without the use of any dye, stains, or other contrast agent. These methods are based on spectral techniques that detect inherent spectroscopic properties of biochemical constituents of cells, or parts thereof. Two different modalities have been developed for this task. One of them is infrared micro-spectroscopy, in which an average snapshot of a cell’s biochemical composition is collected at a spatial resolution of typically 25 mm. This technique, which is extremely sensitive and can collect such a snapshot in fractions of a second, is particularly suited for studying gross biochemical changes. The other technique, Raman microscopy (also known as Raman micro-spectroscopy), is ideally suited to study variations of cellular composition on the scale of subcellular organelles, since its spatial resolution is as good as that of fluorescence microscopy. Both techniques exhibit the fingerprint sensitivity of vibrational spectroscopy toward biochemical composition, and can be used to follow a variety of cellular processes. PMID:19118679

CLSI-based transference of the CALIPER database of pediatric reference intervals from Abbott to Beckman, Ortho, Roche and Siemens Clinical Chemistry Assays: direct validation using reference samples from the CALIPER cohort.

PubMed

Estey, Mathew P; Cohen, Ashley H; Colantonio, David A; Chan, Man Khun; Marvasti, Tina Binesh; Randell, Edward; Delvin, Edgard; Cousineau, Jocelyne; Grey, Vijaylaxmi; Greenway, Donald; Meng, Qing H; Jung, Benjamin; Bhuiyan, Jalaluddin; Seccombe, David; Adeli, Khosrow

2013-09-01

The CALIPER program recently established a comprehensive database of age- and sex-stratified pediatric reference intervals for 40 biochemical markers. However, this database was only directly applicable for Abbott ARCHITECT assays. We therefore sought to expand the scope of this database to biochemical assays from other major manufacturers, allowing for a much wider application of the CALIPER database. Based on CLSI C28-A3 and EP9-A2 guidelines, CALIPER reference intervals were transferred (using specific statistical criteria) to assays performed on four other commonly used clinical chemistry platforms including Beckman Coulter DxC800, Ortho Vitros 5600, Roche Cobas 6000, and Siemens Vista 1500. The resulting reference intervals were subjected to a thorough validation using 100 reference specimens (healthy community children and adolescents) from the CALIPER bio-bank, and all testing centers participated in an external quality assessment (EQA) evaluation. In general, the transferred pediatric reference intervals were similar to those established in our previous study. However, assay-specific differences in reference limits were observed for many analytes, and in some instances were considerable. The results of the EQA evaluation generally mimicked the similarities and differences in reference limits among the five manufacturers' assays. In addition, the majority of transferred reference intervals were validated through the analysis of CALIPER reference samples. This study greatly extends the utility of the CALIPER reference interval database which is now directly applicable for assays performed on five major analytical platforms in clinical use, and should permit the worldwide application of CALIPER pediatric reference intervals. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

CLSI-based transference and verification of CALIPER pediatric reference intervals for 29 Ortho VITROS 5600 chemistry assays.

PubMed

Higgins, Victoria; Truong, Dorothy; Woroch, Amy; Chan, Man Khun; Tahmasebi, Houman; Adeli, Khosrow

2018-03-01

Evidence-based reference intervals (RIs) are essential to accurately interpret pediatric laboratory test results. To fill gaps in pediatric RIs, the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) project developed an age- and sex-specific pediatric RI database based on healthy pediatric subjects. Originally established for Abbott ARCHITECT assays, CALIPER RIs were transferred to assays on Beckman, Roche, Siemens, and Ortho analytical platforms. This study provides transferred reference intervals for 29 biochemical assays for the Ortho VITROS 5600 Chemistry System (Ortho). Based on Clinical Laboratory Standards Institute (CLSI) guidelines, a method comparison analysis was performed by measuring approximately 200 patient serum samples using Abbott and Ortho assays. The equation of the line of best fit was calculated and the appropriateness of the linear model was assessed. This equation was used to transfer RIs from Abbott to Ortho assays. Transferred RIs were verified using 84 healthy pediatric serum samples from the CALIPER cohort. RIs for most chemistry analytes successfully transferred from Abbott to Ortho assays. Calcium and CO 2 did not meet statistical criteria for transference (r 2 <0.70). Of the 32 transferred reference intervals, 29 successfully verified with approximately 90% of results from reference samples falling within transferred confidence limits. Transferred RIs for total bilirubin, magnesium, and LDH did not meet verification criteria and are not reported. This study broadens the utility of the CALIPER pediatric RI database to laboratories using Ortho VITROS 5600 biochemical assays. Clinical laboratories should verify CALIPER reference intervals for their specific analytical platform and local population as recommended by CLSI. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Autonomous mobile platform for enhanced situational awareness in Mass Casualty Incidents.

PubMed

Yang, Dongyi; Schafer, James; Wang, Sili; Ganz, Aura

2014-01-01

To enhance the efficiency of the search and rescue process of a Mass Casualty Incident, we introduce a low cost autonomous mobile platform. The mobile platform motion is controlled by an Android Smartphone mounted on a robot. The pictures and video captured by the Smartphone camera can significantly enhance the situational awareness of the incident commander leading to a more efficient search and rescue process. Moreover, the active RFID readers mounted on the mobile platform can improve the localization accuracy of victims in the disaster site in areas where the paramedics are not present, reducing the triage and evacuation time.

Platform C South Arrival

NASA Image and Video Library

2016-08-05

The second section of the first half of the C-level work platforms, C South, for NASA’s Space Launch System (SLS) rocket was offloaded from a heavy transport truck in a staging area on the west side of the Vehicle Assembly Building (VAB) at the agency’s Kennedy Space Center in Florida. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft and provide access for testing and processing.

Future of antibody purification.

PubMed

Low, Duncan; O'Leary, Rhona; Pujar, Narahari S

2007-03-15

Antibody purification seems to be safely ensconced in a platform, now well-established by way of multiple commercialized antibody processes. However, natural evolution compels us to peer into the future. This is driven not only by a large, projected increase in the number of antibody therapies, but also by dramatic improvements in upstream productivity, and process economics. Although disruptive technologies have yet escaped downstream processes, evolution of the so-called platform is already evident in antibody processes in late-stage development. Here we perform a wide survey of technologies that are competing to be part of that platform, and provide our [inherently dangerous] assessment of those that have the most promise.

A midas plugin to enable construction of reproducible web-based image processing pipelines

PubMed Central

Grauer, Michael; Reynolds, Patrick; Hoogstoel, Marion; Budin, Francois; Styner, Martin A.; Oguz, Ipek

2013-01-01

Image processing is an important quantitative technique for neuroscience researchers, but difficult for those who lack experience in the field. In this paper we present a web-based platform that allows an expert to create a brain image processing pipeline, enabling execution of that pipeline even by those biomedical researchers with limited image processing knowledge. These tools are implemented as a plugin for Midas, an open-source toolkit for creating web based scientific data storage and processing platforms. Using this plugin, an image processing expert can construct a pipeline, create a web-based User Interface, manage jobs, and visualize intermediate results. Pipelines are executed on a grid computing platform using BatchMake and HTCondor. This represents a new capability for biomedical researchers and offers an innovative platform for scientific collaboration. Current tools work well, but can be inaccessible for those lacking image processing expertise. Using this plugin, researchers in collaboration with image processing experts can create workflows with reasonable default settings and streamlined user interfaces, and data can be processed easily from a lab environment without the need for a powerful desktop computer. This platform allows simplified troubleshooting, centralized maintenance, and easy data sharing with collaborators. These capabilities enable reproducible science by sharing datasets and processing pipelines between collaborators. In this paper, we present a description of this innovative Midas plugin, along with results obtained from building and executing several ITK based image processing workflows for diffusion weighted MRI (DW MRI) of rodent brain images, as well as recommendations for building automated image processing pipelines. Although the particular image processing pipelines developed were focused on rodent brain MRI, the presented plugin can be used to support any executable or script-based pipeline. PMID:24416016

A midas plugin to enable construction of reproducible web-based image processing pipelines.

PubMed

Grauer, Michael; Reynolds, Patrick; Hoogstoel, Marion; Budin, Francois; Styner, Martin A; Oguz, Ipek

2013-01-01

Image processing is an important quantitative technique for neuroscience researchers, but difficult for those who lack experience in the field. In this paper we present a web-based platform that allows an expert to create a brain image processing pipeline, enabling execution of that pipeline even by those biomedical researchers with limited image processing knowledge. These tools are implemented as a plugin for Midas, an open-source toolkit for creating web based scientific data storage and processing platforms. Using this plugin, an image processing expert can construct a pipeline, create a web-based User Interface, manage jobs, and visualize intermediate results. Pipelines are executed on a grid computing platform using BatchMake and HTCondor. This represents a new capability for biomedical researchers and offers an innovative platform for scientific collaboration. Current tools work well, but can be inaccessible for those lacking image processing expertise. Using this plugin, researchers in collaboration with image processing experts can create workflows with reasonable default settings and streamlined user interfaces, and data can be processed easily from a lab environment without the need for a powerful desktop computer. This platform allows simplified troubleshooting, centralized maintenance, and easy data sharing with collaborators. These capabilities enable reproducible science by sharing datasets and processing pipelines between collaborators. In this paper, we present a description of this innovative Midas plugin, along with results obtained from building and executing several ITK based image processing workflows for diffusion weighted MRI (DW MRI) of rodent brain images, as well as recommendations for building automated image processing pipelines. Although the particular image processing pipelines developed were focused on rodent brain MRI, the presented plugin can be used to support any executable or script-based pipeline.

Platform C South Arrival

NASA Image and Video Library

2016-08-04

A heavy load transport truck from Tillett Heavy Hauling in Titusville, Florida, arrives at the Vehicle Assembly Building (VAB) at NASA’s Kennedy Space Center in Florida, carrying a section of the first half of the C-level work platforms, C South, for the agency’s Space Launch System (SLS) rocket. The platform is being lifted and transferred onto support stands in the VAB staging area in the west parking lot. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to VAB High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft and provide access for testing and processing.

A novel 3D bioprinted flexible and biocompatible hydrogel bioelectronic platform.

PubMed

Agarwala, Shweta; Lee, Jia Min; Ng, Wei Long; Layani, Michael; Yeong, Wai Yee; Magdassi, Shlomo

2018-04-15

Bioelectronics platforms are gaining widespread attention as they provide a template to study the interactions between biological species and electronics. Decoding the effect of the electrical signals on the cells and tissues holds the promise for treating the malignant tissue growth, regenerating organs and engineering new-age medical devices. This work is a step forward in this direction, where bio- and electronic materials co-exist on one platform without any need for post processing. We fabricate a freestanding and flexible hydrogel based platform using 3D bioprinting. The fabrication process is simple, easy and provides a flexible route to print materials with preferred shapes, size and spatial orientation. Through the design of interdigitated electrodes and heating coil, the platform can be tailored to print various circuits for different functionalities. The biocompatibility of the printed platform is tested using C2C12 murine myoblasts cell line. Furthermore, normal human dermal fibroblasts (primary cells) are also seeded on the platform to ascertain the compatibility. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative life cycle assessment of lignocellulosic ethanol production: biochemical versus thermochemical conversion.

PubMed

Mu, Dongyan; Seager, Thomas; Rao, P Suresh; Zhao, Fu

2010-10-01

Lignocellulosic biomass can be converted into ethanol through either biochemical or thermochemical conversion processes. Biochemical conversion involves hydrolysis and fermentation while thermochemical conversion involves gasification and catalytic synthesis. Even though these routes produce comparable amounts of ethanol and have similar energy efficiency at the plant level, little is known about their relative environmental performance from a life cycle perspective. Especially, the indirect impacts, i.e. emissions and resource consumption associated with the production of various process inputs, are largely neglected in previous studies. This article compiles material and energy flow data from process simulation models to develop life cycle inventory and compares the fossil fuel consumption, greenhouse gas emissions, and water consumption of both biomass-to-ethanol production processes. The results are presented in terms of contributions from feedstock, direct, indirect, and co-product credits for four representative biomass feedstocks i.e., wood chips, corn stover, waste paper, and wheat straw. To explore the potentials of the two conversion pathways, different technological scenarios are modeled, including current, 2012 and 2020 technology targets, as well as different production/co-production configurations. The modeling results suggest that biochemical conversion has slightly better performance on greenhouse gas emission and fossil fuel consumption, but that thermochemical conversion has significantly less direct, indirect, and life cycle water consumption. Also, if the thermochemical plant operates as a biorefinery with mixed alcohol co-products separated for chemicals, it has the potential to achieve better performance than biochemical pathway across all environmental impact categories considered due to higher co-product credits associated with chemicals being displaced. The results from this work serve as a starting point for developing full life cycle assessment model that facilitates effective decision-making regarding lignocellulosic ethanol production.

Comparative Life Cycle Assessment of Lignocellulosic Ethanol Production: Biochemical Versus Thermochemical Conversion

NASA Astrophysics Data System (ADS)

Mu, Dongyan; Seager, Thomas; Rao, P. Suresh; Zhao, Fu

2010-10-01

Lignocellulosic biomass can be converted into ethanol through either biochemical or thermochemical conversion processes. Biochemical conversion involves hydrolysis and fermentation while thermochemical conversion involves gasification and catalytic synthesis. Even though these routes produce comparable amounts of ethanol and have similar energy efficiency at the plant level, little is known about their relative environmental performance from a life cycle perspective. Especially, the indirect impacts, i.e. emissions and resource consumption associated with the production of various process inputs, are largely neglected in previous studies. This article compiles material and energy flow data from process simulation models to develop life cycle inventory and compares the fossil fuel consumption, greenhouse gas emissions, and water consumption of both biomass-to-ethanol production processes. The results are presented in terms of contributions from feedstock, direct, indirect, and co-product credits for four representative biomass feedstocks i.e., wood chips, corn stover, waste paper, and wheat straw. To explore the potentials of the two conversion pathways, different technological scenarios are modeled, including current, 2012 and 2020 technology targets, as well as different production/co-production configurations. The modeling results suggest that biochemical conversion has slightly better performance on greenhouse gas emission and fossil fuel consumption, but that thermochemical conversion has significantly less direct, indirect, and life cycle water consumption. Also, if the thermochemical plant operates as a biorefinery with mixed alcohol co-products separated for chemicals, it has the potential to achieve better performance than biochemical pathway across all environmental impact categories considered due to higher co-product credits associated with chemicals being displaced. The results from this work serve as a starting point for developing full life cycle assessment model that facilitates effective decision-making regarding lignocellulosic ethanol production.

The Design of a High Performance Earth Imagery and Raster Data Management and Processing Platform

NASA Astrophysics Data System (ADS)

Xie, Qingyun

2016-06-01

This paper summarizes the general requirements and specific characteristics of both geospatial raster database management system and raster data processing platform from a domain-specific perspective as well as from a computing point of view. It also discusses the need of tight integration between the database system and the processing system. These requirements resulted in Oracle Spatial GeoRaster, a global scale and high performance earth imagery and raster data management and processing platform. The rationale, design, implementation, and benefits of Oracle Spatial GeoRaster are described. Basically, as a database management system, GeoRaster defines an integrated raster data model, supports image compression, data manipulation, general and spatial indices, content and context based queries and updates, versioning, concurrency, security, replication, standby, backup and recovery, multitenancy, and ETL. It provides high scalability using computer and storage clustering. As a raster data processing platform, GeoRaster provides basic operations, image processing, raster analytics, and data distribution featuring high performance computing (HPC). Specifically, HPC features include locality computing, concurrent processing, parallel processing, and in-memory computing. In addition, the APIs and the plug-in architecture are discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Synthetic Biology Research Program, National University of Singapore, Singapore

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fattymore » acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.« less

Stretching Fibroblasts Remodels Fibronectin and Alters Cancer Cell Migration

NASA Astrophysics Data System (ADS)

Ao, Mingfang; Brewer, Bryson M.; Yang, Lijie; Franco Coronel, Omar E.; Hayward, Simon W.; Webb, Donna J.; Li, Deyu

2015-02-01

Most investigations of cancer-stroma interactions have focused on biochemical signaling effects, with much less attention being paid to biophysical factors. In this study, we investigated the role of mechanical stimuli on human prostatic fibroblasts using a microfluidic platform that was adapted for our experiments and further developed for both repeatable performance among multiple assays and for compatibility with high-resolution confocal microscopy. Results show that mechanical stretching of normal tissue-associated fibroblasts (NAFs) alters the structure of secreted fibronectin. Specifically, unstretched NAFs deposit and assemble fibronectin in a random, mesh-like arrangement, while stretched NAFs produce matrix with a more organized, linearly aligned structure. Moreover, the stretched NAFs exhibited an enhanced capability for directing co-cultured cancer cell migration in a persistent manner. Furthermore, we show that stretching NAFs triggers complex biochemical signaling events through the observation of increased expression of platelet derived growth factor receptor α (PDGFRα). A comparison of these behaviors with those of cancer-associated fibroblasts (CAFs) indicates that the observed phenotypes of stretched NAFs are similar to those associated with CAFs, suggesting that mechanical stress is a critical factor in NAF activation and CAF genesis.

Ultralocalized thermal reactions in subnanoliter droplets-in-air.

PubMed

Salm, Eric; Guevara, Carlos Duarte; Dak, Piyush; Dorvel, Brian Ross; Reddy, Bobby; Alam, Muhammad Ashraf; Bashir, Rashid

2013-02-26

Miniaturized laboratory-on-chip systems promise rapid, sensitive, and multiplexed detection of biological samples for medical diagnostics, drug discovery, and high-throughput screening. Within miniaturized laboratory-on-chips, static and dynamic droplets of fluids in different immiscible media have been used as individual vessels to perform biochemical reactions and confine the products. Approaches to perform localized heating of these individual subnanoliter droplets can allow for new applications that require parallel, time-, and space-multiplex reactions on a single integrated circuit. Our method positions droplets on an array of individual silicon microwave heaters on chip to precisely control the temperature of droplets-in-air, allowing us to perform biochemical reactions, including DNA melting and detection of single base mismatches. We also demonstrate that ssDNA probe molecules can be placed on heaters in solution, dried, and then rehydrated by ssDNA target molecules in droplets for hybridization and detection. This platform enables many applications in droplets including hybridization of low copy number DNA molecules, lysing of single cells, interrogation of ligand-receptor interactions, and rapid temperature cycling for amplification of DNA molecules.

Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

PubMed Central

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

2014-01-01

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes. PMID:25566540

Disruption of SMIM1 causes the Vel− blood type

PubMed Central

Ballif, Bryan A; Helias, Virginie; Peyrard, Thierry; Menanteau, Cécile; Saison, Carole; Lucien, Nicole; Bourgouin, Sébastien; Le Gall, Maude; Cartron, Jean-Pierre; Arnaud, Lionel

2013-01-01

Here, we report the biochemical and genetic basis of the Vel blood group antigen, which has been a vexing mystery for decades, especially as anti-Vel regularly causes severe haemolytic transfusion reactions. The protein carrying the Vel blood group antigen was biochemically purified from red blood cell membranes. Mass spectrometry-based de novo peptide sequencing identified this protein to be small integral membrane protein 1 (SMIM1), a previously uncharacterized single-pass membrane protein. Expression of SMIM1 cDNA in Vel− cultured cells generated anti-Vel cell surface reactivity, confirming that SMIM1 encoded the Vel blood group antigen. A cohort of 70 Vel− individuals was found to be uniformly homozygous for a 17 nucleotide deletion in the coding sequence of SMIM1. The genetic homogeneity of the Vel− blood type, likely having a common origin, facilitated the development of two highly specific DNA-based tests for rapid Vel genotyping, which can be easily integrated into blood group genotyping platforms. These results answer a 60-year-old riddle and provide tools of immediate assistance to all clinicians involved in the care of Vel− patients. PMID:23505126

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

Preparations are underway to lift the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket up from High Bay 4 inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform will be lifted up and over the transfer aisle and then lowered into High Bay 3 for installation. It will be secured about 86 feet above the VAB floor, on tower E of the high bay. The K work platforms will provide access to the SLS core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

A 250-ton crane is used to lift the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket up from High Bay 4 inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform will be lifted up and over the transfer aisle and then lowered into High Bay 3 for installation. It will be secured about 86 feet above the VAB floor, on tower E of the high bay. The K work platforms will provide access to the SLS core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

VAB Platform K(2) Lift & Install into Highbay 3

NASA Image and Video Library

2016-03-07

A 250-ton crane is used to lift the second half of the K-level work platforms for NASA’s Space Launch System (SLS) rocket up from High Bay 4 inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platform is being lifted up and over the transfer aisle and will be lowered into High Bay 3 for installation. It will be secured about 86 feet above the VAB floor, on tower E of the high bay. The K work platforms will provide access to the SLS core stage and solid rocket boosters during processing and stacking operations on the mobile launcher. The Ground Systems Development and Operations Program is overseeing upgrades and modifications to High Bay 3 to support processing of the SLS and Orion spacecraft. A total of 10 levels of new platforms, 20 platform halves altogether, will surround the SLS rocket and Orion spacecraft.

A holistic approach to SIM platform and its application to early-warning satellite system

NASA Astrophysics Data System (ADS)

Sun, Fuyu; Zhou, Jianping; Xu, Zheyao

2018-01-01

This study proposes a new simulation platform named Simulation Integrated Management (SIM) for the analysis of parallel and distributed systems. The platform eases the process of designing and testing both applications and architectures. The main characteristics of SIM are flexibility, scalability, and expandability. To improve the efficiency of project development, new models of early-warning satellite system were designed based on the SIM platform. Finally, through a series of experiments, the correctness of SIM platform and the aforementioned early-warning satellite models was validated, and the systematical analyses for the orbital determination precision of the ballistic missile during its entire flight process were presented, as well as the deviation of the launch/landing point. Furthermore, the causes of deviation and prevention methods will be fully explained. The simulation platform and the models will lay the foundations for further validations of autonomy technology in space attack-defense architecture research.

Hierarchical thinking in network biology: the unbiased modularization of biochemical networks.

PubMed

Papin, Jason A; Reed, Jennifer L; Palsson, Bernhard O

2004-12-01

As reconstructed biochemical reaction networks continue to grow in size and scope, there is a growing need to describe the functional modules within them. Such modules facilitate the study of biological processes by deconstructing complex biological networks into conceptually simple entities. The definition of network modules is often based on intuitive reasoning. As an alternative, methods are being developed for defining biochemical network modules in an unbiased fashion. These unbiased network modules are mathematically derived from the structure of the whole network under consideration.

Monitoring adsorption of gold nanoparticles on gold nanodisk array using dark-field hyperspectral microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhao, Fusheng; Zenasni, Oussama; Li, Jingting; Shih, Wei-Chuan

2017-02-01

Localized surface plasmon resonance (LSPR) arises from the interaction of light with noble metal nanoparticles, which induces a collective oscillation in the free electrons. The size and shape of the metallic nanostructure significantly impact LSPR frequency and strength. Nanoplasmonic sensor has become a recent research focus due to its significant signal enhancement and robust signal transduction measured by extinction spectroscopy, fluorescence, Raman scattering, and absorption spectroscopy. Dark-field microscopy, in contrast, reports the scattered photons after light-matter interactions. In this case, the nanoparticles can be understood as dipole radiators whose free electrons oscillate in concert. Coupled with spectroscopy, this platform allows the collection of plasmonically scattered spectra from gold nanoparticles. Plasmonic coupling between electron-beam lithography patterned gold nanodisks (AuND) and colloidal gold nanoparticles (AuNP) can change the plasmonic resonance of the original entities, and can be effectively studied by dark-field hyperspectral microscopy. Typically, a pronounced redshift can be observed when plasmonic coupling occurs. When these nano-entities are functionalized with interactive surface moieties, biochemistry and molecular processes can be studied. In this paper, we will present the capability of assessing the process of immobilizing streptavidin-functionalized AuNPs on an array of biotin-terminated AuNDs. By monitoring changes in the LSPR band of AuNDs, we are able to evaluate similar processes in other molecular systems. In addition, plasmon coupling induced scattering intensity variations can be measured by an electron-multiplied charge-coupled device camera for rapid in situ monitoring. This method can potentially be useful in studying dynamic biophysical and biochemical processes in situ.

Tailoring cyanobacterial cell factory for improved industrial properties.

PubMed

Luan, Guodong; Lu, Xuefeng

Photosynthetic biomanufacturing provides a promising solution for sustainable production of biofuels and biochemicals. Cyanobacteria are among the most promising microbial platforms for the construction of photosynthetic cell factories. Metabolic engineering of cyanobacteria has enabled effective photosynthetic synthesis of diverse natural or non-natural metabolites, while commercialization of photosynthetic biomanufacturing is usually restricted by process and economic feasibilities. In actual outdoor conditions, active cell growth and product synthesis is restricted to narrow light exposure windows of the day-night cycles and is threatened by diverse physical, chemical, and biological environmental stresses. For biomass harvesting and bioproduct recovery, energy and cost consuming processing and equipment is required, which further decreases the economic and environmental competitiveness of the entire process. To facilitate scaled photosynthetic biomanufacturing, lots of efforts have been made to engineer cyanobacterial cell properties required by robust & continual cultivation and convenient & efficient recovery. In this review, we specifically summarized recently reported engineering strategies on optimizing industrial properties of cyanobacterial cells. Through systematically re-editing the metabolism, morphology, mutualism interaction of cyanobacterial chassis cells, the adaptabilities and compatibilities of the cyanobacterial cell factories to the industrial process could be significantly improved. Cell growth and product synthesis of the tailored cyanobacterial cells could be expanded and maintained at night and in stressful environments, while convenient biomass harvesting could also be expected. For developing more feasible cyanobacterial photosynthetic biomanufacturing in large scale, we here propose the importance of tailoring industrial properties of cyanobacteria and outline the directions that should be exploited in the future. Copyright © 2018 Elsevier Inc. All rights reserved.

[Image processing system of visual prostheses based on digital signal processor DM642].

PubMed

Xie, Chengcheng; Lu, Yanyu; Gu, Yun; Wang, Jing; Chai, Xinyu

2011-09-01

This paper employed a DSP platform to create the real-time and portable image processing system, and introduced a series of commonly used algorithms for visual prostheses. The results of performance evaluation revealed that this platform could afford image processing algorithms to be executed in real time.

MATLAB-Based Teaching Modules in Biochemical Engineering

ERIC Educational Resources Information Center

Lee, Kilho; Comolli, Noelle K.; Kelly, William J.; Huang, Zuyi

2015-01-01

Mathematical models play an important role in biochemical engineering. For example, the models developed in the field of systems biology have been used to identify drug targets to treat pathogens such as Pseudomonas aeruginosa in biofilms. In addition, competitive binding models for chromatography processes have been developed to predict expanded…

Mapping of MPEG-4 decoding on a flexible architecture platform

NASA Astrophysics Data System (ADS)

van der Tol, Erik B.; Jaspers, Egbert G.

2001-12-01

In the field of consumer electronics, the advent of new features such as Internet, games, video conferencing, and mobile communication has triggered the convergence of television and computers technologies. This requires a generic media-processing platform that enables simultaneous execution of very diverse tasks such as high-throughput stream-oriented data processing and highly data-dependent irregular processing with complex control flows. As a representative application, this paper presents the mapping of a Main Visual profile MPEG-4 for High-Definition (HD) video onto a flexible architecture platform. A stepwise approach is taken, going from the decoder application toward an implementation proposal. First, the application is decomposed into separate tasks with self-contained functionality, clear interfaces, and distinct characteristics. Next, a hardware-software partitioning is derived by analyzing the characteristics of each task such as the amount of inherent parallelism, the throughput requirements, the complexity of control processing, and the reuse potential over different applications and different systems. Finally, a feasible implementation is proposed that includes amongst others a very-long-instruction-word (VLIW) media processor, one or more RISC processors, and some dedicated processors. The mapping study of the MPEG-4 decoder proves the flexibility and extensibility of the media-processing platform. This platform enables an effective HW/SW co-design yielding a high performance density.

The interactions between soil-biosphere-atmosphere land surface model with a multi-energy balance (ISBA-MEB) option in SURFEXv8 - Part 1: Model description

NASA Astrophysics Data System (ADS)

Boone, Aaron; Samuelsson, Patrick; Gollvik, Stefan; Napoly, Adrien; Jarlan, Lionel; Brun, Eric; Decharme, Bertrand

2017-02-01

Land surface models (LSMs) are pushing towards improved realism owing to an increasing number of observations at the local scale, constantly improving satellite data sets and the associated methodologies to best exploit such data, improved computing resources, and in response to the user community. As a part of the trend in LSM development, there have been ongoing efforts to improve the representation of the land surface processes in the interactions between the soil-biosphere-atmosphere (ISBA) LSM within the EXternalized SURFace (SURFEX) model platform. The force-restore approach in ISBA has been replaced in recent years by multi-layer explicit physically based options for sub-surface heat transfer, soil hydrological processes, and the composite snowpack. The representation of vegetation processes in SURFEX has also become much more sophisticated in recent years, including photosynthesis and respiration and biochemical processes. It became clear that the conceptual limits of the composite soil-vegetation scheme within ISBA had been reached and there was a need to explicitly separate the canopy vegetation from the soil surface. In response to this issue, a collaboration began in 2008 between the high-resolution limited area model (HIRLAM) consortium and Météo-France with the intention to develop an explicit representation of the vegetation in ISBA under the SURFEX platform. A new parameterization has been developed called the ISBA multi-energy balance (MEB) in order to address these issues. ISBA-MEB consists in a fully implicit numerical coupling between a multi-layer physically based snowpack model, a variable-layer soil scheme, an explicit litter layer, a bulk vegetation scheme, and the atmosphere. It also includes a feature that permits a coupling transition of the snowpack from the canopy air to the free atmosphere. It shares many of the routines and physics parameterizations with the standard version of ISBA. This paper is the first of two parts; in part one, the ISBA-MEB model equations, numerical schemes, and theoretical background are presented. In part two (Napoly et al., 2016), which is a separate companion paper, a local scale evaluation of the new scheme is presented along with a detailed description of the new forest litter scheme.

Real-time biochemical sensor based on Raman scattering with CMOS contact imaging.

PubMed

Muyun Cao; Yuhua Li; Yadid-Pecht, Orly

2015-08-01

This work presents a biochemical sensor based on Raman scattering with Complementary metal-oxide-semiconductor (CMOS) contact imaging. This biochemical optical sensor is designed for detecting the concentration of solutions. The system is built with a laser diode, an optical filter, a sample holder and a commercial CMOS sensor. The output of the system is analyzed by an image processing program. The system provides instant measurements with a resolution of 0.2 to 0.4 Mol. This low cost and easy-operated small scale system is useful in chemical, biomedical and environmental labs for quantitative bio-chemical concentration detection with results reported comparable to a highly cost commercial spectrometer.

Micromagnetics on high-performance workstation and mobile computational platforms

NASA Astrophysics Data System (ADS)

Fu, S.; Chang, R.; Couture, S.; Menarini, M.; Escobar, M. A.; Kuteifan, M.; Lubarda, M.; Gabay, D.; Lomakin, V.

2015-05-01

The feasibility of using high-performance desktop and embedded mobile computational platforms is presented, including multi-core Intel central processing unit, Nvidia desktop graphics processing units, and Nvidia Jetson TK1 Platform. FastMag finite element method-based micromagnetic simulator is used as a testbed, showing high efficiency on all the platforms. Optimization aspects of improving the performance of the mobile systems are discussed. The high performance, low cost, low power consumption, and rapid performance increase of the embedded mobile systems make them a promising candidate for micromagnetic simulations. Such architectures can be used as standalone systems or can be built as low-power computing clusters.

An economic analysis of the processing technologies in CDW recycling platforms.

PubMed

Oliveira Neto, Raul; Gastineau, Pascal; Cazacliu, Bogdan Grigore; Le Guen, Lauredan; Paranhos, Régis Sebben; Petter, Carlos Otávio

2017-02-01

This paper proposes an economic analysis of three different types of processing in CDW (construction and demolition waste) recycling platforms, according to the sophistication of the processing technologies (current advanced, advanced and advanced sorting). The methodology that is adopted is in the economic evaluation concept of projects and is classified with a scoping study phase. In these contexts, three levels of CDW processing capabilities for recycling platforms are analyzed (100, 300 and 600 thousand tons per year). This article considers databases obtained from similar projects that have been published in the specialized literature; the data sources are primarily from the European continent. The paper shows that current advanced process has better economic performance, in terms of IRR, related to the other two processes. The IRR associated with advanced and advanced sorting processes could be raised by, (i) higher price of secondary primary material, and/or (ii) higher capacity of platforms, and/or (iii) higher sharing of secondary primary material in the total production. The first two points depend on the market conditions (prices and total quantity of CDW available) and (potential) fiscal or incentive policies. The last one depends on technological progress. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Software Platform for Post-Processing Waveform-Based NDE

NASA Technical Reports Server (NTRS)

Roth, Donald J.; Martin, Richard E.; Seebo, Jeff P.; Trinh, Long B.; Walker, James L.; Winfree, William P.

2007-01-01

Ultrasonic, microwave, and terahertz nondestructive evaluation imaging systems generally require the acquisition of waveforms at each scan point to form an image. For such systems, signal and image processing methods are commonly needed to extract information from the waves and improve resolution of, and highlight, defects in the image. Since some similarity exists for all waveform-based NDE methods, it would seem a common software platform containing multiple signal and image processing techniques to process the waveforms and images makes sense where multiple techniques, scientists, engineers, and organizations are involved. This presentation describes NASA Glenn Research Center's approach in developing a common software platform for processing waveform-based NDE signals and images. This platform is currently in use at NASA Glenn and at Lockheed Martin Michoud Assembly Facility for processing of pulsed terahertz and ultrasonic data. Highlights of the software operation will be given. A case study will be shown for use with terahertz data. The authors also request scientists and engineers who are interested in sharing customized signal and image processing algorithms to contribute to this effort by letting the authors code up and include these algorithms in future releases.

Multi-modal spectroscopic imaging with synchrotron light to study mechanisms of brain disease

NASA Astrophysics Data System (ADS)

Summers, Kelly L.; Fimognari, Nicholas; Hollings, Ashley; Kiernan, Mitchell; Lam, Virginie; Tidy, Rebecca J.; Takechi, Ryu; George, Graham N.; Pickering, Ingrid J.; Mamo, John C.; Harris, Hugh H.; Hackett, Mark J.

2017-04-01

The international health care costs associated with Alzheimer's disease (AD) and dementia have been predicted to reach $2 trillion USD by 2030. As such, there is urgent need to develop new treatments and diagnostic methods to stem an international health crisis. A major limitation to therapy and diagnostic development is the lack of complete understanding about the disease mechanisms. Spectroscopic methods at synchrotron light sources, such as FTIR, XRF, and XAS, offer a "multi-modal imaging platform" to reveal a wealth of important biochemical information in situ within ex vivo tissue sections, to increase our understanding of disease mechanisms.

Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors

PubMed Central

Frett, Brendan; McConnell, Nick; Smith, Catherine C.; Wang, Yuanxiang; Shah, Neil P.; Li, Hong-yu

2015-01-01

The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. PMID:25765758

MVAPACK: A Complete Data Handling Package for NMR Metabolomics

PubMed Central

2015-01-01

Data handling in the field of NMR metabolomics has historically been reliant on either in-house mathematical routines or long chains of expensive commercial software. Thus, while the relatively simple biochemical protocols of metabolomics maintain a low barrier to entry, new practitioners of metabolomics experiments are forced to either purchase expensive software packages or craft their own data handling solutions from scratch. This inevitably complicates the standardization and communication of data handling protocols in the field. We report a newly developed open-source platform for complete NMR metabolomics data handling, MVAPACK, and describe its application on an example metabolic fingerprinting data set. PMID:24576144

Fast and Precise Emulation of Stochastic Biochemical Reaction Networks With Amplified Thermal Noise in Silicon Chips.

PubMed

Kim, Jaewook; Woo, Sung Sik; Sarpeshkar, Rahul

2018-04-01

The analysis and simulation of complex interacting biochemical reaction pathways in cells is important in all of systems biology and medicine. Yet, the dynamics of even a modest number of noisy or stochastic coupled biochemical reactions is extremely time consuming to simulate. In large part, this is because of the expensive cost of random number and Poisson process generation and the presence of stiff, coupled, nonlinear differential equations. Here, we demonstrate that we can amplify inherent thermal noise in chips to emulate randomness physically, thus alleviating these costs significantly. Concurrently, molecular flux in thermodynamic biochemical reactions maps to thermodynamic electronic current in a transistor such that stiff nonlinear biochemical differential equations are emulated exactly in compact, digitally programmable, highly parallel analog "cytomorphic" transistor circuits. For even small-scale systems involving just 80 stochastic reactions, our 0.35-μm BiCMOS chips yield a 311× speedup in the simulation time of Gillespie's stochastic algorithm over COPASI, a fast biochemical-reaction software simulator that is widely used in computational biology; they yield a 15 500× speedup over equivalent MATLAB stochastic simulations. The chip emulation results are consistent with these software simulations over a large range of signal-to-noise ratios. Most importantly, our physical emulation of Poisson chemical dynamics does not involve any inherently sequential processes and updates such that, unlike prior exact simulation approaches, they are parallelizable, asynchronous, and enable even more speedup for larger-size networks.

Analysis of Lipids and Lipid Rafts in Borrelia.

PubMed

Toledo, Alvaro; Huang, Zhen; Benach, Jorge L; London, Erwin

2018-01-01

Lipid rafts are membrane microdomains that are involved in cellular processes such as protein trafficking and signaling processes, and which play a fundamental role in membrane fluidity and budding. The lipid composition of the membrane and the biochemical characteristics of the lipids found within rafts define the ability of cells to form microdomains and compartmentalize the membrane. In this chapter, we describe the biophysical, biochemical, and molecular approaches used to define and characterize lipid rafts in the Lyme disease agent, Borrelia burgdorferi.

Visualization of Proton and Electron Transfer Processes of a Biochemical Reaction by μSR

NASA Astrophysics Data System (ADS)

Kiyotani, Tamiko; Kobayashi, Masayoshi; Tanaka, Ichiro; Niimura, Nobuo

For the last several years, we have discussed and conducted experiments toward realization of visualization of electron and proton transfer process in an enzyme reaction using muon. As the first step for exploring the useful application of the μSR for the biological system, which is "μSR in Biology". A first μSR experiment on biochemical reaction was conducted using the complex of a digestive enzyme, a kind of serine-protease and the inhibitor at J-PARC and PSI.

Molecular Mechanisms of Neuroplasticity: An Expanding Universe.

PubMed

Gulyaeva, N V

2017-03-01

Biochemical processes in synapses and other neuronal compartments underlie neuroplasticity (functional and structural alterations in the brain enabling adaptation to the environment, learning, memory, as well as rehabilitation after brain injury). This basic molecular level of brain plasticity covers numerous specific proteins (enzymes, receptors, structural proteins, etc.) participating in many coordinated and interacting signal and metabolic processes, their modulation forming a molecular basis for brain plasticity. The articles in this issue are focused on different "hot points" in the research area of biochemical mechanisms supporting neuroplasticity.

The geomorphic effect of recent storms - Quantifying meso scale abrasion across a shore platform

NASA Astrophysics Data System (ADS)

Cullen, Niamh; Bourke, Mary; Naylor, Larissa

2017-04-01

Boulder abrasion trails (BATs) are lineations on the surface of rock platforms formed by the movement of traction-load clasts by waves. They have been observed on a variety of platform lithologies, including limestone, granite and basalt. Despite previous reporting of these features, the abrasion styles and geomorphic work done by boulder transport has not been quantified. We present the first quantitative measurement of shore platform erosion by boulder transport during extreme storms that occurred in the winter of 2015-2016. Following two storm events in 2016 we mapped and measured 33 individual BATs on a sandstone platform on the west coast of Ireland. The total (minimum) abraded surface area was 10m2. The total (minimum) volume of material abraded was 0.2m3. In order to test the efficacy of this process during non-storm conditions we conducted field experiments on the same platform. We identified two sites on the platform that were similar, but differed in their intertidal roughness. We installed an RBR solo wave pressure transducer (PT) at 0m OD at both locations to record wave data. We measured platform roughness, determined as the fractal dimension of the platform profiles at both sites. We deployed an array of boulders of known dimensions and mass, parallel to the shoreline at 0.5m intervals from the PTs. The experiments were conducted 1. during relatively calm conditions and 2. during higher energy conditions. Data was collected for one tidal cycle. Any boulder displacement distance and direction was measured and geomorphic effects were documented. We find that BATs are formed under a range of wave energy conditions. Our observations indicate that along the North Atlantic coastline, BATs can occur at a high frequency, only limited by sediment supply. Our data show that abrasion by boulder transport is a potentially significant geomorphological process acting to abrade platforms under contemporary climate conditions. In addition, our preliminary findings suggest that platform roughness exerts a strong influence on wave energy and potential boulder transport. We find that abrasion of the platform surface is a fundamentally important process which contributes to lowering of the platform surface over time.

A compact and versatile microfluidic probe for local processing of tissue sections and biological specimens

NASA Astrophysics Data System (ADS)

Cors, J. F.; Lovchik, R. D.; Delamarche, E.; Kaigala, G. V.

2014-03-01

The microfluidic probe (MFP) is a non-contact, scanning microfluidic technology for local (bio)chemical processing of surfaces based on hydrodynamically confining nanoliter volumes of liquids over tens of micrometers. We present here a compact MFP (cMFP) that can be used on a standard inverted microscope and assist in the local processing of tissue sections and biological specimens. The cMFP has a footprint of 175 × 100 × 140 mm3 and can scan an area of 45 × 45 mm2 on a surface with an accuracy of ±15 μm. The cMFP is compatible with standard surfaces used in life science laboratories such as microscope slides and Petri dishes. For ease of use, we developed self-aligned mounted MFP heads with standardized "chip-to-world" and "chip-to-platform" interfaces. Switching the processing liquid in the flow confinement is performed within 90 s using a selector valve with a dead-volume of approximately 5 μl. We further implemented height-compensation that allows a cMFP head to follow non-planar surfaces common in tissue and cellular ensembles. This was shown by patterning different macroscopic copper-coated topographies with height differences up to 750 μm. To illustrate the applicability to tissue processing, 5 μm thick M000921 BRAF V600E+ melanoma cell blocks were stained with hematoxylin to create contours, lines, spots, gradients of the chemicals, and multiple spots over larger areas. The local staining was performed in an interactive manner using a joystick and a scripting module. The compactness, user-friendliness, and functionality of the cMFP will enable it to be adapted as a standard tool in research, development and diagnostic laboratories, particularly for the interaction with tissues and cells.

The contribution of the Geohazards Exploitation Platform for the GEO Supersites community

NASA Astrophysics Data System (ADS)

Manunta, Michele; Caumont, Hervé; Mora, Oscar; Casu, Francesco; Zinno, Ivana; De Luca, Claudio; Pepe, Susi; Pepe, Antonio; Brito, Fabrice; Romero, Laia; Stumpf, Andre; Malet, Jean-Philippe; Brcic, Ramon; Rodriguez Gonzalez, Fernando; Musacchio, Massimo; Buongiorno, Fabrizia; Briole, Pierre

2016-04-01

The European Space Agency (ESA) initiative for the creation of an ecosystem of Thematic Exploitation Platforms (TEP) focuses on the capitalization of Ground Segment capabilities and ICT technologies to maximize the exploitation of EO data from past and future missions. A TEP refers to a computing platform that complies to a set of exploitation scenarios involving scientific users, data providers and ICT providers, aggregated around an Earth Science thematic area. The Exploitation Platforms are targeted to cover different capacities and they define, implement and validate a platform for effective data exploitation of EO data sources in a given thematic area. In this framework, the Geohazards Thematic Exploitation Platform or Geohazards TEP (GEP) aims at providing on-demand processing services for specific user needs as well as systematic processing services to address the need of the geohazards community for common information layers and, finally, to integrate newly developed processors for scientists and other expert users. The GEP has now on-boarded over 40 European early adopters and will transition during 2016 to pre-operations by developing six new Pilot applications that will significantly augment the Platform's capabilities for systematic production and community building. Each project on the Platform is concerned with either integrating an application, running on demand processing using an application available in the platform or systematically generating a new product collection. The platform will also expand its user base in 2016, to gradually reach a total of about 65 individual users. Under a Consortium lead by Terradue Srl, six new pilot projects have been taken on board: photogrammetric processing using optical EO data with University of Strasbourg (FR), optical based processing method for volcanic hazard monitoring with INGV (IT), systematic generation of deformation time-series with Sentinel-1 data with CNR IREA (IT), systematic processing of Sentinel-1 interferometric imagery with DLR (DE), precise terrain motion mapping with SPN Persistent Scatterers Interferometric chain of Altamira Information (ES) and a campaign to test and exploit GEP applications with the Corinth Rift Laboratory in which Greek and French experts of seismic hazards are engaged. The consortium is in charge of the resources and services management under a sustainable and fair governance model to ensure alignment of the Platform with user community needs, broad collaboration with main data and service providers in the domain, and excellence among user initiatives willing to contribute. In this work we show how the GEO Geohazards Supersites community can fully benefit from availability of an advanced IT infrastructure, where satellite and in-situ data, processing tools and web-based visualization instruments are at the disposal of users to address scientific questions. In particular, we focus on the contributions provided by GEP for the management of EO data, for the implementation of a European e-infrastructure, and for the monitoring and modelling of ground deformations and seismic activity.

ALBOREX: an intensive multi-platform and multidisciplinary experiment in the Alboran Sea

NASA Astrophysics Data System (ADS)

Ruiz, Simón; Pascual, Ananda; Allen, John; Olita, Antonio; Tovar, Antonio; Oguz, Temel; Mahadevan, Amala; Poulain, Pierre; Tintoré, Joaquín

2015-04-01

An intensive multi-platform and multidisciplinary experiment was completed in May 2014 as part of PERSEUS EU Project. 25 drifters, 2 gliders, 3 Argo floats and one ship were dedicated to sample an area of about 50x50 km in the eastern Alboran Sea during one week. The experiment, which also includes 66 CTD stations and 500 water samples (salinity, chlorophyll and nutrients), was designed to capture the intense but transient vertical exchanges associated with mesoscale and submesoscale features. The vertical motion associated with mesoscale and submesoscale features such as ocean eddies, filaments and fronts plays a major role in determining ocean productivity, due to the exchange of properties between the surface and the ocean interior. Understanding the relationship between these physical and biological processes is crucial for predicting the marine ecosystems response to changes in the climate system and to sustainable marine resource management. However, to understand the links between mesoscale and submesoscale features and ecosystem responses, it is necessary to collect data at a range of temporal and spatial scales, and then combine these data with coupled physical and biochemical models. Data from thermosalinograph revealed a sharp surface salinity front with values ranging from 36.6 (Atlantic Waters) to 38.2 (Mediterranean Waters) in conjunction with a filament in temperature. Drifters followed a massive anticyclonic gyre. Near real time data from ADCP showed coherent patterns with currents up to 1m/s. Gliders detected a subduction of chlorophyll located in areas adjacent to the front. We also present results on the horizontal strain rate, relative vorticity and quasi-geostrophic vertical motion to understand the dynamics of this intense ocean front.

Developing a Customized Perfusion Bioreactor Prototype with Controlled Positional Variability in Oxygen Partial Pressure for Bone and Cartilage Tissue Engineering.

PubMed

Lee, Poh Soo; Eckert, Hagen; Hess, Ricarda; Gelinsky, Michael; Rancourt, Derrick; Krawetz, Roman; Cuniberti, Gianaurelio; Scharnweber, Dieter

2017-05-01

Skeletal development is a multistep process that involves the complex interplay of multiple cell types at different stages of development. Besides biochemical and physical cues, oxygen tension also plays a pivotal role in influencing cell fate during skeletal development. At physiological conditions, bone cells generally reside in a relatively oxygenated environment whereas chondrocytes reside in a hypoxic environment. However, it is technically challenging to achieve such defined, yet diverse oxygen distribution on traditional in vitro cultivation platforms. Instead, engineered osteochondral constructs are commonly cultivated in a homogeneous, stable environment. In this study, we describe a customized perfusion bioreactor having stable positional variability in oxygen tension at defined regions. Further, engineered collagen constructs were coaxed into adopting the shape and dimensions of defined cultivation platforms that were precasted in 1.5% agarose bedding. After cultivating murine embryonic stem cells that were embedded in collagen constructs for 50 days, mineralized constructs of specific dimensions and a stable structural integrity were achieved. The end-products, specifically constructs cultivated without chondroitin sulfate A (CSA), showed a significant increase in mechanical stiffness compared with their initial gel-like constructs. More importantly, the localization of osteochondral cell types was specific and corresponded to the oxygen tension gradient generated in the bioreactor. In addition, CSA in complementary with low oxygen tension was also found to be a potent inducer of chondrogenesis in this system. In summary, we have demonstrated a customized perfusion bioreactor prototype that is capable of generating a more dynamic, yet specific cultivation environment that could support propagation of multiple osteochondral lineages within a single engineered construct in vitro. Our system opens up new possibilities for in vitro research on human skeletal development.

Gesture therapy: an upper limb virtual reality-based motor rehabilitation platform.

PubMed

Sucar, Luis Enrique; Orihuela-Espina, Felipe; Velazquez, Roger Luis; Reinkensmeyer, David J; Leder, Ronald; Hernández-Franco, Jorge

2014-05-01

Virtual reality platforms capable of assisting rehabilitation must provide support for rehabilitation principles: promote repetition, task oriented training, appropriate feedback, and a motivating environment. As such, development of these platforms is a complex process which has not yet reached maturity. This paper presents our efforts to contribute to this field, presenting Gesture Therapy, a virtual reality-based platform for rehabilitation of the upper limb. We describe the system architecture and main features of the platform and provide preliminary evidence of the feasibility of the platform in its current status.

The Next Frontier: Quantitative Biochemistry in Living Cells.

PubMed

Honigmann, Alf; Nadler, André

2018-01-09

Researchers striving to convert biology into an exact science foremost rely on structural biology and biochemical reconstitution approaches to obtain quantitative data. However, cell biological research is moving at an ever-accelerating speed into areas where these approaches lose much of their edge. Intrinsically unstructured proteins and biochemical interaction networks composed of interchangeable, multivalent, and unspecific interactions pose unique challenges to quantitative biology, as do processes that occur in discrete cellular microenvironments. Here we argue that a conceptual change in our way of conducting biochemical experiments is required to take on these new challenges. We propose that reconstitution of cellular processes in vitro should be much more focused on mimicking the cellular environment in vivo, an approach that requires detailed knowledge of the material properties of cellular compartments, essentially requiring a material science of the cell. In a similar vein, we suggest that quantitative biochemical experiments in vitro should be accompanied by corresponding experiments in vivo, as many newly relevant cellular processes are highly context-dependent. In essence, this constitutes a call for chemical biologists to convert their discipline from a proof-of-principle science to an area that could rightfully be called quantitative biochemistry in living cells. In this essay, we discuss novel techniques and experimental strategies with regard to their potential to fulfill such ambitious aims.

Cloud Based Earth Observation Data Exploitation Platforms

NASA Astrophysics Data System (ADS)

Romeo, A.; Pinto, S.; Loekken, S.; Marin, A.

2017-12-01

In the last few years data produced daily by several private and public Earth Observation (EO) satellites reached the order of tens of Terabytes, representing for scientists and commercial application developers both a big opportunity for their exploitation and a challenge for their management. New IT technologies, such as Big Data and cloud computing, enable the creation of web-accessible data exploitation platforms, which offer to scientists and application developers the means to access and use EO data in a quick and cost effective way. RHEA Group is particularly active in this sector, supporting the European Space Agency (ESA) in the Exploitation Platforms (EP) initiative, developing technology to build multi cloud platforms for the processing and analysis of Earth Observation data, and collaborating with larger European initiatives such as the European Plate Observing System (EPOS) and the European Open Science Cloud (EOSC). An EP is a virtual workspace, providing a user community with access to (i) large volume of data, (ii) algorithm development and integration environment, (iii) processing software and services (e.g. toolboxes, visualization routines), (iv) computing resources, (v) collaboration tools (e.g. forums, wiki, etc.). When an EP is dedicated to a specific Theme, it becomes a Thematic Exploitation Platform (TEP). Currently, ESA has seven TEPs in a pre-operational phase dedicated to geo-hazards monitoring and prevention, costal zones, forestry areas, hydrology, polar regions, urban areas and food security. On the technology development side, solutions like the multi cloud EO data processing platform provides the technology to integrate ICT resources and EO data from different vendors in a single platform. In particular it offers (i) Multi-cloud data discovery, (ii) Multi-cloud data management and access and (iii) Multi-cloud application deployment. This platform has been demonstrated with the EGI Federated Cloud, Innovation Platform Testbed Poland and the Amazon Web Services cloud. This work will present an overview of the TEPs and the multi-cloud EO data processing platform, and discuss their main achievements and their impacts in the context of distributed Research Infrastructures such as EPOS and EOSC.

SU-D-BRD-02: A Web-Based Image Processing and Plan Evaluation Platform (WIPPEP) for Future Cloud-Based Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chai, X; Liu, L; Xing, L

Purpose: Visualization and processing of medical images and radiation treatment plan evaluation have traditionally been constrained to local workstations with limited computation power and ability of data sharing and software update. We present a web-based image processing and planning evaluation platform (WIPPEP) for radiotherapy applications with high efficiency, ubiquitous web access, and real-time data sharing. Methods: This software platform consists of three parts: web server, image server and computation server. Each independent server communicates with each other through HTTP requests. The web server is the key component that provides visualizations and user interface through front-end web browsers and relay informationmore » to the backend to process user requests. The image server serves as a PACS system. The computation server performs the actual image processing and dose calculation. The web server backend is developed using Java Servlets and the frontend is developed using HTML5, Javascript, and jQuery. The image server is based on open source DCME4CHEE PACS system. The computation server can be written in any programming language as long as it can send/receive HTTP requests. Our computation server was implemented in Delphi, Python and PHP, which can process data directly or via a C++ program DLL. Results: This software platform is running on a 32-core CPU server virtually hosting the web server, image server, and computation servers separately. Users can visit our internal website with Chrome browser, select a specific patient, visualize image and RT structures belonging to this patient and perform image segmentation running Delphi computation server and Monte Carlo dose calculation on Python or PHP computation server. Conclusion: We have developed a webbased image processing and plan evaluation platform prototype for radiotherapy. This system has clearly demonstrated the feasibility of performing image processing and plan evaluation platform through a web browser and exhibited potential for future cloud based radiotherapy.« less

Alterations in metabolic pathways and networks in Alzheimer's disease

PubMed Central

Kaddurah-Daouk, R; Zhu, H; Sharma, S; Bogdanov, M; Rozen, S G; Matson, W; Oki, N O; Motsinger-Reif, A A; Churchill, E; Lei, Z; Appleby, D; Kling, M A; Trojanowski, J Q; Doraiswamy, P M; Arnold, S E

2013-01-01

The pathogenic mechanisms of Alzheimer's disease (AD) remain largely unknown and clinical trials have not demonstrated significant benefit. Biochemical characterization of AD and its prodromal phase may provide new diagnostic and therapeutic insights. We used targeted metabolomics platform to profile cerebrospinal fluid (CSF) from AD (n=40), mild cognitive impairment (MCI, n=36) and control (n=38) subjects; univariate and multivariate analyses to define between-group differences; and partial least square-discriminant analysis models to classify diagnostic groups using CSF metabolomic profiles. A partial correlation network was built to link metabolic markers, protein markers and disease severity. AD subjects had elevated methionine (MET), 5-hydroxyindoleacetic acid (5-HIAA), vanillylmandelic acid, xanthosine and glutathione versus controls. MCI subjects had elevated 5-HIAA, MET, hypoxanthine and other metabolites versus controls. Metabolite ratios revealed changes within tryptophan, MET and purine pathways. Initial pathway analyses identified steps in several pathways that appear altered in AD and MCI. A partial correlation network showed total tau most directly related to norepinephrine and purine pathways; amyloid-β (Ab42) was related directly to an unidentified metabolite and indirectly to 5-HIAA and MET. These findings indicate that MCI and AD are associated with an overlapping pattern of perturbations in tryptophan, tyrosine, MET and purine pathways, and suggest that profound biochemical alterations are linked to abnormal Ab42 and tau metabolism. Metabolomics provides powerful tools to map interlinked biochemical pathway perturbations and study AD as a disease of network failure. PMID:23571809

Elastin-like Protein-Hyaluronic acid (ELP-HA) Hydrogels with Decoupled Mechanical and Biochemical cues for Cartilage Regeneration

PubMed Central

Zhu, Danqing; Wang, Huiyuan; Trinh, Pavin; Heilshorn, Sarah C.; Yang, Fan

2018-01-01

Hyaluronic acid (HA) is a major component of cartilage extracellular matrix and is an attractive material for use as 3D injectable matrices for cartilage regeneration. While previous studies have shown the promise of HA-based hydrogels to support cell-based cartilage formation, varying HA concentration generally led to simultaneous changes in both biochemical cues and stiffness. How cells respond to the change of biochemical content of HA remains largely unknown. Here we report an adaptable elastin-like protein-hyaluronic acid (ELP-HA) hydrogel platform using dynamic covalent chemistry, which allows varyiation of HA concentration without affecting matrix stiffness. ELP-HA hydrogels were created through dynamic hydrazone bonds via the reaction between hydrazine-modified ELP (ELP-HYD) and aldehyde-modified HA (HA-ALD). By tuning the stoichiometric ratio of aldehyde groups to hydrazine groups while maintaining ELP-HYD concentration constant, hydrogels with variable HA concentration (1.5%, 3%, or 5%) (w/v) were fabricated with comparable stiffness. To evaluate the effects of HA concentration on cell-based cartilage regeneration, chondrocytes were encapsulated within ELP-HA hydrogels with varying HA concentration. Increasing HA concentration led to a dose-dependent increase in cartilage-marker gene expression and enhanced sGAG deposition while minimizing undesirable fibrocartilage phenotype. The use of adaptable protein hydrogels formed via dynamic covalent chemistry may be broadly applicable as 3D scaffolds with decoupled niche properties to guide other desirable cell fates and tissue repair. PMID:28268018

Elastin-like protein-hyaluronic acid (ELP-HA) hydrogels with decoupled mechanical and biochemical cues for cartilage regeneration.

PubMed

Zhu, Danqing; Wang, Huiyuan; Trinh, Pavin; Heilshorn, Sarah C; Yang, Fan

2017-05-01

Hyaluronic acid (HA) is a major component of cartilage extracellular matrix and is an attractive material for use as 3D injectable matrices for cartilage regeneration. While previous studies have shown the promise of HA-based hydrogels to support cell-based cartilage formation, varying HA concentration generally led to simultaneous changes in both biochemical cues and stiffness. How cells respond to the change of biochemical content of HA remains largely unknown. Here we report an adaptable elastin-like protein-hyaluronic acid (ELP-HA) hydrogel platform using dynamic covalent chemistry, which allows variation of HA concentration without affecting matrix stiffness. ELP-HA hydrogels were created through dynamic hydrazone bonds via the reaction between hydrazine-modified ELP (ELP-HYD) and aldehyde-modified HA (HA-ALD). By tuning the stoichiometric ratio of aldehyde groups to hydrazine groups while maintaining ELP-HYD concentration constant, hydrogels with variable HA concentration (1.5%, 3%, or 5%) (w/v) were fabricated with comparable stiffness. To evaluate the effects of HA concentration on cell-based cartilage regeneration, chondrocytes were encapsulated within ELP-HA hydrogels with varying HA concentration. Increasing HA concentration led to a dose-dependent increase in cartilage-marker gene expression and enhanced sGAG deposition while minimizing undesirable fibrocartilage phenotype. The use of adaptable protein hydrogels formed via dynamic covalent chemistry may be broadly applicable as 3D scaffolds with decoupled niche properties to guide other desirable cell fates and tissue repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alterations in metabolic pathways and networks in Alzheimer's disease.

PubMed

Kaddurah-Daouk, R; Zhu, H; Sharma, S; Bogdanov, M; Rozen, S G; Matson, W; Oki, N O; Motsinger-Reif, A A; Churchill, E; Lei, Z; Appleby, D; Kling, M A; Trojanowski, J Q; Doraiswamy, P M; Arnold, S E

2013-04-09

The pathogenic mechanisms of Alzheimer's disease (AD) remain largely unknown and clinical trials have not demonstrated significant benefit. Biochemical characterization of AD and its prodromal phase may provide new diagnostic and therapeutic insights. We used targeted metabolomics platform to profile cerebrospinal fluid (CSF) from AD (n=40), mild cognitive impairment (MCI, n=36) and control (n=38) subjects; univariate and multivariate analyses to define between-group differences; and partial least square-discriminant analysis models to classify diagnostic groups using CSF metabolomic profiles. A partial correlation network was built to link metabolic markers, protein markers and disease severity. AD subjects had elevated methionine (MET), 5-hydroxyindoleacetic acid (5-HIAA), vanillylmandelic acid, xanthosine and glutathione versus controls. MCI subjects had elevated 5-HIAA, MET, hypoxanthine and other metabolites versus controls. Metabolite ratios revealed changes within tryptophan, MET and purine pathways. Initial pathway analyses identified steps in several pathways that appear altered in AD and MCI. A partial correlation network showed total tau most directly related to norepinephrine and purine pathways; amyloid-β (Ab42) was related directly to an unidentified metabolite and indirectly to 5-HIAA and MET. These findings indicate that MCI and AD are associated with an overlapping pattern of perturbations in tryptophan, tyrosine, MET and purine pathways, and suggest that profound biochemical alterations are linked to abnormal Ab42 and tau metabolism. Metabolomics provides powerful tools to map interlinked biochemical pathway perturbations and study AD as a disease of network failure.

ESTEST: An Open Science Platform for Electronic Structure Research

ERIC Educational Resources Information Center

Yuan, Gary

2012-01-01

Open science platforms in support of data generation, analysis, and dissemination are becoming indispensible tools for conducting research. These platforms use informatics and information technologies to address significant problems in open science data interoperability, verification & validation, comparison, analysis, post-processing,…

gProcess and ESIP Platforms for Satellite Imagery Processing over the Grid

NASA Astrophysics Data System (ADS)

Bacu, Victor; Gorgan, Dorian; Rodila, Denisa; Pop, Florin; Neagu, Gabriel; Petcu, Dana

2010-05-01

The Environment oriented Satellite Data Processing Platform (ESIP) is developed through the SEE-GRID-SCI (SEE-GRID eInfrastructure for regional eScience) co-funded by the European Commission through FP7 [1]. The gProcess Platform [2] is a set of tools and services supporting the development and the execution over the Grid of the workflow based processing, and particularly the satelite imagery processing. The ESIP [3], [4] is build on top of the gProcess platform by adding a set of satellite image processing software modules and meteorological algorithms. The satellite images can reveal and supply important information on earth surface parameters, climate data, pollution level, weather conditions that can be used in different research areas. Generally, the processing algorithms of the satellite images can be decomposed in a set of modules that forms a graph representation of the processing workflow. Two types of workflows can be defined in the gProcess platform: abstract workflow (PDG - Process Description Graph), in which the user defines conceptually the algorithm, and instantiated workflow (iPDG - instantiated PDG), which is the mapping of the PDG pattern on particular satellite image and meteorological data [5]. The gProcess platform allows the definition of complex workflows by combining data resources, operators, services and sub-graphs. The gProcess platform is developed for the gLite middleware that is available in EGEE and SEE-GRID infrastructures [6]. gProcess exposes the specific functionality through web services [7]. The Editor Web Service retrieves information on available resources that are used to develop complex workflows (available operators, sub-graphs, services, supported resources, etc.). The Manager Web Service deals with resources management (uploading new resources such as workflows, operators, services, data, etc.) and in addition retrieves information on workflows. The Executor Web Service manages the execution of the instantiated workflows on the Grid infrastructure. In addition, this web service monitors the execution and generates statistical data that are important to evaluate performances and to optimize execution. The Viewer Web Service allows access to input and output data. To prove and to validate the utility of the gProcess and ESIP platforms there were developed the GreenView and GreenLand applications. The GreenView related functionality includes the refinement of some meteorological data such as temperature, and the calibration of the satellite images based on field measurements. The GreenLand application performs the classification of the satellite images by using a set of vegetation indices. The gProcess and ESIP platforms are used as well in GiSHEO project [8] to support the processing of Earth Observation data over the Grid in eGLE (GiSHEO eLearning Environment). Experiments of performance assessment were conducted and they have revealed that the workflow-based execution could improve the execution time of a satellite image processing algorithm [9]. It is not a reliable solution to execute all the workflow nodes on different machines. The execution of some nodes can be more time consuming and they will be performed in a longer time than other nodes. The total execution time will be affected because some nodes will slow down the execution. It is important to correctly balance the workflow nodes. Based on some optimization strategy the workflow nodes can be grouped horizontally, vertically or in a hybrid approach. In this way, those operators will be executed on one machine and also the data transfer between workflow nodes will be lower. The dynamic nature of the Grid infrastructure makes it more exposed to the occurrence of failures. These failures can occur at worker node, services availability, storage element, etc. Currently gProcess has support for some basic error prevention and error management solutions. In future, some more advanced error prevention and management solutions will be integrated in the gProcess platform. References [1] SEE-GRID-SCI Project, http://www.see-grid-sci.eu/ [2] Bacu V., Stefanut T., Rodila D., Gorgan D., Process Description Graph Composition by gProcess Platform. HiPerGRID - 3rd International Workshop on High Performance Grid Middleware, 28 May, Bucharest. Proceedings of CSCS-17 Conference, Vol.2., ISSN 2066-4451, pp. 423-430, (2009). [3] ESIP Platform, http://wiki.egee-see.org/index.php/JRA1_Commonalities [4] Gorgan D., Bacu V., Rodila D., Pop Fl., Petcu D., Experiments on ESIP - Environment oriented Satellite Data Processing Platform. SEE-GRID-SCI User Forum, 9-10 Dec 2009, Bogazici University, Istanbul, Turkey, ISBN: 978-975-403-510-0, pp. 157-166 (2009). [5] Radu, A., Bacu, V., Gorgan, D., Diagrammatic Description of Satellite Image Processing Workflow. Workshop on Grid Computing Applications Development (GridCAD) at the SYNASC Symposium, 28 September 2007, Timisoara, IEEE Computer Press, ISBN 0-7695-3078-8, 2007, pp. 341-348 (2007). [6] Gorgan D., Bacu V., Stefanut T., Rodila D., Mihon D., Grid based Satellite Image Processing Platform for Earth Observation Applications Development. IDAACS'2009 - IEEE Fifth International Workshop on "Intelligent Data Acquisition and Advanced Computing Systems: Technology and Applications", 21-23 September, Cosenza, Italy, IEEE Published in Computer Press, 247-252 (2009). [7] Rodila D., Bacu V., Gorgan D., Integration of Satellite Image Operators as Workflows in the gProcess Application. Proceedings of ICCP2009 - IEEE 5th International Conference on Intelligent Computer Communication and Processing, 27-29 Aug, 2009 Cluj-Napoca. ISBN: 978-1-4244-5007-7, pp. 355-358 (2009). [8] GiSHEO consortium, Project site, http://gisheo.info.uvt.ro [9] Bacu V., Gorgan D., Graph Based Evaluation of Satellite Imagery Processing over Grid. ISPDC 2008 - 7th International Symposium on Parallel and Distributed Computing, July 1-5, 2008, Krakow, Poland. IEEE Computer Society 2008, ISBN: 978-0-7695-3472-5, pp. 147-154.

Investigation on biochemical compositional changes during the microbial fermentation process of Fu brick tea by LC-MS based metabolomics.

PubMed

Xu, Jie; Hu, Feng-Lin; Wang, Wei; Wan, Xiao-Chun; Bao, Guan-Hu

2015-11-01

Fu brick tea (FBT) is a unique post-fermented tea product which is fermented with fungi during the manufacturing process. In this study, we investigated the biochemical compositional changes occurring during the microbial fermentation process (MFP) of FBT based on non-targeted LC-MS, which was a comprehensive and unbiased methodology. Our data analysis took a two-phase approach: (1) comparison of FBT with other tea products using PCA analysis to exhibit the characteristic effect of MFP on the formation of Fu brick tea and (2) comparison of tea samples throughout the MFP of FBT to elucidate the possible key metabolic pathways produced by the fungi. Non-targeted LC-MS analysis clearly distinguished FBT with other tea samples and highlighted some interesting metabolic pathways during the MFP including B ring fission catechin. Our study demonstrated that those fungi had a significant influence on the biochemical profiles in the FBT and consequently contributed to its unique quality. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oxygen-controlled automated neural differentiation of mouse embryonic stem cells.

PubMed

Mondragon-Teran, Paul; Tostoes, Rui; Mason, Chris; Lye, Gary J; Veraitch, Farlan S

2013-03-01

Automation and oxygen tension control are two tools that provide significant improvements to the reproducibility and efficiency of stem cell production processes. the aim of this study was to establish a novel automation platform capable of controlling oxygen tension during both the cell-culture and liquid-handling steps of neural differentiation processes. We built a bespoke automation platform, which enclosed a liquid-handling platform in a sterile, oxygen-controlled environment. An airtight connection was used to transfer cell culture plates to and from an automated oxygen-controlled incubator. Our results demonstrate that our system yielded comparable cell numbers, viabilities, metabolism profiles and differentiation efficiencies when compared with traditional manual processes. Interestingly, eliminating exposure to ambient conditions during the liquid-handling stage resulted in significant improvements in the yield of MAP2-positive neural cells, indicating that this level of control can improve differentiation processes. This article describes, for the first time, an automation platform capable of maintaining oxygen tension control during both the cell-culture and liquid-handling stages of a 2D embryonic stem cell differentiation process.

Application of online measures to monitor and evaluate multiplatform fusion performance

NASA Astrophysics Data System (ADS)

Stubberud, Stephen C.; Kowalski, Charlene; Klamer, Dale M.

1999-07-01

A primary concern of multiplatform data fusion is assessing the quality and utility of data shared among platforms. Constraints such as platform and sensor capability and task load necessitate development of an on-line system that computes a metric to determine which other platform can provide the best data for processing. To determine data quality, we are implementing an approach based on entropy coupled with intelligent agents. To determine data quality, we are implementing an approach based on entropy coupled with intelligent agents. Entropy measures quality of processed information such as localization, classification, and ambiguity in measurement-to-track association. Lower entropy scores imply less uncertainty about a particular target. When new information is provided, we compuete the level of improvement a particular track obtains from one measurement to another. The measure permits us to evaluate the utility of the new information. We couple entropy with intelligent agents that provide two main data gathering functions: estimation of another platform's performance and evaluation of the new measurement data's quality. Both functions result from the entropy metric. The intelligent agent on a platform makes an estimate of another platform's measurement and provides it to its own fusion system, which can then incorporate it, for a particular target. A resulting entropy measure is then calculated and returned to its own agent. From this metric, the agent determines a perceived value of the offboard platform's measurement. If the value is satisfactory, the agent requests the measurement from the other platform, usually by interacting with the other platform's agent. Once the actual measurement is received, again entropy is computed and the agent assesses its estimation process and refines it accordingly.

Effects of Short-Period Whole-Body Vibration of 20 Hz on Selected Blood Biomarkers in Wistar Rats.

PubMed

Monteiro, Milena de Oliveira Bravo; de Sá-Caputo, Danúbia da Cunha; Carmo, Fernanda Santos do; Bernardo, Raquel Mattos; Pacheco, Raphaelle; Arnóbio, Adriano; Guimarães, Carlos Alberto Sampaio; Bernardo, Luciana Camargo; Santos-Filho, Sebastião David; Asad, Nasser Ribeiro; Unger, Marianne; Marin, Pedro Jesus; Bernardo-Filho, Mario

2015-08-31

There is a growing interest in the use of vibration generated by oscillating/vibratory platforms - also known as whole-body vibration (WBV) - for achieving therapeutic, preventative and/or physical performance goals. This study investigated the effects of vibration generated by an oscillating platform on the concentration of blood biomarkers in rats. Wistar rats (n = 8) were divided in 2 groups, sedated and individually positioned on an oscillating platform. The experimental group (EG) was subjected to vibrations of 20 Hz for one min per day for one week while the control group (CG) experienced no vibration. Samples of heparinized whole blood were drawn by cardiac puncture for biochemical analysis. Concentrations of total cholesterol, triglycerides, HDL, LDL, VLDL, glucose, CK, albumin, alkaline phosphates, TGP, TGO, γGT, lipase, amylase, urea and creatinine were determined. White blood cell count and a platelet hemogram were also performed. Following seven sessions of exposure to the vibration, a significant (P < 0.05) reduction in γGT, VLDL and leukocytes was found. A weekly 1-min/day exposure of 20 Hz vibration can was shown to alter the concentrations of selected blood biomarkers in rats. The action mechanism associated with these effects seems highly complex, but the findings might contribute to the understanding of these mechanisms related to the exposure to 20 Hz vibration.

Dip-pen nanolithography on (bio)reactive monolayer and block-copolymer platforms: deposition of lines of single macromolecules.

PubMed

Salazar, Ramon B; Shovsky, Alexander; Schönherr, Holger; Vancso, G Julius

2006-11-01

The application of atomic force microscopy (AFM) tip-mediated molecular transfer (dip-pen nanolithography or DPN) to fabricate nanopatterned (bio)reactive platforms based on dendrimers on reactive self-assembled monolayer (SAM) and polymer thin films is discussed. The transfer of high-molar-mass polyamidoamine (PAMAM) dendrimers (generation 5) and the rapid in situ covalent attachment of the deposited adsorbates onto reactive N-hydroxysuccinimide (NHS) terminated SAMs on gold and NHS-activated polystyrene-block-poly(tert-butyl acrylate) (PS(690)-b-PtBA(1210)) block copolymer thin films were investigated as strategies to suppress line broadening by surface diffusion in DPN. By exploiting carefully controlled environmental conditions (such as temperature and relative humidity), scan rates, and in particular the covalent attachment of the dendrimers to the reactive films, the observed line broadening and hence the lateral diffusion of dendrimers was substantially less pronounced compared to that observed with DPN of thiols on gold. By this method, high-definition patterns of dendrimers were conveniently fabricated down to 30-nm length scales. The presence of primary amino groups in the deposited dendrimers ultimately offers the possibility to anchor biochemically relevant molecules, such as proteins and polypeptides, to these nanostructured platforms for a wide range of possible applications in the life sciences and in particular for the investigation of controlled cell-surface interactions.

Dose-Escalated Robotic SBRT for Stage I–II Prostate Cancer

PubMed Central

Meier, Robert

2015-01-01

Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I–II prostate cancer. PMID:25905037

Multidimensional biochemical information processing of dynamical patterns

NASA Astrophysics Data System (ADS)

Hasegawa, Yoshihiko

2018-02-01

Cells receive signaling molecules by receptors and relay information via sensory networks so that they can respond properly depending on the type of signal. Recent studies have shown that cells can extract multidimensional information from dynamical concentration patterns of signaling molecules. We herein study how biochemical systems can process multidimensional information embedded in dynamical patterns. We model the decoding networks by linear response functions, and optimize the functions with the calculus of variations to maximize the mutual information between patterns and output. We find that, when the noise intensity is lower, decoders with different linear response functions, i.e., distinct decoders, can extract much information. However, when the noise intensity is higher, distinct decoders do not provide the maximum amount of information. This indicates that, when transmitting information by dynamical patterns, embedding information in multiple patterns is not optimal when the noise intensity is very large. Furthermore, we explore the biochemical implementations of these decoders using control theory and demonstrate that these decoders can be implemented biochemically through the modification of cascade-type networks, which are prevalent in actual signaling pathways.

Optimal Cytoplasmic Transport in Viral Infections

PubMed Central

D'Orsogna, Maria R.; Chou, Tom

2009-01-01

For many viruses, the ability to infect eukaryotic cells depends on their transport through the cytoplasm and across the nuclear membrane of the host cell. During this journey, viral contents are biochemically processed into complexes capable of both nuclear penetration and genomic integration. We develop a stochastic model of viral entry that incorporates all relevant aspects of transport, including convection along microtubules, biochemical conversion, degradation, and nuclear entry. Analysis of the nuclear infection probabilities in terms of the transport velocity, degradation, and biochemical conversion rates shows how certain values of key parameters can maximize the nuclear entry probability of the viral material. The existence of such “optimal” infection scenarios depends on the details of the biochemical conversion process and implies potentially counterintuitive effects in viral infection, suggesting new avenues for antiviral treatment. Such optimal parameter values provide a plausible transport-based explanation of the action of restriction factors and of experimentally observed optimal capsid stability. Finally, we propose a new interpretation of how genetic mutations unrelated to the mechanism of drug action may nonetheless confer novel types of overall drug resistance. PMID:20046829

Multidimensional biochemical information processing of dynamical patterns.

PubMed

Hasegawa, Yoshihiko

2018-02-01

Cells receive signaling molecules by receptors and relay information via sensory networks so that they can respond properly depending on the type of signal. Recent studies have shown that cells can extract multidimensional information from dynamical concentration patterns of signaling molecules. We herein study how biochemical systems can process multidimensional information embedded in dynamical patterns. We model the decoding networks by linear response functions, and optimize the functions with the calculus of variations to maximize the mutual information between patterns and output. We find that, when the noise intensity is lower, decoders with different linear response functions, i.e., distinct decoders, can extract much information. However, when the noise intensity is higher, distinct decoders do not provide the maximum amount of information. This indicates that, when transmitting information by dynamical patterns, embedding information in multiple patterns is not optimal when the noise intensity is very large. Furthermore, we explore the biochemical implementations of these decoders using control theory and demonstrate that these decoders can be implemented biochemically through the modification of cascade-type networks, which are prevalent in actual signaling pathways.

Physiological and molecular biochemical mechanisms of bile formation

PubMed Central

Reshetnyak, Vasiliy Ivanovich

2013-01-01

This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis and conjugation of bile acids, bile phospholipids, formation of bile micellar structures, and enterohepatic circulation of bile acids are described. In general, the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical membranes. Knowledge of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes, associated with diseases of the liver and biliary tract. PMID:24259965

Optofluidic UV-Vis spectrophotometer for online monitoring of photocatalytic reactions

NASA Astrophysics Data System (ADS)

Wang, Ning; Tan, Furui; Zhao, Yu; Tsoi, Chi Chung; Fan, Xudong; Yu, Weixing; Zhang, Xuming

2016-06-01

On-chip integration of optical detection units into the microfluidic systems for online monitoring is highly desirable for many applications and is also well in line with the spirit of optofluidics technology-fusion of optics and microfluidics for advanced functionalities. This paper reports the construction of a UV-Vis spectrophotometer on a microreactor, and demonstrates the online monitoring of the photocatalytic degradations of methylene blue and methyl orange under different flow rates and different pH values by detecting the intensity change and/or the peak shift. The integrated device consists of a TiO2-coated glass substrate, a PDMS micro-sized reaction chamber and two flow cells. By comparing with the results of commercial equipment, we have found that the measuring range and the sensitivity are acceptable, especially when the transmittance is in the range of 0.01-0.9. This integrated optofluidic device can significantly cut down the test time and the sample volume, and would provide a versatile platform for real-time characterization of photochemical performance. Moreover, its online monitoring capability may enable to access the usually hidden information in biochemical reactions like intermediate products, time-dependent processes and reaction kinetics.

Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides.

PubMed

Allred, Benjamin E; Rupert, Peter B; Gauny, Stacey S; An, Dahlia D; Ralston, Corie Y; Sturzbecher-Hoehne, Manuel; Strong, Roland K; Abergel, Rebecca J

2015-08-18

Synthetic radionuclides, such as the transuranic actinides plutonium, americium, and curium, present severe health threats as contaminants, and understanding the scope of the biochemical interactions involved in actinide transport is instrumental in managing human contamination. Here we show that siderocalin, a mammalian siderophore-binding protein from the lipocalin family, specifically binds lanthanide and actinide complexes through molecular recognition of the ligands chelating the metal ions. Using crystallography, we structurally characterized the resulting siderocalin-transuranic actinide complexes, providing unprecedented insights into the biological coordination of heavy radioelements. In controlled in vitro assays, we found that intracellular plutonium uptake can occur through siderocalin-mediated endocytosis. We also demonstrated that siderocalin can act as a synergistic antenna to sensitize the luminescence of trivalent lanthanide and actinide ions in ternary protein-ligand complexes, dramatically increasing the brightness and efficiency of intramolecular energy transfer processes that give rise to metal luminescence. Our results identify siderocalin as a potential player in the biological trafficking of f elements, but through a secondary ligand-based metal sequestration mechanism. Beyond elucidating contamination pathways, this work is a starting point for the design of two-stage biomimetic platforms for photoluminescence, separation, and transport applications.

The β2 clamp in the Mycobacterium tuberculosis DNA polymerase III αβ2ε replicase promotes polymerization and reduces exonuclease activity

PubMed Central

Gu, Shoujin; Li, Wenjuan; Zhang, Hongtai; Fleming, Joy; Yang, Weiqiang; Wang, Shihua; Wei, Wenjing; Zhou, Jie; Zhu, Guofeng; Deng, Jiaoyu; Hou, Jian; Zhou, Ying; Lin, Shiqiang; Zhang, Xian-En; Bi, Lijun

2016-01-01

DNA polymerase III (DNA pol III) is a multi-subunit replication machine responsible for the accurate and rapid replication of bacterial genomes, however, how it functions in Mycobacterium tuberculosis (Mtb) requires further investigation. We have reconstituted the leading-strand replication process of the Mtb DNA pol III holoenzyme in vitro, and investigated the physical and functional relationships between its key components. We verify the presence of an αβ2ε polymerase-clamp-exonuclease replicase complex by biochemical methods and protein-protein interaction assays in vitro and in vivo and confirm that, in addition to the polymerase activity of its α subunit, Mtb DNA pol III has two potential proofreading subunits; the α and ε subunits. During DNA replication, the presence of the β2 clamp strongly promotes the polymerization of the αβ2ε replicase and reduces its exonuclease activity. Our work provides a foundation for further research on the mechanism by which the replication machinery switches between replication and proofreading and provides an experimental platform for the selection of antimicrobials targeting DNA replication in Mtb. PMID:26822057

Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using Human Skin Models

PubMed Central

Brendtke, Rico; Wiehl, Michael; Groeber, Florian; Schwarz, Thomas; Walles, Heike; Hansmann, Jan

2016-01-01

Tissue dehydration results in three major types of exsiccosis—hyper-, hypo-, or isonatraemia. All three types entail alterations of salt concentrations leading to impaired biochemical processes, and can finally cause severe morbidity. The aim of our study was to demonstrate the feasibility of a microwave-based sensor technology for the non-invasive measurement of the hydration status. Electromagnetic waves at high frequencies interact with molecules, especially water. Hence, if a sample contains free water molecules, this can be detected in a reflected microwave signal. To develop the sensor system, human three-dimensional skin equivalents were instituted as a standardized test platform mimicking reproducible exsiccosis scenarios. Therefore, skin equivalents with a specific hydration and density of matrix components were generated and microwave measurements were performed. Hydration-specific spectra allowed deriving the hydration state of the skin models. A further advantage of the skin equivalents was the characterization of the impact of distinct skin components on the measured signals to investigate mechanisms of signal generation. The results demonstrate the feasibility of a non-invasive microwave-based hydration sensor technology. The sensor bears potential to be integrated in a wearable medical device for personal health monitoring. PMID:27046226

A fluorescent aptasensor for amplified label-free detection of adenosine triphosphate based on core-shell Ag@SiO2 nanoparticles.

PubMed

Song, Quanwei; Peng, Manshu; Wang, Le; He, Dacheng; Ouyang, Jin

2016-03-15

The novel, facile and universal aptamer-based methods for the highly sensitive and selective fluorescence detection of important biomolecules have attracted considerable interest. Here, we present a label-free aptasensor for adenosine triphosphate (ATP) detection in aqueous solutions by using an ultra-sensitive nucleic acid stain PicoGreen (PG) as a fluorescent indicator and core-shell Ag@SiO2 nanoparticles (NPs) as a metal-enhanced fluorescence (MEF) platform. In the presence of ATP, the complementary DNA (cDNA)/aptamer duplexes confined onto the Ag@SiO2 NPs surface can release their aptamers into the buffered solution, causing a significant reduction in fluorescence intensity. By virtue of the amplified fluorescence signal, this aptasensor toward ATP can achieve a detection limit of 14.2 nM with a wide linear range and exhibit a good assay performance in complex biological samples. This sensing approach is cost-effective and efficient because it avoids the fluorescence labeling process and the use of any enzymes. Hence, this method may offer an alternative tool for determining the concentrations of ATP in biochemical and biomedical research. Copyright © 2015 Elsevier B.V. All rights reserved.

Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using Human Skin Models.

PubMed

Brendtke, Rico; Wiehl, Michael; Groeber, Florian; Schwarz, Thomas; Walles, Heike; Hansmann, Jan

2016-01-01

Tissue dehydration results in three major types of exsiccosis--hyper-, hypo-, or isonatraemia. All three types entail alterations of salt concentrations leading to impaired biochemical processes, and can finally cause severe morbidity. The aim of our study was to demonstrate the feasibility of a microwave-based sensor technology for the non-invasive measurement of the hydration status. Electromagnetic waves at high frequencies interact with molecules, especially water. Hence, if a sample contains free water molecules, this can be detected in a reflected microwave signal. To develop the sensor system, human three-dimensional skin equivalents were instituted as a standardized test platform mimicking reproducible exsiccosis scenarios. Therefore, skin equivalents with a specific hydration and density of matrix components were generated and microwave measurements were performed. Hydration-specific spectra allowed deriving the hydration state of the skin models. A further advantage of the skin equivalents was the characterization of the impact of distinct skin components on the measured signals to investigate mechanisms of signal generation. The results demonstrate the feasibility of a non-invasive microwave-based hydration sensor technology. The sensor bears potential to be integrated in a wearable medical device for personal health monitoring.

O-Succinyl-L-homoserine-based C4-chemical production: succinic acid, homoserine lactone, γ-butyrolactone, γ-butyrolactone derivatives, and 1,4-butanediol.

PubMed

Hong, Kuk-Ki; Kim, Jeong Hyun; Yoon, Jong Hyun; Park, Hye-Min; Choi, Su Jin; Song, Gyu Hyeon; Lee, Jea Chun; Yang, Young-Lyeol; Shin, Hyun Kwan; Kim, Ju Nam; Cho, Kyung Ho; Lee, Jung Ho

2014-10-01

There has been a significant global interest to produce bulk chemicals from renewable resources using engineered microorganisms. Large research programs have been launched by academia and industry towards this goal. Particularly, C4 chemicals such as succinic acid (SA) and 1,4-butanediol have been leading the path towards the commercialization of biobased technology with the effort of replacing chemical production. Here we present O-Succinyl-L-homoserine (SH) as a new, potentially important platform biochemical and demonstrate its central role as an intermediate in the production of SA, homoserine lactone (HSL), γ-butyrolactone (GBL) and its derivatives, and 1,4-butanediol (BDO). This technology encompasses (1) the genetic manipulation of Escherichia coli to produce SH with high productivity, (2) hydrolysis into SA and homoserine (HS) or homoserine lactone hydrochloride, and (3) chemical conversion of either HS or homoserine lactone HCL (HSL·HCl) into drop-in chemicals in polymer industry. This production strategy with environmental benefits is discussed in the perspective of targeting of fermented product and a process direction compared to petroleum-based chemical conversion, which may reduce the overall manufacturing cost.

Optofluidic UV-Vis spectrophotometer for online monitoring of photocatalytic reactions

PubMed Central

Wang, Ning; Tan, Furui; Zhao, Yu; Tsoi, Chi Chung; Fan, Xudong; Yu, Weixing; Zhang, Xuming

2016-01-01

On-chip integration of optical detection units into the microfluidic systems for online monitoring is highly desirable for many applications and is also well in line with the spirit of optofluidics technology–fusion of optics and microfluidics for advanced functionalities. This paper reports the construction of a UV-Vis spectrophotometer on a microreactor, and demonstrates the online monitoring of the photocatalytic degradations of methylene blue and methyl orange under different flow rates and different pH values by detecting the intensity change and/or the peak shift. The integrated device consists of a TiO2-coated glass substrate, a PDMS micro-sized reaction chamber and two flow cells. By comparing with the results of commercial equipment, we have found that the measuring range and the sensitivity are acceptable, especially when the transmittance is in the range of 0.01–0.9. This integrated optofluidic device can significantly cut down the test time and the sample volume, and would provide a versatile platform for real-time characterization of photochemical performance. Moreover, its online monitoring capability may enable to access the usually hidden information in biochemical reactions like intermediate products, time-dependent processes and reaction kinetics. PMID:27352840

Optofluidic UV-Vis spectrophotometer for online monitoring of photocatalytic reactions.

PubMed

Wang, Ning; Tan, Furui; Zhao, Yu; Tsoi, Chi Chung; Fan, Xudong; Yu, Weixing; Zhang, Xuming

2016-06-29

On-chip integration of optical detection units into the microfluidic systems for online monitoring is highly desirable for many applications and is also well in line with the spirit of optofluidics technology-fusion of optics and microfluidics for advanced functionalities. This paper reports the construction of a UV-Vis spectrophotometer on a microreactor, and demonstrates the online monitoring of the photocatalytic degradations of methylene blue and methyl orange under different flow rates and different pH values by detecting the intensity change and/or the peak shift. The integrated device consists of a TiO2-coated glass substrate, a PDMS micro-sized reaction chamber and two flow cells. By comparing with the results of commercial equipment, we have found that the measuring range and the sensitivity are acceptable, especially when the transmittance is in the range of 0.01-0.9. This integrated optofluidic device can significantly cut down the test time and the sample volume, and would provide a versatile platform for real-time characterization of photochemical performance. Moreover, its online monitoring capability may enable to access the usually hidden information in biochemical reactions like intermediate products, time-dependent processes and reaction kinetics.

Metabonomics of ageing - Towards understanding metabolism of a long and healthy life.

PubMed

Martin, Francois-Pierre J; Montoliu, Ivan; Kussmann, Martin

2017-07-01

Systems biology approaches have been increasingly employed in clinical studies to enhance our understanding of the role of genetics, environmental factors and their interactions on nutritional, health and disease status. Amongst the new omics technologies, metabonomics has emerged as a robust platform to capture metabolic and nutritional requirements by enabling, in a minimally invasive fashion, the monitoring of a wide range of biochemical compounds. Their variations reflect comprehensively the various molecular regulatory processes, which are tightly controlled and under the influence of genetics, diet, gut microbiota and other environmental factors. They are providing key insights into complex metabolic phenomena as well as into differences and specificities at individual and population level. The aim of this review is to evaluate promising metabolic insights towards understanding metabolism of a long and healthy life from pre-clinical and clinical metabonomics studies. We will also discuss analytical approaches to enable data integration, with an emphasis on the longitudinal component. Herein, we will illustrate current examples, challenges and perspectives in the applications of metabonomics monitoring and modelling approaches in the context of healthy ageing research. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides

PubMed Central

Allred, Benjamin E.; Rupert, Peter B.; Gauny, Stacey S.; An, Dahlia D.; Ralston, Corie Y.; Sturzbecher-Hoehne, Manuel; Strong, Roland K.; Abergel, Rebecca J.

2015-01-01

Synthetic radionuclides, such as the transuranic actinides plutonium, americium, and curium, present severe health threats as contaminants, and understanding the scope of the biochemical interactions involved in actinide transport is instrumental in managing human contamination. Here we show that siderocalin, a mammalian siderophore-binding protein from the lipocalin family, specifically binds lanthanide and actinide complexes through molecular recognition of the ligands chelating the metal ions. Using crystallography, we structurally characterized the resulting siderocalin–transuranic actinide complexes, providing unprecedented insights into the biological coordination of heavy radioelements. In controlled in vitro assays, we found that intracellular plutonium uptake can occur through siderocalin-mediated endocytosis. We also demonstrated that siderocalin can act as a synergistic antenna to sensitize the luminescence of trivalent lanthanide and actinide ions in ternary protein–ligand complexes, dramatically increasing the brightness and efficiency of intramolecular energy transfer processes that give rise to metal luminescence. Our results identify siderocalin as a potential player in the biological trafficking of f elements, but through a secondary ligand-based metal sequestration mechanism. Beyond elucidating contamination pathways, this work is a starting point for the design of two-stage biomimetic platforms for photoluminescence, separation, and transport applications. PMID:26240330

Grace: A cross-platform micromagnetic simulator on graphics processing units

NASA Astrophysics Data System (ADS)

Zhu, Ru

2015-12-01

A micromagnetic simulator running on graphics processing units (GPUs) is presented. Different from GPU implementations of other research groups which are predominantly running on NVidia's CUDA platform, this simulator is developed with C++ Accelerated Massive Parallelism (C++ AMP) and is hardware platform independent. It runs on GPUs from venders including NVidia, AMD and Intel, and achieves significant performance boost as compared to previous central processing unit (CPU) simulators, up to two orders of magnitude. The simulator paved the way for running large size micromagnetic simulations on both high-end workstations with dedicated graphics cards and low-end personal computers with integrated graphics cards, and is freely available to download.

SPAIDE: A Real-time Research Platform for the Clarion CII/90K Cochlear Implant

NASA Astrophysics Data System (ADS)

Van Immerseel, L.; Peeters, S.; Dykmans, P.; Vanpoucke, F.; Bracke, P.

2005-12-01

SPAIDE ( sound-processing algorithm integrated development environment) is a real-time platform of Advanced Bionics Corporation (Sylmar, Calif, USA) to facilitate advanced research on sound-processing and electrical-stimulation strategies with the Clarion CII and 90K implants. The platform is meant for testing in the laboratory. SPAIDE is conceptually based on a clear separation of the sound-processing and stimulation strategies, and, in specific, on the distinction between sound-processing and stimulation channels and electrode contacts. The development environment has a user-friendly interface to specify sound-processing and stimulation strategies, and includes the possibility to simulate the electrical stimulation. SPAIDE allows for real-time sound capturing from file or audio input on PC, sound processing and application of the stimulation strategy, and streaming the results to the implant. The platform is able to cover a broad range of research applications; from noise reduction and mimicking of normal hearing, over complex (simultaneous) stimulation strategies, to psychophysics. The hardware setup consists of a personal computer, an interface board, and a speech processor. The software is both expandable and to a great extent reusable in other applications.

270GHz SiGe BiCMOS manufacturing process platform for mmWave applications

NASA Astrophysics Data System (ADS)

Kar-Roy, Arjun; Preisler, Edward J.; Talor, George; Yan, Zhixin; Booth, Roger; Zheng, Jie; Chaudhry, Samir; Howard, David; Racanelli, Marco

2011-11-01

TowerJazz has been offering the high volume commercial SiGe BiCMOS process technology platform, SBC18, for more than a decade. In this paper, we describe the TowerJazz SBC18H3 SiGe BiCMOS process which integrates a production ready 240GHz FT / 270 GHz FMAX SiGe HBT on a 1.8V/3.3V dual gate oxide CMOS process in the SBC18 technology platform. The high-speed NPNs in SBC18H3 process have demonstrated NFMIN of ~2dB at 40GHz, a BVceo of 1.6V and a dc current gain of 1200. This state-of-the-art process also comes with P-I-N diodes with high isolation and low insertion losses, Schottky diodes capable of exceeding cut-off frequencies of 1THz, high density stacked MIM capacitors, MOS and high performance junction varactors characterized up to 50GHz, thick upper metal layers for inductors, and various resistors such as low value and high value unsilicided poly resistors, metal and nwell resistors. Applications of the SBC18H3 platform for millimeter-wave products for automotive radars, phased array radars and Wband imaging are presented.

One-pot synthesis of glutathione by a two-enzyme cascade using a thermophilic ATP regeneration system.

PubMed

Zhang, Xing; Wu, Hui; Huang, Bing; Li, Zhimin; Ye, Qin

2017-01-10

In vitro cascade catalysis using enzyme-based system is becoming a promising biomanufacturing platform for biofuels and biochemicals production. Glutathione is a pivotal non-protein thiol compound and widely applied in food and pharmaceutical industries. In this study, glutathione was synthesized by a bifunctional glutathione synthetase together with a thermophilic ATP regeneration system through a two-enzyme cascade in vitro. Four bifunctional glutathione synthetases from Streptococcus sanguinis, S. gordonii, S. uberis and Bacillus cereus were applied for glutathione synthesis. The bifunctional glutathione synthetase from S. sanguinis was selected and coupled with the polyphosphate kinase from Thermosynechococcus elongatus BP-1 for regenerating ATP to produce glutathione in one pot. In the optimized system, 28.5mM glutathione was produced within 5h due to efficient ATP regeneration from low-cost polyphosphate. The yield based on added l-cysteine reached 81.4% and the productivity of glutathione achieved 5.7mM/h. The one-pot system indicated a potential biotransformation platform for industrial production of glutathione. Copyright © 2016 Elsevier B.V. All rights reserved.

Photoresponsive biomaterials for targeted drug delivery and 4D cell culture

NASA Astrophysics Data System (ADS)

Ruskowitz, Emily R.; Deforest, Cole A.

2018-02-01

Biological signalling is regulated through a complex and tightly choreographed interplay between cells and their extracellular matrix. The spatiotemporal control of these interactions is essential for tissue function, and disruptions to this dialogue often result in aberrant cell fate and disease. When disturbances are well understood, correct biological function can be restored through the precise introduction of therapeutics. Moreover, model systems with modifiable physiochemical properties are needed to probe the effects of therapeutic molecules and to investigate cell-matrix interactions. Photoresponsive biomaterials benefit from spatiotemporal tunability, which allows for site-specific therapeutic delivery in vivo and 4D modulation of synthetic cell culture platforms to mimic the dynamic heterogeneity of the human body in vitro. In this Review, we discuss how light can be exploited to modify different biomaterials in the context of photomediated drug delivery and phototunable cell culture platforms. We survey various photochemistries for their applicability in vitro and in vivo and for the biochemical and biophysical modification of materials. Finally, we highlight emerging tools and provide an outlook for the field of photoresponsive biomaterials.

Plasmon-enhanced Raman detection of body-fluid components

NASA Astrophysics Data System (ADS)

Matteini, Paolo; Banchelli, Martina; De Angelis, Marella; D'Andrea, Cristiano; Pini, Roberto

2018-02-01

Plasmon-enhanced spectroscopies such as surface-enhanced Raman spectroscopy (SERS) concern the detection of enhanced optical responses of molecules in close proximity to plasmonic structures, which results in a strong increase in sensitivity. Recent advancements in nanofabrication methods have paved the way for a controlled design of tailor-made nanostructures with fine-tuning of their optical and surface properties. Among these, silver nanocubes (AgNCs) represent a convenient choice in SERS owing to intense electromagnetic fields localized at their extremities, which are further intensified in the gap regions between closely spaced nanoparticles. The integration of AgNCs assemblies within an optofluidic platform may confer potential for superior optical investigation due to a molecular enrichment on the plasmonic structures to collect an enhanced photonic response. We developed a novel sensing platform based on an optofluidic system involving assembled silver nanocubes of 50 nm in size for ultrasensitive SERS detection of biomolecules in wet conditions. The proposed system offers the perspective of advanced biochemical and biological characterizations of molecules as well as of effective detection of body fluid components and other molecules of biomedical interest in their own environment.

Transcriptome analysis of lentil (Lens culinaris Medikus) in response to seedling drought stress.

PubMed

Singh, Dharmendra; Singh, Chandan Kumar; Taunk, Jyoti; Tomar, Ram Sewak Singh; Chaturvedi, Ashish Kumar; Gaikwad, Kishor; Pal, Madan

2017-02-27

Drought stress is one of the most harmful abiotic stresses in crop plants. As a moderately drought tolerant crop, lentil is a major crop in rainfed areas and a suitable candidate for drought stress tolerance research work. Screening for drought tolerance stress under hydroponic conditions at seedling stage with air exposure is an efficient technique to select genotypes with contrasting traits. Transcriptome analysis provides valuable resources, especially for lentil, as here the information on complete genome sequence is not available. Hence, the present studies were carried out. This study was undertaken to understand the biochemical mechanisms and transcriptome changes involved in imparting adaptation to drought stress at seedling stage in drought-tolerant (PDL-2) and drought-sensitive (JL-3) cultivars. Among different physiological and biochemical parameters, a significant increase was recorded in proline, glycine betaine contents and activities of SOD, APX and GPX in PDL-2 compared to JL-3while chlorophyll, RWC and catalase activity decreased significantly in JL-3. Transcriptome changes between the PDL-2 and JL-3 under drought stress were evaluated using Illumina HiSeq 2500 platform. Total number of bases ranged from 5.1 to 6.7 Gb. Sequence analysis of control and drought treated cDNA libraries of PDL-2 and JL-3 produced 74032, 75500, 78328 and 81523 contigs, respectively with respective N50 value of 2011, 2008, 2000 and 1991. Differential gene expression of drought treated genotypes along with their controls revealed a total of 11,435 upregulated and 6,934 downregulated transcripts. For functional classification of DEGs, KEGG pathway annotation analysis extracted a total of 413 GO annotation terms where 176 were within molecular process, 128 in cellular and 109 in biological process groups. The transcriptional profiles provide a foundation for deciphering the underlying mechanism for drought tolerance in lentil. Transcriptional regulation, signal transduction and secondary metabolism in two genotypes revealed significant differences at seedling stage under severe drought. Our finding suggests role of candidate genes for improving drought tolerance in lentil.

Biochemical Reconstitution of the WAVE Regulatory Complex

PubMed Central

Chen, Baoyu; Padrick, Shae B.; Henry, Lisa; Rosen, Michael K.

2014-01-01

The WAVE regulatory complex (WRC) is a 400-KDa heteropentameric protein assembly that plays a central role in controlling actin cytoskeletal dynamics in many cellular processes. The WRC acts by integrating diverse cellular cues and stimulating the actin nucleating activity of the Arp2/3 complex at membranes. Biochemical and biophysical studies of the underlying mechanisms of these processes require large amounts of purified WRC. Recent success in recombinant expression, reconstitution, purification and crystallization of the WRC has greatly advanced our understanding of the inhibition, activation and membrane recruitment mechanisms of this complex. But many important questions remain to be answered. Here we summarize and update the methods developed in our laboratory, which allow reliable and flexible production of tens of milligrams of recombinant WRC of crystallographic quality, sufficient for many biochemical and structural studies. PMID:24630101

Optimal Information Processing in Biochemical Networks

NASA Astrophysics Data System (ADS)

Wiggins, Chris

2012-02-01

A variety of experimental results over the past decades provide examples of near-optimal information processing in biological networks, including in biochemical and transcriptional regulatory networks. Computing information-theoretic quantities requires first choosing or computing the joint probability distribution describing multiple nodes in such a network --- for example, representing the probability distribution of finding an integer copy number of each of two interacting reactants or gene products while respecting the `intrinsic' small copy number noise constraining information transmission at the scale of the cell. I'll given an overview of some recent analytic and numerical work facilitating calculation of such joint distributions and the associated information, which in turn makes possible numerical optimization of information flow in models of noisy regulatory and biochemical networks. Illustrating cases include quantification of form-function relations, ideal design of regulatory cascades, and response to oscillatory driving.

Organic solvent pretreatment of lignocellulosic biomass for biofuels and biochemicals: A review.

PubMed

Zhang, Ke; Pei, Zhijian; Wang, Donghai

2016-01-01

Lignocellulosic biomass represents the largest potential volume and lowest cost for biofuel and biochemical production. Pretreatment is an essential component of biomass conversion process, affecting a majority of downstream processes, including enzymatic hydrolysis, fermentation, and final product separation. Organic solvent pretreatment is recognized as an emerging way ahead because of its inherent advantages, such as the ability to fractionate lignocellulosic biomass into cellulose, lignin, and hemicellulose components with high purity, as well as easy solvent recovery and solvent reuse. Objectives of this review were to update and extend previous works on pretreatment of lignocellulosic biomass for biofuels and biochemicals using organic solvents, especially on ethanol, methanol, ethylene glycol, glycerol, acetic acid, and formic acid. Perspectives and recommendations were given to fully describe implementation of proper organic solvent pretreatment for future research. Copyright © 2015 Elsevier Ltd. All rights reserved.

System and method for measuring ocean surface currents at locations remote from land masses using synthetic aperture radar

NASA Technical Reports Server (NTRS)

Young, Lawrence E. (Inventor)

1991-01-01

A system for measuring ocean surface currents from an airborne platform is disclosed. A radar system having two spaced antennas wherein one antenna is driven and return signals from the ocean surface are detected by both antennas is employed to get raw ocean current data which are saved for later processing. There are a pair of global positioning system (GPS) systems including a first antenna carried by the platform at a first location and a second antenna carried by the platform at a second location displaced from the first antenna for determining the position of the antennas from signals from orbiting GPS navigational satellites. Data are also saved for later processing. The saved data are subsequently processed by a ground-based computer system to determine the position, orientation, and velocity of the platform as well as to derive measurements of currents on the ocean surface.

Design and Simulation of Material-Integrated Distributed Sensor Processing with a Code-Based Agent Platform and Mobile Multi-Agent Systems

PubMed Central

Bosse, Stefan

2015-01-01

Multi-agent systems (MAS) can be used for decentralized and self-organizing data processing in a distributed system, like a resource-constrained sensor network, enabling distributed information extraction, for example, based on pattern recognition and self-organization, by decomposing complex tasks in simpler cooperative agents. Reliable MAS-based data processing approaches can aid the material-integration of structural-monitoring applications, with agent processing platforms scaled to the microchip level. The agent behavior, based on a dynamic activity-transition graph (ATG) model, is implemented with program code storing the control and the data state of an agent, which is novel. The program code can be modified by the agent itself using code morphing techniques and is capable of migrating in the network between nodes. The program code is a self-contained unit (a container) and embeds the agent data, the initialization instructions and the ATG behavior implementation. The microchip agent processing platform used for the execution of the agent code is a standalone multi-core stack machine with a zero-operand instruction format, leading to a small-sized agent program code, low system complexity and high system performance. The agent processing is token-queue-based, similar to Petri-nets. The agent platform can be implemented in software, too, offering compatibility at the operational and code level, supporting agent processing in strong heterogeneous networks. In this work, the agent platform embedded in a large-scale distributed sensor network is simulated at the architectural level by using agent-based simulation techniques. PMID:25690550

Design and simulation of material-integrated distributed sensor processing with a code-based agent platform and mobile multi-agent systems.

PubMed

Bosse, Stefan

2015-02-16

Multi-agent systems (MAS) can be used for decentralized and self-organizing data processing in a distributed system, like a resource-constrained sensor network, enabling distributed information extraction, for example, based on pattern recognition and self-organization, by decomposing complex tasks in simpler cooperative agents. Reliable MAS-based data processing approaches can aid the material-integration of structural-monitoring applications, with agent processing platforms scaled to the microchip level. The agent behavior, based on a dynamic activity-transition graph (ATG) model, is implemented with program code storing the control and the data state of an agent, which is novel. The program code can be modified by the agent itself using code morphing techniques and is capable of migrating in the network between nodes. The program code is a self-contained unit (a container) and embeds the agent data, the initialization instructions and the ATG behavior implementation. The microchip agent processing platform used for the execution of the agent code is a standalone multi-core stack machine with a zero-operand instruction format, leading to a small-sized agent program code, low system complexity and high system performance. The agent processing is token-queue-based, similar to Petri-nets. The agent platform can be implemented in software, too, offering compatibility at the operational and code level, supporting agent processing in strong heterogeneous networks. In this work, the agent platform embedded in a large-scale distributed sensor network is simulated at the architectural level by using agent-based simulation techniques.

47 CFR 64.617 - Neutral Video Communication Service Platform.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Neutral Video Communication Service Platform... Related Customer Premises Equipment for Persons With Disabilities § 64.617 Neutral Video Communication... Neutral Video Communication Service Platform to process VRS calls. Each VRS CA service provider shall be...

47 CFR 64.617 - Neutral Video Communication Service Platform.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Neutral Video Communication Service Platform... Related Customer Premises Equipment for Persons With Disabilities § 64.617 Neutral Video Communication... Neutral Video Communication Service Platform to process VRS calls. Each VRS CA service provider shall be...

Thiolene and SIFEL-based Microfluidic Platforms for Liquid-Liquid Extraction

PubMed Central

Goyal, Sachit; Desai, Amit V.; Lewis, Robert W.; Ranganathan, David R.; Li, Hairong; Zeng, Dexing; Reichert, David E.; Kenis, Paul J.A.

2014-01-01

Microfluidic platforms provide several advantages for liquid-liquid extraction (LLE) processes over conventional methods, for example with respect to lower consumption of solvents and enhanced extraction efficiencies due to the inherent shorter diffusional distances. Here, we report the development of polymer-based parallel-flow microfluidic platforms for LLE. To date, parallel-flow microfluidic platforms have predominantly been made out of silicon or glass due to their compatibility with most organic solvents used for LLE. Fabrication of silicon and glass-based LLE platforms typically requires extensive use of photolithography, plasma or laser-based etching, high temperature (anodic) bonding, and/or wet etching with KOH or HF solutions. In contrast, polymeric microfluidic platforms can be fabricated using less involved processes, typically photolithography in combination with replica molding, hot embossing, and/or bonding at much lower temperatures. Here we report the fabrication and testing of microfluidic LLE platforms comprised of thiolene or a perfluoropolyether-based material, SIFEL, where the choice of materials was mainly guided by the need for solvent compatibility and fabrication amenability. Suitable designs for polymer-based LLE platforms that maximize extraction efficiencies within the constraints of the fabrication methods and feasible operational conditions were obtained using analytical modeling. To optimize the performance of the polymer-based LLE platforms, we systematically studied the effect of surface functionalization and of microstructures on the stability of the liquid-liquid interface and on the ability to separate the phases. As demonstrative examples, we report (i) a thiolene-based platform to determine the lipophilicity of caffeine, and (ii) a SIFEL-based platform to extract radioactive copper from an acidic aqueous solution. PMID:25246730

Developing a social media platform for nurses.

PubMed

Jackson, Jennifer; Kennedy, Maggie

2015-11-18

Social media tools provide opportunities for nurses to connect with colleagues and patients and to advance personally and professionally. This article describes the process of developing an innovative social media platform at a large, multi-centre teaching hospital, The Ottawa Hospital, Canada, and its benefits for nurses. The platform, TOH Nurses, was developed using a nursing process approach, involving assessment, planning, implementation and evaluation. The aim of this initiative was to address the barriers to communication inherent in the large number of nurses employed by the organisation, the physical size of the multi-centre hospital and the shift-work nature of nursing. The platform was used to provide educational materials for clinical nurses, and to share information about professional practice. The implications of using a social media platform in a healthcare setting were considered carefully during its development and implementation, including concerns regarding privacy and confidentiality.

Raspberry Pi-powered imaging for plant phenotyping.

PubMed

Tovar, Jose C; Hoyer, J Steen; Lin, Andy; Tielking, Allison; Callen, Steven T; Elizabeth Castillo, S; Miller, Michael; Tessman, Monica; Fahlgren, Noah; Carrington, James C; Nusinow, Dmitri A; Gehan, Malia A

2018-03-01

Image-based phenomics is a powerful approach to capture and quantify plant diversity. However, commercial platforms that make consistent image acquisition easy are often cost-prohibitive. To make high-throughput phenotyping methods more accessible, low-cost microcomputers and cameras can be used to acquire plant image data. We used low-cost Raspberry Pi computers and cameras to manage and capture plant image data. Detailed here are three different applications of Raspberry Pi-controlled imaging platforms for seed and shoot imaging. Images obtained from each platform were suitable for extracting quantifiable plant traits (e.g., shape, area, height, color) en masse using open-source image processing software such as PlantCV. This protocol describes three low-cost platforms for image acquisition that are useful for quantifying plant diversity. When coupled with open-source image processing tools, these imaging platforms provide viable low-cost solutions for incorporating high-throughput phenomics into a wide range of research programs.

Cooperative Search by UAV Teams: A Model Predictive Approach Using Dynamic Graphs

DTIC Science & Technology

2011-10-01

decentralized processing and control architecture. SLAMEM asset models accurately represent the Unicorn UAV platforms and other standard military platforms in...IMPLEMENTATION The CGBMPS algorithm has been successfully field-tested using both Unicorn [27] and Raven [20] UAV platforms. This section describes...the hardware-software system setup and implementation used for testing with Unicorns , Toyon’s UAV test platform. We also present some results from the

Biochemical and physiological processes associated with the differential ozone response in ozone-tolerant and sensitive soybean genotypes

USDA-ARS?s Scientific Manuscript database

Biochemical and physiological traits of two soybean [Glycine max (L.) Merr.] genotypes that differ in sensitivity to ozone (O3) were investigated to determine the possible basis for the differential response. Fiskeby III (O3-tolerant) and Mandarin (Ottawa) (O3-sensitive) were grown in a greenhouse ...

Acidic deposition, cation mobilization, and biochemical indicators of stress in healthy red spruce

Treesearch

Walter C. Shortle; Kevin T. Smith; Rakesh Minocha; Gregory B. Lawrence; Mark B. David

1997-01-01

Dendrochemical and biochemical markers link stress in apparently healthy red spruce trees (Picea rubens) to acidic deposition. Acidic deposition to spruce forests of the northeastern USA increased sharply during the 1960s. Previous reports related visible damage of trees at high elevations to root and soil processes. In this report, dendrochemical...

Methods of mesophyll conductance estimation: its impact on key biochemical parameters and photosynthetic limitations in phosphorus-stressed soybean across CO2

USDA-ARS?s Scientific Manuscript database

Photosynthetic potential in C3 plants is largely limited by CO2 diffusion through stomata (Ls) and mesophyll (Lm) and photo-biochemical (Lb) processes. Accurate estimation of mesophyll conductance (gm) using gas exchange (GE) and chlorophyll fluorescence (CF) parameters of the photosynthetic proces...

Services provided in support of the planetary quarantine requirements of the National Aeronautics and Space Administration

NASA Technical Reports Server (NTRS)

Favero, M. S.

1972-01-01

The evaluation is discussed of the terminal sterilization process for unmanned lander spacecraft. Results of biochemical test deviations encountered with the identification schemes are tabulated. Studies to examine the possibility of shifts in biochemical reaction patterns during storage and subculture of the environmental Bacillius isolates are also reported.

[Application of the life sciences platform based on oracle to biomedical informations].

PubMed

Zhao, Zhi-Yun; Li, Tai-Huan; Yang, Hong-Qiao

2008-03-01

The life sciences platform based on Oracle database technology is introduced in this paper. By providing a powerful data access, integrating a variety of data types, and managing vast quantities of data, the software presents a flexible, safe and scalable management platform for biomedical data processing.

Observing the ocean with different platforms/methods. Advantages, disadvantages and lessons learnt

NASA Astrophysics Data System (ADS)

Petihakis, George; Potiris, Manolis; Ntoumas, Manolis; Frangoulis, Kostas; Tsiaras, Kostas; Triantafyllou, George; Pollani, Annika

2015-04-01

Methods for observing/measuring the ocean, present remarkable diversity. In situ sampling or remote sensing, automated or not measurements with sensing probes, utilize different measuring principles, sample different parts of the system, are characterized by different accuracy/precision and sample over a large range of spatial and temporal scales with variable resolution. Measurements, quite often are dependent on the platform design and the platform interaction with the highly variable ambient environment. To add to the aforementioned issues that render the combination of data from different sources challenging from a scientific perspective, there are also a number of technical and data issues. These are important for the good operational status of the platforms, the smooth data flow and the collection of appropriate meta-data. Finally the raw data files need to be processed into a user friendly output format so the operator will be able to identify as early as possible sensor drift and failures. In this work, data from different observation platforms/sensors is analysed and compared, while mechanisms and processes responsible for differences are identified. More detailed, temperature, salinity and chlorophyll data from four fixed observing stations, one Ferry Box, satellites and a monthly in situ sampling program, is used. Main results indicate that a) regular calibration according to expected parameter range and well-defined, consistent deployment plan of proven sensors is sufficient for acquiring high quality data in the long term. Better knowledge of site specific response of new instrumentation is required for producing consistent long term data b) duplicate sensors on one platform considerably improve data flow and data quality c) if an area is sampled by multiple platforms, then platform dependent errors can be quantified d) fixed point observatories are efficient tools for assessing regional performance of satellite products. Higher vertical and temporal sampling rate of the upper 20m of the water column increase inter-comparability between the two platforms e) delayed mode, lower processing level data/meta-data should be archived and disseminated in addition to standard formatted files due to analysis artifacts and loss of information during transmission and processing.

NiftyPET: a High-throughput Software Platform for High Quantitative Accuracy and Precision PET Imaging and Analysis.

PubMed

Markiewicz, Pawel J; Ehrhardt, Matthias J; Erlandsson, Kjell; Noonan, Philip J; Barnes, Anna; Schott, Jonathan M; Atkinson, David; Arridge, Simon R; Hutton, Brian F; Ourselin, Sebastien

2018-01-01

We present a standalone, scalable and high-throughput software platform for PET image reconstruction and analysis. We focus on high fidelity modelling of the acquisition processes to provide high accuracy and precision quantitative imaging, especially for large axial field of view scanners. All the core routines are implemented using parallel computing available from within the Python package NiftyPET, enabling easy access, manipulation and visualisation of data at any processing stage. The pipeline of the platform starts from MR and raw PET input data and is divided into the following processing stages: (1) list-mode data processing; (2) accurate attenuation coefficient map generation; (3) detector normalisation; (4) exact forward and back projection between sinogram and image space; (5) estimation of reduced-variance random events; (6) high accuracy fully 3D estimation of scatter events; (7) voxel-based partial volume correction; (8) region- and voxel-level image analysis. We demonstrate the advantages of this platform using an amyloid brain scan where all the processing is executed from a single and uniform computational environment in Python. The high accuracy acquisition modelling is achieved through span-1 (no axial compression) ray tracing for true, random and scatter events. Furthermore, the platform offers uncertainty estimation of any image derived statistic to facilitate robust tracking of subtle physiological changes in longitudinal studies. The platform also supports the development of new reconstruction and analysis algorithms through restricting the axial field of view to any set of rings covering a region of interest and thus performing fully 3D reconstruction and corrections using real data significantly faster. All the software is available as open source with the accompanying wiki-page and test data.

Investigation into Cloud Computing for More Robust Automated Bulk Image Geoprocessing

NASA Technical Reports Server (NTRS)

Brown, Richard B.; Smoot, James C.; Underwood, Lauren; Armstrong, C. Duane

2012-01-01

Geospatial resource assessments frequently require timely geospatial data processing that involves large multivariate remote sensing data sets. In particular, for disasters, response requires rapid access to large data volumes, substantial storage space and high performance processing capability. The processing and distribution of this data into usable information products requires a processing pipeline that can efficiently manage the required storage, computing utilities, and data handling requirements. In recent years, with the availability of cloud computing technology, cloud processing platforms have made available a powerful new computing infrastructure resource that can meet this need. To assess the utility of this resource, this project investigates cloud computing platforms for bulk, automated geoprocessing capabilities with respect to data handling and application development requirements. This presentation is of work being conducted by Applied Sciences Program Office at NASA-Stennis Space Center. A prototypical set of image manipulation and transformation processes that incorporate sample Unmanned Airborne System data were developed to create value-added products and tested for implementation on the "cloud". This project outlines the steps involved in creating and testing of open source software developed process code on a local prototype platform, and then transitioning this code with associated environment requirements into an analogous, but memory and processor enhanced cloud platform. A data processing cloud was used to store both standard digital camera panchromatic and multi-band image data, which were subsequently subjected to standard image processing functions such as NDVI (Normalized Difference Vegetation Index), NDMI (Normalized Difference Moisture Index), band stacking, reprojection, and other similar type data processes. Cloud infrastructure service providers were evaluated by taking these locally tested processing functions, and then applying them to a given cloud-enabled infrastructure to assesses and compare environment setup options and enabled technologies. This project reviews findings that were observed when cloud platforms were evaluated for bulk geoprocessing capabilities based on data handling and application development requirements.

Biochemical and physicochemical analysis of fish protein isolate recovered from red snapper (Lutjanus sp.) by-product using isoelectric solubilization/precipitation method

NASA Astrophysics Data System (ADS)

Pramono, H.; Pujiastuti, D. Y.; Sahidu, A. M.

2018-04-01

The effect of acid- and alkali-process on biochemical and physicochemical characteristics of fish protein isolate from red snapper (Lutjanus sp) by-product was evaluated. Protein recovered by alkali process (16.79%) was higher compared to acid process (13.75%). Reduction of lipid content and total volatile basic nitrogen (TVB-N) exhibited in both treatments indicated both process improved fish protein isolate recovered from red snapper by-product. In addition, the increasing of water holding capacity and oil binding capacity were observed. However, high peroxide value of fish protein isolate was showed in both treatment. This finding indicated that acid and alkali process can be used as a useful method to recover proteins from red snapper by-product. Alkali process gave a protein isolate with better overall quality compared to acid process.

An integrated biotechnology platform for developing sustainable chemical processes.

PubMed

Barton, Nelson R; Burgard, Anthony P; Burk, Mark J; Crater, Jason S; Osterhout, Robin E; Pharkya, Priti; Steer, Brian A; Sun, Jun; Trawick, John D; Van Dien, Stephen J; Yang, Tae Hoon; Yim, Harry

2015-03-01

Genomatica has established an integrated computational/experimental metabolic engineering platform to design, create, and optimize novel high performance organisms and bioprocesses. Here we present our platform and its use to develop E. coli strains for production of the industrial chemical 1,4-butanediol (BDO) from sugars. A series of examples are given to demonstrate how a rational approach to strain engineering, including carefully designed diagnostic experiments, provided critical insights about pathway bottlenecks, byproducts, expression balancing, and commercial robustness, leading to a superior BDO production strain and process.

The big data processing platform for intelligent agriculture

NASA Astrophysics Data System (ADS)

Huang, Jintao; Zhang, Lichen

2017-08-01

Big data technology is another popular technology after the Internet of Things and cloud computing. Big data is widely used in many fields such as social platform, e-commerce, and financial analysis and so on. Intelligent agriculture in the course of the operation will produce large amounts of data of complex structure, fully mining the value of these data for the development of agriculture will be very meaningful. This paper proposes an intelligent data processing platform based on Storm and Cassandra to realize the storage and management of big data of intelligent agriculture.

Bio-jETI: a service integration, design, and provisioning platform for orchestrated bioinformatics processes.

PubMed

Margaria, Tiziana; Kubczak, Christian; Steffen, Bernhard

2008-04-25

With Bio-jETI, we introduce a service platform for interdisciplinary work on biological application domains and illustrate its use in a concrete application concerning statistical data processing in R and xcms for an LC/MS analysis of FAAH gene knockout. Bio-jETI uses the jABC environment for service-oriented modeling and design as a graphical process modeling tool and the jETI service integration technology for remote tool execution. As a service definition and provisioning platform, Bio-jETI has the potential to become a core technology in interdisciplinary service orchestration and technology transfer. Domain experts, like biologists not trained in computer science, directly define complex service orchestrations as process models and use efficient and complex bioinformatics tools in a simple and intuitive way.

A scalable moment-closure approximation for large-scale biochemical reaction networks

PubMed Central

Kazeroonian, Atefeh; Theis, Fabian J.; Hasenauer, Jan

2017-01-01

Abstract Motivation: Stochastic molecular processes are a leading cause of cell-to-cell variability. Their dynamics are often described by continuous-time discrete-state Markov chains and simulated using stochastic simulation algorithms. As these stochastic simulations are computationally demanding, ordinary differential equation models for the dynamics of the statistical moments have been developed. The number of state variables of these approximating models, however, grows at least quadratically with the number of biochemical species. This limits their application to small- and medium-sized processes. Results: In this article, we present a scalable moment-closure approximation (sMA) for the simulation of statistical moments of large-scale stochastic processes. The sMA exploits the structure of the biochemical reaction network to reduce the covariance matrix. We prove that sMA yields approximating models whose number of state variables depends predominantly on local properties, i.e. the average node degree of the reaction network, instead of the overall network size. The resulting complexity reduction is assessed by studying a range of medium- and large-scale biochemical reaction networks. To evaluate the approximation accuracy and the improvement in computational efficiency, we study models for JAK2/STAT5 signalling and NFκB signalling. Our method is applicable to generic biochemical reaction networks and we provide an implementation, including an SBML interface, which renders the sMA easily accessible. Availability and implementation: The sMA is implemented in the open-source MATLAB toolbox CERENA and is available from https://github.com/CERENADevelopers/CERENA. Contact: jan.hasenauer@helmholtz-muenchen.de or atefeh.kazeroonian@tum.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28881983

Integrated Kerr comb-based reconfigurable transversal differentiator for microwave photonic signal processing

NASA Astrophysics Data System (ADS)

Xu, Xingyuan; Wu, Jiayang; Shoeiby, Mehrdad; Nguyen, Thach G.; Chu, Sai T.; Little, Brent E.; Morandotti, Roberto; Mitchell, Arnan; Moss, David J.

2018-01-01

An arbitrary-order intensity differentiator for high-order microwave signal differentiation is proposed and experimentally demonstrated on a versatile transversal microwave photonic signal processing platform based on integrated Kerr combs. With a CMOS-compatible nonlinear micro-ring resonator, high quality Kerr combs with broad bandwidth and large frequency spacings are generated, enabling a larger number of taps and an increased Nyquist zone. By programming and shaping individual comb lines' power, calculated tap weights are realized, thus achieving a versatile microwave photonic signal processing platform. Arbitrary-order intensity differentiation is demonstrated on the platform. The RF responses are experimentally characterized, and systems demonstrations for Gaussian input signals are also performed.

Towards a consensus-based biokinetic model for green microalgae - The ASM-A.

PubMed

Wágner, Dorottya S; Valverde-Pérez, Borja; Sæbø, Mariann; Bregua de la Sotilla, Marta; Van Wagenen, Jonathan; Smets, Barth F; Plósz, Benedek Gy

2016-10-15

Cultivation of microalgae in open ponds and closed photobioreactors (PBRs) using wastewater resources offers an opportunity for biochemical nutrient recovery. Effective reactor system design and process control of PBRs requires process models. Several models with different complexities have been developed to predict microalgal growth. However, none of these models can effectively describe all the relevant processes when microalgal growth is coupled with nutrient removal and recovery from wastewaters. Here, we present a mathematical model developed to simulate green microalgal growth (ASM-A) using the systematic approach of the activated sludge modelling (ASM) framework. The process model - identified based on a literature review and using new experimental data - accounts for factors influencing photoautotrophic and heterotrophic microalgal growth, nutrient uptake and storage (i.e. Droop model) and decay of microalgae. Model parameters were estimated using laboratory-scale batch and sequenced batch experiments using the novel Latin Hypercube Sampling based Simplex (LHSS) method. The model was evaluated using independent data obtained in a 24-L PBR operated in sequenced batch mode. Identifiability of the model was assessed. The model can effectively describe microalgal biomass growth, ammonia and phosphate concentrations as well as the phosphorus storage using a set of average parameter values estimated with the experimental data. A statistical analysis of simulation and measured data suggests that culture history and substrate availability can introduce significant variability on parameter values for predicting the reaction rates for bulk nitrate and the intracellularly stored nitrogen state-variables, thereby requiring scenario specific model calibration. ASM-A was identified using standard cultivation medium and it can provide a platform for extensions accounting for factors influencing algal growth and nutrient storage using wastewater resources. Copyright © 2016 Elsevier Ltd. All rights reserved.

Surrogate biochemical markers: precise measurement for strategic drug and biologics development.

PubMed

Lee, J W; Hulse, J D; Colburn, W A

1995-05-01

More efficient drug and biologics development is necessary for future success of pharmaceutical and biotechnology companies. One way to achieve this objective is to use rationally selected surrogate markers to improve the early decision-making process. Using typical clinical chemistry methods to measure biochemical markers may not ensure adequate precision and reproducibility. In contrast, using analytical methods that meet good laboratory practices along with rational selection and validation of biochemical markers can give those who use them a competitive advantage over those who do not by providing meaningful data for earlier decision making.

Xi-cam: Flexible High Throughput Data Processing for GISAXS

NASA Astrophysics Data System (ADS)

Pandolfi, Ronald; Kumar, Dinesh; Venkatakrishnan, Singanallur; Sarje, Abinav; Krishnan, Hari; Pellouchoud, Lenson; Ren, Fang; Fournier, Amanda; Jiang, Zhang; Tassone, Christopher; Mehta, Apurva; Sethian, James; Hexemer, Alexander

With increasing capabilities and data demand for GISAXS beamlines, supporting software is under development to handle larger data rates, volumes, and processing needs. We aim to provide a flexible and extensible approach to GISAXS data treatment as a solution to these rising needs. Xi-cam is the CAMERA platform for data management, analysis, and visualization. The core of Xi-cam is an extensible plugin-based GUI platform which provides users an interactive interface to processing algorithms. Plugins are available for SAXS/GISAXS data and data series visualization, as well as forward modeling and simulation through HipGISAXS. With Xi-cam's advanced mode, data processing steps are designed as a graph-based workflow, which can be executed locally or remotely. Remote execution utilizes HPC or de-localized resources, allowing for effective reduction of high-throughput data. Xi-cam is open-source and cross-platform. The processing algorithms in Xi-cam include parallel cpu and gpu processing optimizations, also taking advantage of external processing packages such as pyFAI. Xi-cam is available for download online.

Monoclonal Antibodies Production Platforms: An Opportunity Study of a Non-Protein-A Chromatographic Platform Based on Process Economics.

PubMed

Grilo, António L; Mateus, Marília; Aires-Barros, Maria R; Azevedo, Ana M

2017-12-01

Monoclonal antibodies currently dominate the biopharmaceutical market with growing sales having reached 80 billion USD in 2016. As most top-selling mAbs are approaching the end of their patent life, biopharmaceutical companies compete fiercely in the biosimilars market. These two factors present a strong motivation for alternative process strategies and process optimization. In this work a novel purification strategy for monoclonal antibodies comprising phenylboronic acid multimodal chromatography for capture followed by polishing by ion-exchange monolithic chromatography and packed bed hydrophobic interaction chromatography is presented and compared to the traditional protein-A-based process. Although the capital investment is similar for both processes, the operation cost is 20% lower for the novel strategy. This study shows that the new process is worthwhile investing in and could present a viable alternative to the platform process used by most industrial players. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fair Oaks Dairy Farms Cellulosic Ethanol Technology Review Summary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrew Wold; Robert Divers

2011-06-23

At Fair Oaks Dairy, dried manure solids (''DMS'') are currently used as a low value compost. United Power was engaged to evaluate the feasibility of processing these DMS into ethanol utilizing commercially available cellulosic biofuels conversion platforms. The Fair Oaks Dairy group is transitioning their traditional ''manure to methane'' mesophilic anaerobic digester platform to an integrated bio-refinery centered upon thermophilic digestion. Presently, the Digested Manure Solids (DMS) are used as a low value soil amendment (compost). United Power evaluated the feasibility of processing DMS into higher value ethanol utilizing commercially available cellulosic biofuels conversion platforms. DMS was analyzed and overmore » 100 potential technology providers were reviewed and evaluated. DMS contains enough carbon to be suitable as a biomass feedstock for conversion into ethanol by gasification technology, or as part of a conversion process that would include combined heat and power. In the first process, 100% of the feedstock is converted into ethanol. In the second process, the feedstock is combusted to provide heat to generate electrical power supporting other processes. Of the 100 technology vendors evaluated, a short list of nine technology providers was developed. From this, two vendors were selected as finalists (one was an enzymatic platform and one was a gasification platform). Their selection was based upon the technical feasibility of their systems, engineering expertise, experience in commercial or pilot scale operations, the ability or willingness to integrate the system into the Fair Oaks Biorefinery, the know-how or experience in producing bio-ethanol, and a clear path to commercial development.« less

Overview of Piezoelectric Biosensors, Immunosensors and DNA Sensors and Their Applications.

PubMed

Pohanka, Miroslav

2018-03-19

Piezoelectric biosensors are a group of analytical devices working on a principle of affinity interaction recording. A piezoelectric platform or piezoelectric crystal is a sensor part working on the principle of oscillations change due to a mass bound on the piezoelectric crystal surface. In this review, biosensors having their surface modified with an antibody or antigen, with a molecularly imprinted polymer, with genetic information like single stranded DNA, and biosensors with bound receptors of organic of biochemical origin, are presented and discussed. The mentioned recognition parts are frequently combined with use of nanoparticles and applications in this way are also introduced. An overview of the current literature is given and the methods presented are commented upon.

Pathway engineering and synthetic biology using acetogens.

PubMed

Schiel-Bengelsdorf, Bettina; Dürre, Peter

2012-07-16

Acetogenic anaerobic bacteria are defined as organisms employing the Wood-Ljungdahl pathway to synthesize acetyl-CoA from CO(2) or CO. Their autotrophic mode of metabolism offers the biotechnological chance to combine use of abundantly available substrates with reduction of greenhouse gases. Several companies have already established pilot and demonstration plants for converting waste gases into ethanol, an important biofuel and a natural product of many acetogens. Recombinant DNA approaches now opened the door to construct acetogens, synthesizing important industrial bulk chemicals and biofuels such as acetone and butanol. Thus, novel microbial production platforms are available that no longer compete with nutritional feedstocks. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors.

PubMed

Frett, Brendan; McConnell, Nick; Smith, Catherine C; Wang, Yuanxiang; Shah, Neil P; Li, Hong-yu

2015-04-13

The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Organic Arsenicals as Functional Motifs in Polymer and Biomaterials Science.

PubMed

Tanaka, Joji; Davis, Thomas P; Wilson, Paul

2018-05-28

Arsenic (As) exhibits diverse (bio)chemical reactivity and biological activity depending upon its oxidation state. However, this distinctive reactivity has been largely overlooked across many fields owing to concerns regarding the toxicity of arsenic. Recently, a clinical renaissance in the use of arsenicals, including organic arsenicals that are known to be less toxic than inorganic arsenicals, alludes to the possibility of broader acceptance and application in the field of polymer and biomaterials science. Here, current examples of polymeric/macromolecular arsenicals are reported to stimulate interest and highlight their potential as a novel platform for functional, responsive, and bioactive materials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification and detoxification of glycolaldehyde, an unattended bioethanol fermentation inhibitor.

PubMed

Jayakody, Lahiru N; Ferdouse, Jannatul; Hayashi, Nobuyuki; Kitagaki, Hiroshi

2017-03-01

Although there have been approximately 60 chemical compounds identified as potent fermentation inhibitors in lignocellulose hydrolysate, our research group recently discovered glycolaldehyde as a key fermentation inhibitor during second generation biofuel production. Accordingly, we have developed a yeast S. cerevisiae strain exhibiting tolerance to glycolaldehyde. During this glycolaldehyde study, we established novel approaches for rational engineering of inhibitor-tolerant S. cerevisiae strains, including engineering redox cofactors and engineering the SUMOylation pathway. These new technical dimensions provide a novel platform for engineering S. cerevisiae strains to overcome one of the key barriers for industrialization of lignocellulosic ethanol production. As such, this review discusses novel biochemical insight of glycolaldehyde in the context of the biofuel industry.

Comparison of different photoresist buffer layers in SPR sensors based on D-shaped POF and gold film

NASA Astrophysics Data System (ADS)

Cennamo, Nunzio; Pesavento, Maria; De Maria, Letizia; Galatus, Ramona; Mattiello, Francesco; Zeni, Luigi

2017-04-01

A comparative analysis of two optical fiber sensing platforms is presented. The sensors are based on surface plasmon resonance (SPR) in a D-shaped plastic optical fiber (POF) with a photoresist buffer layer between the exposed POF core and the thin gold film. We show how the sensor's performances change when the photoresist layer changes. The photoresist layers proposed in this analysis are SU-8 3005 and S1813. The experimental results are congruent with the numerical studies and it is instrumental for chemical and bio-chemical applications. Usually, the photoresist layer is required in order to increase the performance of the SPR-POF sensor.

α,ω-dihexyl-sexithiophene thin films for solution-gated organic field-effect transistors

NASA Astrophysics Data System (ADS)

Schamoni, Hannah; Noever, Simon; Nickel, Bert; Stutzmann, Martin; Garrido, Jose A.

2016-02-01

While organic semiconductors are being widely investigated for chemical and biochemical sensing applications, major drawbacks such as the poor device stability and low charge carrier mobility in aqueous electrolytes have not yet been solved to complete satisfaction. In this work, solution-gated organic field-effect transistors (SGOFETs) based on the molecule α,ω-dihexyl-sexithiophene (DH6T) are presented as promising platforms for in-electrolyte sensing. Thin films of DH6T were investigated with regard to the influence of the substrate temperature during deposition on the grain size and structural order. The performance of SGOFETs can be improved by choosing suitable growth parameters that lead to a two-dimensional film morphology and a high degree of structural order. Furthermore, the capability of the SGOFETs to detect changes in the pH or ionic strength of the gate electrolyte is demonstrated and simulated. Finally, excellent transistor stability is confirmed by continuously operating the device over a period of several days, which is a consequence of the low threshold voltage of DH6T-based SGOFETs. Altogether, our results demonstrate the feasibility of high performance and highly stable organic semiconductor devices for chemical or biochemical applications.

Refractive Index Sensing with D-Shaped Plastic Optical Fibers for Chemical and Biochemical Applications

PubMed Central

Sequeira, Filipa; Duarte, Daniel; Bilro, Lúcia; Rudnitskaya, Alisa; Pesavento, Maria; Zeni, Luigi; Cennamo, Nunzio

2016-01-01

We report the optimization of the length of a D-shaped plastic optical fiber (POF) sensor for refractive index (RI) sensing from a numerical and experimental point of view. The sensing principle is based on total internal reflection (TIR). POFs with 1 mm in diameter were embedded in grooves, realized in planar supports with different lengths, and polished to remove the cladding and part of the core. All D-shaped POF sensors were tested using aqueous medium with different refractive indices (from 1.332 to 1.471) through intensity-based configuration. Results showed two different responses. Considering the refractive index (RI) range (1.33–1.39), the sensitivity and the resolution of the sensor were strongly dependent on the sensing region length. The highest sensitivity (resolution of 6.48 × 10−3 refractive index units, RIU) was obtained with 6 cm sensing length. In the RI range (1.41–1.47), the length of the sensing region was not a critical aspect to obtain the best resolution. These results enable the application of this optical platform for chemical and biochemical evanescent field sensing. The sensor production procedure is very simple, fast, and low-cost. PMID:27983608

Biochemical characterization of two thermostable xylanolytic enzymes encoded by a gene cluster of Caldicellulosiruptor owensensis.

PubMed

Mi, Shuofu; Jia, Xiaojing; Wang, Jinzhi; Qiao, Weibo; Peng, Xiaowei; Han, Yejun

2014-01-01

The xylanolytic extremely thermophilic bacterium Caldicellulosiruptor owensensis provides a promising platform for xylan utilization. In the present study, two novel xylanolytic enzymes, GH10 endo-β-1,4-xylanase (Coxyn A) and GH39 β-1,4-xylosidase (Coxyl A) encoded in one gene cluster of C.owensensis were heterogeneously expressed and biochemically characterized. The optimum temperature of the two xylanlytic enzymes was 75°C, and the respective optimum pH for Coxyn A and Coxyl A was 7.0 and 5.0. The difference of Coxyn A and Coxyl A in solution was existing as monomer and homodimer respectively, it was also observed in predicted secondary structure. Under optimum condition, the catalytic efficiency (kcat/Km) of Coxyn A was 366 mg ml(-1) s(-1) on beechwood xylan, and the catalytic efficiency (kcat/Km) of Coxyl A was 2253 mM(-1) s(-1) on pNP-β-D-xylopyranoside. Coxyn A degraded xylan to oligosaccharides, which were converted to monomer by Coxyl A. The two intracellular enzymes might be responsible for xylooligosaccharides utilization in C.owensensis, also provide a potential way for xylan degradation in vitro.

Refractive Index Sensing with D-Shaped Plastic Optical Fibers for Chemical and Biochemical Applications.

PubMed

Sequeira, Filipa; Duarte, Daniel; Bilro, Lúcia; Rudnitskaya, Alisa; Pesavento, Maria; Zeni, Luigi; Cennamo, Nunzio

2016-12-13

We report the optimization of the length of a D-shaped plastic optical fiber (POF) sensor for refractive index (RI) sensing from a numerical and experimental point of view. The sensing principle is based on total internal reflection (TIR). POFs with 1 mm in diameter were embedded in grooves, realized in planar supports with different lengths, and polished to remove the cladding and part of the core. All D-shaped POF sensors were tested using aqueous medium with different refractive indices (from 1.332 to 1.471) through intensity-based configuration. Results showed two different responses. Considering the refractive index (RI) range (1.33-1.39), the sensitivity and the resolution of the sensor were strongly dependent on the sensing region length. The highest sensitivity (resolution of 6.48 × 10 -3 refractive index units, RIU) was obtained with 6 cm sensing length. In the RI range (1.41-1.47), the length of the sensing region was not a critical aspect to obtain the best resolution. These results enable the application of this optical platform for chemical and biochemical evanescent field sensing. The sensor production procedure is very simple, fast, and low-cost.

A new large-scale manufacturing platform for complex biopharmaceuticals.

PubMed

Vogel, Jens H; Nguyen, Huong; Giovannini, Roberto; Ignowski, Jolene; Garger, Steve; Salgotra, Anil; Tom, Jennifer

2012-12-01

Complex biopharmaceuticals, such as recombinant blood coagulation factors, are addressing critical medical needs and represent a growing multibillion-dollar market. For commercial manufacturing of such, sometimes inherently unstable, molecules it is important to minimize product residence time in non-ideal milieu in order to obtain acceptable yields and consistently high product quality. Continuous perfusion cell culture allows minimization of residence time in the bioreactor, but also brings unique challenges in product recovery, which requires innovative solutions. In order to maximize yield, process efficiency, facility and equipment utilization, we have developed, scaled-up and successfully implemented a new integrated manufacturing platform in commercial scale. This platform consists of a (semi-)continuous cell separation process based on a disposable flow path and integrated with the upstream perfusion operation, followed by membrane chromatography on large-scale adsorber capsules in rapid cycling mode. Implementation of the platform at commercial scale for a new product candidate led to a yield improvement of 40% compared to the conventional process technology, while product quality has been shown to be more consistently high. Over 1,000,000 L of cell culture harvest have been processed with 100% success rate to date, demonstrating the robustness of the new platform process in GMP manufacturing. While membrane chromatography is well established for polishing in flow-through mode, this is its first commercial-scale application for bind/elute chromatography in the biopharmaceutical industry and demonstrates its potential in particular for manufacturing of potent, low-dose biopharmaceuticals. Copyright © 2012 Wiley Periodicals, Inc.

Application of GNSS Methods for Monitoring Offshore Platform Deformation

NASA Astrophysics Data System (ADS)

Myint, Khin Cho; Nasir Matori, Abd; Gohari, Adel

2018-03-01

Global Navigation Satellite System (GNSS) has become a powerful tool for high-precision deformation monitoring application. Monitoring of deformation and subsidence of offshore platform due to factors such as shallow gas phenomena. GNSS is the technical interoperability and compatibility between various satellite navigation systems such as modernized GPS, Galileo, reconstructed GLONASS to be used by civilian users. It has been known that excessive deformation affects platform structurally, causing loss of production and affects the efficiency of the machinery on board the platform. GNSS have been proven to be one of the most precise positioning methods where by users can get accuracy to the nearest centimeter of a given position from carrier phase measurement processing of GPS signals. This research is aimed at using GNSS technique, which is one of the most standard methods to monitor the deformation of offshore platforms. Therefore, station modeling, which accounts for the spatial correlated errors, and hence speeds up the ambiguity resolution process is employed. It was found that GNSS combines the high accuracy of the results monitoring the offshore platforms deformation with the possibility of survey.

Carboxylate platform: the MixAlco process part 1: comparison of three biomass conversion platforms.

PubMed

Holtzapple, Mark T; Granda, Cesar B

2009-05-01

To convert biomass to liquid fuels, three platforms are compared: thermochemical, sugar, and carboxylate. To create a common basis, each platform is fed "ideal biomass," which contains polysaccharides (68.3%) and lignin (31.7%). This ratio is typical of hardwood biomass and was selected so that when gasified and converted to hydrogen, the lignin has sufficient energy to produce ethanol from the carboxylic acids produced by the carboxylate platform. Using balanced chemical reactions, the theoretical yield and energy efficiency were determined for each platform. For all platforms, the ethanol yield can be increased by 71% to 107% by supplying external hydrogen produced from other sources (e.g., solar, wind, nuclear, fossil fuels). The alcohols can be converted to alkanes with a modest loss of energy efficiency (3 to 5 percentage points). Of the three platforms considered, the carboxylate platform has demonstrated the highest product yields.

Spike processing with a graphene excitable laser

PubMed Central

Shastri, Bhavin J.; Nahmias, Mitchell A.; Tait, Alexander N.; Rodriguez, Alejandro W.; Wu, Ben; Prucnal, Paul R.

2016-01-01

Novel materials and devices in photonics have the potential to revolutionize optical information processing, beyond conventional binary-logic approaches. Laser systems offer a rich repertoire of useful dynamical behaviors, including the excitable dynamics also found in the time-resolved “spiking” of neurons. Spiking reconciles the expressiveness and efficiency of analog processing with the robustness and scalability of digital processing. We demonstrate a unified platform for spike processing with a graphene-coupled laser system. We show that this platform can simultaneously exhibit logic-level restoration, cascadability and input-output isolation—fundamental challenges in optical information processing. We also implement low-level spike-processing tasks that are critical for higher level processing: temporal pattern detection and stable recurrent memory. We study these properties in the context of a fiber laser system and also propose and simulate an analogous integrated device. The addition of graphene leads to a number of advantages which stem from its unique properties, including high absorption and fast carrier relaxation. These could lead to significant speed and efficiency improvements in unconventional laser processing devices, and ongoing research on graphene microfabrication promises compatibility with integrated laser platforms. PMID:26753897

Metabonomics and medicine: the Biochemical Oracle.

PubMed

Mitchell, Steve; Holmes, Elaine; Carmichael, Paul

2002-10-01

Occasionally, a new idea emerges that has the potential to revolutionize an entire field of scientific endeavour. It is now within our grasp to be able to detect subtle perturbations within the phenomenally complex biochemical matrix of living organisms. The discipline of metabonomics promises an all-encompassing approach to understanding total, yet fundamental, changes occurring in disease processes, drug toxicity and cell function.

Organization of biogeochemical nitrogen pathways with switch-like adjustment in fluctuating soil redox conditions

PubMed Central

Lamba, Sanjay; Bera, Soumen; Rashid, Mubasher; Medvinsky, Alexander B.; Acquisti, Claudia; Li, Bai-Lian

2017-01-01

Nitrogen is cycled throughout ecosystems by a suite of biogeochemical processes. The high complexity of the nitrogen cycle resides in an intricate interplay between reversible biochemical pathways alternatively and specifically activated in response to diverse environmental cues. Despite aggressive research, how the fundamental nitrogen biochemical processes are assembled and maintained in fluctuating soil redox conditions remains elusive. Here, we address this question using a kinetic modelling approach coupled with dynamical systems theory and microbial genomics. We show that alternative biochemical pathways play a key role in keeping nitrogen conversion and conservation properties invariant in fluctuating environments. Our results indicate that the biochemical network holds inherent adaptive capacity to stabilize ammonium and nitrate availability, and that the bistability in the formation of ammonium is linked to the transient upregulation of the amo-hao mediated nitrification pathway. The bistability is maintained by a pair of complementary subsystems acting as either source or sink type systems in response to soil redox fluctuations. It is further shown how elevated anthropogenic pressure has the potential to break down the stability of the system, altering substantially ammonium and nitrate availability in the soil, with dramatic effects on biodiversity. PMID:28280580

Functional analysis of H. sapiens DNA polymerase γ spacer mutation W748S with and without common variant E1143G

PubMed Central

Palin, Eino JH; Lesonen, Annamari; Farr, Carol L; Euro, Liliya; Suomalainen, Anu; Kaguni, Laurie S

2010-01-01

Mitochondrial DNA polymerase, POLG, is the sole DNA polymerase found in animal mitochondria. In humans, POLGα W748S in cis with an E1143G mutation has been linked to a new type of recessive ataxia, MIRAS, which is the most common inherited ataxia in Finland. We investigated the biochemical phenotypes of the W748S amino acid change, using recombinant human POLG. We measured processive and non-processive DNA polymerase activity, DNA binding affinity, enzyme processivity, and subunit interaction with recombinant POLGβ. In addition, we studied the effects of the W748S and E1143G mutations in primary human cell cultures using retroviral transduction. Here, we examined cell viability, mitochondrial DNA copy number, and products of mitochondrial translation. Our results indicate that the W748S mutant POLGα does not exhibit a clear biochemical phenotype, making it indistinguishable from wild type POLGα and as such, fail to replicate previously published results. Furthermore, results from the cell models were concurrent with the findings from patients, and support our biochemical findings. PMID:20153822

Embedded-Based Graphics Processing Unit Cluster Platform for Multiple Sequence Alignments

PubMed Central

Wei, Jyh-Da; Cheng, Hui-Jun; Lin, Chun-Yuan; Ye, Jin; Yeh, Kuan-Yu

2017-01-01

High-end graphics processing units (GPUs), such as NVIDIA Tesla/Fermi/Kepler series cards with thousands of cores per chip, are widely applied to high-performance computing fields in a decade. These desktop GPU cards should be installed in personal computers/servers with desktop CPUs, and the cost and power consumption of constructing a GPU cluster platform are very high. In recent years, NVIDIA releases an embedded board, called Jetson Tegra K1 (TK1), which contains 4 ARM Cortex-A15 CPUs and 192 Compute Unified Device Architecture cores (belong to Kepler GPUs). Jetson Tegra K1 has several advantages, such as the low cost, low power consumption, and high applicability, and it has been applied into several specific applications. In our previous work, a bioinformatics platform with a single TK1 (STK platform) was constructed, and this previous work is also used to prove that the Web and mobile services can be implemented in the STK platform with a good cost-performance ratio by comparing a STK platform with the desktop CPU and GPU. In this work, an embedded-based GPU cluster platform will be constructed with multiple TK1s (MTK platform). Complex system installation and setup are necessary procedures at first. Then, 2 job assignment modes are designed for the MTK platform to provide services for users. Finally, ClustalW v2.0.11 and ClustalWtk will be ported to the MTK platform. The experimental results showed that the speedup ratios achieved 5.5 and 4.8 times for ClustalW v2.0.11 and ClustalWtk, respectively, by comparing 6 TK1s with a single TK1. The MTK platform is proven to be useful for multiple sequence alignments. PMID:28835734

Embedded-Based Graphics Processing Unit Cluster Platform for Multiple Sequence Alignments.

PubMed

Wei, Jyh-Da; Cheng, Hui-Jun; Lin, Chun-Yuan; Ye, Jin; Yeh, Kuan-Yu

2017-01-01

High-end graphics processing units (GPUs), such as NVIDIA Tesla/Fermi/Kepler series cards with thousands of cores per chip, are widely applied to high-performance computing fields in a decade. These desktop GPU cards should be installed in personal computers/servers with desktop CPUs, and the cost and power consumption of constructing a GPU cluster platform are very high. In recent years, NVIDIA releases an embedded board, called Jetson Tegra K1 (TK1), which contains 4 ARM Cortex-A15 CPUs and 192 Compute Unified Device Architecture cores (belong to Kepler GPUs). Jetson Tegra K1 has several advantages, such as the low cost, low power consumption, and high applicability, and it has been applied into several specific applications. In our previous work, a bioinformatics platform with a single TK1 (STK platform) was constructed, and this previous work is also used to prove that the Web and mobile services can be implemented in the STK platform with a good cost-performance ratio by comparing a STK platform with the desktop CPU and GPU. In this work, an embedded-based GPU cluster platform will be constructed with multiple TK1s (MTK platform). Complex system installation and setup are necessary procedures at first. Then, 2 job assignment modes are designed for the MTK platform to provide services for users. Finally, ClustalW v2.0.11 and ClustalWtk will be ported to the MTK platform. The experimental results showed that the speedup ratios achieved 5.5 and 4.8 times for ClustalW v2.0.11 and ClustalWtk, respectively, by comparing 6 TK1s with a single TK1. The MTK platform is proven to be useful for multiple sequence alignments.

Evaluating the enhancement and improvement of China's technology and financial services platform innovation strategy.

PubMed

Wu, Ching-Sung; Hu, Kuang-Hua; Chen, Fu-Hsiang

2016-01-01

The development of high-tech industry has been prosperous around the world in past decades, while technology and finance have already become the most significant issues in the information era. While high-tech firms are a major force behind a country's economic development, it requires a lot of money for the development process, as well as the financing difficulties for its potential problems, thus, how to evaluate and establish appropriate technology and financial services platforms innovation strategy has become one of the most critical and difficult issues. Moreover, how the chosen intertwined financial environment can be optimized in order that high-tech firms financing problems can be decided has seldom been addressed. Thus, this research aims to establish a technology and financial services platform innovation strategy improvement model, as based on the hybrid MADM model, which addresses the main causal factors and amended priorities in order to strengthen ongoing planning. A DEMATEL technique, as based on Analytic Network Process, as well as modified VIKOR, will be proposed for selecting and re-configuring the aspired technology and financial services platform. An empirical study, as based on China's technology and financial services platform innovation strategy, will be provided for verifying the effectiveness of this proposed methodology. Based on expert interviews, technology and financial services platforms innovation strategy improvement should be made in the following order: credit guarantee platform ( C )_credit rating platform ( B )_investment and finance platform ( A ).

Platform based design of EAP transducers in Danfoss PolyPower A/S

NASA Astrophysics Data System (ADS)

Sarban, Rahimullah; Gudlaugsson, Tómas V.

2013-04-01

Electroactive Polymer (EAP) has gained increasing focus, in research communities, in last two decades. Research within the field of EAP has, so far, been mainly focused on material improvements, characterization, modeling and developing demonstrators. As the EAP technology matures, the need for a new area of research namely product development emerges. Product development can be based on an isolated design and production for a single product or platform design where a product family is developed. In platform design the families of products exploits commonality of platform modules while satisfying a variety of different market segments. Platform based approach has the primary benefit of being cost efficient and short lead time to market when new products emerges. Products development based on EAP technology is challenging both technologically as well as from production and processing point of view. Both the technological and processing challenges need to be addressed before a successful implementation of EAP technology into products. Based on this need Danfoss PolyPower A/S has, in 2011, launched a EAP platform project in collaboration with three Danish universities and three commercial organizations. The aim of the project is to develop platform based designs and product family for the EAP components to be used in variety of applications. This paper presents the structure of the platform project as a whole and specifically the platform based designs of EAP transducers. The underlying technologies, essential for EAP transducers, are also presented. Conceptual design and solution for the concepts are presented as well.

Efficient ethanol production from dried oil palm trunk treated by hydrothermolysis and subsequent enzymatic hydrolysis.

PubMed

Eom, In-Yong; Yu, Ju-Hyun; Jung, Chan-Duck; Hong, Kyung-Sik

2015-01-01

Oil palm trunk (OPT) is a valuable bioresource for the biorefinery industry producing biofuels and biochemicals. It has the distinct feature of containing a large amount of starch, which, unlike cellulose, can be easily solubilized by water when heated and hydrolyzed to glucose by amylolytic enzymes without pretreatment for breaking down the biomass recalcitrance. Therefore, it is suggested as beneficial to extract most of the starch from OPT through autoclaving and subsequent amylolytic hydrolysis prior to pretreatment. However, this treatment requires high capital and operational costs, and there could be a high probability of microbial contamination during starch processing. In terms of biochemical conversion of OPT, this study aimed to develop a simple and efficient ethanol conversion process without any chemical use such as acids and bases or detoxification. For comparison with the proposed efficient ethanol conversion process, OPT was subjected to hydrothermal treatment at 180 °C for 30 min. After enzymatic hydrolysis of PWS, 43.5 g of glucose per 100 g dry biomass was obtained, which corresponds to 81.3 % of the theoretical glucose yield. Through subsequent alcohol fermentation, 81.4 % ethanol yield of the theoretical ethanol yield was achieved. To conduct the proposed new process, starch in OPT was converted to ethanol through enzymatic hydrolysis and subsequent fermentation prior to hydrothermal treatment, and the resulting slurry was subjected to identical processes that were applied to control. Consequently, a high-glucose yield of 96.3 % was achieved, and the resulting ethanol yield was 93.5 %. The proposed new process was a simple method for minimizing the loss of starch during biochemical conversion and maximizing ethanol production as well as fermentable sugars from OPT. In addition, this methodology offers the advantage of reducing operational and capital costs due to minimizing the process for ethanol production by excluding expensive processes related to detoxification prior to enzymatic hydrolysis and fermentation such as washing/conditioning and solid-liquid separation of pretreated slurry. The potential future use of xylose-digestible microorganisms could further increase the ethanol yield from the proposed process, thereby increasing its effectiveness for the conversion of OPT into biofuels and biochemicals.

Bio-Spectroscopic Imaging Provides Evidence of Hippocampal Zn Deficiency and Decreased Lipid Unsaturation in an Accelerated Ageing Mouse Model.

PubMed

Fimognari, Nicholas; Hollings, Ashley; Lam, Virginie; Tidy, Rebecca J; Kewish, Cameron M; Albrecht, Matthew A; Takechi, Ryu; Mamo, John C L; Hackett, Mark J

2018-06-14

Western society is facing a health epidemic due to the increasing incidence of dementia in ageing populations, and there are still few effective diagnostic methods, minimal treatment options, and no cure. Ageing is the greatest risk factor for memory loss that occurs during the natural ageing process, as well as being the greatest risk factor for neurodegenerative disease such as Alzheimer's disease. Therefore, greater understanding of the biochemical pathways that drive a healthy ageing brain towards dementia (pathological ageing or Alzheimer's disease), is required to accelerate the development of improved diagnostics and therapies. Unfortunately, many animal models of dementia model chronic amyloid precursor protein over-expression, which although highly relevant to mechanisms of amyloidosis and familial Alzheimer's disease, does not model well dementia during the natural ageing process. A promising animal model reported to model mechanisms of accelerated natural ageing and memory impairments, is the senescence accelerated murine prone strain 8 (SAMP8), which has been adopted by many research group to study the biochemical transitions that occur during brain ageing. A limitation to traditional methods of biochemical characterisation is that many important biochemical and elemental markers (lipid saturation, lactate, transition metals) cannot be imaged at meso- or micro-spatial resolution. Therefore, in this investigation we report the first multi-modal biospectroscopic characterisation of the SAMP8 model, and have identified important biochemical and elemental alterations, and co-localisations, between 4 month old SAMP8 mice and the relevant control (SAMR1) mice. Specifically, we demonstrate direct evidence of altered metabolism and disturbed lipid homeostasis within corpus callosum white matter, in addition to localised hippocampal metal deficiencies, in the accelerated ageing phenotype. Such findings have important implication for future research aimed at elucidating specific biochemical pathways for therapeutic intervention.

Lab-on-a-chip platform for high throughput drug discovery with DNA-encoded chemical libraries

NASA Astrophysics Data System (ADS)

Grünzner, S.; Reddavide, F. V.; Steinfelder, C.; Cui, M.; Busek, M.; Klotzbach, U.; Zhang, Y.; Sonntag, F.

2017-02-01

The fast development of DNA-encoded chemical libraries (DECL) in the past 10 years has received great attention from pharmaceutical industries. It applies the selection approach for small molecular drug discovery. Because of the limited choices of DNA-compatible chemical reactions, most DNA-encoded chemical libraries have a narrow structural diversity and low synthetic yield. There is also a poor correlation between the ranking of compounds resulted from analyzing the sequencing data and the affinity measured through biochemical assays. By combining DECL with dynamical chemical library, the resulting DNA-encoded dynamic library (EDCCL) explores the thermodynamic equilibrium of reversible reactions as well as the advantages of DNA encoded compounds for manipulation/detection, thus leads to enhanced signal-to-noise ratio of the selection process and higher library quality. However, the library dynamics are caused by the weak interactions between the DNA strands, which also result in relatively low affinity of the bidentate interaction, as compared to a stable DNA duplex. To take advantage of both stably assembled dual-pharmacophore libraries and EDCCLs, we extended the concept of EDCCLs to heat-induced EDCCLs (hi-EDCCLs), in which the heat-induced recombination process of stable DNA duplexes and affinity capture are carried out separately. To replace the extremely laborious and repetitive manual process, a fully automated device will facilitate the use of DECL in drug discovery. Herein we describe a novel lab-on-a-chip platform for high throughput drug discovery with hi-EDCCL. A microfluidic system with integrated actuation was designed which is able to provide a continuous sample circulation by reducing the volume to a minimum. It consists of a cooled and a heated chamber for constant circulation. The system is capable to generate stable temperatures above 75 °C in the heated chamber to melt the double strands of the DNA and less than 15 °C in the cooled chamber, to reanneal the reshuffled library. In the binding chamber (the cooled chamber) specific retaining structures are integrated. These hold back beads functionalized with the target protein, while the chamber is continuously flushed with library molecules. Afterwards the whole system can be flushed with buffer to wash out unspecific bound molecules. Finally the protein-loaded beads with attached molecules can be eluted for further investigation.

Metabolomic signatures of aggressive prostate cancer.

PubMed

McDunn, Jonathan E; Li, Zhen; Adam, Klaus-Peter; Neri, Bruce P; Wolfert, Robert L; Milburn, Michael V; Lotan, Yair; Wheeler, Thomas M

2013-10-01

Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings. A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer-free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement. Prostate tumors had significantly altered metabolite profiles compared to cancer-free prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate-specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness-associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NAD+ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5-year recurrence (AUROC from 0.53 to 0.64). These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests. Copyright © 2013 Wiley Periodicals, Inc.

Genetic and biochemical changes of the serotonergic system in migraine pathobiology.

PubMed

Gasparini, Claudia Francesca; Smith, Robert Anthony; Griffiths, Lyn Robyn

2017-12-01

Migraine is a brain disorder characterized by a piercing headache which affects one side of the head, located mainly at the temples and in the area around the eye. Migraine imparts substantial suffering to the family in addition to the sufferer, particularly as it affects three times more women than men and is most prevalent between the ages of 25 and 45, the years of child rearing. Migraine typically occurs in individuals with a genetic predisposition and is aggravated by specific environmental triggers. Attempts to study the biochemistry of migraine began as early as the 1960s and were primarily directed at serotonin metabolism after an increase of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin was observed in urine of migraineurs. Genetic and biochemical studies have primarily focused on the neurotransmitter serotonin, considering receptor binding, transport and synthesis of serotonin and have investigated serotonergic mediators including enzymes, receptors as well as intermediary metabolites. These studies have been mainly assayed in blood, CSF and urine as the most accessible fluids. More recently PET imaging technology integrated with a metabolomics and a systems biology platform are being applied to study serotonergic biology. The general trend observed is that migraine patients have alterations of neurotransmitter metabolism detected in biological fluids with different biochemistry from controls, however the interpretation of the biological significance of these peripheral changes is unresolved. In this review we present the biology of the serotonergic system and metabolic routes for serotonin and discuss results of biochemical studies with regard to alterations in serotonin in brain, cerebrospinal fluid, saliva, platelets, plasma and urine of migraine patients.

The application of Fourier transform infrared microspectroscopy for the study of diseased central nervous system tissue.

PubMed

Caine, Sally; Heraud, Philip; Tobin, Mark J; McNaughton, Donald; Bernard, Claude C A

2012-02-15

In the last two decades the field of infrared spectroscopy has seen enormous advances in both instrumentation and the development of bioinformatic methods for spectral analysis, allowing the examination of a large variety of healthy and diseased samples, including biological fluids, isolated cells, whole tissues, and tissue sections. The non-destructive nature of the technique, together with the ability to directly probe biochemical changes without the addition of stains or contrast agents, enables a range of complementary analyses. This review focuses on the application of Fourier transform infrared (FTIR) microspectroscopy to analyse central nervous system tissues, with the aim of understanding the biochemical and structural changes associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathies, multiple sclerosis, as well as brain tumours. Modern biospectroscopic methods that combine FTIR microspectroscopy with bioinformatic analysis constitute a powerful new methodology that can discriminate pathology from normal healthy tissue in a rapid, unbiased fashion, with high sensitivity and specificity. Notably, the ability to detect protein secondary structural changes associated with Alzheimer's plaques, neurons in Parkinson's disease, and in some spectra from meningioma, as well as in the animal models of Alzheimer's disease, transmissible spongiform encephalopathies, and multiple sclerosis, illustrates the power of this technology. The capacity to offer insight into the biochemical and structural changes underpinning aetio-pathogenesis of diseases in tissues provides both a platform to investigate early pathologies occurring in a variety of experimentally induced and naturally occurring central nervous system diseases, and the potential to evaluate new therapeutic approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

Bio-jETI: a service integration, design, and provisioning platform for orchestrated bioinformatics processes

PubMed Central

Margaria, Tiziana; Kubczak, Christian; Steffen, Bernhard

2008-01-01

Background With Bio-jETI, we introduce a service platform for interdisciplinary work on biological application domains and illustrate its use in a concrete application concerning statistical data processing in R and xcms for an LC/MS analysis of FAAH gene knockout. Methods Bio-jETI uses the jABC environment for service-oriented modeling and design as a graphical process modeling tool and the jETI service integration technology for remote tool execution. Conclusions As a service definition and provisioning platform, Bio-jETI has the potential to become a core technology in interdisciplinary service orchestration and technology transfer. Domain experts, like biologists not trained in computer science, directly define complex service orchestrations as process models and use efficient and complex bioinformatics tools in a simple and intuitive way. PMID:18460173

Beijing: a conference of commitments?

PubMed

Davis, S

1996-05-01

The author of this article holds the view that the Declaration and Platform for Action at the UN Fourth World Conference on Women held in Beijing in 1995 was the product of the most highly participatory process ever organized under the auspices of the UN. The Declaration and Platform expressed the strongest views on gender equality, empowerment, and justice that governments have ever endorsed. These documents were the consolidation of gains made by women in previous UN conferences. The 135-page Platform can be used at all levels of decision making. Governments and international can be held accountable for its provisions. The Platform exposes the problems violence and exploitation against women and girls as well as the revelation that environmental destruction is due to an unsustainable pattern of consumption and production, particularly in developed countries. Conference participants included about 3000 nongovernmental groups (NGOs). The Women's Linkage Caucus and WEDO served to facilitate the advocacy process by providing briefings on text still under negotiation and providing on-line recommendations from the 1995 and 1994 Commission on the Status of Women preparatory committee meetings. A scoreboard that tracked government's commitment at the 1995 preparatory committee meetings was reinstated in Beijing. The information was conveyed on the Internet. The European Union is credited with diluting the language about government commitment to the Platform. Governments are still given responsibility for implementation, and the need for political will is stressed (paragraph 293). Paragraph 297 indicates the process for implementation of the Platform and coordination with NGOs. Although the Platform recognizes the importance of women's groups and other NGOs, the responsibility for implementation is still given to governments.

Diagenetic patterns and pore space distribution along a platform to outer-shelf transect (Urgonian limestone, Barremian-Aptian, SE France)

NASA Astrophysics Data System (ADS)

Léonide, Philippe; Fournier, François; Reijmer, John J. G.; Vonhof, Hubert; Borgomano, Jean; Dijk, Jurrien; Rosenthal, Maelle; van Goethem, Manon; Cochard, Jean; Meulenaars, Karlien

2014-06-01

The Urgonian limestones of Late Barremian/Early Aptian from Provence (SE, France) are characterized by the occurrence of microporous limestones at regional scale alternating with tight carbonates. This study, based on petrographical (sediment texture, facies) and diagenetical analyses (cement stratigraphy, porosity and isotope geochemistry) of more than 800 limestone samples provides insight into the parameters controlling the genesis, preservation or occlusion of microporosity along an inner platform to outer shelf transect. The tight and microporous Urgonian limestones from Provence can be grouped into 5 rock-types based on textures, associated depositional environments, porosity and pore-type, being: (1) tight inner-platform: TIP; (2) porous inner platform: PIP; (3) tight outer platform: TOP; (4) porous outer platform: POP and (5) tight outer shelf: TOS. In tight (TIP, TOP and TOS types) limestones intergranular and intragranular pore spaces were entirely occluded by early marine and/or early meteoric cementation, whereas in microporous (PIP, POP) limestones a significant fraction of the intergranular macroporosity was preserved during early and shallow burial diagenesis. Micrite neomorphism (hybrid Ostwald ripening process) occurred during meteoric shallow burial diagenesis in PIP and POP limestones during the regional Durancian Uplift event (Albian-Lower Cenomanian). This process resulted in microporosity enhancement and preservation. Circulation of meteoric fluids during exhumation produces intercrystalline microporosity enhancement and moldic porosity development. The present study documents the important role that both early diagenetic and depositional cycles and long-term tectonic processes have on pore space evolution and distribution in Mesozoic platform carbonates.

Participatory Planning, Monitoring and Evaluation of Multi-Stakeholder Platforms in Integrated Landscape Initiatives.

PubMed

Kusters, Koen; Buck, Louise; de Graaf, Maartje; Minang, Peter; van Oosten, Cora; Zagt, Roderick

2018-07-01

Integrated landscape initiatives typically aim to strengthen landscape governance by developing and facilitating multi-stakeholder platforms. These are institutional coordination mechanisms that enable discussions, negotiations, and joint planning between stakeholders from various sectors in a given landscape. Multi-stakeholder platforms tend to involve complex processes with diverse actors, whose objectives and focus may be subjected to periodic re-evaluation, revision or reform. In this article we propose a participatory method to aid planning, monitoring, and evaluation of such platforms, and we report on experiences from piloting the method in Ghana and Indonesia. The method is comprised of three components. The first can be used to look ahead, identifying priorities for future multi-stakeholder collaboration in the landscape. It is based on the identification of four aspirations that are common across multi-stakeholder platforms in integrated landscape initiatives. The second can be used to look inward. It focuses on the processes within an existing multi-stakeholder platform in order to identify areas for possible improvement. The third can be used to look back, identifying the main outcomes of an existing platform and comparing them to the original objectives. The three components can be implemented together or separately. They can be used to inform planning and adaptive management of the platform, as well as to demonstrate performance and inform the design of new interventions.

High-resolution onshore-offshore morpho-bathymetric records of modern chalk and granitic shore platforms in NW France

NASA Astrophysics Data System (ADS)

Duperret, Anne; Raimbault, Céline; Le Gall, Bernard; Authemayou, Christine; van Vliet-Lanoë, Brigitte; Regard, Vincent; Dromelet, Elsa; Vandycke, Sara

2016-07-01

Modern shore platforms developed on rocky coasts are key areas for understanding coastal erosion processes during the Holocene. This contribution offers a detailed picture of two contrasted shore-platform systems, based on new high-resolution shallow-water bathymetry, further coupled with aerial LiDAR topography. Merged land-sea digital elevation models were achieved on two distinct types of rocky coasts along the eastern English Channel in France (Picardy and Upper-Normandy: PUN) and in a NE Atlantic area (SW Brittany: SWB) in NW France. About the PUN case, submarine steps, identified as paleo-shorelines, parallel the actual coastline. Coastal erosive processes appear to be continuous and regular through time, since mid-Holocene at least. In SWB, there is a discrepancy between contemporary coastline orientation and a continuous step extending from inland to offshore, identified as a paleo-shoreline. This illustrates a polyphased and inherited shore platform edification, mainly controlled by tectonic processes.

Project Report: Design and Analysis for the Deep Space Network BWG Type 2 Antenna Feed Platform

NASA Technical Reports Server (NTRS)

Crawford, Andrew

2011-01-01

The following report explains in detail the solid modeling design process and structural analysis of the LNA (Low Noise Amplifier) feed platform to be constructed and installed on the new BWG (Beam Wave Guide) Type-2 tracking antenna in Canberra, Australia, as well as all future similar BWG Type-2 antennas builds. The Deep Space Networks new BWG Type-2 antennas use beam waveguides to funnel and 'extract' the desired signals received from spacecraft, and the feed platform supports and houses the LNA(Low Noise Amplifier) feed-cone and cryogenic cooling equipment used in the signal transmission and receiving process. The mandated design and construction of this platform to be installed on the new tracking antenna will be used and incorporated on all future similar antenna builds.

Apparatus for sequentially transporting containers

NASA Technical Reports Server (NTRS)

Hudgins, J. L. (Inventor)

1982-01-01

Apparatus for transferring and manipulating a plurality of containers in a sequence is disclosed including a mechanical manipulator arm having a gripping device which automatically picks up a container at a fixed pickup position P and transfers it to a processing station. At a processing station X, the container is loaded with silicon wafers and thereafter returned by the arm to the fixed position P at the pickup and return station Y. A plurality of the containers may be processed in sequence from the fixed pickup position by providing a movable carriage upon which container pedestal platforms are supported, at least one of which is an elevator platform. The platforms include abutments for properly positioning the containers for accurate pickup by the manipulator arm.

Stability of Intercellular Exchange of Biochemical Substances Affected by Variability of Environmental Parameters

NASA Astrophysics Data System (ADS)

Mihailović, Dragutin T.; Budinčević, Mirko; Balaž, Igor; Mihailović, Anja

Communication between cells is realized by exchange of biochemical substances. Due to internal organization of living systems and variability of external parameters, the exchange is heavily influenced by perturbations of various parameters at almost all stages of the process. Since communication is one of essential processes for functioning of living systems it is of interest to investigate conditions for its stability. Using previously developed simplified model of bacterial communication in a form of coupled difference logistic equations we investigate stability of exchange of signaling molecules under variability of internal and external parameters.

Method and apparatus for energy efficient self-aeration in chemical, biochemical, and wastewater treatment processes

DOEpatents

Gao, Johnway [Richland, WA; Skeen, Rodney S [Pendleton, OR

2002-05-28

The present invention is a pulse spilling self-aerator (PSSA) that has the potential to greatly lower the installation, operation, and maintenance cost associated with aerating and mixing aqueous solutions. Currently, large quantities of low-pressure air are required in aeration systems to support many biochemical production processes and wastewater treatment plants. Oxygen is traditionally supplied and mixed by a compressor or blower and a mechanical agitator. These systems have high-energy requirements and high installation and maintenance costs. The PSSA provides a mixing and aeration capability that can increase operational efficiency and reduce overall cost.

Orbiter processing facility service platform failure and redesign

NASA Technical Reports Server (NTRS)

Harris, Jesse L.

1988-01-01

In a high bay of the Orbiter Processing Facility (OPF) at the Kennedy Space Center, technicians were preparing the space shuttle orbiter Discovery for rollout to the Vehicle Assembly Building (VAB). A service platform, commonly referred to as an OPF Bucket, was being retracted when it suddenly fell, striking a technician and impacting Discovery's payload bay door. A critical component in the OPF Bucket hoist system had failed, allowing the platform to fall. The incident was thoroughly investigated by both NASA and Lockheed, revealing many design deficiencies within the system. The deficiencies and the design changes made to correct them are reviewed.

Tier-scalable reconnaissance: the challenge of sensor optimization, sensor deployment, sensor fusion, and sensor interoperability

NASA Astrophysics Data System (ADS)

Fink, Wolfgang; George, Thomas; Tarbell, Mark A.

2007-04-01

Robotic reconnaissance operations are called for in extreme environments, not only those such as space, including planetary atmospheres, surfaces, and subsurfaces, but also in potentially hazardous or inaccessible operational areas on Earth, such as mine fields, battlefield environments, enemy occupied territories, terrorist infiltrated environments, or areas that have been exposed to biochemical agents or radiation. Real time reconnaissance enables the identification and characterization of transient events. A fundamentally new mission concept for tier-scalable reconnaissance of operational areas, originated by Fink et al., is aimed at replacing the engineering and safety constrained mission designs of the past. The tier-scalable paradigm integrates multi-tier (orbit atmosphere surface/subsurface) and multi-agent (satellite UAV/blimp surface/subsurface sensing platforms) hierarchical mission architectures, introducing not only mission redundancy and safety, but also enabling and optimizing intelligent, less constrained, and distributed reconnaissance in real time. Given the mass, size, and power constraints faced by such a multi-platform approach, this is an ideal application scenario for a diverse set of MEMS sensors. To support such mission architectures, a high degree of operational autonomy is required. Essential elements of such operational autonomy are: (1) automatic mapping of an operational area from different vantage points (including vehicle health monitoring); (2) automatic feature extraction and target/region-of-interest identification within the mapped operational area; and (3) automatic target prioritization for close-up examination. These requirements imply the optimal deployment of MEMS sensors and sensor platforms, sensor fusion, and sensor interoperability.

TIR-domain-containing adapter-inducing interferon-β (TRIF) forms filamentous structures, whose pro-apoptotic signalling is terminated by autophagy.

PubMed

Gentle, Ian E; McHenry, Kevin T; Weber, Arnim; Metz, Arlena; Kretz, Oliver; Porter, Dale; Häcker, Georg

2017-07-01

The formation of amyloid-like protein structures has recently emerged as a feature in signal transduction, particularly in innate immunity. These structures appear to depend on defined domains for their formation but likely also require dedicated ways to terminate signalling. We, here, define the innate immunity protein/Toll-like receptor adaptor TIR-domain-containing adapter-inducing interferon-β (TRIF) as a novel platform of fibril formation and probe signal initiation through TRIF as well as its termination in Toll-like receptor 3 (TLR3)-stimulated melanoma cells. A main signalling pathway triggered by TLR3 caused apoptosis, which was controlled by inhibitor of apoptosis proteins and was dependent on RIPK1 and independent of TNF. Using correlative electron/fluorescence microscopy, we visualised fibrillar structures formed through both Toll/interleukin-1 receptor and RIP homotypic interacting motif regions of TRIF. We provide evidence that these fibrillary structures are active signalling platforms whose activity is terminated by autophagy. TRIF-signalling enhanced autophagy, and fibrillary structures were partly contained within autophagosomes. Inhibition of autophagy increased levels of pro-apoptotic TRIF complexes, leading to the accumulation of active caspase-8 and enhanced apoptosis while stimulation of autophagy reduced TRIF-dependent death. We conclude that pro-death signals through TRIF are regulated by autophagy and propose that pro-apoptotic signalling through TRIF/RIPK1/caspase-8 occurs in fibrillary platforms. © 2017 Federation of European Biochemical Societies.

40 CFR 405.41 - Specialized definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Butter Subcategory § 405.41 Specialized... term “BOD5 input” shall mean the biochemical oxygen demand of the materials entered into process. It...

A Preliminary Study on Building an E-Education Platform for Indian School-Level Curricula

ERIC Educational Resources Information Center

Kanth, Rajeev Kumar; Laakso, Mikko-Jussi

2016-01-01

In this study, we explore the possibilities of utilizing and implementing an e-Education platform for Indian school-level curricula. This study will demonstrate how the e-Education platform provides a positive result to the students' learning and how this tool helps in managing the overall teaching processes efficiently. Before describing the…

Creating Math Videos: Comparing Platforms and Software

ERIC Educational Resources Information Center

Abbasian, Reza O.; Sieben, John T.

2016-01-01

In this paper we present a short tutorial on creating mini-videos using two platforms--PCs and tablets such as iPads--and software packages that work with these devices. Specifically, we describe the step-by-step process of creating and editing videos using a Wacom Intuos pen-tablet plus Camtasia software on a PC platform and using the software…

Can the Integration of a PLE in an E-Portfolio Platform Improve Generic Competences?

ERIC Educational Resources Information Center

Galván-Fernández, Cristina; Rubio-Hurtado, María José; Martínez-Olmo, Francesc; Rodríguez-Illera, José Luis

2017-01-01

The study analyzes the improvement in generic competences through e-portfolio/PLE platform and didactic planning. The new version of the platform, Digital Folder, contains utilities for students and teachers and some PLE components that help the learning process through e-portfolios. Didactic planning is compared for students from the University…

Computing molecular fluctuations in biochemical reaction systems based on a mechanistic, statistical theory of irreversible processes.

PubMed

Kulasiri, Don

2011-01-01

We discuss the quantification of molecular fluctuations in the biochemical reaction systems within the context of intracellular processes associated with gene expression. We take the molecular reactions pertaining to circadian rhythms to develop models of molecular fluctuations in this chapter. There are a significant number of studies on stochastic fluctuations in intracellular genetic regulatory networks based on single cell-level experiments. In order to understand the fluctuations associated with the gene expression in circadian rhythm networks, it is important to model the interactions of transcriptional factors with the E-boxes in the promoter regions of some of the genes. The pertinent aspects of a near-equilibrium theory that would integrate the thermodynamical and particle dynamic characteristics of intracellular molecular fluctuations would be discussed, and the theory is extended by using the theory of stochastic differential equations. We then model the fluctuations associated with the promoter regions using general mathematical settings. We implemented ubiquitous Gillespie's algorithms, which are used to simulate stochasticity in biochemical networks, for each of the motifs. Both the theory and the Gillespie's algorithms gave the same results in terms of the time evolution of means and variances of molecular numbers. As biochemical reactions occur far away from equilibrium-hence the use of the Gillespie algorithm-these results suggest that the near-equilibrium theory should be a good approximation for some of the biochemical reactions. © 2011 Elsevier Inc. All rights reserved.

Plant-pathogen interactions: what microarray tells about it?

PubMed

Lodha, T D; Basak, J

2012-01-01

Plant defense responses are mediated by elementary regulatory proteins that affect expression of thousands of genes. Over the last decade, microarray technology has played a key role in deciphering the underlying networks of gene regulation in plants that lead to a wide variety of defence responses. Microarray is an important tool to quantify and profile the expression of thousands of genes simultaneously, with two main aims: (1) gene discovery and (2) global expression profiling. Several microarray technologies are currently in use; most include a glass slide platform with spotted cDNA or oligonucleotides. Till date, microarray technology has been used in the identification of regulatory genes, end-point defence genes, to understand the signal transduction processes underlying disease resistance and its intimate links to other physiological pathways. Microarray technology can be used for in-depth, simultaneous profiling of host/pathogen genes as the disease progresses from infection to resistance/susceptibility at different developmental stages of the host, which can be done in different environments, for clearer understanding of the processes involved. A thorough knowledge of plant disease resistance using successful combination of microarray and other high throughput techniques, as well as biochemical, genetic, and cell biological experiments is needed for practical application to secure and stabilize yield of many crop plants. This review starts with a brief introduction to microarray technology, followed by the basics of plant-pathogen interaction, the use of DNA microarrays over the last decade to unravel the mysteries of plant-pathogen interaction, and ends with the future prospects of this technology.

Differential gene transcription across the life cycle in Daphnia magna using a new all genome custom-made microarray.

PubMed

Campos, Bruno; Fletcher, Danielle; Piña, Benjamín; Tauler, Romà; Barata, Carlos

2018-05-18

Unravelling the link between genes and environment across the life cycle is a challenging goal that requires model organisms with well-characterized life-cycles, ecological interactions in nature, tractability in the laboratory, and available genomic tools. Very few well-studied invertebrate model species meet these requirements, being the waterflea Daphnia magna one of them. Here we report a full genome transcription profiling of D. magna during its life-cycle. The study was performed using a new microarray platform designed from the complete set of gene models representing the whole transcribed genome of D. magna. Up to 93% of the existing 41,317 D. magna gene models showed differential transcription patterns across the developmental stages of D. magna, 59% of which were functionally annotated. Embryos showed the highest number of unique transcribed genes, mainly related to DNA, RNA, and ribosome biogenesis, likely related to cellular proliferation and morphogenesis of the several body organs. Adult females showed an enrichment of transcripts for genes involved in reproductive processes. These female-specific transcripts were essentially absent in males, whose transcriptome was enriched in specific genes of male sexual differentiation genes, like doublesex. Our results define major characteristics of transcriptional programs involved in the life-cycle, differentiate males and females, and show that large scale gene-transcription data collected in whole animals can be used to identify genes involved in specific biological and biochemical processes.

Novel metals and metal complexes as platforms for cancer therapy.

PubMed

Frezza, Michael; Hindo, Sarmad; Chen, Di; Davenport, Andrew; Schmitt, Sara; Tomco, Dajena; Dou, Q Ping

2010-06-01

Metals are essential cellular components selected by nature to function in several indispensable biochemical processes for living organisms. Metals are endowed with unique characteristics that include redox activity, variable coordination modes, and reactivity towards organic substrates. Due to their reactivity, metals are tightly regulated under normal conditions and aberrant metal ion concentrations are associated with various pathological disorders, including cancer. For these reasons, coordination complexes, either as drugs or prodrugs, become very attractive probes as potential anticancer agents. The use of metals and their salts for medicinal purposes, from iatrochemistry to modern day, has been present throughout human history. The discovery of cisplatin, cis-[Pt(II) (NH(3))(2)Cl(2)], was a defining moment which triggered the interest in platinum(II)- and other metal-containing complexes as potential novel anticancer drugs. Other interests in this field address concerns for uptake, toxicity, and resistance to metallodrugs. This review article highlights selected metals that have gained considerable interest in both the development and the treatment of cancer. For example, copper is enriched in various human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However the use of copper-binding ligands to target tumor copper could provide a novel strategy for cancer selective treatment. The use of nonessential metals as probes to target molecular pathways as anticancer agents is also emphasized. Finally, based on the interface between molecular biology and bioinorganic chemistry the design of coordination complexes for cancer treatment is reviewed and design strategies and mechanisms of action are discussed.

Sequential programmable self-assembly: Role of cooperative interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jonathan D. Halverson; Tkachenko, Alexei V.

Here, we propose a general strategy of “sequential programmable self-assembly” that enables a bottom-up design of arbitrary multi-particle architectures on nano- and microscales. We show that a naive realization of this scheme, based on the pairwise additive interactions between particles, has fundamental limitations that lead to a relatively high error rate. This can be overcome by using cooperative interparticle binding. The cooperativity is a well known feature of many biochemical processes, responsible, e.g., for signaling and regulations in living systems. Here we propose to utilize a similar strategy for high precision self-assembly, and show that DNA-mediated interactions provide a convenientmore » platform for its implementation. In particular, we outline a specific design of a DNA-based complex which we call “DNA spider,” that acts as a smart interparticle linker and provides a built-in cooperativity of binding. We demonstrate versatility of the sequential self-assembly based on spider-functionalized particles by designing several mesostructures of increasing complexity and simulating their assembly process. This includes a number of finite and repeating structures, in particular, the so-called tetrahelix and its several derivatives. Due to its generality, this approach allows one to design and successfully self-assemble virtually any structure made of a “GEOMAG” magnetic construction toy, out of nanoparticles. According to our results, once the binding cooperativity is strong enough, the sequential self-assembly becomes essentially error-free.« less

Sequential programmable self-assembly: Role of cooperative interactions

DOE PAGES

Jonathan D. Halverson; Tkachenko, Alexei V.

2016-03-04

Here, we propose a general strategy of “sequential programmable self-assembly” that enables a bottom-up design of arbitrary multi-particle architectures on nano- and microscales. We show that a naive realization of this scheme, based on the pairwise additive interactions between particles, has fundamental limitations that lead to a relatively high error rate. This can be overcome by using cooperative interparticle binding. The cooperativity is a well known feature of many biochemical processes, responsible, e.g., for signaling and regulations in living systems. Here we propose to utilize a similar strategy for high precision self-assembly, and show that DNA-mediated interactions provide a convenientmore » platform for its implementation. In particular, we outline a specific design of a DNA-based complex which we call “DNA spider,” that acts as a smart interparticle linker and provides a built-in cooperativity of binding. We demonstrate versatility of the sequential self-assembly based on spider-functionalized particles by designing several mesostructures of increasing complexity and simulating their assembly process. This includes a number of finite and repeating structures, in particular, the so-called tetrahelix and its several derivatives. Due to its generality, this approach allows one to design and successfully self-assemble virtually any structure made of a “GEOMAG” magnetic construction toy, out of nanoparticles. According to our results, once the binding cooperativity is strong enough, the sequential self-assembly becomes essentially error-free.« less

Measurement of baseline and orientation between distributed aerospace platforms.

PubMed

Wang, Wen-Qin

2013-01-01

Distributed platforms play an important role in aerospace remote sensing, radar navigation, and wireless communication applications. However, besides the requirement of high accurate time and frequency synchronization for coherent signal processing, the baseline between the transmitting platform and receiving platform and the orientation of platform towards each other during data recording must be measured in real time. In this paper, we propose an improved pulsed duplex microwave ranging approach, which allows determining the spatial baseline and orientation between distributed aerospace platforms by the proposed high-precision time-interval estimation method. This approach is novel in the sense that it cancels the effect of oscillator frequency synchronization errors due to separate oscillators that are used in the platforms. Several performance specifications are also discussed. The effectiveness of the approach is verified by simulation results.

Mechanically latchable tiltable platform for forming micromirrors and micromirror arrays

DOEpatents

Garcia, Ernest J [Albuquerque, NM; Polosky, Marc A [Tijeras, NM; Sleefe, Gerard E [Cedar Crest, NM

2006-12-12

A microelectromechanical (MEM) apparatus is disclosed which includes a platform that can be electrostatically tilted from being parallel to a substrate on which the platform to being tilted at an angle of 1 20 degrees with respect to the substrate. Once the platform has been tilted to a maximum angle of tilt, the platform can be locked in position using an electrostatically-operable latching mechanism which engages a tab protruding below the platform. The platform has a light-reflective upper surface which can be optionally coated to provide an enhanced reflectivity and form a micromirror. An array of such micromirrors can be formed on a common substrate for applications including optical switching (e.g. for fiber optic communications), optical information processing, image projection displays or non-volatile optical memories.

Stakeholders Opinions on Multi-Use Deep Water Offshore Platform in Hsiao-Liu-Chiu, Taiwan

PubMed Central

Sie, Ya-Tsune; Chang, Yang-Chi; Lu, Shiau-Yun

2018-01-01

This paper describes a group model building activity designed to elicit the potential effects a projected multi-use deep water offshore platform may have on its local environment, including ecological and socio-economic issues. As such a platform is proposed for construction around the island of Hsiao-Liu-Chiu, Taiwan, we organized several meetings with the local stakeholders and structured the debates using group modeling methods to promote consensus. During the process, the participants iteratively built and revised a causal-loop diagram that summarizes their opinions. Overall, local stakeholders concluded that a multi-use deep water offshore marine platform might have beneficial effects for Hsiao-Liu-Chiu because more tourists and fish could be attracted by the structure, but they also raised some potential problems regarding the law in Taiwan and the design of the offshore platform, especially its resistance to extreme weather. We report the method used and the main results and insights gained during the process. PMID:29415521

Counting and behavior of an individual fluorescent molecule without hydrodynamic flow, immobilization, or photon count statistics.

PubMed

Földes-Papp, Zeno; Baumann, Gerd; Demel, Ulrike; Tilz, Gernot P

2004-04-01

Many theoretical models of molecular interactions, biochemical and chemical reactions are described on the single-molecule level, although our knowledge about the biochemical/chemical structure and dynamics primarily originates from the investigation of many-molecule systems. At present, there are four experimental platforms to observe the movement and the behavior of single fluorescent molecules: wide-field epi-illumination, near-field optical scanning, and laser scanning confocal and multiphoton microscopy. The platforms are combined with analytical methods such as fluorescence resonance energy transfer (FRET), fluorescence auto-or two-color cross-correlation spectroscopy (FCS), fluorescence polarizing anisotropy, fluorescence quenching and fluorescence lifetime measurements. The original contribution focuses on counting and characterization of freely diffusing single molecules in a single-phase like a solution or a membrane without hydrodynamic flow, immobilization or burst size analysis of intensity traces. This can be achieved, for example, by Fluorescence auto- or two-color cross-Correlation Spectroscopy as demonstrated in this original article. Three criteria (Földes-Papp (2002) Pteridines, 13, 73-82; Földes-Papp et al. (2004a) J. Immunol. Meth., 286, 1-11; Földes-Papp et al. (2004b) J. Immunol. Meth., 286, 13-20) are discussed for performing continuous measurements with one and the same single (individual) molecule, freely diffusing in a solution or a membrane, from sub-milliseconds up to severals hours. The 'algorithms' developed for single-molecule fluorescence detection are called the 'selfsame single-fluorescent-molecule regime'. An interesting application of the results found is in the field of immunology. The application of the theory to experimental results shows that the theory is consistent with the experiments. The exposition of the novel ideas on Single (Solution)-Phase Single-Molecule Fluorescence auto- or two-color cross-Correlation Spectroscopy (SPSM-FCS) are comprehensively presented. As technology continues to improve, the limits of what FCS/FCCS is being asked to do are concomitantly pushed.

PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems.

PubMed

Ghaffarizadeh, Ahmadreza; Heiland, Randy; Friedman, Samuel H; Mumenthaler, Shannon M; Macklin, Paul

2018-02-01

Many multicellular systems problems can only be understood by studying how cells move, grow, divide, interact, and die. Tissue-scale dynamics emerge from systems of many interacting cells as they respond to and influence their microenvironment. The ideal "virtual laboratory" for such multicellular systems simulates both the biochemical microenvironment (the "stage") and many mechanically and biochemically interacting cells (the "players" upon the stage). PhysiCell-physics-based multicellular simulator-is an open source agent-based simulator that provides both the stage and the players for studying many interacting cells in dynamic tissue microenvironments. It builds upon a multi-substrate biotransport solver to link cell phenotype to multiple diffusing substrates and signaling factors. It includes biologically-driven sub-models for cell cycling, apoptosis, necrosis, solid and fluid volume changes, mechanics, and motility "out of the box." The C++ code has minimal dependencies, making it simple to maintain and deploy across platforms. PhysiCell has been parallelized with OpenMP, and its performance scales linearly with the number of cells. Simulations up to 105-106 cells are feasible on quad-core desktop workstations; larger simulations are attainable on single HPC compute nodes. We demonstrate PhysiCell by simulating the impact of necrotic core biomechanics, 3-D geometry, and stochasticity on the dynamics of hanging drop tumor spheroids and ductal carcinoma in situ (DCIS) of the breast. We demonstrate stochastic motility, chemical and contact-based interaction of multiple cell types, and the extensibility of PhysiCell with examples in synthetic multicellular systems (a "cellular cargo delivery" system, with application to anti-cancer treatments), cancer heterogeneity, and cancer immunology. PhysiCell is a powerful multicellular systems simulator that will be continually improved with new capabilities and performance improvements. It also represents a significant independent code base for replicating results from other simulation platforms. The PhysiCell source code, examples, documentation, and support are available under the BSD license at http://PhysiCell.MathCancer.org and http://PhysiCell.sf.net.

Biochemical differences in the mass and activity tests of lipoprotein-associated phospholipase A2 explain the discordance in results between the two assay methods.

PubMed

Zhuo, Shaoqiu; Wolfert, Robert L; Yuan, Chong

2017-12-01

There are two platforms for the detection of Lp-PLA 2 in sera or plasmas: by its enzymatic activity (PLAC® activity test) and by its mass concentration (PLAC® mass test). It has been long recognized that these two platforms are not correlated well. The underlying cause for this is therefore investigated by the biochemical characterization of the two PLAC tests. Human sera with and without the treatment by detergent were fractionated by using a Superose-6 column in phosphate buffered saline and the phospholipid associated Lp-PLA 2 was assessed by both PLAC mass and activity tests. The Lp-PLA 2 values of the two PLAC tests were compared under such conditions. Fractionation of sera and plasmas indicates that the association of Lp-PLA 2 with phospholipids, especially LDL and other large size phospholipid vesicles, may block the detection of the enzyme by antibodies in the immunoassay format under the conditions of the PLAC mass test. Inclusion of high concentration (>CMC, critical micelle concentration) of detergents in the assay buffer of PLAC mass test dissociates Lp-PLA 2 from phospholipid vesicles and results in the full detection of all Lp-PLA 2 in sera or plasmas for concentration. Such assay modification significantly improves the correlation between the PLAC mass and PLAC activity tests. PLAC mass test only detects a small portion of the total Lp-PLA 2 , mainly the Lp-PLA 2 associated with HDL. This is the main cause of the discordance and poor correlation between the PLAC mass and activity tests. Our results demonstrate the PLAC activity test is more accurate in assessing the total level of circulating Lp-PLA 2 . Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

40 CFR 405.31 - Specialized definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Cultured Products Subcategory § 405.31 Specialized... term “BOD5 input” shall mean the biochemical oxygen demand of the materials entered into process. It...

40 CFR 405.91 - Specialized definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Condensed Milk Subcategory § 405.91 Specialized... term “BOD5 input” shall mean the biochemical oxygen demand of the materials entered into process. It...

40 CFR 405.21 - Specialized definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Fluid Products Subcategory § 405.21 Specialized... term “BOD5 input” shall mean the biochemical oxygen demand of the materials entered into process. It...

Innovation through developing consumers communities. Part II: Digitalizing the innovation processes

NASA Astrophysics Data System (ADS)

Avasilcai, S.; Galateanu (Avram, E.

2015-11-01

The current research recognises the concept of innovation as the main driver for organisational growth and profitability. The companies seek to develop new ways to engage consumers and customers into co - creation value through the product design, development and distribution processes. However the main concern is manifested for new and creative ways of customization products based on consumers’ requirements and needs. Thus the need for innovative virtual instruments arose as the demand from social communities for personalised products or services increased. Basically companies should develop own innovative platforms, where consumers can participate, with ideas, concepts or other relevant contributions, and interact with designers or engineers for product development. This paper aims to present the most important features of platform development within BMW Group as a concept and as innovative instrument. From this point of view it is important to enhance past experiences of the company in the field of co - creation projects. There will be highlighted the dual consumers’ character as co - creator and co - evaluator based on their involvement in the proposed and developed projects and platform structure. The significant impact on platform functioning it has the diversity of company's concerns for Research & Development and innovation activities. From this point of view there will be assessed the platform structure, the main proposed themes and the evaluation process. The main outcome is to highlight the significance of platform development as innovative tool for consumers’ communities’ enhancement. Based on the analysis of “BMW Co-Creation Lab”, there will be revealed the main consumers concerns in terms of safety, comfort and appearance of the products. Thus it is important to understand the evaluation process of gathered ideas and intellectual property policy. The importance of platform development and implementation will be highlighted by company's results in terms of Research & Development investments and future projects which will be proposed, assessed and implemented by BMW Group in order to show the responsibility for their products and consumers.

Run-length encoding graphic rules, biochemically editable designs and steganographical numeric data embedment for DNA-based cryptographical coding system.

PubMed

Kawano, Tomonori

2013-03-01

There have been a wide variety of approaches for handling the pieces of DNA as the "unplugged" tools for digital information storage and processing, including a series of studies applied to the security-related area, such as DNA-based digital barcodes, water marks and cryptography. In the present article, novel designs of artificial genes as the media for storing the digitally compressed data for images are proposed for bio-computing purpose while natural genes principally encode for proteins. Furthermore, the proposed system allows cryptographical application of DNA through biochemically editable designs with capacity for steganographical numeric data embedment. As a model case of image-coding DNA technique application, numerically and biochemically combined protocols are employed for ciphering the given "passwords" and/or secret numbers using DNA sequences. The "passwords" of interest were decomposed into single letters and translated into the font image coded on the separate DNA chains with both the coding regions in which the images are encoded based on the novel run-length encoding rule, and the non-coding regions designed for biochemical editing and the remodeling processes revealing the hidden orientation of letters composing the original "passwords." The latter processes require the molecular biological tools for digestion and ligation of the fragmented DNA molecules targeting at the polymerase chain reaction-engineered termini of the chains. Lastly, additional protocols for steganographical overwriting of the numeric data of interests over the image-coding DNA are also discussed.

Application of the GNU Radio platform in the multistatic radar

NASA Astrophysics Data System (ADS)

Szlachetko, Boguslaw; Lewandowski, Andrzej

2009-06-01

This document presents the application of the Software Defined Radio-based platform in the multistatic radar. This platform consists of four-sensor linear antenna, Universal Software Radio Peripheral (USRP) hardware (radio frequency frontend) and GNU-Radio PC software. The paper provides information about architecture of digital signal processing performed by USRP's FPGA (digital down converting blocks) and PC host (implementation of the multichannel digital beamforming). The preliminary results of the signal recording performed by our experimental platform are presented.

Informatics in radiology (infoRAD): free DICOM image viewing and processing software for the Macintosh computer: what's available and what it can do for you.

PubMed

Escott, Edward J; Rubinstein, David

2004-01-01

It is often necessary for radiologists to use digital images in presentations and conferences. Most imaging modalities produce images in the Digital Imaging and Communications in Medicine (DICOM) format. The image files tend to be large and thus cannot be directly imported into most presentation software, such as Microsoft PowerPoint; the large files also consume storage space. There are many free programs that allow viewing and processing of these files on a personal computer, including conversion to more common file formats such as the Joint Photographic Experts Group (JPEG) format. Free DICOM image viewing and processing software for computers running on the Microsoft Windows operating system has already been evaluated. However, many people use the Macintosh (Apple Computer) platform, and a number of programs are available for these users. The World Wide Web was searched for free DICOM image viewing or processing software that was designed for the Macintosh platform or is written in Java and is therefore platform independent. The features of these programs and their usability were evaluated. There are many free programs for the Macintosh platform that enable viewing and processing of DICOM images. (c) RSNA, 2004.

Improvement in the amine glass platform by bubbling method for a DNA microarray

PubMed Central

Jee, Seung Hyun; Kim, Jong Won; Lee, Ji Hyeong; Yoon, Young Soo

2015-01-01

A glass platform with high sensitivity for sexually transmitted diseases microarray is described here. An amino-silane-based self-assembled monolayer was coated on the surface of a glass platform using a novel bubbling method. The optimized surface of the glass platform had highly uniform surface modifications using this method, as well as improved hybridization properties with capture probes in the DNA microarray. On the basis of these results, the improved glass platform serves as a highly reliable and optimal material for the DNA microarray. Moreover, in this study, we demonstrated that our glass platform, manufactured by utilizing the bubbling method, had higher uniformity, shorter processing time, lower background signal, and higher spot signal than the platforms manufactured by the general dipping method. The DNA microarray manufactured with a glass platform prepared using bubbling method can be used as a clinical diagnostic tool. PMID:26468293

Improvement in the amine glass platform by bubbling method for a DNA microarray.

PubMed

Jee, Seung Hyun; Kim, Jong Won; Lee, Ji Hyeong; Yoon, Young Soo

2015-01-01

A glass platform with high sensitivity for sexually transmitted diseases microarray is described here. An amino-silane-based self-assembled monolayer was coated on the surface of a glass platform using a novel bubbling method. The optimized surface of the glass platform had highly uniform surface modifications using this method, as well as improved hybridization properties with capture probes in the DNA microarray. On the basis of these results, the improved glass platform serves as a highly reliable and optimal material for the DNA microarray. Moreover, in this study, we demonstrated that our glass platform, manufactured by utilizing the bubbling method, had higher uniformity, shorter processing time, lower background signal, and higher spot signal than the platforms manufactured by the general dipping method. The DNA microarray manufactured with a glass platform prepared using bubbling method can be used as a clinical diagnostic tool.

Risk Management of P2P Internet Financing Service Platform

NASA Astrophysics Data System (ADS)

Yalei, Li

2017-09-01

Since 2005, the world’s first P2P Internet financing service platform Zopa in UK was introduced, in the development of “Internet +” trend, P2P Internet financing service platform has been developed rapidly. In 2007, China’s first P2P platform “filming loan” was established, marking the P2P Internet financing service platform to enter China and the rapid development. At the same time, China’s P2P Internet financing service platform also appeared in different forms of risk. This paper focuses on the analysis of the causes of risk of P2P Internet financing service platform and the performance of risk management process. It provides a solution to the Internet risk management plan, and explains the risk management system of the whole P2P Internet financing service platform and the future development direction.

An Integrated Web-Based 3d Modeling and Visualization Platform to Support Sustainable Cities

NASA Astrophysics Data System (ADS)

Amirebrahimi, S.; Rajabifard, A.

2012-07-01

Sustainable Development is found as the key solution to preserve the sustainability of cities in oppose to ongoing population growth and its negative impacts. This is complex and requires a holistic and multidisciplinary decision making. Variety of stakeholders with different backgrounds also needs to be considered and involved. Numerous web-based modeling and visualization tools have been designed and developed to support this process. There have been some success stories; however, majority failed to bring a comprehensive platform to support different aspects of sustainable development. In this work, in the context of SDI and Land Administration, CSDILA Platform - a 3D visualization and modeling platform -was proposed which can be used to model and visualize different dimensions to facilitate the achievement of sustainability, in particular, in urban context. The methodology involved the design of a generic framework for development of an analytical and visualization tool over the web. CSDILA Platform was then implemented via number of technologies based on the guidelines provided by the framework. The platform has a modular structure and uses Service-Oriented Architecture (SOA). It is capable of managing spatial objects in a 4D data store and can flexibly incorporate a variety of developed models using the platform's API. Development scenarios can be modeled and tested using the analysis and modeling component in the platform and the results are visualized in seamless 3D environment. The platform was further tested using number of scenarios and showed promising results and potentials to serve a wider need. In this paper, the design process of the generic framework, the implementation of CSDILA Platform and technologies used, and also findings and future research directions will be presented and discussed.

Exploring Google Earth Engine platform for big data processing: classification of multi-temporal satellite imagery for crop mapping

NASA Astrophysics Data System (ADS)

Shelestov, Andrii; Lavreniuk, Mykola; Kussul, Nataliia; Novikov, Alexei; Skakun, Sergii

2017-02-01

Many applied problems arising in agricultural monitoring and food security require reliable crop maps at national or global scale. Large scale crop mapping requires processing and management of large amount of heterogeneous satellite imagery acquired by various sensors that consequently leads to a “Big Data” problem. The main objective of this study is to explore efficiency of using the Google Earth Engine (GEE) platform when classifying multi-temporal satellite imagery with potential to apply the platform for a larger scale (e.g. country level) and multiple sensors (e.g. Landsat-8 and Sentinel-2). In particular, multiple state-of-the-art classifiers available in the GEE platform are compared to produce a high resolution (30 m) crop classification map for a large territory ( 28,100 km2 and 1.0 M ha of cropland). Though this study does not involve large volumes of data, it does address efficiency of the GEE platform to effectively execute complex workflows of satellite data processing required with large scale applications such as crop mapping. The study discusses strengths and weaknesses of classifiers, assesses accuracies that can be achieved with different classifiers for the Ukrainian landscape, and compares them to the benchmark classifier using a neural network approach that was developed in our previous studies. The study is carried out for the Joint Experiment of Crop Assessment and Monitoring (JECAM) test site in Ukraine covering the Kyiv region (North of Ukraine) in 2013. We found that Google Earth Engine (GEE) provides very good performance in terms of enabling access to the remote sensing products through the cloud platform and providing pre-processing; however, in terms of classification accuracy, the neural network based approach outperformed support vector machine (SVM), decision tree and random forest classifiers available in GEE.

KENNEDY SPACE CENTER, FLA. - This bird's-eye view of a high bay in the Orbiter Processing Facility (OPF) shows Space Shuttle Atlantis surrounded by the standard platforms and equipment required to process a Space Shuttle orbiter for flight. The high bay is 197 feet (60 meters) long, 150 feet (46 meters) wide, 95 feet (29 meters) high, and encompasses a 29,000-square-foot (2,694-meter) area. Platforms, a main access bridge, and two rolling bridges with trucks provide access to various parts of the orbiter. The next mission scheduled for Atlantis is STS-114, a utilization and logistics flight to the International Space Station.

NASA Image and Video Library

2003-09-03

KENNEDY SPACE CENTER, FLA. - This bird's-eye view of a high bay in the Orbiter Processing Facility (OPF) shows Space Shuttle Atlantis surrounded by the standard platforms and equipment required to process a Space Shuttle orbiter for flight. The high bay is 197 feet (60 meters) long, 150 feet (46 meters) wide, 95 feet (29 meters) high, and encompasses a 29,000-square-foot (2,694-meter) area. Platforms, a main access bridge, and two rolling bridges with trucks provide access to various parts of the orbiter. The next mission scheduled for Atlantis is STS-114, a utilization and logistics flight to the International Space Station.

Biochemical quality of the pharmaceutically licensed plasma OctaplasLG after implementation of a novel prion protein (PrPSc) removal technology and reduction of the solvent/detergent (S/D) process time.

PubMed

Heger, A; Svae, T-E; Neisser-Svae, A; Jordan, S; Behizad, M; Römisch, J

2009-10-01

A new chromatographic step for the selective binding of pathological prion proteins (PrP(Sc)) to an affinity ligand, developed and optimized for PrP(Sc) capture and attached to synthetic resin particles (PRDT, USA; ProMetic BioSciences Ltd, Isle of Man, UK) was implemented into the manufacturing process of the solvent/detergent (S/D) treated biopharmaceutical quality plasma Octaplas. Pilot batches of Octaplas with the implemented chromatographic step [labelled as OctaplasLG (ligand gel)] were manufactured by Octapharma PPGmbH, Vienna, Austria. The biochemical quality was compared directly after manufacturing as well as after 18 months storage. All samples were tested on global coagulation parameters, fibrinogen levels, activities of coagulation factors and protease inhibitors, ADAMTS13 levels, as well as markers of activated coagulation and fibrinolysis. In addition, von Willebrand factor multimeric analysis was performed. The incorporation of this novel chromatography into the large-scale routine manufacturing process was shown to be technically feasible and the performance of the column was assessed to be excellent. The biochemical studies showed that Octaplas and OctaplasLG produced without and with the new column, respectively, demonstrate an identical biochemical quality. OctaplasLG remained stable over a period of 18 months stored frozen. A parallel reduction of the S/D virus inactivation step from 4-4.5 to 1-1.5 h led to significantly higher activities of plasmin inhibitor. The studies confirmed that the affinity ligand chromatography under the developed conditions can be introduced into the Octaplas manufacturing process, as a mean to reduce potentially present PrP(Sc), without hampering the proven quality of this product.

Missile signal processing common computer architecture for rapid technology upgrade

NASA Astrophysics Data System (ADS)

Rabinkin, Daniel V.; Rutledge, Edward; Monticciolo, Paul

2004-10-01

Interceptor missiles process IR images to locate an intended target and guide the interceptor towards it. Signal processing requirements have increased as the sensor bandwidth increases and interceptors operate against more sophisticated targets. A typical interceptor signal processing chain is comprised of two parts. Front-end video processing operates on all pixels of the image and performs such operations as non-uniformity correction (NUC), image stabilization, frame integration and detection. Back-end target processing, which tracks and classifies targets detected in the image, performs such algorithms as Kalman tracking, spectral feature extraction and target discrimination. In the past, video processing was implemented using ASIC components or FPGAs because computation requirements exceeded the throughput of general-purpose processors. Target processing was performed using hybrid architectures that included ASICs, DSPs and general-purpose processors. The resulting systems tended to be function-specific, and required custom software development. They were developed using non-integrated toolsets and test equipment was developed along with the processor platform. The lifespan of a system utilizing the signal processing platform often spans decades, while the specialized nature of processor hardware and software makes it difficult and costly to upgrade. As a result, the signal processing systems often run on outdated technology, algorithms are difficult to update, and system effectiveness is impaired by the inability to rapidly respond to new threats. A new design approach is made possible three developments; Moore's Law - driven improvement in computational throughput; a newly introduced vector computing capability in general purpose processors; and a modern set of open interface software standards. Today's multiprocessor commercial-off-the-shelf (COTS) platforms have sufficient throughput to support interceptor signal processing requirements. This application may be programmed under existing real-time operating systems using parallel processing software libraries, resulting in highly portable code that can be rapidly migrated to new platforms as processor technology evolves. Use of standardized development tools and 3rd party software upgrades are enabled as well as rapid upgrade of processing components as improved algorithms are developed. The resulting weapon system will have a superior processing capability over a custom approach at the time of deployment as a result of a shorter development cycles and use of newer technology. The signal processing computer may be upgraded over the lifecycle of the weapon system, and can migrate between weapon system variants enabled by modification simplicity. This paper presents a reference design using the new approach that utilizes an Altivec PowerPC parallel COTS platform. It uses a VxWorks-based real-time operating system (RTOS), and application code developed using an efficient parallel vector library (PVL). A quantification of computing requirements and demonstration of interceptor algorithm operating on this real-time platform are provided.

Biochemical study of leaf browning in minimally processed leaves of lettuce (Lactuca sativa L. var. acephala).

PubMed

Degl'Innocenti, E; Guidi, L; Pardossi, A; Tognoni, F

2005-12-28

A series of biochemical parameters, including the concentration of total ascorbic acid (ASA(tot)) and the activities of phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidases (PODs), was investigated during cold storage (72 h at 4 degrees C in the dark) in fresh-cut (minimally processed) leaves of two lettuce (Lactuca sativa L. var. acephala) cultivars differing in the susceptibility to tissue browning: Green Salade Bowl (GSB), susceptible, and Red Salade Bowl (RSB), resistant. The two cultivars showed differences also at the biochemical level. The content in ASA(tot) increased in RSB, as a consequence of increased DHA concentration; conversely, ASA(tot) diminished in GSB, in which ASA was not detectable after 72 h of storage, thus suggesting a disappearance of ascorbate (both ASA and DHA) into nonactive forms. The antioxidant capacity (as determined by using FRAP analysis) decreased significantly during storage in RSB, while a strong increase was observed in GSB. PAL activity increased soon after processing reaching a maximum by 3 h, then it declined to a relatively constant value in RSB, while in GSB it showed a tendency to decrease in the first few hours from harvest and processing. POD activity, at least for chlorogenic acid, increased significantly during storage only in GSB.

Cloud Based Applications and Platforms (Presentation)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brodt-Giles, D.

2014-05-15

Presentation to the Cloud Computing East 2014 Conference, where we are highlighting our cloud computing strategy, describing the platforms on the cloud (including Smartgrid.gov), and defining our process for implementing cloud based applications.

High-Throughput Platform for Synthesis of Melamine-Formaldehyde Microcapsules.

PubMed

Çakir, Seda; Bauters, Erwin; Rivero, Guadalupe; Parasote, Tom; Paul, Johan; Du Prez, Filip E

2017-07-10

The synthesis of microcapsules via in situ polymerization is a labor-intensive and time-consuming process, where many composition and process factors affect the microcapsule formation and its morphology. Herein, we report a novel combinatorial technique for the preparation of melamine-formaldehyde microcapsules, using a custom-made and automated high-throughput platform (HTP). After performing validation experiments for ensuring the accuracy and reproducibility of the novel platform, a design of experiment study was performed. The influence of different encapsulation parameters was investigated, such as the effect of the surfactant, surfactant type, surfactant concentration and core/shell ratio. As a result, this HTP-platform is suitable to be used for the synthesis of different types of microcapsules in an automated and controlled way, allowing the screening of different reaction parameters in a shorter time compared to the manual synthetic techniques.

GATECloud.net: a platform for large-scale, open-source text processing on the cloud.

PubMed

Tablan, Valentin; Roberts, Ian; Cunningham, Hamish; Bontcheva, Kalina

2013-01-28

Cloud computing is increasingly being regarded as a key enabler of the 'democratization of science', because on-demand, highly scalable cloud computing facilities enable researchers anywhere to carry out data-intensive experiments. In the context of natural language processing (NLP), algorithms tend to be complex, which makes their parallelization and deployment on cloud platforms a non-trivial task. This study presents a new, unique, cloud-based platform for large-scale NLP research--GATECloud. net. It enables researchers to carry out data-intensive NLP experiments by harnessing the vast, on-demand compute power of the Amazon cloud. Important infrastructural issues are dealt with by the platform, completely transparently for the researcher: load balancing, efficient data upload and storage, deployment on the virtual machines, security and fault tolerance. We also include a cost-benefit analysis and usage evaluation.

Microfluidic Lab-on-a-Chip Platforms: Requirements, Characteristics and Applications

NASA Astrophysics Data System (ADS)

Mark, D.; Haeberle, S.; Roth, G.; Von Stetten, F.; Zengerle, R.

This review summarizes recent developments in microfluidic platform approaches. In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the implementation of different application-specific (bio-) chemical processes, automated by microfluidic process integration [1]. A brief introduction into technical advances, major market segments and promising applications is followed by a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electro-kinetics, electrowetting, surface acoustic waves, and systems for massively parallel analysis. The review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposable, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols.

A resilient and secure software platform and architecture for distributed spacecraft

NASA Astrophysics Data System (ADS)

Otte, William R.; Dubey, Abhishek; Karsai, Gabor

2014-06-01

A distributed spacecraft is a cluster of independent satellite modules flying in formation that communicate via ad-hoc wireless networks. This system in space is a cloud platform that facilitates sharing sensors and other computing and communication resources across multiple applications, potentially developed and maintained by different organizations. Effectively, such architecture can realize the functions of monolithic satellites at a reduced cost and with improved adaptivity and robustness. Openness of these architectures pose special challenges because the distributed software platform has to support applications from different security domains and organizations, and where information flows have to be carefully managed and compartmentalized. If the platform is used as a robust shared resource its management, configuration, and resilience becomes a challenge in itself. We have designed and prototyped a distributed software platform for such architectures. The core element of the platform is a new operating system whose services were designed to restrict access to the network and the file system, and to enforce resource management constraints for all non-privileged processes Mixed-criticality applications operating at different security labels are deployed and controlled by a privileged management process that is also pre-configuring all information flows. This paper describes the design and objective of this layer.

Technology Enhanced Learning for People with Intellectual Disabilities and Cerebral Paralysis: The MAS Platform

NASA Astrophysics Data System (ADS)

Colomo-Palacios, Ricardo; Paniagua-Martín, Fernando; García-Crespo, Ángel; Ruiz-Mezcua, Belén

Education for students with disabilities now takes place in a wide range of settings, thus, including a wider range of assistive tools. As a result of this, one of the most interesting application domains of technology enhanced learning is related to the adoption of learning technologies and designs for people with disabilities. Following this unstoppable trend, this paper presents MAS, a software platform aimed to help people with severe intellectual disabilities and cerebral paralysis in their learning processes. MAS, as a technology enhanced learning platform, provides several tools that supports learning and monitoring for people with special needs, including adaptative games, data processing and monitoring tools. Installed in a special needs education institution in Madrid, Spain, MAS provides special educators with a tool that improved students education processes.

40 CFR 405.61 - Specialized definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Natural and Processed Cheese Subcategory § 405.61... subpart. (b) The term “BOD5 input” shall mean the biochemical oxygen demand of the materials entered into...

Design of a dynamic test platform for autonomous robot vision systems

NASA Technical Reports Server (NTRS)

Rich, G. C.

1980-01-01

The concept and design of a dynamic test platform for development and evluation of a robot vision system is discussed. The platform is to serve as a diagnostic and developmental tool for future work with the RPI Mars Rover's multi laser/multi detector vision system. The platform allows testing of the vision system while its attitude is varied, statically or periodically. The vision system is mounted on the test platform. It can then be subjected to a wide variety of simulated can thus be examined in a controlled, quantitative fashion. Defining and modeling Rover motions and designing the platform to emulate these motions are also discussed. Individual aspects of the design process are treated separately, as structural, driving linkages, and motors and transmissions.

Bacteriophage lambda: The path from biology to theranostic agent.

PubMed

Catalano, Carlos E

2018-03-13

Viral particles provide an attractive platform for the engineering of semisynthetic therapeutic nanoparticles. They can be modified both genetically and chemically in a defined manner to alter their surface characteristics, for targeting specific cell types, to improve their pharmacokinetic features and to attenuate (or enhance) their antigenicity. These advantages derive from a detailed understanding of virus biology, gleaned from decades of fundamental genetic, biochemical, and structural studies that have provided mechanistic insight into virus assembly pathways. In particular, bacteriophages offer significant advantages as nanoparticle platforms and several have been adapted toward the design and engineering of "designer" nanoparticles for therapeutic and diagnostic (theranostic) applications. The present review focuses on one such virus, bacteriophage lambda; I discuss the biology of lambda, the tools developed to faithfully recapitulate the lambda assembly reactions in vitro and the observations that have led to cooptation of the lambda system for nanoparticle design. This discussion illustrates how a fundamental understanding of virus assembly has allowed the rational design and construction of semisynthetic nanoparticles as potential theranostic agents and illustrates the concept of benchtop to bedside translational research. This article is categorized under: Biology-Inspired Nanomaterials> Protein and Virus-Based Structures Biology-Inspired Nanomaterials> Nucleic Acid-Based Structures. © 2018 Wiley Periodicals, Inc.

Bacterial cell-free expression technology to in vitro systems engineering and optimization.

PubMed

Caschera, Filippo

2017-06-01

Cell-free expression system is a technology for the synthesis of proteins in vitro . The system is a platform for several bioengineering projects, e.g. cell-free metabolic engineering, evolutionary design of experiments, and synthetic minimal cell construction. Bacterial cell-free protein synthesis system (CFPS) is a robust tool for synthetic biology. The bacteria lysate, the DNA, and the energy module, which are the three optimized sub-systems for in vitro protein synthesis, compose the integrated system. Currently, an optimized E. coli cell-free expression system can produce up to ∼2.3 mg/mL of a fluorescent reporter protein. Herein, I will describe the features of ATP-regeneration systems for in vitro protein synthesis, and I will present a machine-learning experiment for optimizing the protein yield of E. coli cell-free protein synthesis systems. Moreover, I will introduce experiments on the synthesis of a minimal cell using liposomes as dynamic containers, and E. coli cell-free expression system as biochemical platform for metabolism and gene expression. CFPS can be further integrated with other technologies for novel applications in environmental, medical and material science.

Controlled Endolysosomal Release of Agents by pH-responsive Polymer Blend Particles.

PubMed

Zhan, Xi; Tran, Kenny K; Wang, Liguo; Shen, Hong

2015-07-01

A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly(lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer. We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space. We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes. This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity.

Controlled endolysosomal release of agents by pH-responsive polymer blend particles

PubMed Central

Zhan, Xi; Tran, Kenny K.; Wang, Liguo; Shen, Hong

2015-01-01

Purpose A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly (lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer. Methods We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space. Results We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes. Conclusions This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity. PMID:25592550

A novel approach to construct a horseradish peroxidase|hydrophilic ionic liquids|Au nanoparticles dotted titanate nanotubes biosensor for amperometric sensing of hydrogen peroxide.

PubMed

Liu, Xiaoqiang; Feng, Heqing; Zhao, Ruoxia; Wang, Yanbing; Liu, Xiuhua

2012-01-15

The direct electrochemistry of horseradish peroxidase (HRP) on a novel sensing platform modified glassy carbon electrode (GCE) has been achieved. This sensing platform consists of Nafion, hydrophilic room-temperature ionic liquid (RTIL) and Au nanoparticles dotted titanate nanotubes (GNPs-TNTs). The composite of RTIL and GNPs-TNTs was immobilized on the electrode surface through the gelation of a small amount of HRP aqueous solution. The composite was characterized by transmission electron microscopy (TEM), powder X-ray diffraction (XRD) and infrared spectroscopy (IR). UV-Vis and IR spectroscopy demonstrated that HRP in the composite could retain its native secondary structure and biochemical activity. The HRP-immobilized electrode was investigated by cyclic voltammetry and chronoamperometry. The results from both techniques showed that the direct electron transfer between the nanocomposite modified electrodes and heme in HRP could be realized. The biosensor responded to H(2)O(2) in the linear range from 5×10(-6) to 1×10(-3) mol L(-1) with a detection limit of 2.1×10(-6) mol L(-1) (based on the S/N=3). Copyright © 2011 Elsevier B.V. All rights reserved.

Chemomechanically engineered 3D organotypic platforms of bladder cancer dormancy and reactivation.

PubMed

Pavan Grandhi, Taraka Sai; Potta, Thrimoorthy; Nitiyanandan, Rajeshwar; Deshpande, Indrani; Rege, Kaushal

2017-10-01

Tumors undergo periods of dormancy followed by reactivation leading to metastatic disease. Arrest in the G0/G1 phase of the cell cycle and resistance to chemotherapeutic drugs are key hallmarks of dormant tumor cells. Here, we describe a 3D platform of bladder cancer cell dormancy and reactivation facilitated by a novel aminoglycoside-derived hydrogel, Amikagel. These 3D dormant tumor microenvironments (3D-DTMs) were arrested in the G0/G1 phase and were highly resistant to anti-proliferative drugs. Inhibition of targets in the cellular protein production machinery led to induction of endoplasmic reticulum (ER) stress and complete ablation of 3D-DTMs. Nanoparticle-mediated calcium delivery significantly accelerated ER stress-mediated 3D-DTM death. Transfer of 3D-DTMs onto weaker and adhesive Amikagels resulted in selective reactivation of a sub-population of N-cadherin deficient cells from dormancy. Whole-transcriptome analyses further indicated key biochemical differences between dormant and proliferative cancer cells. Taken together, our results indicate that 3D bladder cancer microenvironments of dormancy and reactivation can facilitate fundamental advances and novel drug discovery in cancer. Copyright © 2017. Published by Elsevier Ltd.

Effect of altitude on biochemical composition and quality of green arabica coffee beans can be affected by shade and postharvest processing method.

PubMed

Worku, Mohammed; de Meulenaer, Bruno; Duchateau, Luc; Boeckx, Pascal

2018-03-01

Although various studies have assessed altitude, shade and postharvest processing effects on biochemical content and quality of coffee beans, data on their interactions are scarce. The individual and interactive effects of these factors on the caffeine, chlorogenic acids (CGA) and sucrose contents as well as physical and sensory qualities of green coffee beans from large plantations in southwestern Ethiopia were evaluated. Caffeine and CGA contents decreased with increasing altitude; they respectively declined 0.12 and 1.23gkg -1 100m -1 . Sucrose content increased with altitude; however, the altitude effect was significant for wet-processed beans (3.02gkg -1 100m -1 ), but not for dry-processed beans (0.36g kg -1 100m -1 ). Similarly, sucrose content increased with altitude with much stronger effect for coffee grown without shade (2.11gkg -1 100m -1 ) compared to coffee grown under shade (0.93gkg -1 100m -1 ). Acidity increased with altitude when coffee was grown under shade (0.22 points 100m -1 ), but no significant altitude effect was observed on coffee grown without shade. Beans grown without shade showed a higher physical quality score for dry (37.2) than for wet processing (29.1). These results generally underline the complex interaction effects between altitude and shade or postharvest processing on biochemical composition and quality of green arabica coffee beans. Copyright © 2017. Published by Elsevier Ltd.

A Web Tool for Research in Nonlinear Optics

NASA Astrophysics Data System (ADS)

Prikhod'ko, Nikolay V.; Abramovsky, Viktor A.; Abramovskaya, Natalia V.; Demichev, Andrey P.; Kryukov, Alexandr P.; Polyakov, Stanislav P.

2016-02-01

This paper presents a project of developing the web platform called WebNLO for computer modeling of nonlinear optics phenomena. We discuss a general scheme of the platform and a model for interaction between the platform modules. The platform is built as a set of interacting RESTful web services (SaaS approach). Users can interact with the platform through a web browser or command line interface. Such a resource has no analogues in the field of nonlinear optics and will be created for the first time therefore allowing researchers to access high-performance computing resources that will significantly reduce the cost of the research and development process.

An Inductive Logic Programming Approach to Validate Hexose Binding Biochemical Knowledge.

PubMed

Nassif, Houssam; Al-Ali, Hassan; Khuri, Sawsan; Keirouz, Walid; Page, David

2010-01-01

Hexoses are simple sugars that play a key role in many cellular pathways, and in the regulation of development and disease mechanisms. Current protein-sugar computational models are based, at least partially, on prior biochemical findings and knowledge. They incorporate different parts of these findings in predictive black-box models. We investigate the empirical support for biochemical findings by comparing Inductive Logic Programming (ILP) induced rules to actual biochemical results. We mine the Protein Data Bank for a representative data set of hexose binding sites, non-hexose binding sites and surface grooves. We build an ILP model of hexose-binding sites and evaluate our results against several baseline machine learning classifiers. Our method achieves an accuracy similar to that of other black-box classifiers while providing insight into the discriminating process. In addition, it confirms wet-lab findings and reveals a previously unreported Trp-Glu amino acids dependency.

Performance limits and trade-offs in entropy-driven biochemical computers.

PubMed

Chu, Dominique

2018-04-14

It is now widely accepted that biochemical reaction networks can perform computations. Examples are kinetic proof reading, gene regulation, or signalling networks. For many of these systems it was found that their computational performance is limited by a trade-off between the metabolic cost, the speed and the accuracy of the computation. In order to gain insight into the origins of these trade-offs, we consider entropy-driven computers as a model of biochemical computation. Using tools from stochastic thermodynamics, we show that entropy-driven computation is subject to a trade-off between accuracy and metabolic cost, but does not involve time-trade-offs. Time trade-offs appear when it is taken into account that the result of the computation needs to be measured in order to be known. We argue that this measurement process, although usually ignored, is a major contributor to the cost of biochemical computation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Vitreous humour - routine or alternative material for analysis in forensic medicine.

PubMed

Markowska, Joanna; Szopa, Monika; Zawadzki, Marcin; Piekoszewski, Wojciech

2017-01-01

Biological materials used in toxicological analyses in forensic medicine traditionally include blood, urine and vitreous humour. Forensic use of the vitreous body is mostly due to the need to assess the endogenous concentration of ethyl alcohol in the process of human body decomposition. The vitreous body is an underestimated biological material, even though its biochemical properties and anatomical location make it suitable for specific forensic toxicology tests as a reliable material for the preparation of forensic expert opinions. Based on the available literature the paper gathers information on the biochemical structure of the vitreous body, ways to secure the material after collection and its use in postmortem diagnostics. Specific applications of the vitreous humour for biochemical and toxicological tests are discussed, with a focus on its advantages and limitations in forensic medical assessment which are attributable to its biochemical properties, anatomical location and limited scientific studies on the distribution of xenobiotics in the vitreous body.

CADLIVE toolbox for MATLAB: automatic dynamic modeling of biochemical networks with comprehensive system analysis.

PubMed

Inoue, Kentaro; Maeda, Kazuhiro; Miyabe, Takaaki; Matsuoka, Yu; Kurata, Hiroyuki

2014-09-01

Mathematical modeling has become a standard technique to understand the dynamics of complex biochemical systems. To promote the modeling, we had developed the CADLIVE dynamic simulator that automatically converted a biochemical map into its associated mathematical model, simulated its dynamic behaviors and analyzed its robustness. To enhance the feasibility by CADLIVE and extend its functions, we propose the CADLIVE toolbox available for MATLAB, which implements not only the existing functions of the CADLIVE dynamic simulator, but also the latest tools including global parameter search methods with robustness analysis. The seamless, bottom-up processes consisting of biochemical network construction, automatic construction of its dynamic model, simulation, optimization, and S-system analysis greatly facilitate dynamic modeling, contributing to the research of systems biology and synthetic biology. This application can be freely downloaded from http://www.cadlive.jp/CADLIVE_MATLAB/ together with an instruction.

TERMINAL ELECTRON ACCEPTING PROCESSES IN THE ALLUVIAL SEDIMENTS OF A HEADWATER STREAM

EPA Science Inventory

Chemical fluxes between catchments and streams are influenced by biochemical processes in the groundwater-stream water (GW-SW) ecotone, the interface between stream surface water and groundwater. Terminal electron accepting processes (TEAPs) that are utilized in respiration of ...

Development of efficient, integrated cellulosic biorefineries : LDRD final report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teh, Kwee-Yan; Hecht, Ethan S.; Shaddix, Christopher R.

2010-09-01

Cellulosic ethanol, generated from lignocellulosic biomass sources such as grasses and trees, is a promising alternative to conventional starch- and sugar-based ethanol production in terms of potential production quantities, CO{sub 2} impact, and economic competitiveness. In addition, cellulosic ethanol can be generated (at least in principle) without competing with food production. However, approximately 1/3 of the lignocellulosic biomass material (including all of the lignin) cannot be converted to ethanol through biochemical means and must be extracted at some point in the biochemical process. In this project we gathered basic information on the prospects for utilizing this lignin residue material inmore » thermochemical conversion processes to improve the overall energy efficiency or liquid fuel production capacity of cellulosic biorefineries. Two existing pretreatment approaches, soaking in aqueous ammonia (SAA) and the Arkenol (strong sulfuric acid) process, were implemented at Sandia and used to generated suitable quantities of residue material from corn stover and eucalyptus feedstocks for subsequent thermochemical research. A third, novel technique, using ionic liquids (IL) was investigated by Sandia researchers at the Joint Bioenergy Institute (JBEI), but was not successful in isolating sufficient lignin residue. Additional residue material for thermochemical research was supplied from the dilute-acid simultaneous saccharification/fermentation (SSF) pilot-scale process at the National Renewable Energy Laboratory (NREL). The high-temperature volatiles yields of the different residues were measured, as were the char combustion reactivities. The residue chars showed slightly lower reactivity than raw biomass char, except for the SSF residue, which had substantially lower reactivity. Exergy analysis was applied to the NREL standard process design model for thermochemical ethanol production and from a prototypical dedicated biochemical process, with process data supplied by a recent report from the National Research Council (NRC). The thermochemical system analysis revealed that most of the system inefficiency is associated with the gasification process and subsequent tar reforming step. For the biochemical process, the steam generation from residue combustion, providing the requisite heating for the conventional pretreatment and alcohol distillation processes, was shown to dominate the exergy loss. An overall energy balance with different potential distillation energy requirements shows that as much as 30% of the biomass energy content may be available in the future as a feedstock for thermochemical production of liquid fuels.« less

High density electronic circuit and process for making

DOEpatents

Morgan, William P.

1999-01-01

High density circuits with posts that protrude beyond one surface of a substrate to provide easy mounting of devices such as integrated circuits. The posts also provide stress relief to accommodate differential thermal expansion. The process allows high interconnect density with fewer alignment restrictions and less wasted circuit area than previous processes. The resulting substrates can be test platforms for die testing and for multi-chip module substrate testing. The test platform can contain active components and emulate realistic operational conditions, replacing shorts/opens net testing.

Exercise-induced biochemical changes and their potential influence on cancer: a scientific review

PubMed Central

Thomas, Robert James; Kenfield, Stacey A; Jimenez, Alfonso

2017-01-01

Aim To review and discuss the available international literature regarding the indirect and direct biochemical mechanisms that occur after exercise, which could positively, or negatively, influence oncogenic pathways. Methods The PubMed, MEDLINE, Embase and Cochrane libraries were searched for papers up to July 2016 addressing biochemical changes after exercise with a particular reference to cancer. The three authors independently assessed their appropriateness for inclusion in this review based on their scientific quality and relevance. Results 168 papers were selected and categorised into indirect and direct biochemical pathways. The indirect effects included changes in vitamin D, weight reduction, sunlight exposure and improved mood. The direct effects included insulin-like growth factor, epigenetic effects on gene expression and DNA repair, vasoactive intestinal peptide, oxidative stress and antioxidant pathways, heat shock proteins, testosterone, irisin, immunity, chronic inflammation and prostaglandins, energy metabolism and insulin resistance. Summary Exercise is one of several lifestyle factors known to lower the risk of developing cancer and is associated with lower relapse rates and better survival. This review highlights the numerous biochemical processes, which explain these potential anticancer benefits. PMID:27993842

Microfluidics: innovative approaches for rapid diagnosis of antibiotic-resistant bacteria.

PubMed

Aroonnual, Amornrat; Janvilisri, Tavan; Ounjai, Puey; Chankhamhaengdecha, Surang

2017-02-28

The emergence of antibiotic-resistant bacteria has become a major global health concern. Rapid and accurate diagnostic strategies to determine the antibiotic susceptibility profile prior to antibiotic prescription and treatment are critical to control drug resistance. The standard diagnostic procedures for the detection of antibiotic-resistant bacteria, which rely mostly on phenotypic characterization, are time consuming, insensitive and often require skilled personnel, making them unsuitable for point-of-care (POC) diagnosis. Various molecular techniques have therefore been implemented to help speed up the process and increase sensitivity. Over the past decade, microfluidic technology has gained great momentum in medical diagnosis as a series of fluid handling steps in a laboratory can be simplified and miniaturized on to a small platform, allowing marked reduction of sample amount, high portability and tremendous possibility for integration with other detection technologies. These advantages render the microfluidic system a great candidate to be developed into an easy-to-use sample-to-answer POC diagnosis suitable for application in remote clinical settings. This review provides an overview of the current development of microfluidic technologies for the nucleic acid based and phenotypic-based detections of antibiotic resistance. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Whole cell quenched flow analysis.

PubMed

Chiang, Ya-Yu; Haeri, Sina; Gizewski, Carsten; Stewart, Joanna D; Ehrhard, Peter; Shrimpton, John; Janasek, Dirk; West, Jonathan

2013-12-03

This paper describes a microfluidic quenched flow platform for the investigation of ligand-mediated cell surface processes with unprecedented temporal resolution. A roll-slip behavior caused by cell-wall-fluid coupling was documented and acts to minimize the compression and shear stresses experienced by the cell. This feature enables high-velocity (100-400 mm/s) operation without impacting the integrity of the cell membrane. In addition, rotation generates localized convection paths. This cell-driven micromixing effect causes the cell to become rapidly enveloped with ligands to saturate the surface receptors. High-speed imaging of the transport of a Janus particle and fictitious domain numerical simulations were used to predict millisecond-scale biochemical switching times. Dispersion in the incubation channel was characterized by microparticle image velocimetry and minimized by using a horizontal Hele-Shaw velocity profile in combination with vertical hydrodynamic focusing to achieve highly reproducible incubation times (CV = 3.6%). Microfluidic quenched flow was used to investigate the pY1131 autophosphorylation transition in the type I insulin-like growth factor receptor (IGF-1R). This predimerized receptor undergoes autophosphorylation within 100 ms of stimulation. Beyond this demonstration, the extreme temporal resolution can be used to gain new insights into the mechanisms underpinning a tremendous variety of important cell surface events.

Effect of microbial activities on stored raw buffalo hide.

PubMed

Shede, P N; Kanekar, P P; Polkade, A V; Sarnaik, S S; Dhakephalkar, P K; Chiplonkar, S A; Nilegaonkar, S S

2009-11-01

'Keeping qualities' of hides are dependent on the total microbial flora associated with the hides and the biochemical changes brought about by these microorganisms during short-term storage at ambient temperature (28 +/- 2 degrees C). It was evident that within first 24 hr of hide's ambient storage, bacterial load was raised to 8.8 log cfu g(-1) hide from 6.1 log cfu g(-1) hide. Nonlinear parabolic increase in release of hydroxyproline and tyrosine from stored hide was observed starting from 0 hr and confirming proteolytic activities. Continuous release of CO2 from the stored hide suggested its mineralization. Exponential release of free fatty acids during storage indicated simultaneous lipolysis. Thus the process of biodegradation during the course of ambient storage of hide piece was found to progress steadily and seems to be interrelated as well as very complex. During the storage period, the liquefaction of hide piece was also observed visually within 96 hr. Present studies of assessment of bacterial activities on hide with respect to total bacterial load, release of amino acids, free fatty acids and evolved CO2 provide data that can be used to formulate and evaluate hide curing agent(s) other than salt, thus rendering leather industry a platform to design bio-based technologies for efficient and ecofriendly preservation of raw materials.

In Silico Dynamics: computer simulation in a Virtual Embryo ...

EPA Pesticide Factsheets

Abstract: Utilizing cell biological information to predict higher order biological processes is a significant challenge in predictive toxicology. This is especially true for highly dynamical systems such as the embryo where morphogenesis, growth and differentiation require precisely orchestrated interactions between diverse cell populations. In patterning the embryo, genetic signals setup spatial information that cells then translate into a coordinated biological response. This can be modeled as ‘biowiring diagrams’ representing genetic signals and responses. Because the hallmark of multicellular organization resides in the ability of cells to interact with one another via well-conserved signaling pathways, multiscale computational (in silico) models that enable these interactions provide a platform to translate cellular-molecular lesions perturbations into higher order predictions. Just as ‘the Cell’ is the fundamental unit of biology so too should it be the computational unit (‘Agent’) for modeling embryogenesis. As such, we constructed multicellular agent-based models (ABM) with ‘CompuCell3D’ (www.compucell3d.org) to simulate kinematics of complex cell signaling networks and enable critical tissue events for use in predictive toxicology. Seeding the ABMs with HTS/HCS data from ToxCast demonstrated the potential to predict, quantitatively, the higher order impacts of chemical disruption at the cellular or biochemical level. This is demonstrate

On-demand generation and mixing of liquid-in-gas slugs with digitally-programmable composition and size

PubMed Central

Chen, Yi-Chun; Liu, Kan; Shen, Clifton Kwang-Fu; van Dam, R. Michael

2017-01-01

Microscopic droplets or slugs of mixed reagents provide a convenient platform for performing large numbers of isolated biochemical or chemical reactions for many screening and optimization applications. Myriad microfluidic approaches have emerged for creating droplets or slugs with controllable size and composition, generally using an immiscible carrier fluid to assist with the formation or merging processes. We report a novel device for generation of liquid slugs in air when the use of a carrier liquid is not compatible with the application. The slug generator contains two adjacent chambers, each of which has a volume that can be digitally adjusted by closing selected microvalves. Reagents are filled into the two chambers, merged together into a contiguous liquid slug, ejected at the desired time from the device using gas pressure, and mixed by flowing in a downstream channel. Programmable size and composition of slugs is achieved by dynamically adjusting the volume of each chamber prior to filling. Slug formation in this fashion is independent of fluid properties and can easily be scaled to mix larger numbers of reagents. This device has already been used to screen monomer ratios in supramolecular nanoparticle assembly and radiolabeling conditions of engineered antibodies, and here we provide a detailed description of the underlying device. PMID:29167603

Ex-vivo evaluation of an early caries detector based on integrated OCT and polarized Raman spectroscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lamouche, Guy; Padioleau, Christian; Hewko, Mark; Smith, Michael S. D.; Schattka, Bernie J.; Fulton, Crystal; Gauthier, Bruno; Beauchesne, André; Ko, Alex C.; Choo-Smith, Lin-P'ing; Sowa, Michael G.

2017-02-01

Early detection of incipient caries would allow dentists to provide more effective measures to delay or to reverse caries' progression at earlier stage. Such earlier intervention could lead to improved oral health for the patients and reduced burden to the health system. Previously, we have demonstrated that the combination of morphological and biochemical information furnished by optical coherence tomography (OCT) and polarized Raman spectroscopy (PRS), respectively, provided a unique tool for dental caries management. In this study we will report the first pre-clinical caries detection system that includes a hand-held probe with a size slightly larger than a tooth brush. This probe presents a novel platform combining both OCT and PRS optics in a very tight space ideal for clinical practice. OCT cross-sectional images of near-surface enamel morphology are obtained with miniaturized MEMS scanning device and are processed in real-time to identify culprit regions. These regions are sequentially analyzed with polarized Raman spectroscopy for further confirmation. PRS is performed using 830nm laser line and four detection channels in order to obtain polarized Raman spectroscopic data, i.e. depolarization ratio of the hydroxyapatite Raman band at 960 cm-1. A detailed description of this hand-held caries detector and ex-vivo/in-vivo test results will be presented.

RNA synthetic mechanisms employed by diverse families of RNA viruses.

PubMed

McDonald, Sarah M

2013-01-01

RNA viruses are ubiquitous in nature, infecting every known organism on the planet. These viruses can also be notorious human pathogens with significant medical and economic burdens. Central to the lifecycle of an RNA virus is the synthesis of new RNA molecules, a process that is mediated by specialized virally encoded enzymes called RNA-dependent RNA polymerases (RdRps). RdRps directly catalyze phosphodiester bond formation between nucleoside triphosphates in an RNA-templated manner. These enzymes are strikingly conserved in their structural and functional features, even among diverse RNA viruses belonging to different families. During host cell infection, the activities of viral RdRps are often regulated by viral cofactor proteins. Cofactors can modulate the type and timing of RNA synthesis by directly engaging the RdRp and/or by indirectly affecting its capacity to recognize template RNA. High-resolution structures of RdRps as apoenzymes, bound to RNA templates, in the midst of catalysis, and/or interacting with regulatory cofactor proteins, have dramatically increased our understanding of viral RNA synthetic mechanisms. Combined with elegant biochemical studies, such structures are providing a scientific platform for the rational design of antiviral agents aimed at preventing and treating RNA virus-induced diseases. Copyright © 2013 John Wiley & Sons, Ltd.

Smart single-chip gas sensor microsystem

NASA Astrophysics Data System (ADS)

Hagleitner, C.; Hierlemann, A.; Lange, D.; Kummer, A.; Kerness, N.; Brand, O.; Baltes, H.

2001-11-01

Research activity in chemical gas sensing is currently directed towards the search for highly selective (bio)chemical layer materials, and to the design of arrays consisting of different partially selective sensors that permit subsequent pattern recognition and multi-component analysis. Simultaneous use of various transduction platforms has been demonstrated, and the rapid development of integrated-circuit technology has facilitated the fabrication of planar chemical sensors and sensors based on three-dimensional microelectromechanical systems. Complementary metal-oxide silicon processes have previously been used to develop gas sensors based on metal oxides and acoustic-wave-based sensor devices. Here we combine several of these developments to fabricate a smart single-chip chemical microsensor system that incorporates three different transducers (mass-sensitive, capacitive and calorimetric), all of which rely on sensitive polymeric layers to detect airborne volatile organic compounds. Full integration of the microelectronic and micromechanical components on one chip permits control and monitoring of the sensor functions, and enables on-chip signal amplification and conditioning that notably improves the overall sensor performance. The circuitry also includes analog-to-digital converters, and an on-chip interface to transmit the data to off-chip recording units. We expect that our approach will provide a basis for the further development and optimization of gas microsystems.

Advanced biomaterials and microengineering technologies to recapitulate the stepwise process of cancer metastasis.

PubMed

Peela, Nitish; Truong, Danh; Saini, Harpinder; Chu, Hunghao; Mashaghi, Samaneh; Ham, Stephanie L; Singh, Sunil; Tavana, Hossein; Mosadegh, Bobak; Nikkhah, Mehdi

2017-07-01

Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic in vitro models with physiologically relevant (i.e. in vivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions. Copyright © 2017 Elsevier Ltd. All rights reserved.

An orthosteric inhibitor of the RAS-SOS interaction.

PubMed

Nickerson, Seth; Joy, Stephen T; Arora, Paramjit S; Bar-Sagi, Dafna

2013-01-01

Rat sarcoma (RAS) proteins are signaling nodes that transduce extracellular cues into precise alterations in cellular physiology by engaging effector pathways. RAS signaling thus regulates diverse cell processes including proliferation, migration, differentiation, and survival. Owing to this central role in governing mitogenic signals, RAS pathway components are often dysregulated in human diseases. Targeted therapy of RAS pathways has generally not been successful, largely because of the robust biochemistry of the targets and their multifaceted network of molecular regulators. The rate-limiting step of RAS activation is Son of Sevenless (SOS)-mediated nucleotide exchange involving a single evolutionarily conserved catalytic helix from SOS. Structure function data of this mechanism provided a strong platform to design an SOS-derived, helically constrained peptide mimic as an inhibitor of the RAS-SOS interaction. In this chapter, we review RAS-SOS signaling dynamics and present evidence supporting the novel paradigm of inhibiting their interaction as a therapeutic strategy. We then describe a method of generating helically constrained peptide mimics of protein surfaces, which we have employed to inhibit the RAS-SOS active site interaction. The biochemical and functional properties of this SOS mimic support the premise that inhibition of RAS-nucleotide exchange can effectively block RAS activation and downstream signaling. © 2013 Elsevier Inc. All rights reserved.

Proteome-wide association studies identify biochemical modules associated with a wing-size phenotype in Drosophila melanogaster.

PubMed

Okada, Hirokazu; Ebhardt, H Alexander; Vonesch, Sibylle Chantal; Aebersold, Ruedi; Hafen, Ernst

2016-09-01

The manner by which genetic diversity within a population generates individual phenotypes is a fundamental question of biology. To advance the understanding of the genotype-phenotype relationships towards the level of biochemical processes, we perform a proteome-wide association study (PWAS) of a complex quantitative phenotype. We quantify the variation of wing imaginal disc proteomes in Drosophila genetic reference panel (DGRP) lines using SWATH mass spectrometry. In spite of the very large genetic variation (1/36 bp) between the lines, proteome variability is surprisingly small, indicating strong molecular resilience of protein expression patterns. Proteins associated with adult wing size form tight co-variation clusters that are enriched in fundamental biochemical processes. Wing size correlates with some basic metabolic functions, positively with glucose metabolism but negatively with mitochondrial respiration and not with ribosome biogenesis. Our study highlights the power of PWAS to filter functional variants from the large genetic variability in natural populations.