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Sample records for advanced molecular tools

  1. Advances in Coupling of Kinetics and Molecular Scale Tools to Shed Light on Soil Biogeochemical Processes

    SciTech Connect

    Sparks, Donald

    2014-09-02

    Biogeochemical processes in soils such as sorption, precipitation, and redox play critical roles in the cycling and fate of nutrients, metal(loid)s and organic chemicals in soil and water environments. Advanced analytical tools enable soil scientists to track these processes in real-time and at the molecular scale. Our review focuses on recent research that has employed state-of-the-art molecular scale spectroscopy, coupled with kinetics, to elucidate the mechanisms of nutrient and metal(loid) reactivity and speciation in soils. We found that by coupling kinetics with advanced molecular and nano-scale tools major advances have been made in elucidating important soil chemical processes including sorption, precipitation, dissolution, and redox of metal(loids) and nutrients. Such advances will aid in better predicting the fate and mobility of nutrients and contaminants in soils and water and enhance environmental and agricultural sustainability.

  2. Synthetic biology and molecular genetics in non-conventional yeasts: Current tools and future advances.

    PubMed

    Wagner, James M; Alper, Hal S

    2016-04-01

    Coupling the tools of synthetic biology with traditional molecular genetic techniques can enable the rapid prototyping and optimization of yeast strains. While the era of yeast synthetic biology began in the well-characterized model organism Saccharomyces cerevisiae, it is swiftly expanding to include non-conventional yeast production systems such as Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. These yeasts already have roles in the manufacture of vaccines, therapeutic proteins, food additives, and biorenewable chemicals, but recent synthetic biology advances have the potential to greatly expand and diversify their impact on biotechnology. In this review, we summarize the development of synthetic biological tools (including promoters and terminators) and enabling molecular genetics approaches that have been applied in these four promising alternative biomanufacturing platforms. An emphasis is placed on synthetic parts and genome editing tools. Finally, we discuss examples of synthetic tools developed in other organisms that can be adapted or optimized for these hosts in the near future.

  3. Molecular tools for functional genomics in filamentous fungi: recent advances and new strategies.

    PubMed

    Jiang, Dewei; Zhu, Wei; Wang, Yunchuan; Sun, Chang; Zhang, Ke-Qin; Yang, Jinkui

    2013-12-01

    Advances in genetic transformation techniques have made important contributions to molecular genetics. Various molecular tools and strategies have been developed for functional genomic analysis of filamentous fungi since the first DNA transformation was successfully achieved in Neurospora crassa in 1973. Increasing amounts of genomic data regarding filamentous fungi are continuously reported and large-scale functional studies have become common in a wide range of fungal species. In this review, various molecular tools used in filamentous fungi are compared and discussed, including methods for genetic transformation (e.g., protoplast transformation, electroporation, and microinjection), the construction of random mutant libraries (e.g., restriction enzyme mediated integration, transposon arrayed gene knockout, and Agrobacterium tumefaciens mediated transformation), and the analysis of gene function (e.g., RNA interference and transcription activator-like effector nucleases). We also focused on practical strategies that could enhance the efficiency of genetic manipulation in filamentous fungi, such as choosing a proper screening system and marker genes, assembling target-cassettes or vectors effectively, and transforming into strains that are deficient in the nonhomologous end joining pathway. In summary, we present an up-to-date review on the different molecular tools and latest strategies that have been successfully used in functional genomics in filamentous fungi.

  4. Molecular tools for chemical biotechnology

    PubMed Central

    Galanie, Stephanie; Siddiqui, Michael S.; Smolke, Christina D.

    2013-01-01

    Biotechnological production of high value chemical products increasingly involves engineering in vivo multi-enzyme pathways and host metabolism. Recent approaches to these engineering objectives have made use of molecular tools to advance de novo pathway identification, tunable enzyme expression, and rapid pathway construction. Molecular tools also enable optimization of single enzymes and entire genomes through diversity generation and screening, whole cell analytics, and synthetic metabolic control networks. In this review, we focus on advanced molecular tools and their applications to engineered pathways in host organisms, highlighting the degree to which each tool is generalizable. PMID:23528237

  5. Recent advances in developing molecular tools for targeted genome engineering of mammalian cells.

    PubMed

    Lim, Kwang-il

    2015-01-01

    Various biological molecules naturally existing in diversified species including fungi, bacteria, and bacteriophage have functionalities for DNA binding and processing. The biological molecules have been recently actively engineered for use in customized genome editing of mammalian cells as the molecule-encoding DNA sequence information and the underlying mechanisms how the molecules work are unveiled. Excitingly, multiple novel methods based on the newly constructed artificial molecular tools have enabled modifications of specific endogenous genetic elements in the genome context at efficiencies that are much higher than that of the conventional homologous recombination based methods. This minireview introduces the most recently spotlighted molecular genome engineering tools with their key features and ongoing modifications for better performance. Such ongoing efforts have mainly focused on the removal of the inherent DNA sequence recognition rigidity from the original molecular platforms, the addition of newly tailored targeting functions into the engineered molecules, and the enhancement of their targeting specificity. Effective targeted genome engineering of mammalian cells will enable not only sophisticated genetic studies in the context of the genome, but also widely-applicable universal therapeutics based on the pinpointing and correction of the disease-causing genetic elements within the genome in the near future.

  6. The Advanced Light Source: A new tool for research in atomic and molecular physics

    NASA Astrophysics Data System (ADS)

    Schlachter, F.; Robinson, A.

    1991-04-01

    The Advanced Light Source at the Lawrence Berkeley Laboratory will be the world's brightest synchrotron radiation source in the extreme ultraviolet and soft x-ray regions of the spectrum when it begins operation in 1993. It will be available as a national user facility to researchers in a broad range of disciplines, including materials science, atomic and molecular physics, chemistry, biology, imaging, and technology. The high brightness of the ALS will be particularly well suited to high-resolution studies of tenuous targets, such as excited atoms, ions, and clusters.

  7. Contemporary molecular tools in microbial ecology and their application to advancing biotechnology.

    PubMed

    Rashid, Mamoon; Stingl, Ulrich

    2015-12-01

    Novel methods in microbial ecology are revolutionizing our understanding of the structure and function of microbes in the environment, but concomitant advances in applications of these tools to biotechnology are mostly lagging behind. After more than a century of efforts to improve microbial culturing techniques, about 70-80% of microbial diversity - recently called the "microbial dark matter" - remains uncultured. In early attempts to identify and sample these so far uncultured taxonomic lineages, methods that amplify and sequence ribosomal RNA genes were extensively used. Recent developments in cell separation techniques, DNA amplification, and high-throughput DNA sequencing platforms have now made the discovery of genes/genomes of uncultured microorganisms from different environments possible through the use of metagenomic techniques and single-cell genomics. When used synergistically, these metagenomic and single-cell techniques create a powerful tool to study microbial diversity. These genomics techniques have already been successfully exploited to identify sources for i) novel enzymes or natural products for biotechnology applications, ii) novel genes from extremophiles, and iii) whole genomes or operons from uncultured microbes. More can be done to utilize these tools more efficiently in biotechnology.

  8. Advances in developing molecular-diagnostic tools for strongyloid nematodes of equids: fundamental and applied implications.

    PubMed

    Gasser, Robin B; Hung, Guo-Chiuan; Chilton, Neil B; Beveridge, Ian

    2004-02-01

    Infections of equids with parasitic nematodes of the order Strongylida (subfamilies Strongylinae and Cyathostominae) are of major veterinary importance. In last decades, the widespread use of drugs against these parasites has led to problems of resistance within the Cyathostominae, and to an increase in their prevalence and intensity of infection. Novel control strategies, based on improved knowledge of parasite biology and epidemiology, have thus become important. However, there are substantial limitations in the understanding of fundamental biological and systematic aspects of these parasites, which have been due largely to limitations in their specific identification and diagnosis using traditional, morphological approaches. Recently, there has been progress in the development of DNA-based approaches for the specific identification of strongyloids of equids for systematic studies and disease diagnosis. The present article briefly reviews information on the classification, biology, pathogenesis, epidemiology of equine strongyloids and the diagnosis of infections, highlights knowledge gaps in these areas, describes recent advances in the use of molecular techniques for the genetic characterisation, specific identification and differentiation of strongyloids of equids as a basis for fundamental investigations of the systematics, population biology and ecology.

  9. Advanced Prosthetic Gait Training Tool

    DTIC Science & Technology

    2011-09-01

    AD_________________ Award Number: W81XWH-10-1-0870 TITLE: Advanced Prosthetic Gait Training Tool...Advanced Prosthetic Gait Training Tool 5b. GRANT NUMBER W81XWH-10-1-0870 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Rajankumar...produce a computer-based Advanced Prosthetic Gait Training Tool to aid in the training of clinicians at military treatment facilities providing care for

  10. Advanced Prosthetic Gait Training Tool

    DTIC Science & Technology

    2015-12-01

    study is to produce a computer-based Advanced Prosthetic Gait Training Tool to aid in the training of clinicians at military treatment facilities...providing care for wounded service members. In Phase I of the effort, significant work was completed at the University of Iowa Center for Computer- Aided ...Gait Training Tool Introduction The objective of our study is to produce a computer-based Advanced Prosthetic Gait Training Tool (APGTT) to aid in

  11. Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective.

    PubMed

    Roeber, Florian; Jex, Aaron R; Gasser, Robin B

    2013-05-27

    Parasitic nematodes (roundworms) of small ruminants and other livestock have major economic impacts worldwide. Despite the impact of the diseases caused by these nematodes and the discovery of new therapeutic agents (anthelmintics), there has been relatively limited progress in the development of practical molecular tools to study the epidemiology of these nematodes. Specific diagnosis underpins parasite control, and the detection and monitoring of anthelmintic resistance in livestock parasites, presently a major concern around the world. The purpose of the present article is to provide a concise account of the biology and knowledge of the epidemiology of the gastrointestinal nematodes (order Strongylida), from an Australian perspective, and to emphasize the importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods. It also gives a perspective on the possibility of harnessing genetic, genomic and bioinformatic technologies to better understand parasites and control parasitic diseases.

  12. Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective

    PubMed Central

    2013-01-01

    Parasitic nematodes (roundworms) of small ruminants and other livestock have major economic impacts worldwide. Despite the impact of the diseases caused by these nematodes and the discovery of new therapeutic agents (anthelmintics), there has been relatively limited progress in the development of practical molecular tools to study the epidemiology of these nematodes. Specific diagnosis underpins parasite control, and the detection and monitoring of anthelmintic resistance in livestock parasites, presently a major concern around the world. The purpose of the present article is to provide a concise account of the biology and knowledge of the epidemiology of the gastrointestinal nematodes (order Strongylida), from an Australian perspective, and to emphasize the importance of utilizing advanced molecular tools for the specific diagnosis of nematode infections for refined investigations of parasite epidemiology and drug resistance detection in combination with conventional methods. It also gives a perspective on the possibility of harnessing genetic, genomic and bioinformatic technologies to better understand parasites and control parasitic diseases. PMID:23711194

  13. Advanced Welding Tool

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Accutron Tool & Instrument Co.'s welder was originally developed as a tool specifically for joining parts made of plastic or composite materials in any atmosphere to include the airless environment of space. Developers decided on induction or magnetic heating to avoid causing deformation and it also can be used with almost any type of thermoplastic material. Induction coil transfers magnetic flux through the plastic to a metal screen that is sandwiched between the sheets of plastic to be joined. When welder is energized, alternating current produces inductive heating on the screen causing the adjacent plastic surfaces to melt and flow into the mesh, creating a bond on the total surface area. Dave Brown, owner of Great Falls Canoe and Kayak Repair, Vienna, VA, uses a special repair technique based on operation of the Induction Toroid Welder to fix canoes. Whitewater canoeing poses the problem of frequent gashes that are difficult to repair. The main reason is that many canoes are made of plastics. The commercial Induction model is a self-contained, portable welding gun with a switch on the handle to regulate the temperature of the plastic melting screen. Welder has a broad range of applications in the automobile, appliance, aerospace and construction industries.

  14. Molecular tools used in agriculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A summary of molecular tools used for research in agriculture were presented. Examples of DNA sequencing, library preparation, use of fingerprinting for pathogens and plant crops, high throughput sequencing, whole-genome amplification, reporter genes, and other methods....

  15. Modeling Tool Advances Rotorcraft Design

    NASA Technical Reports Server (NTRS)

    2007-01-01

    Continuum Dynamics Inc. (CDI), founded in 1979, specializes in advanced engineering services, including fluid dynamic modeling and analysis for aeronautics research. The company has completed a number of SBIR research projects with NASA, including early rotorcraft work done through Langley Research Center, but more recently, out of Ames Research Center. NASA Small Business Innovation Research (SBIR) grants on helicopter wake modeling resulted in the Comprehensive Hierarchical Aeromechanics Rotorcraft Model (CHARM), a tool for studying helicopter and tiltrotor unsteady free wake modeling, including distributed and integrated loads, and performance prediction. Application of the software code in a blade redesign program for Carson Helicopters, of Perkasie, Pennsylvania, increased the payload and cruise speeds of its S-61 helicopter. Follow-on development resulted in a $24 million revenue increase for Sikorsky Aircraft Corporation, of Stratford, Connecticut, as part of the company's rotor design efforts. Now under continuous development for more than 25 years, CHARM models the complete aerodynamics and dynamics of rotorcraft in general flight conditions. CHARM has been used to model a broad spectrum of rotorcraft attributes, including performance, blade loading, blade-vortex interaction noise, air flow fields, and hub loads. The highly accurate software is currently in use by all major rotorcraft manufacturers, NASA, the U.S. Army, and the U.S. Navy.

  16. Advanced Human Factors Engineering Tool Technologies.

    DTIC Science & Technology

    1987-03-20

    identified the types of tools they would like to see V developed to fill the existing technology gaps. The advanced tools were catego- rized using an...the prototype phase of development were considered candidates for inclusion. The advanced tools were next categorized using an eight point...role, application, status and cost. Decision criteria were then developed as the basis for the tradeoff process to aid in tool selection. To

  17. ADVANCED POWER SYSTEMS ANALYSIS TOOLS

    SciTech Connect

    Robert R. Jensen; Steven A. Benson; Jason D. Laumb

    2001-08-31

    The use of Energy and Environmental Research Center (EERC) modeling tools and improved analytical methods has provided key information in optimizing advanced power system design and operating conditions for efficiency, producing minimal air pollutant emissions and utilizing a wide range of fossil fuel properties. This project was divided into four tasks: the demonstration of the ash transformation model, upgrading spreadsheet tools, enhancements to analytical capabilities using the scanning electron microscopy (SEM), and improvements to the slag viscosity model. The ash transformation model, Atran, was used to predict the size and composition of ash particles, which has a major impact on the fate of the combustion system. To optimize Atran key factors such as mineral fragmentation and coalescence, the heterogeneous and homogeneous interaction of the organically associated elements must be considered as they are applied to the operating conditions. The resulting model's ash composition compares favorably to measured results. Enhancements to existing EERC spreadsheet application included upgrading interactive spreadsheets to calculate the thermodynamic properties for fuels, reactants, products, and steam with Newton Raphson algorithms to perform calculations on mass, energy, and elemental balances, isentropic expansion of steam, and gasifier equilibrium conditions. Derivative calculations can be performed to estimate fuel heating values, adiabatic flame temperatures, emission factors, comparative fuel costs, and per-unit carbon taxes from fuel analyses. Using state-of-the-art computer-controlled scanning electron microscopes and associated microanalysis systems, a method to determine viscosity using the incorporation of grey-scale binning acquired by the SEM image was developed. The image analysis capabilities of a backscattered electron image can be subdivided into various grey-scale ranges that can be analyzed separately. Since the grey scale's intensity is

  18. Cryptosporidium infections: molecular advances.

    PubMed

    Lendner, Matthias; Daugschies, Arwid

    2014-09-01

    Cryptosporidium host cell interaction remains fairly obscure compared with other apicomplexans such as Plasmodium or Toxoplasma. The reason for this is probably the inability of this parasite to complete its life cycle in vitro and the lack of a system to genetically modify Cryptosporidium. However, there is a substantial set of data about the molecules involved in attachment and invasion and about the host cell pathways involved in actin arrangement that are altered by the parasite. Here we summarize the recent advances in research on host cell infection regarding the excystation process, attachment and invasion, survival in the cell, egress and the available data on omics.

  19. Molecular Advancements in Forensic Odontology.

    PubMed

    Babu Rs, A; Rose, D

    2015-05-11

    Forensic odontology explores the field of human identification through dental tissues in cases where there is destruction of body tissues in criminal investigations and mass disasters. Forensic odontology involves dentists participating in legal and criminal issues. Parameters such as age and gender identification are important in identifying the person or persons. Over the last two decades, the molecular aspect of forensic sciences has increased, and these molecular techniques now provide a novel approach to forensic odontology. Molecular advancements in science like DNA analysis has extended the range of forensic dentistry as teeth possess the character of resistance toward physical or chemical aggressions. Teeth provide the abundant space for DNA, and hence teeth represent an excellent source of genomic DNA. The present paper focusses on molecular advancements in the field of forensic odontology.

  20. Integrating Advanced Molecular Technologies into Public Health.

    PubMed

    Gwinn, Marta; MacCannell, Duncan R; Khabbaz, Rima F

    2017-03-01

    Advances in laboratory and information technologies are transforming public health microbiology. High-throughput genome sequencing and bioinformatics are enhancing our ability to investigate and control outbreaks, detect emerging infectious diseases, develop vaccines, and combat antimicrobial resistance, all with increased accuracy, timeliness, and efficiency. The Advanced Molecular Detection (AMD) initiative has allowed the Centers for Disease Control and Prevention (CDC) to provide leadership and coordination in integrating new technologies into routine practice throughout the U.S. public health laboratory system. Collaboration and partnerships are the key to navigating this transition and to leveraging the next generation of methods and tools most effectively for public health.

  1. Recent Advances in Algal Genetic Tool Development

    SciTech Connect

    R. Dahlin, Lukas; T. Guarnieri, Michael

    2016-06-24

    The goal of achieving cost-effective biofuels and bioproducts derived from algal biomass will require improvements along the entire value chain, including identification of robust, high-productivity strains and development of advanced genetic tools. Though there have been modest advances in development of genetic systems for the model alga Chlamydomonas reinhardtii, progress in development of algal genetic tools, especially as applied to non-model algae, has generally lagged behind that of more commonly utilized laboratory and industrial microbes. This is in part due to the complex organellar structure of algae, including robust cell walls and intricate compartmentalization of target loci, as well as prevalent gene silencing mechanisms, which hinder facile utilization of conventional genetic engineering tools and methodologies. However, recent progress in global tool development has opened the door for implementation of strain-engineering strategies in industrially-relevant algal strains. Here, we review recent advances in algal genetic tool development and applications in eukaryotic microalgae.

  2. Advances in multimodal molecular imaging.

    PubMed

    Auletta, Luigi; Gramanzini, Matteo; Gargiulo, Sara; Albanese, Sandra; Salvatore, Marco; Greco, Adelaide

    2017-03-01

    Preclinical molecular imaging is an emerging field. Improving the ability of scientists to study the molecular basis of human pathology in animals is of the utmost importance for future advances in all fields of human medicine. Moreover, the possibility of developing new imaging techniques or of implementing old ones adapted to the clinic is a significant area. Cardiology, neurology, immunology and oncology have all been studied with preclinical molecular imaging. The functional techniques of photoacoustic imaging (PAI), fluorescence molecular tomography (FMT), positron emission tomography (PET), and single photon emission computed tomography (SPECT) in association with each other or with the anatomic reference provided by computed tomography (CT) as well as with anatomic and functional information provided by magnetic resonance (MR) have all been proficiently applied to animal models of human disease. All the above-mentioned imaging techniques have shown their ability to explore the molecular mechanisms involved in animal models of disease. The clinical translatability of most of the techniques motivates the ongoing study of their possible fields of application. The ability to combine two or more techniques allows obtaining as much information as possible on the molecular processes involved in pathologies, reducing the number of animals necessary in each experiment. Merging molecular probes compatible with various imaging technique will further expand the capability to achieve the best results.

  3. Rapid medical advances challenge the tooling industry.

    PubMed

    Conley, B

    2008-01-01

    The requirement for greater performance in smaller spaces has increased demands for product and process innovation in tubing and other medical products. In turn, these developments have placed greater demands on the producers of the advanced tooling for these products. Tooling manufacturers must now continuously design equipment with much tighter tolerances for more sophisticated coextrusions and for newer generations of multilumen and multilayer tubing.

  4. Recent Advances in Algal Genetic Tool Development

    DOE PAGES

    R. Dahlin, Lukas; T. Guarnieri, Michael

    2016-06-24

    The goal of achieving cost-effective biofuels and bioproducts derived from algal biomass will require improvements along the entire value chain, including identification of robust, high-productivity strains and development of advanced genetic tools. Though there have been modest advances in development of genetic systems for the model alga Chlamydomonas reinhardtii, progress in development of algal genetic tools, especially as applied to non-model algae, has generally lagged behind that of more commonly utilized laboratory and industrial microbes. This is in part due to the complex organellar structure of algae, including robust cell walls and intricate compartmentalization of target loci, as well asmore » prevalent gene silencing mechanisms, which hinder facile utilization of conventional genetic engineering tools and methodologies. However, recent progress in global tool development has opened the door for implementation of strain-engineering strategies in industrially-relevant algal strains. Here, we review recent advances in algal genetic tool development and applications in eukaryotic microalgae.« less

  5. Bacteriophage-based tools: recent advances and novel applications

    PubMed Central

    O'Sullivan, Lisa; Buttimer, Colin; McAuliffe, Olivia; Bolton, Declan; Coffey, Aidan

    2016-01-01

    Bacteriophages (phages) are viruses that infect bacterial hosts, and since their discovery over a century ago they have been primarily exploited to control bacterial populations and to serve as tools in molecular biology. In this commentary, we highlight recent diverse advances in the field of phage research, going beyond bacterial control using whole phage, to areas including biocontrol using phage-derived enzybiotics, diagnostics, drug discovery, novel drug delivery systems and bionanotechnology. PMID:27990274

  6. Advanced genetic tools for plant biotechnology.

    PubMed

    Liu, Wusheng; Yuan, Joshua S; Stewart, C Neal

    2013-11-01

    Basic research has provided a much better understanding of the genetic networks and regulatory hierarchies in plants. To meet the challenges of agriculture, we must be able to rapidly translate this knowledge into generating improved plants. Therefore, in this Review, we discuss advanced tools that are currently available for use in plant biotechnology to produce new products in plants and to generate plants with new functions. These tools include synthetic promoters, 'tunable' transcription factors, genome-editing tools and site-specific recombinases. We also review some tools with the potential to enable crop improvement, such as methods for the assembly and synthesis of large DNA molecules, plant transformation with linked multigenes and plant artificial chromosomes. These genetic technologies should be integrated to realize their potential for applications to pressing agricultural and environmental problems.

  7. Advanced genetic tools for plant biotechnology

    SciTech Connect

    Liu, WS; Yuan, JS; Stewart, CN

    2013-10-09

    Basic research has provided a much better understanding of the genetic networks and regulatory hierarchies in plants. To meet the challenges of agriculture, we must be able to rapidly translate this knowledge into generating improved plants. Therefore, in this Review, we discuss advanced tools that are currently available for use in plant biotechnology to produce new products in plants and to generate plants with new functions. These tools include synthetic promoters, 'tunable' transcription factors, genome-editing tools and site-specific recombinases. We also review some tools with the potential to enable crop improvement, such as methods for the assembly and synthesis of large DNA molecules, plant transformation with linked multigenes and plant artificial chromosomes. These genetic technologies should be integrated to realize their potential for applications to pressing agricultural and environmental problems.

  8. Advances in molecular tools for the use of Zygosaccharomyces bailii as host for biotechnological productions and construction of the first auxotrophic mutant.

    PubMed

    Dato, Laura; Branduardi, Paola; Passolunghi, Simone; Cattaneo, Davide; Riboldi, Luca; Frascotti, Gianni; Valli, Minoska; Porro, Danilo

    2010-11-01

    The nonconventional yeast Zygosaccharomyces bailii has been proposed as a new host for biotechnological processes due to convenient properties such as its resistance to high sugar concentrations, relatively high temperatures and especially to acidic environments. We describe a series of new expression vectors specific for Z. bailii and the resulting improvements in production levels. By exploiting the sequences of the endogenous plasmid pSB2, 2microm-like multicopy vectors were obtained, giving a fivefold increase in production. A specific integrative vector was developed which led to 100% stability in the absence of selective pressure; a multiple-integration vector was constructed, based on an rRNA gene unit portion cloned and sequenced for this purpose, driving the insertion of up to 80 copies of the foreign construct. Moreover, we show the construction of the first stable auxotrophic mutant of Z. bailii, obtained by targeted gene deletion applied to ZbLEU2. The development of molecular tools for the Z. bailii manipulation has now reached a level that may be compatible with its industrial exploitation; the production of organic acids is a prominent field of application.

  9. Advances in multimodality molecular imaging

    PubMed Central

    Zaidi, Habib; Prasad, Rameshwar

    2009-01-01

    Multimodality molecular imaging using high resolution positron emission tomography (PET) combined with other modalities is now playing a pivotal role in basic and clinical research. The introduction of combined PET/CT systems in clinical setting has revolutionized the practice of diagnostic imaging. The complementarity between the intrinsically aligned anatomic (CT) and functional or metabolic (PET) information provided in a “one-stop shop” and the possibility to use CT images for attenuation correction of the PET data has been the driving force behind the success of this technology. On the other hand, combining PET with Magnetic Resonance Imaging (MRI) in a single gantry is technically more challenging owing to the strong magnetic fields. Nevertheless, significant progress has been made resulting in the design of few preclinical PET systems and one human prototype dedicated for simultaneous PET/MR brain imaging. This paper discusses recent advances in PET instrumentation and the advantages and challenges of multimodality imaging systems. Future opportunities and the challenges facing the adoption of multimodality imaging instrumentation will also be addressed. PMID:20098557

  10. Self-advancing step-tap tool

    NASA Technical Reports Server (NTRS)

    Pettit, Donald R. (Inventor); Penner, Ronald K. (Inventor); Franklin, Larry D. (Inventor); Camarda, Charles J. (Inventor)

    2008-01-01

    Methods and tool for simultaneously forming a bore in a work piece and forming a series of threads in said bore. In an embodiment, the tool has a predetermined axial length, a proximal end, and a distal end, said tool comprising: a shank located at said proximal end; a pilot drill portion located at said distal end; and a mill portion intermediately disposed between said shank and said pilot drill portion. The mill portion is comprised of at least two drill-tap sections of predetermined axial lengths and at least one transition section of predetermined axial length, wherein each of said at least one transition section is sandwiched between a distinct set of two of said at least two drill-tap sections. The at least two drill-tap sections are formed of one or more drill-tap cutting teeth spirally increasing along said at least two drill-tap sections, wherein said tool is self-advanced in said work piece along said formed threads, and wherein said tool simultaneously forms said bore and said series of threads along a substantially similar longitudinal axis.

  11. Web tools for molecular epidemiology of tuberculosis.

    PubMed

    Shabbeer, Amina; Ozcaglar, Cagri; Yener, Bülent; Bennett, Kristin P

    2012-06-01

    In this study we explore publicly available web tools designed to use molecular epidemiological data to extract information that can be employed for the effective tracking and control of tuberculosis (TB). The application of molecular methods for the epidemiology of TB complement traditional approaches used in public health. DNA fingerprinting methods are now routinely employed in TB surveillance programs and are primarily used to detect recent transmissions and in outbreak investigations. Here we present web tools that facilitate systematic analysis of Mycobacterium tuberculosis complex (MTBC) genotype information and provide a view of the genetic diversity in the MTBC population. These tools help answer questions about the characteristics of MTBC strains, such as their pathogenicity, virulence, immunogenicity, transmissibility, drug-resistance profiles and host-pathogen associativity. They provide an integrated platform for researchers to use molecular epidemiological data to address current challenges in the understanding of TB dynamics and the characteristics of MTBC.

  12. Advances in Molecular Imaging with Ultrasound

    PubMed Central

    Gessner, Ryan; Dayton, Paul A.

    2010-01-01

    Ultrasound imaging has long demonstrated utility in the study and measurement of anatomic features and noninvasive observation of blood flow. Within the last decade, advances in molecular biology and contrast agents have allowed researchers to use ultrasound to detect changes in the expression of molecular markers on the vascular endothelium and other intravascular targets. This new technology, referred to as ultrasonic molecular imaging, is still in its infancy. However, in preclinical studies, ultrasonic molecular imaging has shown promise in assessing angiogenesis, inflammation, and thrombus. In this review, we discuss recent advances in microbubble-type contrast agent development, ultrasound technology, and signal processing strategies that have the potential to substantially improve the capabilities and utility of ultrasonic molecular imaging. PMID:20487678

  13. Advanced cryogenics for cutting tools. Final report

    SciTech Connect

    Lazarus, L.J.

    1996-10-01

    The purpose of the investigation was to determine if cryogenic treatment improved the life and cost effectiveness of perishable cutting tools over other treatments or coatings. Test results showed that in five of seven of the perishable cutting tools tested there was no improvement in tool life. The other two tools showed a small gain in tool life, but not as much as when switching manufacturers of the cutting tool. The following conclusions were drawn from this study: (1) titanium nitride coatings are more effective than cryogenic treatment in increasing the life of perishable cutting tools made from all cutting tool materials, (2) cryogenic treatment may increase tool life if the cutting tool is improperly heat treated during its origination, and (3) cryogenic treatment was only effective on those tools made from less sophisticated high speed tool steels. As a part of a recent detailed investigation, four cutting tool manufacturers and two cutting tool laboratories were queried and none could supply any data to substantiate cryogenic treatment of perishable cutting tools.

  14. Signature molecular descriptor : advanced applications.

    SciTech Connect

    Visco, Donald Patrick, Jr.

    2010-04-01

    In this work we report on the development of the Signature Molecular Descriptor (or Signature) for use in the solution of inverse design problems as well as in highthroughput screening applications. The ultimate goal of using Signature is to identify novel and non-intuitive chemical structures with optimal predicted properties for a given application. We demonstrate this in three studies: green solvent design, glucocorticoid receptor ligand design and the design of inhibitors for Factor XIa. In many areas of engineering, compounds are designed and/or modified in incremental ways which rely upon heuristics or institutional knowledge. Often multiple experiments are performed and the optimal compound is identified in this brute-force fashion. Perhaps a traditional chemical scaffold is identified and movement of a substituent group around a ring constitutes the whole of the design process. Also notably, a chemical being evaluated in one area might demonstrate properties very attractive in another area and serendipity was the mechanism for solution. In contrast to such approaches, computer-aided molecular design (CAMD) looks to encompass both experimental and heuristic-based knowledge into a strategy that will design a molecule on a computer to meet a given target. Depending on the algorithm employed, the molecule which is designed might be quite novel (re: no CAS registration number) and/or non-intuitive relative to what is known about the problem at hand. While CAMD is a fairly recent strategy (dating to the early 1980s), it contains a variety of bottlenecks and limitations which have prevented the technique from garnering more attention in the academic, governmental and industrial institutions. A main reason for this is how the molecules are described in the computer. This step can control how models are developed for the properties of interest on a given problem as well as how to go from an output of the algorithm to an actual chemical structure. This report

  15. Advanced Human Factors Engineering Tool Technologies.

    DTIC Science & Technology

    1988-03-01

    representing the government, the military, academe, and private industry were surveyed to identify those tools that are most frequently used or viewed...tools by HFE researchers and practitioners within the academic, industrial , and military settings. % .. J. &@ossion For XTIS GR&&I DTIC TAS 0...267 E. Human Factors Engineering Tools Questionnaire .. ......... . 279 F. Listing of Industry , Government, and Academe

  16. Simulated Interactive Research Experiments as Educational Tools for Advanced Science.

    PubMed

    Tomandl, Mathias; Mieling, Thomas; Losert-Valiente Kroon, Christiane M; Hopf, Martin; Arndt, Markus

    2015-09-15

    Experimental research has become complex and thus a challenge to science education. Only very few students can typically be trained on advanced scientific equipment. It is therefore important to find new tools that allow all students to acquire laboratory skills individually and independent of where they are located. In a design-based research process we have investigated the feasibility of using a virtual laboratory as a photo-realistic and scientifically valid representation of advanced scientific infrastructure to teach modern experimental science, here, molecular quantum optics. We found a concept based on three educational principles that allows undergraduate students to become acquainted with procedures and concepts of a modern research field. We find a significant increase in student understanding using our Simulated Interactive Research Experiment (SiReX), by evaluating the learning outcomes with semi-structured interviews in a pre/post design. This suggests that this concept of an educational tool can be generalized to disseminate findings in other fields.

  17. Simulated Interactive Research Experiments as Educational Tools for Advanced Science

    PubMed Central

    Tomandl, Mathias; Mieling, Thomas; Losert-Valiente Kroon, Christiane M.; Hopf, Martin; Arndt, Markus

    2015-01-01

    Experimental research has become complex and thus a challenge to science education. Only very few students can typically be trained on advanced scientific equipment. It is therefore important to find new tools that allow all students to acquire laboratory skills individually and independent of where they are located. In a design-based research process we have investigated the feasibility of using a virtual laboratory as a photo-realistic and scientifically valid representation of advanced scientific infrastructure to teach modern experimental science, here, molecular quantum optics. We found a concept based on three educational principles that allows undergraduate students to become acquainted with procedures and concepts of a modern research field. We find a significant increase in student understanding using our Simulated Interactive Research Experiment (SiReX), by evaluating the learning outcomes with semi-structured interviews in a pre/post design. This suggests that this concept of an educational tool can be generalized to disseminate findings in other fields. PMID:26370627

  18. Improved molecular tools for sugar cane biotechnology.

    PubMed

    Kinkema, Mark; Geijskes, Jason; Delucca, Paulo; Palupe, Anthony; Shand, Kylie; Coleman, Heather D; Brinin, Anthony; Williams, Brett; Sainz, Manuel; Dale, James L

    2014-03-01

    Sugar cane is a major source of food and fuel worldwide. Biotechnology has the potential to improve economically-important traits in sugar cane as well as diversify sugar cane beyond traditional applications such as sucrose production. High levels of transgene expression are key to the success of improving crops through biotechnology. Here we describe new molecular tools that both expand and improve gene expression capabilities in sugar cane. We have identified promoters that can be used to drive high levels of gene expression in the leaf and stem of transgenic sugar cane. One of these promoters, derived from the Cestrum yellow leaf curling virus, drives levels of constitutive transgene expression that are significantly higher than those achieved by the historical benchmark maize polyubiquitin-1 (Zm-Ubi1) promoter. A second promoter, the maize phosphonenolpyruvate carboxylate promoter, was found to be a strong, leaf-preferred promoter that enables levels of expression comparable to Zm-Ubi1 in this organ. Transgene expression was increased approximately 50-fold by gene modification, which included optimising the codon usage of the coding sequence to better suit sugar cane. We also describe a novel dual transcriptional enhancer that increased gene expression from different promoters, boosting expression from Zm-Ubi1 over eightfold. These molecular tools will be extremely valuable for the improvement of sugar cane through biotechnology.

  19. Advanced Molecular Surveillance of Hepatitis C Virus

    PubMed Central

    Gonçalves Rossi, Livia Maria; Escobar-Gutierrez, Alejandro; Rahal, Paula

    2015-01-01

    Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted. PMID:25781918

  20. Advanced molecular surveillance of hepatitis C virus.

    PubMed

    Rossi, Livia Maria Gonçalves; Escobar-Gutierrez, Alejandro; Rahal, Paula

    2015-03-13

    Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted.

  1. Recent advances in molecular, multimodal and theranostic ultrasound imaging.

    PubMed

    Kiessling, Fabian; Fokong, Stanley; Bzyl, Jessica; Lederle, Wiltrud; Palmowski, Moritz; Lammers, Twan

    2014-06-01

    Ultrasound (US) imaging is an exquisite tool for the non-invasive and real-time diagnosis of many different diseases. In this context, US contrast agents can improve lesion delineation, characterization and therapy response evaluation. US contrast agents are usually micrometer-sized gas bubbles, stabilized with soft or hard shells. By conjugating antibodies to the microbubble (MB) surface, and by incorporating diagnostic agents, drugs or nucleic acids into or onto the MB shell, molecular, multimodal and theranostic MBs can be generated. We here summarize recent advances in molecular, multimodal and theranostic US imaging, and introduce concepts how such advanced MB can be generated, applied and imaged. Examples are given for their use to image and treat oncological, cardiovascular and neurological diseases. Furthermore, we discuss for which therapeutic entities incorporation into (or conjugation to) MB is meaningful, and how US-mediated MB destruction can increase their extravasation, penetration, internalization and efficacy.

  2. Alternative Fuel and Advanced Vehicle Tools (AFAVT), AFDC (Fact Sheet)

    SciTech Connect

    Not Available

    2010-01-01

    The Alternative Fuels and Advanced Vehicles Web site offers a collection of calculators, interactive maps, and informational tools to assist fleets, fuel providers, and others looking to reduce petroleum consumption in the transportation sector.

  3. Innovative Tools Advance Revolutionary Weld Technique

    NASA Technical Reports Server (NTRS)

    2009-01-01

    The iconic, orange external tank of the space shuttle launch system not only contains the fuel used by the shuttle s main engines during liftoff but also comprises the shuttle s backbone, supporting the space shuttle orbiter and solid rocket boosters. Given the tank s structural importance and the extreme forces (7.8 million pounds of thrust load) and temperatures it encounters during launch, the welds used to construct the tank must be highly reliable. Variable polarity plasma arc welding, developed for manufacturing the external tank and later employed for building the International Space Station, was until 1994 the best process for joining the aluminum alloys used during construction. That year, Marshall Space Flight Center engineers began experimenting with a relatively new welding technique called friction stir welding (FSW), developed in 1991 by The Welding Institute, of Cambridge, England. FSW differs from traditional fusion welding in that it is a solid-state welding technique, using frictional heat and motion to join structural components without actually melting any of the material. The weld is created by a shouldered pin tool that is plunged into the seam of the materials to be joined. The tool traverses the line while rotating at high speeds, generating friction that heats and softens but does not melt the metal. (The heat produced approaches about 80 percent of the metal s melting temperature.) The pin tool s rotation crushes and stirs the plasticized metal, extruding it along the seam as the tool moves forward. The material cools and consolidates, resulting in a weld with superior mechanical properties as compared to those weld properties of fusion welds. The innovative FSW technology promises a number of attractive benefits. Because the welded materials are not melted, many of the undesirables associated with fusion welding porosity, cracking, shrinkage, and distortion of the weld are minimized or avoided. The process is more energy efficient, safe

  4. Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques.

    PubMed

    Put, Stéphanie; Westhovens, René; Lahoutte, Tony; Matthys, Patrick

    2014-04-15

    Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor κB and its ligand, chemokine receptors, vascular cell adhesion molecule-1, αVβ₃ integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein.

  5. New Instrumental Tools for Advanced Astrochemical Applications

    NASA Astrophysics Data System (ADS)

    Steber, Amanda; Zinn, Sabrina; Schnell, Melanie; Rijs, Anouk

    2015-06-01

    Astrochemistry has been a growing field over the past several years. As the data from the Atacama Large Millimeter Array (ALMA) becomes publicly available, new and fast techniques for the analysis of the data will need to be developed, as well as fast, sensitive laboratory techniques. This lab is in the process of building up instrumentation that will be dedicated to the measurement of astrochemically relevant species, both in the microwave and the millimeter wave regimes. Discharge experiments, laser ablation experiments, as well as time of flight measurements will be possible with this instrumentation. Coupled with instrumentation capabilities will be new software aimed at a speeding up the analysis. The laboratory data will be used to search for new molecular signatures in the interstellar medium (ISM), and help to elucidate molecular reaction pathways occurring in the ISM.

  6. Intelligent Software Tools for Advanced Computing

    SciTech Connect

    Baumgart, C.W.

    2001-04-03

    Feature extraction and evaluation are two procedures common to the development of any pattern recognition application. These features are the primary pieces of information which are used to train the pattern recognition tool, whether that tool is a neural network, a fuzzy logic rulebase, or a genetic algorithm. Careful selection of the features to be used by the pattern recognition tool can significantly streamline the overall development and training of the solution for the pattern recognition application. This report summarizes the development of an integrated, computer-based software package called the Feature Extraction Toolbox (FET), which can be used for the development and deployment of solutions to generic pattern recognition problems. This toolbox integrates a number of software techniques for signal processing, feature extraction and evaluation, and pattern recognition, all under a single, user-friendly development environment. The toolbox has been developed to run on a laptop computer, so that it may be taken to a site and used to develop pattern recognition applications in the field. A prototype version of this toolbox has been completed and is currently being used for applications development on several projects in support of the Department of Energy.

  7. Terahertz Tools Advance Imaging for Security, Industry

    NASA Technical Reports Server (NTRS)

    2010-01-01

    Picometrix, a wholly owned subsidiary of Advanced Photonix Inc. (API), of Ann Arbor, Michigan, invented the world s first commercial terahertz system. The company improved the portability and capabilities of their systems through Small Business Innovation Research (SBIR) agreements with Langley Research Center to provide terahertz imaging capabilities for inspecting the space shuttle external tanks and orbiters. Now API s systems make use of the unique imaging capacity of terahertz radiation on manufacturing floors, for thickness measurements of coatings, pharmaceutical tablet production, and even art conservation.

  8. Developing molecular tools for Chlamydomonas reinhardtii

    NASA Astrophysics Data System (ADS)

    Noor-Mohammadi, Samaneh

    Microalgae have garnered increasing interest over the years for their ability to produce compounds ranging from biofuels to neutraceuticals. A main focus of researchers has been to use microalgae as a natural bioreactor for the production of valuable and complex compounds. Recombinant protein expression in the chloroplasts of green algae has recently become more routine; however, the heterologous expression of multiple proteins or complete biosynthetic pathways remains a significant challenge. To take full advantage of these organisms' natural abilities, sophisticated molecular tools are needed to be able to introduce and functionally express multiple gene biosynthetic pathways in its genome. To achieve the above objective, we have sought to establish a method to construct, integrate and express multigene operons in the chloroplast and nuclear genome of the model microalgae Chlamydomonas reinhardtii. Here we show that a modified DNA Assembler approach can be used to rapidly assemble multiple-gene biosynthetic pathways in yeast and then integrate these assembled pathways at a site-specific location in the chloroplast, or by random integration in the nuclear genome of C. reinhardtii. As a proof of concept, this method was used to successfully integrate and functionally express up to three reporter proteins (AphA6, AadA, and GFP) in the chloroplast of C. reinhardtii and up to three reporter proteins (Ble, AphVIII, and GFP) in its nuclear genome. An analysis of the relative gene expression of the engineered strains showed significant differences in the mRNA expression levels of the reporter genes and thus highlights the importance of proper promoter/untranslated-region selection when constructing a target pathway. In addition, this work focuses on expressing the cofactor regeneration enzyme phosphite dehydrogenase (PTDH) in the chloroplast and nuclear genomes of C. reinhardtii. The PTDH enzyme converts phosphite into phosphate and NAD(P)+ into NAD(P)H. The reduced

  9. Functional toxicology: tools to advance the future of toxicity testing

    PubMed Central

    Gaytán, Brandon D.; Vulpe, Chris D.

    2014-01-01

    The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

  10. A Teaching Tool for Molecular Kinetics

    ERIC Educational Resources Information Center

    Imai, Izumi; Kamata, Masahiro; Miura, Naosuke

    2003-01-01

    Kinetic models of a gas can be hard for students to understand. Typical tools do not display events at the microscopic level, yet computer simulations of the molecules lack a hands-on aspect. Here a new tool is described that combines the squeezing of a syringe with a computer simulation, and it is shown that this has worked well in class for both…

  11. Recent Advances in Cardiac Computed Tomography: Dual Energy, Spectral and Molecular CT Imaging

    PubMed Central

    Danad, Ibrahim; Fayad, Zahi A.; Willemink, Martin J.; Min, James K.

    2015-01-01

    Computed tomography (CT) evolved into a powerful diagnostic tool and it is impossible to imagine current clinical practice without CT imaging. Due to its widespread availability, ease of clinical application, superb sensitivity for detection of CAD, and non-invasive nature, CT has become a valuable tool within the armamentarium of the cardiologist. In the last few years, numerous technological advances in CT have occurred—including dual energy CT (DECT), spectral CT and CT-based molecular imaging. By harnessing the advances in technology, cardiac CT has advanced beyond the mere evaluation of coronary stenosis to an imaging modality tool that permits accurate plaque characterization, assessment of myocardial perfusion and even probing of molecular processes that are involved in coronary atherosclerosis. Novel innovations in CT contrast agents and pre-clinical spectral CT devices have paved the way for CT-based molecular imaging. PMID:26068288

  12. Advanced Computing Tools and Models for Accelerator Physics

    SciTech Connect

    Ryne, Robert; Ryne, Robert D.

    2008-06-11

    This paper is based on a transcript of my EPAC'08 presentation on advanced computing tools for accelerator physics. Following an introduction I present several examples, provide a history of the development of beam dynamics capabilities, and conclude with thoughts on the future of large scale computing in accelerator physics.

  13. Machine Tool Advanced Skills Technology Program (MAST). Overview and Methodology.

    ERIC Educational Resources Information Center

    Texas State Technical Coll., Waco.

    The Machine Tool Advanced Skills Technology Program (MAST) is a geographical partnership of six of the nation's best two-year colleges located in the six states that have about one-third of the density of metals-related industries in the United States. The purpose of the MAST grant is to develop and implement a national training model to overcome…

  14. Advanced Technology Lifecycle Analysis System (ATLAS) Technology Tool Box (TTB)

    NASA Technical Reports Server (NTRS)

    Doyle, Monica; ONeil, Daniel A.; Christensen, Carissa B.

    2005-01-01

    The Advanced Technology Lifecycle Analysis System (ATLAS) is a decision support tool designed to aid program managers and strategic planners in determining how to invest technology research and development dollars. It is an Excel-based modeling package that allows a user to build complex space architectures and evaluate the impact of various technology choices. ATLAS contains system models, cost and operations models, a campaign timeline and a centralized technology database. Technology data for all system models is drawn from a common database, the ATLAS Technology Tool Box (TTB). The TTB provides a comprehensive, architecture-independent technology database that is keyed to current and future timeframes.

  15. Advanced techniques for constrained internal coordinate molecular dynamics.

    PubMed

    Wagner, Jeffrey R; Balaraman, Gouthaman S; Niesen, Michiel J M; Larsen, Adrien B; Jain, Abhinandan; Vaidehi, Nagarajan

    2013-04-30

    Internal coordinate molecular dynamics (ICMD) methods provide a more natural description of a protein by using bond, angle, and torsional coordinates instead of a Cartesian coordinate representation. Freezing high-frequency bonds and angles in the ICMD model gives rise to constrained ICMD (CICMD) models. There are several theoretical aspects that need to be developed to make the CICMD method robust and widely usable. In this article, we have designed a new framework for (1) initializing velocities for nonindependent CICMD coordinates, (2) efficient computation of center of mass velocity during CICMD simulations, (3) using advanced integrators such as Runge-Kutta, Lobatto, and adaptive CVODE for CICMD simulations, and (4) cancelling out the "flying ice cube effect" that sometimes arises in Nosé-Hoover dynamics. The Generalized Newton-Euler Inverse Mass Operator (GNEIMO) method is an implementation of a CICMD method that we have developed to study protein dynamics. GNEIMO allows for a hierarchy of coarse-grained simulation models based on the ability to rigidly constrain any group of atoms. In this article, we perform tests on the Lobatto and Runge-Kutta integrators to determine optimal simulation parameters. We also implement an adaptive coarse-graining tool using the GNEIMO Python interface. This tool enables the secondary structure-guided "freezing and thawing" of degrees of freedom in the molecule on the fly during molecular dynamics simulations and is shown to fold four proteins to their native topologies. With these advancements, we envision the use of the GNEIMO method in protein structure prediction, structure refinement, and in studying domain motion.

  16. Recent advances in molecular diagnostics of hepatitis B virus.

    PubMed

    Datta, Sibnarayan; Chatterjee, Soumya; Veer, Vijay

    2014-10-28

    Hepatitis B virus (HBV) is one of the important global health problems today. Infection with HBV can lead to a variety of clinical manifestations including severe hepatic complications like liver cirrhosis and hepatocellular carcinoma. Presently, routine HBV screening and diagnosis is primarily based on the immuno-detection of HBV surface antigen (HBsAg). However, identification of HBV DNA positive cases, who do not have detectable HBsAg has greatly encouraged the use of nucleic acid amplification based assays, that are highly sensitive, specific and are to some extent tolerant to sequence variation. In the last few years, the field of HBV molecular diagnostics has evolved rapidly with advancements in the molecular biology tools, such as polymerase chain reaction (PCR) and real-time PCR. Recently, apart of PCR based amplification methods, a number of isothermal amplification assays, such as loop mediated isothermal amplification, transcription mediated amplification, ligase chain reaction, and rolling circle amplification have been utilized for HBV diagnosis. These assays also offer options for real time detection and integration into biosensing devices. In this manuscript, we review the molecular technologies that are presently available for HBV diagnostics, with special emphasis on isothermal amplification based technologies. We have also included the recent trends in the development of biosensors and use of next generation sequencing technologies for HBV.

  17. Knowledge, Models and Tools in Support of Advanced Distance Learning

    DTIC Science & Technology

    2006-06-01

    authoring iRides simulations and training, Rivets , is a fast C++ program that has been compiled for three Unix-type operating systems: Linux, Silicon...School instructors to introduce core concepts of the tool in advance of teaching about expected value theory. 4.0 Rivets -Linux-based Authoring of...Simulations and Instruction Functioning versions of Rivets , a descendent of the classic RIDES program have been developed for Linux and for the Macintosh

  18. Anvil Tool in the Advanced Weather Interactive Processing System

    NASA Technical Reports Server (NTRS)

    Barrett, Joe, III; Bauman, William, III; Keen, Jeremy

    2007-01-01

    Meteorologists from the 45th Weather Squadron (45 WS) and Spaceflight Meteorology Group (SMG) have identified anvil forecasting as one of their most challenging tasks when predicting the probability of violations of the lightning Launch Commit Criteria and Space Shuttle Flight Rules. As a result, the Applied Meteorology Unit (AMU) created a graphical overlay tool for the Meteorological Interactive Data Display Systems (MIDDS) to indicate the threat of thunderstorm anvil clouds, using either observed or model forecast winds as input. In order for the Anvil Tool to remain available to the meteorologists, the AMU was tasked to transition the tool to the Advanced Weather interactive Processing System (AWIPS). This report describes the work done by the AMU to develop the Anvil Tool for AWIPS to create a graphical overlay depicting the threat from thunderstorm anvil clouds. The AWIPS Anvil Tool is based on the previously deployed AMU MIDDS Anvil Tool. SMG and 45 WS forecasters have used the MIDDS Anvil Tool during launch and landing operations. SMG's primary weather analysis and display system is now AWIPS and the 45 WS has plans to replace MIDDS with AWIPS. The Anvil Tool creates a graphic that users can overlay on satellite or radar imagery to depict the potential location of thunderstorm anvils one, two, and three hours into the future. The locations are based on an average of the upper-level observed or forecasted winds. The graphic includes 10 and 20 nm standoff circles centered at the location of interest, in addition to one-, two-, and three-hour arcs in the upwind direction. The arcs extend outward across a 30 degree sector width based on a previous AMU study which determined thunderstorm anvils move in a direction plus or minus 15 degrees of the upper-level (300- to 150-mb) wind direction. This report briefly describes the history of the MIDDS Anvil Tool and then explains how the initial development of the AWIPS Anvil Tool was carried out. After testing was

  19. Advanced computational tools for 3-D seismic analysis

    SciTech Connect

    Barhen, J.; Glover, C.W.; Protopopescu, V.A.

    1996-06-01

    The global objective of this effort is to develop advanced computational tools for 3-D seismic analysis, and test the products using a model dataset developed under the joint aegis of the United States` Society of Exploration Geophysicists (SEG) and the European Association of Exploration Geophysicists (EAEG). The goal is to enhance the value to the oil industry of the SEG/EAEG modeling project, carried out with US Department of Energy (DOE) funding in FY` 93-95. The primary objective of the ORNL Center for Engineering Systems Advanced Research (CESAR) is to spearhead the computational innovations techniques that would enable a revolutionary advance in 3-D seismic analysis. The CESAR effort is carried out in collaboration with world-class domain experts from leading universities, and in close coordination with other national laboratories and oil industry partners.

  20. Evaluation of reliability modeling tools for advanced fault tolerant systems

    NASA Technical Reports Server (NTRS)

    Baker, Robert; Scheper, Charlotte

    1986-01-01

    The Computer Aided Reliability Estimation (CARE III) and Automated Reliability Interactice Estimation System (ARIES 82) reliability tools for application to advanced fault tolerance aerospace systems were evaluated. To determine reliability modeling requirements, the evaluation focused on the Draper Laboratories' Advanced Information Processing System (AIPS) architecture as an example architecture for fault tolerance aerospace systems. Advantages and limitations were identified for each reliability evaluation tool. The CARE III program was designed primarily for analyzing ultrareliable flight control systems. The ARIES 82 program's primary use was to support university research and teaching. Both CARE III and ARIES 82 were not suited for determining the reliability of complex nodal networks of the type used to interconnect processing sites in the AIPS architecture. It was concluded that ARIES was not suitable for modeling advanced fault tolerant systems. It was further concluded that subject to some limitations (the difficulty in modeling systems with unpowered spare modules, systems where equipment maintenance must be considered, systems where failure depends on the sequence in which faults occurred, and systems where multiple faults greater than a double near coincident faults must be considered), CARE III is best suited for evaluating the reliability of advanced tolerant systems for air transport.

  1. Molecular Tools for Exploring Polyploid Genomes in Plants

    PubMed Central

    Aversano, Riccardo; Ercolano, Maria Raffaella; Caruso, Immacolata; Fasano, Carlo; Rosellini, Daniele; Carputo, Domenico

    2012-01-01

    Polyploidy is a very common phenomenon in the plant kingdom, where even diploid species are often described as paleopolyploids. The polyploid condition may bring about several advantages compared to the diploid state. Polyploids often show phenotypes that are not present in their diploid progenitors or exceed the range of the contributing species. Some of these traits may play a role in heterosis or could favor adaptation to new ecological niches. Advances in genomics and sequencing technology may create unprecedented opportunities for discovering and monitoring the molecular effects of polyploidization. Through this review, we provide an overview of technologies and strategies that may allow an in-depth analysis of polyploid genomes. After introducing some basic aspects on the origin and genetics of polyploids, we highlight the main tools available for genome and gene expression analysis and summarize major findings. In the last part of this review, the implications of next generation sequencing are briefly discussed. The accumulation of knowledge on polyploid formation, maintenance, and divergence at whole-genome and subgenome levels will not only help plant biologists to understand how plants have evolved and diversified, but also assist plant breeders in designing new strategies for crop improvement. PMID:22949863

  2. Anvil Forecast Tool in the Advanced Weather Interactive Processing System

    NASA Technical Reports Server (NTRS)

    Barrett, Joe H., III; Hood, Doris

    2009-01-01

    Meteorologists from the 45th Weather Squadron (45 WS) and National Weather Service Spaceflight Meteorology Group (SMG) have identified anvil forecasting as one of their most challenging tasks when predicting the probability of violations of the Lightning Launch Commit Criteria and Space Shuttle Flight Rules. As a result, the Applied Meteorology Unit (AMU) was tasked to create a graphical overlay tool for the Meteorological Interactive Data Display System (MIDDS) that indicates the threat of thunderstorm anvil clouds, using either observed or model forecast winds as input. The tool creates a graphic depicting the potential location of thunderstorm anvils one, two, and three hours into the future. The locations are based on the average of the upper level observed or forecasted winds. The graphic includes 10 and 20 n mi standoff circles centered at the location of interest, as well as one-, two-, and three-hour arcs in the upwind direction. The arcs extend outward across a 30 sector width based on a previous AMU study that determined thunderstorm anvils move in a direction plus or minus 15 of the upper-level wind direction. The AMU was then tasked to transition the tool to the Advanced Weather Interactive Processing System (AWIPS). SMG later requested the tool be updated to provide more flexibility and quicker access to model data. This presentation describes the work performed by the AMU to transition the tool into AWIPS, as well as the subsequent improvements made to the tool.

  3. VCMM: a visual tool for continuum molecular modeling.

    PubMed

    Bai, Shiyang; Lu, Benzhuo

    2014-05-01

    This paper describes the design and function of a visualization tool, VCMM, for visualizing and analyzing data, and interfacing solvers for generic continuum molecular modeling. In particular, an emphasis of the program is to treat the data set based on unstructured mesh as used in finite/boundary element simulations, which largely enhances the capabilities of current visualization tools in this area that only support structured mesh. VCMM is segmented into molecular, meshing and numerical modules. The capabilities of molecular module include molecular visualization and force field assignment. Meshing module contains mesh generation, analysis and visualization tools. Numerical module currently provides a few finite/boundary element solvers of continuum molecular modeling, and contains several common visualization tools for the numerical result such as line and plane interpolations, surface probing, volume rendering and stream rendering. Three modules can exchange data with each other and carry out a complete process of modeling. Interfaces are also designed in order to facilitate usage of other mesh generation tools and numerical solvers. We develop a technique to accelerate data retrieval and have combined many graphical techniques in visualization. VCMM is highly extensible, and users can obtain more powerful functions by introducing relevant plug-ins. VCMM can also be useful in other fields such as computational quantum chemistry, image processing, and material science.

  4. Advances in molecular serotyping and subtyping of Escherichia coli

    DOE PAGES

    Fratamico, Pina M.; DebRoy, Chitrita; Liu, Yanhong; ...

    2016-05-03

    Escherichia coli plays an important role as a member of the gut microbiota; however, pathogenic strains also exist, including various diarrheagenic E. coli pathotypes and extraintestinal pathogenic E. coli that cause illness outside of the GI-tract. E. coli have traditionally been serotyped using antisera against the ca. 186 O-antigens and 53 H-flagellar antigens. Phenotypic methods, including bacteriophage typing and O- and H- serotyping for differentiating and characterizing E. coli have been used for many years; however, these methods are generally time consuming and not always accurate. Advances in next generation sequencing technologies have made it possible to develop genetic-based subtypingmore » and molecular serotyping methods for E. coli, which are more discriminatory compared to phenotypic typing methods. Furthermore, whole genome sequencing (WGS) of E. coli is replacing established subtyping methods such as pulsedfield gel electrophoresis, providing a major advancement in the ability to investigate food-borne disease outbreaks and for trace-back to sources. Furthermore, a variety of sequence analysis tools and bioinformatic pipelines are being developed to analyze the vast amount of data generated by WGS and to obtain specific information such as O- and H-group determination and the presence of virulence genes and other genetic markers.« less

  5. Advances and applications of molecular cloning in clinical microbiology.

    PubMed

    Sharma, Kamal; Mishra, Ajay Kumar; Mehraj, Vikram; Duraisamy, Ganesh Selvaraj

    2014-10-01

    Molecular cloning is based on isolation of a DNA sequence of interest to obtain multiple copies of it in vitro. Application of this technique has become an increasingly important tool in clinical microbiology due to its simplicity, cost effectiveness, rapidity, and reliability. This review entails the recent advances in molecular cloning and its application in the clinical microbiology in the context of polymicrobial infections, recombinant antigens, recombinant vaccines, diagnostic probes, antimicrobial peptides, and recombinant cytokines. Culture-based methods in polymicrobial infection have many limitation, which has been overcome by cloning techniques and provide gold standard technique. Recombinant antigens produced by cloning technique are now being used for screening of HIV, HCV, HBV, CMV, Treponema pallidum, and other clinical infectious agents. Recombinant vaccines for hepatitis B, cholera, influenza A, and other diseases also use recombinant antigens which have replaced the use of live vaccines and thus reduce the risk for adverse effects. Gene probes developed by gene cloning have many applications including in early diagnosis of hereditary diseases, forensic investigations, and routine diagnosis. Industrial application of this technology produces new antibiotics in the form of antimicrobial peptides and recombinant cytokines that can be used as therapeutic agents.

  6. Advanced Techniques for Constrained Internal Coordinate Molecular Dynamics

    PubMed Central

    Wagner, Jeffrey R.; Balaraman, Gouthaman S.; Niesen, Michiel J. M.; Larsen, Adrien B.; Jain, Abhinandan; Vaidehi, Nagarajan

    2013-01-01

    Internal coordinate molecular dynamics (ICMD) methods provide a more natural description of a protein by using bond, angle and torsional coordinates instead of a Cartesian coordinate representation. Freezing high frequency bonds and angles in the ICMD model gives rise to constrained ICMD (CICMD) models. There are several theoretical aspects that need to be developed in order to make the CICMD method robust and widely usable. In this paper we have designed a new framework for 1) initializing velocities for non-independent CICMD coordinates, 2) efficient computation of center of mass velocity during CICMD simulations, 3) using advanced integrators such as Runge-Kutta, Lobatto and adaptive CVODE for CICMD simulations, and 4) cancelling out the “flying ice cube effect” that sometimes arises in Nosé-Hoover dynamics. The Generalized Newton-Euler Inverse Mass Operator (GNEIMO) method is an implementation of a CICMD method that we have developed to study protein dynamics. GNEIMO allows for a hierarchy of coarse-grained simulation models based on the ability to rigidly constrain any group of atoms. In this paper, we perform tests on the Lobatto and Runge-Kutta integrators to determine optimal simulation parameters. We also implement an adaptive coarse graining tool using the GNEIMO Python interface. This tool enables the secondary structure-guided “freezing and thawing” of degrees of freedom in the molecule on the fly during MD simulations, and is shown to fold four proteins to their native topologies. With these advancements we envision the use of the GNEIMO method in protein structure prediction, structure refinement, and in studying domain motion. PMID:23345138

  7. Advances in Mass Spectrometric Tools for Probing Neuropeptides

    NASA Astrophysics Data System (ADS)

    Buchberger, Amanda; Yu, Qing; Li, Lingjun

    2015-07-01

    Neuropeptides are important mediators in the functionality of the brain and other neurological organs. Because neuropeptides exist in a wide range of concentrations, appropriate characterization methods are needed to provide dynamic, chemical, and spatial information. Mass spectrometry and compatible tools have been a popular choice in analyzing neuropeptides. There have been several advances and challenges, both of which are the focus of this review. Discussions range from sample collection to bioinformatic tools, although avenues such as quantitation and imaging are included. Further development of the presented methods for neuropeptidomic mass spectrometric analysis is inevitable, which will lead to a further understanding of the complex interplay of neuropeptides and other signaling molecules in the nervous system.

  8. Advanced Electric Submersible Pump Design Tool for Geothermal Applications

    SciTech Connect

    Xuele Qi; Norman Turnquist; Farshad Ghasripoor

    2012-05-31

    Electrical Submersible Pumps (ESPs) present higher efficiency, larger production rate, and can be operated in deeper wells than the other geothermal artificial lifting systems. Enhanced Geothermal Systems (EGS) applications recommend lifting 300 C geothermal water at 80kg/s flow rate in a maximum 10-5/8-inch diameter wellbore to improve the cost-effectiveness. In this paper, an advanced ESP design tool comprising a 1D theoretical model and a 3D CFD analysis has been developed to design ESPs for geothermal applications. Design of Experiments was also performed to optimize the geometry and performance. The designed mixed-flow type centrifugal impeller and diffuser exhibit high efficiency and head rise under simulated EGS conditions. The design tool has been validated by comparing the prediction to experimental data of an existing ESP product.

  9. Constructing an advanced software tool for planetary atmospheric modeling

    NASA Technical Reports Server (NTRS)

    Keller, Richard M.; Sims, Michael; Podolak, Ester; Mckay, Christopher

    1990-01-01

    Scientific model building can be an intensive and painstaking process, often involving the development of large and complex computer programs. Despite the effort involved, scientific models cannot be easily distributed and shared with other scientists. In general, implemented scientific models are complex, idiosyncratic, and difficult for anyone but the original scientist/programmer to understand. We believe that advanced software techniques can facilitate both the model building and model sharing process. In this paper, we describe a prototype for a scientific modeling software tool that serves as an aid to the scientist in developing and using models. This tool includes an interactive intelligent graphical interface, a high level domain specific modeling language, a library of physics equations and experimental datasets, and a suite of data display facilities. Our prototype has been developed in the domain of planetary atmospheric modeling, and is being used to construct models of Titan's atmosphere.

  10. Review on advanced composite materials boring mechanism and tools

    NASA Astrophysics Data System (ADS)

    Shi, Runping; Wang, Chengyong

    2011-05-01

    With the rapid development of aviation and aerospace manufacturing technology, advanced composite materials represented by carbon fibre reinforced plastics (CFRP) and super hybrid composites (fibre/metal plates) are more and more widely applied. The fibres are mainly carbon fibre, boron fibre, Aramid fiber and Sic fibre. The matrixes are resin matrix, metal matrix and ceramic matrix. Advanced composite materials have higher specific strength and higher specific modulus than glass fibre reinforced resin composites of the 1st generation. They are widely used in aviation and aerospace industry due to their high specific strength, high specific modulus, excellent ductility, anticorrosion, heat-insulation, sound-insulation, shock absorption and high&low temperature resistance. They are used for radomes, inlets, airfoils(fuel tank included), flap, aileron, vertical tail, horizontal tail, air brake, skin, baseboards and tails, etc. Its hardness is up to 62~65HRC. The holes are greatly affected by the fibre laminates direction of carbon fibre reinforced composite material due to its anisotropy when drilling in unidirectional laminates. There are burrs, splits at the exit because of stress concentration. Besides there is delamination and the hole is prone to be smaller. Burrs are caused by poor sharpness of cutting edge, delamination, tearing, splitting are caused by the great stress caused by high thrust force. Poorer sharpness of cutting edge leads to lower cutting performance and higher drilling force at the same time. The present research focuses on the interrelation between rotation speed, feed, drill's geometry, drill life, cutting mode, tools material etc. and thrust force. At the same time, holes quantity and holes making difficulty of composites have also increased. It requires high performance drills which won't bring out defects and have long tool life. It has become a trend to develop super hard material tools and tools with special geometry for drilling

  11. Review on advanced composite materials boring mechanism and tools

    NASA Astrophysics Data System (ADS)

    Shi, Runping; Wang, Chengyong

    2010-12-01

    With the rapid development of aviation and aerospace manufacturing technology, advanced composite materials represented by carbon fibre reinforced plastics (CFRP) and super hybrid composites (fibre/metal plates) are more and more widely applied. The fibres are mainly carbon fibre, boron fibre, Aramid fiber and Sic fibre. The matrixes are resin matrix, metal matrix and ceramic matrix. Advanced composite materials have higher specific strength and higher specific modulus than glass fibre reinforced resin composites of the 1st generation. They are widely used in aviation and aerospace industry due to their high specific strength, high specific modulus, excellent ductility, anticorrosion, heat-insulation, sound-insulation, shock absorption and high&low temperature resistance. They are used for radomes, inlets, airfoils(fuel tank included), flap, aileron, vertical tail, horizontal tail, air brake, skin, baseboards and tails, etc. Its hardness is up to 62~65HRC. The holes are greatly affected by the fibre laminates direction of carbon fibre reinforced composite material due to its anisotropy when drilling in unidirectional laminates. There are burrs, splits at the exit because of stress concentration. Besides there is delamination and the hole is prone to be smaller. Burrs are caused by poor sharpness of cutting edge, delamination, tearing, splitting are caused by the great stress caused by high thrust force. Poorer sharpness of cutting edge leads to lower cutting performance and higher drilling force at the same time. The present research focuses on the interrelation between rotation speed, feed, drill's geometry, drill life, cutting mode, tools material etc. and thrust force. At the same time, holes quantity and holes making difficulty of composites have also increased. It requires high performance drills which won't bring out defects and have long tool life. It has become a trend to develop super hard material tools and tools with special geometry for drilling

  12. DockingShop: A Tool for Interactive Molecular Docking

    SciTech Connect

    Lu, Ting-Cheng; Max, Nelson L.; Ding, Jinhui; Bethel, E. Wes; Crivelli, Silvia N.

    2005-04-24

    Given two independently determined molecular structures, the molecular docking problem predicts the bound association, or best fit between them, while allowing for conformational changes of the individual molecules during construction of a molecular complex. Docking Shop is an integrated environment that permits interactive molecular docking by navigating a ligand or protein to an estimated binding site of a receptor with real-time graphical feedback of scoring factors as visual guides. Our program can be used to create initial configurations for a protein docking prediction process. Its output--the structure of aprotein-ligand or protein-protein complex--may serve as an input for aprotein docking algorithm, or an optimization process. This tool provides molecular graphics interfaces for structure modeling, interactive manipulation, navigation, optimization, and dynamic visualization to aid users steer the prediction process using their biological knowledge.

  13. Advances in molecular breeding of flowering dogwood (Cornus florida L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although the production and sales of ornamental crops represent significant contributions to the global economy, breeding and selection of ornamental plants using molecular markers lags far behind that used for agronomic crops. However, with the recent advances in molecular technologies including r...

  14. ADVISOR: a systems analysis tool for advanced vehicle modeling

    NASA Astrophysics Data System (ADS)

    Markel, T.; Brooker, A.; Hendricks, T.; Johnson, V.; Kelly, K.; Kramer, B.; O'Keefe, M.; Sprik, S.; Wipke, K.

    This paper provides an overview of Advanced Vehicle Simulator (ADVISOR)—the US Department of Energy's (DOE's) ADVISOR written in the MATLAB/Simulink environment and developed by the National Renewable Energy Laboratory. ADVISOR provides the vehicle engineering community with an easy-to-use, flexible, yet robust and supported analysis package for advanced vehicle modeling. It is primarily used to quantify the fuel economy, the performance, and the emissions of vehicles that use alternative technologies including fuel cells, batteries, electric motors, and internal combustion engines in hybrid (i.e. multiple power sources) configurations. It excels at quantifying the relative change that can be expected due to the implementation of technology compared to a baseline scenario. ADVISOR's capabilities and limitations are presented and the power source models that are included in ADVISOR are discussed. Finally, several applications of the tool are presented to highlight ADVISOR's functionality. The content of this paper is based on a presentation made at the 'Development of Advanced Battery Engineering Models' workshop held in Crystal City, Virginia in August 2001.

  15. Molecular dynamics simulations: advances and applications

    PubMed Central

    Hospital, Adam; Goñi, Josep Ramon; Orozco, Modesto; Gelpí, Josep L

    2015-01-01

    Molecular dynamics simulations have evolved into a mature technique that can be used effectively to understand macromolecular structure-to-function relationships. Present simulation times are close to biologically relevant ones. Information gathered about the dynamic properties of macromolecules is rich enough to shift the usual paradigm of structural bioinformatics from studying single structures to analyze conformational ensembles. Here, we describe the foundations of molecular dynamics and the improvements made in the direction of getting such ensemble. Specific application of the technique to three main issues (allosteric regulation, docking, and structure refinement) is discussed. PMID:26604800

  16. A perfect time to harness advanced molecular technologies to explore the fundamental biology of Toxocara species.

    PubMed

    Gasser, Robin B

    2013-04-15

    Toxocarosis is of major canine health and socioeconomic importance worldwide. Although many studies have given insights into toxocarosis, to date, there has been limited exploration of the molecular biology, biochemistry, genetics, epidemiology and ecology of Toxocara species as well as parasite-host interactions using '-omic' technologies. The present article gives a background on Toxocara species and toxocarosis, describes molecular tools for specific identification and genetic analysis, and provides a prospective view of the benefits that advanced molecular technologies will have towards better understanding the parasites and disease. Tackling key biological questions employing a 'systems biology' approach should lead to new and improved strategies for the treatment, diagnosis and control of toxocarosis.

  17. How to Train a Cell–Cutting-Edge Molecular Tools

    PubMed Central

    Czapiński, Jakub; Kiełbus, Michał; Kałafut, Joanna; Kos, Michał; Stepulak, Andrzej; Rivero-Müller, Adolfo

    2017-01-01

    In biological systems, the formation of molecular complexes is the currency for all cellular processes. Traditionally, functional experimentation was targeted to single molecular players in order to understand its effects in a cell or animal phenotype. In the last few years, we have been experiencing rapid progress in the development of ground-breaking molecular biology tools that affect the metabolic, structural, morphological, and (epi)genetic instructions of cells by chemical, optical (optogenetic) and mechanical inputs. Such precise dissection of cellular processes is not only essential for a better understanding of biological systems, but will also allow us to better diagnose and fix common dysfunctions. Here, we present several of these emerging and innovative techniques by providing the reader with elegant examples on how these tools have been implemented in cells, and, in some cases, organisms, to unravel molecular processes in minute detail. We also discuss their advantages and disadvantages with particular focus on their translation to multicellular organisms for in vivo spatiotemporal regulation. We envision that further developments of these tools will not only help solve the processes of life, but will give rise to novel clinical and industrial applications. PMID:28344971

  18. Lightweight object oriented structure analysis: tools for building tools to analyze molecular dynamics simulations.

    PubMed

    Romo, Tod D; Leioatts, Nicholas; Grossfield, Alan

    2014-12-15

    LOOS (Lightweight Object Oriented Structure-analysis) is a C++ library designed to facilitate making novel tools for analyzing molecular dynamics simulations by abstracting out the repetitive tasks, allowing developers to focus on the scientifically relevant part of the problem. LOOS supports input using the native file formats of most common biomolecular simulation packages, including CHARMM, NAMD, Amber, Tinker, and Gromacs. A dynamic atom selection language based on the C expression syntax is included and is easily accessible to the tool-writer. In addition, LOOS is bundled with over 140 prebuilt tools, including suites of tools for analyzing simulation convergence, three-dimensional histograms, and elastic network models. Through modern C++ design, LOOS is both simple to develop with (requiring knowledge of only four core classes and a few utility functions) and is easily extensible. A python interface to the core classes is also provided, further facilitating tool development.

  19. Bioinformatics Methods and Tools to Advance Clinical Care

    PubMed Central

    Lecroq, T.

    2015-01-01

    Summary Objectives To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain and clinical care. Method We provide a synopsis of the articles selected for the IMIA Yearbook 2015, from which we attempt to derive a synthetic overview of current and future activities in the field. As last year, a first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section. Each section editor has evaluated separately the set of 1,594 articles and the evaluation results were merged for retaining 15 articles for peer-review. Results The selection and evaluation process of this Yearbook’s section on Bioinformatics and Translational Informatics yielded four excellent articles regarding data management and genome medicine that are mainly tool-based papers. In the first article, the authors present PPISURV a tool for uncovering the role of specific genes in cancer survival outcome. The second article describes the classifier PredictSNP which combines six performing tools for predicting disease-related mutations. In the third article, by presenting a high-coverage map of the human proteome using high resolution mass spectrometry, the authors highlight the need for using mass spectrometry to complement genome annotation. The fourth article is also related to patient survival and decision support. The authors present datamining methods of large-scale datasets of past transplants. The objective is to identify chances of survival. Conclusions The current research activities still attest the continuous convergence of Bioinformatics and Medical Informatics, with a focus this year on dedicated tools and methods to advance clinical care. Indeed, there is a need for powerful tools for managing and interpreting complex, large-scale genomic and biological datasets, but also a need for user-friendly tools developed for the clinicians in their

  20. Clinical holistic health: advanced tools for holistic medicine.

    PubMed

    Ventegodt, Søren; Clausen, Birgitte; Nielsen, May Lyck; Merrick, Joav

    2006-02-24

    According to holistic medical theory, the patient will heal when old painful moments, the traumatic events of life that are often called "gestalts", are integrated in the present "now". The advanced holistic physician's expanded toolbox has many different tools to induce this healing, some that are more dangerous and potentially traumatic than others. The more intense the therapeutic technique, the more emotional energy will be released and contained in the session, but the higher also is the risk for the therapist to lose control of the session and lose the patient to his or her own dark side. To avoid harming the patient must be the highest priority in holistic existential therapy, making sufficient education and training an issue of highest importance. The concept of "stepping up" the therapy by using more and more "dramatic" methods to get access to repressed emotions and events has led us to a "therapeutic staircase" with ten steps: (1) establishing the relationship; (2) establishing intimacy, trust, and confidentiality; (3) giving support and holding; (4) taking the patient into the process of physical, emotional, and mental healing; (5) social healing of being in the family; (6) spiritual healing--returning to the abstract wholeness of the soul; (7) healing the informational layer of the body; (8) healing the three fundamental dimensions of existence: love, power, and sexuality in a direct way using, among other techniques, "controlled violence" and "acupressure through the vagina"; (9) mind-expanding and consciousness-transformative techniques like psychotropic drugs; and (10) techniques transgressing the patient's borders and, therefore, often traumatizing (for instance, the use of force against the will of the patient). We believe that the systematic use of the staircase will greatly improve the power and efficiency of holistic medicine for the patient and we invite a broad cooperation in scientifically testing the efficiency of the advanced holistic

  1. Advances of Molecular Imaging in Epilepsy.

    PubMed

    Galovic, Marian; Koepp, Matthias

    2016-06-01

    Positron emission tomography (PET) is a neuroimaging method that offers insights into the molecular functioning of a human brain. It has been widely used to study metabolic and neurotransmitter abnormalities in people with epilepsy. This article reviews the development of several PET radioligands and their application in studying the molecular mechanisms of epilepsy. Over the last decade, tracers binding to serotonin and γ-aminobutyric acid (GABA) receptors have been used to delineate the location of the epileptic focus. PET studies have examined the role of opioids, cannabinoids, acetylcholine, and dopamine in modulating neuronal hyperexcitability and seizure termination. In vivo analyses of drug transporters, e.g., P-glycoprotein, have increased our understanding of pharmacoresistance that could inform new therapeutic strategies. Finally, PET experiments targeting neuroinflammation and glutamate receptors might guide the development of novel biomarkers of epileptogenesis.

  2. Advanced Tools and Techniques for Formal Techniques in Aerospace Systems

    NASA Technical Reports Server (NTRS)

    Knight, John C.

    2005-01-01

    This is the final technical report for grant number NAG-1-02101. The title of this grant was "Advanced Tools and Techniques for Formal Techniques In Aerospace Systems". The principal investigator on this grant was Dr. John C. Knight of the Computer Science Department, University of Virginia, Charlottesville, Virginia 22904-4740. This report summarizes activities under the grant during the period 7/01/2002 to 9/30/2004. This report is organized as follows. In section 2, the technical background of the grant is summarized. Section 3 lists accomplishments and section 4 lists students funded under the grant. In section 5, we present a list of presentations given at various academic and research institutions about the research conducted. Finally, a list of publications generated under this grant is included in section 6.

  3. Sandia Advanced MEMS Design Tools, Version 2.0

    SciTech Connect

    Allen, Jim; McBrayer, John; Miller, Sam; Rodgers, Steve; montague, Steve; Sniegowski, Jeff; Jakubczak, Jay; Yarberry, Vic; Barnes, Steve; Priddy, Brian; Reyes, David; Westling, Belinda

    2002-06-13

    Sandia Advanced MEMS Design Tools is a 5-level surface micromachine fabrication technology, which customers internal and external to Sandia can access to fabricate prototype MEMS devices. This CD contains an integrated set of electronic files that: a) Describe the SUMMiT V fabrication process b) Provide enabling educational information (including pictures, videos, technical information) c)Facilitate the process of designing MEMS with the SUMMiT process (prototype file, Design Rule Checker, Standard Parts Library) d) Facilitate the process of having MEMS fabricated at SNL e) Facilitate the process of having post-fabrication services performed While there exist some files on the CD that are used in conjunction with the software AutoCAD, these files are not intended for use independent of the CD. NOTE: THE CUSTOMER MUST PURCHASE HIS/HER OWN COPY OF AutoCAD TO USE WITH THESE FILES.

  4. Sandia Advanced MEMS Design Tools v. 3.0

    SciTech Connect

    Yarberry, Victor R.; Allen, James J.; Lantz, Jeffrey W.; Priddy, Brian; Westlin, Belinda; Young, Andrew

    2016-08-25

    This is a major revision to the Sandia Advanced MEMS Design Tools. It replaces all previous versions. New features in this version: Revised to support AutoCAD 2014 and 2015 This CD contains an integrated set of electronic files that: a) Describe the SUMMiT V fabrication process b) Provide enabling educational information (including pictures, videos, technical information) c) Facilitate the process of designing MEMS with the SUMMiT process (prototype file, Design Rule Checker, Standard Parts Library) d) Facilitate the process of having MEMS fabricated at Sandia National Laboratories e) Facilitate the process of having post-fabrication services performed. While there exists some files on the CD that are used in conjunction with software package AutoCAD, these files are not intended for use independent of the CD. Note that the customer must purchase his/her own copy of AutoCAD to use with these files.

  5. Tool for Sizing Analysis of the Advanced Life Support System

    NASA Technical Reports Server (NTRS)

    Yeh, Hue-Hsie Jannivine; Brown, Cheryl B.; Jeng, Frank J.

    2005-01-01

    Advanced Life Support Sizing Analysis Tool (ALSSAT) is a computer model for sizing and analyzing designs of environmental-control and life support systems (ECLSS) for spacecraft and surface habitats involved in the exploration of Mars and Moon. It performs conceptual designs of advanced life support (ALS) subsystems that utilize physicochemical and biological processes to recycle air and water, and process wastes in order to reduce the need of resource resupply. By assuming steady-state operations, ALSSAT is a means of investigating combinations of such subsystems technologies and thereby assisting in determining the most cost-effective technology combination available. In fact, ALSSAT can perform sizing analysis of the ALS subsystems that are operated dynamically or steady in nature. Using the Microsoft Excel spreadsheet software with Visual Basic programming language, ALSSAT has been developed to perform multiple-case trade studies based on the calculated ECLSS mass, volume, power, and Equivalent System Mass, as well as parametric studies by varying the input parameters. ALSSAT s modular format is specifically designed for the ease of future maintenance and upgrades.

  6. Advanced REACH Tool: A Bayesian Model for Occupational Exposure Assessment

    PubMed Central

    McNally, Kevin; Warren, Nicholas; Fransman, Wouter; Entink, Rinke Klein; Schinkel, Jody; van Tongeren, Martie; Cherrie, John W.; Kromhout, Hans; Schneider, Thomas; Tielemans, Erik

    2014-01-01

    This paper describes a Bayesian model for the assessment of inhalation exposures in an occupational setting; the methodology underpins a freely available web-based application for exposure assessment, the Advanced REACH Tool (ART). The ART is a higher tier exposure tool that combines disparate sources of information within a Bayesian statistical framework. The information is obtained from expert knowledge expressed in a calibrated mechanistic model of exposure assessment, data on inter- and intra-individual variability in exposures from the literature, and context-specific exposure measurements. The ART provides central estimates and credible intervals for different percentiles of the exposure distribution, for full-shift and long-term average exposures. The ART can produce exposure estimates in the absence of measurements, but the precision of the estimates improves as more data become available. The methodology presented in this paper is able to utilize partially analogous data, a novel approach designed to make efficient use of a sparsely populated measurement database although some additional research is still required before practical implementation. The methodology is demonstrated using two worked examples: an exposure to copper pyrithione in the spraying of antifouling paints and an exposure to ethyl acetate in shoe repair. PMID:24665110

  7. Sandia Advanced MEMS Design Tools, Version 2.2.5

    SciTech Connect

    Yarberry, Victor; Allen, James; Lantz, Jeffery; Priddy, Brian; & Westling, Belinda

    2010-01-19

    The Sandia National Laboratories Advanced MEMS Design Tools, Version 2.2.5, is a collection of menus, prototype drawings, and executables that provide significant productivity enhancements when using AutoCAD to design MEMS components. This release is designed for AutoCAD 2000i, 2002, or 2004 and is supported under Windows NT 4.0, Windows 2000, or XP. SUMMiT V (Sandia Ultra planar Multi level MEMS Technology) is a 5 level surface micromachine fabrication technology, which customers internal and external to Sandia can access to fabricate prototype MEMS devices. This CD contains an integrated set of electronic files that: a) Describe the SUMMiT V fabrication process b) Facilitate the process of designing MEMS with the SUMMiT process (prototype file, Design Rule Checker, Standard Parts Library) New features in this version: AutoCAD 2004 support has been added. SafeExplode ? a new feature that explodes blocks without affecting polylines (avoids exploding polylines into objects that are ignored by the DRC and Visualization tools). Layer control menu ? a pull-down menu for selecting layers to isolate, freeze, or thaw. Updated tools: A check has been added to catch invalid block names. DRC features: Added username/password validation, added a method to update the user?s password. SNL_DRC_WIDTH ? a value to control the width of the DRC error lines. SNL_BIAS_VALUE ? a value use to offset selected geometry SNL_PROCESS_NAME ? a value to specify the process name Documentation changes: The documentation has been updated to include the new features. While there exist some files on the CD that are used in conjunction with software package AutoCAD, these files are not intended for use independent of the CD. Note that the customer must purchase his/her own copy of AutoCAD to use with these files.

  8. Advances in understanding angiogenesis through molecular studies

    SciTech Connect

    Kwon, Mijung; Libutti, Steven K. . E-mail: steven_libutti@nih.gov

    2006-01-01

    Tumors, in most cases, need angiogenesis for their sustained growth. A great deal of evidence has suggested that the process of angiogenesis is regulated by the balance between proangiogenic and antiangiogenic factors. Thus, the inhibition of tumor angiogenesis has been considered to be one of the key targets in anticancer therapy, and more than 60 antiangiogenic compounds are currently under clinical evaluation in cancer patients. However, the molecular mechanisms responsible for the activity of many of these antiangiogenic compounds are still not well understood. The recent development of microarray technology has allowed us to investigate the mechanism of action of these inhibitors more rapidly and extensively. With the use of microarray technology, novel molecules and pathways are shown to play a role in angiogenesis. This article also reviews new experimental approaches combined with microarray analysis to identify the molecular pathways involved in tumor-host interactions. Elucidation of the pathways that mediate both angiogenic and antiangiogenic responses will help us to develop better anticancer therapies.

  9. Tools for Modeling & Simulation of Molecular and Nanoelectronics Devices

    DTIC Science & Technology

    2012-06-14

    1) Tools for Modeling & Simulation of Molecular and Nanoelectronics Devices 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...parallel algorithms to allow for simulations of realistic device structures. In Phase II, these methods will be developed and will be integrated into...the integration of other simulation engines into the ATK package. This allows these codes, which are all of academic origin to date, to be driven from

  10. Bioceramics for osteogenesis, molecular and cellular advances.

    PubMed

    Demirkiran, Hande

    2012-01-01

    The remarkable need for bone tissue replacement in clinical situations, its limited availability and some major drawbacks of autologous (from the patient) and allogeneic (from a donor) bone grafts are driving researchers to search for alternative approaches for bone repair. In order to develop an appropriate bone substitute, one should understand bone structure and properties and its growth, which will guide researchers to select the optimal conditions for tissue culture and implantation. It's well accepted that bioceramics are excellent candidates as bone replacement with osteogenesis, osteoinduction and osteoconduction capacity. Therefore, the molecular and cellular interactions that take place at the surface of bioceramics and their relevance in osteogenesis excites many researchers to delve deeper into this line of research.

  11. Molecular engineering of industrial enzymes: recent advances and future prospects.

    PubMed

    Yang, Haiquan; Li, Jianghua; Shin, Hyun-Dong; Du, Guocheng; Liu, Long; Chen, Jian

    2014-01-01

    Many enzymes are efficiently produced by microbes. However, the use of natural enzymes as biocatalysts has limitations such as low catalytic efficiency, low activity, and low stability, especially under industrial conditions. Many protein engineering technologies have been developed to modify natural enzymes and eliminate these limitations. Commonly used protein engineering strategies include directed evolution, site-directed mutagenesis, truncation, and terminal fusion. This review summarizes recent advances in the molecular engineering of industrial enzymes and discusses future prospects in this field. We expect this review to increase interest in and advance the molecular engineering of industrial enzymes.

  12. Advances in molecular imaging for breast cancer detection and characterization

    PubMed Central

    2012-01-01

    Advances in our ability to assay molecular processes, including gene expression, protein expression, and molecular and cellular biochemistry, have fueled advances in our understanding of breast cancer biology and have led to the identification of new treatments for patients with breast cancer. The ability to measure biologic processes without perturbing them in vivo allows the opportunity to better characterize tumor biology and to assess how biologic and cytotoxic therapies alter critical pathways of tumor response and resistance. By accurately characterizing tumor properties and biologic processes, molecular imaging plays an increasing role in breast cancer science, clinical care in diagnosis and staging, assessment of therapeutic targets, and evaluation of responses to therapies. This review describes the current role and potential of molecular imaging modalities for detection and characterization of breast cancer and focuses primarily on radionuclide-based methods. PMID:22423895

  13. Biliary tract cancers: molecular profiling as a tool for treatment decisions. A literature review.

    PubMed

    Berardi, Rossana; Rossana, Berardi; Scartozzi, Mario; Mario, Scartozzi; Freddari, Federica; Federica, Freddari; Squadroni, Michela; Michela, Squadroni; Santinelli, Alfredo; Alfredo, Santinelli; Bearzi, Italo; Italo, Bearzi; Fabris, Guidalberto; Guidalberto, Fabris; Cascinu, Stefano; Stefano, Cascinu

    2006-08-01

    Biliary tract cancer is a quite rare disease; despite recent significant advances in imaging modalities, most of the patients have advanced disease at presentation thus making radical surgery not feasible. Many different chemotherapeutic regimens have been investigated in small uncontrolled studies, with generally disappointing results. We extensively reviewed the literature on this topic trying to give an explanation to chemoresistance in this setting of patients and considering the molecular profiling as a tool for treatment decision. This review is divided in two parts, in the first one we illustrated chemotherapy results and possible mechanisms of resistance. In the second part we analysed the new molecular targets developing an hypothesis about the future therapeutics perspectives.

  14. Advanced Infusion Techniques with 3-D Printed Tooling

    SciTech Connect

    Nuttall, David; Elliott, Amy; Post, Brian K.; Love, Lonnie J.

    2016-05-10

    The manufacturing of tooling for large, contoured surfaces for fiber-layup applications requires significant effort to understand the geometry and then to subtractively manufacture the tool. Traditional methods for the auto industry use clay that is hand sculpted. In the marine pleasure craft industry, the exterior of the model is formed from a foam lay-up that is either hand cut or machined to create smooth lines. Engineers and researchers at Oak Ridge National Laboratory s Manufacturing Demonstration Facility (ORNL MDF) collaborated with Magnum Venus Products (MVP) in the development of a process for reproducing legacy whitewater adventure craft via digital scanning and large scale 3-D printed layup molds. The process entailed 3D scanning a legacy canoe form, converting that form to a CAD model, additively manufacturing (3-D Print) the mold tool, and subtractively finishing the mold s transfer surfaces. Future work will include applying a gelcoat to the mold transfer surface and infusing using vacuum assisted resin transfer molding, or VARTM principles, to create a watertight vessel. The outlined steps were performed on a specific canoe geometry found by MVP s principal participant. The intent of utilizing this geometry is to develop an energy efficient and marketable process for replicating complex shapes, specifically focusing on this particular watercraft, and provide a finished product for demonstration to the composites industry. The culminating part produced through this agreement has been slated for public presentation and potential demonstration at the 2016 CAMX (Composites and Advanced Materials eXpo) exposition in Anaheim, CA. Phase I of this collaborative research and development agreement (MDF-15-68) was conducted under CRADA NFE-15-05575 and was initiated on May 7, 2015, with an introduction to the MVP product line, and concluded in March of 2016 with the printing of and processing of a canoe mold. The project partner Magnum Venous Products (MVP) is

  15. Advanced fault diagnosis methods in molecular networks.

    PubMed

    Habibi, Iman; Emamian, Effat S; Abdi, Ali

    2014-01-01

    Analysis of the failure of cell signaling networks is an important topic in systems biology and has applications in target discovery and drug development. In this paper, some advanced methods for fault diagnosis in signaling networks are developed and then applied to a caspase network and an SHP2 network. The goal is to understand how, and to what extent, the dysfunction of molecules in a network contributes to the failure of the entire network. Network dysfunction (failure) is defined as failure to produce the expected outputs in response to the input signals. Vulnerability level of a molecule is defined as the probability of the network failure, when the molecule is dysfunctional. In this study, a method to calculate the vulnerability level of single molecules for different combinations of input signals is developed. Furthermore, a more complex yet biologically meaningful method for calculating the multi-fault vulnerability levels is suggested, in which two or more molecules are simultaneously dysfunctional. Finally, a method is developed for fault diagnosis of networks based on a ternary logic model, which considers three activity levels for a molecule instead of the previously published binary logic model, and provides equations for the vulnerabilities of molecules in a ternary framework. Multi-fault analysis shows that the pairs of molecules with high vulnerability typically include a highly vulnerable molecule identified by the single fault analysis. The ternary fault analysis for the caspase network shows that predictions obtained using the more complex ternary model are about the same as the predictions of the simpler binary approach. This study suggests that by increasing the number of activity levels the complexity of the model grows; however, the predictive power of the ternary model does not appear to be increased proportionally.

  16. The scientific modeling assistant: An advanced software tool for scientific model building

    NASA Technical Reports Server (NTRS)

    Keller, Richard M.; Sims, Michael H.

    1991-01-01

    Viewgraphs on the scientific modeling assistant: an advanced software tool for scientific model building are presented. The objective is to build a specialized software tool to assist in scientific model-building.

  17. Advances in molecular preclinical therapy mediated by imaging.

    PubMed

    Greco, Adelaide; Albanese, Sandra; Auletta, Luigi; DE Carlo, Flavia; Salvatore, Marco; Howard, Candace M; Claudio, Pier P

    2017-03-01

    Several advances have been made toward understanding the biology of cancer and most of them are due to robust genetic studies that led to the scientific recognition that although many patients have the same type of cancer their tumors may have harbored different molecular alterations. Personalized therapy and the development of advanced techniques of preclinical imaging and new murine models of disease are emerging concepts that are allowing mapping of disease markers in vivo and in some cases also receptor targeted therapy. Aim of this review is to illustrate some emerging models of disease that allow patient tumor implantation in mice for subsequent drug testing and advanced approaches for therapy mediated by preclinical imaging. In particular we discuss targeted therapy mediated by high frequency ultrasound and magnetic resonance, two emerging techniques in molecular preclinical therapy.

  18. Molecular dynamics simulation: A tool for exploration and discovery

    NASA Astrophysics Data System (ADS)

    Rapaport, Dennis C.

    2009-03-01

    The exploratory and didactic aspects of science both benefit from the ever-growing role played by computer simulation. One particularly important simulational approach is the molecular dynamics method, used for studying the nature of matter from the molecular to much larger scales. The effectiveness of molecular dynamics can be enhanced considerably by employing visualization and interactivity during the course of the computation and afterwards, allowing the modeler not only to observe the detailed behavior of the systems simulated in different ways, but also to steer the computations in alternative directions by manipulating parameters that govern the actual behavior. This facilitates the creation of potentially rich simulational environments for examining a multitude of complex phenomena, as well as offering an opportunity for enriching the learning process. A series of relatively advanced examples involving molecular dynamics will be used to demonstrate the value of this approach, in particular, atomistic simulations of spontaneously emergent structured fluid flows (the classic Rayleigh--B'enard and Taylor--Couette problems), supramolecular self-assembly of highly symmetric shell structures (involved in the formation of viral capsids), and that most counterintuitive of phenomena, granular segregation (e.g., axial and radial separation in a rotating cylinder).

  19. Atomic force microscopy as an advanced tool in neuroscience

    PubMed Central

    Jembrek, Maja Jazvinšćak; Šimić, Goran; Hof, Patrick R.; Šegota, Suzana

    2015-01-01

    This review highlights relevant issues about applications and improvements of atomic force microscopy (AFM) toward a better understanding of neurodegenerative changes at the molecular level with the hope of contributing to the development of effective therapeutic strategies for neurodegenerative illnesses. The basic principles of AFM are briefly discussed in terms of evaluation of experimental data, including the newest PeakForce Quantitative Nanomechanical Mapping (QNM) and the evaluation of Young’s modulus as the crucial elasticity parameter. AFM topography, revealed in imaging mode, can be used to monitor changes in live neurons over time, representing a valuable tool for high-resolution detection and monitoring of neuronal morphology. The mechanical properties of living cells can be quantified by force spectroscopy as well as by new AFM. A variety of applications are described, and their relevance for specific research areas discussed. In addition, imaging as well as non-imaging modes can provide specific information, not only about the structural and mechanical properties of neuronal membranes, but also on the cytoplasm, cell nucleus, and particularly cytoskeletal components. Moreover, new AFM is able to provide detailed insight into physical structure and biochemical interactions in both physiological and pathophysiological conditions. PMID:28123795

  20. Polymerase chain reaction: A molecular diagnostic tool in periodontology.

    PubMed

    Maheaswari, Rajendran; Kshirsagar, Jaishree Tukaram; Lavanya, Nallasivam

    2016-01-01

    This review discusses the principles of polymerase chain reaction (PCR) and its application as a diagnostic tool in periodontology. The relevant MEDLINE and PubMed indexed journals were searched manually and electronically by typing PCR, applications of PCR, PCR in periodontics, polymorphism studies in periodontitis, and molecular techniques in periodontology. The searches were limited to articles in English language and the articles describing PCR process and its relation to periodontology were collected and used to prepare a concise review. PCR has now become a standard diagnostic and research tool in periodontology. Various studies reveal that its sensitivity and specificity allow it as a rapid, efficient method of detecting, identifying, and quantifying organism. Different immune and inflammatory markers can be identified at the mRNA expression level, and also the determination of genetic polymorphisms, thus providing the deeper insight into the mechanisms underlying the periodontal disease.

  1. Polymerase chain reaction: A molecular diagnostic tool in periodontology

    PubMed Central

    Maheaswari, Rajendran; Kshirsagar, Jaishree Tukaram; Lavanya, Nallasivam

    2016-01-01

    This review discusses the principles of polymerase chain reaction (PCR) and its application as a diagnostic tool in periodontology. The relevant MEDLINE and PubMed indexed journals were searched manually and electronically by typing PCR, applications of PCR, PCR in periodontics, polymorphism studies in periodontitis, and molecular techniques in periodontology. The searches were limited to articles in English language and the articles describing PCR process and its relation to periodontology were collected and used to prepare a concise review. PCR has now become a standard diagnostic and research tool in periodontology. Various studies reveal that its sensitivity and specificity allow it as a rapid, efficient method of detecting, identifying, and quantifying organism. Different immune and inflammatory markers can be identified at the mRNA expression level, and also the determination of genetic polymorphisms, thus providing the deeper insight into the mechanisms underlying the periodontal disease. PMID:27143822

  2. Molecular diagnostic and surveillance tools for global malaria control.

    PubMed

    Erdman, Laura K; Kain, Kevin C

    2008-01-01

    Malaria is the most devastating parasitic infection in the world, annually causing over 1 million deaths and extensive morbidity. The global burden of malaria has increased over the last several decades, as have rates of imported malaria into non-endemic regions. Rapid and accurate diagnostics are a crucial component of malaria control strategies, and epidemiological surveillance is required to monitor trends in malaria prevalence and antimalarial drug resistance. Conventional malaria diagnostic and surveillance tools can be cumbersome and slow with limitations in both sensitivity and specificity. New molecular techniques have been developed in an attempt to overcome these restrictions. These molecular techniques are discussed with regard to their technical advantages and disadvantages, with an emphasis on the practicality of implementation in malaria-endemic and non-endemic regions.

  3. Yada: a novel tool for molecular docking calculations

    NASA Astrophysics Data System (ADS)

    Piotto, S.; Di Biasi, L.; Fino, R.; Parisi, R.; Sessa, L.; Concilio, S.

    2016-09-01

    Molecular docking is a computational method employed to estimate the binding between a small ligand (the drug candidate) and a protein receptor that has become a standard part of workflow in drug discovery. Generally, when the binding site is known and a molecule is similar to known ligands, the most popular docking methods are rather accurate in the prediction of the geometry. Unfortunately, when the binding site is unknown, the blind docking analysis requires large computational resources and the results are often not accurate. Here we present Yada, a new tool for molecular docking that is capable to distribute efficiently calculations onto general purposes computer grid and that combines biological and structural information of the receptor. Yada is available for Windows and Linux and it is free to download at >www.yada.unisa.it.

  4. Yada: a novel tool for molecular docking calculations.

    PubMed

    Piotto, S; Di Biasi, L; Fino, R; Parisi, R; Sessa, L; Concilio, S

    2016-09-01

    Molecular docking is a computational method employed to estimate the binding between a small ligand (the drug candidate) and a protein receptor that has become a standard part of workflow in drug discovery. Generally, when the binding site is known and a molecule is similar to known ligands, the most popular docking methods are rather accurate in the prediction of the geometry. Unfortunately, when the binding site is unknown, the blind docking analysis requires large computational resources and the results are often not accurate. Here we present Yada, a new tool for molecular docking that is capable to distribute efficiently calculations onto general purposes computer grid and that combines biological and structural information of the receptor. Yada is available for Windows and Linux and it is free to download at www.yada.unisa.it .

  5. STRING 3: An Advanced Groundwater Flow Visualization Tool

    NASA Astrophysics Data System (ADS)

    Schröder, Simon; Michel, Isabel; Biedert, Tim; Gräfe, Marius; Seidel, Torsten; König, Christoph

    2016-04-01

    The visualization of 3D groundwater flow is a challenging task. Previous versions of our software STRING [1] solely focused on intuitive visualization of complex flow scenarios for non-professional audiences. STRING, developed by Fraunhofer ITWM (Kaiserslautern, Germany) and delta h Ingenieurgesellschaft mbH (Witten, Germany), provides the necessary means for visualization of both 2D and 3D data on planar and curved surfaces. In this contribution we discuss how to extend this approach to a full 3D tool and its challenges in continuation of Michel et al. [2]. This elevates STRING from a post-production to an exploration tool for experts. In STRING moving pathlets provide an intuition of velocity and direction of both steady-state and transient flows. The visualization concept is based on the Lagrangian view of the flow. To capture every detail of the flow an advanced method for intelligent, time-dependent seeding is used building on the Finite Pointset Method (FPM) developed by Fraunhofer ITWM. Lifting our visualization approach from 2D into 3D provides many new challenges. With the implementation of a seeding strategy for 3D one of the major problems has already been solved (see Schröder et al. [3]). As pathlets only provide an overview of the velocity field other means are required for the visualization of additional flow properties. We suggest the use of Direct Volume Rendering and isosurfaces for scalar features. In this regard we were able to develop an efficient approach for combining the rendering through raytracing of the volume and regular OpenGL geometries. This is achieved through the use of Depth Peeling or A-Buffers for the rendering of transparent geometries. Animation of pathlets requires a strict boundary of the simulation domain. Hence, STRING needs to extract the boundary, even from unstructured data, if it is not provided. In 3D we additionally need a good visualization of the boundary itself. For this the silhouette based on the angle of

  6. Advanced Fuel Cycle Economic Tools, Algorithms, and Methodologies

    SciTech Connect

    David E. Shropshire

    2009-05-01

    The Advanced Fuel Cycle Initiative (AFCI) Systems Analysis supports engineering economic analyses and trade-studies, and requires a requisite reference cost basis to support adequate analysis rigor. In this regard, the AFCI program has created a reference set of economic documentation. The documentation consists of the “Advanced Fuel Cycle (AFC) Cost Basis” report (Shropshire, et al. 2007), “AFCI Economic Analysis” report, and the “AFCI Economic Tools, Algorithms, and Methodologies Report.” Together, these documents provide the reference cost basis, cost modeling basis, and methodologies needed to support AFCI economic analysis. The application of the reference cost data in the cost and econometric systems analysis models will be supported by this report. These methodologies include: the energy/environment/economic evaluation of nuclear technology penetration in the energy market—domestic and internationally—and impacts on AFCI facility deployment, uranium resource modeling to inform the front-end fuel cycle costs, facility first-of-a-kind to nth-of-a-kind learning with application to deployment of AFCI facilities, cost tradeoffs to meet nuclear non-proliferation requirements, and international nuclear facility supply/demand analysis. The economic analysis will be performed using two cost models. VISION.ECON will be used to evaluate and compare costs under dynamic conditions, consistent with the cases and analysis performed by the AFCI Systems Analysis team. Generation IV Excel Calculations of Nuclear Systems (G4-ECONS) will provide static (snapshot-in-time) cost analysis and will provide a check on the dynamic results. In future analysis, additional AFCI measures may be developed to show the value of AFCI in closing the fuel cycle. Comparisons can show AFCI in terms of reduced global proliferation (e.g., reduction in enrichment), greater sustainability through preservation of a natural resource (e.g., reduction in uranium ore depletion), value from

  7. Molecular Beacons: Powerful Tools for Imaging RNA in Living Cells

    PubMed Central

    Monroy-Contreras, Ricardo; Vaca, Luis

    2011-01-01

    Recent advances in RNA functional studies highlights the pivotal role of these molecules in cell physiology. Diverse methods have been implemented to measure the expression levels of various RNA species, using either purified RNA or fixed cells. Despite the fact that fixed cells offer the possibility to observe the spatial distribution of RNA, assays with capability to real-time monitoring RNA transport into living cells are needed to further understand the role of RNA dynamics in cellular functions. Molecular beacons (MBs) are stem-loop hairpin-structured oligonucleotides equipped with a fluorescence quencher at one end and a fluorescent dye (also called reporter or fluorophore) at the opposite end. This structure permits that MB in the absence of their target complementary sequence do not fluoresce. Upon binding to targets, MBs emit fluorescence, due to the spatial separation of the quencher and the reporter. Molecular beacons are promising probes for the development of RNA imaging techniques; nevertheless much work remains to be done in order to obtain a robust technology for imaging various RNA molecules together in real time and in living cells. The present work concentrates on the different requirements needed to use successfully MB for cellular studies, summarizing recent advances in this area. PMID:21876785

  8. Development of molecular tools to monitor conjugative transfer in rhizobia.

    PubMed

    Tejerizo, Gonzalo Torres; Bañuelos, Luis Alfredo; Cervantes, Laura; Gaytán, Paul; Pistorio, Mariano; Romero, David; Brom, Susana

    2015-10-01

    Evolution of bacterial populations has been extensively driven by horizontal transfer events. Conjugative plasmid transfer is considered the principal contributor to gene exchange among bacteria. Several conjugative and mobilizable plasmids have been identified in rhizobia, and two major molecular mechanisms that regulate their transfer have been described, under laboratory conditions. The knowledge of rhizobial plasmid transfer regulation in natural environments is very poor. In this work we developed molecular tools to easily monitor the conjugative plasmid transfer in rhizobia by flow cytometry (FC) or microscopy. 24 cassettes were constructed by combining a variety of promotors, fluorescent proteins and antibiotic resistance genes, and used to tag plasmids and chromosome of donor strains. We were able to detect plasmid transfer after conversion of non-fluorescent recipients into fluorescent transconjugants. Flow cytometry (FC) was optimized to count donor, recipient and transconjugant strains to determine conjugative transfer frequencies. Results were similar, when determined either by FC or by viable counts. Our constructions also allowed the visualization of transconjugants in crosses performed on bean roots. The tools presented here may also be used for other purposes, such as analysis of transcriptional fusions or single-cell tagging. Application of the system will allow the survey of how different environmental conditions or other regulators modulate plasmid transfer in rhizobia.

  9. Plant Aquaporins: Genome-Wide Identification, Transcriptomics, Proteomics, and Advanced Analytical Tools

    PubMed Central

    Deshmukh, Rupesh K.; Sonah, Humira; Bélanger, Richard R.

    2016-01-01

    Aquaporins (AQPs) are channel-forming integral membrane proteins that facilitate the movement of water and many other small molecules. Compared to animals, plants contain a much higher number of AQPs in their genome. Homology-based identification of AQPs in sequenced species is feasible because of the high level of conservation of protein sequences across plant species. Genome-wide characterization of AQPs has highlighted several important aspects such as distribution, genetic organization, evolution and conserved features governing solute specificity. From a functional point of view, the understanding of AQP transport system has expanded rapidly with the help of transcriptomics and proteomics data. The efficient analysis of enormous amounts of data generated through omic scale studies has been facilitated through computational advancements. Prediction of protein tertiary structures, pore architecture, cavities, phosphorylation sites, heterodimerization, and co-expression networks has become more sophisticated and accurate with increasing computational tools and pipelines. However, the effectiveness of computational approaches is based on the understanding of physiological and biochemical properties, transport kinetics, solute specificity, molecular interactions, sequence variations, phylogeny and evolution of aquaporins. For this purpose, tools like Xenopus oocyte assays, yeast expression systems, artificial proteoliposomes, and lipid membranes have been efficiently exploited to study the many facets that influence solute transport by AQPs. In the present review, we discuss genome-wide identification of AQPs in plants in relation with recent advancements in analytical tools, and their availability and technological challenges as they apply to AQPs. An exhaustive review of omics resources available for AQP research is also provided in order to optimize their efficient utilization. Finally, a detailed catalog of computational tools and analytical pipelines is

  10. Comparing Simple and Advanced Video Tools as Supports for Complex Collaborative Design Processes

    ERIC Educational Resources Information Center

    Zahn, Carmen; Pea, Roy; Hesse, Friedrich W.; Rosen, Joe

    2010-01-01

    Working with digital video technologies, particularly advanced video tools with editing capabilities, offers new prospects for meaningful learning through design. However, it is also possible that the additional complexity of such tools does "not" advance learning. We compared in an experiment the design processes and learning outcomes…

  11. ms2: A molecular simulation tool for thermodynamic properties

    NASA Astrophysics Data System (ADS)

    Deublein, Stephan; Eckl, Bernhard; Stoll, Jürgen; Lishchuk, Sergey V.; Guevara-Carrion, Gabriela; Glass, Colin W.; Merker, Thorsten; Bernreuther, Martin; Hasse, Hans; Vrabec, Jadran

    2011-11-01

    This work presents the molecular simulation program ms2 that is designed for the calculation of thermodynamic properties of bulk fluids in equilibrium consisting of small electro-neutral molecules. ms2 features the two main molecular simulation techniques, molecular dynamics (MD) and Monte-Carlo. It supports the calculation of vapor-liquid equilibria of pure fluids and multi-component mixtures described by rigid molecular models on the basis of the grand equilibrium method. Furthermore, it is capable of sampling various classical ensembles and yields numerous thermodynamic properties. To evaluate the chemical potential, Widom's test molecule method and gradual insertion are implemented. Transport properties are determined by equilibrium MD simulations following the Green-Kubo formalism. ms2 is designed to meet the requirements of academia and industry, particularly achieving short response times and straightforward handling. It is written in Fortran90 and optimized for a fast execution on a broad range of computer architectures, spanning from single processor PCs over PC-clusters and vector computers to high-end parallel machines. The standard Message Passing Interface (MPI) is used for parallelization and ms2 is therefore easily portable to different computing platforms. Feature tools facilitate the interaction with the code and the interpretation of input and output files. The accuracy and reliability of ms2 has been shown for a large variety of fluids in preceding work. Program summaryProgram title:ms2 Catalogue identifier: AEJF_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEJF_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Special Licence supplied by the authors No. of lines in distributed program, including test data, etc.: 82 794 No. of bytes in distributed program, including test data, etc.: 793 705 Distribution format: tar.gz Programming language: Fortran90 Computer: The

  12. Molecular Genetic Tools and Techniques in Fission Yeast.

    PubMed

    Murray, Johanne M; Watson, Adam T; Carr, Antony M

    2016-05-02

    The molecular genetic tools used in fission yeast have generally been adapted from methods and approaches developed for use in the budding yeast, Saccharomyces cerevisiae Initially, the molecular genetics of Schizosaccharomyces pombe was developed to aid gene identification, but it is now applied extensively to the analysis of gene function and the manipulation of noncoding sequences that affect chromosome dynamics. Much current research using fission yeast thus relies on the basic processes of introducing DNA into the organism and the extraction of DNA for subsequent analysis. Targeted integration into specific genomic loci is often used to create site-specific mutants or changes to noncoding regulatory elements for subsequent phenotypic analysis. It is also regularly used to introduce additional sequences that generate tagged proteins or to create strains in which the levels of wild-type protein can be manipulated through transcriptional regulation and/or protein degradation. Here, we draw together a collection of core molecular genetic techniques that underpin much of modern research using S. pombe We summarize the most useful methods that are routinely used and provide guidance, learned from experience, for the successful application of these methods.

  13. Synthetic Peptide templates for molecular recognition: recent advances and applications.

    PubMed

    Singh, Yashveer; Dolphin, Gunnar T; Razkin, Jesus; Dumy, Pascal

    2006-09-01

    The creation of molecular systems that can mimic some of the properties of natural macromolecules is one of the major endeavors in contemporary protein chemistry. However, the construction of artificial proteins with predetermined structure and function is difficult on account of complex folding pathways. The use of topological peptide templates has been suggested to induce and stabilize defined secondary and tertiary structures. This is because the recent advances in the chemistry of coupling reagents, protecting groups, and solid-phase synthesis have made the chemical synthesis of peptides with conformationally controlled and complex structures feasible. Besides their use as structure-inducing devices, these peptide templates can also be utilized to construct novel structures with tailor-made functions. Herein, we present recent advances in the field of peptide-template-based approaches with particular emphasis on the demonstrated utility of this approach in molecular recognition, along with related applications.

  14. New advanced radio diagnostics tools for Space Weather Program

    NASA Astrophysics Data System (ADS)

    Krankowski, A.; Rothkaehl, H.; Atamaniuk, B.; Morawski, M.; Zakharenkova, I.; Cherniak, I.; Otmianowska-Mazur, K.

    2013-12-01

    To give a more detailed and complete understanding of physical plasma processes that govern the solar-terrestrial space, and to develop qualitative and quantitative models of the magnetosphere-ionosphere-thermosphere coupling, it is necessary to design and build the next generation of instruments for space diagnostics and monitoring. Novel ground- based wide-area sensor networks, such as the LOFAR (Low Frequency Array) radar facility, comprising wide band, and vector-sensing radio receivers and multi-spacecraft plasma diagnostics should help solve outstanding problems of space physics and describe long-term environmental changes. The LOw Frequency ARray - LOFAR - is a new fully digital radio telescope designed for frequencies between 30 MHz and 240 MHz located in Europe. The three new LOFAR stations will be installed until summer 2015 in Poland. The LOFAR facilities in Poland will be distributed among three sites: Lazy (East of Krakow), Borowiec near Poznan and Baldy near Olsztyn. All they will be connected via PIONIER dedicated links to Poznan. Each site will host one LOFAR station (96 high-band+96 low-band antennas). They will most time work as a part of European network, however, when less charged, they can operate as a national network The new digital radio frequency analyzer (RFA) on board the low-orbiting RELEC satellite was designed to monitor and investigate the ionospheric plasma properties. This two-point ground-based and topside ionosphere-located space plasma diagnostic can be a useful new tool for monitoring and diagnosing turbulent plasma properties. The RFA on board the RELEC satellite is the first in a series of experiments which is planned to be launched into the near-Earth environment. In order to improve and validate the large scales and small scales ionospheric structures we will used the GPS observations collected at IGS/EPN network employed to reconstruct diurnal variations of TEC using all satellite passes over individual GPS stations and the

  15. Recent Advances in the Molecular Characterization of Circulating Tumor Cells

    PubMed Central

    Lowes, Lori E.; Allan, Alison L.

    2014-01-01

    Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch® system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs hold for oncology lies at the level of molecular characterization. Clinical treatment decisions may be more effective if they are based on molecular characteristics of metastatic cells rather than on those of the primary tumor alone. Molecular characterization of CTCs (which can be repeatedly isolated in a minimally invasive fashion) provides the opportunity for a “real-time liquid biopsy” that allows assessment of genetic drift, investigation of molecular disease evolution, and identification of actionable genomic characteristics. This review focuses on recent advances in this area, including approaches involving immunophenotyping, fluorescence in situ hybridization (FISH), multiplex RT-PCR, microarray, and genomic sequencing. PMID:24633084

  16. Molecular Targeted Viral Nanoparticles as Tools for Imaging Cancer

    PubMed Central

    Cho, C.F.; Sourabh, S.; Simpson, E.J.; Steinmetz, N.F.; Luyt, L.G.; Lewis, J.D.

    2015-01-01

    Viral nanoparticles (VNPs) are a novel class of bionanomaterials that harness the natural biocompatibility of viruses for the development of therapeutics, vaccines, and imaging tools. The plant virus, cowpea mosaic virus (CPMV), has been successfully engineered to create novel cancer-targeted imaging agents by incorporating fluorescent dyes, polyethylene glycol (PEG) polymers, and targeting moieties. Using straightforward conjugation strategies, VNPs with high selectivity for cancer-specific molecular targets can be synthesized for in vivo imaging of tumors. Here we describe the synthesis and purification of CPMV-based VNPs, the functionalization of these VNPs using click chemistry, and their use for imaging xenograft tumors in animal models. VNPs decorated with fluorescent dyes, PEG, and targeting ligands can be synthesized in one day, and imaging studies can be performed over hours, days, or weeks, depending on the application. PMID:24243252

  17. Molecular tools in understanding the evolution of Vibrio cholerae

    PubMed Central

    Rahaman, Md. Habibur; Islam, Tarequl; Colwell, Rita R.; Alam, Munirul

    2015-01-01

    Vibrio cholerae, the etiological agent of cholera, has been a scourge for centuries. Cholera remains a serious health threat for developing countries and has been responsible for millions of deaths globally over the past 200 years. Identification of V. cholerae has been accomplished using a variety of methods, ranging from phenotypic strategies to DNA based molecular typing and currently whole genomic approaches. This array of methods has been adopted in epidemiological investigations, either singly or in the aggregate, and more recently for evolutionary analyses of V. cholerae. Because the new technologies have been developed at an ever increasing pace, this review of the range of fingerprinting strategies, their relative advantages and limitations, and cholera case studies was undertaken. The task was challenging, considering the vast amount of the information available. To assist the study, key references representative of several areas of research are provided with the intent to provide readers with a comprehensive view of recent advances in the molecular epidemiology of V. cholerae. Suggestions for ways to obviate many of the current limitations of typing techniques are also provided. In summary, a comparative report has been prepared that includes the range from traditional typing to whole genomic strategies. PMID:26500613

  18. Molecular tools in understanding the evolution of Vibrio cholerae.

    PubMed

    Rahaman, Md Habibur; Islam, Tarequl; Colwell, Rita R; Alam, Munirul

    2015-01-01

    Vibrio cholerae, the etiological agent of cholera, has been a scourge for centuries. Cholera remains a serious health threat for developing countries and has been responsible for millions of deaths globally over the past 200 years. Identification of V. cholerae has been accomplished using a variety of methods, ranging from phenotypic strategies to DNA based molecular typing and currently whole genomic approaches. This array of methods has been adopted in epidemiological investigations, either singly or in the aggregate, and more recently for evolutionary analyses of V. cholerae. Because the new technologies have been developed at an ever increasing pace, this review of the range of fingerprinting strategies, their relative advantages and limitations, and cholera case studies was undertaken. The task was challenging, considering the vast amount of the information available. To assist the study, key references representative of several areas of research are provided with the intent to provide readers with a comprehensive view of recent advances in the molecular epidemiology of V. cholerae. Suggestions for ways to obviate many of the current limitations of typing techniques are also provided. In summary, a comparative report has been prepared that includes the range from traditional typing to whole genomic strategies.

  19. Development and Application of Camelid Molecular Cytogenetic Tools

    PubMed Central

    Avila, Felipe; Das, Pranab J.; Kutzler, Michelle; Owens, Elaine; Perelman, Polina; Rubes, Jiri; Hornak, Miroslav; Johnson, Warren E.

    2014-01-01

    Cytogenetic chromosome maps offer molecular tools for genome analysis and clinical cytogenetics and are of particular importance for species with difficult karyotypes, such as camelids (2n = 74). Building on the available human–camel zoo-fluorescence in situ hybridization (FISH) data, we developed the first cytogenetic map for the alpaca (Lama pacos, LPA) genome by isolating and identifying 151 alpaca bacterial artificial chromosome (BAC) clones corresponding to 44 specific genes. The genes were mapped by FISH to 31 alpaca autosomes and the sex chromosomes; 11 chromosomes had 2 markers, which were ordered by dual-color FISH. The STS gene mapped to Xpter/Ypter, demarcating the pseudoautosomal region, whereas no markers were assigned to chromosomes 14, 21, 22, 28, and 36. The chromosome-specific markers were applied in clinical cytogenetics to identify LPA20, the major histocompatibility complex (MHC)-carrying chromosome, as a part of an autosomal translocation in a sterile male llama (Lama glama, LGL; 2n = 73,XY). FISH with LPAX BACs and LPA36 paints, as well as comparative genomic hybridization, were also used to investigate the origin of the minute chromosome, an abnormally small LPA36 in infertile female alpacas. This collection of cytogenetically mapped markers represents a new tool for camelid clinical cytogenetics and has applications for the improvement of the alpaca genome map and sequence assembly. PMID:23109720

  20. [Tools of molecular biology, what can be expected from them?].

    PubMed

    Delpech, M

    1993-01-01

    The techniques of molecular biology represent a new tool for research and diagnosis. They have been used routinely since the middle 80s. The first applications were mainly in hereditary diseases. These techniques investigated an information and not direct biological activity and so new strategies had to be developed. Two techniques have played key roles. They are Southern's method which enables the detection of specific sequences among DNA fragments in any individual within a few days, and the method of in vitro selective amplification (PCR) which is the equivalent of cloning a sequence of several hundred pairs of bases in any individual in less than 3 hours. In hereditary diseases, molecular biological techniques enable diagnosis of the genetic abnormality responsible for the condition, even when the defect is not known. To this end, two strategies are available. The first, and the most satisfactory, is the direct strategy of characterising the genetic defect itself. This is possible when the mutation is a major alteration of the DNA molecule such as a deletion, an insertion or a recombination or when the mutation is isolated and known. In other cases, an indirect approach may be used which consists of determining whether the subject has received normal or defective chromosomes from his or her parents. The identification of good or bad chromosomes is based on the study of DNA markers: polymorphism. The indirect strategy can only be used under certain conditions: presence of an index case, informativity of polymorphisms, complete family study.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Constructing an advanced software tool for planetary atmospheric modeling

    NASA Technical Reports Server (NTRS)

    Keller, Richard M.; Sims, Michael H.; Podolak, Esther; Mckay, Christopher P.

    1990-01-01

    A prototype is described that can serve as a scientific-modeling software tool to facilitate the development of useful scientific models. The prototype is developed for applications to planetary modeling, and specific examples are given that relate to the atmosphere of Titan. The scientific modeling tool employs a high-level domain-specific modeling language, several data-display facilities, and a library of experimental datasets and scientific equations. The planetary modeling prototype links uncomputed physical variables to computed variables with computational transformations based on a backchaining procedure. The system - implemented in LISP with an object-oriented knowledge-representation tool - is run on a workstation that provides interface with several models. The prototype is expected to form the basis for a sophisticated modeling tool that can permit active experimentation.

  2. Recent advances in the molecular diagnostics of gastric cancer

    PubMed Central

    Kanda, Mitsuro; Kodera, Yasuhiro

    2015-01-01

    Gastric cancer (GC) is the third most common cause of cancer-related death in the world, representing a major global health issue. Although the incidence of GC is declining, the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC, including serum carcinoembryonic antigen and carbohydrate antigen 19-9, are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules, including oncogenes, tumor suppressor genes, microRNAs and long non-coding RNAs, and DNA methylation, as novel molecular markers, although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review, the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized, and certain highlighted papers are examined. PMID:26379391

  3. Recent advances of molecular toolbox construction expand Pichia pastoris in synthetic biology applications.

    PubMed

    Kang, Zhen; Huang, Hao; Zhang, Yunfeng; Du, Guocheng; Chen, Jian

    2017-01-01

    Pichia pastoris: (reclassified as Komagataella phaffii), a methylotrophic yeast strain has been widely used for heterologous protein production because of its unique advantages, such as readily achievable high-density fermentation, tractable genetic modifications and typical eukaryotic post-translational modifications. More recently, P. pastoris as a metabolic pathway engineering platform has also gained much attention. In this mini-review, we addressed recent advances of molecular toolboxes, including synthetic promoters, signal peptides, and genome engineering tools that established for P. pastoris. Furthermore, the applications of P. pastoris towards synthetic biology were also discussed and prospected especially in the context of genome-scale metabolic pathway analysis.

  4. genepopedit: a simple and flexible tool for manipulating multilocus molecular data in R.

    PubMed

    Stanley, Ryan R E; Jeffery, Nicholas W; Wringe, Brendan F; DiBacco, Claudio; Bradbury, Ian R

    2017-01-01

    Advances in genetic sequencing technologies and techniques have made large, genome-wide data sets comprised of hundreds or even thousands of individuals and loci the norm rather than the exception even for nonmodel organisms. While such data present new opportunities for evaluating population structure and demographic processes, the large size of these genomic data sets brings new computational challenges for researchers needing to parse, convert and manipulate data often into a variety of software-specific formats required of genomic analyses. We developed genepopedit as a flexible tool for the manipulation of multilocus molecular data sets. Functionality can be divided among diagnostic-, manipulation-, sampling-, simulation-, and transformation-based tools. Metadata from large genomic data sets can be efficiently extracted, without the need to view data in a text-editing program. genepopedit provides tools to manipulate loci, individual samples and populations included in genomic data sets, in addition to the ability to convert directly to a variety of software formats. Functions are compiled as an R package, which can integrate into existing analysis workflows. Importantly, genepopedit provides a simple yet robust code-based tool for repeatable genomic data manipulation, which has been proven to be stable for data sets in excess of 200 000 SNPs. The latest version of the package and associated documentation are available on Github (github.com/rystanley/genepopedit).

  5. Recent Advances of Radionuclide-based Molecular Imaging of Atherosclerosis

    PubMed Central

    Kazuma, Soraya M.; Sultan, Deborah; Zhao, Yongfeng; Detering, Lisa; You, Meng; Luehmann, Hannah P.; Abdalla, Dulcineia S.P.; Liu, Yongjian

    2015-01-01

    Atherosclerosis is a systemic disease characterized by the development of multifocal plaque lesions within vessel walls and extending into the vascular lumen. The disease takes decades to develop symptomatic lesions, affording opportunities for accurate detection of plaque progression, analysis of risk factors responsible for clinical events, and planning personalized treatment. Of the available molecular imaging modalities, radionuclide-based imaging strategies have been favored due to their sensitivity, quantitative detection and pathways for translational research. This review summarizes recent advances of radiolabeled small molecules, peptides, antibodies and nanoparticles for atherosclerotic plaque imaging during disease progression. PMID:26369676

  6. Recent Molecular Advances on Downstream Plant Responses to Abiotic Stress

    PubMed Central

    dos Reis, Sávio Pinho; Lima, Aline Medeiros; de Souza, Cláudia Regina Batista

    2012-01-01

    Abiotic stresses such as extremes of temperature and pH, high salinity and drought, comprise some of the major factors causing extensive losses to crop production worldwide. Understanding how plants respond and adapt at cellular and molecular levels to continuous environmental changes is a pre-requisite for the generation of resistant or tolerant plants to abiotic stresses. In this review we aimed to present the recent advances on mechanisms of downstream plant responses to abiotic stresses and the use of stress-related genes in the development of genetically engineered crops. PMID:22942725

  7. DNA technological progress toward advanced diagnostic tools to support human hookworm control.

    PubMed

    Gasser, R B; Cantacessi, C; Loukas, A

    2008-01-01

    Blood-feeding hookworms are parasitic nematodes of major human health importance. Currently, it is estimated that 740 million people are infected worldwide, and more than 80 million of them are severely affected clinically by hookworm disease. In spite of the health problems caused and the advances toward the development of vaccines against some hookworms, limited attention has been paid to the need for improved, practical methods of diagnosis. Accurate diagnosis and genetic characterization of hookworms is central to their effective control. While traditional diagnostic methods have considerable limitations, there has been some progress toward the development of molecular-diagnostic tools. The present article provides a brief background on hookworm disease of humans, reviews the main methods that have been used for diagnosis and describes progress in establishing polymerase chain reaction (PCR)-based methods for the specific diagnosis of hookworm infection and the genetic characterisation of the causative agents. This progress provides a foundation for the rapid development of practical, highly sensitive and specific diagnostic and analytical tools to be used in improved hookworm prevention and control programmes.

  8. Advances in the genetic dissection of plant cell walls: tools and resources available in Miscanthus

    PubMed Central

    Slavov, Gancho; Allison, Gordon; Bosch, Maurice

    2013-01-01

    Tropical C4 grasses from the genus Miscanthus are believed to have great potential as biomass crops. However, Miscanthus species are essentially undomesticated, and genetic, molecular and bioinformatics tools are in very early stages of development. Furthermore, similar to other crops targeted as lignocellulosic feedstocks, the efficient utilization of biomass is hampered by our limited knowledge of the structural organization of the plant cell wall and the underlying genetic components that control this organization. The Institute of Biological, Environmental and Rural Sciences (IBERS) has assembled an extensive collection of germplasm for several species of Miscanthus. In addition, an integrated, multidisciplinary research programme at IBERS aims to inform accelerated breeding for biomass productivity and composition, while also generating fundamental knowledge. Here we review recent advances with respect to the genetic characterization of the cell wall in Miscanthus. First, we present a summary of recent and on-going biochemical studies, including prospects and limitations for the development of powerful phenotyping approaches. Second, we review current knowledge about genetic variation for cell wall characteristics of Miscanthus and illustrate how phenotypic data, combined with high-density arrays of single-nucleotide polymorphisms, are being used in genome-wide association studies to generate testable hypotheses and guide biological discovery. Finally, we provide an overview of the current knowledge about the molecular biology of cell wall biosynthesis in Miscanthus and closely related grasses, discuss the key conceptual and technological bottlenecks, and outline the short-term prospects for progress in this field. PMID:23847628

  9. Molecular risk stratification in advanced heart failure patients

    PubMed Central

    Lamirault, Guillaume; Meur, Nolwenn Le; Roussel, Jean-Christian; Cunff, Marie-France Le; Baron, Daniel; Bihouée, Audrey; Guisle, Isabelle; Raharijaona, Mahatsangy; Ramstein, Gérard; Teusan, Raluca; Chevalier, Catherine; Gueffet, Jean-Pierre; Trochu, Jean-Noël; Léger, Jean J; Houlgatte, Rémi; Steenman, Marja

    2010-01-01

    Abstract Risk stratification in advanced heart failure (HF) is crucial for the individualization of therapeutic strategy, in particular for heart transplantation and ventricular assist device implantation. We tested the hypothesis that cardiac gene expression profiling can distinguish between HF patients with different disease severity. We obtained tissue samples from both left (LV) and right (RV) ventricle of explanted hearts of 44 patients undergoing cardiac transplantation or ventricular assist device placement. Gene expression profiles were obtained using an in-house microarray containing 4217 muscular organ-relevant genes. Based on their clinical status, patients were classified into three HF-severity groups: deteriorating (n= 12), intermediate (n= 19) and stable (n= 13). Two-class statistical analysis of gene expression profiles of deteriorating and stable patients identified a 170-gene and a 129-gene predictor for LV and RV samples, respectively. The LV molecular predictor identified patients with stable and deteriorating status with a sensitivity of 88% and 92%, and a specificity of 100% and 96%, respectively. The RV molecular predictor identified patients with stable and deteriorating status with a sensitivity of 100% and 96%, and a specificity of 100% and 100%, respectively. The molecular prediction was reproducible across biological replicates in LV and RV samples. Gene expression profiling has the potential to reproducibly detect HF patients with highest HF severity with high sensitivity and specificity. In addition, not only LV but also RV samples could be used for molecular risk stratification with similar predictive power. PMID:19793385

  10. XML based tools for assessing potential impact of advanced technology space validation

    NASA Technical Reports Server (NTRS)

    Some, Raphael R.; Weisbin, Charles

    2004-01-01

    A hierarchical XML database and related analysis tools are being developed by the New Millennium Program to provide guidance on the relative impact, to future NASA missions, of advanced technologies under consideration for developmental funding.

  11. Human Factors Evaluation of Advanced Electric Power Grid Visualization Tools

    SciTech Connect

    Greitzer, Frank L.; Dauenhauer, Peter M.; Wierks, Tamara G.; Podmore, Robin

    2009-04-01

    This report describes initial human factors evaluation of four visualization tools (Graphical Contingency Analysis, Force Directed Graphs, Phasor State Estimator and Mode Meter/ Mode Shapes) developed by PNNL, and proposed test plans that may be implemented to evaluate their utility in scenario-based experiments.

  12. Advanced Vibration Analysis Tool Developed for Robust Engine Rotor Designs

    NASA Technical Reports Server (NTRS)

    Min, James B.

    2005-01-01

    The primary objective of this research program is to develop vibration analysis tools, design tools, and design strategies to significantly improve the safety and robustness of turbine engine rotors. Bladed disks in turbine engines always feature small, random blade-to-blade differences, or mistuning. Mistuning can lead to a dramatic increase in blade forced-response amplitudes and stresses. Ultimately, this results in high-cycle fatigue, which is a major safety and cost concern. In this research program, the necessary steps will be taken to transform a state-of-the-art vibration analysis tool, the Turbo- Reduce forced-response prediction code, into an effective design tool by enhancing and extending the underlying modeling and analysis methods. Furthermore, novel techniques will be developed to assess the safety of a given design. In particular, a procedure will be established for using natural-frequency curve veerings to identify ranges of operating conditions (rotational speeds and engine orders) in which there is a great risk that the rotor blades will suffer high stresses. This work also will aid statistical studies of the forced response by reducing the necessary number of simulations. Finally, new strategies for improving the design of rotors will be pursued.

  13. Molecular tools for the detection of nitrogen cycling Archaea.

    PubMed

    Rusch, Antje

    2013-01-01

    Archaea are widespread in extreme and temperate environments, and cultured representatives cover a broad spectrum of metabolic capacities, which sets them up for potentially major roles in the biogeochemistry of their ecosystems. The detection, characterization, and quantification of archaeal functions in mixed communities require Archaea-specific primers or probes for the corresponding metabolic genes. Five pairs of degenerate primers were designed to target archaeal genes encoding key enzymes of nitrogen cycling: nitrite reductases NirA and NirB, nitrous oxide reductase (NosZ), nitrogenase reductase (NifH), and nitrate reductases NapA/NarG. Sensitivity towards their archaeal target gene, phylogenetic specificity, and gene specificity were evaluated in silico and in vitro. Owing to their moderate sensitivity/coverage, the novel nirB-targeted primers are suitable for pure culture studies only. The nirA-targeted primers showed sufficient sensitivity and phylogenetic specificity, but poor gene specificity. The primers designed for amplification of archaeal nosZ performed well in all 3 criteria; their discrimination against bacterial homologs appears to be weakened when Archaea are strongly outnumbered by bacteria in a mixed community. The novel nifH-targeted primers showed high sensitivity and gene specificity, but failed to discriminate against bacterial homologs. Despite limitations, 4 of the new primer pairs are suitable tools in several molecular methods applied in archaeal ecology.

  14. Construction of an advanced software tool for planetary atmospheric modeling

    NASA Technical Reports Server (NTRS)

    Friedland, Peter; Keller, Richard M.; Mckay, Christopher P.; Sims, Michael H.; Thompson, David E.

    1992-01-01

    Scientific model-building can be a time intensive and painstaking process, often involving the development of large complex computer programs. Despite the effort involved, scientific models cannot be distributed easily and shared with other scientists. In general, implemented scientific models are complicated, idiosyncratic, and difficult for anyone but the original scientist/programmer to understand. We propose to construct a scientific modeling software tool that serves as an aid to the scientist in developing, using and sharing models. The proposed tool will include an interactive intelligent graphical interface and a high-level domain-specific modeling language. As a test bed for this research, we propose to develop a software prototype in the domain of planetary atmospheric modeling.

  15. Construction of an advanced software tool for planetary atmospheric modeling

    NASA Technical Reports Server (NTRS)

    Friedland, Peter; Keller, Richard M.; Mckay, Christopher P.; Sims, Michael H.; Thompson, David E.

    1993-01-01

    Scientific model-building can be a time intensive and painstaking process, often involving the development of large complex computer programs. Despite the effort involved, scientific models cannot be distributed easily and shared with other scientists. In general, implemented scientific models are complicated, idiosyncratic, and difficult for anyone but the original scientist/programmer to understand. We propose to construct a scientific modeling software tool that serves as an aid to the scientist in developing, using and sharing models. The proposed tool will include an interactive intelligent graphical interface and a high-level domain-specific modeling language. As a testbed for this research, we propose to develop a software prototype in the domain of planetary atmospheric modeling.

  16. Primer: genomic and proteomic tools for the molecular dissection of disease.

    PubMed

    Walker, Erin J; Siminovitch, Katherine A

    2007-10-01

    Completion of the Human Genome Project has been rapidly followed by the emergence of high-throughput technologies that combine automation, miniaturization, and many other strategies and tools to enable systematic surveys of genome composition and gene expression. Of particular relevance to the prevention and management of disease are technologies such as high-throughput DNA genotyping, microarray-based gene-expression profiling, and mass spectrometry-facilitated protein profiling--platforms that collectively support the comprehensive analysis of DNA sequence variants across the genome and the global gene and protein expression changes that distinguish health from disease. Now used extensively in all facets of biomedical investigation, genomic and proteomic tools are already beginning to pinpoint molecular variants that influence risk and outcome in common diseases, and to thereby inform and direct development of novel molecular biomarkers and drug targets. As evidenced by recent advances in DNA sequencing methods, continued improvements in the scope, power, and cost efficiency of genomic and proteomic technologies should ensure their capacity to provide the scale and depth of knowledge required for translating genome sequence information into major medical impact.

  17. Advances in the cellular and molecular biology of angiogenesis.

    PubMed

    Egginton, Stuart; Bicknell, Roy

    2011-12-01

    Capillaries have been recognized for over a century as one of the most important components in regulating tissue oxygen transport, and their formation or angiogenesis a pivotal element of tissue remodelling during development and adaptation. Clinical interest stems from observations that both excessive and inadequate vascular growth plays a major role in human diseases, and novel developments in treatments for cancer and eye disease increasingly rely on anti-angiogenic therapies. Although the discovery of VEGF (vascular endothelial growth factor) provided the first clue for specificity of signalling in endothelial cell activation, understanding the integrative response that drives angiogenesis requires a much broader perspective. The Advances in the Cellular and Molecular Biology of Angiogenesis meeting brought together researchers at the forefront of this rapidly moving field to provide an update on current understanding, and the most recent insights into molecular and cellular mechanisms of vascular growth. The plenary lecture highlighted the integrative nature of the angiogenic process, whereas invited contributions from basic and clinician scientists described fundamental mechanisms and disease-associated issues of blood vessel formation, grouped under a number of themes to aid discussion. These articles will appeal to academic, clinical and pharmaceutical scientists interested in the molecular and cellular basis of angiogenesis, their modulation or dysfunction in human diseases, and application of these findings towards translational medicine.

  18. Advanced tools and framework for historical film restoration

    NASA Astrophysics Data System (ADS)

    Croci, Simone; Aydın, Tunç Ozan; Stefanoski, Nikolce; Gross, Markus; Smolic, Aljosa

    2017-01-01

    Digital restoration of film content that has historical value is crucial for the preservation of cultural heritage. Also, digital restoration is not only a relevant application area of various video processing technologies that have been developed in computer graphics literature but also involves a multitude of unresolved research challenges. Currently, the digital restoration workflow is highly labor intensive and often heavily relies on expert knowledge. We revisit some key steps of this workflow and propose semiautomatic methods for performing them. To do that we build upon state-of-the-art video processing techniques by adding the components necessary for enabling (i) restoration of chemically degraded colors of the film stock, (ii) removal of excessive film grain through spatiotemporal filtering, and (iii) contrast recovery by transferring contrast from the negative film stock to the positive. We show that when applied individually our tools produce compelling results and when applied in concert significantly improve the degraded input content. Building on a conceptual framework of film restoration ensures the best possible combination of tools and use of available materials.

  19. Recent advances on host plants and expression cassettes' structure and function in plant molecular pharming.

    PubMed

    Makhzoum, Abdullah; Benyammi, Roukia; Moustafa, Khaled; Trémouillaux-Guiller, Jocelyne

    2014-04-01

    Plant molecular pharming is a promising system to produce important recombinant proteins such as therapeutic antibodies, pharmaceuticals, enzymes, growth factors, and vaccines. The system provides an interesting alternative method to the direct extraction of proteins from inappropriate source material while offering the possibility to overcome problems related to product safety and source availability. Multiple factors including plant hosts, genes of interest, expression vector cassettes, and extraction and purification techniques play important roles in the plant molecular pharming. Plant species, as a biosynthesis platform, are a crucial factor in achieving high yields of recombinant protein in plant. The choice of recombinant gene and its expression strategy is also of great importance in ensuring a high amount of the recombinant proteins. Many studies have been conducted to improve expression, accumulation, and purification of the recombinant protein from molecular pharming systems. Re-engineered vectors and expression cassettes are also pivotal tools in enhancing gene expression at the transcription and translation level, and increasing protein accumulation, stability, retention and targeting of specific organelles. In this review, we report recent advances and strategies of plant molecular pharming while focusing on the choice of plant hosts and the role of some molecular pharming elements and approaches: promoters, codon optimization, signal sequences, and peptides used for upstream design, purification and downstream processing.

  20. Advances in molecular design and synthesis of regioregular polythiophenes.

    PubMed

    Osaka, Itaru; McCullough, Richard D

    2008-09-01

    Regioregular poly(3-alkylthiophene)s (rrP3ATs) are an important class of pi-conjugated polymers that can be used in plastic electronic devices such as solar cells and field-effect transistors. rrP3ATs can be ordered in three dimensions: conformational ordering along the backbone, pi-stacking of flat polymer chains, and lamellar stacking between chains. All of these features lead to the excellent electrical properties of these materials. Creative molecular design and advanced synthesis are critical in controlling the properties of the materials as well as their device performance. This Account reports the advances in molecular design of new functional polythiophenes as well as the associated polymerization methods. Many functionalized regioregular polythiophenes have been designed and synthesized and show fascinating properties such as high conductivity, mobility, chemosensitivity, liquid crystallinity, or chirality. The methods for the synthesis of rrP3ATs are also applicable to other functional side chains. Di- and triblock copolymers consisting of rrP3AT and polyacrylate or polystyrene have also been successfully synthesized, which can facilitate the assembly of the polythiophene segments. The synthesis of rrP3ATs has evolved into a simple and economical system in which the synthesis can be carried out quickly at room temperature and is thus suitable for large-scale manufacturing. Intensive study has revealed that the regioregular polymerization of 3-alkylthiophenes proceeds by a chain-growth mechanism and can be made into a living system. This feature enables precise control of the molecular weight and facile end-group functionalization of the polymer chains, leading to tailor-made regioregular polythiophenes for specific applications. In addition, researchers have recently designed and synthesized regiosymmetric polythiophenesthese are regioregular but not coupled in a head-to-tail fashionby various methods. These reports indicate that these regiosymmetric

  1. Advances in Time Estimation Methods for Molecular Data.

    PubMed

    Kumar, Sudhir; Hedges, S Blair

    2016-04-01

    Molecular dating has become central to placing a temporal dimension on the tree of life. Methods for estimating divergence times have been developed for over 50 years, beginning with the proposal of molecular clock in 1962. We categorize the chronological development of these methods into four generations based on the timing of their origin. In the first generation approaches (1960s-1980s), a strict molecular clock was assumed to date divergences. In the second generation approaches (1990s), the equality of evolutionary rates between species was first tested and then a strict molecular clock applied to estimate divergence times. The third generation approaches (since ∼2000) account for differences in evolutionary rates across the tree by using a statistical model, obviating the need to assume a clock or to test the equality of evolutionary rates among species. Bayesian methods in the third generation require a specific or uniform prior on the speciation-process and enable the inclusion of uncertainty in clock calibrations. The fourth generation approaches (since 2012) allow rates to vary from branch to branch, but do not need prior selection of a statistical model to describe the rate variation or the specification of speciation model. With high accuracy, comparable to Bayesian approaches, and speeds that are orders of magnitude faster, fourth generation methods are able to produce reliable timetrees of thousands of species using genome scale data. We found that early time estimates from second generation studies are similar to those of third and fourth generation studies, indicating that methodological advances have not fundamentally altered the timetree of life, but rather have facilitated time estimation by enabling the inclusion of more species. Nonetheless, we feel an urgent need for testing the accuracy and precision of third and fourth generation methods, including their robustness to misspecification of priors in the analysis of large phylogenies and data

  2. Advanced Epi Tools for Gallium Nitride Light Emitting Diode Devices

    SciTech Connect

    Patibandla, Nag; Agrawal, Vivek

    2012-12-01

    Over the course of this program, Applied Materials, Inc., with generous support from the United States Department of Energy, developed a world-class three chamber III-Nitride epi cluster tool for low-cost, high volume GaN growth for the solid state lighting industry. One of the major achievements of the program was to design, build, and demonstrate the world’s largest wafer capacity HVPE chamber suitable for repeatable high volume III-Nitride template and device manufacturing. Applied Materials’ experience in developing deposition chambers for the silicon chip industry over many decades resulted in many orders of magnitude reductions in the price of transistors. That experience and understanding was used in developing this GaN epi deposition tool. The multi-chamber approach, which continues to be unique in the ability of the each chamber to deposit a section of the full device structure, unlike other cluster tools, allows for extreme flexibility in the manufacturing process. This robust architecture is suitable for not just the LED industry, but GaN power devices as well, both horizontal and vertical designs. The new HVPE technology developed allows GaN to be grown at a rate unheard of with MOCVD, up to 20x the typical MOCVD rates of 3{micro}m per hour, with bulk crystal quality better than the highest-quality commercial GaN films grown by MOCVD at a much cheaper overall cost. This is a unique development as the HVPE process has been known for decades, but never successfully commercially developed for high volume manufacturing. This research shows the potential of the first commercial-grade HVPE chamber, an elusive goal for III-V researchers and those wanting to capitalize on the promise of HVPE. Additionally, in the course of this program, Applied Materials built two MOCVD chambers, in addition to the HVPE chamber, and a robot that moves wafers between them. The MOCVD chambers demonstrated industry-leading wavelength yield for GaN based LED wafers and industry

  3. AN ADVANCED TOOL FOR APPLIED INTEGRATED SAFETY MANAGEMENT

    SciTech Connect

    Potts, T. Todd; Hylko, James M.; Douglas, Terence A.

    2003-02-27

    WESKEM, LLC's Environmental, Safety and Health (ES&H) Department had previously assessed that a lack of consistency, poor communication and using antiquated communication tools could result in varying operating practices, as well as a failure to capture and disseminate appropriate Integrated Safety Management (ISM) information. To address these issues, the ES&H Department established an Activity Hazard Review (AHR)/Activity Hazard Analysis (AHA) process for systematically identifying, assessing, and controlling hazards associated with project work activities during work planning and execution. Depending on the scope of a project, information from field walkdowns and table-top meetings are collected on an AHR form. The AHA then documents the potential failure and consequence scenarios for a particular hazard. Also, the AHA recommends whether the type of mitigation appears appropriate or whether additional controls should be implemented. Since the application is web based, the information is captured into a single system and organized according to the >200 work activities already recorded in the database. Using the streamlined AHA method improved cycle time from over four hours to an average of one hour, allowing more time to analyze unique hazards and develop appropriate controls. Also, the enhanced configuration control created a readily available AHA library to research and utilize along with standardizing hazard analysis and control selection across four separate work sites located in Kentucky and Tennessee. The AHR/AHA system provides an applied example of how the ISM concept evolved into a standardized field-deployed tool yielding considerable efficiency gains in project planning and resource utilization. Employee safety is preserved through detailed planning that now requires only a portion of the time previously necessary. The available resources can then be applied to implementing appropriate engineering, administrative and personal protective equipment

  4. Recent advances in molecular biology of parasitic viruses.

    PubMed

    Banik, Gouri Rani; Stark, Damien; Rashid, Harunor; Ellis, John T

    2014-01-01

    The numerous protozoa that can inhabit the human gastro-intestinal tract are known, yet little is understood of the viruses which infect these protozoa. The discovery, morphologic details, purification methods of virus-like particles, genome and proteome of the parasitic viruses, Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, and the Eimeria sp. are described in this review. The protozoan viruses share many common features: most of them are RNA or double-stranded RNA viruses, ranging between 5 and 8 kilobases, and are spherical or icosahedral in shape with an average diameter of 30-40 nm. These viruses may influence the function and pathogenicity of the protozoa which they infect, and may be important to investigate from a clinical perspective. The viruses may be used as specific genetic transfection vectors for the parasites and may represent a research tool. This review provides an overview on recent advances in the field of protozoan viruses.

  5. Advancing the cellular and molecular therapy for intervertebral disc disease.

    PubMed

    Sakai, Daisuke; Grad, Sibylle

    2015-04-01

    The healthy intervertebral disc (IVD) fulfils the essential function of load absorption, while maintaining multi-axial flexibility of the spine. The interrelated tissues of the IVD, the annulus fibrosus, the nucleus pulposus, and the cartilaginous endplate, are characterised by their specific niche, implying avascularity, hypoxia, acidic environment, low nutrition, and low cellularity. Anabolic and catabolic factors balance a slow physiological turnover of extracellular matrix synthesis and breakdown. Deviations in mechanical load, nutrient supply, cellular activity, matrix composition and metabolism may initiate a cascade ultimately leading to tissue dehydration, fibrosis, nerve and vessel ingrowth, disc height loss and disc herniation. Spinal instability, inflammation and neural sensitisation are sources of back pain, a worldwide leading burden that is challenging to cure. In this review, advances in cell and molecular therapy, including mobilisation and activation of endogenous progenitor cells, progenitor cell homing, and targeted delivery of cells, genes, or bioactive factors are discussed.

  6. [Research advances in soil fungal diversity and molecular ecology].

    PubMed

    Zhang, Jing; Zhang, Huiwen; Li, Xinyu; Zhang, Chenggang

    2004-10-01

    Fungi are a kind of important soil microorganisms that participate in the decomposition of organic materials and supply nutrients to the plant through symbiosis. But, they can also reduce the output of food due to the existence of pathogenic fungi. Soil fungal diversity plays a fundamentally unique role in maintaining the balance of ecosystem and in supplying large amount of undeveloped resources for the people. In this paper, soil fungal diversity was expatiated from the viewpoints of species diversity, habitant diversity and functional diversity, and furthermore, the research advances in the molecular ecology of soil fungal diversity were reviewed from the aspects of the fungal diversity of farmland, woodland, pasture, extreme environment, and other complex environments. The affecting factors of soil fungal diversity were discussed, and the development trend of the study on soil fungal diversity was also approached.

  7. Advanced Flow Control as a Management Tool in the National Airspace System

    NASA Technical Reports Server (NTRS)

    Wugalter, S.

    1974-01-01

    Advanced Flow Control is closely related to Air Traffic Control. Air Traffic Control is the business of the Federal Aviation Administration. To formulate an understanding of advanced flow control and its use as a management tool in the National Airspace System, it becomes necessary to speak somewhat of air traffic control, the role of FAA, and their relationship to advanced flow control. Also, this should dispell forever, any notion that advanced flow control is the inspirational master valve scheme to be used on the Alaskan Oil Pipeline.

  8. Advanced tools for astronomical time series and image analysis

    NASA Astrophysics Data System (ADS)

    Scargle, Jeffrey D.

    The algorithms described here, which I have developed for applications in X-ray and γ-ray astronomy, will hopefully be of use in other ways, perhaps aiding in the exploration of modern astronomy's data cornucopia. The goal is to describe principled approaches to some ubiquitous problems, such as detection and characterization of periodic and aperiodic signals, estimation of time delays between multiple time series, and source detection in noisy images with noisy backgrounds. The latter problem is related to detection of clusters in data spaces of various dimensions. A goal of this work is to achieve a unifying view of several related topics: signal detection and characterization, cluster identification, classification, density estimation, and multivariate regression. In addition to being useful for analysis of data from space-based and ground-based missions, these algorithms may be a basis for a future automatic science discovery facility, and in turn provide analysis tools for the Virtual Observatory. This chapter has ties to those by Larry Bretthorst, Tom Loredo, Alanna Connors, Fionn Murtagh, Jim Berger, David van Dyk, Vicent Martinez & Enn Saar.

  9. [Advances of molecular targeted therapy in squamous cell lung cancer].

    PubMed

    Ma, Li; Zhang, Shucai

    2013-12-01

    Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

  10. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research.

  11. Electrochemical Processing Tools for Advanced Copper Interconnects: An Introduction

    NASA Astrophysics Data System (ADS)

    Datta, Madhav

    The change from vacuum-deposited aluminum to electroplated copper in 1997 brought about a paradigm shift in interconnect technology and in chip making [1]. Since then, most of the leading chip manufacturers have converted to electroplated Cu technology for chip interconnects. Cu interconnects are fabricated by dual Damascene process which is referred to a metallization patterning process by which two insulator (dielectric) levels are patterned, filled with copper, and planarized to create a metal layer consisting of vias and lines. The process steps consist of laying a sandwich of two levels of insulator and etch stop layers that are patterned as holes for vias and troughs for lines. They are then filled with a single metallization step. Finally, the excess material is removed, and the wafer is planarized by chemical mechanical polishing (CMP). While finer details of exact sequence of fabrication steps vary, the end result of forming a metal layer remains the same in which vias are formed in the lower layer, and trenches are formed in the upper layer. Electroplating enables deposition of Cu in via holes and overlying trenches in a single step thus eliminating a via/line interface and significantly reducing the cycle time. Due to these reasons and due to relatively less expensive tooling, electroplating is a cost-effective and efficient process for Cu interconnects [2, 3]. Compared with vacuum deposition processes, electroplated Cu provides improved super filling capabilities and abnormal grain growth phenomena. These properties contribute significantly to improved reliability of Cu interconnects. With the proper choice of additives and plating conditions, void-free, seam-free Damascene deposits are obtained which eliminates surface-like fast diffusion paths for Cu electromigration.

  12. Advancing alternate tools: why science education needs CRP and CRT

    NASA Astrophysics Data System (ADS)

    Dodo Seriki, Vanessa

    2016-09-01

    Ridgeway and Yerrick's paper, Whose banner are we waving?: exploring STEM partnerships for marginalized urban youth, unearthed the tensions that existed between a local community "expert" and a group of students and their facilitator in an afterschool program. Those of us who work with youth who are traditionally marginalized, understand the importance of teaching in culturally relevant ways, but far too often—as Ridgeway and Yerrick shared—community partners have beliefs, motives, and ideologies that are incompatible to the program's mission and goals. Nevertheless, we often enter partnerships assuming that the other party understands the needs of the students or community; understands how in U.S. society White is normative while all others are deficient; and understands how to engage with students in culturally relevant ways. This forum addresses the underlying assumption, described in the Ridgeway and Yerrick article, that educators—despite their background and experiences—are able to teach in culturally relevant ways. Additionally, I assert based on the finding in the article that just as Ladson-Billings and Tate (Teach Coll Rec 97(1):47-68, 1995) asserted, race in the U.S. society, as a scholarly pursuit, was under theorized. The same is true of science education; race in science education is under theorized and the use of culturally relevant pedagogy and critical race theory as a pedagogical model and analytical tool, respectively, in science education is minimal. The increased use of both would impact our understanding of who does science, and how to broaden participation among people of color.

  13. Cysticercosis/taeniasis: recent advances in serological and molecular diagnoses.

    PubMed

    Yamasaki, H; Sato, M O; Sako, Y; Nakao, M; Nakaya, K; Mamuti, W; Craig, P S; Margono, S S; Ito, A

    2003-01-01

    Serodiagnosis by immunoblot, using recombinant chimeric T. solium antigen and native glycoprotein antigens, has been applied for neurocysticercosis cases. Specific antibodies against both antigens were detected in serum samples from NCC patients involving multiple cysts in the brain, whereas it was not always easy to detect specific antibodies in NCC cases with a solitary cyst or calcified lesion(s). On the other hand, the diagnosis for human taeniasis or worm carriers has been routinely performed by stool examination. In this study, multiplex PCR has been established to differentiate taeniasis using Taenia mitochondrial DNA in fecal samples from worm carriers. Furthermore, the molecular identification of human taeniid cestodes by base excision sequence scanning thymine-base analysis has also been introduced. This method provides four thymine-base peak profiles unique for Asian and American/African genotypes of T. solium, T. saginata and T. asiatica. By comparing thymine base peak profiles, it is possible to differentiate human taeniid cestodes without DNA sequencing. The approaches are powerful tools for the routine diagnosis of taeniasis and the molecular identification of taeniid cestodes.

  14. Teaching Advanced Data Analysis Tools to High School Astronomy Students

    NASA Astrophysics Data System (ADS)

    Black, David V.; Herring, Julie; Hintz, Eric G.

    2015-01-01

    A major barrier to becoming an astronomer is learning how to analyze astronomical data, such as using photometry to compare the brightness of stars. Most fledgling astronomers learn observation, data reduction, and analysis skills through an upper division college class. If the same skills could be taught in an introductory high school astronomy class, then more students would have an opportunity to do authentic science earlier, with implications for how many choose to become astronomers. Several software tools have been developed that can analyze astronomical data ranging from fairly straightforward (AstroImageJ and DS9) to very complex (IRAF and DAOphot). During the summer of 2014, a study was undertaken at Brigham Young University through a Research Experience for Teachers (RET) program to evaluate the effectiveness and ease-of-use of these four software packages. Standard tasks tested included creating a false-color IR image using WISE data in DS9, Adobe Photoshop, and The Gimp; a multi-aperture analyses of variable stars over time using AstroImageJ; creating Spectral Energy Distributions (SEDs) of stars using photometry at multiple wavelengths in AstroImageJ and DS9; and color-magnitude and hydrogen alpha index diagrams for open star clusters using IRAF and DAOphot. Tutorials were then written and combined with screen captures to teach high school astronomy students at Walden School of Liberal Arts in Provo, UT how to perform these same tasks. They analyzed image data using the four software packages, imported it into Microsoft Excel, and created charts using images from BYU's 36-inch telescope at their West Mountain Observatory. The students' attempts to complete these tasks were observed, mentoring was provided, and the students then reported on their experience through a self-reflection essay and concept test. Results indicate that high school astronomy students can successfully complete professional-level astronomy data analyses when given detailed

  15. [Consideration on molecular imaging technology as a tool for drug research and development].

    PubMed

    Yajima, Kazuyoshi; Nishimura, Shintaro

    2009-03-01

    Molecular imaging technology such as positron emission tomography (PET) and magnetic resonance imaging (MRI) are known as powerful tools for clinical diagnosis in neurology, oncology and so on. As applications to new drug research and development, there are three methodologies which are PK (Pharmacokinetics study), PD (Pharmacodynamic study), and efficacy study. When we use these methodologies for the drug research, we must consider construction of technological environment (tracer, animal model, imaging analysis software, and clinical database) and regulatory environment for GMP (Good Manufacturing Practice) and GCP (Good Clinical Practice) level. Additionally, concept of microdosing and exploratory clinical study was proposed in western countries and the guidance on microdosing study was also announced by Health, Labor and Welfare Ministry on June 3rd 2008. However they may be still in learning phase, we must meet with complexity, high cost, and indigestion. To promote molecular imaging technology into the drug research, integration of the scientists between academia and industry is important because it needs much type of the advanced technologies and skills.

  16. Utility of the advanced chronic kidney disease patient management tools: case studies.

    PubMed

    Patwardhan, Meenal B; Matchar, David B; Samsa, Gregory P; Haley, William E

    2008-01-01

    Appropriate management of advanced chronic kidney disease (CKD) delays or limits its progression. The Advanced CKD Patient Management Toolkit was developed using a process-improvement technique to assist patient management and address CKD-specific management issues. We pilot tested the toolkit in 2 community nephrology practices, assessed the utility of individual tools, and evaluated the impact on conformance to an advanced CKD guideline through patient chart abstraction. Tool use was distinct in the 2 sites and depended on the site champion's involvement, the extent of process reconfiguration demanded by a tool, and its perceived value. Baseline conformance varied across guideline recommendations (averaged 54%). Posttrial conformance increased in all clinical areas (averaged 59%). Valuable features of the toolkit in real-world settings were its ability to: facilitate tool selection, direct implementation efforts in response to a baseline performance audit, and allow selection of tool versions and customizing them. Our results suggest that systematically created, multifaceted, and customizable tools can promote guideline conformance.

  17. Advanced Characterization of Molecular Interactions in TALSPEAK-like Separations Systems

    SciTech Connect

    Nash, Kenneth; Guelis, Artem; Lumetta, Gregg J.; Sinkov, Sergey

    2015-10-21

    Combining unit operations in advanced aqueous reprocessing schemes brings obvious process compactness advantages, but at the same time greater complexity in process design and operation. Unraveling these interactions requires increasingly sophisticated analytical tools and unique approaches for adequate analysis and characterization that probe molecular scale interactions. Conventional slope analysis methods of solvent extraction are too indirect to provide much insight into such interactions. This project proposed the development and verification of several analytical tools based on studies of TALSPEAK-like aqueous processes. As such, the chemistry of trivalent fission product lanthanides, americium, curium, plutonium, neptunium and uranium figure prominently in these studies. As the project was executed, the primary focus fell upon the chemistry or trivalent lanthanides and actinides. The intent of the investigation was to compare and contrast the results from these various complementary techniques/studies to provide a stronger basis for predicting the performance of extractant/diluent mixtures as media for metal ion separations. As many/most of these techniques require the presence of metal ions at elevated concentrations, it was expected that these studies would take this investigation into the realm of patterns of supramolecular organization of metal complexes and extractants in concentrated aqueous/organic media. We expected to advance knowledge of the processes that enable and limit solvent extraction reactions as a result of the application of fundamental chemical principles to explaining interactions in complex media.

  18. Second NASA Technical Interchange Meeting (TIM): Advanced Technology Lifecycle Analysis System (ATLAS) Technology Tool Box (TTB)

    NASA Technical Reports Server (NTRS)

    ONeil, D. A.; Mankins, J. C.; Christensen, C. B.; Gresham, E. C.

    2005-01-01

    The Advanced Technology Lifecycle Analysis System (ATLAS), a spreadsheet analysis tool suite, applies parametric equations for sizing and lifecycle cost estimation. Performance, operation, and programmatic data used by the equations come from a Technology Tool Box (TTB) database. In this second TTB Technical Interchange Meeting (TIM), technologists, system model developers, and architecture analysts discussed methods for modeling technology decisions in spreadsheet models, identified specific technology parameters, and defined detailed development requirements. This Conference Publication captures the consensus of the discussions and provides narrative explanations of the tool suite, the database, and applications of ATLAS within NASA s changing environment.

  19. [Recent advances in molecular genetics of GM2 gangliosidosis].

    PubMed

    Wakamatsu, N

    1995-12-01

    Recent advances in molecular genetics of GM2 gangliosidosis are reviewed. GM2 gangliosidosis is an autosomal recessive, neurodegenerative disease caused by a deficiency of beta-hexosaminidase (Hex, EC 3.2.1.52) A activity, resulting in accumulation of GM2 ganglioside in the lysosomes of neuronal cells. There are two catalytically active forms of this enzyme: Hex A, composed of one alpha and one beta subunits. Three forms of this disease, Tay-Sachs disease, Sandhoff disease, and GM2 activator deficiency, have been recognized according to whether the defect involves the alpha subunit, beta subunit, or GM2 activator protein, respectively. A number of gene abnormalities responsible for the disease have been identified and mutations specific for phenotypes and racial backgrounds are summarized. Recently, the murine models of human Tay-Sachs disease and Sandhoff disease have been produced. With the finding of dramatically clinical phenotypes in these mice, these models could be useful for research on the pathogenesis or therapy of these diseases.

  20. Recent research in flaxseed (oil seed) on molecular structure and metabolic characteristics of protein, heat processing-induced effect and nutrition with advanced synchrotron-based molecular techniques.

    PubMed

    Doiron, Kevin J; Yu, Peiqiang

    2017-01-02

    Advanced synchrotron radiation-based infrared microspectroscopy is able to reveal feed and food structure feature at cellular and molecular levels and simultaneously provides composition, structure, environment, and chemistry within intact tissue. However, to date, this advanced synchrotron-based technique is still seldom known to food and feed scientists. This article aims to provide detailed background for flaxseed (oil seed) protein research and then review recent progress and development in flaxseed research in ruminant nutrition in the areas of (1) dietary inclusion of flaxseed in rations; (2) heat processing effect; (3) assessing dietary protein; (4) synchrotron-based Fourier transform infrared microspectroscopy as a tool of nutritive evaluation within cellular and subcellular dimensions; (5) recent synchrotron applications in flaxseed research on a molecular basis. The information described in this paper gives better insight in flaxseed research progress and update.

  1. Earthquake information products and tools from the Advanced National Seismic System (ANSS)

    USGS Publications Warehouse

    Wald, Lisa

    2006-01-01

    This Fact Sheet provides a brief description of postearthquake tools and products provided by the Advanced National Seismic System (ANSS) through the U.S. Geological Survey Earthquake Hazards Program. The focus is on products specifically aimed at providing situational awareness in the period immediately following significant earthquake events.

  2. WWW Entrez: A Hypertext Retrieval Tool for Molecular Biology.

    ERIC Educational Resources Information Center

    Epstein, Jonathan A.; Kans, Jonathan A.; Schuler, Gregory D.

    This article describes the World Wide Web (WWW) Entrez server which is based upon the National Center for Biotechnology Information's (NCBI) Entrez retrieval database and software. Entrez is a molecular sequence retrieval system that contains an integrated view of portions of Medline and all publicly available nucleotide and protein databases,…

  3. Continuous Symmetry and Chemistry Teachers: Learning Advanced Chemistry Content through Novel Visualization Tools

    ERIC Educational Resources Information Center

    Tuvi-Arad, Inbal; Blonder, Ron

    2010-01-01

    In this paper we describe the learning process of a group of experienced chemistry teachers in a specially designed workshop on molecular symmetry and continuous symmetry. The workshop was based on interactive visualization tools that allow molecules and their symmetry elements to be rotated in three dimensions. The topic of continuous symmetry is…

  4. Molecular tools for investigating ANME community structure and function

    SciTech Connect

    Hallam, Steven J.; Page, Antoine P.; Constan, Lea; Song, Young C.; Norbeck, Angela D.; Brewer, Heather M.; Pasa-Tolic, Ljiljana

    2011-05-20

    Methane production and consumption in anaerobic marine sediments 1 is catalyzed by a series of reversible tetramethanopterin (H4MPT)-linked C1 transfer reactions. Although many of these reactions are conserved between one-carbon compound utilizing microorganisms, two remain diagnostic for archaeal methane metabolism. These include reactions catalyzed by N5-methyltetrahydromethanopterin: coenzyme M methyltransferase and methyl coenzyme M reductase. The latter enzyme is central to C-H bond formation and cleavage underlying methanogenic and reverse methanogenic phenotypes. Here we describe a set of novel tools for the detection and functional analysis of H4MPT-linked C1 transfer reactions mediated by uncultivated anaerobic methane oxidizing archaea (ANME). These tools include polymerase chain reaction primers targeting ANME methyl coenzyme M reductase subunit A subgroups and protein extraction methods from marine sediments compatible with high-resolution mass spectrometry for profiling population structure and functional dynamics. [910, 1,043

  5. Recent advances in molecular recognition based on nanoengineered platforms.

    PubMed

    Mu, Bin; Zhang, Jingqing; McNicholas, Thomas P; Reuel, Nigel F; Kruss, Sebastian; Strano, Michael S

    2014-04-15

    Nanoparticles and nanoengineered platforms have great potential for technologies involving biomoleuclar detection or cell-related biosensing, and have provided effective chemical interfaces for molecular recognition. Typically, chemists work on the modification of synthetic polymers or macromolecules, which they link to the nanoparticles by covalent or noncovalent approaches. The motivation for chemical modification is to enhance the selectivity and sensitivity, and to improve the biocompatibility for the in vivo applications. In this Account, we present recent advances in the development and application of chemical interfaces for molecular recognition for nanoparticles and nanoengineered platforms, in particular single-walled carbon nanotubes (SWNTs). We discuss emerging approaches for recognizing small molecules, glycosylated proteins, and serum biomarkers. For example, we compare and discuss detection methods for ATP, NO, H2O2, and monosaccharides for recent nanomaterials. Fluorometric detection appears to have great potential for quantifying concentration gradients and determining their location in living cells. For macromolecular detection, new methods for glycoprofiling using such interfaces appear promising, and benefit specifically from the potential elimination of cumbersome labeling and liberation steps during conventional analysis of glycans, augmenting the currently used mass spectrometry (MS), capillary electrophoresis (CE), and liquid chromatography (LC) methods. In particular, we demonstrated the great potential of fluorescent SWNTs for glycan-lectin interactions sensing. In this case, SWNTs are noncovalently functionalized to introduce a chelated nickel group. This group provides a docking site for the His-tagged lectin and acts as the signal modulator. As the nickel proximity to the SWNT surface changes, the fluorescent signal is increased or attenuated. When a free glycan or glycosylated probe interacts with the lectin, the signal increases and

  6. Measuring political commitment and opportunities to advance food and nutrition security: piloting a rapid assessment tool.

    PubMed

    Fox, Ashley M; Balarajan, Yarlini; Cheng, Chloe; Reich, Michael R

    2015-06-01

    Lack of political commitment has been identified as a primary reason for the low priority that food and nutrition interventions receive from national governments relative to the high disease burden caused by malnutrition. Researchers have identified a number of factors that contribute to food and nutrition's 'low-priority cycle' on national policy agendas, but few tools exist to rapidly measure political commitment and identify opportunities to advance food and nutrition on the policy agenda. This article presents a theory-based rapid assessment approach to gauging countries' level of political commitment to food and nutrition security and identifying opportunities to advance food and nutrition on the policy agenda. The rapid assessment tool was piloted among food and nutrition policymakers and planners in 10 low- and middle-income countries in April to June 2013. Food and nutrition commitment and policy opportunity scores were calculated for each country and strategies to advance food and nutrition on policy agendas were designed for each country. The article finds that, in a majority of countries, political leaders had verbally and symbolically committed to addressing food and nutrition, but adequate financial resources were not allocated to implement specific programmes. In addition, whereas the low cohesion of the policy community has been viewed a major underlying cause of the low-priority status of food and nutrition, the analysis finds that policy community cohesion and having a well thought-out policy alternative were present in most countries. This tool may be useful to policymakers and planners providing information that can be used to benchmark and/or evaluate advocacy efforts to advance reforms in the food and nutrition sector; furthermore, the results can help identify specific strategies that can be employed to move the food and nutrition agenda forward. This tool complements others that have been recently developed to measure national commitment to

  7. Mutants of Arabidopsis as tools for physiology and molecular biology

    SciTech Connect

    Somerville, C.R.; Artus, N.; Browse, J.; Caspar, T.; Estelle, M.; Haughn, G.; Kunst, L.; Martinez, J.; McCourt, P.; Moffatt, B.

    1986-04-01

    The authors discuss the importance of developing a facile system for genetic analysis in higher plants which can be used to approach problems specific to plant biology in much the same way that molecular genetic approaches have been used in other classes of organisms such as yeast and Drosophila. Toward this end, they have developed methods for the isolation and analysis of mutants of Arabidopsis with specific alterations in photosynthesis, photorespiration, starch metabolism, lipid metabolism, purine metabolism, amino acid metabolism and phytohormone responses. The utility of this collection of mutants for studying problems in physiology and biochemistry is illustrated with selected examples.

  8. Graphene nanoribbon thermopower as a tool for molecular spectroscopy

    NASA Astrophysics Data System (ADS)

    Rosales, L.; Nunez, C. D.; Pacheco, M.; Latgé, A.; Orellana, P. A.

    2013-10-01

    In this work, we study thermoelectric properties of graphene nanoribbons with side-attached organic molecules. By adopting a single-band tight binding Hamiltonian and the Green's function formalism, we calculated the transmission and Seebeck coefficients for different hybrid systems. The corresponding thermopower profiles exhibit a series of sharp peaks at the eigenenergies of the isolated molecule indicating that the system can be proposed as a molecular thermo-device. We have studied the effects of the temperature on the thermoelectric response, and considered random configurations of molecule distributions, in different disorder regimes. We have found that the main features of the thermopower are robust under temperature and disorder.

  9. Molecular Genetic Tools and Techniques for Marchantia polymorpha Research.

    PubMed

    Ishizaki, Kimitsune; Nishihama, Ryuichi; Yamato, Katsuyuki T; Kohchi, Takayuki

    2016-02-01

    Liverworts occupy a basal position in the evolution of land plants, and are a key group to address a wide variety of questions in plant biology. Marchantia polymorpha is a common, easily cultivated, dioecious liverwort species, and is emerging as an experimental model organism. The haploid gametophytic generation dominates the diploid sporophytic generation in its life cycle. Genetically homogeneous lines in the gametophyte generation can be established easily and propagated through asexual reproduction, which aids genetic and biochemical experiments. Owing to its dioecy, male and female sexual organs are formed in separate individuals, which enables crossing in a fully controlled manner. Reproductive growth can be induced at the desired times under laboratory conditions, which helps genetic analysis. The developmental process from a single-celled spore to a multicellular body can be observed directly in detail. As a model organism, molecular techniques for M. polymorpha are well developed; for example, simple and efficient protocols of Agrobacterium-mediated transformation have been established. Based on them, various strategies for molecular genetics, such as introduction of reporter constructs, overexpression, gene silencing and targeted gene modification, are available. Herein, we describe the technologies and resources for reverse and forward genetics in M. polymorpha, which offer an excellent experimental platform to study the evolution and diversity of regulatory systems in land plants.

  10. Molecular markers and imaging tools to identify malignant potential in Barrett's esophagus

    PubMed Central

    Bennett, Michael; Mashimo, Hiroshi

    2014-01-01

    Due to its rapidly rising incidence and high mortality, esophageal adenocarcinoma is a major public health concern, particularly in Western countries. The steps involved in the progression from its predisposing condition, gastroesophageal reflux disease, to its premalignant disorder, Barrett’s esophagus, and to cancer, are incompletely understood. Current screening and surveillance methods are limited by the lack of population-wide utility, incomplete sampling of standard biopsies, and subjectivity of evaluation. Advances in endoscopic ablation have raised the hope of effective therapy for eradication of high-risk Barrett’s lesions, but improvements are needed in determining when to apply this treatment and how to follow patients clinically. Researchers have evaluated numerous potential molecular biomarkers with the goal of detecting dysplasia, with varying degrees of success. The combination of biomarker panels with epidemiologic risk factors to yield clinical risk scoring systems is promising. New approaches to sample tissue may also be combined with these biomarkers for less invasive screening and surveillance. The development of novel endoscopic imaging tools in recent years has the potential to markedly improve detection of small foci of dysplasia in vivo. Current and future efforts will aim to determine the combination of markers and imaging modalities that will most effectively improve the rate of early detection of high-risk lesions in Barrett’s esophagus. PMID:25400987

  11. Advances in molecular electronics: Synthesis and testing of potential molecular electronic devices

    NASA Astrophysics Data System (ADS)

    Price, David Wilson, Jr.

    New potential molecular electronics devices have been synthesized based on our knowledge of previous systems that have come out of our group. Previous studies and current studies have shown that simple molecular systems demonstrate negative differential resistance (NDR) and memory characteristics. The new systems rely primarily on the redox properties of the compounds to improve upon the solid state properties already observed. Most of these new organic compounds use thiol-based "alligator clips" for attachment to metal surfaces. Some of the compounds, however, contain different "alligator clips," primarily isonitriles, for attachment to metal substrates. It is our hope that these new "alligator clips" will offer lower conductivity barriers (higher current density). Electrochemical tests have been performed in order to evaluate those redox properties and in the hope of using those electrochemical results as a predictive tool to evaluate the usefulness of those compounds. Also, organic structures with polymerizable functionalities have been synthesized in order to cross-link the molecules once they are a part of a self-assembled monolayer (SAM). This has been shown to enable the electrochemical growth of polypyrrole from a SAM in a controllable manner.

  12. Molecular simulation as a tool for studying lignin

    SciTech Connect

    Sangha, Amandeep K; Petridis, Loukas; Smith, Jeremy C; Ziebell, Angela L; Parks, Jerry M

    2012-01-01

    Lignocellulosic biomass provides a sustainable source of sugars for biofuel and biomaterial production. However, biomass resistance to degradation imposes difficulties for economical conversion of plant carbohydrates to fermentable sugars. One of the key contributors to recalcitrance is lignin. Understanding the properties of lignin macromolecules in the cell wall matrix is useful for manipulating biomass structure to generate more easily degradable biomass. Along with experimental techniques such as 2D-NMR and mass spectrometry, computational techniques can be useful for characterizing the structural and energetic properties of the biomass assembly and its individual constituents. Here, we provide a brief introduction to lignin, review some of the recent, relevant scientific literature, and give our perspectives on the role of molecular simulation in understanding lignin structure.

  13. Web-based cheminformatics and molecular property prediction tools supporting drug design and development at Novartis.

    PubMed

    Ertl, P; Mühlbacher, J; Rohde, B; Selzer, P

    2003-01-01

    Web-based tools offer many advantages for processing chemical information, most notably ease of use and high interactivity. Therefore more and more pharmaceutical companies are using web technology to deliver sophisticated molecular processing tools directly to the desks of their chemists, to assist them in the process of designing and developing new drugs. In this paper, the web-based cheminformatics system developed at Novartis and currently used by more than thousand users is described. The system allows various molecular modeling and molecular processing tasks, including the calculation of molecular and substituent properties, property-based virtual screening, visualization of molecules, bioisosteric design, diversity analysis, and support of combinatorial chemistry. The methodology to calculate various molecular properties relevant to drug design is described, including the prediction of intestinal absorption, blood-brain barrier penetration, efflux, and water solubility. Information about the web technology used is also provided.

  14. Advances in molecular serotyping and subtyping of Escherichia coli

    SciTech Connect

    Fratamico, Pina M.; DebRoy, Chitrita; Liu, Yanhong; Needleman, David S.; Baranzoni, Gian Marco; Feng, Peter

    2016-05-03

    Escherichia coli plays an important role as a member of the gut microbiota; however, pathogenic strains also exist, including various diarrheagenic E. coli pathotypes and extraintestinal pathogenic E. coli that cause illness outside of the GI-tract. E. coli have traditionally been serotyped using antisera against the ca. 186 O-antigens and 53 H-flagellar antigens. Phenotypic methods, including bacteriophage typing and O- and H- serotyping for differentiating and characterizing E. coli have been used for many years; however, these methods are generally time consuming and not always accurate. Advances in next generation sequencing technologies have made it possible to develop genetic-based subtyping and molecular serotyping methods for E. coli, which are more discriminatory compared to phenotypic typing methods. Furthermore, whole genome sequencing (WGS) of E. coli is replacing established subtyping methods such as pulsedfield gel electrophoresis, providing a major advancement in the ability to investigate food-borne disease outbreaks and for trace-back to sources. Furthermore, a variety of sequence analysis tools and bioinformatic pipelines are being developed to analyze the vast amount of data generated by WGS and to obtain specific information such as O- and H-group determination and the presence of virulence genes and other genetic markers.

  15. Molecular beam epitaxy for advanced gate stack materials and processes

    NASA Astrophysics Data System (ADS)

    Locquet, Jean-Pierre

    2005-03-01

    The material requirements for future CMOS generations - as given by the ITRS roadmap - are very challenging. This includes a high K dielectric without a low K interfacial layer, a high mobility channel and the appropriate metal gate. With the help of two projects INVEST and ET4US, we are building up a molecular beam epitaxy (MBE) infrastructure to grow this material set on large area wafers that can be further processed into small scale devices. In the INVEST project, we have developed an MBE system for the growth of complex oxides on semiconductors. The system follows the overall design of a production tool and is equipped with an RF atomic oxygen source, effusion cells, e-beam evaporators and a differential pumping stage. The oxide growth process starts with desorbing the initial surface oxide on the Si wafers in ultra-high vacuum and high temperature to create a clean reconstructed 2x1 surface. Using the atomic oxygen it is possible to oxidize the surface in a well controlled manner at low temperature and to grow very thin and dense SiOx layers, followed by the growth of 2-6 nm amorphous high K dielectrics. The process parameters permit to tune the interface layer from a SiOx rich to a silicide rich interface with a significant impact on the capacitance and the leakage. Initial focus is on developing an optimized growth recipe for high quality amorphous HfO2 and LaHfO3.5 films. This recipe was subsequently used to make wafers for a transistor batch that gave us the first N short channel MBE MOSFET's (100 nm) using an etched gate process flow. Some highlights of the first batch for 3nm HfO2 MOSFET are a high mobility (> 270 cm^2/Vs) with a corresponding low leakage current of 2 mA/cm^2). While there were some process issues for LaHfO3.5, the 3 nm MOSFET showed very low leakage currents below 10-6 A/cm^2. Interestingly all the LaHFO3.5 MOSFETs showed very low threshold voltage instabilities. In collaboration with C. Marchiori, M. Sousa, A.Guiller, H. Siegwart, D

  16. How Molecular Structure Affects Mechanical Properties of an Advanced Polymer

    NASA Technical Reports Server (NTRS)

    Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.; Hinkley, Jeffrey A.

    2000-01-01

    density was performed over a range of temperatures below the glass transition temperature. The physical characterization, elastic properties and notched tensile strength all as a function of molecular weight and test temperature were determined. For the uncrosslinked SI material, it was shown that notched tensile strength is a strong function of both temperature and molecular weight, whereas stiffness is only a strong function of temperature. For the crosslinked PETI-SI material, it was shown that the effect of crosslinking significantly enhances the mechanical performance of the low molecular weight material; comparable to that exhibited by the high molecular weight material.

  17. Advanced Risk Reduction Tool (ARRT) Special Case Study Report: Science and Engineering Technical Assessments (SETA) Program

    NASA Technical Reports Server (NTRS)

    Kirsch, Paul J.; Hayes, Jane; Zelinski, Lillian

    2000-01-01

    This special case study report presents the Science and Engineering Technical Assessments (SETA) team's findings for exploring the correlation between the underlying models of Advanced Risk Reduction Tool (ARRT) relative to how it identifies, estimates, and integrates Independent Verification & Validation (IV&V) activities. The special case study was conducted under the provisions of SETA Contract Task Order (CTO) 15 and the approved technical approach documented in the CTO-15 Modification #1 Task Project Plan.

  18. Advances in molecular quantum chemistry contained in the Q-Chem 4 program package

    NASA Astrophysics Data System (ADS)

    Shao, Yihan; Gan, Zhengting; Epifanovsky, Evgeny; Gilbert, Andrew T. B.; Wormit, Michael; Kussmann, Joerg; Lange, Adrian W.; Behn, Andrew; Deng, Jia; Feng, Xintian; Ghosh, Debashree; Goldey, Matthew; Horn, Paul R.; Jacobson, Leif D.; Kaliman, Ilya; Khaliullin, Rustam Z.; Kuś, Tomasz; Landau, Arie; Liu, Jie; Proynov, Emil I.; Rhee, Young Min; Richard, Ryan M.; Rohrdanz, Mary A.; Steele, Ryan P.; Sundstrom, Eric J.; Woodcock, H. Lee, III; Zimmerman, Paul M.; Zuev, Dmitry; Albrecht, Ben; Alguire, Ethan; Austin, Brian; Beran, Gregory J. O.; Bernard, Yves A.; Berquist, Eric; Brandhorst, Kai; Bravaya, Ksenia B.; Brown, Shawn T.; Casanova, David; Chang, Chun-Min; Chen, Yunqing; Chien, Siu Hung; Closser, Kristina D.; Crittenden, Deborah L.; Diedenhofen, Michael; DiStasio, Robert A., Jr.; Do, Hainam; Dutoi, Anthony D.; Edgar, Richard G.; Fatehi, Shervin; Fusti-Molnar, Laszlo; Ghysels, An; Golubeva-Zadorozhnaya, Anna; Gomes, Joseph; Hanson-Heine, Magnus W. D.; Harbach, Philipp H. P.; Hauser, Andreas W.; Hohenstein, Edward G.; Holden, Zachary C.; Jagau, Thomas-C.; Ji, Hyunjun; Kaduk, Benjamin; Khistyaev, Kirill; Kim, Jaehoon; Kim, Jihan; King, Rollin A.; Klunzinger, Phil; Kosenkov, Dmytro; Kowalczyk, Tim; Krauter, Caroline M.; Lao, Ka Un; Laurent, Adèle D.; Lawler, Keith V.; Levchenko, Sergey V.; Lin, Ching Yeh; Liu, Fenglai; Livshits, Ester; Lochan, Rohini C.; Luenser, Arne; Manohar, Prashant; Manzer, Samuel F.; Mao, Shan-Ping; Mardirossian, Narbe; Marenich, Aleksandr V.; Maurer, Simon A.; Mayhall, Nicholas J.; Neuscamman, Eric; Oana, C. Melania; Olivares-Amaya, Roberto; O'Neill, Darragh P.; Parkhill, John A.; Perrine, Trilisa M.; Peverati, Roberto; Prociuk, Alexander; Rehn, Dirk R.; Rosta, Edina; Russ, Nicholas J.; Sharada, Shaama M.; Sharma, Sandeep; Small, David W.; Sodt, Alexander; Stein, Tamar; Stück, David; Su, Yu-Chuan; Thom, Alex J. W.; Tsuchimochi, Takashi; Vanovschi, Vitalii; Vogt, Leslie; Vydrov, Oleg; Wang, Tao; Watson, Mark A.; Wenzel, Jan; White, Alec; Williams, Christopher F.; Yang, Jun; Yeganeh, Sina; Yost, Shane R.; You, Zhi-Qiang; Zhang, Igor Ying; Zhang, Xing; Zhao, Yan; Brooks, Bernard R.; Chan, Garnet K. L.; Chipman, Daniel M.; Cramer, Christopher J.; Goddard, William A., III; Gordon, Mark S.; Hehre, Warren J.; Klamt, Andreas; Schaefer, Henry F., III; Schmidt, Michael W.; Sherrill, C. David; Truhlar, Donald G.; Warshel, Arieh; Xu, Xin; Aspuru-Guzik, Alán; Baer, Roi; Bell, Alexis T.; Besley, Nicholas A.; Chai, Jeng-Da; Dreuw, Andreas; Dunietz, Barry D.; Furlani, Thomas R.; Gwaltney, Steven R.; Hsu, Chao-Ping; Jung, Yousung; Kong, Jing; Lambrecht, Daniel S.; Liang, WanZhen; Ochsenfeld, Christian; Rassolov, Vitaly A.; Slipchenko, Lyudmila V.; Subotnik, Joseph E.; Van Voorhis, Troy; Herbert, John M.; Krylov, Anna I.; Gill, Peter M. W.; Head-Gordon, Martin

    2015-01-01

    A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Møller-Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube.

  19. Dopamine receptor genes: new tools for molecular psychiatry.

    PubMed Central

    Niznik, H B; Van Tol, H H

    1992-01-01

    For over a decade it has been generally assumed that all the pharmacological and biochemical actions of dopamine within the central nervous system and periphery were mediated by two distinct dopamine receptors. These receptors, termed D1 and D2, were defined as those coupled to the stimulation or inhibition of adenylate cyclase, respectively, and by their selectivity and avidity for various drugs and compounds. The concept that two dopamine receptors were sufficient to account for all the effects mediated by dopamine was an oversimplification. Recent molecular biological studies have identified five distinct genes which encode at least eight functional dopamine receptors. The members of the expanded dopamine receptor family, however, can still be codifed by way of the original D1 and D2 receptor dichotomy. These include two genes encoding dopamine D1-like receptors (D1 [D1A]/D5 [D1B]) and three genes encoding D2-like receptors (D2/D3/D4). We review here our recent work on the cloning and characterization of some of the members of the dopamine receptor gene family (D1, D2, D4, D5), their relationship to neuropsychiatric disorders and their potential role in antipsychotic drug action. Images Fig. 1 PMID:1450188

  20. Acetylenic Coupling: A Powerful Tool in Molecular Construction.

    PubMed

    Siemsen; Livingston; Diederich

    2000-08-04

    Acetylenic coupling is currently experiencing some of the most intensive study of its long history. Rigid and sterically undemanding di- and oligoacetylene moieties, which are frequently encountered in natural products, are finding increasing application as key structural elements in synthetic receptors for molecular recognition. Interesting electronic and optical properties of extensively pi-conjugated systems have spurred research into new linear oligoalkynes and acetylenic carbon allotropes. The synthetic challenges associated with these efforts have in turn spawned new methods. While classical Glaser conditions are still frequently used for homocoupling, the demand for increasingly selective heterocoupling conditions has provided the focus of research over the past decades. These efforts have undoubtedly been hampered by a relatively poor mechanistic understanding of these processes. More recently, palladium-catalyzed coupling methods have led to improvements in both the selectivity and reliability of acetylenic homo- and heterocouplings and paved the way for their application to ever more complicated systems. The variety of acetylenic coupling protocols, the current mechanistic understanding, and their application in natural product and targeted synthesis are discussed comprehensively for the first time in this review, with an emphasis on the most recently developed methods, and their application to the synthesis of complex macromolecular structures.

  1. Advanced gradient-index lens design tools to maximize system performance and reduce SWaP

    NASA Astrophysics Data System (ADS)

    Campbell, Sawyer D.; Nagar, Jogender; Brocker, Donovan E.; Easum, John A.; Turpin, Jeremiah P.; Werner, Douglas H.

    2016-05-01

    GRadient-INdex (GRIN) lenses have long been of interest due to their potential for providing levels of performance unachievable with traditional homogeneous lenses. While historically limited by a lack of suitable materials, rapid advancements in manufacturing techniques, including 3D printing, have recently kindled a renewed interest in GRIN optics. Further increasing the desire for GRIN devices has been the advent of Transformation Optics (TO), which provides the mathematical framework for representing the behavior of electromagnetic radiation in a given geometry by "transforming" it to an alternative, usually more desirable, geometry through an appropriate mapping of the constituent material parameters. Using TO, aspherical lenses can be transformed to simpler spherical and flat geometries or even rotationally-asymmetric shapes which result in true 3D GRIN profiles. Meanwhile, there is a critical lack of suitable design tools which can effectively evaluate the optical wave propagation through 3D GRIN profiles produced by TO. Current modeling software packages for optical lens systems also lack advanced multi-objective global optimization capability which allows the user to explicitly view the trade-offs between all design objectives such as focus quality, FOV, ▵nand focal drift due to chromatic aberrations. When coupled with advanced design methodologies such as TO, wavefront matching (WFM), and analytical achromatic GRIN theory, these tools provide a powerful framework for maximizing SWaP (Size, Weight and Power) reduction in GRIN-enabled optical systems. We provide an overview of our advanced GRIN design tools and examples which minimize the presence of mono- and polychromatic aberrations in the context of reducing SWaP.

  2. Current advances in molecular, biochemical, and computational modeling analysis of microalgal triacylglycerol biosynthesis.

    PubMed

    Lenka, Sangram K; Carbonaro, Nicole; Park, Rudolph; Miller, Stephen M; Thorpe, Ian; Li, Yantao

    2016-01-01

    Triacylglycerols (TAGs) are highly reduced energy storage molecules ideal for biodiesel production. Microalgal TAG biosynthesis has been studied extensively in recent years, both at the molecular level and systems level through experimental studies and computational modeling. However, discussions of the strategies and products of the experimental and modeling approaches are rarely integrated and summarized together in a way that promotes collaboration among modelers and biologists in this field. In this review, we outline advances toward understanding the cellular and molecular factors regulating TAG biosynthesis in unicellular microalgae with an emphasis on recent studies on rate-limiting steps in fatty acid and TAG synthesis, while also highlighting new insights obtained from the integration of multi-omics datasets with mathematical models. Computational methodologies such as kinetic modeling, metabolic flux analysis, and new variants of flux balance analysis are explained in detail. We discuss how these methods have been used to simulate algae growth and lipid metabolism in response to changing culture conditions and how they have been used in conjunction with experimental validations. Since emerging evidence indicates that TAG synthesis in microalgae operates through coordinated crosstalk between multiple pathways in diverse subcellular destinations including the endoplasmic reticulum and plastids, we discuss new experimental studies and models that incorporate these findings for discovering key regulatory checkpoints. Finally, we describe tools for genetic manipulation of microalgae and their potential for future rational algal strain design. This comprehensive review explores the potential synergistic impact of pathway analysis, computational approaches, and molecular genetic manipulation strategies on improving TAG production in microalgae.

  3. FDA Bioinformatics Tool for Microbial Genomics Research on Molecular Characterization of Bacterial Foodborne Pathogens Using Microarrays

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Advances in microbial genomics and bioinformatics are offering greater insights into the emergence and spread of foodborne pathogens in outbreak scenarios. The Food and Drug Administration (FDA) has developed the genomics tool ArrayTrackTM, which provides extensive functionalities to man...

  4. Cellulosome-based, Clostridium-derived multi-functional enzyme complexes for advanced biotechnology tool development: advances and applications.

    PubMed

    Hyeon, Jeong Eun; Jeon, Sang Duck; Han, Sung Ok

    2013-11-01

    The cellulosome is one of nature's most elegant and elaborate nanomachines and a key biological and biotechnological macromolecule that can be used as a multi-functional protein complex tool. Each protein module in the cellulosome system is potentially useful in an advanced biotechnology application. The high-affinity interactions between the cohesin and dockerin domains can be used in protein-based biosensors to improve both sensitivity and selectivity. The scaffolding protein includes a carbohydrate-binding module (CBM) that attaches strongly to cellulose substrates and facilitates the purification of proteins fused with the dockerin module through a one-step CBM purification method. Although the surface layer homology (SLH) domain of CbpA is not present in other strains, replacement of the cell surface anchoring domain allows a foreign protein to be displayed on the surface of other strains. The development of a hydrolysis enzyme complex is a useful strategy for consolidated bioprocessing (CBP), enabling microorganisms with biomass hydrolysis activity. Thus, the development of various configurations of multi-functional protein complexes for use as tools in whole-cell biocatalyst systems has drawn considerable attention as an attractive strategy for bioprocess applications. This review provides a detailed summary of the current achievements in Clostridium-derived multi-functional complex development and the impact of these complexes in various areas of biotechnology.

  5. Molecular Docking of Enzyme Inhibitors: A Computational Tool for Structure-Based Drug Design

    ERIC Educational Resources Information Center

    Rudnitskaya, Aleksandra; Torok, Bela; Torok, Marianna

    2010-01-01

    Molecular docking is a frequently used method in structure-based rational drug design. It is used for evaluating the complex formation of small ligands with large biomolecules, predicting the strength of the bonding forces and finding the best geometrical arrangements. The major goal of this advanced undergraduate biochemistry laboratory exercise…

  6. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    PubMed

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

  7. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms

    PubMed Central

    Mooney, Michael A.; Simon, Elias D.; Little, Andrew S.

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  8. Anvil Forecast Tool in the Advanced Weather Interactive Processing System (AWIPS)

    NASA Technical Reports Server (NTRS)

    Barrett, Joe H., III; Hood, Doris

    2009-01-01

    Launch Weather Officers (LWOs) from the 45th Weather Squadron (45 WS) and forecasters from the National Weather Service (NWS) Spaceflight Meteorology Group (SMG) have identified anvil forecasting as one of their most challenging tasks when predicting the probability of violating the Lightning Launch Commit Criteria (LLCC) (Krider et al. 2006; Space Shuttle Flight Rules (FR), NASA/JSC 2004)). As a result, the Applied Meteorology Unit (AMU) developed a tool that creates an anvil threat corridor graphic that can be overlaid on satellite imagery using the Meteorological Interactive Data Display System (MIDDS, Short and Wheeler, 2002). The tool helps forecasters estimate the locations of thunderstorm anvils at one, two, and three hours into the future. It has been used extensively in launch and landing operations by both the 45 WS and SMG. The Advanced Weather Interactive Processing System (AWIPS) is now used along with MIDDS for weather analysis and display at SMG. In Phase I of this task, SMG tasked the AMU to transition the tool from MIDDS to AWIPS (Barrett et aI., 2007). For Phase II, SMG requested the AMU make the Anvil Forecast Tool in AWIPS more configurable by creating the capability to read model gridded data from user-defined model files instead of hard-coded files. An NWS local AWIPS application called AGRID was used to accomplish this. In addition, SMG needed to be able to define the pressure levels for the model data, instead of hard-coding the bottom level as 300 mb and the top level as 150 mb. This paper describes the initial development of the Anvil Forecast Tool for MIDDS, followed by the migration of the tool to AWIPS in Phase I. It then gives a detailed presentation of the Phase II improvements to the AWIPS tool.

  9. Genetic tools for wildlife management: New TWS Working Group focuses on molecular ecology

    USGS Publications Warehouse

    Latch, Emily; Crowhurst, Rachel S.; Oyler-McCance, Sara J.; Robinson, Stacie

    2014-01-01

    Granted interim status in November, 2013, The Wildlife Society’s (TWS) Molecular Ecology Working Group aims to promote scientific advancement by applying molecular techniques to wildlife ecology, management, and conservation. The working group—composed of sci - entists from diverse backgrounds—met for the first time in Pittsburgh at the TWS Annual Conference held in October. Our overarching goal is to enhance awareness of molecular ecology and genetic applica - tions to wildlife biology and act as an informational and networking resource. During the group’s interim status, which runs for three years, we intend to focus on a broad scope of molecular ecology that is applicable to wildlife including genetic and ge - nomic methods, conservation genetics, non-invasive genetic population monitoring, landscape genetics, evolutionary genetics, and molecular forensics

  10. Recovery Act: Advanced Interaction, Computation, and Visualization Tools for Sustainable Building Design

    SciTech Connect

    Greenberg, Donald P.; Hencey, Brandon M.

    2013-08-20

    Current building energy simulation technology requires excessive labor, time and expertise to create building energy models, excessive computational time for accurate simulations and difficulties with the interpretation of the results. These deficiencies can be ameliorated using modern graphical user interfaces and algorithms which take advantage of modern computer architectures and display capabilities. To prove this hypothesis, we developed an experimental test bed for building energy simulation. This novel test bed environment offers an easy-to-use interactive graphical interface, provides access to innovative simulation modules that run at accelerated computational speeds, and presents new graphics visualization methods to interpret simulation results. Our system offers the promise of dramatic ease of use in comparison with currently available building energy simulation tools. Its modular structure makes it suitable for early stage building design, as a research platform for the investigation of new simulation methods, and as a tool for teaching concepts of sustainable design. Improvements in the accuracy and execution speed of many of the simulation modules are based on the modification of advanced computer graphics rendering algorithms. Significant performance improvements are demonstrated in several computationally expensive energy simulation modules. The incorporation of these modern graphical techniques should advance the state of the art in the domain of whole building energy analysis and building performance simulation, particularly at the conceptual design stage when decisions have the greatest impact. More importantly, these better simulation tools will enable the transition from prescriptive to performative energy codes, resulting in better, more efficient designs for our future built environment.

  11. Improving human forensics through advances in genetics, genomics and molecular biology.

    PubMed

    Kayser, Manfred; de Knijff, Peter

    2011-03-01

    Forensic DNA profiling currently allows the identification of persons already known to investigating authorities. Recent advances have produced new types of genetic markers with the potential to overcome some important limitations of current DNA profiling methods. Moreover, other developments are enabling completely new kinds of forensically relevant information to be extracted from biological samples. These include new molecular approaches for finding individuals previously unknown to investigators, and new molecular methods to support links between forensic sample donors and criminal acts. Such advances in genetics, genomics and molecular biology are likely to improve human forensic case work in the near future.

  12. Advances in simulation study on organic small molecular solar cells

    NASA Astrophysics Data System (ADS)

    Zhang, Xuan; Guo, Wenge; Li, Ming; Ma, Wentao; Meng, Sen

    2015-02-01

    Recently, more focuses have been put on organic semiconductors because of its advantages, such as its flexibility, ease of fabrication and potential low cost, etc. The reasons we pay highlight on small molecular photovoltaic material are its ease of purification, easy to adjust and determine structure, easy to assemble range units and get high carrier mobility, etc. Simulation study on organic small molecular solar cells before the experiment can help the researchers find relationship between the efficiency and structure parameters, properties of material, estimate the performance of the device, bring the optimization of guidance. Also, the applicability of the model used in simulation can be discussed by comparison with experimental data. This paper summaries principle, structure, progress of numerical simulation on organic small molecular solar cells.

  13. Molecular Tools for the Selective Detection of Nine Diatom Species Biomarkers of Various Water Quality Levels

    PubMed Central

    Cimarelli, Lucia; Singh, Kumar Saurabh; Mai, Nguyen Thi Nhu; Dhar, Bidhan Chandra; Brandi, Anna; Brandi, Letizia; Spurio, Roberto

    2015-01-01

    Our understanding of the composition of diatom communities and their response to environmental changes is currently limited by laborious taxonomic identification procedures. Advances in molecular technologies are expected to contribute more efficient, robust and sensitive tools for the detection of these ecologically relevant microorganisms. There is a need to explore and test phylogenetic markers as an alternative to the use of rRNA genes, whose limited sequence divergence does not allow the accurate discrimination of diatoms at the species level. In this work, nine diatom species belonging to eight genera, isolated from epylithic environmental samples collected in central Italy, were chosen to implement a panel of diatoms covering the full range of ecological status of freshwaters. The procedure described in this work relies on the PCR amplification of specific regions in two conserved diatom genes, elongation factor 1-a (eEF1-a) and silicic acid transporter (SIT), as a first step to narrow down the complexity of the targets, followed by microarray hybridization experiments. Oligonucleotide probes with the potential to discriminate closely related species were designed taking into account the genetic polymorphisms found in target genes. These probes were tested, refined and validated on a small-scale prototype DNA chip. Overall, we obtained 17 highly specific probes targeting eEF1-a and SIT, along with 19 probes having lower discriminatory power recognizing at the same time two or three species. This basic array was validated in a laboratory setting and is ready for tests with crude environmental samples eventually to be scaled-up to include a larger panel of diatoms. Its possible use for the simultaneous detection of diatoms selected from the classes of water quality identified by the European Water Framework Directive is discussed. PMID:26006124

  14. Molecular tools for the selective detection of nine diatom species biomarkers of various water quality levels.

    PubMed

    Cimarelli, Lucia; Singh, Kumar Saurabh; Mai, Nguyen Thi Nhu; Dhar, Bidhan Chandra; Brandi, Anna; Brandi, Letizia; Spurio, Roberto

    2015-05-22

    Our understanding of the composition of diatom communities and their response to environmental changes is currently limited by laborious taxonomic identification procedures. Advances in molecular technologies are expected to contribute more efficient, robust and sensitive tools for the detection of these ecologically relevant microorganisms. There is a need to explore and test phylogenetic markers as an alternative to the use of rRNA genes, whose limited sequence divergence does not allow the accurate discrimination of diatoms at the species level. In this work, nine diatom species belonging to eight genera, isolated from epylithic environmental samples collected in central Italy, were chosen to implement a panel of diatoms covering the full range of ecological status of freshwaters. The procedure described in this work relies on the PCR amplification of specific regions in two conserved diatom genes, elongation factor 1-a (eEF1-a) and silicic acid transporter (SIT), as a first step to narrow down the complexity of the targets, followed by microarray hybridization experiments. Oligonucleotide probes with the potential to discriminate closely related species were designed taking into account the genetic polymorphisms found in target genes. These probes were tested, refined and validated on a small-scale prototype DNA chip. Overall, we obtained 17 highly specific probes targeting eEF1-a and SIT, along with 19 probes having lower discriminatory power recognizing at the same time two or three species. This basic array was validated in a laboratory setting and is ready for tests with crude environmental samples eventually to be scaled-up to include a larger panel of diatoms. Its possible use for the simultaneous detection of diatoms selected from the classes of water quality identified by the European Water Framework Directive is discussed.

  15. Technical advances in molecular simulation since the 1980s.

    PubMed

    Field, Martin J

    2015-09-15

    This review describes how the theory and practice of molecular simulation have evolved since the beginning of the 1980s when the author started his career in this field. The account is of necessity brief and subjective and highlights the changes that the author considers have had significant impact on his research and mode of working.

  16. Recent advances in yeast molecular biology: recombinant DNA. [Lead abstract

    SciTech Connect

    Not Available

    1982-09-01

    Separate abstracts were prepared for the 25 papers presented at a workshop focusing on chromosomal structure, gene regulation, recombination, DNA repair, and cell type control, that have been obtained by experimental approaches incorporating the new technologies of yeast DNA transformation, molecular cloning, and DNA sequence analysis. (KRM)

  17. Advances in Omics and Bioinformatics Tools for Systems Analyses of Plant Functions

    PubMed Central

    Mochida, Keiichi; Shinozaki, Kazuo

    2011-01-01

    Omics and bioinformatics are essential to understanding the molecular systems that underlie various plant functions. Recent game-changing sequencing technologies have revitalized sequencing approaches in genomics and have produced opportunities for various emerging analytical applications. Driven by technological advances, several new omics layers such as the interactome, epigenome and hormonome have emerged. Furthermore, in several plant species, the development of omics resources has progressed to address particular biological properties of individual species. Integration of knowledge from omics-based research is an emerging issue as researchers seek to identify significance, gain biological insights and promote translational research. From these perspectives, we provide this review of the emerging aspects of plant systems research based on omics and bioinformatics analyses together with their associated resources and technological advances. PMID:22156726

  18. Clinical Significance of Molecular Diagnostic Tools for Bacterial Bloodstream Infections: A Systematic Review

    PubMed Central

    Nyirahabimana, Therese

    2016-01-01

    Bacterial bloodstream infection (bBSI) represents any form of invasiveness of the blood circulatory system caused by bacteria and can lead to death among critically ill patients. Thus, there is a need for rapid and accurate diagnosis and treatment of patients with septicemia. So far, different molecular diagnostic tools have been developed. The majority of these tools focus on amplification based techniques such as polymerase chain reaction (PCR) which allows the detection of nucleic acids (both DNA and small RNAs) that are specific to bacterial species and sequencing or nucleic acid hybridization that allows the detection of bacteria in order to reduce delay of appropriate antibiotic therapy. However, there is still a need to improve sensitivity of most molecular techniques to enhance their accuracy and allow exact and on time antibiotic therapy treatment. In this regard, we conducted a systematic review of the existing studies conducted in molecular diagnosis of bBSIs, with the main aim of reporting on clinical significance and benefits of molecular diagnosis to patients. We searched both Google Scholar and PubMed. In total, eighteen reviewed papers indicate that shift from conventional diagnostic methods to molecular tools is needed and would lead to accurate diagnosis and treatment of bBSI. PMID:27974890

  19. Advanced computational tools for optimization and uncertainty quantification of carbon capture processes

    SciTech Connect

    Miller, David C.; Ng, Brenda; Eslick, John

    2014-01-01

    Advanced multi-scale modeling and simulation has the potential to dramatically reduce development time, resulting in considerable cost savings. The Carbon Capture Simulation Initiative (CCSI) is a partnership among national laboratories, industry and universities that is developing, demonstrating, and deploying a suite of multi-scale modeling and simulation tools. One significant computational tool is FOQUS, a Framework for Optimization and Quantification of Uncertainty and Sensitivity, which enables basic data submodels, including thermodynamics and kinetics, to be used within detailed process models to rapidly synthesize and optimize a process and determine the level of uncertainty associated with the resulting process. The overall approach of CCSI is described with a more detailed discussion of FOQUS and its application to carbon capture systems.

  20. Proposal for constructing an advanced software tool for planetary atmospheric modeling

    NASA Technical Reports Server (NTRS)

    Keller, Richard M.; Sims, Michael H.; Podolak, Esther; Mckay, Christopher P.; Thompson, David E.

    1990-01-01

    Scientific model building can be a time intensive and painstaking process, often involving the development of large and complex computer programs. Despite the effort involved, scientific models cannot easily be distributed and shared with other scientists. In general, implemented scientific models are complex, idiosyncratic, and difficult for anyone but the original scientist/programmer to understand. We believe that advanced software techniques can facilitate both the model building and model sharing process. We propose to construct a scientific modeling software tool that serves as an aid to the scientist in developing and using models. The proposed tool will include an interactive intelligent graphical interface and a high level, domain specific, modeling language. As a testbed for this research, we propose development of a software prototype in the domain of planetary atmospheric modeling.

  1. NASA Technical Interchange Meeting (TIM): Advanced Technology Lifecycle Analysis System (ATLAS) Technology Tool Box

    NASA Technical Reports Server (NTRS)

    ONeil, D. A.; Craig, D. A.; Christensen, C. B.; Gresham, E. C.

    2005-01-01

    The objective of this Technical Interchange Meeting was to increase the quantity and quality of technical, cost, and programmatic data used to model the impact of investing in different technologies. The focus of this meeting was the Technology Tool Box (TTB), a database of performance, operations, and programmatic parameters provided by technologists and used by systems engineers. The TTB is the data repository used by a system of models known as the Advanced Technology Lifecycle Analysis System (ATLAS). This report describes the result of the November meeting, and also provides background information on ATLAS and the TTB.

  2. Global search tool for the Advanced Photon Source Integrated Relational Model of Installed Systems (IRMIS) database.

    SciTech Connect

    Quock, D. E. R.; Cianciarulo, M. B.; APS Engineering Support Division; Purdue Univ.

    2007-01-01

    The Integrated Relational Model of Installed Systems (IRMIS) is a relational database tool that has been implemented at the Advanced Photon Source to maintain an updated account of approximately 600 control system software applications, 400,000 process variables, and 30,000 control system hardware components. To effectively display this large amount of control system information to operators and engineers, IRMIS was initially built with nine Web-based viewers: Applications Organizing Index, IOC, PLC, Component Type, Installed Components, Network, Controls Spares, Process Variables, and Cables. However, since each viewer is designed to provide details from only one major category of the control system, the necessity for a one-stop global search tool for the entire database became apparent. The user requirements for extremely fast database search time and ease of navigation through search results led to the choice of Asynchronous JavaScript and XML (AJAX) technology in the implementation of the IRMIS global search tool. Unique features of the global search tool include a two-tier level of displayed search results, and a database data integrity validation and reporting mechanism.

  3. An Analysis of Energy Savings Possible Through Advances in Automotive Tooling Technology

    SciTech Connect

    Rick Schmoyer, RLS

    2004-12-03

    The use of lightweight and highly formable advanced materials in automobile and truck manufacturing has the potential to save fuel. Advances in tooling technology would promote the use of these materials. This report describes an energy savings analysis performed to approximate the potential fuel savings and consequential carbon-emission reductions that would be possible because of advances in tooling in the manufacturing of, in particular, non-powertrain components of passenger cars and heavy trucks. Separate energy analyses are performed for cars and heavy trucks. Heavy trucks are considered to be Class 7 and 8 trucks (trucks rated over 26,000 lbs gross vehicle weight). A critical input to the analysis is a set of estimates of the percentage reductions in weight and drag that could be achieved by the implementation of advanced materials, as a consequence of improved tooling technology, which were obtained by surveying tooling industry experts who attended a DOE Workshop, Tooling Technology for Low-Volume Vehicle Production, held in Seattle and Detroit in October and November 2003. The analysis is also based on 2001 fuel consumption totals and on energy-audit component proportions of fuel use due to drag, rolling resistance, and braking. The consumption proportions are assumed constant over time, but an allowance is made for fleet growth. The savings for a particular component is then the product of total fuel consumption, the percentage reduction of the component, and the energy audit component proportion. Fuel savings estimates for trucks also account for weight-limited versus volume-limited operations. Energy savings are assumed to be of two types: (1) direct energy savings incurred through reduced forces that must be overcome to move the vehicle or to slow it down in braking. and (2) indirect energy savings through reductions in the required engine power, the production and transmission of which incur thermodynamic losses, internal friction, and other

  4. Recent advances in the molecular design of synthetic vaccines

    NASA Astrophysics Data System (ADS)

    Jones, Lyn H.

    2015-12-01

    Vaccines have typically been prepared using whole organisms. These are normally either attenuated bacteria or viruses that are live but have been altered to reduce their virulence, or pathogens that have been inactivated and effectively killed through exposure to heat or formaldehyde. However, using whole organisms to elicit an immune response introduces the potential for infections arising from a reversion to a virulent form in live pathogens, unproductive reactions to vaccine components or batch-to-batch variability. Synthetic vaccines, in which a molecular antigen is conjugated to a carrier protein, offer the opportunity to circumvent these problems. This Perspective will highlight the progress that has been achieved in developing synthetic vaccines using a variety of molecular antigens. In particular, the different approaches used to develop conjugate vaccines using peptide/proteins, carbohydrates and other small molecule haptens as antigens are compared.

  5. Molecular underpinnings of corneal angiogenesis: advances over the past decade

    PubMed Central

    Abdelfattah, Nizar Saleh; Amgad, Mohamed; Zayed, Amira A.; Hussein, Heba; Abd El-Baky, Nawal

    2016-01-01

    The cornea is maintained in an avascular state by maintaining an environment whereby anti-angiogenic factors take the upper hand over factors promoting angiogenesis. Many of the common pathologies affecting the cornea involve the disruption of such equilibrium and the shift towards new vessel formation, leading to corneal opacity and eventually-vision loss. Therefore it is of paramount importance that the molecular underpinnings of corneal neovascularization (CNV) be clearly understood, in order to develop better targeted treatments. This article is a review of the literature on the recent discoveries regarding pro-angiogenic factors of the cornea (such as vascular endothelial growth factors, fibroblast growth factor and matrix metalloproteinases) and anti-angiogenic factors of the cornea (such as endostatins and neostatins). Further, we review the molecular underpinnings of lymphangiogenesis, a process now known to be almost separate from (yet related to) hemangiogenesis. PMID:27275438

  6. Molecular diagnosis of endemic and invasive mycoses: advances and challenges.

    PubMed

    Gómez, Beatriz L

    2014-01-01

    The diagnosis of endemic and invasive fungal disease remains challenging. Molecular techniques for identification of fungi now play a significant and growing role in clinical mycology and offer distinct advantages as they are faster, more sensitive and more specific. The aim of this mini-review is to provide an overview of the state of the art of molecular diagnosis of endemic and invasive fungal diseases, and to emphasize the challenges and current need for standardization of the different methods. The European Aspergillus PCR Initiative (EAPCRI) has made significant progress in developing a standard for Aspergillus polymerase chain reaction (PCR), but recognizes that the process will not be finished until clinical utility has been established in formal and extensive clinical trials. Similar efforts should be implemented for the diagnosis of the other mycoses in order to fully validate the current methods or reinforce the need to design new ones. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).

  7. Molecular strategies to prevent, inhibit, and degrade advanced glycoxidation and advanced lipoxidation end products.

    PubMed

    Aldini, Giancarlo; Vistoli, Giulio; Stefek, Milan; Chondrogianni, N; Grune, Tilman; Sereikaite, Jolanta; Sadowska-Bartosz, Izabela; Bartosz, Grzegorz

    2013-08-01

    The advanced glycoxidation end products (AGEs) and lipoxidation end products (ALEs) contribute to the development of diabetic complications and of other pathologies. The review discusses the possibilities of counteracting the formation and stimulating the degradation of these species by pharmaceuticals and natural compounds. The review discusses inhibitors of ALE and AGE formation, cross-link breakers, ALE/AGE elimination by enzymes and proteolytic systems, receptors for advanced glycation end products (RAGEs) and blockade of the ligand-RAGE axis.

  8. Clinical impact of extensive molecular profiling in advanced cancer patients.

    PubMed

    Cousin, Sophie; Grellety, Thomas; Toulmonde, Maud; Auzanneau, Céline; Khalifa, Emmanuel; Laizet, Yec'han; Tran, Kevin; Le Moulec, Sylvestre; Floquet, Anne; Garbay, Delphine; Robert, Jacques; Hostein, Isabelle; Soubeyran, Isabelle; Italiano, Antoine

    2017-02-08

    Previous precision medicine studies have investigated conventional molecular techniques and/or limited sets of gene alterations. The aim of this study was to describe the impact of the next-generation sequencing of the largest panel of genes used to date in tumour tissue and blood in the context of institutional molecular screening programmes. DNA analysis was performed by next-generation sequencing using a panel of 426 cancer-related genes and by comparative genomic hybridization from formalin-fixed and paraffin-embedded archived tumour samples when available or from fresh tumour samples. Five hundred sixty-eight patients were enrolled. The median number of prior lines of treatment was 2 (range 0-9). The most common primary tumour types were lung (16.9%), colorectal (14.4%), breast (10.6%), ovarian (10.2%) and sarcoma (10.2%). The median patient age was 63 years (range 19-88). A total of 292 patients (51.4%) presented with at least one actionable genetic alteration. The 20 genes most frequently altered were TP53, CDKN2A, KRAS, PTEN, PI3KCA, RB1, APC, ERBB2, MYC, EGFR, CDKN2B, ARID1A, SMAD4, FGFR1, MDM2, BRAF, ATM, CCNE1, FGFR3 and FRS2. One hundred fifty-nine patients (28%) were included in early phase trials. The treatment was matched with a tumour profile in 86 cases (15%). The two main reasons for non-inclusion were non-progressive disease (31.5%) and general status deterioration (25%). Twenty-eight percent of patients presented with a growth modulation index (time to progression under the early phase trial treatment/time to progression of the previous line of treatment) >1.3.Extensive molecular profiling using high-throughput techniques allows for the identification of actionable mutations in the majority of cases and is associated with substantial clinical benefit in up to one in four patients.

  9. Microbiology and Molecular Biology Tools for Biogas Process Analysis, Diagnosis and Control.

    PubMed

    Lebuhn, Michael; Weiß, Stefan; Munk, Bernhard; Guebitz, Georg M

    2015-01-01

    Many biotechnological processes such as biogas production or defined biotransformations are carried out by microorganisms or tightly cooperating microbial communities. Process breakdown is the maximum credible accident for the operator. Any time savings that can be provided by suitable early-warning systems and allow for specific countermeasures are of great value. Process disturbance, frequently due to nutritional shortcomings, malfunction or operational deficits, is evidenced conventionally by process chemistry parameters. However, knowledge on systems microbiology and its function has essentially increased in the last two decades, and molecular biology tools, most of which are directed against nucleic acids, have been developed to analyze and diagnose the process. Some of these systems have been shown to indicate changes of the process status considerably earlier than the conventionally applied process chemistry parameters. This is reasonable because the triggering catalyst is determined, activity changes of the microbes that perform the reaction. These molecular biology tools have thus the potential to add to and improve the established process diagnosis system. This chapter is dealing with the actual state of the art of biogas process analysis in practice, and introduces molecular biology tools that have been shown to be of particular value in complementing the current systems of process monitoring and diagnosis, with emphasis on nucleic acid targeted molecular biology systems.

  10. Recent advances in visualizing vulnerable plaque: focus on noninvasive molecular imaging.

    PubMed

    Bala, Gezim; Cosyns, Bernard

    2014-09-01

    Traditional imaging methods in atherosclerosis have focused primarily on anatomic information. Imaging approaches that visualize molecular targets rather than anatomic structures may emphasize biologic aspects of atherosclerosis. Molecular imaging of atherosclerotic lesions has become a crucial experimental tool and is now emerging in the clinical arena. In this review, we briefly highlight the rationale and fundamental principles of molecular imaging. We then discuss the promising imaging modalities, along with their potential limitations, and the molecular targets being investigated in experimental research. Finally, we summarize the most important clinical studies recently performed in humans.

  11. Advancing neuroscience through epigenetics: molecular mechanisms of learning and memory.

    PubMed

    Molfese, David L

    2011-01-01

    Humans share 96% of our 30,000 genes with Chimpanzees. The 1,200 genes that differ appear at first glance insufficient to describe what makes us human and them apes. However, we are now discovering that the mechanisms that regulate how genes are expressed tell a much richer story than our DNA alone. Sections of our DNA are constantly being turned on or off, marked for easy access, or secluded and hidden away, all in response to ongoing cellular activity. In the brain, neurons encode information-in effect memories-at the cellular level. Yet while memories may last a lifetime, neurons are dynamic structures. Every protein in the synapse undergoes some form of turnover, some with half-lives of only hours. How can a memory persist beyond the lifetimes of its constitutive molecular building blocks? Epigenetics-changes in gene expression that do not alter the underlying DNA sequence-may be the answer. In this article, epigenetic mechanisms including DNA methylation and acetylation or methylation of the histone proteins that package DNA are described in the context of animal learning. Through the interaction of these modifications a "histone code" is emerging wherein individual memories leave unique memory traces at the molecular level with distinct time courses. A better understanding of these mechanisms has implications for treatment of memory disorders caused by normal aging or diseases including schizophrenia, Alzheimer's, depression, and drug addiction.

  12. Laser vision: lidar as a transformative tool to advance critical zone science

    NASA Astrophysics Data System (ADS)

    Harpold, A. A.; Marshall, J. A.; Lyon, S. W.; Barnhart, T. B.; Fisher, B.; Donovan, M.; Brubaker, K. M.; Crosby, C. J.; Glenn, N. F.; Glennie, C. L.; Kirchner, P. B.; Lam, N.; Mankoff, K. D.; McCreight, J. L.; Molotch, N. P.; Musselman, K. N.; Pelletier, J.; Russo, T.; Sangireddy, H.; Sjöberg, Y.; Swetnam, T.; West, N.

    2015-01-01

    Laser vision: lidar as a transformative tool to advance critical zone science. Observation and quantification of the Earth surface is undergoing a revolutionary change due to the increased spatial resolution and extent afforded by light detection and ranging (lidar) technology. As a consequence, lidar-derived information has led to fundamental discoveries within the individual disciplines of geomorphology, hydrology, and ecology. These disciplines form the cornerstones of Critical Zone (CZ) science, where researchers study how interactions among the geosphere, hydrosphere, and ecosphere shape and maintain the "zone of life", extending from the groundwater to the vegetation canopy. Lidar holds promise as a transdisciplinary CZ research tool by simultaneously allowing for quantification of topographic, vegetative, and hydrological data. Researchers are just beginning to utilize lidar datasets to answer synergistic questions in CZ science, such as how landforms and soils develop in space and time as a function of the local climate, biota, hydrologic properties, and lithology. This review's objective is to demonstrate the transformative potential of lidar by critically assessing both challenges and opportunities for transdisciplinary lidar applications. A review of 147 peer-reviewed studies utilizing lidar showed that 38 % of the studies were focused in geomorphology, 18 % in hydrology, 32 % in ecology, and the remaining 12 % have an interdisciplinary focus. We find that using lidar to its full potential will require numerous advances across CZ applications, including new and more powerful open-source processing tools, exploiting new lidar acquisition technologies, and improved integration with physically-based models and complementary in situ and remote-sensing observations. We provide a five-year vision to utilize and advocate for the expanded use of lidar datasets to benefit CZ science applications.

  13. Molecular tools for bathing water assessment in Europe: Balancing social science research with a rapidly developing environmental science evidence-base.

    PubMed

    Oliver, David M; Hanley, Nick D; van Niekerk, Melanie; Kay, David; Heathwaite, A Louise; Rabinovici, Sharyl J M; Kinzelman, Julie L; Fleming, Lora E; Porter, Jonathan; Shaikh, Sabina; Fish, Rob; Chilton, Sue; Hewitt, Julie; Connolly, Elaine; Cummins, Andy; Glenk, Klaus; McPhail, Calum; McRory, Eric; McVittie, Alistair; Giles, Amanna; Roberts, Suzanne; Simpson, Katherine; Tinch, Dugald; Thairs, Ted; Avery, Lisa M; Vinten, Andy J A; Watts, Bill D; Quilliam, Richard S

    2016-02-01

    The use of molecular tools, principally qPCR, versus traditional culture-based methods for quantifying microbial parameters (e.g., Fecal Indicator Organisms) in bathing waters generates considerable ongoing debate at the science-policy interface. Advances in science have allowed the development and application of molecular biological methods for rapid (~2 h) quantification of microbial pollution in bathing and recreational waters. In contrast, culture-based methods can take between 18 and 96 h for sample processing. Thus, molecular tools offer an opportunity to provide a more meaningful statement of microbial risk to water-users by providing near-real-time information enabling potentially more informed decision-making with regard to water-based activities. However, complementary studies concerning the potential costs and benefits of adopting rapid methods as a regulatory tool are in short supply. We report on findings from an international Working Group that examined the breadth of social impacts, challenges, and research opportunities associated with the application of molecular tools to bathing water regulations.

  14. Development of Experimental and Computational Aeroacoustic Tools for Advanced Liner Evaluation

    NASA Technical Reports Server (NTRS)

    Jones, Michael G.; Watson, Willie R.; Nark, Douglas N.; Parrott, Tony L.; Gerhold, Carl H.; Brown, Martha C.

    2006-01-01

    Acoustic liners in aircraft engine nacelles suppress radiated noise. Therefore, as air travel increases, increasingly sophisticated tools are needed to maximize noise suppression. During the last 30 years, NASA has invested significant effort in development of experimental and computational acoustic liner evaluation tools. The Curved Duct Test Rig is a 152-mm by 381- mm curved duct that supports liner evaluation at Mach numbers up to 0.3 and source SPLs up to 140 dB, in the presence of user-selected modes. The Grazing Flow Impedance Tube is a 51- mm by 63-mm duct currently being fabricated to operate at Mach numbers up to 0.6 with source SPLs up to at least 140 dB, and will replace the existing 51-mm by 51-mm duct. Together, these test rigs allow evaluation of advanced acoustic liners over a range of conditions representative of those observed in aircraft engine nacelles. Data acquired with these test ducts are processed using three aeroacoustic propagation codes. Two are based on finite element solutions to convected Helmholtz and linearized Euler equations. The third is based on a parabolic approximation to the convected Helmholtz equation. The current status of these computational tools and their associated usage with the Langley test rigs is provided.

  15. Molecular Engineering of Vector-Based Oncolytic and Imaging Approaches for Advanced Prostate Cancer

    DTIC Science & Technology

    2006-02-01

    Oncolytic and Imaging Approaches for Advanced Prostate Cancer PRINCIPAL INVESTIGATOR: Lily Wu, M.D., Ph.D. CONTRACTING ORGANIZATION...SUBTITLE Molecular Engineering of Vector-based Oncolytic and Imaging Approaches for 5a. CONTRACT NUMBER Advanced Prostate Cancer 5b. GRANT...reproductions will be in black and white. 14. ABSTRACT Hormone refractory and metastatic prostate cancer are not well understood. Better animal models

  16. Molecular tools for differentiation of non-typeable Haemophilus influenzae from Haemophilus haemolyticus

    PubMed Central

    Pickering, Janessa; Richmond, Peter C.; Kirkham, Lea-Ann S.

    2014-01-01

    Non-typeable Haemophilus influenzae (NTHi) and Haemophilus haemolyticus are closely related bacteria that reside in the upper respiratory tract. NTHi is associated with respiratory tract infections that frequently result in antibiotic prescription whilst H. haemolyticus is rarely associated with disease. NTHi and H. haemolyticus can be indistinguishable by traditional culture methods and molecular differentiation has proven difficult. This current review chronologically summarizes the molecular approaches that have been developed for differentiation of NTHi from H. haemolyticus, highlighting the advantages and disadvantages of each target and/or technique. We also provide suggestions for the development of new tools that would be suitable for clinical and research laboratories. PMID:25520712

  17. [Targeted molecular therapy based on advanced cancer stem cell model].

    PubMed

    Hirao, Atsushi

    2015-08-01

    Improvement of cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (TICs). Although it was hypothesized that tumors are organized as hierarchies of tumor cells that are sustained by rare TICs, like normal tissue stem cells, there are several controversies towards such cancer stem cell model, e.g. reversible change of stem cell like population based on epigenetic changes, clonal genetic evolution and problems in xenotransplantation system. Despite complexity in cancer stem cell models, studies in cancer stem cell field have revealed that there are close relationship between cancer malignancy and stem cell properties, called "stemness". Understanding molecular mechanisms for controlling stemness would contribute to establishment of novel diagnostics or therapeutics for cancer.

  18. Recent Advances in Molecular Mechanisms of Taste Signaling and Modifying.

    PubMed

    Shigemura, Noriatsu; Ninomiya, Yuzo

    2016-01-01

    The sense of taste conveys crucial information about the quality and nutritional value of foods before it is ingested. Taste signaling begins with taste cells via taste receptors in oral cavity. Activation of these receptors drives the transduction systems in taste receptor cells. Then particular transmitters are released from the taste cells and activate corresponding afferent gustatory nerve fibers. Recent studies have revealed that taste sensitivities are defined by distinct taste receptors and modulated by endogenous humoral factors in a specific group of taste cells. Such peripheral taste generations and modifications would directly influence intake of nutritive substances. This review will highlight current understanding of molecular mechanisms for taste reception, signal transduction in taste bud cells, transmission between taste cells and nerves, regeneration from taste stem cells, and modification by humoral factors at peripheral taste organs.

  19. [Status and advances of RGD molecular imaging in lung cancer].

    PubMed

    Yue, Ning; Yuan, Shuanghu; Yang, Guoren

    2014-12-01

    Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD) peptides could combine with integrins specifically, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to reflect its changes. The lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

  20. Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC).

    PubMed

    Kumarakulasinghe, Nesaretnam Barr; van Zanwijk, Nico; Soo, Ross A

    2015-04-01

    Historically, patients with advanced stage non-small cell lung cancer (NSCLC) were treated with chemotherapy alone, but a therapeutic plateau has been reached. Advances in the understanding of molecular genetics have led to the recognition of multiple molecularly distinct subsets of NSCLC. This in turn has led to the development of rationally directed molecular targeted therapy, leading to improved clinical outcomes. Tumour genotyping for EGFR mutations and ALK rearrangement has meant chemotherapy is no longer given automatically as first-line treatment but reserved for when patients do not have a 'druggable' driver oncogene. In this review, we will address the current status of clinically relevant driver mutations and emerging new molecular subsets in lung adenocarcinoma and squamous cell carcinoma, and the role of targeted therapy and mechanisms of acquired resistance to targeted therapy.

  1. Molecular imprinting of proteins emerging as a tool for protein recognition.

    PubMed

    Takeuchi, Toshifumi; Hishiya, Takayuki

    2008-07-21

    This article gives the recent developments in molecular imprinting for proteins. Currently bio-macromolecules such as antibodies and enzymes are mainly employed for protein recognition purposes. However, such bio-macromolecules are sometimes difficult to find and/or produce, therefore, receptor-like synthetic materials such as protein-imprinted polymers have been intensively studied as substitutes for natural receptors. Recent advances in protein imprinting shown here demonstrate the possibility of this technique as a future technology of protein recognition.

  2. Solvation thermodynamic mapping of molecular surfaces in AmberTools: GIST.

    PubMed

    Ramsey, Steven; Nguyen, Crystal; Salomon-Ferrer, Romelia; Walker, Ross C; Gilson, Michael K; Kurtzman, Tom

    2016-08-05

    The expulsion of water from surfaces upon molecular recognition and nonspecific association makes a major contribution to the free energy changes of these processes. In order to facilitate the characterization of water structure and thermodynamics on surfaces, we have incorporated Grid Inhomogeneous Solvation Theory (GIST) into the CPPTRAJ toolset of AmberTools. GIST is a grid-based implementation of Inhomogeneous Fluid Solvation Theory, which analyzes the output from molecular dynamics simulations to map out solvation thermodynamic and structural properties on a high-resolution, three-dimensional grid. The CPPTRAJ implementation, called GIST-cpptraj, has a simple, easy-to-use command line interface, and is open source and freely distributed. We have also developed a set of open-source tools, called GISTPP, which facilitate the analysis of GIST output grids. Tutorials for both GIST-cpptraj and GISTPP can be found at ambermd.org. © 2016 Wiley Periodicals, Inc.

  3. Recent advances toward a molecular mechanism of efflux pump inhibition

    PubMed Central

    Opperman, Timothy J.; Nguyen, Son T.

    2015-01-01

    Multidrug resistance (MDR) in Gram-negative pathogens, such as the Enterobacteriaceae and Pseudomonas aeruginosa, poses a significant threat to our ability to effectively treat infections caused by these organisms. A major component in the development of the MDR phenotype in Gram-negative bacteria is overexpression of Resistance-Nodulation-Division (RND)-type efflux pumps, which actively pump antibacterial agents and biocides from the periplasm to the outside of the cell. Consequently, bacterial efflux pumps are an important target for developing novel antibacterial treatments. Potent efflux pump inhibitors (EPIs) could be used as adjunctive therapies that would increase the potency of existing antibiotics and decrease the emergence of MDR bacteria. Several potent inhibitors of RND-type efflux pump have been reported in the literature, and at least three of these EPI series were optimized in a pre-clinical development program. However, none of these compounds have been tested in the clinic. One of the major hurdles to the development of EPIs has been the lack of biochemical, computational, and structural methods that could be used to guide rational drug design. Here, we review recent reports that have advanced our understanding of the mechanism of action of several potent EPIs against RND-type pumps. PMID:25999939

  4. Molecular advancements in the development of thermostable phytases.

    PubMed

    Rebello, Sharrel; Jose, Leny; Sindhu, Raveendran; Aneesh, Embalil Mathachan

    2017-04-01

    Since the discovery of phytic acid in 1903 and phytase in 1907, extensive research has been carried out in the field of phytases, the phytic acid degradatory enzymes. Apart from forming backbone enzyme in the multimillion dollar-based feed industry, phytases extend a multifaceted role in animal nutrition, industries, human physiology, and agriculture. The utilization of phytases in industries is not effectively achieved most often due to the loss of its activity at high temperatures. The growing demand of thermostable phytases with high residual activity could be addressed by the combinatorial use of efficient phytase sources, protein engineering techniques, heterologous expression hosts, or thermoprotective coatings. The progress in phytase research can contribute to its economized production with a simultaneous reduction of various environmental problems such as eutrophication, greenhouse gas emission, and global warming. In the current review, we address the recent advances in the field of various natural as well as recombinant thermotolerant phytases, their significance, and the factors contributing to their thermotolerance.

  5. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    NASA Astrophysics Data System (ADS)

    Subramaniam, Prasad

    Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on

  6. The Congenital Muscular Dystrophies: Recent Advances and Molecular Insights

    PubMed Central

    Mendell, Jerry R.; Boué, Daniel R.; Martin, Paul T.

    2010-01-01

    Over the past decade, molecular understanding of the congenital muscular dystrophies (CMDs) has greatly expanded. The diseases can be classified into 3 major groups based on the affected genes and the location of their expressed protein: abnormalities of extracellular matrix proteins (LAMA2, COL6A1, COL6A2, COL6A3), abnormalities of membrane receptors for the extracellular matrix (fukutin, POMGnT1, POMT1, POMT2, FKRP, LARGE, and ITGA7), and abnormal endoplasmic reticulum protein (SEPN1). The diseases begin in the perinatal period or shortly thereafter. A specific diagnosis can be challenging because the muscle pathology is usually not distinctive. Immunostaining of muscle using a battery of antibodies can help define a disorder that will need confirmation by gene testing. In muscle diseases with overlapping pathological features, such as CMD, careful attention to the clinical clues (e.g., family history, central nervous system features) can help guide the battery of immunostains necessary to target an unequivocal diagnosis. PMID:17163796

  7. Advances in the Molecular Genetics of Non-syndromic Syndactyly

    PubMed Central

    Deng, Hao; Tan, Ting

    2015-01-01

    Syndactyly, webbing of adjacent digits with or without bony fusion, is one of the most common hereditary limb malformations. It occurs either as an isolated abnormality or as a component of more than 300 syndromic anomalies. There are currently nine types of phenotypically diverse nonsyndromic syndactyly. Non-syndromic syndactyly is usually inherited as an autosomal dominant trait, although the more severe presenting types and subtypes may show autosomal recessive or X-linked pattern of inheritance. The phenotype appears to be not only caused by a main gene, but also dependant on genetic background and subsequent signaling pathways involved in limb formation. So far, the principal genes identified to be involved in congenital syndactyly are mainly involved in the zone of polarizing activity and sonic hedgehog pathway. This review summarizes the recent progress made in the molecular genetics, including known genes and loci responsible for non-syndromic syndactyly, and the signaling pathways those genetic factors involved in, as well as clinical features and animal models. We hope our review will contribute to the understanding of underlying pathogenesis of this complicated disorder and have implication on genetic counseling. PMID:26069458

  8. Advances in the molecular genetics of non-syndromic polydactyly.

    PubMed

    Deng, Hao; Tan, Ting; Yuan, Lamei

    2015-10-30

    Polydactyly is one of the most common inherited limb abnormalities, characterised by supernumerary fingers or toes. It results from disturbances in the normal programme of the anterior-posterior axis of the developing limb, with diverse aetiology and variable inter- and intra-familial clinical features. Polydactyly can occur as an isolated disorder (non-syndromic polydactyly) or as a part of an anomaly syndrome (syndromic polydactyly). On the basis of the anatomic location of the duplicated digits, non-syndromic polydactyly is divided into three kinds, including preaxial polydactyly, axial polydactyly and postaxial polydactyly. Non-syndromic polydactyly frequently exhibits an autosomal dominant inheritance with variable penetrance. To date, in human, at least ten loci and four disease-causing genes, including the GLI3 gene, the ZNF141 gene, the MIPOL1 gene and the PITX1 gene, have been identified. In this paper, we review clinical features of non-syndromic polydactyly and summarise the recent progress in the molecular genetics, including loci and genes that are responsible for the disorder, the signalling pathways that these genetic factors are involved in, as well as animal models of the disorder. These progresses will improve our understanding of the complex disorder and have implications on genetic counselling such as prenatal diagnosis.

  9. Advanced Molecular Probes for Sequence-Specific DNA Recognition

    NASA Astrophysics Data System (ADS)

    Bertucci, Alessandro; Manicardi, Alex; Corradini, Roberto

    DNA detection can be achieved using the Watson-Crick base pairing with oligonucleotides or oligonucleotide analogs, followed by generation of a physical or chemical signal coupled with a transducer device. The nature of the probe is an essential feature which determines the performances of the sensing device. Many synthetic processes are presently available for "molecular engineering" of DNA probes, enabling label-free and PCR-free detection to be performed. Furthermore, many DNA analogs with improved performances are available and are under development; locked nucleic acids (LNA), peptide nucleic acids (PNA) and their analogs, morpholino oligonucleotides (MO) and other modified probes have shown improved properties of affinity and selectivity in target recognition compared to those of simple DNA probes. The performances of these probes in sensing devices, and the requirements for detection of unamplified DNA will be discussed in this chapter. Chemistry and architectures for conjugation of probes to reporter units, surfaces and nanostructures will also be discussed. Examples of probes used in ultrasensitive detection of unamplified DNA are listed.

  10. Molecular docking as a popular tool in drug design, an in silico travel

    PubMed Central

    de Ruyck, Jerome; Brysbaert, Guillaume; Blossey, Ralf; Lensink, Marc F

    2016-01-01

    New molecular modeling approaches, driven by rapidly improving computational platforms, have allowed many success stories for the use of computer-assisted drug design in the discovery of new mechanism-or structure-based drugs. In this overview, we highlight three aspects of the use of molecular docking. First, we discuss the combination of molecular and quantum mechanics to investigate an unusual enzymatic mechanism of a flavoprotein. Second, we present recent advances in anti-infectious agents’ synthesis driven by structural insights. At the end, we focus on larger biological complexes made by protein–protein interactions and discuss their relevance in drug design. This review provides information on how these large systems, even in the presence of the solvent, can be investigated with the outlook of drug discovery. PMID:27390530

  11. Molecular profiling--a tool for addressing emerging gaps in the comparative risk assessment of GMOs.

    PubMed

    Heinemann, Jack A; Kurenbach, Brigitta; Quist, David

    2011-10-01

    Assessing the risks of genetically modified organisms (GMOs) is required by both international agreement and domestic legislation. Many view the use of the "omics" tools for profiling classes of molecules as useful in risk assessment, but no consensus has formed on the need or value of these techniques for assessing the risks of all GMOs. In this and many other cases, experts support case-by-case use of molecular profiling techniques for risk assessment. We review the latest research on the applicability and usefulness of molecular profiling techniques for GMO risk assessment. As more and more kinds of GMOs and traits are developed, broader use of molecular profiling in a risk assessment may be required to supplement the comparative approach to risk assessment. The literature-based discussions on the use of profiling appear to have settled on two findings: 1. profiling techniques are reliable and relevant, at least no less so than other techniques used in risk assessment; and 2. although not required routinely, regulators should be aware of when they are needed. The dismissal of routine molecular profiling may be confusing to regulators who then lack guidance on when molecular profiling might be worthwhile. Molecular profiling is an important way to increase confidence in risk assessments if the profiles are properly designed to address relevant risks and are applied at the correct stage of the assessment.

  12. A decision support tool for synchronizing technology advances with strategic mission objectives

    NASA Technical Reports Server (NTRS)

    Hornstein, Rhoda S.; Willoughby, John K.

    1992-01-01

    Successful accomplishment of the objectives of many long-range future missions in areas such as space systems, land-use planning, and natural resource management requires significant technology developments. This paper describes the development of a decision-support data-derived tool called MisTec for helping strategic planners to determine technology development alternatives and to synchronize the technology development schedules with the performance schedules of future long-term missions. Special attention is given to the operations, concept, design, and functional capabilities of the MisTec. The MisTec was initially designed for manned Mars mission, but can be adapted to support other high-technology long-range strategic planning situations, making it possible for a mission analyst, planner, or manager to describe a mission scenario, determine the technology alternatives for making the mission achievable, and to plan the R&D activity necessary to achieve the required technology advances.

  13. Advanced Launch Technology Life Cycle Analysis Using the Architectural Comparison Tool (ACT)

    NASA Technical Reports Server (NTRS)

    McCleskey, Carey M.

    2015-01-01

    Life cycle technology impact comparisons for nanolauncher technology concepts were performed using an Affordability Comparison Tool (ACT) prototype. Examined are cost drivers and whether technology investments can dramatically affect the life cycle characteristics. Primary among the selected applications was the prospect of improving nanolauncher systems. As a result, findings and conclusions are documented for ways of creating more productive and affordable nanolauncher systems; e.g., an Express Lane-Flex Lane concept is forwarded, and the beneficial effect of incorporating advanced integrated avionics is explored. Also, a Functional Systems Breakdown Structure (F-SBS) was developed to derive consistent definitions of the flight and ground systems for both system performance and life cycle analysis. Further, a comprehensive catalog of ground segment functions was created.

  14. Plasmid vectors and molecular building blocks for the development of genetic manipulation tools for Trypanosoma cruzi.

    PubMed

    Bouvier, León A; Cámara, María de los Milagros; Canepa, Gaspar E; Miranda, Mariana R; Pereira, Claudio A

    2013-01-01

    The post genomic era revealed the need for developing better performing, easier to use and more sophisticated genetic manipulation tools for the study of Trypanosoma cruzi, the etiological agent of Chagas disease. In this work a series of plasmids that allow genetic manipulation of this protozoan parasite were developed. First of all we focused on useful tools to establish selection strategies for different strains and which can be employed as expression vectors. On the other hand molecular building blocks in the form of diverse selectable markers, modifiable fluorescent protein and epitope-tag coding sequences were produced. Both types of modules were harboured in backbone molecules conceived to offer multiple construction and sub-cloning strategies. These can be used to confer new properties to already available genetic manipulation tools or as starting points for whole novel designs. The performance of each plasmid and building block was determined independently. For illustration purposes, some simple direct practical applications were conducted.

  15. MO-C-BRE-01: The WMIS-AAPM Joint Symposium: Advances in Molecular Imaging

    SciTech Connect

    Contag, C; Pogue, B; Lewis, J

    2014-06-15

    This joint symposium of the World Molecular Imaging Society (WMIS) and the AAPM includes three luminary speakers discussing work in new paradigms of molecular imaging in cancer (Contag), applications of optical imaging technologies to radiation therapy (Pogue) and an update on PET imaging as a surrogate biomarker for cancer progression and response to therapy. Learning Objectives: Appreciate the current trends in molecular and systems imaging. Understand how optical imaging technologies, and particularly Cerenkov detectors, can be used in advancing radiation oncology. Stay current on new PET tracers - and targets - of interest in cancer treatment.

  16. eMovie: a storyboard-based tool for making molecular movies.

    PubMed

    Hodis, Eran; Schreiber, Gideon; Rother, Kristian; Sussman, Joel L

    2007-05-01

    The 3D structures of macromolecules are difficult to grasp and also to communicate. By their nature, movies or animations are particularly useful for highlighting key features by offering a 'guided tour' of structures and conformation changes. However, high-quality movies are rarely seen because they are currently difficult and time consuming to make. By adopting the traditional movie 'storyboard' concept, which gives guidance and direction to filming, eMovie makes the creation of lengthy molecular animations much easier. This tool is a plug-in for the open-source molecular graphics program PyMOL, and enables experts and novices alike to produce informative and high-quality molecular animations.

  17. Clinical applications of recent molecular advances in urologic malignancies: no longer chasing a "mirage"?

    PubMed

    Netto, George J

    2013-05-01

    As our understanding of the molecular events leading to the development and progression of genitourologic malignancies, new markers of detection, prognostication, and therapy prediction can be exploited in the management of these prevalent tumors. The current review discusses the recent advances in prostate, bladder, renal, and testicular neoplasms that are pertinent to the anatomic pathologist.

  18. Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology (Final Report)

    EPA Science Inventory

    EPA announced the release of the final report, Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology. This report describes new approaches that are faster, less resource intensive, and more robust that can help ...

  19. Complex Spine Pathology Simulator: An Innovative Tool for Advanced Spine Surgery Training.

    PubMed

    Gragnaniello, Cristian; Abou-Hamden, Amal; Mortini, Pietro; Colombo, Elena V; Bailo, Michele; Seex, Kevin A; Litvack, Zachary; Caputy, Anthony J; Gagliardi, Filippo

    2016-11-01

    Background Technical advancements in spine surgery have made possible the treatment of increasingly complex pathologies with less morbidity. Time constraints in surgeons' training have made it necessary to develop new training models for spine pathology. Objective To describe the application of a novel compound, Stratathane resin ST-504 derived polymer (SRSDP), that can be injected at different spinal target locations to mimic spinal epidural, subdural extra-axial, and intra-axial pathologies for the use in advanced surgical training. Material and Methods Fresh-frozen thoracolumbar and cervical spine segments of human and sheep cadavers were used to study the model. SRSDP is initially liquid after mixing, allowing it to be injected into target areas where it expands and solidifies, mimicking the entire spectrum of spinal pathologies. Results Different polymer concentrations have been codified to vary adhesiveness, texture, spread capability, deformability, and radiologic visibility. Polymer injection was performed under fluoroscopic guidance through pathology-specific injection sites that avoided compromising the surgical approach for subsequent excision of the artificial lesion. Inflation of a balloon catheter of the desired size was used to displace stiff cadaveric neurovascular structures to mimic pathology-related mass effect. Conclusion The traditional cadaveric training models principally only allow surgeons to practice the surgical approach. The complex spine pathology simulator is a novel educational tool that in a user-friendly, low-cost fashion allows trainees to practice advanced technical skills in the removal of complex spine pathology, potentially shortening some of the aspects of the learning curve of operative skills that may otherwise take many years to acquire.

  20. MATISSE: Multi-purpose Advanced Tool for Instruments for the Solar System Exploration .

    NASA Astrophysics Data System (ADS)

    Zinzi, A.; Capria, M. T.; Antonelli, L. A.

    In planetary sciences, design, assemble and launch onboard instruments are only preliminary steps toward the final aim of converting data into scientific knowledge, as the real challenge is the data analysis and interpretation. Up to now data have been generally stored in "old style" archives, i.e. common ftp servers where the user can manually search for data browsing directories organized in a time order manner. However, as datasets to be stored and searched become particularly large, this latter task absorbs a great part of the time, subtracting time to the real scientific work. In order to reduce the time spent to search and analyze data MATISSE (Multi-purpose Advanced Tool for Instruments for the Solar System Exploration), a new set of software tools developed together with the scientific teams of the instruments involved, is under development at ASDC (ASI Science Data Center), whose experience in space missions data management is well known (e.g., \\citealt{verrecchia07,pittori09,giommi09,massaro11}) and its features and aims will be presented here.

  1. Theoretical descriptions of electron transport through single molecules: Developing design tools for molecular electronic devices

    NASA Astrophysics Data System (ADS)

    Carroll, Natalie R.

    There are vast numbers of organic compounds that could be considered for use in molecular electronics. Hence there is a need for efficient and economical screening tools. Here we develop theoretical methods to describe electron transport through individual molecules, the ultimate goal of which is to establish design tools for molecular electronic devices. To successfully screen a compound for its use as a device component requires a proper representation of the quantum mechanics of electron transmission. In this work we report the development of tools for the description of electron transmission that are: Charge self-consistent, valid in the presence of a finite applied potential field and (in some cases) explicitly time-dependent. In addition, the tools can be extended to any molecular system, including biosystems, because they are free of restrictive parameterizations. Two approaches are explored: (1) correlation of substituent parameter values (sigma), (commonly found in organic chemistry textbooks) to properties associated with electron transport, (2) explicit tracking of the time evolution of the wave function of a nonstationary electron. In (1) we demonstrate that the a correlate strongly with features of the charge migration process, establishing them as useful indicators of electronic properties. In (2) we employ a time-dependent description of electron transport through molecular junctions. To date, the great majority of theoretical treatments of electron transport in molecular junctions have been of the time-independent variety. Time dependence, however, is critical to such properties as switching speeds in binary computer components and alternating current conductance, so we explored methods based on time-dependent quantum mechanics. A molecular junction is modeled as a single molecule sandwiched between two clusters of close-packed metal atoms or other donor and acceptor groups. The time dependence of electron transport is investigated by initially

  2. Laser vision: lidar as a transformative tool to advance critical zone science

    NASA Astrophysics Data System (ADS)

    Harpold, A. A.; Marshall, J. A.; Lyon, S. W.; Barnhart, T. B.; Fisher, B. A.; Donovan, M.; Brubaker, K. M.; Crosby, C. J.; Glenn, N. F.; Glennie, C. L.; Kirchner, P. B.; Lam, N.; Mankoff, K. D.; McCreight, J. L.; Molotch, N. P.; Musselman, K. N.; Pelletier, J.; Russo, T.; Sangireddy, H.; Sjöberg, Y.; Swetnam, T.; West, N.

    2015-06-01

    Observation and quantification of the Earth's surface is undergoing a revolutionary change due to the increased spatial resolution and extent afforded by light detection and ranging (lidar) technology. As a consequence, lidar-derived information has led to fundamental discoveries within the individual disciplines of geomorphology, hydrology, and ecology. These disciplines form the cornerstones of critical zone (CZ) science, where researchers study how interactions among the geosphere, hydrosphere, and biosphere shape and maintain the "zone of life", which extends from the top of unweathered bedrock to the top of the vegetation canopy. Fundamental to CZ science is the development of transdisciplinary theories and tools that transcend disciplines and inform other's work, capture new levels of complexity, and create new intellectual outcomes and spaces. Researchers are just beginning to use lidar data sets to answer synergistic, transdisciplinary questions in CZ science, such as how CZ processes co-evolve over long timescales and interact over shorter timescales to create thresholds, shifts in states and fluxes of water, energy, and carbon. The objective of this review is to elucidate the transformative potential of lidar for CZ science to simultaneously allow for quantification of topographic, vegetative, and hydrological processes. A review of 147 peer-reviewed lidar studies highlights a lack of lidar applications for CZ studies as 38 % of the studies were focused in geomorphology, 18 % in hydrology, 32 % in ecology, and the remaining 12 % had an interdisciplinary focus. A handful of exemplar transdisciplinary studies demonstrate lidar data sets that are well-integrated with other observations can lead to fundamental advances in CZ science, such as identification of feedbacks between hydrological and ecological processes over hillslope scales and the synergistic co-evolution of landscape-scale CZ structure due to interactions amongst carbon, energy, and water cycles

  3. Imaging mass spectrometry of the visual system: Advancing the molecular understanding of retina degenerations.

    PubMed

    Bowrey, Hannah E; Anderson, David M; Pallitto, Patrick; Gutierrez, Danielle B; Fan, Jie; Crouch, Rosalie K; Schey, Kevin L; Ablonczy, Zsolt

    2016-04-01

    Visual sensation is fundamental for quality of life, and loss of vision to retinal degeneration is a debilitating condition. The eye is the only part of the central nervous system that can be noninvasively observed with optical imaging. In the clinics, various spectroscopic methods provide high spatial resolution images of the fundus and the developing degenerative lesions. However, the currently utilized tools are not specific enough to establish the molecular underpinnings of retinal diseases. In contrast, mass spectrometric imaging (MSI) is a powerful tool to identify molecularly specific disease indicators and classification markers. This technique is particularly well suited to the eye, where molecular information can be correlated with clinical data collected via noninvasive diagnostic imaging modalities. Recent studies during the last few recent years have uncovered a plethora of new spatially defined molecular information on several vision-threatening diseases, including age-related macular degeneration, Stargardt disease, glaucoma, cataract, as well as lipid disorders. Even though MS inside the eye cannot be performed noninvasively, by linking diagnostic and molecular information, these studies are the first step toward the development of smart ophthalmic diagnostic and surgical tools. Here, we provide an overview of current approaches applying MSI technology to ocular pathology.

  4. The need for novel informatics tools for integrating and planning research in molecular and cellular cognition.

    PubMed

    Silva, Alcino J; Müller, Klaus-Robert

    2015-09-01

    The sheer volume and complexity of publications in the biological sciences are straining traditional approaches to research planning. Nowhere is this problem more serious than in molecular and cellular cognition, since in this neuroscience field, researchers routinely use approaches and information from a variety of areas in neuroscience and other biology fields. Additionally, the multilevel integration process characteristic of this field involves the establishment of experimental connections between molecular, electrophysiological, behavioral, and even cognitive data. This multidisciplinary integration process requires strategies and approaches that originate in several different fields, which greatly increases the complexity and demands of this process. Although causal assertions, where phenomenon A is thought to contribute or relate to B, are at the center of this integration process and key to research in biology, there are currently no tools to help scientists keep track of the increasingly more complex network of causal connections they use when making research decisions. Here, we propose the development of semiautomated graphical and interactive tools to help neuroscientists and other biologists, including those working in molecular and cellular cognition, to track, map, and weight causal evidence in research papers. There is a great need for a concerted effort by biologists, computer scientists, and funding institutions to develop maps of causal information that would aid in integration of research findings and in experiment planning.

  5. The need for novel informatics tools for integrating and planning research in molecular and cellular cognition

    PubMed Central

    Müller, Klaus-Robert

    2015-01-01

    The sheer volume and complexity of publications in the biological sciences are straining traditional approaches to research planning. Nowhere is this problem more serious than in molecular and cellular cognition, since in this neuroscience field, researchers routinely use approaches and information from a variety of areas in neuroscience and other biology fields. Additionally, the multilevel integration process characteristic of this field involves the establishment of experimental connections between molecular, electrophysiological, behavioral, and even cognitive data. This multidisciplinary integration process requires strategies and approaches that originate in several different fields, which greatly increases the complexity and demands of this process. Although causal assertions, where phenomenon A is thought to contribute or relate to B, are at the center of this integration process and key to research in biology, there are currently no tools to help scientists keep track of the increasingly more complex network of causal connections they use when making research decisions. Here, we propose the development of semiautomated graphical and interactive tools to help neuroscientists and other biologists, including those working in molecular and cellular cognition, to track, map, and weight causal evidence in research papers. There is a great need for a concerted effort by biologists, computer scientists, and funding institutions to develop maps of causal information that would aid in integration of research findings and in experiment planning. PMID:26286658

  6. New tools for the study of chromosome segregation and aneuploidy at the molecular level

    SciTech Connect

    Charlieu, J.P.; Marcais, B.; Laurent, A.M.; Roizes, G.

    1993-12-31

    The molecular mechanisms which allow the correct distribution of chromosomes during cell division are not yet well known. The centromere, because of its possible involvement in the attachment of sister chromatids and its participation in the formation of the kinetochore, may play an important role in these mechanisms. Trisomy 21 (down syndrome, DS) provides a good model for studying aneuploidy resulting from the dysfunction of the chromosome distribution process. A possible means of analyzing the mechanisms leading to non-disjunction (NDJ) could be to determine the origin of the supernumerary chromosome 21 and to attempt to find some structural or physical characteristics of the potentially responsible centromere. This could be performed by using molecular tools which allow each of the two parental chromosomes 21 to be distinguished. Possible markers suitable for this purpose are DNA fragments that exhibit length polymorphisms. We present here some examples of such molecular tools, and discuss ways to use them in order to study the parental origin and the meiotic stage of nondisjunction, and we propose an hypothesis suggesting a possible cause of nondisjunction in human chromosomes.

  7. Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer

    PubMed Central

    ANTONELLI, GIOVANNA; LIBRA, MASSIMO; PANEBIANCO, VINCENZO; RUSSO, ALESSIA ERIKA; VITALE, FELICE VITO; COLINA, PAOLO; D'ANGELO, ALESSANDRO; ROSSELLO, ROSALBA; FERRAÙ, FRANCESCO

    2016-01-01

    Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared with chemotherapy, they are particularly attractive for use in elderly patients, who are potentially more susceptible to the toxicity of systemic oncological therapies. However, studies on the activity of molecular-targeted agents in this aged patient setting are much more limited compared with those in their younger counterparts. In the present review, the literature on molecular-targeted therapy for elderly patients with advanced NSCLC is discussed. It is concluded that bevacizumab should be reserved only for highly select elderly patients with advanced NSCLC when the clinician deems it useful in the face of acceptable toxicities. In elderly patients with advanced epidermal growth factor receptor mutation-positive NSCLC, erlotinib and gefitinib appear to repeat the same favorable performance as that documented on a larger scale in the overall population of patients with activating mutations. A good toxicity profile is also confirmed for active molecules on different pathways, such as crizotinib. PMID:26870160

  8. Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer.

    PubMed

    Antonelli, Giovanna; Libra, Massimo; Panebianco, Vincenzo; Russo, Alessia Erika; Vitale, Felice Vito; Colina, Paolo; D'Angelo, Alessandro; Rossello, Rosalba; Ferraù, Francesco

    2016-01-01

    Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared with chemotherapy, they are particularly attractive for use in elderly patients, who are potentially more susceptible to the toxicity of systemic oncological therapies. However, studies on the activity of molecular-targeted agents in this aged patient setting are much more limited compared with those in their younger counterparts. In the present review, the literature on molecular-targeted therapy for elderly patients with advanced NSCLC is discussed. It is concluded that bevacizumab should be reserved only for highly select elderly patients with advanced NSCLC when the clinician deems it useful in the face of acceptable toxicities. In elderly patients with advanced epidermal growth factor receptor mutation-positive NSCLC, erlotinib and gefitinib appear to repeat the same favorable performance as that documented on a larger scale in the overall population of patients with activating mutations. A good toxicity profile is also confirmed for active molecules on different pathways, such as crizotinib.

  9. Laboratory Molecular Astrophysics as an Invaluable Tool in understanding Astronomical Observations.

    NASA Astrophysics Data System (ADS)

    Fraser, Helen Jane

    2015-08-01

    We are entering the decade of molecular astrochemistry: spectroscopic data pertaining to the interactions between baryonic matter and electromagnetic radiation are now at the forefront of astronomical observations. Elucidating such data is reliant on inputs from laboratory experiments, modeling, and theoretical chemistry / physics, a field that is intended to be a key focus for the proposed new commission in Laboratory Astrophysics.Here, we propose a “tour de force” review of some recent successes since the last GA in molecular astrophysics, particularly those that have been directly facilitated by laboratory data in Astrochemistry. It is vital to highlight to the astronomers that the absence of laboratory data from the literature would otherwise have precluded advances in our astronomical understanding, e.g:the detection of gas-phase water deep in pre-stellar cores,the detection of water and other molecular species in gravitationally lensed galaxies at z~6“Jumps” in the appearance or disappearance of molecules, including the very recent detection of the first branched organic molecule in the ISM, iso-propyl-cyanide,disentangling dense spectroscopic features in the sub-mm as measured by ALMA, Herschel and SOFIA, the so-called “weeds” and “flowers”,the first ''image'' of a CO snow-line in a protoplanetary disk.Looking forward, the advent of high spatial and spectral resolution telescopes, particularly ALMA, SKA E-ELT and JWST, will continue to drive forward the needs and interests of laboratory astrochemistry in the coming decade. We will look forward to five key areas where advances are expected, and both observational and laboratory techniques are evolving:-(a) understanding star forming regions at very high spatial and spectral senstivity and resolution(b) extragalactic astrochemistry(c) (exo-)planetary atmospheres, surfaces and Solar System sample return - linkinginterstellar and planetary chemistry(d) astrobiology - linking simple molecular

  10. Chronic phase advance alters circadian physiological rhythms and peripheral molecular clocks

    PubMed Central

    Wolff, Gretchen; Duncan, Marilyn J.

    2013-01-01

    Shifting the onset of light, acutely or chronically, can profoundly affect responses to infection, tumor progression, development of metabolic disease, and mortality in mammals. To date, the majority of phase-shifting studies have focused on acute exposure to a shift in the timing of the light cycle, whereas the consequences of chronic phase shifts alone on molecular rhythms in peripheral tissues such as skeletal muscle have not been studied. In this study, we tested the effect of chronic phase advance on the molecular clock mechanism in two phenotypically different skeletal muscles. The phase advance protocol (CPA) involved 6-h phase advances (earlier light onset) every 4 days for 8 wk. Analysis of the molecular clock, via bioluminescence recording, in the soleus and flexor digitorum brevis (FDB) muscles and lung demonstrated that CPA advanced the phase of the rhythm when studied immediately after CPA. However, if the mice were placed into free-running conditions (DD) for 2 wk after CPA, the molecular clock was not phase shifted in the two muscles but was still shifted in the lung. Wheel running behavior remained rhythmic in CPA mice; however, the endogenous period length of the free-running rhythm was significantly shorter than that of control mice. Core body temperature, cage activity, and heart rate remained rhythmic throughout the experiment, although the onset of the rhythms was significantly delayed with CPA. These results provide clues that lifestyles associated with chronic environmental desynchrony, such as shift work, can have disruptive effects on the molecular clock mechanism in peripheral tissues, including both types of skeletal muscle. Whether this can contribute, long term, to increased incidence of insulin resistance/metabolic disease requires further study. PMID:23703115

  11. Development, Implementation and Application of Micromechanical Analysis Tools for Advanced High Temperature Composites

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This document contains the final report to the NASA Glenn Research Center (GRC) for the research project entitled Development, Implementation, and Application of Micromechanical Analysis Tools for Advanced High-Temperature Composites. The research supporting this initiative has been conducted by Dr. Brett A. Bednarcyk, a Senior Scientist at OM in Brookpark, Ohio from the period of August 1998 to March 2005. Most of the work summarized herein involved development, implementation, and application of enhancements and new capabilities for NASA GRC's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) software package. When the project began, this software was at a low TRL (3-4) and at release version 2.0. Due to this project, the TRL of MAC/GMC has been raised to 7 and two new versions (3.0 and 4.0) have been released. The most important accomplishments with respect to MAC/GMC are: (1) A multi-scale framework has been built around the software, enabling coupled design and analysis from the global structure scale down to the micro fiber-matrix scale; (2) The software has been expanded to analyze smart materials; (3) State-of-the-art micromechanics theories have been implemented and validated within the code; (4) The damage, failure, and lifing capabilities of the code have been expanded from a very limited state to a vast degree of functionality and utility; and (5) The user flexibility of the code has been significantly enhanced. MAC/GMC is now the premier code for design and analysis of advanced composite and smart materials. It is a candidate for the 2005 NASA Software of the Year Award. The work completed over the course of the project is summarized below on a year by year basis. All publications resulting from the project are listed at the end of this report.

  12. Molecular modeling as a predictive tool for the development of solid dispersions.

    PubMed

    Maniruzzaman, Mohammed; Pang, Jiayun; Morgan, David J; Douroumis, Dennis

    2015-04-06

    In this study molecular modeling is introduced as a novel approach for the development of pharmaceutical solid dispersions. A computational model based on quantum mechanical (QM) calculations was used to predict the miscibility of various drugs in various polymers by predicting the binding strength between the drug and dimeric form of the polymer. The drug/polymer miscibility was also estimated by using traditional approaches such as Van Krevelen/Hoftyzer and Bagley solubility parameters or Flory-Huggins interaction parameter in comparison to the molecular modeling approach. The molecular modeling studies predicted successfully the drug-polymer binding energies and the preferable site of interaction between the functional groups. The drug-polymer miscibility and the physical state of bulk materials, physical mixtures, and solid dispersions were determined by thermal analysis (DSC/MTDSC) and X-ray diffraction. The produced solid dispersions were analyzed by X-ray photoelectron spectroscopy (XPS), which confirmed not only the exact type of the intermolecular interactions between the drug-polymer functional groups but also the binding strength by estimating the N coefficient values. The findings demonstrate that QM-based molecular modeling is a powerful tool to predict the strength and type of intermolecular interactions in a range of drug/polymeric systems for the development of solid dispersions.

  13. Fungal Identification Using Molecular Tools: A Primer for the Natural Products Research Community

    PubMed Central

    2017-01-01

    Fungi are morphologically, ecologically, metabolically, and phylogenetically diverse. They are known to produce numerous bioactive molecules, which makes them very useful for natural products researchers in their pursuit of discovering new chemical diversity with agricultural, industrial, and pharmaceutical applications. Despite their importance in natural products chemistry, identification of fungi remains a daunting task for chemists, especially those who do not work with a trained mycologist. The purpose of this review is to update natural products researchers about the tools available for molecular identification of fungi. In particular, we discuss (1) problems of using morphology alone in the identification of fungi to the species level; (2) the three nuclear ribosomal genes most commonly used in fungal identification and the potential advantages and limitations of the ITS region, which is the official DNA barcoding marker for species-level identification of fungi; (3) how to use NCBI-BLAST search for DNA barcoding, with a cautionary note regarding its limitations; (4) the numerous curated molecular databases containing fungal sequences; (5) the various protein-coding genes used to augment or supplant ITS in species-level identification of certain fungal groups; and (6) methods used in the construction of phylogenetic trees from DNA sequences to facilitate fungal species identification. We recommend that, whenever possible, both morphology and molecular data be used for fungal identification. Our goal is that this review will provide a set of standardized procedures for the molecular identification of fungi that can be utilized by the natural products research community. PMID:28199101

  14. 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

  15. NASA Advanced Concepts Office, Earth-To-Orbit Team Design Process and Tools

    NASA Technical Reports Server (NTRS)

    Waters, Eric D.; Garcia, Jessica; Threet, Grady E., Jr.; Phillips, Alan

    2013-01-01

    The Earth-to-Orbit Team (ETO) of the Advanced Concepts Office (ACO) at NASA Marshall Space Flight Center (MSFC) is considered the pre-eminent "go-to" group for pre-phase A and phase A concept definition. Over the past several years the ETO team has evaluated thousands of launch vehicle concept variations for a significant number of studies including agency-wide efforts such as the Exploration Systems Architecture Study (ESAS), Constellation, Heavy Lift Launch Vehicle (HLLV), Augustine Report, Heavy Lift Propulsion Technology (HLPT), Human Exploration Framework Team (HEFT), and Space Launch System (SLS). The ACO ETO Team is called upon to address many needs in NASA's design community; some of these are defining extremely large trade-spaces, evaluating advanced technology concepts which have not been addressed by a large majority of the aerospace community, and the rapid turn-around of highly time critical actions. It is the time critical actions, those often limited by schedule or little advanced warning, that have forced the five member ETO team to develop a design process robust enough to handle their current output level in order to meet their customer's needs. Based on the number of vehicle concepts evaluated over the past year this output level averages to four completed vehicle concepts per day. Each of these completed vehicle concepts includes a full mass breakdown of the vehicle to a tertiary level of subsystem components and a vehicle trajectory analysis to determine optimized payload delivery to specified orbital parameters, flight environments, and delta v capability. A structural analysis of the vehicle to determine flight loads based on the trajectory output, material properties, and geometry of the concept is also performed. Due to working in this fast-paced and sometimes rapidly changing environment, the ETO Team has developed a finely tuned process to maximize their delivery capabilities. The objective of this paper is to describe the interfaces

  16. NASA Advanced Concepts Office, Earth-To-Orbit Team Design Process and Tools

    NASA Technical Reports Server (NTRS)

    Waters, Eric D.; Creech, Dennis M.; Garcia, Jessica; Threet, Grady E., Jr.; Phillips, Alan

    2012-01-01

    The Earth-to-Orbit Team (ETO) of the Advanced Concepts Office (ACO) at NASA Marshall Space Flight Center (MSFC) is considered the pre-eminent go-to group for pre-phase A and phase A concept definition. Over the past several years the ETO team has evaluated thousands of launch vehicle concept variations for a significant number of studies including agency-wide efforts such as the Exploration Systems Architecture Study (ESAS), Constellation, Heavy Lift Launch Vehicle (HLLV), Augustine Report, Heavy Lift Propulsion Technology (HLPT), Human Exploration Framework Team (HEFT), and Space Launch System (SLS). The ACO ETO Team is called upon to address many needs in NASA s design community; some of these are defining extremely large trade-spaces, evaluating advanced technology concepts which have not been addressed by a large majority of the aerospace community, and the rapid turn-around of highly time critical actions. It is the time critical actions, those often limited by schedule or little advanced warning, that have forced the five member ETO team to develop a design process robust enough to handle their current output level in order to meet their customer s needs. Based on the number of vehicle concepts evaluated over the past year this output level averages to four completed vehicle concepts per day. Each of these completed vehicle concepts includes a full mass breakdown of the vehicle to a tertiary level of subsystem components and a vehicle trajectory analysis to determine optimized payload delivery to specified orbital parameters, flight environments, and delta v capability. A structural analysis of the vehicle to determine flight loads based on the trajectory output, material properties, and geometry of the concept is also performed. Due to working in this fast-paced and sometimes rapidly changing environment, the ETO Team has developed a finely tuned process to maximize their delivery capabilities. The objective of this paper is to describe the interfaces

  17. NACE: A web-based tool for prediction of intercompartmental efficiency of human molecular genetic networks.

    PubMed

    Popik, Olga V; Ivanisenko, Timofey V; Saik, Olga V; Petrovskiy, Evgeny D; Lavrik, Inna N; Ivanisenko, Vladimir A

    2016-06-15

    Molecular genetic processes generally involve proteins from distinct intracellular localisations. Reactions that follow the same process are distributed among various compartments within the cell. In this regard, the reaction rate and the efficiency of biological processes can depend on the subcellular localisation of proteins. Previously, the authors proposed a method of evaluating the efficiency of biological processes based on the analysis of the distribution of protein subcellular localisation (Popik et al., 2014). Here, NACE is presented, which is an open access web-oriented program that implements this method and allows the user to evaluate the intercompartmental efficiency of human molecular genetic networks. The method has been extended by a new feature that provides the evaluation of the tissue-specific efficiency of networks for more than 2800 anatomical structures. Such assessments are important in cases when molecular genetic pathways in different tissues proceed with the participation of various proteins with a number of intracellular localisations. For example, an analysis of KEGG pathways, conducted using the developed program, showed that the efficiencies of many KEGG pathways are tissue-specific. Analysis of efficiencies of regulatory pathways in the liver, linking proteins of the hepatitis C virus with human proteins involved in the KEGG apoptosis pathway, showed that intercompartmental efficiency might play an important role in host-pathogen interactions. Thus, the developed tool can be useful in the study of the effectiveness of functioning of various molecular genetic networks, including metabolic, regulatory, host-pathogen interactions and others taking into account tissue-specific gene expression. The tool is available via the following link: http://www-bionet.sscc.ru/nace/.

  18. Translating molecular advances in fragile X syndrome into therapy: a review.

    PubMed

    Hagerman, Randi J; Des-Portes, Vincent; Gasparini, Fabrizio; Jacquemont, Sébastien; Gomez-Mancilla, Baltazar

    2014-04-01

    Fragile X syndrome is an inherited disease with cognitive, behavioral, and neurologic manifestations, resulting from a single genetic mutation. A variety of treatments that target individual symptoms of fragile X syndrome are currently utilized with limited efficacy. Research in animal models has resulted in the development of potential novel pharmacologic treatments that target the underlying molecular defect in fragile X syndrome, rather than the resultant symptoms. This review describes recent advances in our understanding of the molecular basis of fragile X syndrome and summarizes the ongoing clinical research programs.

  19. Advance of Molecular Imaging Technology and Targeted Imaging Agent in Imaging and Therapy

    PubMed Central

    Chen, Zhi-Yi; Wang, Yi-Xiang; Lin, Yan; Zhang, Jin-Shan; Yang, Feng; Zhou, Qiu-Lan; Liao, Yang-Ying

    2014-01-01

    Molecular imaging is an emerging field that integrates advanced imaging technology with cellular and molecular biology. It can realize noninvasive and real time visualization, measurement of physiological or pathological process in the living organism at the cellular and molecular level, providing an effective method of information acquiring for diagnosis, therapy, and drug development and evaluating treatment of efficacy. Molecular imaging requires high resolution and high sensitive instruments and specific imaging agents that link the imaging signal with molecular event. Recently, the application of new emerging chemical technology and nanotechnology has stimulated the development of imaging agents. Nanoparticles modified with small molecule, peptide, antibody, and aptamer have been extensively applied for preclinical studies. Therapeutic drug or gene is incorporated into nanoparticles to construct multifunctional imaging agents which allow for theranostic applications. In this review, we will discuss the characteristics of molecular imaging, the novel imaging agent including targeted imaging agent and multifunctional imaging agent, as well as cite some examples of their application in molecular imaging and therapy. PMID:24689058

  20. How Project Management Tools Aid in Association to Advance Collegiate Schools of Business (AACSB) International Maintenance of Accreditation

    ERIC Educational Resources Information Center

    Cann, Cynthia W.; Brumagim, Alan L.

    2008-01-01

    The authors present the case of one business college's use of project management techniques as tools for accomplishing Association to Advance Collegiate Schools of Business (AACSB) International maintenance of accreditation. Using these techniques provides an efficient and effective method of organizing maintenance efforts. In addition, using…

  1. Ares First Stage "Systemology" - Combining Advanced Systems Engineering and Planning Tools to Assure Mission Success

    NASA Technical Reports Server (NTRS)

    Seiler, James; Brasfield, Fred; Cannon, Scott

    2008-01-01

    Ares is an integral part of NASA s Constellation architecture that will provide crew and cargo access to the International Space Station as well as low earth orbit support for lunar missions. Ares replaces the Space Shuttle in the post 2010 time frame. Ares I is an in-line, two-stage rocket topped by the Orion Crew Exploration Vehicle, its service module, and a launch abort system. The Ares I first stage is a single, five-segment reusable solid rocket booster derived from the Space Shuttle Program's reusable solid rocket motor. The Ares second or upper stage is propelled by a J-2X main engine fueled with liquid oxygen and liquid hydrogen. This paper describes the advanced systems engineering and planning tools being utilized for the design, test, and qualification of the Ares I first stage element. Included are descriptions of the current first stage design, the milestone schedule requirements, and the marriage of systems engineering, detailed planning efforts, and roadmapping employed to achieve these goals.

  2. Development of molecular targeted drugs for advanced thyroid cancer in Japan.

    PubMed

    Takami, Hiroshi; Ito, Koichi; Sugino, Kiminori

    2014-01-01

    Up until now there have been no promising drugs for the treatment of advanced thyroid cancer, but the development of novel therapeutic agents is now anticipated as a result of the advent of molecular targeted drugs that inhibit tumor growth signals or angiogenesis. Against a background in which the development of numerous molecular targeted drugs for advanced thyroid cancer is being pursued worldwide, the development of sorafenib, vandetanib, and lenvatinib is currently also under way in Japan. All three of these compounds are undergoing phase 3 trials or have been approved abroad, and because they are in the final stage of development in Japan, they are expected to be introduced in clinical settings in the near future. After they have been introduced, it will be necessary to understand the differences between these compounds and to administer them to patients appropriately.

  3. Using molecular visualization to explore protein structure and function and enhance student facility with computational tools.

    PubMed

    Terrell, Cassidy R; Listenberger, Laura L

    2017-02-01

    Recognizing that undergraduate students can benefit from analysis of 3D protein structure and function, we have developed a multiweek, inquiry-based molecular visualization project for Biochemistry I students. This project uses a virtual model of cyclooxygenase-1 (COX-1) to guide students through multiple levels of protein structure analysis. The first assignment explores primary structure by generating and examining a protein sequence alignment. Subsequent assignments introduce 3D visualization software to explore secondary, tertiary, and quaternary structure. Students design an inhibitor, based on scrutiny of the enzyme active site, and evaluate the fit of the molecule using computed binding energies. In the last assignment, students introduce a point mutation to model the active site of the related COX-2 enzyme and analyze the impact of the mutation on inhibitor binding. With this project we aim to increase knowledge about, and confidence in using, online databases and computational tools. Here, we share results of our mixed methods pre- and postsurvey demonstrating student gains in knowledge about, and confidence using, online databases and computational tools. © 2017 by The International Union of Biochemistry and Molecular Biology, 2017.

  4. Molecular Paleoparasitological Hybridization Approach as Effective Tool for Diagnosing Human Intestinal Parasites from Scarce Archaeological Remains

    PubMed Central

    Jaeger, Lauren Hubert; Iñiguez, Alena Mayo

    2014-01-01

    Paleoparasitology is the science that uses parasitological techniques for diagnosing parasitic diseases in the past. Advances in molecular biology brought new insights into this field allowing the study of archaeological material. However, due to technical limitations a proper diagnosis and confirmation of the presence of parasites is not always possible, especially in scarce and degraded archaeological remains. In this study, we developed a Molecular Paleoparasitological Hybridization (MPH) approach using ancient DNA (aDNA) hybridization to confirm and complement paleoparasitological diagnosis. Eight molecular targets from four helminth parasites were included: Ascaris sp., Trichuris trichiura, Enterobius vermicularis, and Strongyloides stercoralis. The MPH analysis using 18th century human remains from Praça XV cemetery (CPXV), Rio de Janeiro, Brazil, revealed for the first time the presence E. vermicularis aDNA (50%) in archaeological sites of Brazil. Besides, the results confirmed T. trichiura and Ascaris sp. infections. The prevalence of infection by Ascaris sp. and E. vermicularis increased considerably when MPH was applied. However, a lower aDNA detection of T. trichiura (40%) was observed when compared to the diagnosis by paleoparasitological analysis (70%). Therefore, based on these data, we suggest a combination of Paleoparasitological and MPH approaches to verify the real panorama of intestinal parasite infection in human archeological samples. PMID:25162694

  5. Malignant pleural mesothelioma and mesothelial hyperplasia: A new molecular tool for the differential diagnosis.

    PubMed

    Bruno, Rossella; Alì, Greta; Giannini, Riccardo; Proietti, Agnese; Lucchi, Marco; Chella, Antonio; Melfi, Franca; Mussi, Alfredo; Fontanini, Gabriella

    2017-01-10

    Malignant pleural mesothelioma (MPM) is a rare asbestos related cancer, aggressive and unresponsive to therapies. Histological examination of pleural lesions is the gold standard of MPM diagnosis, although it is sometimes hard to discriminate the epithelioid type of MPM from benign mesothelial hyperplasia (MH).This work aims to define a new molecular tool for the differential diagnosis of MPM, using the expression profile of 117 genes deregulated in this tumour.The gene expression analysis was performed by nanoString System on tumour tissues from 36 epithelioid MPM and 17 MH patients, and on 14 mesothelial pleural samples analysed in a blind way. Data analysis included raw nanoString data normalization, unsupervised cluster analysis by Pearson correlation, non-parametric Mann Whitney U-test and molecular classification by the Uncorrelated Shrunken Centroid (USC) Algorithm.The Mann-Whitney U-test found 35 genes upregulated and 31 downregulated in MPM. The unsupervised cluster analysis revealed two clusters, one composed only of MPM and one only of MH samples, thus revealing class-specific gene profiles. The Uncorrelated Shrunken Centroid algorithm identified two classifiers, one including 22 genes and the other 40 genes, able to properly classify all the samples as benign or malignant using gene expression data; both classifiers were also able to correctly determine, in a blind analysis, the diagnostic categories of all the 14 unknown samples.In conclusion we delineated a diagnostic tool combining molecular data (gene expression) and computational analysis (USC algorithm), which can be applied in the clinical practice for the differential diagnosis of MPM.

  6. Fluorescent protein-scorpion toxin chimera is a convenient molecular tool for studies of potassium channels

    PubMed Central

    Kuzmenkov, Alexey I.; Nekrasova, Oksana V.; Kudryashova, Kseniya S.; Peigneur, Steve; Tytgat, Jan; Stepanov, Alexey V.; Kirpichnikov, Mikhail P.; Grishin, Eugene V.; Feofanov, Alexey V.; Vassilevski, Alexander A.

    2016-01-01

    Ion channels play a central role in a host of physiological and pathological processes and are the second largest target for existing drugs. There is an increasing need for reliable tools to detect and visualize particular ion channels, but existing solutions suffer from a number of limitations such as high price, poor specificity, and complicated protocols. As an alternative, we produced recombinant chimeric constructs (FP-Tx) consisting of fluorescent proteins (FP) fused with potassium channel toxins from scorpion venom (Tx). In particular, we used two FP, eGFP and TagRFP, and two Tx, OSK1 and AgTx2, to create eGFP-OSK1 and RFP-AgTx2. We show that these chimeras largely retain the high affinity of natural toxins and display selectivity to particular ion channel subtypes. FP-Tx are displaced by other potassium channel blockers and can be used as an imaging tool in ion channel ligand screening setups. We believe FP-Tx chimeras represent a new efficient molecular tool for neurobiology. PMID:27650866

  7. BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine

    NASA Astrophysics Data System (ADS)

    Liu, Zhongyang; Guo, Feifei; Wang, Yong; Li, Chun; Zhang, Xinlei; Li, Honglei; Diao, Lihong; Gu, Jiangyong; Wang, Wei; Li, Dong; He, Fuchu

    2016-02-01

    Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM’s diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients’ target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ’s cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the “multi-component, multi-target and multi-pathway” combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM’s molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm.

  8. Molecular Typing of Mycobacterium Tuberculosis Strains: A Fundamental Tool for Tuberculosis Control and Elimination.

    PubMed

    Cannas, Angela; Mazzarelli, Antonio; Di Caro, Antonino; Delogu, Giovanni; Girardi, Enrico

    2016-06-24

    Tuberculosis (TB) is still an important cause of morbidity and mortality worldwide. An improvement of the strategies for disease control is necessary in both low- and high-incidence TB countries. Clinicians, epidemiologists, laboratory specialists, and public health players should work together in order to achieve a significant reduction in TB transmission and spread of drug-resistant strains. Effective TB surveillance relies on early diagnosis of new cases, appropriate therapy, and accurate detection of outbreaks in the community, in order to implement proper TB control strategies. To achieve this goal, information from classical and molecular epidemiology, together with patient clinical data need to be combined. In this review, we summarize the methodologies currently used in molecular epidemiology, namely molecular typing. We will discuss their efficiency to phylogenetically characterize Mycobacterium tuberculosis isolates, and their ability to provide information that can be useful for disease control. We will also introduce next generation sequencing as the methodology that potentially could provide in a short time both, detection of new outbreaks and identification of resistance patterns. This could envision a potential of next generation sequencing as an important tool for accurate patient management and disease control.

  9. BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine

    PubMed Central

    Liu, Zhongyang; Guo, Feifei; Wang, Yong; Li, Chun; Zhang, Xinlei; Li, Honglei; Diao, Lihong; Gu, Jiangyong; Wang, Wei; Li, Dong; He, Fuchu

    2016-01-01

    Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM’s diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients’ target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ’s cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the “multi-component, multi-target and multi-pathway” combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM’s molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm. PMID:26879404

  10. BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine.

    PubMed

    Liu, Zhongyang; Guo, Feifei; Wang, Yong; Li, Chun; Zhang, Xinlei; Li, Honglei; Diao, Lihong; Gu, Jiangyong; Wang, Wei; Li, Dong; He, Fuchu

    2016-02-16

    Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM's diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients' target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ's cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the "multi-component, multi-target and multi-pathway" combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM's molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm.

  11. Predictive Modeling of Estrogen Receptor Binding Agents Using Advanced Cheminformatics Tools and Massive Public Data

    PubMed Central

    Ribay, Kathryn; Kim, Marlene T.; Wang, Wenyi; Pinolini, Daniel; Zhu, Hao

    2016-01-01

    Estrogen receptors (ERα) are a critical target for drug design as well as a potential source of toxicity when activated unintentionally. Thus, evaluating potential ERα binding agents is critical in both drug discovery and chemical toxicity areas. Using computational tools, e.g., Quantitative Structure-Activity Relationship (QSAR) models, can predict potential ERα binding agents before chemical synthesis. The purpose of this project was to develop enhanced predictive models of ERα binding agents by utilizing advanced cheminformatics tools that can integrate publicly available bioassay data. The initial ERα binding agent data set, consisting of 446 binders and 8307 non-binders, was obtained from the Tox21 Challenge project organized by the NIH Chemical Genomics Center (NCGC). After removing the duplicates and inorganic compounds, this data set was used to create a training set (259 binders and 259 non-binders). This training set was used to develop QSAR models using chemical descriptors. The resulting models were then used to predict the binding activity of 264 external compounds, which were available to us after the models were developed. The cross-validation results of training set [Correct Classification Rate (CCR) = 0.72] were much higher than the external predictivity of the unknown compounds (CCR = 0.59). To improve the conventional QSAR models, all compounds in the training set were used to search PubChem and generate a profile of their biological responses across thousands of bioassays. The most important bioassays were prioritized to generate a similarity index that was used to calculate the biosimilarity score between each two compounds. The nearest neighbors for each compound within the set were then identified and its ERα binding potential was predicted by its nearest neighbors in the training set. The hybrid model performance (CCR = 0.94 for cross validation; CCR = 0.68 for external prediction) showed significant improvement over the original QSAR

  12. The Advanced Dementia Prognostic Tool (ADEPT): A Risk Score to Estimate Survival in Nursing Home Residents with Advanced Dementia

    PubMed Central

    Mitchell, Susan L.; Miller, Susan C.; Teno, Joan M.; Davis, Roger B.; Shaffer, Michele L.

    2010-01-01

    Context Estimating life expectancy is challenging in advanced dementia. Objectives To create a risk score to estimate survival in nursing home (NH) residents with advanced dementia. Methods This was a retrospective cohort study performed in the setting of all licensed US NHs. Residents with advanced dementia living in US NHs in 2002 were identified using Minimum Data Set (MDS) assessments. Mortality data from Medicare files were used to determine 12-month survival. Independent variables were selected from the MDS. Cox proportional hazards regression was used to model survival. The accuracy of the final model was assessed using the area under the receiver operating characteristic curve (AUROC). To develop a risk score, points were assigned to variables in the final model based on parameter estimates. Residents meeting hospice eligibility guidelines for dementia, based on MDS data, were identified. The AUROC assessed the accuracy of hospice guidelines to predict six-month survival. Results Over 12 months, 40.6% of residents with advanced dementia (n=22,405) died. Twelve variables best predicted survival: length of stay, age, male, dyspnea, pressure ulcers, total functional dependence, bedfast, insufficient intake, bowel incontinence, body mass index, weight loss, and congestive heart failure. The AUROC for the final model was 0.68. The risk score ranged from 0–32 points (higher scores indicate worse survival). Only 15.9% of residents met hospice eligibility guidelines for which the AUROC predicting six-month survival was 0.53. Conclusion A mortality risk score derived from MDS data predicted six-month survival in advanced dementia with moderate accuracy. The predictive ability of hospice guidelines, simulated with MDS data, was poor. PMID:20621437

  13. Advanced Differential Radar Interferometry (A-DInSAR) as integrative tool for a structural geological analysis

    NASA Astrophysics Data System (ADS)

    Crippa, B.; Calcagni, L.; Rossi, G.; Sternai, P.

    2009-04-01

    Advanced Differential SAR interferometry (A-DInSAR) is a technique monitoring large-coverage surface deformations using a stack of interferograms generated from several complex SLC SAR images, acquired over the same target area at different times. In this work are described the results of a procedure to calculate terrain motion velocity on highly correlated pixels (E. Biescas, M. Crosetto, M. Agudo, O. Monserrat e B. Crippa: Two Radar Interferometric Approaches to Monitor Slow and Fast Land Deformation, 2007) in two area Gemona - Friuli, Northern Italy, Pollino - Calabria, Southern Italy, and, furthermore, are presented some consideration, based on successful examples of the present analysis. The choice of these pixels whose displacement velocity is calculated depends on the dispersion index value (DA) or using coherence values along the stack interferograms. A-DInSAR technique allows to obtain highly reliable velocity values of the vertical displacement. These values concern the movement of minimum surfaces of about 80m2 at the maximum resolution and the minimum velocity that can be recognized is of the order of mm/y. Because of the high versatility of the technology, because of the large dimensions of the area that can be analyzed (of about 10000Km2) and because of the high precision and reliability of the results obtained, we think it is possible to exploit radar interferometry to obtain some important information about the structural context of the studied area, otherwise very difficult to recognize. Therefore we propose radar interferometry as a valid investigation tool whose results must be considered as an important integration of the data collected in fieldworks.

  14. PGAdb-builder: A web service tool for creating pan-genome allele database for molecular fine typing

    PubMed Central

    Liu, Yen-Yi; Chiou, Chien-Shun; Chen, Chih-Chieh

    2016-01-01

    With the advance of next generation sequencing techniques, whole genome sequencing (WGS) is expected to become the optimal method for molecular subtyping of bacterial isolates. To use WGS as a general subtyping method for disease outbreak investigation and surveillance, the layout of WGS-based typing must be comparable among laboratories. Whole genome multilocus sequence typing (wgMLST) is an approach that achieves this requirement. To apply wgMLST as a standard subtyping approach, a pan-genome allele database (PGAdb) for the population of a bacterial organism must first be established. We present a free web service tool, PGAdb-builder (http://wgmlstdb.imst.nsysu.edu.tw), for the construction of bacterial PGAdb. The effectiveness of PGAdb-builder was tested by constructing a pan-genome allele database for Salmonella enterica serovar Typhimurium, with the database being applied to create a wgMLST tree for a panel of epidemiologically well-characterized S. Typhimurium isolates. The performance of the wgMLST-based approach was as high as that of the SNP-based approach in Leekitcharoenphon’s study used for discerning among epidemiologically related and non-related isolates. PMID:27824078

  15. Fluorescent Resonance Energy Transfer: A Tool for Probing Molecular Cell-Biomaterial Interactions in Three Dimensions

    PubMed Central

    Huebsch, Nathaniel D.; Mooney, David J.

    2007-01-01

    The current paradigm in designing biomaterials is to optimize material chemical and physical parameters based on correlations between these parameters and downstream biological responses, whether in vitro or in vivo. Extensive developments in molecular design of biomaterials have facilitated identification of several biophysical and biochemical variables (e.g. adhesion peptide density, substrate elastic modulus) as being critical to cell response. However, these empirical observations do not indicate whether different parameters elicit cell responses by modulating redundant variables of the cell-material interface (e.g. number of cell-material bonds, cell-matrix mechanics). Recently, a molecular fluorescence technique, Fluorescence Resonance Energy Transfer (FRET) has been applied to quantitatively analyze parameters of the cell-material interface for both two and three-dimensional adhesion substrates. Tools based on FRET have been utilized to quantify several parameters of the cell-material interface relevant to cell response, including molecular changes in matrix proteins induced by interactions both with surfaces and cells, the number of bonds between integrins and their adhesion ligands, and changes in the crosslink density of hydrogel synthetic extracellular matrix analogs. As such techniques allow both dynamic and 3D analyses they will be useful to quantitatively relate downstream cellular responses (e.g. gene expression) to the composition of this interface. Such understanding will allow bioengineers to fully exploit the potential of biomaterials engineered on the molecular scale, by optimizing material chemical and physical properties to a measurable set of interfacial parameters known to elicit a predictable response in a specific cell population. This will facilitate the rational design of complex, multi-functional biomaterials used as model systems for studying diseases or for clinical applications. PMID:17270268

  16. New Tools and New Biology: Recent Miniaturized Systems for Molecular and Cellular Biology

    PubMed Central

    Hamon, Morgan; Hong, Jong Wook

    2013-01-01

    Recent advances in applied physics and chemistry have led to the development of novel microfluidic systems. Microfluidic systems allow minute amounts of reagents to be processed using μm-scale channels and offer several advantages over conventional analytical devices for use in biological sciences: faster, more accurate and more reproducible analytical performance, reduced cell and reagent consumption, portability, and integration of functional components in a single chip. In this review, we introduce how microfluidics has been applied to biological sciences. We first present an overview of the fabrication of microfluidic systems and describe the distinct technologies available for biological research. We then present examples of microsystems used in biological sciences, focusing on applications in molecular and cellular biology. PMID:24305843

  17. Ultrasmall volume molecular isothermal amplification in microfluidic chip with advanced surface processing

    NASA Astrophysics Data System (ADS)

    Huang, Guoliang; Ma, Li; Yang, Xiaoyong; Yang, Xu

    2011-01-01

    In this paper, we developed a metal micro-fluidic chip with advanced surface processing for ultra-small volume molecular isothermal amplification. This method takes advantages of the nucleic acid amplification with good stability and consistency, high sensitivity about 31 genomic DNA copies and bacteria specific gene identification. Based on the advanced surface processing, the bioreaction assays of nucleic acid amplification was dropped about 392nl in volume. A high numerical aperture confocal optical detection system was advanced to sensitively monitor the DNA amplification with low noise and high power collecting fluorescence near to the optical diffraction limit. A speedy nucleic acid isothermal amplification was performed in the ultra-small volume microfluidic chip, where the time at the inflexions of second derivative to DNA exponential amplified curves was brought forward and the sensitivity was improved about 65 folds to that of in current 25μl Ep-tube amplified reaction, which indicates a promising clinic molecular diagnostics in the droplet amplification.

  18. Bio-AIMS Collection of Chemoinformatics Web Tools based on Molecular Graph Information and Artificial Intelligence Models.

    PubMed

    Munteanu, Cristian R; Gonzalez-Diaz, Humberto; Garcia, Rafael; Loza, Mabel; Pazos, Alejandro

    2015-01-01

    The molecular information encoding into molecular descriptors is the first step into in silico Chemoinformatics methods in Drug Design. The Machine Learning methods are a complex solution to find prediction models for specific biological properties of molecules. These models connect the molecular structure information such as atom connectivity (molecular graphs) or physical-chemical properties of an atom/group of atoms to the molecular activity (Quantitative Structure - Activity Relationship, QSAR). Due to the complexity of the proteins, the prediction of their activity is a complicated task and the interpretation of the models is more difficult. The current review presents a series of 11 prediction models for proteins, implemented as free Web tools on an Artificial Intelligence Model Server in Biosciences, Bio-AIMS (http://bio-aims.udc.es/TargetPred.php). Six tools predict protein activity, two models evaluate drug - protein target interactions and the other three calculate protein - protein interactions. The input information is based on the protein 3D structure for nine models, 1D peptide amino acid sequence for three tools and drug SMILES formulas for two servers. The molecular graph descriptor-based Machine Learning models could be useful tools for in silico screening of new peptides/proteins as future drug targets for specific treatments.

  19. Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis.

    PubMed

    Safaee, Michael; Oh, Michael C; Bloch, Orin; Sun, Matthew Z; Kaur, Gurvinder; Auguste, Kurtis I; Tihan, Tarik; Parsa, Andrew T

    2013-03-01

    Choroid plexus papillomas are rare, benign tumors originating from the choroid plexus. Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. We sought to review recent advances in our understanding of the molecular biology and oncogenic pathways associated with this disease. A comprehensive PubMed literature review was conducted to identify manuscripts discussing the clinical, molecular, and genetic features of choroid plexus papillomas. Articles concerning diagnosis, treatment, and long-term patient outcomes were also reviewed. The introduction of atypical choroid plexus papilloma as a distinct entity has increased the need for accurate histopathologic diagnosis. Advances in immunohistochemical staining have improved our ability to differentiate choroid plexus papillomas from other intracranial tumors or metastatic lesions using combinations of key markers and mitotic indices. Recent findings have implicated Notch3 signaling, the transcription factor TWIST1, platelet-derived growth factor receptor, and the tumor necrosis factor-related apoptosis-inducing ligand pathway in choroid plexus papilloma tumorigenesis. A combination of commonly occurring chromosomal duplications and deletions has also been identified. Surgical resection remains the standard of care, although chemotherapy and radiotherapy may be considered for recurrent or metastatic lesions. While generally considered benign, these tumors possess a complex biology that sheds insight into other choroid plexus tumors, particularly malignant choroid plexus carcinomas. Improving our understanding of the molecular biology, genetics, and oncogenic pathways associated with this tumor will allow for the development of targeted therapies and improved outcomes for patients with this disease.

  20. Raman spectroscopy as an advanced structural nanoprobe for conjugated molecular semiconductors

    NASA Astrophysics Data System (ADS)

    Wood, Sebastian; Razzell Hollis, Joseph; Kim, Ji-Seon

    2017-02-01

    Raman spectroscopy has emerged as a powerful and important characterisation tool for probing molecular semiconducting materials. The useful optoelectronic properties of these materials arise from the delocalised π-electron density in the conjugated core of the molecule, which also results in large Raman scattering cross-sections and a strong coupling between its electronic states and vibrational modes. For this reason, Raman spectroscopy offers a unique insight into the properties of molecular semiconductors, including: chemical structure, molecular conformation, molecular orientation, and fundamental photo- and electro-chemical processes—all of which are critically important to the performance of a wide range of optical and electronic organic semiconductor devices. Experimentally, Raman spectroscopy is non-intrusive, non-destructive, and requires no special sample preparation, and so is suitable for a wide range of in situ measurements, which are particularly relevant to issues of thermal and photochemical stability. Here we review the development of the family of Raman spectroscopic techniques, which have been applied to the study of conjugated molecular semiconductors. We consider the suitability of each technique for particular circumstances, and the unique insights it can offer, with a particular focus on the significance of these measurements for the continuing development of stable, high performance organic electronic devices.

  1. Development of 3D multimedia with advanced computer animation tools for outreach activities related to Meteor Science and Meteoritics

    NASA Astrophysics Data System (ADS)

    Madiedo, J. M.

    2012-09-01

    Documentaries related to Astronomy and Planetary Sciences are a common and very attractive way to promote the interest of the public in these areas. These educational tools can get benefit from new advanced computer animation software and 3D technologies, as these allow making these documentaries even more attractive. However, special care must be taken in order to guarantee that the information contained in them is serious and objective. In this sense, an additional value is given when the footage is produced by the own researchers. With this aim, a new documentary produced and directed by Prof. Madiedo has been developed. The documentary, which has been entirely developed by means of advanced computer animation tools, is dedicated to several aspects of Meteor Science and Meteoritics. The main features of this outreach and education initiative are exposed here.

  2. Molecular surveillance as monitoring tool for drug-resistant Plasmodium falciparum in Suriname.

    PubMed

    Adhin, Malti R; Labadie-Bracho, Mergiory; Bretas, Gustavo

    2013-08-01

    The aim of this translational study was to show the use of molecular surveillance for polymorphisms and copy number as a monitoring tool to track the emergence and dynamics of Plasmodium falciparum drug resistance. A molecular baseline for Suriname was established in 2005, with P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance (pfmdr1) markers and copy number in 40 samples. The baseline results revealed the existence of a uniformly distributed mutated genotype corresponding with the fully mefloquine-sensitive 7G8-like genotype (Y184F, S1034C, N1042D, and D1246Y) and a fixed pfmdr1 N86 haplotype. All samples harbored the pivotal pfcrtK76T mutation, showing that chloroquine reintroduction should not yet be contemplated in Suriname. After 5 years, 40 samples were assessed to trace temporal changes in the status of pfmdr1 polymorphisms and copy number and showed minor genetic alterations in the pfmdr1 gene and no significant changes in copy number, thus providing scientific support for prolongation of the current drug policy in Suriname.

  3. Implementation of new tools in molecular epidemiology studies of Echinococcus granulosus sensu lato in South America.

    PubMed

    Avila, Héctor G; Santos, Guilherme B; Cucher, Marcela A; Macchiaroli, Natalia; Pérez, Matías G; Baldi, Germán; Jensen, Oscar; Pérez, Verónica; López, Raúl; Negro, Perla; Scialfa, Exequiel; Zaha, Arnaldo; Ferreira, Henrique B; Rosenzvit, Mara; Kamenetzky, Laura

    2017-06-01

    The aim of this work was to determine Echinococcus granulosus sensu lato species and genotypes in intermediate and definitive hosts and in human isolates from endemic regions of Argentina and Brazil including those where no molecular data is available by a combination of classical and alternative molecular tools. A total of 227 samples were isolated from humans, natural intermediate and definitive hosts. Amplification of cytochrome c oxidase subunit I gene fragment was performed and a combination of AluI digestion assay, High Resolution Melting analysis (HRM) assay and DNA sequencing was implemented for Echinococcus species/genotype determination. E. granulosus sensu stricto (G1) was found in sheep (n=35), cattle (n=67) and dogs (n=5); E. ortleppi (G5) in humans (n=3) and cattle (n=108); E. canadensis (G6) in humans (n=2) and E. canadensis (G7) in pigs (n=7). We reported for the first time the presence of E. ortleppi (G5) and E. canadensis (G6) in humans from San Juan and Catamarca Argentinean provinces and E. canadensis (G7) in pigs from Cordoba Argentinean province. In this work, we widened molecular epidemiology studies of E. granulosus s. l. in South America by analyzing several isolates from definitive and intermediate hosts, including humans from endemic regions were such information was scarce or unavailable. The presence of different species/genotypes in the same region and host species reinforce the need of rapid and specific techniques for accurate determination of Echinococcus species such as the ones proposed in this work.

  4. Update on ORNL TRANSFORM Tool: Simulating Multi-Module Advanced Reactor with End-to-End I&C

    SciTech Connect

    Hale, Richard Edward; Fugate, David L.; Cetiner, Sacit M.; Qualls, A. L.

    2015-05-01

    The Small Modular Reactor (SMR) Dynamic System Modeling Tool project is in the fourth year of development. The project is designed to support collaborative modeling and study of various advanced SMR (non-light water cooled reactor) concepts, including the use of multiple coupled reactors at a single site. The focus of this report is the development of a steam generator and drum system model that includes the complex dynamics of typical steam drum systems, the development of instrumentation and controls for the steam generator with drum system model, and the development of multi-reactor module models that reflect the full power reactor innovative small module design concept. The objective of the project is to provide a common simulation environment and baseline modeling resources to facilitate rapid development of dynamic advanced reactor models; ensure consistency among research products within the Instrumentation, Controls, and Human-Machine Interface technical area; and leverage cross-cutting capabilities while minimizing duplication of effort. The combined simulation environment and suite of models are identified as the TRANSFORM tool. The critical elements of this effort include (1) defining a standardized, common simulation environment that can be applied throughout the Advanced Reactors Technology program; (2) developing a library of baseline component modules that can be assembled into full plant models using available geometry, design, and thermal-hydraulic data; (3) defining modeling conventions for interconnecting component models; and (4) establishing user interfaces and support tools to facilitate simulation development (i.e., configuration and parameterization), execution, and results display and capture.

  5. MLP Tools: a PyMOL plugin for using the molecular lipophilicity potential in computer-aided drug design

    NASA Astrophysics Data System (ADS)

    Oberhauser, Nils; Nurisso, Alessandra; Carrupt, Pierre-Alain

    2014-05-01

    The molecular lipophilicity potential (MLP) is a well-established method to calculate and visualize lipophilicity on molecules. We are here introducing a new computational tool named MLP Tools, written in the programming language Python, and conceived as a free plugin for the popular open source molecular viewer PyMOL. The plugin is divided into several sub-programs which allow the visualization of the MLP on molecular surfaces, as well as in three-dimensional space in order to analyze lipophilic properties of binding pockets. The sub-program Log MLP also implements the virtual log P which allows the prediction of the octanol/water partition coefficients on multiple three-dimensional conformations of the same molecule. An implementation on the recently introduced MLP GOLD procedure, improving the GOLD docking performance in hydrophobic pockets, is also part of the plugin. In this article, all functions of the MLP Tools will be described through a few chosen examples.

  6. Vascular effects of advanced glycation endproducts: Clinical effects and molecular mechanisms☆

    PubMed Central

    Stirban, Alin; Gawlowski, Thomas; Roden, Michael

    2013-01-01

    The enhanced generation and accumulation of advanced glycation endproducts (AGEs) have been linked to increased risk for macrovascular and microvascular complications associated with diabetes mellitus. AGEs result from the nonenzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids, potentially altering their function by disrupting molecular conformation, promoting cross-linking, altering enzyme activity, reducing their clearance, and impairing receptor recognition. AGEs may also activate specific receptors, like the receptor for AGEs (RAGE), which is present on the surface of all cells relevant to atherosclerotic processes, triggering oxidative stress, inflammation and apoptosis. Understanding the pathogenic mechanisms of AGEs is paramount to develop strategies against diabetic and cardiovascular complications. PMID:24634815

  7. Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma.

    PubMed

    Huse, Jason T; Holland, Eric C

    2010-05-01

    Malignant brain tumours continue to be the cause of a disproportionate level of morbidity and mortality across a wide range of individuals. The most common variants in the adult and paediatric populations - malignant glioma and medulloblastoma, respectively - have been the subject of increasingly intensive research over the past two decades that has led to considerable advances in the understanding of their basic biology and pathogenesis. This Review summarizes these developments in the context of the evolving notion of molecular pathology and discusses the implications that this work has on the design of new treatment regimens.

  8. Plant chromium uptake and transport, physiological effects and recent advances in molecular investigations.

    PubMed

    Gomes, Maria Angélica da Conceição; Hauser-Davis, Rachel Ann; Suzuki, Marina Satika; Vitória, Angela Pierre

    2017-06-01

    Increasingly, anthropogenic perturbations of the biosphere manifest in a broad array of global phenomena, causing widespread contamination of most ecosystems, with high dispersion rates of many contaminants throughout different environmental compartments, including metals. Chromium (Cr) contamination in particular, is, increasingly, posing a serious threat to the environment, emerging as a major health hazard to the biota. However, although the molecular and physiological mechanisms of plant responses to many heavy metals, especially lead (Pb) and cadmium (Cd), have been focused upon in recent years, chromium has attracted significantly less attention. In this context, this review discusses aspects of Cr uptake and transport, some physiological and biochemical effects of Cr exposure in plants, and molecular defense mechanisms against this metal. Recent advances in determining these responses, in fields of knowledge such as genomics, proteomics and metallomics, are discussed herein.

  9. [Advancement in the research of early detection of bacterial nucleic acid in molecular diagnosis of sepsis].

    PubMed

    Liu, Xiao; Ren, Hui; Peng, Dai-zhi

    2013-04-01

    Early diagnosis of sepsis helps make effective clinical decisions and improve the survival rate of patients with severe infection. However, the timely and accurate diagnosis of sepsis is still a great challenge in clinic. In order to settle the very problem, the scientists in the world have made a lot of exploration and research in the field of rapid molecular identification of pathogens. Nowadays, the nucleic acid detection of sepsis is mainly composed of 3 types of methodological strategies, either based on positive blood culture, single colonies, or directly on blood specimens. This paper presents a comprehensive overview of advances in the research of early detection of bacterial nucleic acid as molecular diagnosis of sepsis.

  10. Molecularly targeted therapy for advanced hepatocellular carcinoma - a drug development crisis?

    PubMed Central

    Thillai, Kiruthikah; Ross, Paul; Sarker, Debashis

    2016-01-01

    Hepatocellular carcinoma is the fastest growing cause of cancer related death globally. Sorafenib, a multi-targeted kinase inhibitor, is the only drug proven to improve outcomes in patients with advanced disease offering modest survival benefit. Although comprehensive genomic mapping has improved understanding of the genetic aberrations in hepatocellular cancer (HCC), this knowledge has not yet impacted clinical care. The last few years have seen the failure of several first and second line phase III clinical trials of novel molecularly targeted therapies, warranting a change in the way new therapies are investigated in HCC. Potential reasons for these failures include clinical and molecular heterogeneity, trial design and a lack of biomarkers. This review discusses the current crisis in HCC drug development and how we should learn from recent trial failures to develop a more effective personalised treatment paradigm for patients with HCC. PMID:26909132

  11. Severe Impairment Rating Scale: A Useful and Brief Cognitive Assessment Tool for Advanced Dementia for Nursing Home Residents.

    PubMed

    Yeo, Cindy; Lim, Wee Shiong; Chan, Mark; Ho, Xin Qin; Anthony, Philomena Vasantha; Han, Huey Charn; Chong, Mei Sian

    2016-02-01

    To investigate the utility of the Severe Impairment Rating Scale (SIRS) as a cognitive assessment tool among nursing home residents with advanced dementia, we conducted a cross-sectional study of 96 residents in 3 nursing homes with Functional Assessment Staging Test (FAST) stage 6a and above. We compared the discriminatory ability of SIRS with the Chinese version of Mini-Mental State Examination, Abbreviated Mental Test, and Clock Drawing Test. Among the cognitive tests, SIRS showed the least "floor" effect and had the best capacity to distinguish very severe (FAST stages 7d-f) dementia (area under the curve 0.80 vs 0.46-0.76 for the other tools). The SIRS had the best correlation with FAST staging (r = -.59, P < .01) and, unlike the other 3 tools, exhibited only minimal change in correlation when adjusted for education and ethnicity. Our results support the utility of SIRS as a brief cognitive assessment tool for advanced dementia in the nursing home setting.

  12. Advances in Chimera Grid Tools for Multi-Body Dynamics Simulations and Script Creation

    NASA Technical Reports Server (NTRS)

    Chan, William M.

    2004-01-01

    This viewgraph presentation contains information about (1) Framework for multi-body dynamics - Geometry Manipulation Protocol (GMP), (2) Simulation procedure using Chimera Grid Tools (CGT) and OVERFLOW-2 (3) Further recent developments in Chimera Grid Tools OVERGRID, Grid modules, Script library and (4) Future work.

  13. Development of Advanced Life Prediction Tools for Elastic-Plastic Fatigue Crack Growth

    NASA Technical Reports Server (NTRS)

    Gregg, Wayne; McGill, Preston; Swanson, Greg; Wells, Doug; Throckmorton, D. A. (Technical Monitor)

    2001-01-01

    The objective of this viewgraph presentation is to develop a systematic approach to improving the fracture control process, including analytical tools, standards, guidelines, and awareness. Analytical tools specifically for elastic-plastic fracture analysis is a regime that is currently empirical for the Space Shuttle External Tank (ET) and is handled by simulated service testing of pre-cracked panels.

  14. Advancing Research in Second Language Writing through Computational Tools and Machine Learning Techniques: A Research Agenda

    ERIC Educational Resources Information Center

    Crossley, Scott A.

    2013-01-01

    This paper provides an agenda for replication studies focusing on second language (L2) writing and the use of natural language processing (NLP) tools and machine learning algorithms. Specifically, it introduces a range of the available NLP tools and machine learning algorithms and demonstrates how these could be used to replicate seminal studies…

  15. Effects of Molecular Structure in Macroscopic Mechanical Properties of an Advanced Polymer (LARC(sup TM)-SI)

    NASA Technical Reports Server (NTRS)

    Nicholson, Lee M.; Hinkley, Jeffrey A.; Whitley, Karen S.; Gates, Thomas S.

    2004-01-01

    Mechanical testing of an advanced polymer resin with known variations in molecular weight was performed over a range of temperatures below the glass transition temperature. The elastic properties, inelastic elongation behavior, and notched tensile strength all as a function of molecular weight and test temperature were determined. It was shown that notched tensile strength is a strong function of both temperature and molecular weight, whereas stiffness is only a strong function of temperature.

  16. Advances of Molecular Imaging for Monitoring the Anatomical and Functional Architecture of the Olfactory System.

    PubMed

    Zhang, Xintong; Bi, Anyao; Gao, Quansheng; Zhang, Shuai; Huang, Kunzhu; Liu, Zhiguo; Gao, Tang; Zeng, Wenbin

    2016-01-20

    The olfactory system of organisms serves as a genetically and anatomically model for studying how sensory input can be translated into behavior output. Some neurologic diseases are considered to be related to olfactory disturbance, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis, and so forth. However, it is still unclear how the olfactory system affects disease generation processes and olfaction delivery processes. Molecular imaging, a modern multidisciplinary technology, can provide valid tools for the early detection and characterization of diseases, evaluation of treatment, and study of biological processes in living subjects, since molecular imaging applies specific molecular probes as a novel approach to produce special data to study biological processes in cellular and subcellular levels. Recently, molecular imaging plays a key role in studying the activation of olfactory system, thus it could help to prevent or delay some diseases. Herein, we present a comprehensive review on the research progress of the imaging probes for visualizing olfactory system, which is classified on different imaging modalities, including PET, MRI, and optical imaging. Additionally, the probes' design, sensing mechanism, and biological application are discussed. Finally, we provide an outlook for future studies in this field.

  17. ADVANCED TOOLS FOR ASSESSING SELECTED PRESCRIPTION AND ILLICIT DRUGS IN TREATED SEWAGE EFFLUENTS AND SOURCE WATERS

    EPA Science Inventory

    The purpose of this poster is to present the application and assessment of advanced technologies in a real-world environment - wastewater effluent and source waters - for detecting six drugs (azithromycin, fluoxetine, omeprazole, levothyroxine, methamphetamine, and methylenedioxy...

  18. Molecular targeted therapies in advanced or metastatic chordoma patients: facts and hypotheses.

    PubMed

    Lebellec, Loïc; Aubert, Sébastien; Zaïri, Fahed; Ryckewaert, Thomas; Chauffert, Bruno; Penel, Nicolas

    2015-07-01

    Chordomas, derived from undifferentiated notochordal remnants, represent less than 4% of bone primary tumors. Despite surgery followed by radiotherapy, local and metastatic relapses are frequent. In case of locally advanced or metastatic chordomas, medical treatment is frequently discussed. While chemotherapy is ineffective, it would appear that some molecular targeted therapies, in particular imatinib, could slow down the tumor growth in case-reports, retrospective series, and phase I or II trials. Nineteen publications, between January 1990 and September 2014, have been found describing the activity of these targeted therapies. A systematic analysis of these publications shows that the best objective response with targeted therapies was stabilization in 52 to 69% of chordomas. Given the indolent course of advanced chordoma and because of the absence of randomized trial, the level of evidence to treat chordomas with molecular therapy is low (level III), whatever the drug. Furthermore, we could not draw firm conclusion on the activity of imatinib. Other putative targets have also been described. Therefore, further clinical trials are expected, especially with these targets. Nevertheless, it seems essential, in those future studies, to consider the naturally slow course of the disease.

  19. The Use of Gene Modification and Advanced Molecular Structure Analyses towards Improving Alfalfa Forage

    PubMed Central

    Lei, Yaogeng; Hannoufa, Abdelali; Yu, Peiqiang

    2017-01-01

    Alfalfa is one of the most important legume forage crops in the world. In spite of its agronomic and nutritive advantages, alfalfa has some limitations in the usage of pasture forage and hay supplement. High rapid degradation of protein in alfalfa poses a risk of rumen bloat to ruminants which could cause huge economic losses for farmers. Coupled with the relatively high lignin content, which impedes the degradation of carbohydrate in rumen, alfalfa has unbalanced and asynchronous degradation ratio of nitrogen to carbohydrate (N/CHO) in rumen. Genetic engineering approaches have been used to manipulate the expression of genes involved in important metabolic pathways for the purpose of improving the nutritive value, forage yield, and the ability to resist abiotic stress. Such gene modification could bring molecular structural changes in alfalfa that are detectable by advanced structural analytical techniques. These structural analyses have been employed in assessing alfalfa forage characteristics, allowing for rapid, convenient and cost-effective analysis of alfalfa forage quality. In this article, we review two major obstacles facing alfalfa utilization, namely poor protein utilization and relatively high lignin content, and highlight genetic studies that were performed to overcome these drawbacks, as well as to introduce other improvements to alfalfa quality. We also review the use of advanced molecular structural analysis in the assessment of alfalfa forage for its potential usage in quality selection in alfalfa breeding. PMID:28146083

  20. Advanced Molecular Diagnostic Techniques for Detection of Food-borne Pathogens; Current Applications and Future Challenges.

    PubMed

    Umesha, S; Manukumar, H M

    2016-01-08

    The elimination of disease-causing microbes from the food supply is a primary goal and this review deals with the overall techniques availavle for detection of food-borne pathogens. Now-a-days conventional methods are replaced by advanced methods like Biosensors, Nucleic Acid-based Tests (NAT) and different PCR based techniques used in molecular biology to identify specific pathogens. Bacillus cereus, Staphylococcus aureus, Proteus vulgaris, Escherichia coli, Campylobacter, Listeria monocytogenes, Salmonella spp, Aspergillus spp. Fusarium spp. Penicillium spp., and pathogens are detected in contaminated food items which cause always diseases in human in any one or the other way. Identification of food-borne pathogens in a short period of time is still a challenge to the scientific field in general and food technology in particular. The low level of food contamination by major pathogens requires specific sensitive detection platforms and the present area of hot research looking forward to new nanomolecular techniques for nanomaterials, make them suitable for the development of assays with high sensitivity, response time and portability. With the sound of these we attemet to highlight a comprehensive overview about food-borne pathogen detection by rapid, sensitive, accurate and cost affordable in situ analytical methods from conventional methods to recent molecular approaches for advanced food and microbiology research.

  1. Molecular identification of livestock breeds: a tool for modern conservation biology.

    PubMed

    Yaro, Mohammed; Munyard, Kylie A; Stear, Michael J; Groth, David M

    2016-03-22

    Global livestock genetic diversity includes all of the species, breeds and strains of domestic animals, and their variations. Although a recent census indicated that there were 40 species and over 8000 breeds of domestic animals; for the purpose of conservation biology the diversity between and within breeds rather than species is regarded to be of crucial importance. This domestic animal genetic diversity has developed through three main evolutionary events, from speciation (about 3 million years ago) through domestication (about 12000 years ago) to specialised breeding (starting about 200 years ago). These events and their impacts on global animal genetic resources have been well documented in the literature. The key importance of global domestic animal resources in terms of economic, scientific and cultural heritage has also been addressed. In spite of their importance, there is a growing number of reports on the alarming erosion of domestic animal genetic resources. This erosion of is happening in spite of several global conservation initiatives designed to mitigate it. Herein we discuss these conservation interventions and highlight their strengths and weaknesses. However, pivotal to the success of these conservation initiatives is the reliability of the genetic assignment of individual members to a target breed. Finally, we discuss the prospect of using improved breed identification methodologies to develop a reliable breed-specific molecular identification tool that is easily applicable to populations of livestock breeds in various ecosystems. These identification tools, when developed, will not only facilitate the regular monitoring of threatened or endangered breed populations, but also enhance the development of more efficient and sustainable livestock production systems.

  2. Transmission of lungworms of harbour porpoises and harbour seals: molecular tools determine potential vertebrate intermediate hosts.

    PubMed

    Lehnert, K; von Samson-Himmelstjerna, G; Schaudien, D; Bleidorn, C; Wohlsein, P; Siebert, U

    2010-06-01

    Harbour porpoises (Phocoena phocoena) and harbour seals (Phoca vitulina) from German waters are infected by six species of lungworms (Metastrongyloidea). These nematodes parasitise the respiratory tract, are pathogenic and often cause secondary bacterial infections. In spite of their clinical and epidemiological significance, the life cycle and biology of lungworms in the marine environment is still largely unknown. Regions of ribosomal DNA (ITS-2) of all lungworms parasitising harbour porpoises and harbour seals in German waters were sequenced to characterise and compare the different species. The phylogenetic relationship among the lungworm species was analysed by means of their ITS-2 nucleotide sequences and the species-specific traits of the ITS-2 were used to screen wild fish as possible intermediate hosts for larval lungworms. Molecular markers were developed to identify larval nematodes via in-situ hybridisation of tissues of harbour porpoise and harbour seal prey fish. Potential wild intermediate fish hosts from the North Sea were dissected and found to harbour larval nematodes. Histological examination and in-situ hybridisation of tissue samples from these fish showed lungworm larvae within the intestinal wall. Based on larval ITS-2 nucleotide sequences, larval nematodes were identified as Pseudalius inflexus and Parafilaroides gymnurus. Turbot (Psetta maxima) bred and raised in captivity were experimentally infected with live L1s of Otostrongylus circumlitus and ensheathed larvae were recovered from the gastrointestinal tract of turbot and identified using molecular tools. Our results show that fish intermediate hosts play a role in the transmission of metastrongyloid nematodes of harbour porpoises and harbour seals.

  3. CRISPR/Cas9: an advanced tool for editing plant genomes.

    PubMed

    Samanta, Milan Kumar; Dey, Avishek; Gayen, Srimonta

    2016-10-01

    To meet current challenges in agriculture, genome editing using sequence-specific nucleases (SSNs) is a powerful tool for basic and applied plant biology research. Here, we describe the principle and application of available genome editing tools, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeat associated CRISPR/Cas9 system. Among these SSNs, CRISPR/Cas9 is the most recently characterized and rapidly developing genome editing technology, and has been successfully utilized in a wide variety of organisms. This review specifically illustrates the power of CRISPR/Cas9 as a tool for plant genome engineering, and describes the strengths and weaknesses of the CRISPR/Cas9 technology compared to two well-established genome editing tools, ZFNs and TALENs.

  4. Advanced repair solution of clear defects on HTPSM by using nanomachining tool

    NASA Astrophysics Data System (ADS)

    Lee, Hyemi; Kim, Munsik; Jung, Hoyong; Kim, Sangpyo; Yim, Donggyu

    2015-10-01

    As the mask specifications become tighter for low k1 lithography, more aggressive repair accuracy is required below sub 20nm tech. node. To meet tight defect specifications, many maskshops select effective repair tools according to defect types. Normally, pattern defects are repaired by the e-beam repair tool and soft defects such as particles are repaired by the nanomachining tool. It is difficult for an e-beam repair tool to remove particle defects because it uses chemical reaction between gas and electron, and a nanomachining tool, which uses physical reaction between a nano-tip and defects, cannot be applied for repairing clear defects. Generally, film deposition process is widely used for repairing clear defects. However, the deposited film has weak cleaning durability, so it is easily removed by accumulated cleaning process. Although the deposited film is strongly attached on MoSiN(or Qz) film, the adhesive strength between deposited Cr film and MoSiN(or Qz) film becomes weaker and weaker by the accumulated energy when masks are exposed in a scanner tool due to the different coefficient of thermal expansion of each materials. Therefore, whenever a re-pellicle process is needed to a mask, all deposited repair points have to be confirmed whether those deposition film are damaged or not. And if a deposition point is damaged, repair process is needed again. This process causes longer and more complex process. In this paper, the basic theory and the principle are introduced to recover clear defects by using nanomachining tool, and the evaluated results are reviewed at dense line (L/S) patterns and contact hole (C/H) patterns. Also, the results using a nanomachining were compared with those using an e-beam repair tool, including the cleaning durability evaluated by the accumulated cleaning process. Besides, we discuss the phase shift issue and the solution about the image placement error caused by phase error.

  5. Development of Advanced Computational Aeroelasticity Tools at NASA Langley Research Center

    NASA Technical Reports Server (NTRS)

    Bartels, R. E.

    2008-01-01

    NASA Langley Research Center has continued to develop its long standing computational tools to address new challenges in aircraft and launch vehicle design. This paper discusses the application and development of those computational aeroelastic tools. Four topic areas will be discussed: 1) Modeling structural and flow field nonlinearities; 2) Integrated and modular approaches to nonlinear multidisciplinary analysis; 3) Simulating flight dynamics of flexible vehicles; and 4) Applications that support both aeronautics and space exploration.

  6. Advancing molecular-guided surgery through probe development and testing in a moderate cost evaluation pipeline

    NASA Astrophysics Data System (ADS)

    Pogue, Brian W.; Paulsen, Keith D.; Hull, Sally M.; Samkoe, Kimberley S.; Gunn, Jason; Hoopes, Jack; Roberts, David W.; Strong, Theresa V.; Draney, Daniel; Feldwisch, Joachim

    2015-03-01

    Molecular guided oncology surgery has the potential to transform the way decisions about resection are done, and can be critically important in areas such as neurosurgery where the margins of tumor relative to critical normal tissues are not readily apparent from visual or palpable guidance. Yet there are major financial barriers to advancing agents into clinical trials with commercial backing. We observe that development of these agents in the standard biological therapeutic paradigm is not viable, due to the high up front financial investment needed and the limitations in the revenue models of contrast agents for imaging. The hypothesized solution to this problem is to develop small molecular biologicals tagged with an established fluorescent reporter, through the chemical agent approval pathway, targeting a phase 0 trials initially, such that the initial startup phase can be completely funded by a single NIH grant. In this way, fast trials can be completed to de-risk the development pipeline, and advance the idea of fluorescence-guided surgery (FGS) reporters into human testing. As with biological therapies the potential successes of each agent are still moderate, but this process will allow the field to advance in a more stable and productive manner, rather than relying upon isolated molecules developed at high cost and risk. The pathway proposed and tested here uses peptide synthesis of an epidermal growth factor receptor (EGFR)-binding Affibody molecules, uniquely conjugated to IRDye 800CW, developed and tested in academic and industrial laboratories with well-established records for GMP production, fill and finish, toxicity testing, and early phase clinical trials with image guidance.

  7. Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study.

    PubMed

    Epelbaum, Ron; Shacham-Shmueli, Einat; Klein, Baruch; Agbarya, Abed; Brenner, Baruch; Brenner, Ronen; Gez, Eliahu; Golan, Talia; Hubert, Ayala; Purim, Ofer; Temper, Mark; Tepper, Ella; Voss, Andreas; Russell, Kenneth; Dvir, Addie; Soussan-Gutman, Lior; Stemmer, Salomon M; Geva, Ravit

    2015-01-01

    This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing ≥ 1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was ≥ 1.3. The null hypothesis was that ≤ 15% of patients gain such benefit. Overall, ≥ 1 actionable (i.e., predictive of response to specific therapies) biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions) identified 1-6 (median: 4) actionable biomarkers per patient. After MP, patients received 1-4 (median: 1) regimens/patient (most commonly, FOLFIRI/XELIRI). In a decision-impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was ≥ 1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC.

  8. Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study

    PubMed Central

    Epelbaum, Ron; Shacham-Shmueli, Einat; Klein, Baruch; Agbarya, Abed; Brenner, Baruch; Brenner, Ronen; Gez, Eliahu; Golan, Talia; Hubert, Ayala; Purim, Ofer; Temper, Mark; Tepper, Ella; Voss, Andreas; Russell, Kenneth; Dvir, Addie; Soussan-Gutman, Lior; Stemmer, Salomon M.; Geva, Ravit

    2015-01-01

    This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing ≥1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. Overall, ≥1 actionable (i.e., predictive of response to specific therapies) biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions) identified 1–6 (median: 4) actionable biomarkers per patient. After MP, patients received 1–4 (median: 1) regimens/patient (most commonly, FOLFIRI/XELIRI). In a decision-impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was ≥1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC. PMID:26161408

  9. Advances in the Development of Molecularly Targeted Agents in Non-Small-Cell Lung Cancer.

    PubMed

    Dolly, Saoirse O; Collins, Dearbhaile C; Sundar, Raghav; Popat, Sanjay; Yap, Timothy A

    2017-04-04

    Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that involves personalized strategies based on histological and molecular subtypes. The molecular era has revolutionized the treatment of patients harboring epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 gene aberrations. In the appropriately selected population, anti-tumor agents against these molecular targets can significantly improve progression-free survival. However, the emergence of acquired resistance is inevitable. Novel potent compounds with much improved and rational selectivity profiles, such as third-generation EGFR T790M resistance mutation-specific inhibitors, have been developed and added to the NSCLC armamentarium. To date, attempts to overcome resistance bypass pathways through downstream signaling blockade has had limited success. Furthermore, the majority of patients still do not harbor known driver genetic or epigenetic alterations and/or have no new available treatment options, with chemotherapy remaining their standard of care. Several potentially actionable driver aberrations have recently been identified, with the early clinical development of multiple inhibitors against these promising targets currently in progress. The advent of immune checkpoint inhibitors has led to significant benefit for advanced NSCLC patients with durable responses observed. Further interrogation of the underlying biology of NSCLC, coupled with modern clinical trial designs, is now required to develop novel targeted therapeutics rationally matched with predictive biomarkers of response, so as to further advance NSCLC therapeutics through the next decade.

  10. Molecular tools and bumble bees: revealing hidden details of ecology and evolution in a model system.

    PubMed

    Woodard, S Hollis; Lozier, Jeffrey D; Goulson, David; Williams, Paul H; Strange, James P; Jha, Shalene

    2015-06-01

    Bumble bees are a longstanding model system for studies on behaviour, ecology and evolution, due to their well-studied social lifestyle, invaluable role as wild and managed pollinators, and ubiquity and diversity across temperate ecosystems. Yet despite their importance, many aspects of bumble bee biology have remained enigmatic until the rise of the genetic and, more recently, genomic eras. Here, we review and synthesize new insights into the ecology, evolution and behaviour of bumble bees that have been gained using modern genetic and genomic techniques. Special emphasis is placed on four areas of bumble bee biology: the evolution of eusociality in this group, population-level processes, large-scale evolutionary relationships and patterns, and immunity and resistance to pesticides. We close with a prospective on the future of bumble bee genomics research, as this rapidly advancing field has the potential to further revolutionize our understanding of bumble bees, particularly in regard to adaptation and resilience. Worldwide, many bumble bee populations are in decline. As such, throughout the review, connections are drawn between new molecular insights into bumble bees and our understanding of the causal factors involved in their decline. Ongoing and potential applications to bumble bee management and conservation are also included to demonstrate how genetics- and genomics-enabled research aids in the preservation of this threatened group.

  11. Imaging Mass Spectrometry: A New Tool for Pathology in a Molecular Age

    PubMed Central

    Norris, Jeremy L.; Caprioli, Richard M.

    2014-01-01

    Mass spectrometry provides unique advantages for the analysis of clinical specimens, and these capabilities have been critical to the advancement of diagnostic medicine. To date, liquid chromatography mass spectrometry (LC-MS) is the platform most commonly used for diagnostics; however, LC-MS based proteomics is very labor intensive and costly to implement for high volume assays. Furthermore, when analyzing tissue samples, additional laborious sample preparation steps must be employed (e.g., extraction methods or laser microdissection). The direct analysis of cells and tissues by matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) has developed significant momentum for applications that have diagnostic potential. MALDI IMS provides molecular information from specific cell types within tissue sections; however, this laser-based approach significantly reduces the analysis time for each location sampled. This Viewpoint discusses the technologies for direct analysis of tissues, the potential for diagnostic applications using MALDI IMS, and the challenges faced in the transfer of the technology to the clinical laboratory. PMID:24178781

  12. Molecular Investigations of Bacteroides as Microbial Source Tracking Tools in Southeast Louisiana Watersheds

    NASA Astrophysics Data System (ADS)

    Schulz, C. J.; Childers, G. W.; Engel, A. S.

    2006-12-01

    Microbial Source Tracking (MST) is a developing field that is gaining increased attention. MST refers to a host of techniques that discriminates among the origins of fecal material found in natural waters from different sources (e.g. human, livestock, and wildlife) by using microbial indicator species with specificity to only certain host organisms. The development of species-specific molecular markers would allow for better evaluation of public health risks and tracking of nutrient sources impacting a watershed. Although several MST methods have been reported with varying levels of success, few offer general applicability for natural waters due to spatial and temporal constraints associated with these methods. One group of molecular MST markers that show promise for broad environmental applications are molecular 16S rDNA probes for Bacteroides. This method is based on 16S rDNA detection directly from environmental samples without the need for a preliminary cultivation step. In this study we have expanded previous sampling efforts to compile a database of over 1000 partial 16S rRNA Bacteroides genes retrieved from the fecal material of 15 different host species (human, cat, dog, pig, kangaroo). To characterize survival of Bacteroides outside of the host, survival time of the Bacteroides marker was compared to that of E.coli under varying natural environmental conditions (temperature and salinity). Bacteroides displayed a survival curve with shouldering and tailing similar to that of E.coli, but log reduction times differed with treatment. In summary, MST marker stability was identified within host species and the overall Bacteroides community structure correlated to host diet, suggesting that detection of a Bacteroides community could confidently identify fecal contamination point sources. Natural water samples from southeast Louisiana were collected for MST including the Tangipahoa River watershed where the source of fecal contamination has been hotly debated. The

  13. Reevaluating establishment and potential hybridization of different biotypes of the biological control agent Longitarsus jacobaeae using molecular tools

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Evaluation of past and current biological control programs using molecular tools can clarify establishment success of agent biotypes, and can contribute to our understanding of best practice for natural enemy importations. The flea beetle, Longitarsus jacobaeae has been quite successful at controlli...

  14. Biosynthesis of Polyunsaturated Fatty Acids in Marine Invertebrates: Recent Advances in Molecular Mechanisms

    PubMed Central

    Monroig, Óscar; Tocher, Douglas R.; Navarro, Juan C.

    2013-01-01

    Virtually all polyunsaturated fatty acids (PUFA) originate from primary producers but can be modified by bioconversions as they pass up the food chain in a process termed trophic upgrading. Therefore, although the main primary producers of PUFA in the marine environment are microalgae, higher trophic levels have metabolic pathways that can produce novel and unique PUFA. However, little is known about the pathways of PUFA biosynthesis and metabolism in the levels between primary producers and fish that are largely filled by invertebrates. It has become increasingly apparent that, in addition to trophic upgrading, de novo synthesis of PUFA is possible in some lower animals. The unequivocal identification of PUFA biosynthetic pathways in many invertebrates is complicated by the presence of other organisms within them. These organisms include bacteria and algae with PUFA biosynthesis pathways, and range from intestinal flora to symbiotic relationships that can involve PUFA translocation to host organisms. This emphasizes the importance of studying biosynthetic pathways at a molecular level, and the continual expansion of genomic resources and advances in molecular analysis is facilitating this. The present paper highlights recent research into the molecular and biochemical mechanisms of PUFA biosynthesis in marine invertebrates, particularly focusing on cephalopod molluscs. PMID:24152561

  15. Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders

    PubMed Central

    Rajan-Babu, Indhu-Shree; Chong, Samuel S.

    2016-01-01

    Fragile X syndrome (FXS) is the most common monogenic cause of intellectual disability and autism. Molecular diagnostic testing of FXS and related disorders (fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS)) relies on a combination of polymerase chain reaction (PCR) and Southern blot (SB) for the fragile X mental retardation 1 (FMR1) CGG-repeat expansion and methylation analyses. Recent advancements in PCR-based technologies have enabled the characterization of the complete spectrum of CGG-repeat mutation, with or without methylation assessment, and, as a result, have reduced our reliance on the labor- and time-intensive SB, which is the gold standard FXS diagnostic test. The newer and more robust triplet-primed PCR or TP-PCR assays allow the mapping of AGG interruptions and enable the predictive analysis of the risks of unstable CGG expansion during mother-to-child transmission. In this review, we have summarized the correlation between several molecular elements, including CGG-repeat size, methylation, mosaicism and skewed X-chromosome inactivation, and the extent of clinical involvement in patients with FMR1-related disorders, and reviewed key developments in PCR-based methodologies for the molecular diagnosis of FXS, FXTAS and FXPOI, and large-scale (CGG)n expansion screening in newborns, women of reproductive age and high-risk populations. PMID:27754417

  16. Biosynthesis of polyunsaturated fatty acids in marine invertebrates: recent advances in molecular mechanisms.

    PubMed

    Monroig, Óscar; Tocher, Douglas R; Navarro, Juan C

    2013-10-21

    Virtually all polyunsaturated fatty acids (PUFA) originate from primary producers but can be modified by bioconversions as they pass up the food chain in a process termed trophic upgrading. Therefore, although the main primary producers of PUFA in the marine environment are microalgae, higher trophic levels have metabolic pathways that can produce novel and unique PUFA. However, little is known about the pathways of PUFA biosynthesis and metabolism in the levels between primary producers and fish that are largely filled by invertebrates. It has become increasingly apparent that, in addition to trophic upgrading, de novo synthesis of PUFA is possible in some lower animals. The unequivocal identification of PUFA biosynthetic pathways in many invertebrates is complicated by the presence of other organisms within them. These organisms include bacteria and algae with PUFA biosynthesis pathways, and range from intestinal flora to symbiotic relationships that can involve PUFA translocation to host organisms. This emphasizes the importance of studying biosynthetic pathways at a molecular level, and the continual expansion of genomic resources and advances in molecular analysis is facilitating this. The present paper highlights recent research into the molecular and biochemical mechanisms of PUFA biosynthesis in marine invertebrates, particularly focusing on cephalopod molluscs.

  17. The Evolution of Advanced Molecular Diagnostics for the Detection and Characterization of Mycoplasma pneumoniae.

    PubMed

    Diaz, Maureen H; Winchell, Jonas M

    2016-01-01

    Over the past decade there have been significant advancements in the methods used for detecting and characterizing Mycoplasma pneumoniae, a common cause of respiratory illness and community-acquired pneumonia worldwide. The repertoire of available molecular diagnostics has greatly expanded from nucleic acid amplification techniques (NAATs) that encompass a variety of chemistries used for detection, to more sophisticated characterizing methods such as multi-locus variable-number tandem-repeat analysis (MLVA), Multi-locus sequence typing (MLST), matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), single nucleotide polymorphism typing, and numerous macrolide susceptibility profiling methods, among others. These many molecular-based approaches have been developed and employed to continually increase the level of discrimination and characterization in order to better understand the epidemiology and biology of M. pneumoniae. This review will summarize recent molecular techniques and procedures and lend perspective to how each has enhanced the current understanding of this organism and will emphasize how Next Generation Sequencing may serve as a resource for researchers to gain a more comprehensive understanding of the genomic complexities of this insidious pathogen.

  18. Optimization of preservation and processing of sea anemones for microbial community analysis using molecular tools

    PubMed Central

    Rocha, Joana; Coelho, Francisco J. R. C.; Peixe, Luísa; Gomes, Newton C. M.; Calado, Ricardo

    2014-01-01

    For several years, knowledge on the microbiome associated with marine invertebrates was impaired by the challenges associated with the characterization of bacterial communities. With the advent of culture independent molecular tools it is possible to gain new insights on the diversity and richness of microorganisms associated with marine invertebrates. In the present study, we evaluated if different preservation and processing methodologies (prior to DNA extraction) can affect the bacterial diversity retrieved from snakelocks anemone Anemonia viridis. Denaturing gradient gel electrophoresis (DGGE) community fingerprints were used as proxy to determine the bacterial diversity retrieved (H′). Statistical analyses indicated that preservation significantly affects H′. The best approach to preserve and process A. viridis biomass for bacterial community fingerprint analysis was flash freezing in liquid nitrogen (preservation) followed by the use of a mechanical homogenizer (process), as it consistently yielded higher H′. Alternatively, biomass samples can be processed fresh followed by cell lyses using a mechanical homogenizer or mortar & pestle. The suitability of employing these two alternative procedures was further reinforced by the quantification of the 16S rRNA gene; no significant differences were recorded when comparing these two approaches and the use of liquid nitrogen followed by processing with a mechanical homogenizer. PMID:25384534

  19. UMI-tools: modeling sequencing errors in Unique Molecular Identifiers to improve quantification accuracy.

    PubMed

    Smith, Tom; Heger, Andreas; Sudbery, Ian

    2017-03-01

    Unique Molecular Identifiers (UMIs) are random oligonucleotide barcodes that are increasingly used in high-throughput sequencing experiments. Through a UMI, identical copies arising from distinct molecules can be distinguished from those arising through PCR amplification of the same molecule. However, bioinformatic methods to leverage the information from UMIs have yet to be formalized. In particular, sequencing errors in the UMI sequence are often ignored or else resolved in an ad hoc manner. We show that errors in the UMI sequence are common and introduce network-based methods to account for these errors when identifying PCR duplicates. Using these methods, we demonstrate improved quantification accuracy both under simulated conditions and real iCLIP and single-cell RNA-seq data sets. Reproducibility between iCLIP replicates and single-cell RNA-seq clustering are both improved using our proposed network-based method, demonstrating the value of properly accounting for errors in UMIs. These methods are implemented in the open source UMI-tools software package.

  20. UMI-tools: modeling sequencing errors in Unique Molecular Identifiers to improve quantification accuracy

    PubMed Central

    2017-01-01

    Unique Molecular Identifiers (UMIs) are random oligonucleotide barcodes that are increasingly used in high-throughput sequencing experiments. Through a UMI, identical copies arising from distinct molecules can be distinguished from those arising through PCR amplification of the same molecule. However, bioinformatic methods to leverage the information from UMIs have yet to be formalized. In particular, sequencing errors in the UMI sequence are often ignored or else resolved in an ad hoc manner. We show that errors in the UMI sequence are common and introduce network-based methods to account for these errors when identifying PCR duplicates. Using these methods, we demonstrate improved quantification accuracy both under simulated conditions and real iCLIP and single-cell RNA-seq data sets. Reproducibility between iCLIP replicates and single-cell RNA-seq clustering are both improved using our proposed network-based method, demonstrating the value of properly accounting for errors in UMIs. These methods are implemented in the open source UMI-tools software package. PMID:28100584

  1. [Use of molecular typing tools for the study of hospital outbreaks of candidemia].

    PubMed

    Marcos-Zambrano, Laura Judith; Escribano, Pilar; Bouza, Emilio; Guinea, Jesús

    2014-01-01

    Candidemia is an infectious complication mainly affecting hospitalized patients, particularly those admitted to intensive care units. Patient mortality can reach up to 40%. Candidemia is typically nosocomially-acquired, and horizontal transmission of Candida spp. can lead to the presence of outbreaks of candidemia. Genotyping of isolates of Candida causing candidemia can help us to understand the source of the infection, detect the hospital wards with active Candida spp. transmission and, consequently, improve the prevention of the infection. Several genotyping tools have been used for the molecular characterization of Candida isolates involved in outbreaks of candidemia. Genotyping procedures based on microsatellites are reproducible and show a high discriminatory power. Microsatellites are recommended for the study of outbreaks of candidemia. In most hospital outbreaks of candidemia, patients admitted to intensive care units are involved, mostly neonatal patients. The role of genotyping Candida isolates causing candidemia for the study of nosocomial outbreaks of candidemia is reviewed, as well as the patients more commonly affected by epidemic strains.

  2. Malaria parasite mutants with altered erythrocyte permeability: a new drug resistance mechanism and important molecular tool

    PubMed Central

    Hill, David A; Desai, Sanjay A

    2010-01-01

    Erythrocytes infected with plasmodia, including those that cause human malaria, have increased permeability to a diverse collection of organic and inorganic solutes. While these increases have been known for decades, their mechanistic basis was unclear until electrophysiological studies revealed flux through one or more ion channels on the infected erythrocyte membrane. Current debates have centered on the number of distinct ion channels, which channels mediate the transport of each solute and whether the channels represent parasite-encoded proteins or human channels activated after infection. This article reviews the identification of the plasmodial surface anion channel and other proposed channels with an emphasis on two distinct channel mutants generated through in vitro selection. These mutants implicate parasite genetic elements in the parasite-induced permeability, reveal an important new antimalarial drug resistance mechanism and provide tools for molecular studies. We also critically examine the technical issues relevant to the detection of ion channels by electrophysiological methods; these technical considerations have general applicability for interpreting studies of various ion channels proposed for the infected erythrocyte membrane. PMID:20020831

  3. Single-stranded DNA phages: from early molecular biology tools to recent revolutions in environmental microbiology.

    PubMed

    Székely, Anna J; Breitbart, Mya

    2016-03-01

    Single-stranded DNA (ssDNA) phages are profoundly different from tailed phages in many aspects including the nature and size of their genome, virion size and morphology, mutation rate, involvement in horizontal gene transfer, infection dynamics and cell lysis mechanisms. Despite the importance of ssDNA phages as molecular biology tools and model systems, the environmental distribution and ecological roles of these phages have been largely unexplored. Viral metagenomics and other culture-independent viral diversity studies have recently challenged the perspective of tailed, double-stranded DNA (dsDNA) phages, dominance by demonstrating the prevalence of ssDNA phages in diverse habitats. However, the differences between ssDNA and dsDNA phages also substantially limit the efficacy of simultaneously assessing the abundance and diversity of these two phage groups. Here we provide an overview of the major differences between ssDNA and tailed dsDNA phages that may influence their effects on bacterial communities. Furthermore, through the analysis of 181 published metaviromes we demonstrate the environmental distribution of ssDNA phages and present an analysis of the methodological biases that distort their study through metagenomics.

  4. Monocyte-targeting supramolecular micellar assemblies: a molecular diagnostic tool for atherosclerosis.

    PubMed

    Chung, Eun Ji; Mlinar, Laurie B; Nord, Kathryn; Sugimoto, Matthew J; Wonder, Emily; Alenghat, Francis J; Fang, Yun; Tirrell, Matthew

    2015-02-18

    Atherosclerosis is a multifactorial inflammatory disease that can progress silently for decades and result in myocardial infarction, stroke, and death. Diagnostic imaging technologies have made great strides to define the degree of atherosclerotic plaque burden through the severity of arterial stenosis. However, current technologies cannot differentiate more lethal "vulnerable plaques," and are not sensitive enough for preventive medicine. Imaging early molecular markers and quantifying the extent of disease progression continues to be a major challenge in the field. To this end, monocyte-targeting, peptide amphiphile micelles (PAMs) are engineered through the incorporation of the chemokine receptor CCR2-binding motif of monocyte chemoattractant protein-1 (MCP-1) and MCP-1 PAMs are evaluated preclinically as diagnostic tools for atherosclerosis. Monocyte-targeting is desirable as the influx of monocytes is a marker of early lesions, accumulation of monocytes is linked to atherosclerosis progression, and rupture-prone plaques have higher numbers of monocytes. MCP-1 PAMs bind to monocytes in vitro, and MCP-1 PAMs detect and discriminate between early- and late-stage atherosclerotic aortas. Moreover, MCP-1 PAMs are found to be eliminated via renal clearance and the mononuclear phagocyte system (MPS) without adverse side effects. Thus, MCP-1 PAMs are a promising new class of diagnostic agents capable of monitoring the progression of atherosclerosis.

  5. Implementation of a professional portfolio: a tool to demonstrate professional development for advanced practice.

    PubMed

    Chamblee, Tracy B; Dale, Juanita Conkin; Drews, Barbie; Spahis, Joanna; Hardin, Teri

    2015-01-01

    The literature has a gap related to professional development for APRNs. In the United States, many health care organizations use clinical advancement programs for registered nurses, but APRNs are not often included in these programs. If APRNs are included, advancement opportunities are very limited. At CMC, implementation of a professional portfolio resulted in increased satisfaction among APPs regarding their ability to showcase professional growth and expertise, as well as the uniqueness of their advanced practice. Use of the professional portfolio led to improved recognition by APS and organizational leaders of APP performance excellence during the annual performance evaluation, as well as improved recognition among APP colleagues in terms of nominations for honors and awards.

  6. New methodology to baseline and match AME polysilicon etcher using advanced diagnostic tools

    NASA Astrophysics Data System (ADS)

    Poppe, James; Shipman, John; Reinhardt, Barbara E.; Roussel, Myriam; Hedgecock, Raymond; Fonda, Arturo

    1999-09-01

    As process controls tighten in the semiconductor industry, the need to understand the variables that determine system performance become more important. For plasma etch systems, process success depends on the control of key parameters such as: vacuum integrity, pressure, gas flows, and RF power. It is imperative to baseline, monitor, and control these variables. This paper presents an overview of the methods and tools used by Motorola BMC fabrication facility to characterize an Applied Materials polysilicon etcher. Tool performance data obtained from our traditional measurement techniques are limited in their scope and do not provide a complete picture of the ultimate tool performance. Presently the BMC traditional characterization tools provide a snapshot of the static operation of the equipment under test (EUT); however, complete evaluation of the dynamic performance cannot be monitored without the aid of specialized diagnostic equipment. To provide us with a complete system baseline evaluation of the polysilicon etcher, three diagnostic tools were utilized: Lucas Labs Vacuum Diagnostic System, Residual Gas Analyzer, and the ENI Voltage/Impedance Probe. The diagnostic methodology used to baseline and match key parameters of qualified production equipment has had an immense impact on other equipment characterization in the facility. It has resulted in reduced cycle time for new equipment introduction as well.

  7. ADVANCED TOOLS FOR ASSESSING SELECTED PRESCRIPTION AND ILLICIT DRUGS IN TREATED SEWAGE EFFLUENTS AND SOURCE WATERS

    EPA Science Inventory

    The purpose of this poster is to present the application and assessment of advanced state-of-the-art technologies in a real-world environment - wastewater effluent and source waters - for detecting six drugs [azithromycin, fluoxetine, omeprazole, levothyroxine, methamphetamine, m...

  8. Just-in-Time Teaching: A Tool for Enhancing Student Engagement in Advanced Foreign Language Learning

    ERIC Educational Resources Information Center

    Abreu, Laurel; Knouse, Stephanie

    2014-01-01

    Scholars have indicated a need for further research on effective pedagogical strategies designed for advanced foreign language courses in the postsecondary setting, especially in light of decreased enrollments at this level and the elimination of foreign language programs altogether in some institutions (Paesani & Allen, 2012). This article…

  9. Advanced Technologies as Educational Tools in Science: Concepts, Applications, and Issues. Monograph Series Number 8.

    ERIC Educational Resources Information Center

    Kumar, David D.; And Others

    Systems incorporating two advanced technologies, hypermedia systems and intelligent tutors, are examined with respect to their potential impact on science education. The conceptual framework underlying these systems is discussed first. Applications of systems are then presented with examples of each in operation within the context of science…

  10. Genetic tools for advancement of Synechococcus sp. PCC 7002 as a cyanobacterial chassis

    DOE PAGES

    Ruffing, Anne M.; Jensen, Travis J.; Strickland, Lucas M.

    2016-11-10

    Successful implementation of modified cyanobacteria as hosts for industrial applications requires the development of a cyanobacterial chassis. The cyanobacterium Synechococcus sp. PCC 7002 embodies key attributes for an industrial host, including a fast growth rate and high salt, light, and temperature tolerances. Here, this study addresses key limitations in the advancement of Synechococcus sp. PCC 7002 as an industrial chassis.

  11. Teaching Advanced Concepts in Computer Networks: VNUML-UM Virtualization Tool

    ERIC Educational Resources Information Center

    Ruiz-Martinez, A.; Pereniguez-Garcia, F.; Marin-Lopez, R.; Ruiz-Martinez, P. M.; Skarmeta-Gomez, A. F.

    2013-01-01

    In the teaching of computer networks the main problem that arises is the high price and limited number of network devices the students can work with in the laboratories. Nowadays, with virtualization we can overcome this limitation. In this paper, we present a methodology that allows students to learn advanced computer network concepts through…

  12. POLYANA-A tool for the calculation of molecular radial distribution functions based on Molecular Dynamics trajectories

    NASA Astrophysics Data System (ADS)

    Dimitroulis, Christos; Raptis, Theophanes; Raptis, Vasilios

    2015-12-01

    We present an application for the calculation of radial distribution functions for molecular centres of mass, based on trajectories generated by molecular simulation methods (Molecular Dynamics, Monte Carlo). When designing this application, the emphasis was placed on ease of use as well as ease of further development. In its current version, the program can read trajectories generated by the well-known DL_POLY package, but it can be easily extended to handle other formats. It is also very easy to 'hack' the program so it can compute intermolecular radial distribution functions for groups of interaction sites rather than whole molecules.

  13. Recent advances in microbial production of fuels and chemicals using tools and strategies of systems metabolic engineering.

    PubMed

    Cho, Changhee; Choi, So Young; Luo, Zi Wei; Lee, Sang Yup

    2015-11-15

    The advent of various systems metabolic engineering tools and strategies has enabled more sophisticated engineering of microorganisms for the production of industrially useful fuels and chemicals. Advances in systems metabolic engineering have been made in overproducing natural chemicals and producing novel non-natural chemicals. In this paper, we review the tools and strategies of systems metabolic engineering employed for the development of microorganisms for the production of various industrially useful chemicals belonging to fuels, building block chemicals, and specialty chemicals, in particular focusing on those reported in the last three years. It was aimed at providing the current landscape of systems metabolic engineering and suggesting directions to address future challenges towards successfully establishing processes for the bio-based production of fuels and chemicals from renewable resources.

  14. Towards the characterization of noise sources in a supersonic three-stream jet using advanced analysis tools

    NASA Astrophysics Data System (ADS)

    Ruscher, Christopher; Gogineni, Sivaram

    2016-11-01

    Strict noise regulation set by governing bodies currently make supersonic commercial aviation impractical. One of the many challenges that exist in developing practical supersonic commercial aircraft is the noise produced by the engine's exhaust jet. A promising method of jet noise reduction for supersonic applications is through the addition of extra exhaust streams. Data for an axisymmetric three-stream nozzle were generated using the Naval Research Laboratory's JENRE code. This data will be compared to experimental results obtained by NASA for validation purposes. Once the simulation results show satisfactory agreement to the experiments, advanced analysis tools will be applied to the simulation data to characterize potential noise sources. The tools to be applied include methods that are based on proper orthogonal decomposition, wavelet decomposition, and stochastic estimation. Additionally, techniques such as empirical mode decomposition and momentum potential theorem will be applied to the data as well.

  15. Advanced Algorithms and Automation Tools for Discrete Ordinates Methods in Parallel Environments

    SciTech Connect

    Alireza Haghighat

    2003-05-07

    This final report discusses major accomplishments of a 3-year project under the DOE's NEER Program. The project has developed innovative and automated algorithms, codes, and tools for solving the discrete ordinates particle transport method efficiently in parallel environments. Using a number of benchmark and real-life problems, the performance and accuracy of the new algorithms have been measured and analyzed.

  16. The Impact of New Technologic and Molecular Advances in the Daily Practice of Gastrointestinal and Hepatobiliary Pathology.

    PubMed

    Xue, Yue; Farris, Alton Brad; Quigley, Brian; Krasinskas, Alyssa

    2017-04-01

    The practice of anatomic pathology, and of gastrointestinal pathology in particular, has been dramatically transformed in the past decade. In addition to the multitude of diseases, syndromes, and clinical entities encountered in daily clinical practice, the increasing integration of new technologic and molecular advances into the field of gastroenterology is occurring at a fast pace. Application of these advances has challenged pathologists to correlate newer methodologies with existing morphologic criteria, which in many instances still provide the gold standard for diagnosis. This review describes the impact of new technologic and molecular advances on the daily practice of gastrointestinal and hepatobiliary pathology. We discuss new drugs that can affect the gastrointestinal tract and liver, new endoluminal techniques, new molecular tests that are often performed reflexively, new imaging techniques for evaluating hepatocellular carcinoma, and modified approaches to the gross and histologic assessment of tissues that have been exposed to neoadjuvant therapies.

  17. Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

    PubMed Central

    Bayraktar, Soley; Rocha-Lima, Caio M

    2013-01-01

    Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death in both men and women in the United States. Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease. Improvements in overall survival and quality of life have been modest. Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics, thus changing the treatment paradigm for many NSCLC patients. In this review, we present a summary of many of the currently investigated biologic targets in NSCLC, discuss their current clinical trial status, and also discuss the potential for development of other targeted agents. PMID:23696960

  18. Vibrio parahaemolyticus: a review on the pathogenesis, prevalence, and advance molecular identification techniques.

    PubMed

    Letchumanan, Vengadesh; Chan, Kok-Gan; Lee, Learn-Han

    2014-01-01

    Vibrio parahaemolyticus is a Gram-negative halophilic bacterium that is found in estuarine, marine and coastal environments. V. parahaemolyticus is the leading causal agent of human acute gastroenteritis following the consumption of raw, undercooked, or mishandled marine products. In rare cases, V. parahaemolyticus causes wound infection, ear infection or septicaemia in individuals with pre-existing medical conditions. V. parahaemolyticus has two hemolysins virulence factors that are thermostable direct hemolysin (tdh)-a pore-forming protein that contributes to the invasiveness of the bacterium in humans, and TDH-related hemolysin (trh), which plays a similar role as tdh in the disease pathogenesis. In addition, the bacterium is also encodes for adhesions and type III secretion systems (T3SS1 and T3SS2) to ensure its survival in the environment. This review aims at discussing the V. parahaemolyticus growth and characteristics, pathogenesis, prevalence and advances in molecular identification techniques.

  19. Recent Advances in the Molecular Pathogenesis of Dystonia-Plus Syndromes and Heredodegenerative Dystonias

    PubMed Central

    Casper, Catharina; Kalliolia, Eirini; Warner, Thomas T

    2013-01-01

    The majority of studies investigating the molecular pathogenesis and cell biology underlying dystonia have been performed in individuals with primary dystonia. This includes monogenic forms such as DYT1and DYT6 dystonia, and primary focal dystonia which is likely to be multifactorial in origin. In recent years there has been renewed interest in non-primary forms of dystonia including the dystonia-plus syndromes and heredodegenerative disorders. These are caused by a variety of genetic mutations and their study has contributed to our understanding of the neuronal dysfunction that leads to dystonia These findings have reinforced themes identified from study of primary dystonia including abnormal dopaminergic signalling, cellular trafficking and mitochondrial function. In this review we highlight recent advances in the understanding of the dystonia-plus syndromes and heredodegenerative dystonias. PMID:23814535

  20. Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

    PubMed

    Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

    2014-06-01

    The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

  1. Vibrio parahaemolyticus: a review on the pathogenesis, prevalence, and advance molecular identification techniques

    PubMed Central

    Letchumanan, Vengadesh; Chan, Kok-Gan; Lee, Learn-Han

    2014-01-01

    Vibrio parahaemolyticus is a Gram-negative halophilic bacterium that is found in estuarine, marine and coastal environments. V. parahaemolyticus is the leading causal agent of human acute gastroenteritis following the consumption of raw, undercooked, or mishandled marine products. In rare cases, V. parahaemolyticus causes wound infection, ear infection or septicaemia in individuals with pre-existing medical conditions. V. parahaemolyticus has two hemolysins virulence factors that are thermostable direct hemolysin (tdh)-a pore-forming protein that contributes to the invasiveness of the bacterium in humans, and TDH-related hemolysin (trh), which plays a similar role as tdh in the disease pathogenesis. In addition, the bacterium is also encodes for adhesions and type III secretion systems (T3SS1 and T3SS2) to ensure its survival in the environment. This review aims at discussing the V. parahaemolyticus growth and characteristics, pathogenesis, prevalence and advances in molecular identification techniques. PMID:25566219

  2. Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment

    PubMed Central

    Polireddy, Kishore; Chen, Qi

    2016-01-01

    Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of <1 year and a 5-year survival of ~5%. The dismal survival rate and prognosis are likely due to lack of early diagnosis, fulminant disease course, high metastasis rate, and disappointing treatment outcome. Pancreatic cancers harbor a variety of genetic alternations that render it difficult to treat even with targeted therapy. Recent studies revealed that pancreatic cancers are highly enriched with a cancer stem cell (CSC) population, which is resistant to chemotherapeutic drugs, and therefore escapes chemotherapy and promotes tumor recurrence. Cancer cell epithelial to mesenchymal transition (EMT) is highly associated with metastasis, generation of CSCs, and treatment resistance in pancreatic cancer. Reviewed here are the molecular biology of pancreatic cancer, the major signaling pathways regulating pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreatic cancer. PMID:27471566

  3. Genetic tools for advancement of Synechococcus sp. PCC 7002 as a cyanobacterial chassis

    SciTech Connect

    Ruffing, Anne M.; Jensen, Travis J.; Strickland, Lucas M.

    2016-11-10

    Successful implementation of modified cyanobacteria as hosts for industrial applications requires the development of a cyanobacterial chassis. The cyanobacterium Synechococcus sp. PCC 7002 embodies key attributes for an industrial host, including a fast growth rate and high salt, light, and temperature tolerances. Here, this study addresses key limitations in the advancement of Synechococcus sp. PCC 7002 as an industrial chassis.

  4. The R.E.D. tools: advances in RESP and ESP charge derivation and force field library building.

    PubMed

    Dupradeau, François-Yves; Pigache, Adrien; Zaffran, Thomas; Savineau, Corentin; Lelong, Rodolphe; Grivel, Nicolas; Lelong, Dimitri; Rosanski, Wilfried; Cieplak, Piotr

    2010-07-28

    Deriving atomic charges and building a force field library for a new molecule are key steps when developing a force field required for conducting structural and energy-based analysis using molecular mechanics. Derivation of popular RESP charges for a set of residues is a complex and error prone procedure because it depends on numerous input parameters. To overcome these problems, the R.E.D. Tools (RESP and ESP charge Derive, ) have been developed to perform charge derivation in an automatic and straightforward way. The R.E.D. program handles chemical elements up to bromine in the periodic table. It interfaces different quantum mechanical programs employed for geometry optimization and computing molecular electrostatic potential(s), and performs charge fitting using the RESP program. By defining tight optimization criteria and by controlling the molecular orientation of each optimized geometry, charge values are reproduced at any computer platform with an accuracy of 0.0001 e. The charges can be fitted using multiple conformations, making them suitable for molecular dynamics simulations. R.E.D. allows also for defining charge constraints during multiple molecule charge fitting, which are used to derive charges for molecular fragments. Finally, R.E.D. incorporates charges into a force field library, readily usable in molecular dynamics computer packages. For complex cases, such as a set of homologous molecules belonging to a common family, an entire force field topology database is generated. Currently, the atomic charges and force field libraries have been developed for more than fifty model systems and stored in the RESP ESP charge DDataBase. Selected results related to non-polarizable charge models are presented and discussed.

  5. Using Enabling Technologies to Advance Data Intensive Analysis Tools in the JPL Tropical Cyclone Information System

    NASA Astrophysics Data System (ADS)

    Knosp, B.; Gangl, M. E.; Hristova-Veleva, S. M.; Kim, R. M.; Lambrigtsen, B.; Li, P.; Niamsuwan, N.; Shen, T. P. J.; Turk, F. J.; Vu, Q. A.

    2014-12-01

    The JPL Tropical Cyclone Information System (TCIS) brings together satellite, aircraft, and model forecast data from several NASA, NOAA, and other data centers to assist researchers in comparing and analyzing data related to tropical cyclones. The TCIS has been supporting specific science field campaigns, such as the Genesis and Rapid Intensification Processes (GRIP) campaign and the Hurricane and Severe Storm Sentinel (HS3) campaign, by creating near real-time (NRT) data visualization portals. These portals are intended to assist in mission planning, enhance the understanding of current physical processes, and improve model data by comparing it to satellite and aircraft observations. The TCIS NRT portals allow the user to view plots on a Google Earth interface. To compliment these visualizations, the team has been working on developing data analysis tools to let the user actively interrogate areas of Level 2 swath and two-dimensional plots they see on their screen. As expected, these observation and model data are quite voluminous and bottlenecks in the system architecture can occur when the databases try to run geospatial searches for data files that need to be read by the tools. To improve the responsiveness of the data analysis tools, the TCIS team has been conducting studies on how to best store Level 2 swath footprints and run sub-second geospatial searches to discover data. The first objective was to improve the sampling accuracy of the footprints being stored in the TCIS database by comparing the Java-based NASA PO.DAAC Level 2 Swath Generator with a TCIS Python swath generator. The second objective was to compare the performance of four database implementations - MySQL, MySQL+Solr, MongoDB, and PostgreSQL - to see which database management system would yield the best geospatial query and storage performance. The final objective was to integrate our chosen technologies with our Joint Probability Density Function (Joint PDF), Wave Number Analysis, and

  6. Australian endemic pest tephritids: genetic, molecular and microbial tools for improved Sterile Insect Technique

    PubMed Central

    2014-01-01

    Among Australian endemic tephritid fruit flies, the sibling species Bactrocera tryoni and Bactrocera neohumeralis have been serious horticultural pests since the introduction of horticulture in the nineteenth century. More recently, Bactrocera jarvisi has also been declared a pest in northern Australia. After several decades of genetic research there is now a range of classical and molecular genetic tools that can be used to develop improved Sterile Insect Technique (SIT) strains for control of these pests. Four-way crossing strategies have the potential to overcome the problem of inbreeding in mass-reared strains of B. tryoni. The ability to produce hybrids between B. tryoni and the other two species in the laboratory has proved useful for the development of genetically marked strains. The identification of Y-chromosome markers in B. jarvisi means that male and female embryos can be distinguished in any strain that carries a B. jarvisi Y chromosome. This has enabled the study of homologues of the sex-determination genes during development of B jarvisi and B. tryoni, which is necessary for the generation of genetic-sexing strains. Germ-line transformation has been established and a draft genome sequence for B. tryoni released. Transcriptomes from various species, tissues and developmental stages, to aid in identification of manipulation targets for improving SIT, have been assembled and are in the pipeline. Broad analyses of the microbiome have revealed a metagenome that is highly variable within and across species and defined by the environment. More specific analyses detected Wolbachia at low prevalence in the tropics but absent in temperate regions, suggesting a possible role for this endosymbiont in future control strategies. PMID:25470996

  7. Advances in the field of high-molecular-weight polycyclic aromatic hydrocarbon biodegradation by bacteria.

    PubMed

    Kanaly, Robert A; Harayama, Shigeaki

    2010-03-01

    Interest in understanding prokaryotic biotransformation of high-molecular-weight polycyclic aromatic hydrocarbons (HMW PAHs) has continued to grow and the scientific literature shows that studies in this field are originating from research groups from many different locations throughout the world. In the last 10 years, research in regard to HMW PAH biodegradation by bacteria has been further advanced through the documentation of new isolates that represent diverse bacterial types that have been isolated from different environments and that possess different metabolic capabilities. This has occurred in addition to the continuation of in-depth comprehensive characterizations of previously isolated organisms, such as Mycobacterium vanbaalenii PYR-1. New metabolites derived from prokaryotic biodegradation of four- and five-ring PAHs have been characterized, our knowledge of the enzymes involved in these transformations has been advanced and HMW PAH biodegradation pathways have been further developed, expanded upon and refined. At the same time, investigation of prokaryotic consortia has furthered our understanding of the capabilities of microorganisms functioning as communities during HMW PAH biodegradation.

  8. Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

    PubMed Central

    Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

    2017-01-01

    Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

  9. Advanced contrast nanoagents for photoacoustic molecular imaging, cytometry, blood test and photothermal theranostics†

    PubMed Central

    de la Zerda, Adam; Kim, Jin-Woo; Galanzha, Ekaterina I.; Gambhir, Sanjiv S.; Zharov, Vladimir P.

    2013-01-01

    Various nanoparticles have raised significant interest over the past decades for their unique physical and optical properties and biological utilities. Here we summarize the vast applications of advanced nanoparticles with a focus on carbon nanotube (CNT)-based or CNT-catalyzed contrast agents for photoacoustic (PA) imaging, cytometry and theranostics applications based on the photothermal (PT) effect. We briefly review the safety and potential toxicity of the PA/PT contrast nanoagents, while showing how the physical properties as well as multiple biological coatings change their toxicity profiles and contrasts. We provide general guidelines needed for the validation of a new molecular imaging agent in living subjects, and exemplify these guidelines with single-walled CNTs targeted to αvβ3, an integrin associated with tumor angiogenesis, and golden carbon nanotubes targeted to LYVE-1, endothelial lymphatic receptors. An extensive review of the potential applications of advanced contrast agents is provided, including imaging of static targets such as tumor angiogenesis receptors, in vivo cytometry of dynamic targets such as circulating tumor cells and nanoparticles in blood, lymph, bones and plants, methods to enhance the PA and PT effects with transient and stationary bubble conjugates, PT/PA Raman imaging and multispectral histology. Finally, theranostic applications are reviewed, including the nanophotothermolysis of individual tumor cells and bacteria with clustered nanoparticles, nanothrombolysis of blood clots, detection and purging metastasis in sentinel lymph nodes, spectral hole burning and multiplex therapy with ultrasharp rainbow nanoparticles. PMID:22025336

  10. EEGLAB, SIFT, NFT, BCILAB, and ERICA: New Tools for Advanced EEG Processing

    PubMed Central

    Delorme, Arnaud; Mullen, Tim; Kothe, Christian; Akalin Acar, Zeynep; Bigdely-Shamlo, Nima; Vankov, Andrey; Makeig, Scott

    2011-01-01

    We describe a set of complementary EEG data collection and processing tools recently developed at the Swartz Center for Computational Neuroscience (SCCN) that connect to and extend the EEGLAB software environment, a freely available and readily extensible processing environment running under Matlab. The new tools include (1) a new and flexible EEGLAB STUDY design facility for framing and performing statistical analyses on data from multiple subjects; (2) a neuroelectromagnetic forward head modeling toolbox (NFT) for building realistic electrical head models from available data; (3) a source information flow toolbox (SIFT) for modeling ongoing or event-related effective connectivity between cortical areas; (4) a BCILAB toolbox for building online brain-computer interface (BCI) models from available data, and (5) an experimental real-time interactive control and analysis (ERICA) environment for real-time production and coordination of interactive, multimodal experiments. PMID:21687590

  11. Anvil Forecast Tool in the Advanced Weather Interactive Processing System, Phase II

    NASA Technical Reports Server (NTRS)

    Barrett, Joe H., III

    2008-01-01

    Meteorologists from the 45th Weather Squadron (45 WS) and Spaceflight Meteorology Group have identified anvil forecasting as one of their most challenging tasks when predicting the probability of violations of the Lightning Launch Commit Criteria and Space Light Rules. As a result, the Applied Meteorology Unit (AMU) created a graphical overlay tool for the Meteorological Interactive Data Display Systems (MIDDS) to indicate the threat of thunderstorm anvil clouds, using either observed or model forecast winds as input.

  12. ADVANCEMENT OF NUCLEIC ACID-BASED TOOLS FOR MONITORING IN SITU REDUCTIVE DECHLORINATION

    SciTech Connect

    Vangelas, K; ELIZABETH EDWARDS, E; FRANK LOFFLER, F; Brian02 Looney, B

    2006-11-17

    Regulatory protocols generally recognize that destructive processes are the most effective mechanisms that support natural attenuation of chlorinated solvents. In many cases, these destructive processes will be biological processes and, for chlorinated compounds, will often be reductive processes that occur under anaerobic conditions. The existing EPA guidance (EPA, 1998) provides a list of parameters that provide indirect evidence of reductive dechlorination processes. In an effort to gather direct evidence of these processes, scientists have identified key microorganisms and are currently developing tools to measure the abundance and activity of these organisms in subsurface systems. Drs. Edwards and Luffler are two recognized leaders in this field. The research described herein continues their development efforts to provide a suite of tools to enable direct measures of biological processes related to the reductive dechlorination of TCE and PCE. This study investigated the strengths and weaknesses of the 16S rRNA gene-based approach to characterizing the natural attenuation capabilities in samples. The results suggested that an approach based solely on 16S rRNA may not provide sufficient information to document the natural attenuation capabilities in a system because it does not distinguish between strains of organisms that have different biodegradation capabilities. The results of the investigations provided evidence that tools focusing on relevant enzymes for functionally desired characteristics may be useful adjuncts to the 16SrRNA methods.

  13. Molecular Engineering with Organic Carbonyl Electrode Materials for Advanced Stationary and Redox Flow Rechargeable Batteries.

    PubMed

    Zhao, Qing; Zhu, Zhiqiang; Chen, Jun

    2017-04-03

    Organic carbonyl electrode materials that have the advantages of high capacity, low cost and being environmentally friendly, are regarded as powerful candidates for next-generation stationary and redox flow rechargeable batteries (RFBs). However, low carbonyl utilization, poor electronic conductivity and undesired dissolution in electrolyte are urgent issues to be solved. Here, we summarize a molecular engineering approach for tuning the capacity, working potential, concentration of active species, kinetics, and stability of stationary and redox flow batteries, which well resolves the problems of organic carbonyl electrode materials. As an example, in stationary batteries, 9,10-anthraquinone (AQ) with two carbonyls delivers a capacity of 257 mAh g(-1) (2.27 V vs Li(+) /Li), while increasing the number of carbonyls to four with the formation of 5,7,12,14-pentacenetetrone results in a higher capacity of 317 mAh g(-1) (2.60 V vs Li(+) /Li). In RFBs, AQ, which is less soluble in aqueous electrolyte, reaches 1 M by grafting -SO3 H with the formation of 9,10-anthraquinone-2,7-disulphonic acid, resulting in a power density exceeding 0.6 W cm(-2) with long cycling life. Therefore, through regulating substituent groups, conjugated structures, Coulomb interactions, and the molecular weight, the electrochemical performance of carbonyl electrode materials can be rationally optimized. This review offers fundamental principles and insight into designing advanced carbonyl materials for the electrodes of next-generation rechargeable batteries.

  14. Novel Advances in Understanding of Molecular Pathogenesis of Hepatoblastoma: A Wnt/β-Catenin Perspective

    PubMed Central

    Bell, Danielle; Ranganathan, Sarangarajan; Tao, Junyan; Monga, Satdarshan P. S.

    2017-01-01

    Hepatoblastoma is the most common pediatric liver malignancy, typically striking children within the first 3 years of their young lives. While advances in chemotherapy and newer surgical techniques have improved survival in patients with localized disease, unfortunately, for the 25% of patients with metastasis, the overall survival remains poor. These tumors, which are thought to arise from hepatic progenitors or hepatoblasts, hence the name hepatoblastoma, can be categorized by histological subtyping based on their level of cell differentiation. Genomic and histological analysis of human tumor samples has shown exon-3 deletions or missense mutations in gene coding for β-catenin, a downstream effector of the Wnt signaling pathway, in up to 90% of hepatoblastoma cases. The current article will review key aberrations in molecular pathways that are implicated in various subtypes of hepatoblastoma with an emphasis on Wnt signaling. It will also discuss cooperation among components of pathways such as β-catenin and Yes-associated protein in cancer development. Understanding the complex network of molecular signaling in oncogenesis will undoubtedly aid in the discovery of new therapeutics to help combat hepatoblastoma. PMID:27938502

  15. Apoptosis: A Four-Week Laboratory Investigation for Advanced Molecular and Cellular Biology Students

    PubMed Central

    DiBartolomeis, Susan M.; Moné, James P.

    2003-01-01

    Over the past decade, apoptosis has emerged as an important field of study central to ongoing research in many diverse fields, from developmental biology to cancer research. Apoptosis proceeds by a highly coordinated series of events that includes enzyme activation, DNA fragmentation, and alterations in plasma membrane permeability. The detection of each of these phenotypic changes is accessible to advanced undergraduate cell and molecular biology students. We describe a 4-week laboratory sequence that integrates cell culture, fluorescence microscopy, DNA isolation and analysis, and western blotting (immunoblotting) to follow apoptosis in cultured human cells. Students working in teams chemically induce apoptosis, and harvest, process, and analyze cells, using their data to determine the order of events during apoptosis. We, as instructors, expose the students to an environment closely simulating what they would encounter in an active cell or molecular biology research laboratory by having students coordinate and perform multiple tasks simultaneously and by having them experience experimental design using current literature, data interpretation, and analysis to answer a single question. Students are assessed by examination of laboratory notebooks for completeness of experimental protocols and analysis of results and for completion of an assignment that includes questions pertaining to data interpretation and apoptosis. PMID:14673493

  16. Assessment of chloroethene biodegradation in the subsurface by microbiological, molecular and isotopic tools

    NASA Astrophysics Data System (ADS)

    Schmidt, K. R.; Kranzioch, I.; Heidinger, M.; Ertl, S.; Tiehm, A.

    2012-04-01

    methods is continuously increasing. For example, microbiological and molecular tools showed the presence and activity of halorespiring bacteria in sediment samples of the Yangtze river, China. PCR-detection demonstrated the presence of five different halorespiring bacterial groups as well as of four different dechlorinating enzymes of Dehalococcoides. In conclusion, our study demonstrates that (i) multiple lines of evidence approaches result in a profound understanding of the biodegradation processes occurring in the field, (ii) stable isotope fractionation is suitable for assessing and quantifying anaerobic and aerobic chloroethene degradation and (iii) detection and quantification of dechlorinating bacteria and enzymes by PCR methods provide more insight into biodegradation processes. Acknowledgement The authors gratefully acknowledge financial support by the German Ministry of Education and Research (BMBF, grant no 02WN0446, 02WN0447 and 02WT1130), the German Ministry of Economics and Technology (BMWi, grant no KF2265705AK9 and KF2285302AK9) and the federal state of Rhineland-Palatinate. We thank all project partners for fruitful cooperation.

  17. A Multi-layer, Data-driven Advanced Reasoning Tool for Intelligent Data Mining and Analysis for Smart Grids

    SciTech Connect

    Lu, Ning; Du, Pengwei; Greitzer, Frank L.; Guo, Xinxin; Hohimer, Ryan E.; Pomiak, Yekaterina G.

    2012-12-31

    This paper presents the multi-layer, data-driven advanced reasoning tool (M-DART), a proof-of-principle decision support tool for improved power system operation. M-DART will cross-correlate and examine different data sources to assess anomalies, infer root causes, and anneal data into actionable information. By performing higher-level reasoning “triage” of diverse data sources, M-DART focuses on early detection of emerging power system events and identifies highest priority actions for the human decision maker. M-DART represents a significant advancement over today’s grid monitoring technologies that apply offline analyses to derive model-based guidelines for online real-time operations and use isolated data processing mechanisms focusing on individual data domains. The development of the M-DART will bridge these gaps by reasoning about results obtained from multiple data sources that are enabled by the smart grid infrastructure. This hybrid approach integrates a knowledge base that is trained offline but tuned online to capture model-based relationships while revealing complex causal relationships among data from different domains.

  18. Performance analysis and optimization of an advanced pharmaceutical wastewater treatment plant through a visual basic software tool (PWWT.VB).

    PubMed

    Pal, Parimal; Thakura, Ritwik; Chakrabortty, Sankha

    2016-05-01

    A user-friendly, menu-driven simulation software tool has been developed for the first time to optimize and analyze the system performance of an advanced continuous membrane-integrated pharmaceutical wastewater treatment plant. The software allows pre-analysis and manipulation of input data which helps in optimization and shows the software performance visually on a graphical platform. Moreover, the software helps the user to "visualize" the effects of the operating parameters through its model-predicted output profiles. The software is based on a dynamic mathematical model, developed for a systematically integrated forward osmosis-nanofiltration process for removal of toxic organic compounds from pharmaceutical wastewater. The model-predicted values have been observed to corroborate well with the extensive experimental investigations which were found to be consistent under varying operating conditions like operating pressure, operating flow rate, and draw solute concentration. Low values of the relative error (RE = 0.09) and high values of Willmott-d-index (d will = 0.981) reflected a high degree of accuracy and reliability of the software. This software is likely to be a very efficient tool for system design or simulation of an advanced membrane-integrated treatment plant for hazardous wastewater.

  19. CONFERENCE NOTE: International Workshop on Advanced Mathematical Tools in Metrology, Villa Gualino, Torino, Italy, 20 22 October 1993

    NASA Astrophysics Data System (ADS)

    1993-01-01

    Preliminary Programme The three-day programme features approximately twenty-five invited contributions. Participants may present a poster on the topic "Applications for Industrial Measurements", concerning applied mathematics, software development and computer-based measurements. 20 October Two plenary talks on mathematical methods and metrological applications "Numerical Methods and Modelling" Partial differential equations and integral equations Methods of identification and validation Algorithms for approximation Geometrical shape determination of industrial solids Round Table 21 October "Data Analysis" Spectral analysis and wavelets Calibration of precision instrumentation Comparison measurement of standards Statistical methods in metrology Robust estimation and outliers Applications of the bootstrap method Round Table 22 October (in cooperation with SIMAI and ASP) "Applications for Industrial Measurements" Data acquisition Measurement software, standard computational modules and their validation Round Table Industrial presentations Discussion of poster presentations Conclusions Lecturers Mathematicians from the international metrological community; mathematicians from Italian universities (Politecnico of Torino, Milano, Università di Genova, Milano, Padova, Roma, Trento); scientists and mathematicians from national standards institutes and the Italian National Research Council. The workshop will be of interest to people in universities, research centres and industry who are involved in measurement and need advanced mathematical tools to solve their problems, and to those who work in the development of these mathematical tools. Metrology is concerned with measurement at the highest level of precision. Advances in metrology depend on many factors: improvements in scientific and technical knowledge, instrumentation quality, better use of advanced mathematical tools and the development of new tools. In some countries, metrological institutions have a tradition of

  20. Pantograph catenary dynamic optimisation based on advanced multibody and finite element co-simulation tools

    NASA Astrophysics Data System (ADS)

    Massat, Jean-Pierre; Laurent, Christophe; Bianchi, Jean-Philippe; Balmès, Etienne

    2014-05-01

    This paper presents recent developments undertaken by SNCF Innovation & Research Department on numerical modelling of pantograph catenary interaction. It aims at describing an efficient co-simulation process between finite element (FE) and multibody (MB) modelling methods. FE catenary models are coupled with a full flexible MB representation with pneumatic actuation of pantograph. These advanced functionalities allow new kind of numerical analyses such as dynamic improvements based on innovative pneumatic suspensions or assessment of crash risks crossing areas that demonstrate the powerful capabilities of this computing approach.

  1. Advanced techniques in IR thermography as a tool for the pest management professional

    NASA Astrophysics Data System (ADS)

    Grossman, Jon L.

    2006-04-01

    Within the past five years, the Pest Management industry has become aware that IR thermography can aid in the detection of pest infestations and locate other conditions that are within the purview of the industry. This paper will review the applications that can be utilized by the pest management professional and discuss the advanced techniques that may be required in conjunction with thermal imaging to locate insect and other pest infestations, moisture within structures, the verification of data and the special challenges associated with the inspection process.

  2. Advancing of Russian ChemBioGrid by bringing Data Management tools into collaborative environment.

    PubMed

    Zhuchkov, Alexey; Tverdokhlebov, Nikolay; Kravchenko, Alexander

    2006-01-01

    Virtual organizations of researchers need effective tools to work collaboratively with huge sets of heterogeneous data distributed over HealthGrid. This paper describes a mechanism of supporting Digital Libraries in High-Performance Computing environment based on Grid technology. The proposed approach provides abilities to assemble heterogeneous data from distributed sources into integrated virtual collections by using OGSA-DAI. The core of the conception is a Repository of Meta-Descriptions that are sets of metadata which define personal and collaborative virtual collections on base of virtualized information resources. The Repository is kept in a native XML-database Sedna and is maintained by Grid Data Services.

  3. NASA Advanced Concepts Office, Earth-To-Orbit Team Design Process and Tools

    NASA Technical Reports Server (NTRS)

    Waters, Eric D.; Garcia, Jessica; Beers, Benjamin; Philips, Alan; Holt, James B.; Threet, Grady E., Jr.

    2013-01-01

    The Earth to Orbit (ETO) Team of the Advanced Concepts Office (ACO) at NASA Marshal Space Flight Center (MSFC) is considered the preeminent group to go to for prephase A and phase A concept definition. The ACO team has been at the forefront of a multitude of launch vehicle studies determining the future direction of the Agency as a whole due, in part, to their rapid turnaround time in analyzing concepts and their ability to cover broad trade spaces of vehicles in that limited timeframe. Each completed vehicle concept includes a full mass breakdown of each vehicle to tertiary subsystem components, along with a vehicle trajectory analysis to determine optimized payload delivery to specified orbital parameters, flight environments, and delta v capability. Additionally, a structural analysis of the vehicle based on material properties and geometries is performed as well as an analysis to determine the flight loads based on the trajectory outputs. As mentioned, the ACO Earth to Orbit Team prides themselves on their rapid turnaround time and often need to fulfill customer requests within limited schedule or little advanced notice. Due to working in this fast paced environment, the ETO team has developed some finely honed skills and methods to maximize the delivery capability to meet their customer needs. This paper will describe the interfaces between the 3 primary disciplines used in the design process; weights and sizing, trajectory, and structural analysis, as well as the approach each discipline employs to streamline their particular piece of the design process.

  4. Analytical tools employed to determine pharmaceutical compounds in wastewaters after application of advanced oxidation processes.

    PubMed

    Afonso-Olivares, Cristina; Montesdeoca-Esponda, Sarah; Sosa-Ferrera, Zoraida; Santana-Rodríguez, José Juan

    2016-12-01

    Today, the presence of contaminants in the environment is a topic of interest for society in general and for the scientific community in particular. A very large amount of different chemical substances reaches the environment after passing through wastewater treatment plants without being eliminated. This is due to the inefficiency of conventional removal processes and the lack of government regulations. The list of compounds entering treatment plants is gradually becoming longer and more varied because most of these compounds come from pharmaceuticals, hormones or personal care products, which are increasingly used by modern society. As a result of this increase in compound variety, to address these emerging pollutants, the development of new and more efficient removal technologies is needed. Different advanced oxidation processes (AOPs), especially photochemical AOPs, have been proposed as supplements to traditional treatments for the elimination of pollutants, showing significant advantages over the use of conventional methods alone. This work aims to review the analytical methodologies employed for the analysis of pharmaceutical compounds from wastewater in studies in which advanced oxidation processes are applied. Due to the low concentrations of these substances in wastewater, mass spectrometry detectors are usually chosen to meet the low detection limits and identification power required. Specifically, time-of-flight detectors are required to analyse the by-products.

  5. Phylemon 2.0: a suite of web-tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing.

    PubMed

    Sánchez, Rubén; Serra, François; Tárraga, Joaquín; Medina, Ignacio; Carbonell, José; Pulido, Luis; de María, Alejandro; Capella-Gutíerrez, Salvador; Huerta-Cepas, Jaime; Gabaldón, Toni; Dopazo, Joaquín; Dopazo, Hernán

    2011-07-01

    Phylemon 2.0 is a new release of the suite of web tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing. It has been designed as a response to the increasing demand of molecular sequence analyses for experts and non-expert users. Phylemon 2.0 has several unique features that differentiates it from other similar web resources: (i) it offers an integrated environment that enables evolutionary analyses, format conversion, file storage and edition of results; (ii) it suggests further analyses, thereby guiding the users through the web server; and (iii) it allows users to design and save phylogenetic pipelines to be used over multiple genes (phylogenomics). Altogether, Phylemon 2.0 integrates a suite of 30 tools covering sequence alignment reconstruction and trimming; tree reconstruction, visualization and manipulation; and evolutionary hypotheses testing.

  6. Emerging tools for continuous nutrient monitoring networks: Sensors advancing science and water resources protection

    USGS Publications Warehouse

    Pellerin, Brian; Stauffer, Beth A; Young, Dwane A; Sullivan, Daniel J.; Bricker, Suzanne B.; Walbridge, Mark R; Clyde, Gerard A; Shaw, Denice M

    2016-01-01

    Sensors and enabling technologies are becoming increasingly important tools for water quality monitoring and associated water resource management decisions. In particular, nutrient sensors are of interest because of the well-known adverse effects of nutrient enrichment on coastal hypoxia, harmful algal blooms, and impacts to human health. Accurate and timely information on nutrient concentrations and loads is integral to strategies designed to minimize risk to humans and manage the underlying drivers of water quality impairment. Using nitrate sensors as an example, we highlight the types of applications in freshwater and coastal environments that are likely to benefit from continuous, real-time nutrient data. The concurrent emergence of new tools to integrate, manage and share large data sets is critical to the successful use of nutrient sensors and has made it possible for the field of continuous nutrient monitoring to rapidly move forward. We highlight several near-term opportunities for Federal agencies, as well as the broader scientific and management community, that will help accelerate sensor development, build and leverage sites within a national network, and develop open data standards and data management protocols that are key to realizing the benefits of a large-scale, integrated monitoring network. Investing in these opportunities will provide new information to guide management and policies designed to protect and restore our nation’s water resources.

  7. GenSAA: A tool for advancing satellite monitoring with graphical expert systems

    NASA Technical Reports Server (NTRS)

    Hughes, Peter M.; Luczak, Edward C.

    1993-01-01

    During numerous contacts with a satellite each day, spacecraft analysts must closely monitor real time data for combinations of telemetry parameter values, trends, and other indications that may signify a problem or failure. As satellites become more complex and the number of data items increases, this task is becoming increasingly difficult for humans to perform at acceptable performance levels. At the NASA Goddard Space Flight Center, fault-isolation expert systems have been developed to support data monitoring and fault detection tasks in satellite control centers. Based on the lessons learned during these initial efforts in expert system automation, a new domain-specific expert system development tool named the Generic Spacecraft Analyst Assistant (GenSAA) is being developed to facilitate the rapid development and reuse of real-time expert systems to serve as fault-isolation assistants for spacecraft analysts. Although initially domain-specific in nature, this powerful tool will support the development of highly graphical expert systems for data monitoring purposes throughout the space and commercial industry.

  8. Development of tools for safety analysis of control software in advanced reactors

    SciTech Connect

    Guarro, S.; Yau, M.; Motamed, M.

    1996-04-01

    Software based control systems have gained a pervasive presence in a wide variety of applications, including nuclear power plant control and protection systems which are within the oversight and licensing responsibility of the US Nuclear Regulatory Commission. While the cost effectiveness and flexibility of software based plant process control is widely recognized, it is very difficult to achieve and prove high levels of demonstrated dependability and safety assurance for the functions performed by process control software, due to the very flexibility and potential complexity of the software itself. The development of tools to model, analyze and test software design and implementations in the context of the system that the software is designed to control can greatly assist the task of providing higher levels of assurance than those obtainable by software testing alone. This report presents and discusses the development of the Dynamic Flowgraph Methodology (DFM) and its application in the dependability and assurance analysis of software-based control systems. The features of the methodology and full-scale examples of application to both generic process and nuclear power plant control systems are presented and discussed in detail. The features of a workstation software tool developed to assist users in the application of DFM are also described.

  9. Neuron-Miner: An Advanced Tool for Morphological Search and Retrieval in Neuroscientific Image Databases.

    PubMed

    Conjeti, Sailesh; Mesbah, Sepideh; Negahdar, Mohammadreza; Rautenberg, Philipp L; Zhang, Shaoting; Navab, Nassir; Katouzian, Amin

    2016-10-01

    The steadily growing amounts of digital neuroscientific data demands for a reliable, systematic, and computationally effective retrieval algorithm. In this paper, we present Neuron-Miner, which is a tool for fast and accurate reference-based retrieval within neuron image databases. The proposed algorithm is established upon hashing (search and retrieval) technique by employing multiple unsupervised random trees, collectively called as Hashing Forests (HF). The HF are trained to parse the neuromorphological space hierarchically and preserve the inherent neuron neighborhoods while encoding with compact binary codewords. We further introduce the inverse-coding formulation within HF to effectively mitigate pairwise neuron similarity comparisons, thus allowing scalability to massive databases with little additional time overhead. The proposed hashing tool has superior approximation of the true neuromorphological neighborhood with better retrieval and ranking performance in comparison to existing generalized hashing methods. This is exhaustively validated by quantifying the results over 31266 neuron reconstructions from Neuromorpho.org dataset curated from 147 different archives. We envisage that finding and ranking similar neurons through reference-based querying via Neuron Miner would assist neuroscientists in objectively understanding the relationship between neuronal structure and function for applications in comparative anatomy or diagnosis.

  10. Integrative genomics--a basic and essential tool for the development of molecular medicine.

    PubMed

    Ostrowski, Jerzy

    2008-01-01

    Understanding the molecular mechanisms of disease requires the introduction of molecular diagnostics into medical practice. Current medicine employs only elements of molecular diagnostics, and usually on the scale of single genes. Medicine in the post-genomic era will utilize thousands of molecular markers associated with disease that are provided by high-throughput sequencing and functional genomic, proteomic and metabolomic studies. Such a spectrum of techniques will link clinical medicine based on molecularly oriented diagnostics with the prediction and prevention of disease. To achieve this task, large-scale and genome-wide biological and medical data must be combined with biostatistical analyses and bioinformatic modeling of biological systems. The collecting, cataloging and comparison of data from molecular studies and the subsequent development of conclusions create the fundamentals of systems biology. This highly complex analytical process reflects a new scientific paradigm called integrative genomics.

  11. Galaxy tools and workflows for sequence analysis with applications in molecular plant pathology.

    PubMed

    Cock, Peter J A; Grüning, Björn A; Paszkiewicz, Konrad; Pritchard, Leighton

    2013-01-01

    The Galaxy Project offers the popular web browser-based platform Galaxy for running bioinformatics tools and constructing simple workflows. Here, we present a broad collection of additional Galaxy tools for large scale analysis of gene and protein sequences. The motivating research theme is the identification of specific genes of interest in a range of non-model organisms, and our central example is the identification and prediction of "effector" proteins produced by plant pathogens in order to manipulate their host plant. This functional annotation of a pathogen's predicted capacity for virulence is a key step in translating sequence data into potential applications in plant pathology. This collection includes novel tools, and widely-used third-party tools such as NCBI BLAST+ wrapped for use within Galaxy. Individual bioinformatics software tools are typically available separately as standalone packages, or in online browser-based form. The Galaxy framework enables the user to combine these and other tools to automate organism scale analyses as workflows, without demanding familiarity with command line tools and scripting. Workflows created using Galaxy can be saved and are reusable, so may be distributed within and between research groups, facilitating the construction of a set of standardised, reusable bioinformatic protocols. The Galaxy tools and workflows described in this manuscript are open source and freely available from the Galaxy Tool Shed (http://usegalaxy.org/toolshed or http://toolshed.g2.bx.psu.edu).

  12. Using explanatory crop models to develop simple tools for Advanced Life Support system studies

    NASA Technical Reports Server (NTRS)

    Cavazzoni, J.

    2004-01-01

    System-level analyses for Advanced Life Support require mathematical models for various processes, such as for biomass production and waste management, which would ideally be integrated into overall system models. Explanatory models (also referred to as mechanistic or process models) would provide the basis for a more robust system model, as these would be based on an understanding of specific processes. However, implementing such models at the system level may not always be practicable because of their complexity. For the area of biomass production, explanatory models were used to generate parameters and multivariable polynomial equations for basic models that are suitable for estimating the direction and magnitude of daily changes in canopy gas-exchange, harvest index, and production scheduling for both nominal and off-nominal growing conditions. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

  13. The advanced light source — a new tool for research in atomic physics

    NASA Astrophysics Data System (ADS)

    Schlachter, A. S.

    1991-03-01

    The Advanced Light Source, a third-generation national synchrotron-radiation facility now under construction at the Lawrence Berkeley Laboratory in Berkeley, California, is scheduled to begin serving qualified users across a broad spectrum of research areas in the spring of 1993. Undulators will generate high-brightness, partially coherent, plane polarized, soft x-ray and ultraviolet (XUV) radiation from below 10 eV to above 2 keV. Wigglers and bend magnets will generate high fluxes of x-rays to photon energies above 10 keV. The ALS will have an extensive research program in which XUV radiation is used to study matter in all its varied gaseous, liquid, and solid forms.

  14. The advanced light source: A new tool for research in atomic physics

    NASA Astrophysics Data System (ADS)

    Schlachter, A. S.

    1990-09-01

    The Advanced Light Source, a third-generation national synchrotron-radiation facility now under construction at the Lawrence Berkeley Laboratory in Berkeley, California, is scheduled to begin serving qualified users across a broad spectrum of research areas in the spring of 1993. Undulators will generate high-brightness, partially coherent, plane polarized, soft-x-ray and ultraviolet (XUV) radiation from below 10 eV to above 2 keV. Wigglers and bend magnets will generate high fluxes of x-rays to photon energies above 10 keV. The ALS will have an extensive research program in which XUV radiation is used to study matter in all its varied gaseous, liquid, and solid forms.

  15. Virtual charge state separator as an advanced tool coupling measurements and simulations

    NASA Astrophysics Data System (ADS)

    Yaramyshev, S.; Vormann, H.; Adonin, A.; Barth, W.; Dahl, L.; Gerhard, P.; Groening, L.; Hollinger, R.; Maier, M.; Mickat, S.; Orzhekhovskaya, A.

    2015-05-01

    A new low energy beam transport for a multicharge uranium beam will be built at the GSI High Current Injector (HSI). All uranium charge states coming from the new ion source will be injected into GSI heavy ion high current HSI Radio Frequency Quadrupole (RFQ), but only the design ions U4 + will be accelerated to the final RFQ energy. A detailed knowledge about injected beam current and emittance for pure design U4 + ions is necessary for a proper beam line design commissioning and operation, while measurements are possible only for a full beam including all charge states. Detailed measurements of the beam current and emittance are performed behind the first quadrupole triplet of the beam line. A dedicated algorithm, based on a combination of measurements and the results of advanced beam dynamics simulations, provides for an extraction of beam current and emittance values for only the U4 + component of the beam. The proposed methods and obtained results are presented.

  16. Support for NATO Advanced Study Institute on molecular ecology of aquatic microbes, August 28--September 9, 1994. Final report

    SciTech Connect

    Joint, I.

    1995-06-16

    This is a summary paper for a NATO Advanced Study Institute sponsored meeting entitled `The Molecular Ecology of Aquatic Microbes` held in Luccia, Italy from August 28 to September 9, 1994. A full reference book for the proceedings is to be published later.

  17. Microfluidic chips with multi-junctions: an advanced tool in recovering proteins from inclusion bodies.

    PubMed

    Yamaguchi, Hiroshi; Miyazaki, Masaya

    2015-01-01

    Active recombinant proteins are used for studying the biological functions of genes and for the development of therapeutic drugs. Overexpression of recombinant proteins in bacteria often results in the formation of inclusion bodies, which are protein aggregates with non-native conformations. Protein refolding is an important process for obtaining active recombinant proteins from inclusion bodies. However, the conventional refolding method of dialysis or dilution is time-consuming and recovered active protein yields are often low, and a cumbersome trial-and-error process is required to achieve success. To circumvent these difficulties, we used controllable diffusion through laminar flow in microchannels to regulate the denaturant concentration. This method largely aims at reducing protein aggregation during the refolding procedure. This Commentary introduces the principles of the protein refolding method using microfluidic chips and the advantage of our results as a tool for rapid and efficient recovery of active recombinant proteins from inclusion bodies.

  18. Evaluation of contaminant removal of reverse osmosis and advanced oxidation in full-scale operation by combining passive sampling with chemical analysis and bioanalytical tools.

    PubMed

    Escher, Beate I; Lawrence, Michael; Macova, Miroslava; Mueller, Jochen F; Poussade, Yvan; Robillot, Cedric; Roux, Annalie; Gernjak, Wolfgang

    2011-06-15

    Advanced water treatment of secondary treated effluent requires stringent quality control to achieve a water quality suitable for augmenting drinking water supplies. The removal of micropollutants such as pesticides, industrial chemicals, endocrine disrupting chemicals (EDC), pharmaceuticals, and personal care products (PPCP) is paramount. As the concentrations of individual contaminants are typically low, frequent analytical screening is both laborious and costly. We propose and validate an approach for continuous monitoring by applying passive sampling with Empore disks in vessels that were designed to slow down the water flow, and thus uptake kinetics, and ensure that the uptake is only marginally dependent on the chemicals' physicochemical properties over a relatively narrow molecular size range. This design not only assured integrative sampling over 27 days for a broad range of chemicals but also permitted the use of a suite of bioanalytical tools as sum parameters, representative of mixtures of chemicals with a common mode of toxic action. Bioassays proved to be more sensitive than chemical analysis to assess the removal of organic micropollutants by reverse osmosis, followed by UV/H₂O₂ treatment, as many individual compounds fell below the quantification limit of chemical analysis, yet still contributed to the observed mixture toxicity. Nonetheless in several cases, the responses in the bioassays were also below their quantification limits and therefore only three bioassays were evaluated here, representing nonspecific toxicity and two specific end points for estrogenicity and photosynthesis inhibition. Chemical analytical techniques were able to quantify 32 pesticides, 62 PCPPs, and 12 EDCs in reverse osmosis concentrate. However, these chemicals could explain only 1% of the nonspecific toxicity in the Microtox assay in the reverse osmosis concentrate and 0.0025% in the treated water. Likewise only 1% of the estrogenic effect in the E-SCREEN could be

  19. A software tool for advanced MRgFUS prostate therapy planning and follow up

    NASA Astrophysics Data System (ADS)

    van Straaten, Dörte; Hoogenboom, Martijn; van Amerongen, Martinus J.; Weiler, Florian; Issawi, Jumana Al; Günther, Matthias; Fütterer, Jurgen; Jenne, Jürgen W.

    2017-03-01

    US guided HIFU/FUS ablation for the therapy of prostate cancer is a clinical established method, while MR guided HIFU/FUS applications for prostate recently started clinical evaluation. Even if MRI examination is an excellent diagnostic tool for prostate cancer, it is a time consuming procedure and not practicable within an MRgFUS therapy session. The aim of our ongoing work is to develop software to support therapy planning and post-therapy follow-up for MRgFUS on localized prostate cancer, based on multi-parametric MR protocols. The clinical workflow of diagnosis, therapy and follow-up of MR guided FUS on prostate cancer was deeply analyzed. Based on this, the image processing workflow was designed and all necessary components, e.g. GUI, viewer, registration tools etc. were defined and implemented. The software bases on MeVisLab with several implemented C++ modules for the image processing tasks. The developed software, called LTC (Local Therapy Control) will register and visualize automatically all images (T1w, T2w, DWI etc.) and ADC or perfusion maps gained from the diagnostic MRI session. This maximum of diagnostic information helps to segment all necessary ROIs, e.g. the tumor, for therapy planning. Final therapy planning will be performed based on these segmentation data in the following MRgFUS therapy session. In addition, the developed software should help to evaluate the therapy success, by synchronization and display of pre-therapeutic, therapy and follow-up image data including the therapy plan and thermal dose information. In this ongoing project, the first stand-alone prototype was completed and will be clinically evaluated.

  20. Advancing spaceborne tools for the characterization of planetary ionospheres and circumstellar environments

    NASA Astrophysics Data System (ADS)

    Douglas, Ewan Streets

    This work explores remote sensing of planetary atmospheres and their circumstellar surroundings. The terrestrial ionosphere is a highly variable space plasma embedded in the thermosphere. Generated by solar radiation and predominantly composed of oxygen ions at high altitudes, the ionosphere is dynamically and chemically coupled to the neutral atmosphere. Variations in ionospheric plasma density impact radio astronomy and communications. Inverting observations of 83.4 nm photons resonantly scattered by singly ionized oxygen holds promise for remotely sensing the ionospheric plasma density. This hypothesis was tested by comparing 83.4 nm limb profiles recorded by the Remote Atmospheric and Ionospheric Detection System aboard the International Space Station to a forward model driven by coincident plasma densities measured independently via ground-based incoherent scatter radar. A comparison study of two separate radar overflights with different limb profile morphologies found agreement between the forward model and measured limb profiles. A new implementation of Chapman parameter retrieval via Markov chain Monte Carlo techniques quantifies the precision of the plasma densities inferred from 83.4 nm emission profiles. This first study demonstrates the utility of 83.4 nm emission for ionospheric remote sensing. Future visible and ultraviolet spectroscopy will characterize the composition of exoplanet atmospheres; therefore, the second study advances technologies for the direct imaging and spectroscopy of exoplanets. Such spectroscopy requires the development of new technologies to separate relatively dim exoplanet light from parent star light. High-contrast observations at short wavelengths require spaceborne telescopes to circumvent atmospheric aberrations. The Planet Imaging Concept Testbed Using a Rocket Experiment (PICTURE) team designed a suborbital sounding rocket payload to demonstrate visible light high-contrast imaging with a visible nulling coronagraph

  1. Turbulence in molecular clouds - A new diagnostic tool to probe their origin

    NASA Technical Reports Server (NTRS)

    Canuto, V. M.; Battaglia, A.

    1985-01-01

    A method is presented to uncover the instability responsible for the type of turbulence observed in molecular clouds and the value of the physical parameters of the 'placental medium' from which turbulence originated. The method utilizes the observational relation between velocities and sizes of molecular clouds, together with a recent model for large-scale turbulence (constructed by Canuto and Goldman, 1985).

  2. The advanced light source at Lawrence Berkeley laboratory: a new tool for research in atomic physics

    NASA Astrophysics Data System (ADS)

    Schlachter, Alfred S.; Robinson, Arthur L.

    1991-04-01

    The Advanced Light Source, a third-generation national synchrotron-radiation facility now under construction at the Lawrence Berkeley Laboratory, is scheduled to begin serving qualified users across a broad spectrum of research areas in the spring of 1993. Based on a low-emittance electron storage ring optimized to operate at 1.5 GeV, the ALS will have 10 long straight sections available for insertion devices (undulators and wigglers) and 24 high-quality bend-magnet ports. The short pulse width (30-50 ps) will be ideal for time-resolved measurements. Undulators will generate high-brightness partially coherent soft X-ray and ultraviolet (XUV) radiation from below 10 eV to above 2 keV; this radiation is plane polarized. Wigglers and bend magnets will extend the spectrum by generating high fluxes of X-rays to photon energies above 10 keV. The ALS will have an extensive research program in which XUV radiation is used to study matter in all its varied gaseous, liquid, and solid forms. The high brightness will open new areas of research in the materials sciences, such as spatially resolved spectroscopy (spectromicroscopy), and in biology, such as X-ray microscopy with element-specific sensitivity; the high flux will allow measurements in atomic physics and chemistry to be made with tenuous gas-phase targets. Technological applications could include lithography and nano-fabrication.

  3. Propulsion Simulations Using Advanced Turbulence Models with the Unstructured Grid CFD Tool, TetrUSS

    NASA Technical Reports Server (NTRS)

    Abdol-Hamid, Khaled S.; Frink, Neal T.; Deere, Karen A.; Pandya, Mohangna J.

    2004-01-01

    A computational investigation has been completed to assess the capability of TetrUSS for exhaust nozzle flows. Three configurations were chosen for this study (1) an axisymmetric supersonic jet, (2) a transonic axisymmetric boattail with solid sting operated at different Reynolds number and Mach number, and (3) an isolated non-axisymmetric nacelle with a supersonic cruise nozzle. These configurations were chosen because existing experimental data provided a means for measuring the ability of TetrUSS for simulating complex nozzle flows. The main objective of this paper is to validate the implementation of advanced two-equation turbulence models in the unstructured-grid CFD code USM3D for propulsion flow cases. USM3D is the flow solver of the TetrUSS system. Three different turbulence models, namely, Menter Shear Stress Transport (SST), basic k epsilon, and the Spalart-Allmaras (SA) are used in the present study. The results are generally in agreement with other implementations of these models in structured-grid CFD codes. Results indicate that USM3D provides accurate simulations for complex aerodynamic configurations with propulsion integration.

  4. Terahertz pulsed imaging as an advanced characterisation tool for film coatings--a review.

    PubMed

    Haaser, Miriam; Gordon, Keith C; Strachan, Clare J; Rades, Thomas

    2013-12-05

    Solid dosage forms are the pharmaceutical drug delivery systems of choice for oral drug delivery. These solid dosage forms are often coated to modify the physico-chemical properties of the active pharmaceutical ingredients (APIs), in particular to alter release kinetics. Since the product performance of coated dosage forms is a function of their critical coating attributes, including coating thickness, uniformity, and density, more advanced quality control techniques than weight gain are required. A recently introduced non-destructive method to quantitatively characterise coating quality is terahertz pulsed imaging (TPI). The ability of terahertz radiation to penetrate many pharmaceutical materials enables structural features of coated solid dosage forms to be probed at depth, which is not readily achievable with other established imaging techniques, e.g. near-infrared (NIR) and Raman spectroscopy. In this review TPI is introduced and various applications of the technique in pharmaceutical coating analysis are discussed. These include evaluation of coating thickness, uniformity, surface morphology, density, defects and buried structures as well as correlation between TPI measurements and drug release performance, coating process monitoring and scale up. Furthermore, challenges and limitations of the technique are discussed.

  5. Advanced Online Survival Analysis Tool for Predictive Modelling in Clinical Data Science.

    PubMed

    Montes-Torres, Julio; Subirats, José Luis; Ribelles, Nuria; Urda, Daniel; Franco, Leonardo; Alba, Emilio; Jerez, José Manuel

    2016-01-01

    One of the prevailing applications of machine learning is the use of predictive modelling in clinical survival analysis. In this work, we present our view of the current situation of computer tools for survival analysis, stressing the need of transferring the latest results in the field of machine learning to biomedical researchers. We propose a web based software for survival analysis called OSA (Online Survival Analysis), which has been developed as an open access and user friendly option to obtain discrete time, predictive survival models at individual level using machine learning techniques, and to perform standard survival analysis. OSA employs an Artificial Neural Network (ANN) based method to produce the predictive survival models. Additionally, the software can easily generate survival and hazard curves with multiple options to personalise the plots, obtain contingency tables from the uploaded data to perform different tests, and fit a Cox regression model from a number of predictor variables. In the Materials and Methods section, we depict the general architecture of the application and introduce the mathematical background of each of the implemented methods. The study concludes with examples of use showing the results obtained with public datasets.

  6. Advanced Online Survival Analysis Tool for Predictive Modelling in Clinical Data Science

    PubMed Central

    Montes-Torres, Julio; Subirats, José Luis; Ribelles, Nuria; Urda, Daniel; Franco, Leonardo; Alba, Emilio; Jerez, José Manuel

    2016-01-01

    One of the prevailing applications of machine learning is the use of predictive modelling in clinical survival analysis. In this work, we present our view of the current situation of computer tools for survival analysis, stressing the need of transferring the latest results in the field of machine learning to biomedical researchers. We propose a web based software for survival analysis called OSA (Online Survival Analysis), which has been developed as an open access and user friendly option to obtain discrete time, predictive survival models at individual level using machine learning techniques, and to perform standard survival analysis. OSA employs an Artificial Neural Network (ANN) based method to produce the predictive survival models. Additionally, the software can easily generate survival and hazard curves with multiple options to personalise the plots, obtain contingency tables from the uploaded data to perform different tests, and fit a Cox regression model from a number of predictor variables. In the Materials and Methods section, we depict the general architecture of the application and introduce the mathematical background of each of the implemented methods. The study concludes with examples of use showing the results obtained with public datasets. PMID:27532883

  7. A new tool to give hospitalists feedback to improve interprofessional teamwork and advance patient care.

    PubMed

    Chesluk, Benjamin J; Bernabeo, Elizabeth; Hess, Brian; Lynn, Lorna A; Reddy, Siddharta; Holmboe, Eric S

    2012-11-01

    Teamwork is a vital skill for health care professionals, but the fragmented systems within which they work frequently do not recognize or support good teamwork. The American Board of Internal Medicine has developed and is testing the Teamwork Effectiveness Assessment Module (TEAM), a tool for physicians to evaluate how they perform as part of an interprofessional patient care team. The assessment provides hospitalist physicians with feedback data drawn from their own work of caring for patients, in a way that is intended to support immediate, concrete change efforts to improve the quality of patient care. Our approach demonstrates the value of looking at teamwork in the real world of health care-that is, as it occurs in the actual contexts in which providers work together to care for patients. The assessment of individual physicians' teamwork competencies may play a role in the larger effort to bring disparate health professions together in a system that supports and rewards a team approach in hope of improving patient care.

  8. Advanced semi-active engine and transmission mounts: tools for modelling, analysis, design, and tuning

    NASA Astrophysics Data System (ADS)

    Farjoud, Alireza; Taylor, Russell; Schumann, Eric; Schlangen, Timothy

    2014-02-01

    This paper is focused on modelling, design, and testing of semi-active magneto-rheological (MR) engine and transmission mounts used in the automotive industry. The purpose is to develop a complete analysis, synthesis, design, and tuning tool that reduces the need for expensive and time-consuming laboratory and field tests. A detailed mathematical model of such devices is developed using multi-physics modelling techniques for physical systems with various energy domains. The model includes all major features of an MR mount including fluid dynamics, fluid track, elastic components, decoupler, rate-dip, gas-charged chamber, MR fluid rheology, magnetic circuit, electronic driver, and control algorithm. Conventional passive hydraulic mounts can also be studied using the same mathematical model. The model is validated using standard experimental procedures. It is used for design and parametric study of mounts; effects of various geometric and material parameters on dynamic response of mounts can be studied. Additionally, this model can be used to test various control strategies to obtain best vibration isolation performance by tuning control parameters. Another benefit of this work is that nonlinear interactions between sub-components of the mount can be observed and investigated. This is not possible by using simplified linear models currently available.

  9. Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes.

    PubMed

    Yamagishi, Sho-Ichi; Nakamura, Nobutaka; Suematsu, Mika; Kaseda, Kuniyoshi; Matsui, Takanori

    2015-10-27

    A nonenzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and subsequently alters their structural integrity and function. This process has been known to progress at an accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent and senescent macroprotein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence indicating that interaction of AGEs with their receptor (RAGE) elicits oxidative stress generation and as a result evokes proliferative, inflammatory, thrombotic and fibrotic reactions in a variety of cells. This evidence supports AGEs' involvement in diabetes- and aging-associated disorders such as diabetic vascular complications, cancer, Alzheimer's disease and osteoporosis. Therefore, inhibition of AGE formation could be a novel molecular target for organ protection in diabetes. This report summarizes the pathophysiological role of AGEs in vascular complications in diabetes and discusses the potential clinical utility of measurement of serum levels of AGEs for evaluating organ damage in diabetes.

  10. Biomarker, Molecular, and Technologic Advances in Urologic Pathology, Oncology, and Imaging.

    PubMed

    Ellis, Carla L; Harik, Lara R; Cohen, Cynthia; Osunkoya, Adeboye O

    2017-04-01

    Urologic pathology is evolving rapidly. Emerging trends include the expanded diagnostic utility of biomarkers and molecular testing, as well as adapting to the plethora of technical advances occurring in genitourinary oncology, surgical practice, and imaging. We illustrate those trends by highlighting our approach to the diagnostic workup of a few selected disease entities that pathologists may encounter, including newly recognized subtypes of renal cell carcinoma, pheochromocytoma, and prostate cancer, some of which harbor a distinctive chromosomal translocation, gene loss, or mutation. We illustrate applications of immunohistochemistry for differential diagnosis of needle core renal biopsies, intraductal carcinoma of the prostate, and amyloidosis and cite encouraging results from early studies using targeted gene expression panels to predict recurrence after prostate cancer surgery. At our institution, pathologists are working closely with urologic surgeons and interventional radiologists to explore the use of intraoperative frozen sections for margins and nerve sparing during robotic prostatectomy, to pioneer minimally invasive videoscopic inguinal lymphadenectomy, and to refine image-guided needle core biopsies and cryotherapy of prostate cancer as well as blue-light/fluorescence cystoscopy. This collaborative, multidisciplinary approach enhances clinical management and research, and optimizes the care of patients with urologic disorders.

  11. Recent advances and perspectives in molecular epidemiology of Taenia solium cysticercosis.

    PubMed

    Ito, Akira; Yanagida, Tetsuya; Nakao, Minoru

    2016-06-01

    Cysticercosis caused by accidental ingestion of eggs of Taenia solium is spreading all over the world through globalization and is one of the most neglected, neglected tropical diseases (NTDs) or neglected zoonotic diseases (NZDs). In the present study, the reason why T. solium cysticercosis has been neglected is discussed at first, and followed with an overview on the most recent advances and perspectives in molecular approaches for epidemiology of T. solium taeniasis/cysticercosis, since although taeniasis does not constitute recognized zoonoses, transmission and complete development are dependent on human definitive hosts. Main topics are discussions on (1) the two, Asian and Afro/American, genotypes of T. solium, (2) comparative analysis of mitochondrial (haploid) and nuclear (diploid) genes, and (3) the presence of hybrids of these two genotypes which indicates out-crossing of two genotypes in hermaphrodite tapeworms in Madagascar. Additional topics are on (4) the usefulness of phylogeographic analyses to discuss where the infection was acquired from, and (5) miscellaneous unsolved topics around these genetic diversity of T. solium.

  12. Recent advances in Hodgkin lymphoma: interim PET and molecular-targeted therapy.

    PubMed

    Nagai, Hirokazu

    2015-02-01

    Hodgkin lymphoma is a highly curative lymphoid malignancy, but some patients relapse or experience adverse events from treatment. Therefore, prognostic markers are needed to allow a more patient-tailored approach to treatment. The positive-predictive value of interim positron emission tomography for progression-free survival was reported as 81%, and the negative-predictive value was reported as 97%. Interim positron emission tomography might identify high-risk patients who would benefit from more intensive treatment regimens as well as identify low-risk patients in whom even the standard treatment regimen might be a form of overtreatment. Indeed, major clinical study groups have conducted risk-adapted treatment protocols based on interim positron emission tomography. The Japan Clinical Oncology Group is also planning a Phase II trial of this concept for advanced Hodgkin lymphoma. These trials are now ongoing, but the data of them are expected soon. Molecular-targeted therapy is another important approach to improve outcomes for these patients. Brentuximab vedotin is an antibody-drug conjugate that targets CD30 on Hodgkin cells and has excellent efficacy when used as monotherapy. The combination of brentuximab vedotin and standard chemotherapies are being investigated in randomized Phase III trials. These approaches might lead to a paradigm shift in the treatment of Hodgkin lymphoma.

  13. Advances in molecular identification, taxonomy, genetic variation and diagnosis of Toxocara spp.

    PubMed

    Chen, Jia; Zhou, Dong-Hui; Nisbet, Alasdair J; Xu, Min-Jun; Huang, Si-Yang; Li, Ming-Wei; Wang, Chun-Ren; Zhu, Xing-Quan

    2012-10-01

    The genus Toxocara contains parasitic nematodes of human and animal health significance, such as Toxocara canis, Toxocara cati and Toxocara vitulorum. T. canis and T. cati are among the most prevalent parasites of dogs and cats with a worldwide distribution. Human infection with T. canis and T. cati, which can cause a number of clinical manifestations such as visceral larva migrans (VLMs), ocular larva migrans (OLMs), eosinophilic meningoencephalitis (EME), covert toxocariasis (CT) and neurotoxocariasis, is considered the most prevalent neglected helminthiasis in industrialized countries. The accurate identification Toxocara spp. and their unequivocal differentiation from each other and from other ascaridoid nematodes causing VLMs and OLMs has important implications for studying their taxonomy, epidemiology, population genetics, diagnosis and control. Due to the limitations of traditional (morphological) approaches for identification and diagnosis of Toxocara spp., PCR-based techniques utilizing a range of genetic markers in the nuclear and mitochondrial genomes have been developed as useful alternative approaches because of their high sensitivity, specificity, rapidity and utility. In this article, we summarize the current state of knowledge and advances in molecular identification, taxonomy, genetic variation and diagnosis of Toxocara spp. with prospects for further studies.

  14. Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

    PubMed

    Halperin, R; Zehavi, S; Dar, P; Habler, L; Hadas, E; Bukovsky, I; Schneider, D

    2001-01-01

    The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.

  15. Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers

    PubMed Central

    Polussa, Jonathan; Schneider, Andrea; Hagerman, Randi

    2014-01-01

    Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and it is characterized by a CGG expansion of more than 200 repeats in the FMR1 gene, leading to methylation of the promoter and gene silencing. The fragile X premutation, characterized by a 55 to 200 CGG repeat expansion, causes health problems and developmental difficulties in some, but not all, carriers. The premutation causes primary ovarian insufficiency in approximately 20% of females, psychiatric problems (including depression and/or anxiety) in approximately 50% of carriers and a neurodegenerative disorder, the fragile X-associated tremor ataxia syndrome (FXTAS), in approximately 40% of males and 16% of females later in life. Recent clinical studies in premutation carriers have expanded the health problems that may be seen. Advances in the molecular pathogenesis of the premutation have shown significant mitochondrial dysfunction and oxidative stress in neurons which may be amenable to treatment. Here we review the clinical problems of carriers and treatment recommendations. PMID:25436181

  16. Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management and controversies

    PubMed Central

    Jensen, Robert T.; Berna, Marc J.; Bingham, David B; Norton, Jeffrey A.

    2008-01-01

    Pancreatic endocrine tumors (PETs) can occur in as part of four inherited disorders including: Multiple Endocrine Neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL), neurofibromatosis 1(NF-1) [von Recklinghausen’s disease] and the tuberous sclerosis complex (TSC). The relative frequency with which patients with these disorders develop PETs is MEN1>VHL>NF-1>TSC. Over the last few years there have been major advances in the understanding of the genetics and molecular pathogenesis of these disorders as well in the localization, medical and surgical treatment of the PETs in these patients. The study of the PETs in these disorders has not only provided insights into the possible pathogenesis of sporadic PETs, but have also presented a number of unique management and treatment issues, some of which are applicable to patients with sporadic PETs. Therefore the study of PETs in these uncommon disorders has provided valuable insights that in many cases are applicable to the general group of patients with sporadic PETs. In this article these areas are briefly reviewed as well as the current state of knowledge of the PETs in these disorders and the controversies that exist in their management are briefly summarized and discussed. PMID:18798544

  17. Randomized Controlled Trial of a Video Decision Support Tool for Cardiopulmonary Resuscitation Decision Making in Advanced Cancer

    PubMed Central

    Volandes, Angelo E.; Paasche-Orlow, Michael K.; Mitchell, Susan L.; El-Jawahri, Areej; Davis, Aretha Delight; Barry, Michael J.; Hartshorn, Kevan L.; Jackson, Vicki Ann; Gillick, Muriel R.; Walker-Corkery, Elizabeth S.; Chang, Yuchiao; López, Lenny; Kemeny, Margaret; Bulone, Linda; Mann, Eileen; Misra, Sumi; Peachey, Matt; Abbo, Elmer D.; Eichler, April F.; Epstein, Andrew S.; Noy, Ariela; Levin, Tomer T.; Temel, Jennifer S.

    2013-01-01

    Purpose Decision making regarding cardiopulmonary resuscitation (CPR) is challenging. This study examined the effect of a video decision support tool on CPR preferences among patients with advanced cancer. Patients and Methods We performed a randomized controlled trial of 150 patients with advanced cancer from four oncology centers. Participants in the control arm (n = 80) listened to a verbal narrative describing CPR and the likelihood of successful resuscitation. Participants in the intervention arm (n = 70) listened to the identical narrative and viewed a 3-minute video depicting a patient on a ventilator and CPR being performed on a simulated patient. The primary outcome was participants' preference for or against CPR measured immediately after exposure to either modality. Secondary outcomes were participants' knowledge of CPR (score range of 0 to 4, with higher score indicating more knowledge) and comfort with video. Results The mean age of participants was 62 years (standard deviation, 11 years); 49% were women, 44% were African American or Latino, and 47% had lung or colon cancer. After the verbal narrative, in the control arm, 38 participants (48%) wanted CPR, 41 (51%) wanted no CPR, and one (1%) was uncertain. In contrast, in the intervention arm, 14 participants (20%) wanted CPR, 55 (79%) wanted no CPR, and 1 (1%) was uncertain (unadjusted odds ratio, 3.5; 95% CI, 1.7 to 7.2; P < .001). Mean knowledge scores were higher in the intervention arm than in the control arm (3.3 ± 1.0 v 2.6 ± 1.3, respectively; P < .001), and 65 participants (93%) in the intervention arm were comfortable watching the video. Conclusion Participants with advanced cancer who viewed a video of CPR were less likely to opt for CPR than those who listened to a verbal narrative. PMID:23233708

  18. Molecular Tools for Plant Protection, True-to-Name Verification and Parentage Analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA-based tools are available to improve ornamental plant cultivars through accelerated breeding and other practical applications. Highlights include examples where DNA fingerprints identified mislabeled cultivars, verified the renaming of cultivars and demonstrated some similar-looking cultivars ar...

  19. Assessing health impacts in complex eco-epidemiological settings in the humid tropics: Advancing tools and methods

    SciTech Connect

    Winkler, Mirko S.; Divall, Mark J.; Krieger, Gary R.; Balge, Marci Z.; Singer, Burton H.; Utzinger, Juerg

    2010-01-15

    In the developing world, large-scale projects in the extractive industry and natural resources sectors are often controversial and associated with long-term adverse health consequences to local communities. In many industrialised countries, health impact assessment (HIA) has been institutionalized for the mitigation of anticipated negative health effects while enhancing the benefits of projects, programmes and policies. However, in developing country settings, relatively few HIAs have been performed. Hence, more HIAs with a focus on low- and middle-income countries are needed to advance and refine tools and methods for impact assessment and subsequent mitigation measures. We present a promising HIA approach, developed within the frame of a large gold-mining project in the Democratic Republic of the Congo. The articulation of environmental health areas, the spatial delineation of potentially affected communities and the use of a diversity of sources to obtain quality baseline health data are utilized for risk profiling. We demonstrate how these tools and data are fed into a risk analysis matrix, which facilitates ranking of potential health impacts for subsequent prioritization of mitigation strategies. The outcomes encapsulate a multitude of environmental and health determinants in a systematic manner, and will assist decision-makers in the development of mitigation measures that minimize potential adverse health effects and enhance positive ones.

  20. Advances in RNA molecular dynamics: a simulator's guide to RNA force fields.

    PubMed

    Vangaveti, Sweta; Ranganathan, Srivathsan V; Chen, Alan A

    2017-03-01

    Molecular simulations have become an essential tool for biochemical research. When they work properly, they are able to provide invaluable interpretations of experimental results and ultimately provide novel, experimentally testable predictions. Unfortunately, not all simulation models are created equal, and with inaccurate models it becomes unclear what is a bona fide prediction versus a simulation artifact. RNA models are still in their infancy compared to the many robust protein models that are widely in use, and for that reason the number of RNA force field revisions in recent years has been rapidly increasing. As there is no universally accepted 'best' RNA force field at the current time, RNA simulators must decide which one is most suited to their purposes, cognizant of its essential assumptions and their inherent strengths and weaknesses. Hopefully, armed with a better understanding of what goes inside the simulation 'black box,' RNA biochemists can devise novel experiments and provide crucial thermodynamic and structural data that will guide the development and testing of improved RNA models. WIREs RNA 2017, 8:e1396. doi: 10.1002/wrna.1396 For further resources related to this article, please visit the WIREs website.

  1. Advances in conservation endocrinology: the application of molecular approaches to the conservation of endangered species.

    PubMed

    Tubbs, Christopher; McDonough, Caitlin E; Felton, Rachel; Milnes, Matthew R

    2014-07-01

    Among the numerous societal benefits of comparative endocrinology is the application of our collective knowledge of hormone signaling towards the conservation of threatened and endangered species - conservation endocrinology. For several decades endocrinologists have used longitudinal hormone profiles to monitor reproductive status in a multitude of species. Knowledge of reproductive status among individuals has been used to assist in the management of captive and free-ranging populations. More recently, researchers have begun utilizing molecular and cell-based techniques to gain a more complete understanding of hormone signaling in wildlife species, and to identify potential causes of disrupted hormone signaling. In this review we examine various in vitro approaches we have used to compare estrogen receptor binding and activation by endogenous hormones and phytoestrogens in two species of rhinoceros; southern white and greater one-horned. We have found many of these techniques valuable and practical in species where access to research subjects and/or tissues is limited due to their conservation status. From cell-free, competitive binding assays to full-length receptor activation assays; each technique has strengths and weaknesses related to cost, sensitivity, complexity of the protocols, and relevance to in vivo signaling. We then present a novel approach, in which receptor activation assays are performed in primary cell lines derived from the species of interest, to minimize the artifacts of traditional heterologous expression systems. Finally, we speculate on the promise of next generation sequencing and transcriptome profiling as tools for characterizing hormone signaling in threatened and endangered species.

  2. Synchrotron-based and globar-sourced molecular (micro)spectroscopy contributions to advances in new hulless barley (with structure alteration) research on molecular structure, molecular nutrition, and nutrient delivery.

    PubMed

    Yang, Ling; Yu, Peiqiang

    2017-01-02

    This paper aimed to review synchrotron-based and globar-sourced molecular infrared (micro)spectroscopy contributions to advances in new hulless barley (with structure alteration) research on molecular structure, molecular nutrition, and nutrient delivery in ruminants. It reviewed recent progress in barley varieties, its utilization for animal and human, inherent structure features and chemical make-up, evaluation and research methodology, breeding progress, rumen degradation, and intestinal digestion. The emphasis of this review was focused on the effect of alteration of carbohydrate traits of newly developed hulless barley on molecular structure changes and nutrient delivery and quantification of the relationship between molecular structure features and changes and truly absorbed nutrient supply to ruminants. This review provides an insight into how inherent structure changes on a molecular basis affect nutrient utilization and availability in ruminants.

  3. Earth remote sensing as an effective tool for the development of advanced innovative educational technologies

    NASA Astrophysics Data System (ADS)

    Mayorova, Vera; Mayorov, Kirill

    2009-11-01

    Current educational system is facing a contradiction between the fundamentality of engineering education and the necessity of applied learning extension, which requires new methods of training to combine both academic and practical knowledge in balance. As a result there are a number of innovations being developed and implemented into the process of education aimed at optimizing the quality of the entire educational system. Among a wide range of innovative educational technologies there is an especially important subset of educational technologies which involve learning through hands-on scientific and technical projects. The purpose of this paper is to describe the implementation of educational technologies based on small satellites development as well as the usage of Earth remote sensing data acquired from these satellites. The increase in public attention to the education through Earth remote sensing is based on the concern that although there is a great progress in the development of new methods of Earth imagery and remote sensing data acquisition there is still a big question remaining open on practical applications of this kind of data. It is important to develop the new way of thinking for the new generation of people so they understand that they are the masters of their own planet and they are responsible for its state. They should desire and should be able to use a powerful set of tools based on modern and perspective Earth remote sensing. For example NASA sponsors "Classroom of the Future" project. The Universities Space Research Association in United States provides a mechanism through which US universities can cooperate effectively with one another, with the government, and with other organizations to further space science and technology, and to promote education in these areas. It also aims at understanding the Earth as a system and promoting the role of humankind in the destiny of their own planet. The Association has founded a Journal of Earth System

  4. Sex chromosomal abnormalities associated with equine infertility: validation of a simple molecular screening tool in the Purebred Spanish Horse.

    PubMed

    Anaya, G; Molina, A; Valera, M; Moreno-Millán, M; Azor, P; Peral-García, P; Demyda-Peyrás, S

    2017-02-22

    Chromosomal abnormalities in the sex chromosome pair (ECAX and ECAY) are widely associated with reproductive problems in horses. However, a large proportion of these abnormalities remains undiagnosed due to the lack of an affordable diagnostic tool that allows for avoiding karyotyping tests. Hereby, we developed an STR (single-tandem-repeat)-based molecular method to determine the presence of the main sex chromosomal abnormalities in horses in a fast, cheap and reliable way. The frequency of five ECAX-linked (LEX026, LEX003, TKY38, TKY270 and UCDEQ502) and two ECAY-linked (EcaYH12 and SRY) markers was characterized in 261 Purebred Spanish Horses to determine the efficiency of the methodology developed to be used as a chromosomal diagnostic tool. All the microsatellites analyzed were highly polymorphic, with a sizeable number of alleles (polymorphic information content > 0.5). Based on this variability, the methodology showed 100% sensitivity and 99.82% specificity to detect the most important sex chromosomal abnormalities reported in horses (chimerism, Turner's syndrome and sex reversal syndromes). The method was also validated with 100% efficiency in 10 individuals previously diagnosed as chromosomally aberrant. This STR screening panel is an efficient and reliable molecular-cytogenetic tool for the early detection of sex chromosomal abnormalities in equines that could be included in breeding programs to save money, effort and time of veterinary practitioners and breeders.

  5. A new tool for the molecular identification of Culicoides species of the Obsoletus group: the glass slide microarray approach.

    PubMed

    Deblauwe, I; de Witte, J C; de Deken, G; de Deken, R; Madder, M; van Erk, S; Hoza, F A; Lathouwers, D; Geysen, D

    2012-03-01

    Culicoides species of the Obsoletus group (Diptera: Ceratopogonidae) are potential vectors of bluetongue virus serotype 8 (BTV 8), which was introduced into central Western Europe in 2006. Correct morphological species identification of Obsoletus group females is especially difficult and molecular identification is the method of choice. In this study we present a new molecular tool based on probe hybridization using a DNA microarray format to identify Culicoides species of the Obsoletus group. The internal transcribed spacer 1 (ITS1) gene sequences of 55 Culicoides belonging to 13 different species were determined and used, together with 19 Culicoides ITS1 sequences sourced from GenBank, to design species-specific probes for the microarray test. This test was evaluated using the amplified ITS1 sequences of another 85 Culicoides specimens, belonging to 11 species. The microarray test successfully identified all samples (100%) of the Obsoletus group, identifying each specimen to species level within the group. This test has several advantages over existing polymerase chain reaction (PCR)-based molecular tools, including possible capability for parallel analysis of many species, high sensitivity and specificity, and low background signal noise. Hand-spotting of the microarray slide and the use of detection chemistry make this alternative technique affordable and feasible for any diagnostic laboratory with PCR facilities.

  6. Transposable elements and two other molecular markers as typing tools for the genus Paracoccidioides.

    PubMed

    Alves, Fernanda Lourenço; Ribeiro, Mariceli Araújo; Hahn, Rosane Christine; de Melo Teixeira, Marcus; de Camargo, Zoilo Pires; Cisalpino, Patrícia Silva; Marini, Marjorie Mendes

    2015-02-01

    Studies comparing Paracoccidioides brasiliensis and Paracoccidioides lutzii have shown that these fungi have significant genomic differences that may have implications in the clinical manifestation, diagnosis, and treatment of paracoccidioidomycosis caused by them. Thus, molecular typing methods are required that can distinguish between various species of Paracoccidioides. The aim of this study was to explore the potential use as molecular markers of the transposable elements Trem A-H recently identified and characterized in the genus Paracoccidioides as a means of differentiating the species. We take advantage of the abundance and distribution of these transposons in the Paracoccidioides genomes to develop a simple and highly reproducible polymerase chain reaction (PCR)-based technique. Furthermore we compare the performance of this test with two other molecular markers already in use to identify these fungi.

  7. Gold and diazo reagents: a fruitful tool for developing molecular complexity.

    PubMed

    Fructos, Manuel R; Díaz-Requejo, M Mar; Pérez, Pedro J

    2016-06-11

    Since the discovery in 2005 of the potential of soluble Au complexes to catalyse the transfer of carbene groups from diazo compounds to organic substrates, an increasing number of transformations have been reported. In this contribution, the advances in the field are presented as foundations for further developments in the incoming years.

  8. Selective photodissociation of tailored molecular tags as a tool for quantum optics

    PubMed Central

    Sezer, Ugur; Geyer, Philipp; Kriegleder, Moritz; Debiossac, Maxime; Shayeghi, Armin; Arndt, Markus; Felix, Lukas

    2017-01-01

    Recent progress in synthetic chemistry and molecular quantum optics has enabled demonstrations of the quantum mechanical wave–particle duality for complex particles, with masses exceeding 10 kDa. Future experiments with even larger objects will require new optical preparation and manipulation methods that shall profit from the possibility to cleave a well-defined molecular tag from a larger parent molecule. Here we present the design and synthesis of two model compounds as well as evidence for the photoinduced beam depletion in high vacuum in one case. PMID:28243571

  9. Selective photodissociation of tailored molecular tags as a tool for quantum optics.

    PubMed

    Sezer, Ugur; Geyer, Philipp; Kriegleder, Moritz; Debiossac, Maxime; Shayeghi, Armin; Arndt, Markus; Felix, Lukas; Mayor, Marcel

    2017-01-01

    Recent progress in synthetic chemistry and molecular quantum optics has enabled demonstrations of the quantum mechanical wave-particle duality for complex particles, with masses exceeding 10 kDa. Future experiments with even larger objects will require new optical preparation and manipulation methods that shall profit from the possibility to cleave a well-defined molecular tag from a larger parent molecule. Here we present the design and synthesis of two model compounds as well as evidence for the photoinduced beam depletion in high vacuum in one case.

  10. Molecular imprinting: a tool of modern chemistry for the preparation of highly selective monolithic sorbents

    NASA Astrophysics Data System (ADS)

    Vlakh, E. G.; Korzhikov, V. A.; Hubina, A. V.; Tennikova, T. B.

    2015-09-01

    Characteristic features of the synthesis of molecularly imprinted polymer systems used as sorbents for separation of complex mixtures into components are discussed. The data about the molecules imprinted in monoliths of various natures and shapes are integrated. Examples of application of new-generation separating media are discussed. Data on the utilization of the molecular imprinting principle for the fabrication of supermacroporous monolithic cryogels specific to particular molecules, which is important for the design of smart biomaterials, are analyzed. The bibliography includes 293 references.

  11. Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy.

    PubMed

    Kumar Pasupulati, Anil; Chitra, P Swathi; Reddy, G Bhanuprakash

    2016-12-01

    Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff's base and an Amadori product to yield advanced glycation end products (AGEs). AGE modification of client proteins from the extracellular matrix induces crosslinking, which is often associated with thickening of the basement membrane. AGEs activate several intracellular signaling cascades upon interaction with receptor for AGEs (RAGE), which manifest in aberrant cellular responses such as inflammation, apoptosis and autophagy, whereas other receptors such as AGE-R1, AGE-R3 and scavenger receptors also bind to AGEs and ensue endocytosis and degradation of AGEs. Elevated levels of both serum and tissue AGEs are associated with adverse renal outcome. Increased evidence supports that attenuation of AGE formation and/or inhibition of RAGE activation manifest(s) in improving renal function. This review provides insights of NEG, discusses the cellular and molecular events triggered by AGEs, which manifest in the pathogenesis of DN including renal fibrosis, podocyte epithelial-mesenchymal transition and activation of renin-angiotensin system. Therapies designed to target AGEs, such as inhibitors of AGEs formation and crosslink breakers, are discussed.

  12. The supersonic molecular beam injector as a reliable tool for plasma fueling and physics experiment on HL-2A.

    PubMed

    Chen, C Y; Yu, D L; Feng, B B; Yao, L H; Song, X M; Zang, L G; Gao, X Y; Yang, Q W; Duan, X R

    2016-09-01

    On HL-2A tokamak, supersonic molecular beam injection (SMBI) has been developed as a routine refueling method. The key components of the system are an electromagnetic valve and a conic nozzle. The valve and conic nozzle are assembled to compose the simplified Laval nozzle for generating the pulsed beam. The appurtenance of the system includes the cooling system serving the cooled SMBI generation and the in situ calibration component for quantitative injection. Compared with the conventional gas puffing, the SMBI features prompt response and larger fueling flux. These merits devote the SMBI a good fueling method, an excellent plasma density feedback control tool, and an edge localized mode mitigation resource.

  13. Taming a wild beast: Developing molecular tools and new methods to understand the biology of Zymoseptoria tritici.

    PubMed

    Talbot, Nicholas J

    2015-06-01

    Septoria blotch of wheat is one of the world's most serious plant diseases, which is difficult to control due to the absence of durable host resistance and the increasing frequency of fungicide-resistance. The ascomycete fungus that causes the disease, Zymoseptoria tritici, has been very challenging to study. This special issue of Fungal Genetics and Biology showcases an integrated approach to method development and the innovation of new molecular tools to study the biology of Z. tritici. When considered together, these new methods will have a rapid and dramatic effect on our ability to combat this significant disease.

  14. The supersonic molecular beam injector as a reliable tool for plasma fueling and physics experiment on HL-2A

    NASA Astrophysics Data System (ADS)

    Chen, C. Y.; Yu, D. L.; Feng, B. B.; Yao, L. H.; Song, X. M.; Zang, L. G.; Gao, X. Y.; Yang, Q. W.; Duan, X. R.

    2016-09-01

    On HL-2A tokamak, supersonic molecular beam injection (SMBI) has been developed as a routine refueling method. The key components of the system are an electromagnetic valve and a conic nozzle. The valve and conic nozzle are assembled to compose the simplified Laval nozzle for generating the pulsed beam. The appurtenance of the system includes the cooling system serving the cooled SMBI generation and the in situ calibration component for quantitative injection. Compared with the conventional gas puffing, the SMBI features prompt response and larger fueling flux. These merits devote the SMBI a good fueling method, an excellent plasma density feedback control tool, and an edge localized mode mitigation resource.

  15. Advances and challenges in the molecular biology and treatment of glioblastoma—is there any hope for the future?

    PubMed Central

    Veliz, Ignacio; Loo, Yong; Castillo, Omar; Karachaliou, Niki; Nigro, Olga

    2015-01-01

    Malignant gliomas, such as glioblastoma multiforme (GBM), present some of the greatest challenges in the management of cancer patients worldwide. Even with aggressive surgical resections and recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal and quality of life is poor. Although new molecular pathways crucial to the biology and invasive ability of GBM are coming to light, translation of basic science achievements into clinical practice is slow. Optimal management requires a multidisciplinary approach and knowledge of potential complications arising from both disease and treatment. To help illustrate “where we are going” with GBM, we here include a detailed depiction of the molecular alterations underlying this fatal disease, as well as intensive research over the past two decades that has led to considerable advances in the understanding of basic GBM biology, pathogenesis and therapeutic approaches. PMID:25705639

  16. Global and local properties used as analyses tools for molecular-dynamics simulations

    NASA Astrophysics Data System (ADS)

    Bachlechner, Martina E.; Anderson, Jonas T.; Cao, Deng; Leonard, Robert H.; Owens, Eli T.; Schiffbauer, Jarrod E.; Burky, Melissa R.; Ducatman, Samuel C.; Guffey, Eric J.; Serrano Ramos2, Fernando

    2006-03-01

    Molecular dynamics simulations have been used to study mechanical failure in realistic interface materials. Averaging over the individual atoms' contributions yields local and global information including displacements, bond angles, strains, stress tensor components, and pair distribution functions. A combined analysis of global and local properties facilitates detailed insight in the mechanisms of failure, which will eventually guide on how to prevent failure of interfaces.

  17. Spatiotemporal Fluctuation Analysis: A Powerful Tool for the Future Nanoscopy of Molecular Processes.

    PubMed

    Di Rienzo, Carmine; Gratton, Enrico; Beltram, Fabio; Cardarelli, Francesco

    2016-08-23

    The enormous wealth of information available today from optical microscopy measurements on living samples is often underexploited. We argue that spatiotemporal analysis of fluorescence fluctuations using multiple detection channels can enhance the performance of current nanoscopy methods and provide further insight into dynamic molecular processes of high biological relevance.

  18. [Molecular markers: an important tool in the diagnosis, treatment and epidemiology of invasive aspergillosis].

    PubMed

    Frías-de León, María Guadalupe; Acosta-Altamirano, Gustavo; Duarte-Escalante, Esperanza; Martínez-Hernández, José Enrique; Martínez-Rivera, María de Los Ángeles; Reyes-Montes, María Del Rocío

    2014-01-01

    Increase in the incidence of invasive aspergillosis has represented a difficult problem for management of patients with this infection due to its high rate of mortality, limited knowledge concerning its diagnosis, and therapeutic practice. The difficulty in management of patients with aspergillosis initiates with detection of the fungus in the specimens of immunosuppressed patients infected with Aspergillus fumigatus; in addition, difficulty exists in terms of the development of resistance to antifungals as a consequence of their indiscriminate use in prophylactic and therapeutic practice and to ignorance concerning the epidemiological data of aspergillosis. With the aim of resolving these problems, molecular markers is employed at present with specific and accurate results. However, in Mexico, the use of molecular markers has not yet been implemented in the routine of intrahospital laboratories; despite the fact that these molecular markers has been widely referred in the literature, it is necessary for it to validated and standardized to ensure that the results obtained in any laboratory would be reliable and comparable. In the present review, we present an update on the usefulness of molecular markers in accurate identification of A. fumigatus, detection of resistance to antifugal triazoles, and epidemiological studies for establishing the necessary measures for prevention and control of aspergillosis.

  19. A new molecular diagnostic tool for quantitatively detecting and genotyping “Candidatus Liberibacter species”

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new molecular diagnostic method was developed for quantitative detection of “Candidatus Liberibacter” species associated with citrus Huanglongbing (“Ca. Liberibacter asiaticus”, “Ca. Liberibacter africanus” and “Ca. Liberibacter americanus”) and potato zebra chip disorder (“Ca. Liberibacter solana...

  20. Application of Machine Learning tools to recognition of molecular patterns in STM images

    NASA Astrophysics Data System (ADS)

    Maksov, Artem; Ziatdinov, Maxim; Fujii, Shintaro; Kiguchi, Manabu; Higashibayashi, Shuhei; Sakurai, Hidehiro; Kalinin, Sergei; Sumpter, Bobby

    The ability to utilize individual molecules and molecular assemblies as data storage elements has motivated scientist for years, concurrent with the continuous effort to shrink a size of data storage devices in microelectronics industry. One of the critical issues in this effort lies in being able to identify individual molecular assembly units (patterns), on a large scale in an automated fashion of complete information extraction. Here we present a novel method of applying machine learning techniques for extraction of positional and rotational information from scanning tunneling microscopy (STM) images of π-bowl sumanene molecules on gold. We use Markov Random Field (MRF) model to decode the polar rotational states for each molecule in a large scale STM image of molecular film. We further develop an algorithm that uses a convolutional Neural Network combined with MRF and input from density functional theory to classify molecules into different azimuthal rotational classes. Our results demonstrate that a molecular film is partitioned into distinctive azimuthal rotational domains consisting typically of 20-30 molecules. In each domain, the ``bowl-down'' molecules are generally surrounded by six nearest neighbor molecules in ``bowl-up'' configuration, and the resultant overall structure form a periodic lattice of rotational and polar states within each domain. Research was supported by the US Department of Energy.

  1. CAChe Molecular Modeling: A Visualization Tool Early in the Undergraduate Chemistry Curriculum.

    ERIC Educational Resources Information Center

    Crouch, R. David; And Others

    1996-01-01

    Describes a "Synthesis and Reactivity" curriculum that focuses on the correlation of laboratory experiments with lecture topics and the extension of laboratory exercises beyond the usual four-hour period. Highlights experiments developed and an out-of-class computational chemistry exercise using CAChe, a versatile molecular modeling…

  2. The Need for Novel Informatics Tools for Integrating and Planning Research in Molecular and Cellular Cognition

    ERIC Educational Resources Information Center

    Silva, Alcino J.; Müller, Klaus-Robert

    2015-01-01

    The sheer volume and complexity of publications in the biological sciences are straining traditional approaches to research planning. Nowhere is this problem more serious than in molecular and cellular cognition, since in this neuroscience field, researchers routinely use approaches and information from a variety of areas in neuroscience and other…

  3. Beyond a pedagogical tool: 30 years of Molecular biology of the cell.

    PubMed

    Serpente, Norberto

    2013-02-01

    In 1983, a bulky and profusely illustrated textbook on molecular and cell biology began to inhabit the shelves of university libraries worldwide. The effect of capturing the eyes and souls of biologists was immediate as the book provided them with a new and invigorating outlook on what cells are and what they do.

  4. Machine Tool Advanced Skills Technology (MAST). Common Ground: Toward a Standards-Based Training System for the U.S. Machine Tool and Metal Related Industries. Volume 11: Computer-Aided Manufacturing & Advanced CNC, of a 15-Volume Set of Skill Standards and Curriculum Training Materials for the Precision Manufacturing Industry.

    ERIC Educational Resources Information Center

    Texas State Technical Coll., Waco.

    This document is intended to help education and training institutions deliver the Machine Tool Advanced Skills Technology (MAST) curriculum to a variety of individuals and organizations. MAST consists of industry-specific skill standards and model curricula for 15 occupational specialty areas within the U.S. machine tool and metals-related…

  5. High-precision frequency measurements: indispensable tools at the core of the molecular-level analysis of complex systems

    PubMed Central

    Ruecker, C.; Meringer, M.; Gugisch, R.; Frommberger, M.; Perdue, E. M.; Witt, M.; Schmitt-Kopplin, P.

    2007-01-01

    This perspective article provides an assessment of the state-of-the-art in the molecular-resolution analysis of complex organic materials. These materials can be divided into biomolecules in complex mixtures (which are amenable to successful separation into unambiguously defined molecular fractions) and complex nonrepetitive materials (which cannot be purified in the conventional sense because they are even more intricate). Molecular-level analyses of these complex systems critically depend on the integrated use of high-performance separation, high-resolution organic structural spectroscopy and mathematical data treatment. At present, only high-precision frequency-derived data exhibit sufficient resolution to overcome the otherwise common and detrimental effects of intrinsic averaging, which deteriorate spectral resolution to the degree of bulk-level rather than molecular-resolution analysis. High-precision frequency measurements are integral to the two most influential organic structural spectroscopic methods for the investigation of complex materials—NMR spectroscopy (which provides unsurpassed detail on close-range molecular order) and FTICR mass spectrometry (which provides unrivalled resolution)—and they can be translated into isotope-specific molecular-resolution data of unprecedented significance and richness. The quality of this standalone de novo molecular-level resolution data is of unparalleled mechanistic relevance and is sufficient to fundamentally advance our understanding of the structures and functions of complex biomolecular mixtures and nonrepetitive complex materials, such as natural organic matter (NOM), aerosols, and soil, plant and microbial extracts, all of which are currently poorly amenable to meaningful target analysis. The discrete analytical volumetric pixel space that is presently available to describe complex systems (defined by NMR, FT mass spectrometry and separation technologies) is in the range of 108–14 voxels, and is

  6. Developing Molecular Genetic Tools to Facilitate Economic Production in Green Algae

    DTIC Science & Technology

    2012-09-10

    species they are not readily available for algae that are being identified as potential biofuel production strains . Our work was focused on developing...the genetic tools required to enable green algae to become efficient biofuel production strains . Being able to efficiently apply genetic...transformation techniques to green algae species will allow us to generate strains that contain ideal traits for maximally efficient fuel production, and will

  7. Surface-enhanced Raman spectroscopy as a tool for characterizing nanostructures containing molecular components

    NASA Astrophysics Data System (ADS)

    Xu, Ke; Abell, Justin; Zhao, Yiping; Qian, Jun; Brenneman, Kimber; Meshik, Xenia; Dutta, Mitra; Stroscio, Michael

    2012-12-01

    Raman spectroscopy, which is based on inelastic scattering of light that interacts with phonons or molecular vibrations in the nanostructure, has been widely used to identify chemical and biological molecules. Surface-Enhanced Raman Spectroscopy (SERS) greatly enhanced the sensitivity of conventional Raman spectroscopy by a factor of >106 through the use of a plasmon-generating substrate [1, 2]. This study investigated the use of Raman spectroscopy/SERS to verify that synthesized nanostructures contain active molecular components critical to their functioning. In particular, this study uses SERS to identify the signature spectrum of Methylene Blue (MB) and uses standard Raman spectroscopy to verify the fictionalization of a DNA aptamer terminated with MB.

  8. Chromatibody, a novel non-invasive molecular tool to explore and manipulate chromatin in living cells

    PubMed Central

    Jullien, Denis; Vignard, Julien; Fedor, Yoann; Béry, Nicolas; Olichon, Aurélien; Crozatier, Michèle; Erard, Monique; Cassard, Hervé; Ducommun, Bernard; Salles, Bernard

    2016-01-01

    ABSTRACT Chromatin function is involved in many cellular processes, its visualization or modification being essential in many developmental or cellular studies. Here, we present the characterization of chromatibody, a chromatin-binding single-domain, and explore its use in living cells. This non-intercalating tool specifically binds the heterodimer of H2A–H2B histones and displays a versatile reactivity, specifically labeling chromatin from yeast to mammals. We show that this genetically encoded probe, when fused to fluorescent proteins, allows non-invasive real-time chromatin imaging. Chromatibody is a dynamic chromatin probe that can be modulated. Finally, chromatibody is an efficient tool to target an enzymatic activity to the nucleosome, such as the DNA damage-dependent H2A ubiquitylation, which can modify this epigenetic mark at the scale of the genome and result in DNA damage signaling and repair defects. Taken together, these results identify chromatibody as a universal non-invasive tool for either in vivo chromatin imaging or to manipulate the chromatin landscape. PMID:27206857

  9. Prospective Molecular Characterization of Burn Wound Colonization: Novel Tools and Analysis

    DTIC Science & Technology

    2014-02-01

    not well understood, but several studies have linked E. coli from retail meat—particularly poultry —to extraintestinal human infections [16, 17...sequencing data analysis To validate our assays we used a collection of 174 E. coli isolates; 133 were recovered from retail poultry products and 41 were...isolates from retail poultry products met the molecular definition of ExPEC. Further studies must be conducted to quantify the risk of colonization and

  10. phenix.mr_rosetta: a new tool for difficult molecular replacement problems

    SciTech Connect

    Terwilliger, Thomas C; Read, Randy; De Maio, Frank; Baker, David

    2011-01-12

    The PHENIX development team is working with the Baker laboratory at the University of Washington to combine the power of Rosetta structure modeling with PHENIX automated molecular replacement (MR), model-building, density modification, and refinement. The basic idea is to find MR solutions with phenix. automr, rebuild them with Rosetta, including electron density map information, then rebuild those models with phenix. autobuild. The combination of Rosetta rebuilding and phenix rebuilding is the key part of this method. MR solutions are found with phenix. automr (Phaser), scored with LLG (optionally following Rosetta relaxation), the best solutions are picked and rebuilt with Rosetta including map information, the resulting models are scored with Rosetta, and then rescored with LLG, and the top models are rebuilt with phenix. autobuild. It can be very useful for cases where the search model used in molecular replacement is slightly too distant to rebuild successfully with phenix. autobuild. It can also be useful in cases where the model is too distant to even find a molecular replacement solution, and prerefinement with Rosetta can yield an improved search model.

  11. Molecularly imprinted polymers: an analytical tool for the determination of benzimidazole compounds in water samples.

    PubMed

    Cacho, Carmen; Turiel, Esther; Pérez-Conde, Concepción

    2009-05-15

    Molecularly imprinted polymers (MIPs) for benzimidazole compounds have been synthesized by precipitation polymerization using thiabendazole (TBZ) as template, methacrylic acid as functional monomer, ethyleneglycol dimethacrylate (EDMA) and divinylbenzene (DVB) as cross-linkers and a mixture of acetonitrile and toluene as porogen. The experiments carried out by molecularly imprinted solid phase extraction (MISPE) in cartridges demonstrated the imprint effect in both imprinted polymers. MIP-DVB enabled a much higher breakthrough volume than MIP-EDMA, and thus was selected for further experiments. The ability of this MIP for the selective recognition of other benzimidazole compounds (albendazole, benomyl, carbendazim, fenbendazole, flubendazole and fuberidazole) was evaluated. The obtained results revealed the high selectivity of the imprinted polymer towards all the selected benzimidazole compounds. An off-line analytical methodology based on a MISPE procedure has been developed for the determination of benzimidazole compounds in tap, river and well water samples at concentration levels below the legislated maximum concentration levels (MCLs) with quantitative recoveries. Additionally, an on-line preconcentration procedure based on the use of a molecularly imprinted polymer as selective stationary phase in HPLC is proposed as a fast screening method for the evaluation of the presence of benzimidazole compounds in water samples.

  12. Comparison of molecular and metabolomic methods as characterization tools of Debaryomyces hansenii cheese isolates.

    PubMed

    Del Bove, Marzia; Lattanzi, Monia; Rellini, Paolo; Pelliccia, Cristina; Fatichenti, Fabrizio; Cardinali, Gianluigi

    2009-08-01

    Debaryomyces hansenii is one of the yeast species most frequently isolated from cheese and salty foods, however little is known about the phenotypic and molecular variability of its strains. In order to explore the possibilities of a large study on its biodiversity, some D. hansenii strains were selectively isolated from pecorino cheese sampled in ten different Italian regions. All isolates were identified as D. hansenii on the basis of conventional and molecular taxonomic analysis. The D1/D2 domain sequences of the 26S-rDNA did not show any variation, confirming the extreme homogeneity of this species. PCR-duplex-RAPD banding patterns analyzed with PCoA showed interesting clustering related to the geographic areas of isolation, although some overlapping between strains derived from different districts could be observed. A FTIR (Fourier Transform Infrared Spectroscopy) metabolomic fingerprint produced groupings weakly related to those observed with RAPD and less associated with the isolation locales. The discriminatory power of metabolomic fingerprint was able to discriminate strains otherwise considered identical. This preliminary study showed that, in spite of the homogeneity at the 26S-rDNA level, the D. hansenii strains exhibit high molecular and metabolomic variability somehow linked to the places of isolation. Further studies will be necessary to better investigate on the link between terroir and strain variability, as well as on the relation between genotypic and metabolomic fingerprints.

  13. In vivo Cerenkov luminescence imaging: a new tool for molecular imaging.

    PubMed

    Mitchell, Gregory S; Gill, Ruby K; Boucher, David L; Li, Changqing; Cherry, Simon R

    2011-11-28

    Cerenkov radiation is a phenomenon where optical photons are emitted when a charged particle moves faster than the speed of light for the medium in which it travels. Recently, we and others have discovered that measurable visible light due to the Cerenkov effect is produced in vivo following the administration of β-emitting radionuclides to small animals. Furthermore, the amounts of injected activity required to produce a detectable signal are consistent with small-animal molecular imaging applications. This surprising observation has led to the development of a new hybrid molecular imaging modality known as Cerenkov luminescence imaging (CLI), which allows the spatial distribution of biomolecules labelled with β-emitting radionuclides to be imaged in vivo using sensitive charge-coupled device cameras. We review the physics of Cerenkov radiation as it relates to molecular imaging, present simulation results for light intensity and spatial distribution, and show an example of CLI in a mouse cancer model. CLI allows many common radiotracers to be imaged in widely available in vivo optical imaging systems, and, more importantly, provides a pathway for directly imaging β(-)-emitting radionuclides that are being developed for therapeutic applications in cancer and that are not readily imaged by existing methods.

  14. Advances in molecular imaging of atherosclerosis and myocardial infarction: shedding new light on in vivo cardiovascular biology

    PubMed Central

    Andia, Marcelo E.; Shah, Ajay M.; Botnar, René M.

    2012-01-01

    Molecular imaging of the cardiovascular system heavily relies on the development of new imaging probes and technologies to facilitate visualization of biological processes underlying or preceding disease. Molecular imaging is a highly active research discipline that has seen tremendous growth over the past decade. It has broadened our understanding of oncologic, neurologic, and cardiovascular diseases by providing new insights into the in vivo biology of disease progression and therapeutic interventions. As it allows for the longitudinal evaluation of biological processes, it is ideally suited for monitoring treatment response. In this review, we will concentrate on the major accomplishments and advances in the field of molecular imaging of atherosclerosis and myocardial infarction with a special focus on magnetic resonance imaging. PMID:23064836

  15. Pulmonary adenocarcinoma: implications of the recent advances in molecular biology, treatment and the IASLC/ATS/ERS classification

    PubMed Central

    Thakur, Priyanka; Bhardwaj, Bhaskar; Susheela, Sridhar Papaiah; Madabhavi, Irappa

    2014-01-01

    A decade ago, lung cancer could conveniently be classified into two broad categories—either the small cell lung carcinoma (SCLC), or the non-small cell lung carcinoma (NSCLC), mainly to assist in further treatment related decision making. However, the understanding regarding the eligibility of adenocarcinoma histology for treatments with agents such as pemetrexed and bevacizumab made it a necessity for NSCLC to be classified into more specific sub-groups. Then, the availability of molecular targeted therapy with oral tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib not only further emphasized the need for accurate sub-classification of lung cancer, but also heralded the important role of molecular profiling of lung adenocarcinomas. Given the remarkable advances in molecular biology, oncology and radiology, a need for felt for a revised classification for lung adenocarcinoma, since the existing World Health Organization (WHO) classification of lung cancer, published in the year 2004 was mainly a pathological system of classification. Thus, there was a combined effort by the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS) and the European Respiratory Society (ERS) with an effort to inculcate newly established perspectives from clinical, molecular and radiological aspects in evolving a modern classification for lung adenocarcinomas. This review provides a summary of the recent advances in molecular biology and molecular targeted therapy with respect to lung adenocarcinoma. Also, a brief summation of the salient recommendations provided in the IASLC/ATS/ERS classification of lung adenocarcinomas is provided. Lastly, a discussion regarding the future prospects with lung adenocarcinoma is included. PMID:25349702

  16. A Tool for Brain-Wide Quantitative Analysis of Molecular Data upon Projection into a Planar View of Choice

    PubMed Central

    Vreysen, Samme; Scheyltjens, Isabelle; Laramée, Marie-Eve; Arckens, Lutgarde

    2017-01-01

    Several techniques, allowing the reconstruction and visualization of functional, anatomical or molecular information from tissue and organ slices, have been developed over the years. Yet none allow direct comparison without reprocessing the same slices. Alternative methods using publicly available reference maps like the Allen Brain Atlas lack flexibility with respect to age and species. We propose a new approach to reconstruct a segmented region of interest from serial slices by projecting the optical density values representing a given molecular signal to a plane of view of choice, and to generalize the results into a reference map, which is built from the individual maps of all animals under study. Furthermore, to allow quantitative comparison between experimental conditions, a non-parametric pseudo t-test has been implemented. This new mapping tool was applied, optimized and validated making use of an in situ hybridization dataset that represents the spatiotemporal expression changes for the neuronal activity reporter gene zif268, in relation to cortical plasticity induced by monocular enucleation, covering the entire mouse visual cortex. The created top view maps of the mouse brain allow precisely delineating and interpreting 11 extrastriate areas surrounding mouse V1. As such, and because of the opportunity to create a planar projection of choice, these molecular maps can in the future easily be compared with functional or physiological imaging maps created with other techniques such as Ca2+, flavoprotein and optical imaging. PMID:28144216

  17. Fundamental Limits:. Developing New Tools for a Better Understanding of Second-Order Molecular Nonlinear Optics

    NASA Astrophysics Data System (ADS)

    Pérez-Moreno, Javier; Clays, Koen

    The generalized Thomas-Kuhn sum rules are used to characterize the nonlinear optical response of organic chromophores in terms of fundamental parameters that can be measured experimentally. The nonlinear optical performance of organic molecules is evaluated from the combination of hyper-Rayleigh scattering measurements and the analysis in terms of the fundamental limits. Different strategies for the enhancement of nonlinear optical behavior at the molecular and supramolecular level are evaluated and new paradigms for the design of more efficient nonlinear optical molecules are proposed and investigated.

  18. The virtual cell animation collection: tools for teaching molecular and cellular biology.

    PubMed

    Reindl, Katie M; White, Alan R; Johnson, Christina; Vender, Bradley; Slator, Brian M; McClean, Phillip

    2015-04-01

    A cell is a minifactory in which structures and molecules are assembled, rearranged, disassembled, packaged, sorted, and transported. Because cellular structures and molecules are invisible to the human eye, students often have difficulty conceptualizing the dynamic nature of cells that function at multiple scales across time and space. To represent these dynamic cellular processes, the Virtual Cell Productions team at North Dakota State University develops freely available multimedia materials to support molecular and cellular biology learning inside and outside the high school and university classroom.

  19. Anthropogenic Molecular Markers: Tools to Identify the Sources and Transport Pathways of Pollutants

    USGS Publications Warehouse

    Takada, H.; Satoh, F.; Bothner, Michael H.; Tripp, B.W.; Johnson, C.G.; Farrington, J.W.

    1997-01-01

    The activities of modern civilization have released to the oceans a wide variety of both mobilized natural compounds and synthetic compounds not found prior to modern times. Many of these compounds provide a means of identifying sources of inputs and pathways of movement of chemicals through oceanic ecosystems and serve as molecular markers of human activities. A coastal ocean (Tokyo Bay) and a deep ocean (Deep Water Dump Site 106 in the Western North Atlantic Ocean) example are presented. In the deep ocean study, the correlation between potential sewage marker, i.e. linear alkylbenzenes (LABs), and polychlorinated biphenyls (PCBs) concentrations indicates a contribution of sewage sludge PCBs to the dump site sediments.

  20. The Virtual Cell Animation Collection: Tools for Teaching Molecular and Cellular Biology

    PubMed Central

    Reindl, Katie M.; White, Alan R.; Johnson, Christina; Vender, Bradley; Slator, Brian M.; McClean, Phillip

    2015-01-01

    A cell is a minifactory in which structures and molecules are assembled, rearranged, disassembled, packaged, sorted, and transported. Because cellular structures and molecules are invisible to the human eye, students often have difficulty conceptualizing the dynamic nature of cells that function at multiple scales across time and space. To represent these dynamic cellular processes, the Virtual Cell Productions team at North Dakota State University develops freely available multimedia materials to support molecular and cellular biology learning inside and outside the high school and university classroom. PMID:25856580

  1. Computational and molecular tools for scalable rAAV-mediated genome editing

    PubMed Central

    Stoimenov, Ivaylo; Ali, Muhammad Akhtar; Pandzic, Tatjana; Sjöblom, Tobias

    2015-01-01

    The rapid discovery of potential driver mutations through large-scale mutational analyses of human cancers generates a need to characterize their cellular phenotypes. Among the techniques for genome editing, recombinant adeno-associated virus (rAAV)-mediated gene targeting is suited for knock-in of single nucleotide substitutions and to a lesser degree for gene knock-outs. However, the generation of gene targeting constructs and the targeting process is time-consuming and labor-intense. To facilitate rAAV-mediated gene targeting, we developed the first software and complementary automation-friendly vector tools to generate optimized targeting constructs for editing human protein encoding genes. By computational approaches, rAAV constructs for editing ∼71% of bases in protein-coding exons were designed. Similarly, ∼81% of genes were predicted to be targetable by rAAV-mediated knock-out. A Gateway-based cloning system for facile generation of rAAV constructs suitable for robotic automation was developed and used in successful generation of targeting constructs. Together, these tools enable automated rAAV targeting construct design, generation as well as enrichment and expansion of targeted cells with desired integrations. PMID:25488813

  2. Application of metabolite profiling tools and time-of-flight mass spectrometry in the identification of transformation products of iopromide and iopamidol during advanced oxidation.

    PubMed

    Singh, Randolph R; Lester, Yaal; Linden, Karl G; Love, Nancy G; Atilla-Gokcumen, G Ekin; Aga, Diana S

    2015-03-03

    The efficiency of wastewater treatment systems in removing pharmaceuticals is often assessed on the basis of the decrease in the concentration of the parent compound. However, what is perceived as "removal" during treatment may not necessarily mean mineralization of the pharmaceutical compound but simply conversion into different transformation products (TPs). Using liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer (LC-QToF-MS), we demonstrated conversion of iopromide in wastewater to at least 14 TPs after an advanced oxidation process (AOP) using UV (fluence = 1500 mJ/cm(2)) and H2O2 (10 mg/L). Due to the complexity of the wastewater matrix, the initial experiments were performed using a high concentration (10 mg/L) of iopromide in order to facilitate the identification of TPs. Despite the high concentration of iopromide used, cursory inspection of UV and mass spectra only revealed four TPs in the chromatograms of the post-AOP samples. However, the use of METLIN database and statistics-based profiling tools commonly used in metabolomics proved effective in discriminating between background signals and TPs derived from iopromide. High-resolution mass data allowed one to predict molecular formulas of putative TPs with errors below 5 ppm relative to the observed m/z. Tandem mass spectrometry (MS/MS) data and isotope pattern comparisons provided necessary information that allowed one to elucidate the structure of iopromide TPs. The presence of the proposed iopromide TPs was determined in unspiked wastewater from a municipal wastewater treatment plant, but no iopromide and TPs were detected. Using analogous structural modifications and oxidation that results from the AOP treatment of iopromide, the potential TPs of iopamidol (a structurally similar compound to iopromide) were predicted. The same mass fragmentation pattern observed in iopromide TPs was applied to the predicted iopamidol TPs. LC-QToF-MS revealed the presence of two iopamidol

  3. Machine Tool Advanced Skills Technology (MAST). Common Ground: Toward a Standards-Based Training System for the U.S. Machine Tool and Metal Related Industries. Volume 9: Tool and Die, of a 15-Volume Set of Skill Standards and Curriculum Training Materials for the Precision Manufacturing Industry.

    ERIC Educational Resources Information Center

    Texas State Technical Coll., Waco.

    This document is intended to help education and training institutions deliver the Machine Tool Advanced Skills Technology (MAST) curriculum to a variety of individuals and organizations. MAST consists of industry-specific skill standards and model curricula for 15 occupational specialty areas within the U.S. machine tool and metals-related…

  4. Molecular bioelectricity in developmental biology: new tools and recent discoveries: control of cell behavior and pattern formation by transmembrane potential gradients.

    PubMed

    Levin, Michael

    2012-03-01

    Significant progress in the molecular investigation of endogenous bioelectric signals during pattern formation in growing tissues has been enabled by recently developed techniques. Ion flows and voltage gradients produced by ion channels and pumps are key regulators of cell proliferation, migration, and differentiation. Now, instructive roles for bioelectrical gradients in embryogenesis, regeneration, and neoplasm are being revealed through the use of fluorescent voltage reporters and functional experiments using well-characterized channel mutants. Transmembrane voltage gradients (V(mem) ) determine anatomical polarity and function as master regulators during appendage regeneration and embryonic left-right patterning. A state-of-the-art recent study reveals that they can also serve as prepatterns for gene expression domains during craniofacial patterning. Continued development of novel tools and better ways to think about physical controls of cell-cell interactions will lead to mastery of the morphogenetic information stored in physiological networks. This will enable fundamental advances in basic understanding of growth and form, as well as transformative biomedical applications in regenerative medicine.

  5. Molecular tools for investigating microbial community structure and function in oxygen-deficient marine waters.

    PubMed

    Hawley, Alyse K; Kheirandish, Sam; Mueller, Andreas; Leung, Hilary T C; Norbeck, Angela D; Brewer, Heather M; Pasa-Tolic, Ljiljana; Hallam, Steven J

    2013-01-01

    Water column oxygen (O2)-deficiency shapes food-web structure by progressively directing nutrients and energy away from higher trophic levels into microbial community metabolism resulting in fixed nitrogen loss and greenhouse gas production. Although respiratory O2 consumption during organic matter degradation is a natural outcome of a productive surface ocean, global-warming-induced stratification intensifies this process leading to oxygen minimum zone (OMZ) expansion. Here, we describe useful tools for detection and quantification of potential key microbial players and processes in OMZ community metabolism including quantitative polymerase chain reaction primers targeting Marine Group I Thaumarchaeota, SUP05, Arctic96BD-19, and SAR324 small-subunit ribosomal RNA genes and protein extraction methods from OMZ waters compatible with high-resolution mass spectrometry for profiling microbial community structure and functional dynamics.

  6. Parasite zoonoses and climate change: molecular tools for tracking shifting boundaries.

    PubMed

    Polley, Lydden; Thompson, R C Andrew

    2009-06-01

    For human, domestic animal and wildlife health, key effects of directional climate change include the risk of the altered occurrence of infectious diseases. Many parasite zoonoses have high potential for vulnerability to the new climate, in part because their free-living life-cycle stages and ectothermic hosts are directly exposed to climatic conditions. For these zoonoses, climate change can shift boundaries for ecosystem components and processes integral to parasite transmission and persistence, and these shifts can impact host health. Vulnerable boundaries include those for spatial distributions, host-parasite assemblages, demographic rates, life-cycle phenologies, associations within ecosystems, virulence, and patterns of infection and disease. This review describes these boundary shifts and how molecular techniques can be applied to defining the new boundaries.

  7. Oscillating Magnet Array−Based Nanomagnetic Gene Transfection: A Valuable Tool for Molecular Neurobiology Studies

    PubMed Central

    Subramanian, Mahendran; Tyler, Aimee-Jayne; Luther, Eva Maria; Daniel, Elena Di; Lim, Jenson; Dobson, Jon

    2017-01-01

    To develop treatments for neurodegenerative disorders, it is critical to understand the biology and function of neurons in both normal and diseased states. Molecular studies of neurons involve the delivery of small biomolecules into cultured neurons via transfection to study genetic variants. However, as cultured primary neurons are sensitive to temperature change, stress, and shifts in pH, these factors make biomolecule delivery difficult, particularly non-viral delivery. Herein we used oscillating nanomagnetic gene transfection to successfully transfect SH-SY5Y cells as well as primary hippocampal and cortical neurons on different days in vitro. This novel technique has been used to effectively deliver genetic material into various cell types, resulting in high transfection efficiency and viability. From these observations and other related studies, we suggest that oscillating nanomagnetic gene transfection is an effective method for gene delivery into hard-to-transfect neuronal cell types. PMID:28336862

  8. Current Tools and Methods in Molecular Dynamics (MD) Simulations for Drug Design.

    PubMed

    Hernández-Rodríguez, Maricarmen; Rosales-Hernández, Martha C; Mendieta-Wejebe, Jessica E; Martínez-Archundia, Marlet; Basurto, José Correa

    2016-01-01

    Molecular Dynamics (MD) simulations is a computational method that employs Newton's laws to evaluate the motions of water, ions, small molecules, and macromolecules or more complex systems, for example, whole viruses, to reproduce the behavior of the biological environment, including water molecules and lipid membranes. Specifically, structural motions, such as those that are dependent of the temperature and solute/ solvent are very important to study the recognition pattern of ligandprotein or protein-protein complexes, in that sense, MD simulations are very useful because these motions can be modeled using this methodology. Furthermore, MD simulations for drug design provide insights into the structural cavities required to design novel structures with higher affinity to the target. Also, the employment of MD simulations to drug design can help to refine the three-dimensional (3D) structure of targets in order to obtain a better sampling of the binding poses and more reliable affinity values with better structural advantages, because they incorporate some biological conditions that include structural motions compared to traditional docking procedures. This work analyzes the concepts and applicability of MD simulations for drug design because molecular structural motions are considered, and these help to identify hot spots, decipher structural details in the reported protein sites, as well as to eliminate sites that could be structural artifacts which could be originated from the structural characterization conditions from MD. Moreover, better free energy values for protein ligand recognition can also be obtained, and these can be validated under experimental procedures due to the robustness of the MD simulation methods.

  9. Treatment algorithm in 2014 for advanced non-small cell lung cancer: therapy selection by tumour histology and molecular biology.

    PubMed

    Manegold, Christian

    2014-09-01

    The availability of antineoplastic monoclonal antibodies, small molecules and newer cytotoxics such as pemetrexed, the EGFR-tyrosine kinase inhibitors erlotinib, gefitinib, afatinib as well as the anti-angiogenic bevacizumab and the ALK-inhibitor crizotinib has recently changes the treatment algorithm of advanced non-small cell lung cancer. Decision making in 2014 is characterized by customizing therapy, by selecting a specific therapeutic regimen based on the histotype and the genotype of the tumour. This refers to first-line induction therapy and maintenance therapy as well, but also to subsequent lines of therapy since anti-neoplastic drugs and regimens used upfront clinically influence the selection of agents/regimes considered for second-/third-line treatment. Consequently, therapy customization through tumour histology and molecular markers has significantly influenced the work of pathologists around the globe and the process of obtaining an extended therapeutically relevant tumour diagnosis. Not only histological sub-typing became standard but molecular information is also considered of increasing importance for treatment selection. Routine molecular testing in certified laboratories must be established, and the diagnostic process should ideally be performed under the guidance of evidence based recommendation. The process of investigating and implementing medical targeting in lung cancer therefore, requires advanced diagnostic techniques and expertise and because of its large dimension is costly and influenced by the limitation of financial and clinical resources.

  10. Image navigation and registration performance assessment tool set for the GOES-R Advanced Baseline Imager and Geostationary Lightning Mapper

    NASA Astrophysics Data System (ADS)

    De Luccia, Frank J.; Houchin, Scott; Porter, Brian C.; Graybill, Justin; Haas, Evan; Johnson, Patrick D.; Isaacson, Peter J.; Reth, Alan D.

    2016-05-01

    The GOES-R Flight Project has developed an Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for measuring Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) INR performance metrics in the post-launch period for performance evaluation and long term monitoring. For ABI, these metrics are the 3-sigma errors in navigation (NAV), channel-to-channel registration (CCR), frame-to-frame registration (FFR), swath-to-swath registration (SSR), and within frame registration (WIFR) for the Level 1B image products. For GLM, the single metric of interest is the 3-sigma error in the navigation of background images (GLM NAV) used by the system to navigate lightning strikes. 3-sigma errors are estimates of the 99. 73rd percentile of the errors accumulated over a 24 hour data collection period. IPATS utilizes a modular algorithmic design to allow user selection of data processing sequences optimized for generation of each INR metric. This novel modular approach minimizes duplication of common processing elements, thereby maximizing code efficiency and speed. Fast processing is essential given the large number of sub-image registrations required to generate INR metrics for the many images produced over a 24 hour evaluation period. Another aspect of the IPATS design that vastly reduces execution time is the off-line propagation of Landsat based truth images to the fixed grid coordinates system for each of the three GOES-R satellite locations, operational East and West and initial checkout locations. This paper describes the algorithmic design and implementation of IPATS and provides preliminary test results.

  11. Image Navigation and Registration Performance Assessment Tool Set for the GOES-R Advanced Baseline Imager and Geostationary Lightning Mapper

    NASA Technical Reports Server (NTRS)

    De Luccia, Frank J.; Houchin, Scott; Porter, Brian C.; Graybill, Justin; Haas, Evan; Johnson, Patrick D.; Isaacson, Peter J.; Reth, Alan D.

    2016-01-01

    The GOES-R Flight Project has developed an Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for measuring Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) INR performance metrics in the post-launch period for performance evaluation and long term monitoring. For ABI, these metrics are the 3-sigma errors in navigation (NAV), channel-to-channel registration (CCR), frame-to-frame registration (FFR), swath-to-swath registration (SSR), and within frame registration (WIFR) for the Level 1B image products. For GLM, the single metric of interest is the 3-sigma error in the navigation of background images (GLM NAV) used by the system to navigate lightning strikes. 3-sigma errors are estimates of the 99.73rd percentile of the errors accumulated over a 24-hour data collection period. IPATS utilizes a modular algorithmic design to allow user selection of data processing sequences optimized for generation of each INR metric. This novel modular approach minimizes duplication of common processing elements, thereby maximizing code efficiency and speed. Fast processing is essential given the large number of sub-image registrations required to generate INR metrics for the many images produced over a 24-hour evaluation period. Another aspect of the IPATS design that vastly reduces execution time is the off-line propagation of Landsat based truth images to the fixed grid coordinates system for each of the three GOES-R satellite locations, operational East and West and initial checkout locations. This paper describes the algorithmic design and implementation of IPATS and provides preliminary test results.

  12. PET/SPECT molecular imaging in clinical neuroscience: recent advances in the investigation of CNS diseases

    PubMed Central

    Lu, Feng-Mei

    2015-01-01

    Molecular imaging is an attractive technology widely used in clinical practice that greatly enhances our understanding of the pathophysiology and treatment in central nervous system (CNS) diseases. It is a novel multidisciplinary technique that can be defined as real-time visualization, in vivo characterization and qualification of biological processes at the molecular and cellular level. It involves the imaging modalities and the corresponding imaging agents. Nowadays, molecular imaging in neuroscience has provided tremendous insights into disturbed human brain function. Among all of the molecular imaging modalities, positron emission tomography (PET) and single photon emission computed tomography (SPECT) have occupied a particular position that visualize and measure the physiological processes using high-affinity and high-specificity molecular radioactive tracers as imaging probes in intact living brain. In this review, we will put emphasis on the PET/SPECT applications in Alzheimer’s disease (AD) and Parkinson’s disease (PD) as major CNS disorders. We will first give an overview of the main classical molecular neuroimaging modalities. Then, the major clinical applications of PET and SPECT along with molecular probes in the fields of psychiatry and neurology will be discussed. PMID:26029646

  13. SU-E-T-398: Feasibility of Automated Tools for Robustness Evaluation of Advanced Photon and Proton Techniques in Oropharyngeal Cancer

    SciTech Connect

    Liu, H; Liang, X; Kalbasi, A; Lin, A; Ahn, P; Both, S

    2014-06-01

    Purpose: Advanced radiotherapy (RT) techniques such as proton pencil beam scanning (PBS) and photon-based volumetric modulated arc therapy (VMAT) have dosimetric advantages in the treatment of head and neck malignancies. However, anatomic or alignment changes during treatment may limit robustness of PBS and VMAT plans. We assess the feasibility of automated deformable registration tools for robustness evaluation in adaptive PBS and VMAT RT of oropharyngeal cancer (OPC). Methods: We treated 10 patients with bilateral OPC with advanced RT techniques and obtained verification CT scans with physician-reviewed target and OAR contours. We generated 3 advanced RT plans for each patient: proton PBS plan using 2 posterior oblique fields (2F), proton PBS plan using an additional third low-anterior field (3F), and a photon VMAT plan using 2 arcs (Arc). For each of the planning techniques, we forward calculated initial (Ini) plans on the verification scans to create verification (V) plans. We extracted DVH indicators based on physician-generated contours for 2 target and 14 OAR structures to investigate the feasibility of two automated tools (contour propagation (CP) and dose deformation (DD)) as surrogates for routine clinical plan robustness evaluation. For each verification scan, we compared DVH indicators of V, CP and DD plans in a head-to-head fashion using Student's t-test. Results: We performed 39 verification scans; each patient underwent 3 to 6 verification scan. We found no differences in doses to target or OAR structures between V and CP, V and DD, and CP and DD plans across all patients (p > 0.05). Conclusions: Automated robustness evaluation tools, CP and DD, accurately predicted dose distributions of verification (V) plans using physician-generated contours. These tools may be further developed as a potential robustness screening tool in the workflow for adaptive treatment of OPC using advanced RT techniques, reducing the need for physician-generated contours.

  14. An interaction network predicted from public data as a discovery tool: application to the Hsp90 molecular chaperone machine.

    PubMed

    Echeverría, Pablo C; Bernthaler, Andreas; Dupuis, Pierre; Mayer, Bernd; Picard, Didier

    2011-01-01

    Understanding the functions of proteins requires information about their protein-protein interactions (PPI). The collective effort of the scientific community generates far more data on any given protein than individual experimental approaches. The latter are often too limited to reveal an interactome comprehensively. We developed a workflow for parallel mining of all major PPI databases, containing data from several model organisms, and to integrate data from the literature for a protein of interest. We applied this novel approach to build the PPI network of the human Hsp90 molecular chaperone machine (Hsp90Int) for which previous efforts have yielded limited and poorly overlapping sets of interactors. We demonstrate the power of the Hsp90Int database as a discovery tool by validating the prediction that the Hsp90 co-chaperone Aha1 is involved in nucleocytoplasmic transport. Thus, we both describe how to build a custom database and introduce a powerful new resource for the scientific community.

  15. Molecular tools and protocols for engineering the acid-tolerant yeast Zygosaccharomyces bailii as a potential cell factory.

    PubMed

    Branduardi, Paola; Dato, Laura; Porro, Danilo

    2014-01-01

    Microorganisms offer a tremendous potential as cell factories, and they are indeed used by humans for centuries for biotransformations. Among them, yeasts combine the advantage of unicellular state with a eukaryotic organization, and, in the era of biorefineries, their biodiversity can offer solutions to specific process constraints. Zygosaccharomyces bailii, an ascomycetales budding yeast, is widely known for its peculiar tolerance to various stresses, among which are organic acids. Despite the possibility to apply with this yeast some of the molecular tools and protocols routinely used to manipulate Saccharomyces cerevisiae, adjustments and optimizations are necessary. Here, we describe in detail protocols for transformation, for target gene disruption or gene integration, and for designing episomal expression plasmids helpful for developing and further studying the yeast Z. bailii.

  16. Major intercontinentally distributed sequence types of Kingella kingae and development of a rapid molecular typing tool.

    PubMed

    Basmaci, Romain; Bidet, Philippe; Yagupsky, Pablo; Muñoz-Almagro, Carmen; Balashova, Nataliya V; Doit, Catherine; Bonacorsi, Stéphane

    2014-11-01

    Although Kingella kingae is the most common etiology of osteoarticular infections in young children, is a frequent cause of bacteremia in those younger than 4 years, and has been involved in clusters of invasive infections among daycare center attendees, the population structure of the species has not been systematically studied. Using multilocus sequence typing, we investigated the genetic diversity of the largest intercontinental collection of K. kingae strains to date. To facilitate typing of bacterial isolates, we developed a novel genotyping tool that targets the DNA uptake sequence (DUS). Among 324 strains isolated from asymptomatic carriers and patients from Israel, Europe, North America, and Australia with various invasive forms of the disease from 1960 to 2013, we identified 64 sequence types (STs) and 12 ST complexes (STcs). Five predominant STcs, comprising 72.2% of all strains, were distributed intercontinentally. ST-6 was the most frequent, showing a worldwide distribution, and appeared genotypically isolated by exhibiting few neighboring STs, suggesting an optimal fitness. ST-14 and ST-23 appeared to be the oldest groups of bacteria, while ST-25 probably emerged more recently from the highly evolutive ST-23. Using the DUS typing method, randomly chosen isolates were correctly classified to one of the major STcs. The comprehensive description of K. kingae evolution would help to detect new emerging clones and decipher virulence and fitness mechanisms. The rapid and reproducible DUS typing method may serve in the initial investigation of K. kingae outbreaks.

  17. Major Intercontinentally Distributed Sequence Types of Kingella kingae and Development of a Rapid Molecular Typing Tool

    PubMed Central

    Basmaci, Romain; Bidet, Philippe; Yagupsky, Pablo; Muñoz-Almagro, Carmen; Balashova, Nataliya V.; Doit, Catherine

    2014-01-01

    Although Kingella kingae is the most common etiology of osteoarticular infections in young children, is a frequent cause of bacteremia in those younger than 4 years, and has been involved in clusters of invasive infections among daycare center attendees, the population structure of the species has not been systematically studied. Using multilocus sequence typing, we investigated the genetic diversity of the largest intercontinental collection of K. kingae strains to date. To facilitate typing of bacterial isolates, we developed a novel genotyping tool that targets the DNA uptake sequence (DUS). Among 324 strains isolated from asymptomatic carriers and patients from Israel, Europe, North America, and Australia with various invasive forms of the disease from 1960 to 2013, we identified 64 sequence types (STs) and 12 ST complexes (STcs). Five predominant STcs, comprising 72.2% of all strains, were distributed intercontinentally. ST-6 was the most frequent, showing a worldwide distribution, and appeared genotypically isolated by exhibiting few neighboring STs, suggesting an optimal fitness. ST-14 and ST-23 appeared to be the oldest groups of bacteria, while ST-25 probably emerged more recently from the highly evolutive ST-23. Using the DUS typing method, randomly chosen isolates were correctly classified to one of the major STcs. The comprehensive description of K. kingae evolution would help to detect new emerging clones and decipher virulence and fitness mechanisms. The rapid and reproducible DUS typing method may serve in the initial investigation of K. kingae outbreaks. PMID:25143574

  18. Genetic Engineering: A Promising Tool to Engender Physiological, Biochemical, and Molecular Stress Resilience in Green Microalgae

    PubMed Central

    Guihéneuf, Freddy; Khan, Asif; Tran, Lam-Son P.

    2016-01-01

    As we march into the 21st century, the prevailing scenario of depleting energy resources, global warming and ever increasing issues of human health and food security will quadruple. In this context, genetic and metabolic engineering of green microalgae complete the quest toward a continuum of environmentally clean fuel and food production. Evolutionarily related, but unlike land plants, microalgae need nominal land or water, and are best described as unicellular autotrophs using light energy to fix atmospheric carbon dioxide (CO2) into algal biomass, mitigating fossil CO2 pollution in the process. Remarkably, a feature innate to most microalgae is synthesis and accumulation of lipids (60–65% of dry weight), carbohydrates and secondary metabolites like pigments and vitamins, especially when grown under abiotic stress conditions. Particularly fruitful, such an application of abiotic stress factors such as nitrogen starvation, salinity, heat shock, etc., can be used in a biorefinery concept for production of multiple valuable products. The focus of this mini-review underlies metabolic reorientation practices and tolerance mechanisms as applied to green microalgae under specific stress stimuli for a sustainable pollution-free future. Moreover, we entail current progress on genetic engineering as a promising tool to grasp adaptive processes for improving strains with potential biotechnological interests. PMID:27066043

  19. The Molecular Bronchoscope: A Tool for Measurement of Spatially Dependent CO2 Concentrations in the Lungs.

    PubMed

    Ciaffoni, Luca; Couper, John H; Richmond, Graham; Hancock, Gus; Ritchie, Grant A D

    2016-09-06

    Respiratory physicians use bronchoscopy for visual assessment of the lungs' topography and collecting tissue samples for external analysis. We propose a novel bronchoscope tool that would enable spatially dependent measurements of the functioning of the lungs by determining local concentrations of carbon dioxide, which will be produced by healthy parts of the lung at rates that are higher than from portions where gas exchange is impaired. The gas analyzer is based on a compact laser absorption spectrometer making use of fiber optics for delivery and return of low intensity diode laser radiation to and from the measurement chamber at the distal end of a flexible conduit. The appropriate optical wavelength was chosen such that light is selectively absorbed only by gaseous CO2. The optical absorption takes place over a short path (8.8 mm) within a rigid, 12 mm long, perforated probe tip. Wavelength modulation spectroscopy was adopted as the analytical technique to reduce the noise on the optical signal and yield measurements of relative CO2 concentration every 180 ms with a precision as low as 600 part-per-million by volume. The primary objective of such a device is to see if additional spatial information about the lungs functionality can be gathered, which will complement visual observation.

  20. Innovative and Advanced Coupled Neutron Transport and Thermal Hydraulic Method (Tool) for the Design, Analysis and Optimization of VHTR/NGNP Prismatic Reactors

    SciTech Connect

    Rahnema, Farzad; Garimeela, Srinivas; Ougouag, Abderrafi; Zhang, Dingkang

    2013-11-29

    This project will develop a 3D, advanced coarse mesh transport method (COMET-Hex) for steady- state and transient analyses in advanced very high-temperature reactors (VHTRs). The project will lead to a coupled neutronics and thermal hydraulic (T/H) core simulation tool with fuel depletion capability. The computational tool will be developed in hexagonal geometry, based solely on transport theory without (spatial) homogenization in complicated 3D geometries. In addition to the hexagonal geometry extension, collaborators will concurrently develop three additional capabilities to increase the code’s versatility as an advanced and robust core simulator for VHTRs. First, the project team will develop and implement a depletion method within the core simulator. Second, the team will develop an elementary (proof-of-concept) 1D time-dependent transport method for efficient transient analyses. The third capability will be a thermal hydraulic method coupled to the neutronics transport module for VHTRs. Current advancements in reactor core design are pushing VHTRs toward greater core and fuel heterogeneity to pursue higher burn-ups, efficiently transmute used fuel, maximize energy production, and improve plant economics and safety. As a result, an accurate and efficient neutron transport, with capabilities to treat heterogeneous burnable poison effects, is highly desirable for predicting VHTR neutronics performance. This research project’s primary objective is to advance the state of the art for reactor analysis.

  1. Efficient tool to calculate two-dimensional optical spectra for photoactive molecular complexes

    NASA Astrophysics Data System (ADS)

    Duan, Hong-Guang; Dijkstra, Arend G.; Nalbach, Peter; Thorwart, Michael

    2015-10-01

    We combine the coherent modified Redfield theory (CMRT) with the equation of motion-phase matching approach (PMA) to calculate two-dimensional photon-echo spectra for photoactive molecular complexes with an intermediate strength of the coupling to their environment. Both techniques are highly efficient, yet they involve approximations at different levels. By explicitly comparing with the numerically exact quasiadiabatic path integral approach, we show for the Fenna-Matthews-Olson complex that the CMRT describes the decay rates in the population dynamics well, but final stationary populations and the oscillation frequencies differ slightly. In addition, we use the combined CMRT+PMA to calculate two-dimensional photon-echo spectra for a simple dimer model. We find excellent agreement with the exact path integral calculations at short waiting times where the dynamics is still coherent. For long waiting times, differences occur due to different final stationary states, specifically for strong system-bath coupling. For weak to intermediate system-bath couplings, which is most important for natural photosynthetic complexes, the combined CMRT+PMA gives reasonable results with acceptable computational efforts.

  2. Evaluation of the Illumigene Malaria LAMP: A Robust Molecular Diagnostic Tool for Malaria Parasites

    PubMed Central

    Lucchi, Naomi W.; Gaye, Marie; Diallo, Mammadou Alpha; Goldman, Ira F.; Ljolje, Dragan; Deme, Awa Bineta; Badiane, Aida; Ndiaye, Yaye Die; Barnwell, John W.; Udhayakumar, Venkatachalam; Ndiaye, Daouda

    2016-01-01

    Isothermal nucleic acid amplification assays such as the loop mediated isothermal amplification (LAMP), are well suited for field use as they do not require thermal cyclers to amplify the DNA. To further facilitate the use of LAMP assays in remote settings, simpler sample preparation methods and lyophilized reagents are required. The performance of a commercial malaria LAMP assay (Illumigene Malaria LAMP) was evaluated using two sample preparation workflows (simple filtration prep (SFP)) and gravity-driven filtration prep (GFP)) and pre-dispensed lyophilized reagents. Laboratory and clinical samples were tested in a field laboratory in Senegal and the results independently confirmed in a reference laboratory in the U.S.A. The Illumigene Malaria LAMP assay was easily implemented in the clinical laboratory and gave similar results to a real-time PCR reference test with limits of detection of ≤2.0 parasites/μl depending on the sample preparation method used. This assay reliably detected Plasmodium sp. parasites in a simple low-tech format, providing a much needed alternative to the more complex molecular tests for malaria diagnosis. PMID:27827432

  3. Molecular inversion probe: a new tool for highly specific detection of plant pathogens.

    PubMed

    Lau, Han Yih; Palanisamy, Ramkumar; Trau, Matt; Botella, Jose R

    2014-01-01

    Highly specific detection methods, capable of reliably identifying plant pathogens are crucial in plant disease management strategies to reduce losses in agriculture by preventing the spread of diseases. We describe a novel molecular inversion probe (MIP) assay that can be potentially developed into a robust multiplex platform to detect and identify plant pathogens. A MIP has been designed for the plant pathogenic fungus Fusarium oxysporum f.sp. conglutinans and the proof of concept for the efficiency of this technology is provided. We demonstrate that this methodology can detect as little as 2.5 ng of pathogen DNA and is highly specific, being able to accurately differentiate Fusarium oxysporum f.sp. conglutinans from other fungal pathogens such as Botrytis cinerea and even pathogens of the same species such as Fusarium oxysporum f.sp. lycopersici. The MIP assay was able to detect the presence of the pathogen in infected Arabidopsis thaliana plants as soon as the tissues contained minimal amounts of pathogen. MIP methods are intrinsically highly multiplexable and future development of specific MIPs could lead to the establishment of a diagnostic method that could potentially screen infected plants for hundreds of pathogens in a single assay.

  4. Assessment of changes in microbial community structure during operation of an ammonia biofilter with molecular tools

    NASA Technical Reports Server (NTRS)

    Sakano, Y.; Kerkhof, L.; Janes, H. W. (Principal Investigator)

    1998-01-01

    Biofiltration has been used for two decades to remove odors and various volatile organic and inorganic compounds in contaminated off-gas streams. Although biofiltration is widely practiced, there have been few studies of the bacteria responsible for the removal of air contaminants in biofilters. In this study, molecular techniques were used to identify bacteria in a laboratory-scale ammonia biofilter. Both 16S rRNA and ammonia monooxygenase (amoA) genes were used to characterize the heterotrophic and ammonia-oxidizing bacteria collected from the biofilter during a 102-day experiment. The overall diversity of the heterotrophic microbial population appeared to decrease by 38% at the end of the experiment. The community structure of the heterotrophic population also shifted from predominantly members of two subdivisions of the Proteobacteria (the beta and gamma subdivisions) to members of one subdivision (the gamma subdivision). An overall decrease in the diversity of ammonia monooxygenase genes was not observed. However, a shift from groups dominated by organisms containing Nitrosomonas-like and Nitrosospira-like amoA genes to groups dominated by organisms containing only Nitrosospira-like amoA genes was observed. In addition, a new amoA gene was discovered. This new gene is the first freshwater amoA gene that is closely affiliated with Nitrosococcus oceanus and the particulate methane monooxygenase gene from the methane oxidizers belonging to the gamma subdivision of the Proteobacteria.

  5. A Molecular Fraction Collecting Tool for the ABI 310 Automated Sequencer

    PubMed Central

    Lin, Ming-Tseh; Rich, Roy G.; Shipley, Royce F.; Hafez, Michael J.; Tseng, Li-Hui; Murphy, Kathleen M.; Gocke, Christopher D.; Eshleman, James R.

    2007-01-01

    Several methods exist to retrieve and purify DNA fragments after agarose or polyacrylamide gel electrophoresis for subsequent analyses. However, molecules present in low concentration and molecules similar in size to their neighbors are difficult to purify. Capillary electrophoresis has become popular in molecular diagnostic laboratories because of its automation, excellent resolution, and high sensitivity. In the current study, the ABI Prism 310 Genetic Analyzer was reconfigured into a fraction collector by adapting the standard gel block to accommodate a collection tube at the distal end of capillary. The time to collect the desired peaks was estimated by extrapolating from standard capillary electrophoresis using the original gel block. Fraction collection from a mixture of DNA fragments amplified from wild type and several internal tandem duplication mutations of the FMS-like tyrosine kinase 3 (Flt3) gene yielded highly purified DNA fragments containing internal tandem duplication mutations and predictable electrokinetics using the reconstructed gel block. The reconfigured instrument could successfully isolate DNA amplicons from extremely low-amplitude peaks (110 relative fluorescent units), which were undetectable using polyacrylamide gel electrophoresis. In addition, we successfully isolated bands that were only three bases apart that comigrated on polyacrylamide gel electrophoresis. DNA sequencing was used to confirm that the correct peaks were recovered at sufficient purity. PMID:17916601

  6. Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal gland and pancreas.

    PubMed

    Müller, Mareike Hildegard; Rödel, Franz; Rüb, Udo; Korf, Horst-Werner

    2015-02-01

    The circadian clock of man and mammals shows a hierarchic organization. The master clock, located in the suprachiasmatic nuclei (SCN), controls peripheral oscillators distributed throughout the body. Rhythm generation depends on molecular clockworks based on transcriptional/translational interaction of clock genes. Numerous studies have shown that the clockwork in peripheral oscillators is capable to maintain circadian rhythms for several cycles in vitro, i.e. in the absence of signals from the SCN. The aim of the present study is to analyze the effects of irradiation with X-rays on the clockwork of liver, adrenal and pancreas. To this end organotypic slice cultures of liver (OLSC) and organotypic explant cultures of adrenal glands (OAEC) and pancreas (OPEC) were prepared from transgenic mPer2(luc) mice which express luciferase under the control of the promoter of an important clock gene, Per2, and allow to study the dynamics of the molecular clockwork by bioluminometry. The preparations were cultured in a membrane-based liquid-air interface culturing system and irradiated with X-rays at doses of 10 Gy and 50 Gy or left untreated. Bioluminometric real-time recordings show a stable oscillation of all OLSC, OAEC and OPEC for up to 12 days in vitro. Oscillations persist after irradiation with X-rays. However, a dose of 50 Gy caused a phase advance in the rhythm of the OLSC by 5 h, in the OPEC by 7 h and in the OAEC by 6 h. Our study shows that X-rays affect the molecular clockwork in liver, pancreas and adrenal leading to phase advances. Our results confirm and extend previous studies showing a phase-advancing effect of X-rays at the level of the whole animal and single cells.

  7. Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

    PubMed Central

    Pusparajah, Priyia; Lee, Learn-Han; Abdul Kadir, Khalid

    2016-01-01

    Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed. PMID:27313539

  8. Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

    PubMed

    Pusparajah, Priyia; Lee, Learn-Han; Abdul Kadir, Khalid

    2016-01-01

    Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed.

  9. Advances in the Molecular Analysis of Soft Tissue Tumors and Clinical Implications

    PubMed Central

    Marino-Enriquez, Adrian

    2016-01-01

    SYNOPSIS The emergence of high-throughput molecular technologies has accelerated the discovery of novel diagnostic, prognostic and predictive molecular markers. Clinical implementation of these technologies is expected to transform the practice of surgical pathology. In soft tissue tumor pathology, accurate interpretation of comprehensive genomic data provides useful diagnostic and prognostic information, and informs therapeutic decisions. Most clinical molecular data will be likely generated by high-throughput genomic technologies, and reporting clinically actionable somatic mutations will be part of the routine pathology workflow, informing patient management and treatment. The purpose of this review is to introduce recently developed molecular technologies and to briefly discuss their potential for clinical implementation, focusing on various applications to the evaluation of soft tissue tumors. A special emphasis is made on practical diagnostic uses relevant to the surgical pathologist, with illustrative examples of how these technologies have helped characterize and diagnose soft tissue lesions. The concept of genomically-informed therapies will be mentioned, as an essential motivation to implement molecular tests to identify targetable molecular alterations in sarcoma. PMID:26297069

  10. Translation of recent advances and discoveries in molecular biology and immunology in the diagnosis and treatment of pancreatic cancer.

    PubMed

    Albo, Daniel; Farrow, Buckminster; Berger, David H

    2008-04-01

    Recent advances in understanding the molecular mechanisms of cancer progression have allowed for targeted approaches to the diagnosis and treatment of pancreatic cancer. New biologic markers are emerging that may improve the ability to detect these tumors earlier. Targeted biologic cancer therapies promise more effective and less toxic systemic treatment options. Although a clear "magic bullet" has yet to emerge, this type of targeted approach offers hope in the management of this dreadful disease. This article offers an update on these promising diagnostic and treatment modalities.

  11. Acidity Constant (pKa ) Calculation of Large Solvated Dye Molecules: Evaluation of Two Advanced Molecular Dynamics Methods.

    PubMed

    De Meyer, Thierry; Ensing, Bernd; Rogge, Sven M J; De Clerck, Karen; Meijer, Evert Jan; Van Speybroeck, Veronique

    2016-11-04

    pH-Sensitive dyes are increasingly applied on polymer substrates for the creation of novel sensor materials. Recently, these dye molecules were modified to form a covalent bond with the polymer host. This had a large influence on the pH-sensitive properties, in particular on the acidity constant (pKa ). Obtaining molecular control over the factors that influence the pKa value is mandatory for the future intelligent design of sensor materials. Herein, we show that advanced molecular dynamics (MD) methods have reached the level at which the pKa values of large solvated dye molecules can be predicted with high accuracy. Two MD methods were used in this work: steered or restrained MD and the insertion/deletion scheme. Both were first calibrated on a set of phenol derivatives and afterwards applied to the dye molecule bromothymol blue. Excellent agreement with experimental values was obtained, which opens perspectives for using these methods for designing dye molecules.

  12. Use of Molecular Diagnostic Tools for the Identification of Species Responsible for Snakebite in Nepal: A Pilot Study

    PubMed Central

    Sharma, Sanjib Kumar; Kuch, Ulrich; Höde, Patrick; Bruhse, Laura; Pandey, Deb P.; Ghimire, Anup; Chappuis, François; Alirol, Emilie

    2016-01-01

    Snakebite is an important medical emergency in rural Nepal. Correct identification of the biting species is crucial for clinicians to choose appropriate treatment and anticipate complications. This is particularly important for neurotoxic envenoming which, depending on the snake species involved, may not respond to available antivenoms. Adequate species identification tools are lacking. This study used a combination of morphological and molecular approaches (PCR-aided DNA sequencing from swabs of bite sites) to determine the contribution of venomous and non-venomous species to the snakebite burden in southern Nepal. Out of 749 patients admitted with a history of snakebite to one of three study centres, the biting species could be identified in 194 (25.9%). Out of these, 87 had been bitten by a venomous snake, most commonly the Indian spectacled cobra (Naja naja; n = 42) and the common krait (Bungarus caeruleus; n = 22). When both morphological identification and PCR/sequencing results were available, a 100% agreement was noted. The probability of a positive PCR result was significantly lower among patients who had used inadequate “first aid” measures (e.g. tourniquets or local application of remedies). This study is the first to report the use of forensic genetics methods for snake species identification in a prospective clinical study. If high diagnostic accuracy is confirmed in larger cohorts, this method will be a very useful reference diagnostic tool for epidemiological investigations and clinical studies. PMID:27105074

  13. Evaluation of four molecular typing methodologies as tools for determining taxonomy relations and for identifying species among Yersinia isolates.

    PubMed

    Souza, Roberto A; Pitondo-Silva, André; Falcão, Deise P; Falcão, Juliana P

    2010-08-01

    In the last few decades, molecular typing has become an important tool in taxonomic, phylogenetic and identification studies of numerous groups of bacteria, including the yersiniae. In this study, Enterobacterial Repetitive Intergenic Consensus PCR (ERIC-PCR), Pulsed-Field Gel Electrophoresis (PFGE), 16S rRNA gene sequencing and Multilocus Sequence Analysis (MLSA) were performed to determine the ability of these techniques to be used in taxonomy and identification of Yersinia strains. A total of 60 Yersinia strains were genotyped by ERIC-PCR and PFGE. Moreover, an in silico analysis was carried out for 16S rRNA gene sequencing and MLSA, using 68 and 49 Yersinia strains, respectively. A phylogenetic tree constructed from the ERIC-PCR, 16S rRNA gene sequencing and MLSA data grouped most of the Yersinia species into distinct species-specific clusters. In the PFGE assay these clusters were not observed. On this basis, ERIC-PCR, 16S rRNA gene sequencing and MLSA seem to be valuable techniques for use in taxonomic and identification studies of the genus Yersinia, whereas PFGE does not. Furthermore, ERIC-PCR has the advantage of being a cheaper, easier and faster assay than 16S rRNA gene sequencing or MLSA, and for these reasons can be considerate an alternative tool in taxonomic studies of yersiniae.

  14. Biochemical and molecular tools reveal two diverse Xanthomonas groups in bananas.

    PubMed

    Adriko, J; Aritua, V; Mortensen, C N; Tushemereirwe, W K; Mulondo, A L; Kubiriba, J; Lund, O S

    2016-02-01

    Xanthomonas campestris pv. musacearum (Xcm) causing the banana Xanthomonas wilt (BXW) disease has been the main xanthomonad associated with bananas in East and Central Africa based on phenotypic and biochemical characteristics. However, biochemical methods cannot effectively distinguish between pathogenic and non-pathogenic xanthomonads. In this study, gram-negative and yellow-pigmented mucoid bacteria were isolated from BXW symptomatic and symptomless bananas collected from different parts of Uganda. Biolog, Xcm-specific (GspDm), Xanthomonas vasicola species-specific (NZ085) and Xanthomonas genus-specific (X1623) primers in PCR, and sequencing of ITS region were used to identify and characterize the isolates. Biolog tests revealed several isolates as xanthomonads. The GspDm and NZ085 primers accurately identified three isolates from diseased bananas as Xcm and these were pathogenic when re-inoculated into bananas. DNA from more isolates than those amplified by GspDm and NZ085 primers were amplified by the X1623 primers implying they are xanthomonads, these were however non-pathogenic on bananas. In the 16-23 ITS sequence based phylogeny, the pathogenic bacteria clustered together with the Xcm reference strain, while the non-pathogenic xanthomonads isolated from both BXW symptomatic and symptomless bananas clustered with group I xanthomonads. The findings reveal dynamic Xanthomonas populations in bananas, which can easily be misrepresented by only using phenotyping and biochemical tests. A combination of tools provides the most accurate identity and characterization of these plant associated bacteria. The interactions between the pathogenic and non-pathogenic xanthomonads in bananas may pave way to understanding effect of microbial interactions on BXW disease development and offer clues to biocontrol of Xcm.

  15. IBiSA_Tools: A Computational Toolkit for Ion-Binding State Analysis in Molecular Dynamics Trajectories of Ion Channels

    PubMed Central

    Kasahara, Kota; Kinoshita, Kengo

    2016-01-01

    Ion conduction mechanisms of ion channels are a long-standing conundrum. Although the molecular dynamics (MD) method has been extensively used to simulate ion conduction dynamics at the atomic level, analysis and interpretation of MD results are not straightforward due to complexity of the dynamics. In our previous reports, we proposed an analytical method called ion-binding state analysis to scrutinize and summarize ion conduction mechanisms by taking advantage of a variety of analytical protocols, e.g., the complex network analysis, sequence alignment, and hierarchical clustering. This approach effectively revealed the ion conduction mechanisms and their dependence on the conditions, i.e., ion concentration and membrane voltage. Here, we present an easy-to-use computational toolkit for ion-binding state analysis, called IBiSA_tools. This toolkit consists of a C++ program and a series of Python and R scripts. From the trajectory file of MD simulations and a structure file, users can generate several images and statistics of ion conduction processes. A complex network named ion-binding state graph is generated in a standard graph format (graph modeling language; GML), which can be visualized by standard network analyzers such as Cytoscape. As a tutorial, a trajectory of a 50 ns MD simulation of the Kv1.2 channel is also distributed with the toolkit. Users can trace the entire process of ion-binding state analysis step by step. The novel method for analysis of ion conduction mechanisms of ion channels can be easily used by means of IBiSA_tools. This software is distributed under an open source license at the following URL: http://www.ritsumei.ac.jp/~ktkshr/ibisa_tools/ PMID:27907142

  16. Electrochemical reverse engineering: A systems-level tool to probe the redox-based molecular communication of biology.

    PubMed

    Li, Jinyang; Liu, Yi; Kim, Eunkyoung; March, John C; Bentley, William E; Payne, Gregory F

    2016-12-29

    The intestine is the site of digestion and forms a critical interface between the host and the outside world. This interface is composed of host epithelium and a complex microbiota which is "connected" through an extensive web of chemical and biological interactions that determine the balance between health and disease for the host. This biology and the associated chemical dialogues occur within a context of a steep oxygen gradient that provides the driving force for a variety of reduction and oxidation (redox) reactions. While some redox couples (e.g., catecholics) can spontaneously exchange electrons, many others are kinetically "insulated" (e.g., biothiols) allowing the biology to set and control their redox states far from equilibrium. It is well known that within cells, such non-equilibrated redox couples are poised to transfer electrons to perform reactions essential to immune defense (e.g., transfer from NADH to O2 for reactive oxygen species, ROS, generation) and protection from such oxidative stresses (e.g., glutathione-based reduction of ROS). More recently, it has been recognized that some of these redox-active species (e.g., H2O2) cross membranes and diffuse into the extracellular environment including lumen to transmit redox information that is received by atomically-specific receptors (e.g., cysteine-based sulfur switches) that regulate biological functions. Thus, redox has emerged as an important modality in the chemical signaling that occurs in the intestine and there have been emerging efforts to develop the experimental tools needed to probe this modality. We suggest that electrochemistry provides a unique tool to experimentally probe redox interactions at a systems level. Importantly, electrochemistry offers the potential to enlist the extensive theories established in signal processing in an effort to "reverse engineer" the molecular communication occurring in this complex biological system. Here, we review our efforts to develop this

  17. Moving from Histopathology to Molecular Tools in the Diagnosis of Molluscs Diseases of Concern under EU Legislation

    PubMed Central

    Aranguren, Raquel; Figueras, Antonio

    2016-01-01

    One of the main factors limiting molluscs production is the presence of pathogens and diseases. Disease agent transfer via transfers of live molluscs has been a major cause of disease outbreaks and epizootics. Because of that, the European Union has adopted several decisions and directives, the last in 2006 (2006/88/EC) to control movements of marine organisms over the European countries. Once the disease is established in a determined area its eradication is a complicated task because life cycle of pathogens are not completely known and only a good and early diagnosis of the disease could be the most appropriate way to deal with it. Besides, molluscs do not have an adaptive immune response and vaccination strategies are not possible. Molluscs listed diseases under EU legislation are mainly protozoan parasites, that's why histological techniques are recognized for their diagnosis. However, molecular techniques are being increasingly used primarily as confirmatory techniques of the presence of the pathogens but also in disease monitoring programs. Research perspectives are mainly focussed in the optimization, of the already described techniques to gain in sensitivity and sensibility and in the development of new molecular biology techniques (quantitative real time PCRs), that are faster and easier to apply and that allow a positive diagnosis even in early stages of infection. However, molecular tools detect DNA sequences of the pathogen which does not imply that pathogen is viable in the cell host and the infection is established. Consequently, it needs to be validated against other techniques, such as histology or in situ hybridization, so that its reliability can be determined. PMID:27895595

  18. Moving from Histopathology to Molecular Tools in the Diagnosis of Molluscs Diseases of Concern under EU Legislation.

    PubMed

    Aranguren, Raquel; Figueras, Antonio

    2016-01-01

    One of the main factors limiting molluscs production is the presence of pathogens and diseases. Disease agent transfer via transfers of live molluscs has been a major cause of disease outbreaks and epizootics. Because of that, the European Union has adopted several decisions and directives, the last in 2006 (2006/88/EC) to control movements of marine organisms over the European countries. Once the disease is established in a determined area its eradication is a complicated task because life cycle of pathogens are not completely known and only a good and early diagnosis of the disease could be the most appropriate way to deal with it. Besides, molluscs do not have an adaptive immune response and vaccination strategies are not possible. Molluscs listed diseases under EU legislation are mainly protozoan parasites, that's why histological techniques are recognized for their diagnosis. However, molecular techniques are being increasingly used primarily as confirmatory techniques of the presence of the pathogens but also in disease monitoring programs. Research perspectives are mainly focussed in the optimization, of the already described techniques to gain in sensitivity and sensibility and in the development of new molecular biology techniques (quantitative real time PCRs), that are faster and easier to apply and that allow a positive diagnosis even in early stages of infection. However, molecular tools detect DNA sequences of the pathogen which does not imply that pathogen is viable in the cell host and the infection is established. Consequently, it needs to be validated against other techniques, such as histology or in situ hybridization, so that its reliability can be determined.

  19. Lipids and Molecular Tools as Biomarkers in Monitoring Air Sparging Bioremediation Processes

    NASA Astrophysics Data System (ADS)

    Heipieper, Hermann J.; Fischer, Janett

    2010-05-01

    The fluctuation of membrane lipids offers a promising tool as biomarkers for the analysis of microbial population changes as well as for the physiological status of micro-organisms. The investigation of changes in lipid composition is of common use for the assessment of physiological conditions in pure cultures. However, as lipid composition does not show drastic diversity among living organisms the use of lipids as biomarkers in mixed cultures and environmental samples has certain limitations. Therefore, special marker phospholipid fatty acids as well as modern statistical analysis of the results are necessary to receive certain information about the qualitative and quantitative changes of e.g. a soil microflora due to a contamination with organic compounds and its bioremediation. The use of lipids as biomarker in monitoring bioremediation are shown at the Hradčany site, a former Russian air force base in the Czech Republic that operated until 1990. In this time in an area of 32 ha soil and groundwater were contaminated with kerosene and BTEX compounds in an amount of 7,150 tons. This highly contaminated site is treated with the so-called air sparging method to clean-up the contamination by aerobic biodegradation. The results of PLFA analysis demonstrated a community shift to a gram-negative bacterial biomass with time. The results, including a principal component analysis (PCA) of the obtained fatty acid profiles, showed that the air sparging leads to substantial differences in microbial communities depending on the contamination levels and length of treatment, respectively. Obviously, the length of air sparging treatment controlling the BTEX concentration in soils causes temporal changes of bacterial community and adaptations of its respective members. This work was supported by the project BIOTOOL (Contract No. 003998) of the European Commission within its Sixth Framework Programme. Kabelitz N., Machackova J., Imfeld G., Brennerova M., Pieper D.H., Heipieper H

  20. Molecular studies in olive (Olea europaea L.): overview on DNA markers applications and recent advances in genome analysis.

    PubMed

    Bracci, T; Busconi, M; Fogher, C; Sebastiani, L

    2011-04-01

    Olive (Olea europaea L.) is one of the oldest agricultural tree crops worldwide and is an important source of oil with beneficial properties for human health. This emblematic tree crop of the Mediterranean Basin, which has conserved a very wide germplasm estimated in more than 1,200 cultivars, is a diploid species (2n = 2x = 46) that is present in two forms, namely wild (Olea europaea subsp. europaea var. sylvestris) and cultivated (Olea europaea subsp. europaea var. europaea). In spite of its economic and nutritional importance, there are few data about the genetic of olive if compared with other fruit crops. Available molecular data are especially related to the application of molecular markers to the analysis of genetic variability in Olea europaea complex and to develop efficient molecular tools for the olive oil origin traceability. With regard to genomic research, in the last years efforts are made for the identification of expressed sequence tag, with particular interest in those sequences expressed during fruit development and in pollen allergens. Very recently the sequencing of chloroplast genome provided new information on the olive nucleotide sequence, opening the olive genomic era. In this article, we provide an overview of the most relevant results in olive molecular studies. A particular attention was given to DNA markers and their application that constitute the most part of published researches. The first important results in genome analysis were reported.

  1. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

    PubMed

    Maroto Rey, José Pablo; Cillán Narvaez, Elena

    2013-06-01

    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  2. Advances on molecular mechanism of the adaptive evolution of Chiroptera (bats).

    PubMed

    Yunpeng, Liang; Li, Yu

    2015-01-01

    As the second biggest animal group in mammals, Chiroptera (bats) demonstrates many unique adaptive features in terms of flight, echolocation, auditory acuity, feeding habit, hibernation and immune defense, providing an excellent system for understanding the molecular basis of how organisms adapt to the living environments encountered. In this review, we summarize the researches on the molecular mechanism of the adaptive evolution of Chiroptera, especially the recent researches at the genome levels, suggesting a far more complex evolutionary pattern and functional diversity than previously thought. In the future, along with the increasing numbers of Chiroptera species genomes available, new evolutionary patterns and functional divergence will be revealed, which can promote the further understanding of this animal group and the molecular mechanism of adaptive evolution.

  3. Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology (Final Report)

    EPA Science Inventory

    Cover of the Next Generation of Risk Assessment Final report This final report, "Next Generation Risk Assessment: Recent Advances in Molec...

  4. 78 FR 59927 - Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... Systems Biology [External Review Draft] AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of... Molecular, Computational, and Systems Biology '' (EPA/600/R-13/214A). EPA is also announcing that Eastern..., Computational, and Systems Biology '' is available primarily via the Internet on the NCEA home page under...

  5. Sedimentation Coefficient, Frictional Coefficient, and Molecular Weight: A Preparative Ultracentrifuge Experiment for the Advanced Undergraduate Laboratory.

    ERIC Educational Resources Information Center

    Halsall, H. B.; Wermeling, J. R.

    1982-01-01

    Describes an experiment using a high-speed preparative centrifuge and calculator to demonstrate effects of the frictional coefficient of a macromolecule on its rate of transport in a force field and to estimate molecular weight of the macromolecule using an empirical relationship. Background information, procedures, and discussion of results are…

  6. Research Advances: Nanoscale Molecular Tweezers; Cinnamon as Pesticide?; Recently Identified Dietary Sources of Antioxidants

    NASA Astrophysics Data System (ADS)

    King, Angela G.

    2004-12-01

    This Report from Other Journals surveys articles of interest to chemists that have been recently published in other science journals. Topics surveyed include reports that receptors have been designed to act as molecular tweezers; cinnamon has potential in the fight against mosquitoes; and high levels of antioxidants are found in some surprising foods. See Featured Molecules .

  7. Technological Advances in Bifidobacterial Molecular Genetics: Application to Functional Genomics and Medical Treatments

    PubMed Central

    FUKIYA, Satoru; HIRAYAMA, Yosuke; SAKANAKA, Mikiyasu; KANO, Yasunobu; YOKOTA, Atsushi

    2012-01-01

    Bifidobacteria are well known as beneficial intestinal bacteria that exert health-promoting effects in humans. In addition to physiological and immunological investigations, molecular genetic technologies have been developed and have recently started to be applied to clarify the molecular bases of host-Bifidobacterium interactions. These technologies include transformation technologies and Escherichia coli-Bifidobacterium shuttle vectors that enable heterologous gene expression. In this context, a plasmid artificial modification method that protects the introduced plasmid from the restriction system in host bifidobacteria has recently been developed to increase transformation efficiency. On the other hand, targeted gene inactivation systems, which are vital for functional genomics, seemed far from being practically applicable in bifidobacteria. However, remarkable progress in this technology has recently been achieved, enabling functional genomics in bifidobacteria. Integrated use of these molecular genetic technologies with omics-based analyses will surely boost characterization of the molecular basis underlying beneficial effects of bifidobacteria. Applications of recombinant bifidobacteria to medical treatments have also progressed. PMID:24936345

  8. New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges.

    PubMed

    Cong, Wen-Ming; Wu, Meng-Chao

    2015-11-01

    Primary liver cancer (PLC) is one of the most common malignancies worldwide with increasing incidence and accounts for the third leading cause of cancer-related mortality. Traditional morphopathology primarily emphasizes qualitative diagnosis of PLC, which is not sufficient to resolve the major concern of increasing the long-term treatment efficacy of PLC in clinical management for the modern era. Since the beginning of the 21st century, molecular pathology has played an active role in the investigation of the evaluation of the metastatic potential of PLC, detection of drug targets, prediction of recurrence risks, analysis of clonal origins, evaluation of the malignancy trend of precancerous lesions, and determination of clinical prognosis. As a result, many new progresses have been obtained, and new strategies of molecular-pathological diagnosis have been formed. Moreover, the new types of pathobiological diagnosis indicator systems for PLC have been preliminarily established. These achievements provide valuable molecular pathology-based guide for clinical formulation of individualized therapy programs for PLC. This review article briefly summarizes some relevant progresses of molecular-pathological diagnosis of PLC from the perspective of clinical translational application other than basic experimental studies.

  9. Machine Tool Advanced Skills Technology (MAST). Common Ground: Toward a Standards-Based Training System for the U.S. Machine Tool and Metal Related Industries. Volume 1: Executive Summary, of a 15-Volume Set of Skills Standards and Curriculum Training Materials for the Precision Manufacturing Industry.

    ERIC Educational Resources Information Center

    Texas State Technical Coll., Waco.

    The Machine Tool Advanced Skills Technology (MAST) consortium was formed to address the shortage of skilled workers for the machine tools and metals-related industries. Featuring six of the nation's leading advanced technology centers, the MAST consortium developed, tested, and disseminated industry-specific skill standards and model curricula for…

  10. Recent advances in soybean transformation and their application to molecular breeding and genomic analysis

    PubMed Central

    Yamada, Tetsuya; Takagi, Kyoko; Ishimoto, Masao

    2012-01-01

    Herbicide-resistant transgenic soybean plants hold a leading market share in the USA and other countries, but soybean has been regarded as recalcitrant to transformation for many years. The cumulative and, at times, exponential advances in genetic manipulation have made possible further choices for soybean transformation. The most widely and routinely used transformation systems are cotyledonary node–Agrobacterium-mediated transformation and somatic embryo–particle-bombardment-mediated transformation. These ready systems enable us to improve seed qualities and agronomic characteristics by transgenic approaches. In addition, with the accumulation of soybean genomic resources, convenient or promising approaches will be requisite for the determination and use of gene function in soybean. In this article, we describe recent advances in and problems of soybean transformation, and survey the current transgenic approaches for applied and basic research in Japan. PMID:23136488

  11. JUST in time health emergency interventions: an innovative approach to training the citizen for emergency situations using virtual reality techniques and advanced IT tools (the VR Tool).

    PubMed

    Manganas, A; Tsiknakis, M; Leisch, E; Ponder, M; Molet, T; Herbelin, B; Magnetat-Thalmann, N; Thalmann, D; Fato, M; Schenone, A

    2004-01-01

    This paper reports the results of the second of the two systems developed by JUST, a collaborative project supported by the European Union under the Information Society Technologies (IST) Programme. The most innovative content of the project has been the design and development of a complementary training course for non-professional health emergency operators, which supports the traditional learning phase, and which purports to improve the retention capability of the trainees. This was achieved with the use of advanced information technology techniques, which provide adequate support and can help to overcome the present weaknesses of the existing training mechanisms.

  12. Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial.

    PubMed

    Braun, Thorsten; Itzykson, Raphael; Renneville, Aline; de Renzis, Benoit; Dreyfus, François; Laribi, Kamel; Bouabdallah, Krimo; Vey, Norbert; Toma, Andrea; Recher, Christian; Royer, Bruno; Joly, Bertrand; Vekhoff, Anne; Lafon, Ingrid; Sanhes, Laurence; Meurice, Guillaume; Oréar, Cédric; Preudhomme, Claude; Gardin, Claude; Ades, Lionel; Fontenay, Michaela; Fenaux, Pierre; Droin, Nathalie; Solary, Eric

    2011-10-06

    Hydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With a median follow-up of 23 months, overall survival was 48% at 2 years. Mutations in ASXL1, TET2, AML1, NRAS, KRAS, CBL, FLT3, and janus kinase 2 (JAK2) genes, and hypermethylation of the promoter of the tumor suppressor gene TIF1γ, did not predict response or survival on DAC therapy. Lower CJUN and CMYB gene expression levels independently predicted improved overall survival. This trial confirmed DAC efficacy in approximately 40% of CMML patients with advanced myeloproliferative or myelodysplastic features and suggested that CJUN and CMYB expression could be potential biomarkers in this setting. This trial is registered at EudraCT (eudract.ema.europa.eu) as #2008-000470-21 and www.clinicaltrials.gov as #NCT01098084.

  13. Assessment of microscopic and molecular tools for the diagnosis and follow-up of cryptosporidiosis in patients at risk.

    PubMed

    Le Govic, Y; Guyot, K; Certad, G; Deschildre, A; Novo, R; Mary, C; Sendid, B; Viscogliosi, E; Favennec, L; Dei-Cas, E; Fréalle, E; Dutoit, E

    2016-01-01

    Cryptosporidiosis is an important though underreported public health concern. Molecular tools might be helpful in improving its diagnosis. In this study, ZR Fecal DNA MiniPrep™ Kit (ZR) and NucliSens® easyMAG® (EM) were compared using four Cryptosporidium-seeded feces and 29 Cryptosporidium-positive stools. Thereafter, ZR was selected for prospective evaluation of Cryptosporidium detection by 18S rDNA and LAXER quantitative PCR (qPCR) in 69 stools from 56 patients after Cryptosporidium detection by glycerin, modified Ziehl-Neelsen (ZN) and auramine-phenol (AP) stainings. The combination of any of the two extraction methods with 18S qPCR yielded adequate detection of Cryptosporidium in seeded stools, but the ZR kit showed the best performance. All 29 Cryptosporidium-positive samples were positive with 18S qPCR, after both ZR and EM extraction. However, false-negative results were found with LAXER qPCR or nested PCR. Cryptosporidiosis was diagnosed in 7/56 patients. All the microscopic methods enabled the initial diagnosis, but Cryptosporidium was detected in 12, 13, and 14 samples from these seven patients after glycerin, ZN, and AP staining respectively. Among these samples, 14 and 12 were positive with 18S and LAXER qPCR respectively. In two patients, Cryptosporidium DNA loads were found to be correlated with clinical evolution. Although little known, glycerin is a sensitive method for the initial detection of Cryptosporidium. When combined with 18S qPCR, ZR extraction, which had not been evaluated so far for Cryptosporidium, was an accurate tool for detecting Cryptosporidium and estimating the oocyst shedding in the course of infection.

  14. A Powerful Molecular Engineering Tool Provided Efficient Chlamydomonas Mutants as Bio-Sensing Elements for Herbicides Detection

    PubMed Central

    Lambreva, Maya D.; Giardi, Maria Teresa; Rambaldi, Irene; Antonacci, Amina; Pastorelli, Sandro; Bertalan, Ivo; Husu, Ivan; Johanningmeier, Udo; Rea, Giuseppina

    2013-01-01

    This study was prompted by increasing concerns about ecological damage and human health threats derived by persistent contamination of water and soil with herbicides, and emerging of bio-sensing technology as powerful, fast and efficient tool for the identification of such hazards. This work is aimed at overcoming principal limitations negatively affecting the whole-cell-based biosensors performance due to inadequate stability and sensitivity of the bio-recognition element. The novel bio-sensing elements for the detection of herbicides were generated exploiting the power of molecular engineering in order to improve the performance of photosynthetic complexes. The new phenotypes were produced by an in vitro directed evolution strategy targeted at the photosystem II (PSII) D1 protein of Chlamydomonas reinhardtii, using exposures to radical-generating ionizing radiation as selection pressure. These tools proved successful to identify D1 mutations conferring enhanced stability, tolerance to free-radical-associated stress and competence for herbicide perception. Long-term stability tests of PSII performance revealed the mutants capability to deal with oxidative stress-related conditions. Furthermore, dose-response experiments indicated the strains having increased sensitivity or resistance to triazine and urea type herbicides with I50 values ranging from 6×10−8 M to 2×10−6 M. Besides stressing the relevance of several amino acids for PSII photochemistry and herbicide sensing, the possibility to improve the specificity of whole-cell-based biosensors, via coupling herbicide-sensitive with herbicide-resistant strains, was verified. PMID:23613953

  15. Molecular fingerprinting of Salmonella typhimurium by IS200-typing as a tool for epidemiological and evolutionary studies.

    PubMed

    Soria, G; Barbé, J; Gibert, I

    1994-01-01

    The aim of this work was to develop and evaluate a molecular typing strategy for Salmonella based on hybridization of chromosomal DNA with two different probes derived from insertion sequence IS200. Probe IS200-TT was specifically constructed for this study as a trimer of a 112 pb TaqI-TaqI fragment of IS200. Among several restriction enzymes evaluated, two were selected: EcoRI, which cuts the insertion sequence in two pieces, each one complementary to one of the probes used, and PstI, a restriction enzyme with no recognition site into IS200. With several combinations of these restrictions enzymes and probes, 43 Salmonella typhimurium strains were analyzed for copy number and location of IS200, as well as reproducibility and stability of the patterns. IS200 types have been shown to be stable, both in strains isolated from different patients implicated in the same salmonellosis outbreak and in strains isolated from the same patient at different times or from different specimens. The discriminatory power of the method has been 0.91 to 0.94. As a comparison, S. typhimurium strains were also ribotyped. Discriminatory power of the ribotypes oscillated between 0.44 and 0.55, depending on the enzyme used, and achieved a 0.78 value when the information obtained with two restriction enzymes was combined. Moreover, IS200 typing was able to differentiate among a group of S. typhimurium strains which were identical by ribotype and enzymatic electrophoretic mobility. These results enable us to conclude that, for the stability, reproducibility and discriminatory power of the patterns generated, IS200 probes can be a very useful tool in the molecular typing of S. typhimurium.

  16. Evaluation of conjunctival swab as a mass-screening tool for molecular diagnosis of canine visceral leishmaniasis.

    PubMed

    Leite, Rodrigo Souza; Souza, Natalia Alves; Barbosa, Amanda Duarte; Ferreira, Aline Leandra Carvalho; de Andrade, Antero Silva Ribeiro

    2015-06-01

    The canine visceral leishmaniasis (CVL) diagnosis is an important step of visceral leishmaniasis control program in Brazil once the dog is the main reservoir host of the disease. The aim of this study was to evaluate the conjunctival swab (CS) as a mass-screening tool for CVL molecular diagnosis in an endemic area classified as priority for the Brazilian Ministry of Healthy for surveillance action. A total of 1350 domiciled dogs were screened. The animals were evaluated by serological tests (enzyme-linked immunosorbent assay (ELISA) as screening and immunofluorescence antibody test (IFAT) for confirmation) and by CS associated to real-time PCR, using primers addressed to kinetoplast DNA (kDNA) minicircles and SYBR Green. Canine β-globin gene amplification was used to evaluate the sample DNA integrity. A subgroup of 484 animals was also submitted to clinical evaluation. Among the 1350 dogs screened, 369 (27.3%) were positive by CS real-time PCR and 126 (9.3%) tested positive by ELISA. Thirty-one percent (39/126) of the ELISA-positive dogs were confirmed by IFAT. CS real-time PCR was able to detect infection in dogs independently of the symptomatology degree (p > 0.05), while ELISA was more sensitive in the group of dogs that present three or more clinical signs related to CVL. The results demonstrated that CS real-time PCR was able to detect a higher number of infected dogs than ELISA and that the prevalence of canine infections has been underestimated by the serological assays. The use of sensitive molecular diagnostic methods like CS real-time PCR, mainly in endemic areas, could greatly contribute to disease control.

  17. Recent Advance of Biological Molecular Imaging Based on Lanthanide-Doped Upconversion-Luminescent Nanomaterials

    PubMed Central

    Min, Yuanzeng; Li, Jinming; Liu, Fang; Padmanabhan, Parasuraman; Yeow, Edwin K. L.; Xing, Bengang

    2014-01-01

    Lanthanide-doped upconversion-luminescent nanoparticles (UCNPs), which can be excited by near-infrared (NIR) laser irradiation to emit multiplex light, have been proven to be very useful for in vitro and in vivo molecular imaging studies. In comparison with the conventionally used down-conversion fluorescence imaging strategies, the NIR light excited luminescence of UCNPs displays high photostability, low cytotoxicity, little background auto-fluorescence, which allows for deep tissue penetration, making them attractive as contrast agents for biomedical imaging applications. In this review, we will mainly focus on the latest development of a new type of lanthanide-doped UCNP material and its main applications for in vitro and in vivo molecular imaging and we will also discuss the challenges and future perspectives.

  18. Recent advances in understanding the molecular mechanism of chloroplast photorelocation movement.

    PubMed

    Kong, Sam-Geun; Wada, Masamitsu

    2014-04-01

    Plants are photosynthetic organisms that have evolved unique systems to adapt fluctuating environmental light conditions. In addition to well-known movement responses such as phototropism, stomatal opening, and nastic leaf movements, chloroplast photorelocation movement is one of the essential cellular responses to optimize photosynthetic ability and avoid photodamage. For these adaptations, chloroplasts accumulate at the areas of cells illuminated with low light (called accumulation response), while they scatter from the area illuminated with strong light (called avoidance response). Plant-specific photoreceptors (phototropin, phytochrome, and/or neochrome) mediate these dynamic directional movements in response to incident light position and intensity. Several factors involved in the mechanisms underlying the processes from light perception to actin-based movements have also been identified through molecular genetic approach. This review aims to discuss recent findings in the field relating to how chloroplasts move at molecular levels. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components.

  19. Advances in enzymology and related areas of molecular biology, Vol. 61

    SciTech Connect

    Meister, A.

    1988-01-01

    The contents of this book are: A Unifying Model of the Thermodynamics of Formation of Dehydrogenase-Ligand Complexes; Sorbitol Dehydrogenase; Molecular Size Determination of Enzymes by Radiation Inactivation; Calcineurin; The Behavior and Significance of Slow-Binding Enzyme Inhibitors; ADP-Ribosylation of Guanyl Nucleotide-Binding Regulatory Proteins by Bacterial Toxins; Kinetics of Substrate Reaction During Irreversible Modification of Enzyme Activity; The Dynamics of DNA Polymerace-Catalyzed Reactions; and Author Index.

  20. Penicillium marneffei Infection and Recent Advances in the Epidemiology and Molecular Biology Aspects

    PubMed Central

    Vanittanakom, Nongnuch; Cooper, Chester R.; Fisher, Matthew C.; Sirisanthana, Thira

    2006-01-01

    Penicillium marneffei infection is an important emerging public health problem, especially among patients infected with human immunodeficiency virus in the areas of endemicity in southeast Asia, India, and China. Within these regions, P. marneffei infection is regarded as an AIDS-defining illness, and the severity of the disease depends on the immunological status of the infected individual. Early diagnosis by serologic and molecular assay-based methods have been developed and are proving to be important in diagnosing infection. The occurrence of natural reservoirs and the molecular epidemiology of P. marneffei have been studied; however, the natural history and mode of transmission of the organism remain unclear. Soil exposure, especially during the rainy season, has been suggested to be a critical risk factor. Using a highly discriminatory molecular technique, multilocus microsatellite typing, to characterize this fungus, several isolates from bamboo rats and humans were shown to share identical multilocus genotypes. These data suggest either that transmission of P. marneffei may occur from rodents to humans or that rodents and humans are coinfected from common environmental sources. These putative natural cycles of P. marneffei infection need further investigation. Studies on the fungal genetics of P. marneffei have been focused on the characterization of genetic determinants that may play important roles in asexual development, mycelial-to-yeast phase transition, and the expression of antigenic determinants. Molecular studies have identified several genes involved in germination, hyphal development, conidiogenesis, and yeast cell polarity. A number of functionally important genes, such as the malate synthase- and catalase-peroxidase protein-encoding genes, have been identified as being upregulated in the yeast phase. Future investigations pertaining to the roles of these genes in host-fungus interactions may provide the key knowledge to understanding the