Design of the MUC-6 Evaluation

DTIC Science & Technology

1995-11-01

to list not just the specific product or service of the joint venture, but also a two- digit code for this product or service, based on the top-level...TEXT] LIBERAL SENATOR FEDERICO ESTRADA VELEZ WAS KIDNAPPED ON 3 APRIL AT THE CORNER OF 60TH AND 48TH STREETS IN WESTERN MEDELLIN , ONLY 100 ME- TERS...LOCATION OF INCIDENT COLOMBIA: MEDELLIN (CITY) 17. EFFECT ON PHYSICAL TARGET(S) * 18. EFFECT ON HUMAN TARGET(S) Figure 1: A sample message and

HARP targets pion production cross section and yield measurements. Implications for MiniBooNE neutrino flux

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

Wickremasinghe, Don Athula Abeyarathna

2015-07-01

The prediction of the muon neutrino flux from a 71.0 cm long beryllium target for the MiniBooNE experiment is based on a measured pion production cross section which was taken from a short beryllium target (2.0 cm thick - 5% nuclear interaction length) in the Hadron Production (HARP) experiment at CERN. To verify the extrapolation to our longer target, HARP also measured the pion production from 20.0 cm and 40.0 cm beryllium targets. The measured production yields, d 2N π± (p; θ )=dpd Ω, on targets of 50% and 100% nuclear interaction lengths in the kinematic rage of momentum frommore » 0.75 GeV/c to 6.5 GeV/c and the range of angle from 30 mrad to 210 mrad are presented along with an update of the short target cross sections. The best fitted extended Sanford-Wang (SW) model parameterization for updated short beryllium target π + production cross section is presented. Yield measurements for all three targets are also compared with that from the Monte Carlo predictions in the MiniBooNE experiment for different SW parameterization. The comparisons of v μ flux predictions for updated SW model is presented.« less

Immobilized magnetic beads-based multi-target affinity selection coupled with HPLC-MS for screening active compounds from traditional Chinese medicine and natural products.

PubMed

Chen, Yaqi; Chen, Zhui; Wang, Yi

2015-01-01

Screening and identifying active compounds from traditional Chinese medicine (TCM) and other natural products plays an important role in drug discovery. Here, we describe a magnetic beads-based multi-target affinity selection-mass spectrometry approach for screening bioactive compounds from natural products. Key steps and parameters including activation of magnetic beads, enzyme/protein immobilization, characterization of functional magnetic beads, screening and identifying active compounds from a complex mixture by LC/MS, are illustrated. The proposed approach is rapid and efficient in screening and identification of bioactive compounds from complex natural products.

Multiple products monitoring as a robust approach for peptide quantification.

PubMed

Baek, Je-Hyun; Kim, Hokeun; Shin, Byunghee; Yu, Myeong-Hee

2009-07-01

Quantification of target peptides and proteins is crucial for biomarker discovery. Approaches such as selected reaction monitoring (SRM) and multiple reaction monitoring (MRM) rely on liquid chromatography and mass spectrometric analysis of defined peptide product ions. These methods are not very widespread because the determination of quantifiable product ion using either SRM or MRM is a very time-consuming process. We developed a novel approach for quantifying target peptides without such an arduous process of ion selection. This method is based on monitoring multiple product ions (multiple products monitoring: MpM) from full-range MS2 spectra of a target precursor. The MpM method uses a scoring system that considers both the absolute intensities of product ions and the similarities between the query MS2 spectrum and the reference MS2 spectrum of the target peptide. Compared with conventional approaches, MpM greatly improves sensitivity and selectivity of peptide quantification using an ion-trap mass spectrometer.

Application of target costing in machining

NASA Astrophysics Data System (ADS)

Gopalakrishnan, Bhaskaran; Kokatnur, Ameet; Gupta, Deepak P.

2004-11-01

In today's intensely competitive and highly volatile business environment, consistent development of low cost and high quality products meeting the functionality requirements is a key to a company's survival. Companies continuously strive to reduce the costs while still producing quality products to stay ahead in the competition. Many companies have turned to target costing to achieve this objective. Target costing is a structured approach to determine the cost at which a proposed product, meeting the quality and functionality requirements, must be produced in order to generate the desired profits. It subtracts the desired profit margin from the company's selling price to establish the manufacturing cost of the product. Extensive literature review revealed that companies in automotive, electronic and process industries have reaped the benefits of target costing. However target costing approach has not been applied in the machining industry, but other techniques based on Geometric Programming, Goal Programming, and Lagrange Multiplier have been proposed for application in this industry. These models follow a forward approach, by first selecting a set of machining parameters, and then determining the machining cost. Hence in this study we have developed an algorithm to apply the concepts of target costing, which is a backward approach that selects the machining parameters based on the required machining costs, and is therefore more suitable for practical applications in process improvement and cost reduction. A target costing model was developed for turning operation and was successfully validated using practical data.

In situ imaging and proteome profiling indicate andrographolide is a highly promiscuous compound

NASA Astrophysics Data System (ADS)

Li, Lin; Wijaya, Hadhi; Samanta, Sanjay; Lam, Yulin; Yao, Shao Q.

2015-06-01

Natural products represent an enormous source of pharmacologically useful compounds, and are often used as the starting point in modern drug discovery. Many biologically interesting natural products are however not being pursued as potential drug candidates, partly due to a lack of well-defined mechanism-of-action. Traditional in vitro methods for target identification of natural products based on affinity protein enrichment from crude cellular lysates cannot faithfully recapitulate protein-drug interactions in living cells. Reported herein are dual-purpose probes inspired by the natural product andrographolide, capable of both reaction-based, real-time bioimaging and in situ proteome profiling/target identification in live mammalian cells. Our results confirm that andrographolide is a highly promiscuous compound and engaged in covalent interactions with numerous previously unknown cellular targets in cell type-specific manner. We caution its potential therapeutic effects should be further investigated in detail.

Diffraction based overlay and image based overlay on production flow for advanced technology node

NASA Astrophysics Data System (ADS)

Blancquaert, Yoann; Dezauzier, Christophe

2013-04-01

One of the main challenges for lithography step is the overlay control. For the advanced technology node like 28nm and 14nm, the overlay budget becomes very tight. Two overlay techniques compete in our advanced semiconductor manufacturing: the Diffraction based Overlay (DBO) with the YieldStar S200 (ASML) and the Image Based Overlay (IBO) with ARCHER (KLA). In this paper we will compare these two methods through 3 critical production layers: Poly Gate, Contact and first metal layer. We will show the overlay results of the 2 techniques, explore the accuracy and compare the total measurement uncertainty (TMU) for the standard overlay targets of both techniques. We will see also the response and impact for the Image Based Overlay and Diffraction Based Overlay techniques through a process change like an additional Hardmask TEOS layer on the front-end stack. The importance of the target design is approached; we will propose more adapted design for image based targets. Finally we will present embedded targets in the 14 FDSOI with first results.

Strategies for target identification of antimicrobial natural products.

PubMed

Farha, Maya A; Brown, Eric D

2016-05-04

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

The National Biofuels Strategy - Importance of sustainable feedstock production systems in regional-based supply chains

USDA-ARS?s Scientific Manuscript database

Region-based production systems are needed to produce the feedstocks that will be turned into the biofuels required to meet Federal mandated targets. Executive and Legislative actions have put into motion significant government responses designed to advance the development and production of domestic...

Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.

PubMed

Fang, J; Cai, C; Wang, Q; Lin, P; Zhao, Z; Cheng, F

2017-03-01

Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Application of Combination High-Throughput Phenotypic Screening and Target Identification Methods for the Discovery of Natural Product-Based Combination Drugs.

PubMed

Isgut, Monica; Rao, Mukkavilli; Yang, Chunhua; Subrahmanyam, Vangala; Rida, Padmashree C G; Aneja, Ritu

2018-03-01

Modern drug discovery efforts have had mediocre success rates with increasing developmental costs, and this has encouraged pharmaceutical scientists to seek innovative approaches. Recently with the rise of the fields of systems biology and metabolomics, network pharmacology (NP) has begun to emerge as a new paradigm in drug discovery, with a focus on multiple targets and drug combinations for treating disease. Studies on the benefits of drug combinations lay the groundwork for a renewed focus on natural products in drug discovery. Natural products consist of a multitude of constituents that can act on a variety of targets in the body to induce pharmacodynamic responses that may together culminate in an additive or synergistic therapeutic effect. Although natural products cannot be patented, they can be used as starting points in the discovery of potent combination therapeutics. The optimal mix of bioactive ingredients in natural products can be determined via phenotypic screening. The targets and molecular mechanisms of action of these active ingredients can then be determined using chemical proteomics, and by implementing a reverse pharmacokinetics approach. This review article provides evidence supporting the potential benefits of natural product-based combination drugs, and summarizes drug discovery methods that can be applied to this class of drugs. © 2017 Wiley Periodicals, Inc.

Cryogenic Hydrogen Fuel for Controlled Inertial Confinement Fusion (Cryogenic Target Factory Concept Based on FST-Layering Method)

NASA Astrophysics Data System (ADS)

Aleksandrova, I. V.; Koresheva, E. R.; Koshelev, I. E.; Krokhin, O. N.; Nikitenko, A. I.; Osipov, I. E.

2017-12-01

A central element of a power plant based on inertial confinement fusion (ICF) is a target with cryogenic hydrogen fuel that should be delivered to the center of a reactor chamber with a high accuracy and repetition rate. Therefore, a cryogenic target factory (CTF) is an integral part of any ICF reactor. A promising way to solve this problem consists in the FST layering method developed at the Lebedev Physical Institute (LPI). This method (rapid fuel layering inside moving free-standing targets) is unique, having no analogs in the world. The further development of FST-layering technologies is implemented in the scope of the LPI program for the creation of a modular CTF and commercialization of the obtained results. In this report, we discuss our concept of CTF (CTF-LPI) that exhibits the following distinctive features: using a FST-layering technology for the elaboration of an in-line production of cryogenic targets, using an effect of quantum levitation of high-temperature superconductors (HTSCs) in magnetic field for noncontacting manipulation, transport, and positioning of the free-standing cryogenic targets, as well as in using a Fourier holography technique for an on-line characterization and tracking of the targets flying into the reactor chamber. The results of original experimental and theoretical investigations performed at LPI indicate that the existing and developing target fabrication capabilities and technologies can be applied to ICF target production. The unique scientific, engineering, and technological base developed in Russia at LPI allows one to make a CTFLPI prototype for mass production of targets and delivery thereof at the required velocity into the ICF reactor chamber.

Self-vapor cooled targets for production of I-123 at high current accelerators. [using Xe-123 production

NASA Technical Reports Server (NTRS)

Blue, J. W.; Scholz, K. L.; Sodd, V. J.

1974-01-01

The basic elements of the vapor cooled target system are shown. This system can be operated as a heat pipe or as a conventional condenser. The choice of target fluid is based on the specific nuclear reaction chosen to produce Xe-123. The reaction using I-127 was studied and shown to have a significant yield for bombarding energies from 47 to 63 MeV. The Cs-133 reaction is also included. Xenon-123 is applied to I-123 production in a purer form for thyroid studies.

Production of an 15O beam using a stable oxygen ion beam for in-beam PET imaging

NASA Astrophysics Data System (ADS)

Mohammadi, Akram; Yoshida, Eiji; Tashima, Hideaki; Nishikido, Fumihiko; Inaniwa, Taku; Kitagawa, Atsushi; Yamaya, Taiga

2017-03-01

In advanced ion therapy, the 15O ion beam is a promising candidate to treat hypoxic tumors and simultaneously monitor the delivered dose to a patient using PET imaging. This study aimed at production of an 15O beam by projectile fragmentation of a stable 16O beam in an optimal material, followed by in-beam PET imaging using a prototype OpenPET system, which was developed in the authors' group. The study was carried out in three steps: selection of the optimal target based on the highest production rate of 15O fragments; experimental production of the beam using the optimal target in the Heavy Ion Medical Accelerator Chiba (HIMAC) secondary beam course; and realization of in-beam PET imaging for the produced beam. The optimal target evaluations were done using the Monte Carlo simulation code PHITS. The fluence and mean energy of the secondary particles were simulated and the optimal target was selected based on the production rate of 15O fragments. The highest production rate of 15O was observed for a liquid hydrogen target, 3.27% for a 53 cm thick target from the 16O beam of 430 MeV/u. Since liquid hydrogen is not practically applicable in the HIMAC secondary beam course a hydrogen-rich polyethylene material, which was the second optimal target from the simulation results, was selected as the experimental target. Three polyethylene targets with thicknesses of 5, 11 or 14 cm were used to produce the 15O beam without any degrader in the beam course. The highest production rate was measured as around 0.87% for the 11 cm thick polyethylene target from the 16O beam of 430 MeV/u when the angular acceptance and momentum acceptance were set at ±13 mrad and ±2.5%, respectively. The purity of the produced beam for the three targets were around 75%, insufficient for clinical application, but it was increased to 97% by inserting a wedge shape aluminum degrader with a thickness of 1.76 cm into the beam course and that is sufficiently high. In-beam PET imaging was also performed for all produced beams using the OpenPET system. The purity improvement of the produced 15O beams was confirmed from the PET images.

Experiencing Production Ramp-Up Education for Engineers

ERIC Educational Resources Information Center

Bassetto, S.; Fiegenwald, V.; Cholez, C.; Mangione, F.

2011-01-01

This paper presents a game of industrialisation, based on a paper airplane, that mimics real world production ramp-up and blends classical engineering courses together. It is based on a low cost product so that it can be mass produced. The game targets graduate students and practitioners in engineering fields. For students, it offers an experiment…

Purchases of ready-to-eat cereals vary across US household sociodemographic categories according to nutritional value and advertising targets.

PubMed

Castetbon, Katia; Harris, Jennifer L; Schwartz, Marlene B

2012-08-01

To describe ready-to-eat (RTE) cereal purchases in 2008 in the USA according to cereal nutritional quality and marketing strategy and household sociodemographic characteristics. Cross-sectional study of purchases in one year. Each type of cereal was assigned to one of four nutrition quality categories (based on Nutrient Profile Index, NPI) and one of four advertising categories based on television exposure and analysis of packaging (child-targeted, family-targeted, adult-targeted and no television advertising). Medians and distributions of purchase indicators were calculated for the cereal categories and the distributions were compared across sociodemographic groups. RTE cereals (n 249) with complete label and nutritional content. RTE cereal purchases according to household sociodemographic characteristics obtained from Nielsen Homescan, a nationally representative panel of households. Purchases of RTE cereals were highest in households with one or more child and lowest in African-American and Asian households, as well as those earning <$US 30 000 per annum. The lowest-quality products were purchased by four times as many households as the highest-quality cereals, but loyalty to these products was lower. Purchases of cereals by households with children and in African-American and Hispanic households increased as cereal nutritional quality declined. Compared with non-advertised products, advertised child-targeted cereals were purchased thirteen times more frequently; family-targeted brand purchases were ten times higher; and adult-targeted cereals were purchased four times more frequently. Our findings suggest that improving the nutritional quality of RTE cereals with advertising targeted to children could also lead to increased consumption of healthier products by young people.

Identification of the Geographic Origin of Parmigiano Reggiano (P.D.O.) Cheeses Deploying Non-Targeted Mass Spectrometry and Chemometrics.

PubMed

Popping, Bert; De Dominicis, Emiliano; Dante, Mario; Nocetti, Marco

2017-02-16

Parmigiano Reggiano is an Italian product with a protected designation of origin (P.D.O.). It is an aged hard cheese made from raw milk. P.D.O. products are protected by European regulations. Approximately 3 million wheels are produced each year, and the product attracts a relevant premium price due to its quality and all around the world well known typicity. Due to the high demand that exceeds the production, several fraudulent products can be found on the market. The rate of fraud is estimated between 20% and 40%, the latter predominantly in the grated form. We have developed a non-target method based on Liquid Chomatography-High Resolution Mass Spectrometry (LC-HRMS) that allows the discrimination of Parmigiano Reggiano from non-authentic products with milk from different geographical origins or products, where other aspects of the production process do not comply with the rules laid down in the production specifications for Parmeggiano Reggiano. Based on a database created with authentic samples provided by the Consortium of Parmigiano Reggiano Cheese, a reliable classification model was built. The overall classification capabilities of this non-targeted method was verified on 32 grated cheese samples. The classification was 87.5% accurate.

An off-line method to characterize the fission product release from uranium carbide-target prototypes developed for SPIRAL2 project

NASA Astrophysics Data System (ADS)

Hy, B.; Barré-Boscher, N.; Özgümüs, A.; Roussière, B.; Tusseau-Nenez, S.; Lau, C.; Cheikh Mhamed, M.; Raynaud, M.; Said, A.; Kolos, K.; Cottereau, E.; Essabaa, S.; Tougait, O.; Pasturel, M.

2012-10-01

In the context of radioactive ion beams, fission targets, often based on uranium compounds, have been used for more than 50 years at isotope separator on line facilities. The development of several projects of second generation facilities aiming at intensities two or three orders of magnitude higher than today puts an emphasis on the properties of the uranium fission targets. A study, driven by Institut de Physique Nucléaire d'Orsay (IPNO), has been started within the SPIRAL2 project to try and fully understand the behavior of these targets. In this paper, we have focused on five uranium carbide based targets. We present an off-line method to characterize their fission product release and the results are examined in conjunction with physical characteristics of each material such as the microstructure, the porosity and the chemical composition.

Neutron Production from In-situ Heavy Ice Coated Targets at Vulcan

NASA Astrophysics Data System (ADS)

Morrison, John; Krygier, A. G.; Kar, S.; Ahmed, H.; Alejo, A.; Clarke, R.; Fuchs, J.; Green, A.; Jung, D.; Kleinschmidt, A.; Najmudin, Z.; Nakamura, H.; Norreys, P.; Notley, M.; Oliver, M.; Roth, M.; Vassura, L.; Zepf, M.; Borghesi, M.; Freeman, R. R.

2015-05-01

Laser based neutron production experiments have been performed utilizing ultra-high intensity laser accelerated ions impinging upon a secondary target. The neutron yield from such experiments may be improved if the accelerated ions were primarily deuterons taking advantage of the d-d cross section. Recent experiments have demonstrated that selective deuteron acceleration from in-situ heavy ice coating of targets can produce ion spectra where deuterons comprise > 99 % of the measured ions. Results will be presented from integrated neutron production experiments from heavy ice targets coated in-situ recently performed on the Vulcan laser at Rutherford Appleton Laboratory. We are grateful for the Staff at RAL and acknowledge funding from the US DoE. AFOSR, European Social Fund, and the Czech Republic.

Integrating geological uncertainty in long-term open pit mine production planning by ant colony optimization

NASA Astrophysics Data System (ADS)

Gilani, Seyed-Omid; Sattarvand, Javad

2016-02-01

Meeting production targets in terms of ore quantity and quality is critical for a successful mining operation. In-situ grade uncertainty causes both deviations from production targets and general financial deficits. A new stochastic optimization algorithm based on ant colony optimization (ACO) approach is developed herein to integrate geological uncertainty described through a series of the simulated ore bodies. Two different strategies were developed based on a single predefined probability value (Prob) and multiple probability values (Pro bnt) , respectively in order to improve the initial solutions that created by deterministic ACO procedure. Application at the Sungun copper mine in the northwest of Iran demonstrate the abilities of the stochastic approach to create a single schedule and control the risk of deviating from production targets over time and also increase the project value. A comparison between two strategies and traditional approach illustrates that the multiple probability strategy is able to produce better schedules, however, the single predefined probability is more practical in projects requiring of high flexibility degree.

Traditional and New Influenza Vaccines

PubMed Central

Wong, Sook-San

2013-01-01

SUMMARY The challenges in successful vaccination against influenza using conventional approaches lie in their variable efficacy in different age populations, the antigenic variability of the circulating virus, and the production and manufacturing limitations to ensure safe, timely, and adequate supply of vaccine. The conventional influenza vaccine platform is based on stimulating immunity against the major neutralizing antibody target, hemagglutinin (HA), by virus attenuation or inactivation. Improvements to this conventional system have focused primarily on improving production and immunogenicity. Cell culture, reverse genetics, and baculovirus expression technology allow for safe and scalable production, while adjuvants, dose variation, and alternate routes of delivery aim to improve vaccine immunogenicity. Fundamentally different approaches that are currently under development hope to signal new generations of influenza vaccines. Such approaches target nonvariable regions of antigenic proteins, with the idea of stimulating cross-protective antibodies and thus creating a “universal” influenza vaccine. While such approaches have obvious benefits, there are many hurdles yet to clear. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated based on the same antigenic target and newer technologies based on different antigenic targets. PMID:23824369

Accelerator-based production of the (99m)Tc-(186)Re diagnostic-therapeutic pair using metal disulfide targets (MoS2, WS2, OsS2).

PubMed

Gott, Matthew D; Hayes, Connor R; Wycoff, Donald E; Balkin, Ethan R; Smith, Bennett E; Pauzauskie, Peter J; Fassbender, Michael E; Cutler, Cathy S; Ketring, Alan R; Wilbur, D Scott; Jurisson, Silvia S

2016-08-01

Novel, natural abundance metal disulfide targets were irradiated for 1h with a 10µA proton beam in a small, medical cyclotron. Osmium disulfide was synthesized by simple distillation and precipitation methods while MoS2 and WS2 were commercially available. The targets dissolved under mild conditions and were analyzed by γ-spectroscopy. Production rates and potential applications are discussed, including target recovery and recycling schemes for OsS2 and WS2. Copyright © 2016 Elsevier Ltd. All rights reserved.

The RIB production target for the SPES project

NASA Astrophysics Data System (ADS)

Monetti, Alberto; Andrighetto, Alberto; Petrovich, Carlo; Manzolaro, Mattia; Corradetti, Stefano; Scarpa, Daniele; Rossetto, Francesco; Martinez Dominguez, Fernando; Vasquez, Jesus; Rossignoli, Massimo; Calderolla, Michele; Silingardi, Roberto; Mozzi, Aldo; Borgna, Francesca; Vivian, Gianluca; Boratto, Enrico; Ballan, Michele; Prete, Gianfranco; Meneghetti, Giovanni

2015-10-01

Facilities making use of the Isotope Separator On-Line (ISOL) method for the production of Radioactive Ion Beams (RIB) attract interest because they can be used for nuclear structure and reaction studies, astrophysics research and interdisciplinary applications. The ISOL technique is based on the fast release of the nuclear reaction products from the chosen target material together with their ionization into short-lived nuclei beams. Within this context, the SPES (Selective Production of Exotic Species) facility is now under construction in Italy at INFN-LNL (Istituto Nazionale di Fisica Nucleare — Laboratori Nazionali di Legnaro). The SPES facility will produce RIBs mainly from n-rich isotopes obtained by a 40 MeV cyclotron proton beam (200 μA) directly impinging on a uranium carbide multi-foil fission target. The aim of this work is to describe and update, from a comprehensive point of view, the most important results obtained by the analysis of the on-line behavior of the SPES production target assembly. In particular an improved target configuration has been studied by comparing different codes and physics models: the thermal analyses and the isotope production are re-evaluated. Then some consequent radioprotection aspects, which are essential for the installation and operation of the facility, are presented.

A Study of Particle Production in Proton Induced Collisions Using the MIPP Detector at Fermilab

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

Mahajan, Sonam

2015-01-01

The Main Injector Particle Production (MIPP) experiment is a fixed target hadron production experiment at Fermilab. MIPP is a high acceptance spectrometer which provides excellent charged particle identification using Time Projection Chamber (TPC), Time of Flight (ToF), multicell Cherenkov (Ckov), ring imaging Cherenkov (RICH) detectors, and Calorimeter for neutrons. The MIPP experiment is designed to measure particle production in interactions of 120 GeV/c primary protons from the Main Injector and secondary beams ofmore » $$\\pi^{\\pm}, \\rm{K}^{\\pm}$$, p and $$\\bar{\\rm{p}}$$ from 5 to 90 GeV/c on nuclear targets which include H, Be, C, Bi and U, and a dedicated run with the NuMI target. The goal of the experiment is to measure hadron production cross sections or yields using these beams and targets. These hadronic interaction data can have a direct impact on the detailed understanding of the neutrino fluxes of several accelerator-based neutrino experiments like MINOS, MINER$$\

Computational Methods to Assess the Production Potential of Bio-Based Chemicals.

PubMed

Campodonico, Miguel A; Sukumara, Sumesh; Feist, Adam M; Herrgård, Markus J

2018-01-01

Elevated costs and long implementation times of bio-based processes for producing chemicals represent a bottleneck for moving to a bio-based economy. A prospective analysis able to elucidate economically and technically feasible product targets at early research phases is mandatory. Computational tools can be implemented to explore the biological and technical spectrum of feasibility, while constraining the operational space for desired chemicals. In this chapter, two different computational tools for assessing potential for bio-based production of chemicals from different perspectives are described in detail. The first tool is GEM-Path: an algorithm to compute all structurally possible pathways from one target molecule to the host metabolome. The second tool is a framework for Modeling Sustainable Industrial Chemicals production (MuSIC), which integrates modeling approaches for cellular metabolism, bioreactor design, upstream/downstream processes, and economic impact assessment. Integrating GEM-Path and MuSIC will play a vital role in supporting early phases of research efforts and guide the policy makers with decisions, as we progress toward planning a sustainable chemical industry.

Estimation of Microbial Concentration in Food Products from Qualitative, Microbiological Test Data with the MPN Technique.

PubMed

Fujikawa, Hiroshi

2017-01-01

Microbial concentration in samples of a food product lot has been generally assumed to follow the log-normal distribution in food sampling, but this distribution cannot accommodate the concentration of zero. In the present study, first, a probabilistic study with the most probable number (MPN) technique was done for a target microbe present at a low (or zero) concentration in food products. Namely, based on the number of target pathogen-positive samples in the total samples of a product found by a qualitative, microbiological examination, the concentration of the pathogen in the product was estimated by means of the MPN technique. The effects of the sample size and the total sample number of a product were then examined. Second, operating characteristic (OC) curves for the concentration of a target microbe in a product lot were generated on the assumption that the concentration of a target microbe could be expressed with the Poisson distribution. OC curves for Salmonella and Cronobacter sakazakii in powdered formulae for infants and young children were successfully generated. The present study suggested that the MPN technique and the Poisson distribution would be useful for qualitative microbiological test data analysis for a target microbe whose concentration in a lot is expected to be low.

PREDICTING THE RISKS OF NEUROTOXIC VOLATILE ORGANIC COMPOUNDS BASED ON TARGET TISSUE DOSE.

EPA Science Inventory

Quantitative exposure-dose-response models relate the external exposure of a substance to the dose in the target tissue, and then relate the target tissue dose to production of adverse outcomes. We developed exposure-dose-response models to describe the affects of acute exposure...

Method for detecting binding efficiencies of synthetic oligonucleotides: Targeting bacteria and insects

USDA-ARS?s Scientific Manuscript database

Expanding applications of gene-based targeting biotechnology in functional genomics and the treatment of plants, animals, and microbes has synergized the need for new methods to measure binding efficiencies of these products to their genetic targets. The adaptation and innovative use of Cell–Penetra...

Male contraception: what is on the horizon?

PubMed

Blithe, Diana

2008-10-01

Male contraception remains an important area of research. Methods can inhibit sperm production or can be targeted to inhibit sperm functions such as motility, orientation or interaction with the egg. Hormonal methods appear to be safe and effective in proof of concept studies but efforts are underway to improve delivery options or lead time until full efficacy is achieved. Nonhormonal methods are based on numerous targets that impact sperm production or function. Several agents that inhibit the sperm-specific or testis-specific targets have been identified and studies in animals have shown promising results.

A systematic study of chemogenomics of carbohydrates.

PubMed

Gu, Jiangyong; Luo, Fang; Chen, Lirong; Yuan, Gu; Xu, Xiaojie

2014-03-04

Chemogenomics focuses on the interactions between biologically active molecules and protein targets for drug discovery. Carbohydrates are the most abundant compounds in natural products. Compared with other drugs, the carbohydrate drugs show weaker side effects. Searching for multi-target carbohydrate drugs can be regarded as a solution to improve therapeutic efficacy and safety. In this work, we collected 60 344 carbohydrates from the Universal Natural Products Database (UNPD) and explored the chemical space of carbohydrates by principal component analysis. We found that there is a large quantity of potential lead compounds among carbohydrates. Then we explored the potential of carbohydrates in drug discovery by using a network-based multi-target computational approach. All carbohydrates were docked to 2389 target proteins. The most potential carbohydrates for drug discovery and their indications were predicted based on a docking score-weighted prediction model. We also explored the interactions between carbohydrates and target proteins to find the pathological networks, potential drug candidates and new indications.

Development of medicine-intended isotope production technologies at Yerevan Physics Institute

NASA Astrophysics Data System (ADS)

Avetisyan, Albert; Avagyan, Robert; Kerobyan, Ivetta; Dallakyan, Ruben; Harutyunyan, Gevorg; Melkonyan, Aleksandr

2015-05-01

Accelerator-based 99mTc and 123I isotopes production technologies were created and developed at A.Alikhanyan National Science Laboratory (former Yerevan Physics Institute - YerPhI). The method involves the irradiation of natural molybdenum (for 99mTc production) and natural xenon (for 123I production) using high-intensity bremsstrahlung photons from the electron beam of the LUE50 linear electron accelerator located at the YerPhI. We have developed and tested the extraction of 99mTc and 123I from the irradiated natural MoO3 and natural Xe, respectively. The production method has been developed and shown to be successful. The current activity is devoted to creation and development of the technology of direct production 99mTc on the 100Mo as target materials using the proton beam from an IBA C18/18 cyclotron. The proton cyclotron C18/18 (producer - IBA, Belgium) was purchased and will be installed nearby AANL (YerPhI) till end 2014. The 18 MeV protons will be used to investigate accelerator-based schemes for the direct production of 99mTc. Main topics of studies will include experimental measurement of 99mTc production yield for different energies of protons, irradiation times, intensities, development of new methods of 99mTc extraction from irradiated materials, development of target preparation technology, development of target material recovery methods for multiple use and others.

Production of Y-86 and other radiometals for research purposes using a solution target system.

PubMed

Oehlke, Elisabeth; Hoehr, Cornelia; Hou, Xinchi; Hanemaayer, Victoire; Zeisler, Stefan; Adam, Michael J; Ruth, Thomas J; Celler, Anna; Buckley, Ken; Benard, Francois; Schaffer, Paul

2015-11-01

Diagnostic radiometals are typically obtained from cyclotrons by irradiating solid targets or from radioisotope generators. These methods have the advantage of high production yields, but require additional solid target handling infrastructure that is not readily available to many cyclotron facilities. Herein, we provide an overview of our results regarding the production of various positron-emitting radiometals using a liquid target system installed on a 13 MeV cyclotron at TRIUMF. Details about the production, purification and quality control of (89)Zr, (68)Ga and for the first time (86)Y are discussed. Aqueous solutions containing 1.35-1.65 g/mL of natural-abundance zinc nitrate, yttrium nitrate, and strontium nitrate were irradiated on a 13 MeV cyclotron using a standard liquid target. Different target body and foil materials were investigated for corrosion. Production yields were calculated using theoretical cross-sections from the EMPIRE code and compared with experimental results. The radioisotopes were extracted from irradiated target material using solid phase extraction methods adapted from previously reported methods, and used for radiolabelling experiments. We demonstrated production quantities that are sufficient for chemical and biological studies for three separate radiometals, (89)Zr (Asat = 360 MBq/μA and yield = 3.17 MBq/μA), (86)Y (Asat = 31 MBq/μA and yield = 1.44 MBq/μA), and (68)Ga (Asat = 141 MBq/μA and yield = 64 MBq/μA) from one hour long irradiations on a typical medical cyclotron. (68)Ga yields were sufficient for potential clinical applications. In order to avoid corrosion of the target body and target foil, nitrate solutions were chosen as well as niobium as target-body material. An automatic loading system enabled up to three production runs per day. The separation efficiency ranged from 82 to 99%. Subsequently, (68)Ga and (86)Y were successfully used to radiolabel DOTA-based chelators while deferoxamine was used to coordinate (89)Zr. Copyright © 2015 Elsevier Inc. All rights reserved.

Proton irradiation of [18O]O2: production of [18F]F2 and [18F]F2 + [18F] OF2.

PubMed

Bishop, A; Satyamurthy, N; Bida, G; Hendry, G; Phelps, M; Barrio, J R

1996-04-01

The production of 18F electrophilic reagents via the 18O(p,n)18F reaction has been investigated in small-volume target bodies made of aluminum, copper, gold-plated copper and nickel, having straight or conical bore shapes. Three irradiation protocols-single-step, two-step and modified two-step-were used for the recovery of the 18F activity. The single-step irradiation protocol was tested in all the target bodies. Based on the single-step performance, aluminum targets were utilized extensively in the investigation of the two-step and modified two-step irradiation protocols. With an 11-MeV cyclotron and using the two-step irradiation protocol, > 1Ci [18F]F2 was recovered reproducibly from an aluminum target body. Probable radical mechanisms for the formation of OF2 and FONO2 (fluorine nitrate) in the single-step and modified two-step targets are proposed based on the amount of ozone generated and the nitrogen impurity present in the target gases, respectively.

Natural products used as a chemical library for protein-protein interaction targeted drug discovery.

PubMed

Jin, Xuemei; Lee, Kyungro; Kim, Nam Hee; Kim, Hyun Sil; Yook, Jong In; Choi, Jiwon; No, Kyoung Tai

2018-01-01

Protein-protein interactions (PPIs), which are essential for cellular processes, have been recognized as attractive therapeutic targets. Therefore, the construction of a PPI-focused chemical library is an inevitable necessity for future drug discovery. Natural products have been used as traditional medicines to treat human diseases for millennia; in addition, their molecular scaffolds have been used in diverse approved drugs and drug candidates. The recent discovery of the ability of natural products to inhibit PPIs led us to use natural products as a chemical library for PPI-targeted drug discovery. In this study, we collected natural products (NPDB) from non-commercial and in-house databases to analyze their similarities to small-molecule PPI inhibitors (iPPIs) and FDA-approved drugs by using eight molecular descriptors. Then, we evaluated the distribution of NPDB and iPPIs in the chemical space, represented by the molecular fingerprint and molecular scaffolds, to identify the promising scaffolds, which could interfere with PPIs. To investigate the ability of natural products to inhibit PPI targets, molecular docking was used. Then, we predicted a set of high-potency natural products by using the iPPI-likeness score based on a docking score-weighted model. These selected natural products showed high binding affinities to the PPI target, namely XIAP, which were validated in an in vitro experiment. In addition, the natural products with novel scaffolds might provide a promising starting point for further medicinal chemistry developments. Overall, our study shows the potency of natural products in targeting PPIs, which might help in the design of a PPI-focused chemical library for future drug discovery. Copyright © 2017 Elsevier Inc. All rights reserved.

Particle production of a graphite target system for the intensity frontier

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

Ding, X.; Kirk, H.; McDonald, K. T.

2015-05-03

A solid graphite target system is considered for an intense muon and/or neutrino source in support of physics at the intensity frontier. We previously optimized the geometric parameters of the beam and target to maximize particle production at low energies by incoming protons with kinetic energy of 6.75 GeV and an rms geometric emittance of 5 mm-mrad using the MARS15(2014) code. In this study, we ran MARS15 with ROOT-based geometry and also considered a mercury-jet target as an upgrade option. The optimization was extended to focused proton beams with transverse emittances from 5 to 50 mm-mrad, showing that the particlemore » production decreases slowly with increasing emittance. We also studied beam-dump configurations to suppress the rate of undesirable high-energy secondary particles in the beam.« less

Progress on the chemical separation of fission fragments from 236Np produced by proton irradiation of natural uranium target

NASA Astrophysics Data System (ADS)

Larijani, C.; Jerome, S. M.; Lorusso, G.; Ivanov, P.; Russell, B.; Pearce, A. K.; Regan, P. H.

2017-11-01

The aim of the current work is to develop and validate a radiochemical separation scheme capable of separating both 236gNp and 236Pu from a uranium target of natural isotopic composition ( 1 g uranium) and 200 MBq of fission decay products. A target containing 1.2 g of UO2 was irradiated with a beam of 25 MeV protons with a typical beam current of 30 μA for 19 h in December 2013 at the University of Birmingham Cyclotron facility. Using literature values for the production cross-section for fusion of protons with uranium targets, we estimate that an upper limit of approximately 250 Bq of activity from the 236Np ground state was produced in this experiment. Using a radiochemical separation scheme, Np and Pu fractions were separated from the produced fission decay products, with analyses of the target-based final reaction products made using Inductively Couple Plasma Mass Spectrometry (ICP-MS) and high-resolution α particle and γ-ray spectrometry.

Enhanced hexose fermentation by Saccharomyces cerevisiae through integration of stoichiometric modeling and genetic screening.

PubMed

Quarterman, Josh; Kim, Soo Rin; Kim, Pan-Jun; Jin, Yong-Su

2015-01-20

In order to determine beneficial gene deletions for ethanol production by the yeast Saccharomyces cerevisiae, we performed an in silico gene deletion experiment based on a genome-scale metabolic model. Genes coding for two oxidative phosphorylation reactions (cytochrome c oxidase and ubiquinol cytochrome c reductase) were identified by the model-based simulation as potential deletion targets for enhancing ethanol production and maintaining acceptable overall growth rate in oxygen-limited conditions. Since the two target enzymes are composed of multiple subunits, we conducted a genetic screening study to evaluate the in silico results and compare the effect of deleting various portions of the respiratory enzyme complexes. Over two-thirds of the knockout mutants identified by the in silico study did exhibit experimental behavior in qualitative agreement with model predictions, but the exceptions illustrate the limitation of using a purely stoichiometric model-based approach. Furthermore, there was a substantial quantitative variation in phenotype among the various respiration-deficient mutants that were screened in this study, and three genes encoding respiratory enzyme subunits were identified as the best knockout targets for improving hexose fermentation in microaerobic conditions. Specifically, deletion of either COX9 or QCR9 resulted in higher ethanol production rates than the parental strain by 37% and 27%, respectively, with slight growth disadvantages. Also, deletion of QCR6 led to improved ethanol production rate by 24% with no growth disadvantage. The beneficial effects of these gene deletions were consistently demonstrated in different strain backgrounds and with four common hexoses. The combination of stoichiometric modeling and genetic screening using a systematic knockout collection was useful for narrowing a large set of gene targets and identifying targets of interest. Copyright © 2014 Elsevier B.V. All rights reserved.

Early Sentence Productions of 3- and 4-Year-Old Children Who Use Augmentative and Alternative Communication

PubMed Central

Kent-Walsh, Jennifer; King, Marika; Mansfield, Lindsay

2017-01-01

Purpose This study investigated the early rule-based sentence productions of 3- and 4-year-old children with severe speech disorders who used single-meaning graphic symbols to communicate. Method Ten 3- and 4-year-olds requiring the use of augmentative and alternative communication, who had largely intact receptive language skills, received instruction in producing up to four different semantic–syntactic targets using an Apple iPad with a communication app. A single-case, multiple-probe, across-targets design was used to assess the progress of each participant and target. Generalization to new vocabulary was assessed, and a subgroup also was taught to produce sentences using grammatical markers. Results Some targets (primarily possessor-entity) were mastered in the baseline phase, and the majority of the remaining targets were mastered during intervention. All four children who completed intervention for grammatical markers quickly learned to use the markers accurately. Conclusions Expressive language potential for preschoolers using graphic symbol–based augmentative and alternative communication systems should not be underestimated. With appropriate presentation and intervention techniques, some preschoolers with profound speech disorders can readily learn to produce rule-based messages via graphic symbols. PMID:28614575

Early Sentence Productions of 3- and 4-Year-Old Children Who Use Augmentative and Alternative Communication.

PubMed

Binger, Cathy; Kent-Walsh, Jennifer; King, Marika; Mansfield, Lindsay

2017-07-12

This study investigated the early rule-based sentence productions of 3- and 4-year-old children with severe speech disorders who used single-meaning graphic symbols to communicate. Ten 3- and 4-year-olds requiring the use of augmentative and alternative communication, who had largely intact receptive language skills, received instruction in producing up to four different semantic-syntactic targets using an Apple iPad with a communication app. A single-case, multiple-probe, across-targets design was used to assess the progress of each participant and target. Generalization to new vocabulary was assessed, and a subgroup also was taught to produce sentences using grammatical markers. Some targets (primarily possessor-entity) were mastered in the baseline phase, and the majority of the remaining targets were mastered during intervention. All four children who completed intervention for grammatical markers quickly learned to use the markers accurately. Expressive language potential for preschoolers using graphic symbol-based augmentative and alternative communication systems should not be underestimated. With appropriate presentation and intervention techniques, some preschoolers with profound speech disorders can readily learn to produce rule-based messages via graphic symbols.

Alternative options for DNA-based experimental therapy of β-thalassemia.

PubMed

Gambari, Roberto

2012-04-01

Beta-thalassemias are caused by more than 200 mutations of the β-globin gene, leading to low or absent production of adult hemoglobin. Achievements have been made with innovative therapeutic strategies for β-thalassemias, based on research conducted at the levels of gene structure, transcription, mRNA processing and protein synthesis. The objective of this review is to describe the development of therapeutic strategies employing viral and non-viral DNA-based approaches for treatment of β-thalassemia. Modification of β-globin gene expression in β-thalassemia cells has been achieved by gene therapy, correction of the mutated β-globin gene and RNA repair. In addition, cellular therapy has been proposed for β-thalassemia, including reprogramming of somatic cells to generate induced pluripotent stem cells to be genetically corrected. Based on the concept that increased production of fetal hemoglobin (HbF) is beneficial in β-thalassemia, DNA-based approaches to increase HbF production have been optimized, including treatment of target cells with lentiviral vectors carrying γ-globin genes. Finally, DNA-based targeting of α-globin gene expression has been applied to reduce the excess of α-globin production by β-thalassemia cells, one of the major causes of the clinical phenotype.

A global comparability approach for biosimilar monoclonal antibodies using LC-tandem MS based proteomics.

PubMed

Chen, Shun-Li; Wu, Shiaw-Lin; Huang, Li-Juan; Huang, Jia-Bao; Chen, Shu-Hui

2013-06-01

Liquid chromatography-tandem mass spectrometry-based proteomics for peptide mapping and sequencing was used to characterize the marketed monoclonal antibody trastuzumab and compare it with two biosimilar products, mAb A containing D359E and L361M variations at the Fc site and mAb B without variants. Complete sequence coverage (100%) including disulfide linkages, glycosylations and other commonly occurring modifications (i.e., deamidation, oxidation, dehydration and K-clipping) were identified using maps generated from multi-enzyme digestions. In addition to the targeted comparison for the relative populations of targeted modification forms, a non-targeted approach was used to globally compare ion intensities in tryptic maps. The non-targeted comparison provided an extra-dimensional view to examine any possible differences related to variants or modifications. A peptide containing the two variants in mAb A, D359E and L361M, was revealed using the non-targeted comparison of the tryptic maps. In contrast, no significant differences were observed when trastuzumab was self-compared or compared with mAb B. These results were consistent with the data derived from peptide sequencing via collision induced dissociation/electron transfer dissociation. Thus, combined targeted and non-targeted approaches using powerful mass spectrometry-based proteomic tools hold great promise for the structural characterization of biosimilar products. Copyright © 2013 Elsevier B.V. All rights reserved.

Using Functional Signature Ontology (FUSION) to Identify Mechanisms of Action for Natural Products

PubMed Central

Potts, Malia B.; Kim, Hyun Seok; Fisher, Kurt W.; Hu, Youcai; Carrasco, Yazmin P.; Bulut, Gamze Betul; Ou, Yi-Hung; Herrera-Herrera, Mireya L.; Cubillos, Federico; Mendiratta, Saurabh; Xiao, Guanghua; Hofree, Matan; Ideker, Trey; Xie, Yang; Huang, Lily Jun-shen; Lewis, Robert E.; MacMillan, John B.; White, Michael A.

2014-01-01

A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, we developed a new marine-derived, renewable natural products resource and a method for linking bioactive derivatives of this library to the proteins and biological processes that they target in cells. We used cell-based screening and computational analysis to match gene expression signatures produced by natural products to those produced by siRNA and synthetic microRNA libraries. With this strategy, we matched proteins and microRNAs with diverse biological processes and also identified putative protein targets and mechanisms of action for several previously undescribed marine-derived natural products. We confirmed mechanistic relationships for selected short-interfering RNAs, microRNAs, and compounds with functional roles in autophagy, chemotaxis mediated by discoidin domain receptor 2, or activation of the kinase AKT. Thus, this approach may be an effective method for screening new drugs while simultaneously identifying their targets. PMID:24129700

Presentation-Practice-Production and Task-Based Learning in the Light of Second Language Learning Theories.

ERIC Educational Resources Information Center

Ritchie, Graeme

2003-01-01

Features of presentation-practice-production (PPP) and task-based learning (TBL) models for language teaching are discussed with reference to language learning theories. Pre-selection of target structures, use of controlled repetition, and explicit grammar instruction in a PPP lesson are given. Suggests TBL approaches afford greater learning…

ANL progress on the cooperation with CNEA for the Mo-99 production : base-side digestion process.

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

Gelis, A. V.; Quigley, K. J.; Aase, S. B.

2004-01-01

Conversion from high-enriched uranium (HEU) to low-enriched uranium (LEU) targets for the Mo-99 production requires certain modifications of the target design, the digestion and the purification processes. ANL is assisting the Argentine Comision Nacional de Energia Atomica (CNEA) to overcome all the concerns caused by the conversion to LEU foil targets. A new digester with stirring system has been successfully applied for the digestion of the low burn-up U foil targets in KMnO4 alkaline media. In this paper, we report the progress on the development of the digestion procedure with stirring focusing on the minimization of the liquid radioactive waste.

Radioisotope Production for Medical and Physics Applications

NASA Astrophysics Data System (ADS)

Mausner, Leonard

2012-10-01

Radioisotopes are critical to the science and technology base of the US. Discoveries and applications made as a result of the availability of radioisotopes span widely from medicine, biology, physics, chemistry and homeland security. The clinical use of radioisotopes for medical diagnosis is the largest sector of use, with about 16 million procedures a year in the US. The use of ^99Mo/^99mTc generator and ^18F make up the majority, but ^201Tl, ^123I, ^111In, and ^67Ga are also used routinely to perform imaging of organ function. Application of radioisotopes for therapy is dominated by use of ^131I for thyroid malignancies, ^90Y for some solid tumors, and ^89Sr for bone cancer, but production of several more exotic species such as ^225Ac and ^211At are of significant current research interest. In physics ^225Ra is of interest for CP violation studies, and the actinides ^242Am, ^249Bk, and ^254Es are needed as targets for experiments to create superheavy elements. Large amounts of ^252Cf are needed as a fission source for the CARIBU experiment at ANL. The process of radioisotope production is multidisciplinary. Nuclear physics input based on nuclear reaction excitation function data is needed to choose an optimum target/projectile in order to maximize desired isotope production and minimize unwanted byproducts. Mechanical engineering is needed to address issues of target heating, induced mechanical stress and material compatibility of target and claddings. Radiochemists are involved as well since chemical separation to purify the desired final radioisotope product from the bulk target and impurities is also usually necessary. Most neutron rich species are produced at a few government and university reactors. Other radioisotopes are produced in cyclotrons in the commercial sector, university/hospital based facilities, and larger devices at the DOE labs. The landscape of US facilities, the techniques involved, and current supply challenges will be reviewed.

Transfer products from the reactions of heavy ions with heavy nuclei. [394 to 1156 MeV

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

Thomas, K.E. III

1979-11-01

Production of nuclides heavier than the target from /sup 86/Kr- and /sup 136/Xe-induced reactions with /sup 181/Ta and /sup 238/U was investigated. Attempts were made to produce new neutron-excess Np and Pu isotopes by the deep inelastic mechanism. No evidence was found for /sup 242/Np or /sup 247/Pu. Estimates were made for the production of /sup 242/Np, /sup 247/Pu, and /sup 248/Am from heavy-ion reactions with uranium targets. Comparisons of reactions of /sup 86/Kr and /sup 136/Xe ions with thick /sup 181/Ta targets and /sup 86/Kr, /sup 136/Xe and /sup 238/U ions with thick /sup 238/U targets indicate that themore » most probable products are not dependent on the projectile. The most probable products can be predicted by the equation Z - Z/sub target/ = 0.43 (A - A/sub target/) + 1.0. The major effect of the projectile is the magnitude of the production cross section of the heavy products. Based on these results, estimates are made of the most probable mass of element 114 produced from heavy-ion reactions with /sup 248/Cm and /sup 254/Es targets. These estimates give the mass number of element 114 as approx. 287 if produced in heavy-ion reactions with these very heavy targets. Excitation functions of gold and bismuth isotopes arising from /sup 86/Kr- and /sup 136/Xe-induced reactions with thin /sup 181/Ta targets were measured. These results indicate that the shape and location (in Z and A above the target) of the isotopic distributions are not strongly dependent on the projectile incident energy. Also, the nuclidic cross sections are found to increase with an increase in projectile energy to a maximum at approximately 1.4 to 1.5 times the Coulomb barrier. Above this maximum, the nuclidic cross sections are found to decrease with an increase in projectile energy. This decrease in cross section is believed to be due to fission of the heavy products caused by high excitation energy and angular momentum. 111 references, 39 figures, 34 tables.« less

Using focus groups in the consumer research phase of a social marketing program to promote moderate-intensity physical activity and walking trail use in Sumter County, South Carolina.

PubMed

Burroughs, Ericka; Peck, Lara E; Sharpe, Patricia A; Granner, Michelle L; Bryant, Carol A; Fields, Regina

2006-01-01

The use of social marketing approaches in public health practice is increasing. Using marketing concepts such as the "four Ps" (product, price, place, and promotion), social marketing borrows from the principles of commercial marketing but promotes beneficial health behaviors. Consumer research is used to segment the population and develop a strategy based on those marketing concepts. In a community-based participatory research study, 17 focus groups were used in consumer research to develop a social marketing program to promote walking and other moderate-intensity physical activities. Two phases of focus groups were conducted. Phase 1 groups, which included both men and women, were asked to respond to questions that would guide the development of a social marketing program based on social marketing concepts. Phase 1 also determined the intervention's target audience, which was irregularly active women aged 35 to 54. Phase 2 groups, composed of members of the target audience, were asked to further define the product and discuss specific promotion strategies. Phase 1 participants determined that the program product, or target behavior, should be walking. In addition, they identified price, place, and promotion strategies. Phase 2 participants determined that moderate-intensity physical activity is best promoted using the term exercise and offered suggestions for marketing walking, or exercise, to the target audience. There have been few published studies of social marketing campaigns to promote physical activity. In this study, focus groups were key to understanding the target audience in a way that would not have been accomplished with quantitative data alone. The group discussions generated important insights into values and motivations that affect consumers' decisions to adopt a product or behavior. The focus group results guided the development of a social marketing program to promote physical activity in the target audience in Sumter County, South Carolina.

A new airborne laser rangefinder dynamic target simulator for non-stationary environment

NASA Astrophysics Data System (ADS)

Ma, Pengge; Pang, Dongdong; Yi, Yang

2017-11-01

For the non-stationary environment simulation in laser range finder product testing, a new dynamic target simulation system is studied. First of all, the three-pulsed laser ranging principle, laser target signal composition and mathematical representation are introduced. Then, the actual nonstationary working environment of laser range finder is analyzed, and points out that the real sunshine background light clutter and target shielding effect in laser echo become the main influencing factors. After that, the dynamic laser target signal simulation method is given. Eventlly, the implementation of automatic test system based on arbitrary waveform generator is described. Practical application shows that the new echo signal automatic test system can simulate the real laser ranging environment of laser range finder, and is suitable for performance test of products.

Creating targeted initial populations for genetic product searches in heterogeneous markets

NASA Astrophysics Data System (ADS)

Foster, Garrett; Turner, Callaway; Ferguson, Scott; Donndelinger, Joseph

2014-12-01

Genetic searches often use randomly generated initial populations to maximize diversity and enable a thorough sampling of the design space. While many of these initial configurations perform poorly, the trade-off between population diversity and solution quality is typically acceptable for small-scale problems. Navigating complex design spaces, however, often requires computationally intelligent approaches that improve solution quality. This article draws on research advances in market-based product design and heuristic optimization to strategically construct 'targeted' initial populations. Targeted initial designs are created using respondent-level part-worths estimated from discrete choice models. These designs are then integrated into a traditional genetic search. Two case study problems of differing complexity are presented to illustrate the benefits of this approach. In both problems, targeted populations lead to computational savings and product configurations with improved market share of preferences. Future research efforts to tailor this approach and extend it towards multiple objectives are also discussed.

Could the employment-based targeting approach serve Egypt in moving towards a social health insurance model?

PubMed

Shawky, S

2010-06-01

The current health insurance system in Egypt targets the productive population through an employment-based scheme bounded by a cost ceiling and focusing on curative care. Egypt Social Contract Survey data from 2005 were used to evaluate the impact of the employment-based scheme on health system accessibility and financing. Only 22.8% of the population in the productive age range (19-59 years) benefited from any health insurance scheme. The employment-based scheme covered 39.3% of the working population and was skewed towards urban areas, older people, females and the wealthier. It did not increase service utilization, but reduced out-of-pocket expenditure. Egypt should blend all health insurance schemes and adopt an innovative approach to reach universal coverage.

Secondary Neutron Production from Space Radiation Interactions: Advances in Model and Experimental Data Base Development

NASA Technical Reports Server (NTRS)

Heilbronn, Lawrence H.; Townsend, Lawrence W.; Braley, G. Scott; Iwata, Yoshiyuki; Iwase, Hiroshi; Nakamura, Takashi; Ronningen, Reginald M.; Cucinotta, Francis A.

2003-01-01

For humans engaged in long-duration missions in deep space or near-Earth orbit, the risk from exposure to galactic and solar cosmic rays is an important factor in the design of spacecraft, spacesuits, and planetary bases. As cosmic rays are transported through shielding materials and human tissue components, a secondary radiation field is produced. Neutrons are an important component of that secondary field, especially in thickly-shielded environments. Calculations predict that 50% of the dose-equivalent in a lunar or Martian base comes from neutrons, and a recent workshop held at the Johnson Space Center concluded that as much as 30% of the dose in the International Space Station may come from secondary neutrons. Accelerator facilities provide a means for measuring the effectiveness of various materials in their ability to limit neutron production, using beams and energies that are present in cosmic radiation. The nearly limitless range of beams, energies, and target materials that are present in space, however, means that accelerator-based experiments will not provide a complete database of cross sections and thick-target yields that are necessary to plan and design long-duration missions. As such, accurate nuclear models of neutron production are needed, as well as data sets that can be used to compare with, and verify, the predictions from such models. Improvements in a model of secondary neutron production from heavy-ion interactions are presented here, along with the results from recent accelerator-based measurements of neutron-production cross sections. An analytical knockout-ablation model capable of predicting neutron production from high-energy hadron-hadron interactions (both nucleon-nucleus and nucleus-nucleus collisions) has been previously developed. In the knockout stage, the collision between two nuclei result in the emission of one or more nucleons from the projectile and/or target. The resulting projectile and target remnants, referred to as prefragments, then decay by the emission of nucleons, composites, and gamma rays. Recent improvements to the model have incorporated coalescence effects, which effectively tie up single nucleons in the formation of composites during final-state interactions. Comparison of the improved model s predictions with neutron production data near 0 deg in the CA-40+ H reaction at 357 and 565 MeV/nucleon show marked improvement.

The Joint Agency Commercial Imagery Evaluation Team and Product Characterization Approach

NASA Technical Reports Server (NTRS)

Zanoni, Vicki; Pagnutti, Mary; Ryan, Robert E.; Snyder, Greg; Lehman, William; Roylance, Spencer

2003-01-01

The Joint Agency Commercial Imagery Evaluation (JACIE) team is a collaborative interagency group focused on the characterization of commercial remote sensing data products. The team members - the National Aeronautics and Space Administration (NASA), the National Imagery and Mapping Agency (NIMA), and the U.S. Geological Survey (USGS) - each have a vested interest in the purchase and use of commercial imagery to support government research and operational applications. For both research and applications, commercial products must be well characterized for precision, accuracy, and repeatability. Since commercial systems are built and operated with no government insight or oversight, the JACIE team provides an independent product characterization of delivered image and image-derived end products. End product characterization differs from the systems calibration approach that is typically used with government systems, where detailed system design information is available. The product characterization approach addresses three primary areas of product performance: geopositional accuracy, image quality, and radiometric accuracy. The JACIE team utilizes well-characterized test sites to support characterization activities. To characterize geopositional accuracy, the team utilizes sites containing several "photo-identifiable" targets and compares their precisely known locations with those defined by the commercial image product. In the area of image quality, spatial response is characterized using edge targets and pulse targets to measure edge response and to estimate image modulation transfer function. Additionally, imagery is also characterized using the National Imagery Interpretability Rating Scale, a means of quantifying the ability to identify certain targets (e.g., rail-cars, airplanes) within an image product. Radiometric accuracy is characterized using reflectance-based vicarious calibration methods at several uniform sites. Each JACIE agency performs an aspect of product characterization based on its area of expertise, thus minimizing duplication of effort. The JACIE team collaborated to perform comprehensive characterization of products from Space Imaging Inc.'s IKONOS satellite and from DigitalGlobe's QuickBird satellite and is currently characterizing products from OrbImage s OrbView-3. JACIE assessments have resulted in several improvements to commercial image product quality and have enhanced working relationships between government and industry. Assessment results are presented at an annual JACIE High Spatial Resolution Commercial Imagery Workshop.

Critical considerations for developing nucleic acid macromolecule based drug products.

PubMed

Muralidhara, Bilikallahalli K; Baid, Rinku; Bishop, Steve M; Huang, Min; Wang, Wei; Nema, Sandeep

2016-03-01

Protein expression therapy using nucleic acid macromolecules (NAMs) as a new paradigm in medicine has recently gained immense therapeutic potential. With the advancement of nonviral delivery it has been possible to target NAMs against cancer, immunodeficiency and infectious diseases. Owing to the complex and fragile structure of NAMs, however, development of a suitable, stable formulation for a reasonable product shelf-life and efficacious delivery is indeed challenging to achieve. This review provides a synopsis of challenges in the formulation and stability of DNA/m-RNA based medicines and probable mitigation strategies including a brief summary of delivery options to the target cells. Nucleic acid based drugs at various stages of ongoing clinical trials are compiled. Copyright © 2016. Published by Elsevier Ltd.

Gold nanoparticles production using reactor and cyclotron based methods in assessment of (196,198)Au production yields by (197)Au neutron absorption for therapeutic purposes.

PubMed

Khorshidi, Abdollah

2016-11-01

Medical nano-gold radioisotopes is produced regularly using high-flux nuclear reactors, and an accelerator-driven neutron activator can turn out higher yield of (197)Au(n,γ)(196,198)Au reactions. Here, nano-gold production via radiative/neutron capture was investigated using irradiated Tehran Research Reactor flux and also simulated proton beam of Karaj cyclotron in Iran. (197)Au nano-solution, including 20nm shaped spherical gold and water, was irradiated under Tehran reactor flux at 2.5E+13n/cm(2)/s for (196,198)Au activity and production yield estimations. Meanwhile, the yield was examined using 30MeV proton beam of Karaj cyclotron via simulated new neutron activator containing beryllium target, bismuth moderator around the target, and also PbF2 reflector enclosed the moderator region. Transmutation in (197)Au nano-solution samples were explored at 15 and 25cm distances from the target. The neutron flux behavior inside the water and bismuth moderators was investigated for nano-gold particles transmutation. The transport of fast neutrons inside bismuth material as heavy nuclei with a lesser lethargy can be contributed in enhanced nano-gold transmutation with long duration time than the water moderator in reactor-based method. Cyclotron-driven production of βeta-emitting radioisotopes for brachytherapy applications can complete the nano-gold production technology as a safer approach as compared to the reactor-based method. Copyright © 2016 Elsevier B.V. All rights reserved.

Doubly Strange Hypernuclei Physics with antiprotons at PANDA

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

Szymanska, K.; Iazzi, F.

2010-04-26

The study of the double hypernuclei will be possible inside the future facility FAIR. A new technique for their production was recently proposed, based on high intensity antiproton beams in connection with a two-target set-up, for the future PANDA experiment at HESR. In particular, the production technique and optimized parameters for the primary target where the hyperon XI{sup -} is produced as well as the expected rates for the stoped XI{sup -} will be discussed.

Design of the MUC-6 Evaluation

DTIC Science & Technology

1996-05-01

also a two- digit code for this product or service, based on the top-level classifica- tion of the Standard Industrial Classification. The TIE_UP...SENATOR FEDERICO ESTRADA VELEZ WAS KIDNAPPED ON 3 APRIL AT THE CORNER OF 60TH AND 48TH STREETS IN WESTERN MEDELLIN , ONLY 100 ME- TERS FROM A...OF INCIDENT COLOMBIA: MEDELLIN (CITY) 17. EFFECT ON PHYSICAL TARGET(S) * 18. EFFECT ON HUMAN TARGET(S) Figure 1: A sample message and associated

Large Scale Accelerator Production of 225Ac: Effective Cross sections for 78-192 MeV Protons Incident on 232Th Targets

DOE PAGES

Griswold, Justin R; Medvedev, Dmitri G.; Engle, Jonathan W.; ...

2016-09-28

Actinium-225 and 213Bi have been used successfully in targeted alpha therapy (TAT) in preclinical and clinical research. This paper is a continuation of research activities aiming to expand the availability of 225Ac. The high energy proton spallation reaction on natural thorium metal target has been utilized to produce millicurie quantities of 225Ac. The results of sixteen irradiation experiments of Th metal at beam energies between 78 and 200 MeV are summarized in this work. Irradiations have been conducted at Brookhaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL), while target dissolution and processing was carried out at Oak Ridgemore » National Laboratory (ORNL). Excitation functions for actinium and thorium isotopes as well as for some of the fission products are presented. The cross sections for production of 225Ac range from 3.6 to 16.7 mb in the incident proton energy range of 78 to 192 MeV. Based on these data, production of Curie quantities of 225Ac is possible by irradiating a 5.0 g cm -2232Th target for 10 days in either BNL or LANL proton irradiation facilities.« less

Impact of cutting meat intake on hidden greenhouse gas emissions in an import-reliant city

NASA Astrophysics Data System (ADS)

Yau, Y. Y.; Thibodeau, B.; Not, C.

2018-06-01

Greenhouse gas emissions embodied in trade is a growing concern for the international community. Multiple studies have highlighted drawbacks in the territorial and production-based accounting of greenhouse gas emissions because it neglects emissions from the consumption of goods in trade. This creates weak carbon leakage and complicates international agreements on emissions regulations. Therefore, we estimated consumption-based emissions using input-output analysis and life cycle assessment to calculate the greenhouse gas emissions hidden in meat and dairy products in Hong Kong, a city predominately reliant on imports. We found that emissions solely from meat and dairy consumption were higher than the city’s total greenhouse gas emissions using conventional production-based calculation. This implies that government reports underestimate more than half of the emissions, as 62% of emissions are embodied in international trade. The discrepancy emphasizes the need of transitioning climate targets and policy to consumption-based accounting. Furthermore, we have shown that dietary change from a meat-heavy diet to a diet in accordance with governmental nutrition guidelines could achieve a 67% reduction in livestock-related emissions, allowing Hong Kong to achieve the Paris Agreement targets for 2030. Consequently, we concluded that consumption-based accounting for greenhouse gas emissions is crucial to target the areas where emissions reduction is realistically achievable, especially for import-reliant cities like Hong Kong.

Hierarchical virtual screening of the dual MMP-2/HDAC-6 inhibitors from natural products based on pharmacophore models and molecular docking.

PubMed

Wang, Yijun; Yang, Limei; Hou, Jiaying; Zou, Qing; Gao, Qi; Yao, Wenhui; Yao, Qizheng; Zhang, Ji

2018-02-12

The dual-target inhibitors tend to improve the response rate in treating tumors, comparing with the single-target inhibitors. Matrix metalloproteinase-2 (MMP-2) and histone deacetylase-6 (HDAC-6) are attractive targets for cancer therapy. In this study, the hierarchical virtual screening of dual MMP-2/HDAC-6 inhibitors from natural products is investigated. The pharmacophore model of MMP-2 inhibitors is built based on ligands, but the pharmacophore model of HDAC-6 inhibitors is built based on the experimental crystal structures of multiple receptor-ligand complexes. The reliability of these two pharmacophore models is validated subsequently. The hierarchical virtual screening, combining these two different pharmacophore models of MMP-2 and HDAC-6 inhibitors with molecular docking, is carried out to identify the dual MMP-2/HDAC-6 inhibitors from a database of natural products. The four potential dual MMP-2/HDAC-6 inhibitors of natural products, STOCK1 N-46177, STOCK1 N-52245, STOCK1 N-55477, and STOCK1 N-69706, are found. The studies of binding modes show that the screened four natural products can simultaneously well bind with the MMP-2 and HDAC-6 active sites by different kinds of interactions, to inhibit the MMP-2 and HDAC-6 activities. In addition, the ADMET properties of screened four natural products are assessed. These found dual MMP-2/HDAC-6 inhibitors of natural products could serve as the lead compounds for designing the new dual MMP-2/HDAC-6 inhibitors having higher biological activities by carrying out structural modifications and optimizations in the future studies.

Use of Natural Products as Chemical Library for Drug Discovery and Network Pharmacology

PubMed Central

Gu, Jiangyong; Gui, Yuanshen; Chen, Lirong; Yuan, Gu; Lu, Hui-Zhe; Xu, Xiaojie

2013-01-01

Background Natural products have been an important source of lead compounds for drug discovery. How to find and evaluate bioactive natural products is critical to the achievement of drug/lead discovery from natural products. Methodology We collected 19,7201 natural products structures, reported biological activities and virtual screening results. Principal component analysis was employed to explore the chemical space, and we found that there was a large portion of overlap between natural products and FDA-approved drugs in the chemical space, which indicated that natural products had large quantity of potential lead compounds. We also explored the network properties of natural product-target networks and found that polypharmacology was greatly enriched to those compounds with large degree and high betweenness centrality. In order to make up for a lack of experimental data, high throughput virtual screening was employed. All natural products were docked to 332 target proteins of FDA-approved drugs. The most potential natural products for drug discovery and their indications were predicted based on a docking score-weighted prediction model. Conclusions Analysis of molecular descriptors, distribution in chemical space and biological activities of natural products was conducted in this article. Natural products have vast chemical diversity, good drug-like properties and can interact with multiple cellular target proteins. PMID:23638153

Quantitative and Systems Pharmacology 3. Network-Based Identification of New Targets for Natural Products Enables Potential Uses in Aging-Associated Disorders.

PubMed

Fang, Jiansong; Gao, Li; Ma, Huili; Wu, Qihui; Wu, Tian; Wu, Jun; Wang, Qi; Cheng, Feixiong

2017-01-01

Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural products. Specifically, we incorporated 411 high-quality aging-associated human genes or human-orthologous genes from mus musculus (MM), saccharomyces cerevisiae (SC), c aenorhabditis elegans (CE), and drosophila melanogaster (DM). We constructed a global drug-target network of natural products by integrating both experimental and computationally predicted drug-target interactions (DTI). We further built the statistical network models for identification of new anti-aging indications of natural products through integration of the curated aging-associated genes and drug-target network of natural products. High accuracy was achieved on the network models. We showcased several network-predicted anti-aging indications of four typical natural products (caffeic acid, metformin, myricetin, and resveratrol) with new mechanism-of-actions. In summary, this study offers a powerful systems pharmacology infrastructure to identify natural products for treatment of aging-associated disorders.

Quantitative and Systems Pharmacology 3. Network-Based Identification of New Targets for Natural Products Enables Potential Uses in Aging-Associated Disorders

PubMed Central

Fang, Jiansong; Gao, Li; Ma, Huili; Wu, Qihui; Wu, Tian; Wu, Jun; Wang, Qi; Cheng, Feixiong

2017-01-01

Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural products. Specifically, we incorporated 411 high-quality aging-associated human genes or human-orthologous genes from mus musculus (MM), saccharomyces cerevisiae (SC), caenorhabditis elegans (CE), and drosophila melanogaster (DM). We constructed a global drug-target network of natural products by integrating both experimental and computationally predicted drug-target interactions (DTI). We further built the statistical network models for identification of new anti-aging indications of natural products through integration of the curated aging-associated genes and drug-target network of natural products. High accuracy was achieved on the network models. We showcased several network-predicted anti-aging indications of four typical natural products (caffeic acid, metformin, myricetin, and resveratrol) with new mechanism-of-actions. In summary, this study offers a powerful systems pharmacology infrastructure to identify natural products for treatment of aging-associated disorders. PMID:29093681

Thin-target excitation functions and optimisation of NCA 64Cu and 66,67Ga production by deuteron induced nuclear reactions on natural zinc target, for radiometabolic therapy and for PET

NASA Astrophysics Data System (ADS)

Groppi, F.; Bonardi, M. L.; Birattari, C.; Gini, L.; Mainardi, C.; Menapace, E.; Abbas, K.; Holzwarth, U.; Stroosnijder, R. M. F.

2004-01-01

A novel method for production of No-Carrier-Added 64Cu and 66,67Ga has been developed, based on reactions induced by deuterons up to 19 MeV on Zn target. HPGe and beta (by LSC) spectrometries proved very effective to determine radionuclidic purity of 64Cu and 66,67Ga fractions. Experimental specific activity for 64Cu was measured by ET-AAS and was of the order of 700 MBq · μg -1. Radiochemical yields for 64Cu and 66,67Ga were >80% and >99%.

Skin exposure to deodorants/antiperspirants in aerosol form.

PubMed

Steiling, W; Buttgereit, P; Hall, B; O'Keeffe, L; Safford, B; Tozer, S; Coroama, M

2012-06-01

Many cosmetic products are available in spray form. Even though the principal targets of these products are the skin and hair, spraying leads to the partitioning of the product between the target and the surrounding air. In the previous COLIPA study (Hall et al., 2007) the daily use of deodorant/antiperspirant (Deo/AP) in spray form was quantified in terms of the amount of product dispensed from the spray can, without specifically quantifying the product fraction reaching the skin during use. Results of the present study provide this additional information, necessary for a reliable safety assessment of sprayed Deo/AP products. In a novel experimental approach the information obtained from real-life movement analysis (automated motion imaging) of volunteers using their own products was integrated with the aerosol cloud sampling data obtained from the same products, leading to the computation of the product deposited on the skin. The 90th percentile values, expressed as percent deposition relative to the can weight loss after spraying, are 23.5% and 11.4% for ethanol-based and non-ethanol-based products, respectively. Additionally, the study has generated data on the skin area covered by the products, spray duration time, spray angle and spray distance from the skin. Copyright © 2012 Elsevier Ltd. All rights reserved.

Three-Dimensional Reconstruction of the Virtual Plant Branching Structure Based on Terrestrial LIDAR Technologies and L-System

NASA Astrophysics Data System (ADS)

Gong, Y.; Yang, Y.; Yang, X.

2018-04-01

For the purpose of extracting productions of some specific branching plants effectively and realizing its 3D reconstruction, Terrestrial LiDAR data was used as extraction source of production, and a 3D reconstruction method based on Terrestrial LiDAR technologies combined with the L-system was proposed in this article. The topology structure of the plant architectures was extracted using the point cloud data of the target plant with space level segmentation mechanism. Subsequently, L-system productions were obtained and the structural parameters and production rules of branches, which fit the given plant, was generated. A three-dimensional simulation model of target plant was established combined with computer visualization algorithm finally. The results suggest that the method can effectively extract a given branching plant topology and describes its production, realizing the extraction of topology structure by the computer algorithm for given branching plant and also simplifying the extraction of branching plant productions which would be complex and time-consuming by L-system. It improves the degree of automation in the L-system extraction of productions of specific branching plants, providing a new way for the extraction of branching plant production rules.

Monoterpene biosynthesis potential of plant subcellular compartments.

PubMed

Dong, Lemeng; Jongedijk, Esmer; Bouwmeester, Harro; Van Der Krol, Alexander

2016-01-01

Subcellular monoterpene biosynthesis capacity based on local geranyl diphosphate (GDP) availability or locally boosted GDP production was determined for plastids, cytosol and mitochondria. A geraniol synthase (GES) was targeted to plastids, cytosol, or mitochondria. Transient expression in Nicotiana benthamiana indicated local GDP availability for each compartment but resulted in different product levels. A GDP synthase from Picea abies (PaGDPS1) was shown to boost GDP production. PaGDPS1 was also targeted to plastids, cytosol or mitochondria and PaGDPS1 and GES were coexpressed in all possible combinations. Geraniol and geraniol-derived products were analyzed by GC-MS and LC-MS, respectively. GES product levels were highest for plastid-targeted GES, followed by mitochondrial- and then cytosolic-targeted GES. For each compartment local boosting of GDP biosynthesis increased GES product levels. GDP exchange between compartments is not equal: while no GDP is exchanged from the cytosol to the plastids, 100% of GDP in mitochondria can be exchanged to plastids, while only 7% of GDP from plastids is available for mitochondria. This suggests a direct exchange mechanism for GDP between plastids and mitochondria. Cytosolic PaGDPS1 competes with plastidial GES activity, suggesting an effective drain of isopentenyl diphosphate from the plastids to the cytosol. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective.

PubMed

Li, Ying Hong; Wang, Pan Pan; Li, Xiao Xu; Yu, Chun Yan; Yang, Hong; Zhou, Jin; Xue, Wei Wei; Tan, Jun; Zhu, Feng

2016-01-01

The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

Cooperative fuzzy games approach to setting target levels of ECs in quality function deployment.

PubMed

Yang, Zhihui; Chen, Yizeng; Yin, Yunqiang

2014-01-01

Quality function deployment (QFD) can provide a means of translating customer requirements (CRs) into engineering characteristics (ECs) for each stage of product development and production. The main objective of QFD-based product planning is to determine the target levels of ECs for a new product or service. QFD is a breakthrough tool which can effectively reduce the gap between CRs and a new product/service. Even though there are conflicts among some ECs, the objective of developing new product is to maximize the overall customer satisfaction. Therefore, there may be room for cooperation among ECs. A cooperative game framework combined with fuzzy set theory is developed to determine the target levels of the ECs in QFD. The key to develop the model is the formulation of the bargaining function. In the proposed methodology, the players are viewed as the membership functions of ECs to formulate the bargaining function. The solution for the proposed model is Pareto-optimal. An illustrated example is cited to demonstrate the application and performance of the proposed approach.

Cooperative Fuzzy Games Approach to Setting Target Levels of ECs in Quality Function Deployment

PubMed Central

Yang, Zhihui; Chen, Yizeng; Yin, Yunqiang

2014-01-01

Quality function deployment (QFD) can provide a means of translating customer requirements (CRs) into engineering characteristics (ECs) for each stage of product development and production. The main objective of QFD-based product planning is to determine the target levels of ECs for a new product or service. QFD is a breakthrough tool which can effectively reduce the gap between CRs and a new product/service. Even though there are conflicts among some ECs, the objective of developing new product is to maximize the overall customer satisfaction. Therefore, there may be room for cooperation among ECs. A cooperative game framework combined with fuzzy set theory is developed to determine the target levels of the ECs in QFD. The key to develop the model is the formulation of the bargaining function. In the proposed methodology, the players are viewed as the membership functions of ECs to formulate the bargaining function. The solution for the proposed model is Pareto-optimal. An illustrated example is cited to demonstrate the application and performance of the proposed approach. PMID:25097884

Approaches to the identification of new nonhormonal targets for male contraception.

PubMed

Kopf, Gregory S

2008-10-01

Fertility control is a global health issue with major personal and societal impact. Although, currently, there are several different options for contraception, the technologies behind these are antiquated, and the options for male-based contraception (i.e., withdrawal, condom and vasectomy) are inadequate. The genomic, proteomic and bioinformatic revolutions have provided new tools and new targets for contraceptive development, and the results of such approaches have identified gene products that play critical roles in male reproduction, thus expanding the array of potential targets for novel and innovative male-based contraceptives. This article will review the types of targets being considered in the development of nonhormonal male contraceptives and the technologies used to identify and validate these targets.

Chemical proteomics approaches for identifying the cellular targets of natural products

PubMed Central

Sieber, S. A.

2016-01-01

Covering: 2010 up to 2016 Deconvoluting the mode of action of natural products and drugs remains one of the biggest challenges in chemistry and biology today. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to understand protein function. In the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of small molecules in live cells. Here, we highlight recent examples of chemical probes based on natural products and their application for target identification. The review focuses on probes that can be covalently linked to their target proteins (either via intrinsic chemical reactivity or via the introduction of photocrosslinkers), and can be applied “in situ” – in living systems rather than cell lysates. We also focus here on strategies that employ a click reaction, the copper-catalysed azide–alkyne cycloaddition reaction (CuAAC), to allow minimal functionalisation of natural product scaffolds with an alkyne or azide tag. We also discuss ‘competitive mode’ approaches that screen for natural products that compete with a well-characterised chemical probe for binding to a particular set of protein targets. Fuelled by advances in mass spectrometry instrumentation and bioinformatics, many modern strategies are now embracing quantitative proteomics to help define the true interacting partners of probes, and we highlight the opportunities this rapidly evolving technology provides in chemical proteomics. Finally, some of the limitations and challenges of chemical proteomics approaches are discussed. PMID:27098809

Chemical proteomics approaches for identifying the cellular targets of natural products.

PubMed

Wright, M H; Sieber, S A

2016-05-04

Covering: 2010 up to 2016Deconvoluting the mode of action of natural products and drugs remains one of the biggest challenges in chemistry and biology today. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to understand protein function. In the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of small molecules in live cells. Here, we highlight recent examples of chemical probes based on natural products and their application for target identification. The review focuses on probes that can be covalently linked to their target proteins (either via intrinsic chemical reactivity or via the introduction of photocrosslinkers), and can be applied "in situ" - in living systems rather than cell lysates. We also focus here on strategies that employ a click reaction, the copper-catalysed azide-alkyne cycloaddition reaction (CuAAC), to allow minimal functionalisation of natural product scaffolds with an alkyne or azide tag. We also discuss 'competitive mode' approaches that screen for natural products that compete with a well-characterised chemical probe for binding to a particular set of protein targets. Fuelled by advances in mass spectrometry instrumentation and bioinformatics, many modern strategies are now embracing quantitative proteomics to help define the true interacting partners of probes, and we highlight the opportunities this rapidly evolving technology provides in chemical proteomics. Finally, some of the limitations and challenges of chemical proteomics approaches are discussed.

Unsold is unseen … or is it? Examining the role of peripheral vision in the consumer choice process using eye-tracking methodology.

PubMed

Wästlund, Erik; Shams, Poja; Otterbring, Tobias

2018-01-01

In visual marketing, the truism that "unseen is unsold" means that products that are not noticed will not be sold. This truism rests on the idea that the consumer choice process is heavily influenced by visual search. However, given that the majority of available products are not seen by consumers, this article examines the role of peripheral vision in guiding attention during the consumer choice process. In two eye-tracking studies, one conducted in a lab facility and the other conducted in a supermarket, the authors investigate the role and limitations of peripheral vision. The results show that peripheral vision is used to direct visual attention when discriminating between target and non-target objects in an eye-tracking laboratory. Target and non-target similarity, as well as visual saliency of non-targets, constitute the boundary conditions for this effect, which generalizes from instruction-based laboratory tasks to preference-based choice tasks in a real supermarket setting. Thus, peripheral vision helps customers to devote a larger share of attention to relevant products during the consumer choice process. Taken together, the results show how the creation of consideration set (sets of possible choice options) relies on both goal-directed attention and peripheral vision. These results could explain how visually similar packaging positively influences market leaders, while making novel brands almost invisible on supermarket shelves. The findings show that even though unsold products might be unseen, in the sense that they have not been directly observed, they might still have been evaluated and excluded by means of peripheral vision. This article is based on controlled lab experiments as well as a field study conducted in a complex retail environment. Thus, the findings are valid both under controlled and ecologically valid conditions. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A target design for irradiation of NaI at high beam current.

NASA Technical Reports Server (NTRS)

Blue, J. W.; Sodd, V. J.

1972-01-01

A solution to the targetry problems encountered when the iodine nucleus is a target for cyclotron irradiation is given as a new target design. A target based on this design has been used in 30 microampere irradiations of 46 MeV alpha particles for one-half hour without significant damage. Such an irradiation produces 6 to 7 mCi of Cs-129, an isotope useful in nuclear medicine. This target should also be considered for cyclotron production of the radioisotopes Cs-127, I-123, and Xe-127.

Ligation with Nucleic Acid Sequence–Based Amplification

PubMed Central

Ong, Carmichael; Tai, Warren; Sarma, Aartik; Opal, Steven M.; Artenstein, Andrew W.; Tripathi, Anubhav

2012-01-01

This work presents a novel method for detecting nucleic acid targets using a ligation step along with an isothermal, exponential amplification step. We use an engineered ssDNA with two variable regions on the ends, allowing us to design the probe for optimal reaction kinetics and primer binding. This two-part probe is ligated by T4 DNA Ligase only when both parts bind adjacently to the target. The assay demonstrates that the expected 72-nt RNA product appears only when the synthetic target, T4 ligase, and both probe fragments are present during the ligation step. An extraneous 38-nt RNA product also appears due to linear amplification of unligated probe (P3), but its presence does not cause a false-positive result. In addition, 40 mmol/L KCl in the final amplification mix was found to be optimal. It was also found that increasing P5 in excess of P3 helped with ligation and reduced the extraneous 38-nt RNA product. The assay was also tested with a single nucleotide polymorphism target, changing one base at the ligation site. The assay was able to yield a negative signal despite only a single-base change. Finally, using P3 and P5 with longer binding sites results in increased overall sensitivity of the reaction, showing that increasing ligation efficiency can improve the assay overall. We believe that this method can be used effectively for a number of diagnostic assays. PMID:22449695

Environmentally Responsible Microbiological Production of Energetic Ingredients

DTIC Science & Technology

2007-11-01

effort was to develop an environmentally benign and economical microbial process for nitro-energetics production . The specific targets of this method...microbial production of nitro-based EM. As the processes and compounds of choice, RDX/HMX (nitramine) generation was selected. Microorganisms capable of...Current synthetic methods for the production of RDX and HMX utilize hexamine as the precursor. Hexamine is an industrial chemical available on a large

Design of the Next Generation Target at the Lujan Neutron Scattering Center, LANSCE

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

Ferres, Laurent

Los Alamos National Laboratory (LANL) supports scientific research in many diverse fields such as biology, chemistry, and nuclear science. The Laboratory was established in 1943 during the Second World War to develop nuclear weapons. Today, LANL is one of the largest laboratories dedicated to nuclear defense and operates an 800 MeV proton linear accelerator for basic and applied research including: production of high- and low-energy neutrons beams, isotope production for medical applications and proton radiography. This accelerator is located at the Los Alamos Neutron Science Center (LANSCE). The work performed involved the redesign of the target for the low-energy neutronmore » source at the Lujan Neutron Scattering Center, which is one of the facilities built around the accelerator. The redesign of the target involves modeling various arrangements of the moderator-reflector-shield for the next generation neutron production target. This is done using Monte Carlo N-Particle eXtended (MCNPX), and ROOT analysis framework, a C++ based-software, to analyze the results.« less

RNAi Experiments in D. melanogaster: Solutions to the Overlooked Problem of Off-Targets Shared by Independent dsRNAs

PubMed Central

Seinen, Erwin; Burgerhof, Johannes G. M.; Jansen, Ritsert C.; Sibon, Ody C. M.

2010-01-01

Background RNAi technology is widely used to downregulate specific gene products. Investigating the phenotype induced by downregulation of gene products provides essential information about the function of the specific gene of interest. When RNAi is applied in Drosophila melanogaster or Caenorhabditis elegans, often large dsRNAs are used. One of the drawbacks of RNAi technology is that unwanted gene products with sequence similarity to the gene of interest can be down regulated too. To verify the outcome of an RNAi experiment and to avoid these unwanted off-target effects, an additional non-overlapping dsRNA can be used to down-regulate the same gene. However it has never been tested whether this approach is sufficient to reduce the risk of off-targets. Methodology We created a novel tool to analyse the occurance of off-target effects in Drosophila and we analyzed 99 randomly chosen genes. Principal Findings Here we show that nearly all genes contain non-overlapping internal sequences that do show overlap in a common off-target gene. Conclusion Based on our in silico findings, off-target effects should not be ignored and our presented on-line tool enables the identification of two RNA interference constructs, free of overlapping off-targets, from any gene of interest. PMID:20957038

Network pharmacology-based virtual screening of natural products from Clerodendrum species for identification of novel anti-cancer therapeutics.

PubMed

Gogoi, Barbi; Gogoi, Dhrubajyoti; Silla, Yumnam; Kakoti, Bibhuti Bhushan; Bhau, Brijmohan Singh

2017-01-31

Plant-derived natural products (NPs) play a vital role in the discovery of new drug molecules and these are used for development of novel therapeutic drugs for a specific disease target. Literature review suggests that natural products possess strong inhibitory efficacy against various types of cancer cells. Clerodendrum indicum and Clerodendrum serratum are reported to have anticancer activity; therefore a study was carried out to identify selective anticancer agents from these plants species. In this report, we employed a docking weighted network pharmacological approach to understand the multi-therapeutics potentiality of C. indicum and C. serratum against various types of cancer. A library of 53 natural products derived from these plants was compiled from the literature and three dimensional space analyses were performed in order to establish the drug-likeness of the NPs library. Further, an NPs-cancer network was built based on docking. We predicted five compounds, namely apigenin 7-glucoside, hispidulin, scutellarein-7-O-beta-d-glucuronate, acteoside and verbascoside, to be potential binding therapeutics for cancer target proteins. Apigenin 7-glucoside and hispidulin were found to have maximum binding interactions (relationship) with 17 cancer drug targets in terms of docking weighted network pharmacological analysis. Hence, we used an integrative approach obtained from network pharmacology for identifying combinatorial drug actions against the cancer targets. We believe that our present study may provide important clues for finding novel drug inhibitors for cancer.

An incentive plan for professional fee collections at an indigent-care teaching hospital.

PubMed

Stewart, M G; Jones, D B; Garson, A T

2001-11-01

The authors describe the implementation and development of an incentive plan to improve professional fee collections at an indigent-care teaching hospital. They theorized that an incentive plan based on relative value unit (RVU) productivity would increase billings and collections of professional fees. Unique RVU targets were set for individual services based on the number of faculty full-time equivalents and average reported productivity for academic physicians by specialty. The incentive plan was based on the level of expected faculty billings, measured in RVUs, for each department. A "base + incentive" model was used, with the base budget being distributed monthly throughout the year, and the incentive held as a "withhold" to be paid at the year's end only if the billing target in RVUs was met. Additionally, a task force worked with physician billing office and the hospital to improve collections. In the first year after implementation of the system was in place, important increases were noted in total RVU productivity (30.5% over the previous year) and in collections (49.5% over the previous year). Sixteen of 23 departments exceeded their incentive targets, and it was possible to make distributions of professional fees to those departments, to be used within the hospital system to enhance clinical services. Moreover, the plan created an overall positive attitude toward billings and documentation of faculty activities. The authors believe that this kind of incentive plan will be increasingly important for academic faculty working in public hospital systems.

Large scale accelerator production of 225Ac: Effective cross sections for 78-192MeV protons incident on 232Th targets.

PubMed

Griswold, J R; Medvedev, D G; Engle, J W; Copping, R; Fitzsimmons, J M; Radchenko, V; Cooley, J C; Fassbender, M E; Denton, D L; Murphy, K E; Owens, A C; Birnbaum, E R; John, K D; Nortier, F M; Stracener, D W; Heilbronn, L H; Mausner, L F; Mirzadeh, S

2016-12-01

Actinium-225 and 213 Bi have been used successfully in targeted alpha therapy (TAT) in preclinical and clinical research. This paper is a continuation of research activities aiming to expand the availability of 225 Ac. The high-energy proton spallation reaction on natural thorium metal targets has been utilized to produce millicurie quantities of 225 Ac. The results of sixteen irradiation experiments of thorium metal at beam energies between 78 and 192MeV are summarized in this work. Irradiations have been conducted at Brookhaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL), while target dissolution and processing was carried out at Oak Ridge National Laboratory (ORNL). Excitation functions for actinium and thorium isotopes, as well as for some of the fission products, are presented. The cross sections for production of 225 Ac range from 3.6 to 16.7mb in the incident proton energy range of 78-192MeV. Based on these data, production of curie quantities of 225 Ac is possible by irradiating a 5.0gcm -2 232 Th target for 10 days in either BNL or LANL proton irradiation facilities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Engineering cell factories for producing building block chemicals for bio-polymer synthesis.

PubMed

Tsuge, Yota; Kawaguchi, Hideo; Sasaki, Kengo; Kondo, Akihiko

2016-01-21

Synthetic polymers are widely used in daily life. Due to increasing environmental concerns related to global warming and the depletion of oil reserves, the development of microbial-based fermentation processes for the production of polymer building block chemicals from renewable resources is desirable to replace current petroleum-based methods. To this end, strains that efficiently produce the target chemicals at high yields and productivity are needed. Recent advances in metabolic engineering have enabled the biosynthesis of polymer compounds at high yield and productivities by governing the carbon flux towards the target chemicals. Using these methods, microbial strains have been engineered to produce monomer chemicals for replacing traditional petroleum-derived aliphatic polymers. These developments also raise the possibility of microbial production of aromatic chemicals for synthesizing high-performance polymers with desirable properties, such as ultraviolet absorbance, high thermal resistance, and mechanical strength. In the present review, we summarize recent progress in metabolic engineering approaches to optimize microbial strains for producing building blocks to synthesize aliphatic and high-performance aromatic polymers.

Identification and validation nucleolin as a target of curcumol in nasopharyngeal carcinoma cells.

PubMed

Wang, Juan; Wu, Jiacai; Li, Xumei; Liu, Haowei; Qin, Jianli; Bai, Zhun; Chi, Bixia; Chen, Xu

2018-06-30

Identification of the specific protein target(s) of a drug is a critical step in unraveling its mechanisms of action (MOA) in many natural products. Curcumol, isolated from well known Chinese medicinal plant Curcuma zedoary, has been shown to possess multiple biological activities. It can inhibit nasopharyngeal carcinoma (NPC) proliferation and induce apoptosis, but its target protein(s) in NPC cells remains unclear. In this study, we employed a mass spectrometry-based chemical proteomics approach reveal the possible protein targets of curcumol in NPC cells. Cellular thermal shift assay (CETSA), molecular docking and cell-based assay was used to validate the binding interactions. Chemical proteomics capturing uncovered that NCL is a target of curcumol in NPC cells, Molecular docking showed that curcumol bound to NCL with an -7.8 kcal/mol binding free energy. Cell function analysis found that curcumol's treatment leads to a degradation of NCL in NPC cells, and it showed slight effects on NP69 cells. In conclusion, our results providing evidences that NCL is a target protein of curcumol. We revealed that the anti-cancer effects of curcumol in NPC cells are mediated, at least in part, by NCL inhibition. Many natural products showed high bioactivity, while their mechanisms of action (MOA) are very poor or completely missed. Understanding the MOA of natural drugs can thoroughly exploit their therapeutic potential and minimize their adverse side effects. Identification of the specific protein target(s) of a drug is a critical step in unraveling its MOA. Compound-centric chemical proteomics is a classic chemical proteomics approach which integrates chemical synthesis with cell biology and mass spectrometry (MS) to identify protein targets of natural products determine the drug mechanism of action, describe its toxicity, and figure out the possible cause of off-target. It is an affinity-based chemical proteomics method to identify small molecule-protein interactions through affinity chromatography approach coupled with mass spectrometry, has been conventionally used to identify target proteins and has yielded good results. Curcumol, has shown effective inhibition on Nasopharyngeal Carcinoma (NPC) Cells, interacted with NCL and then initiated the anti-tumor biological effect. This research demonstrated the effectiveness of chemical proteomics approaches in natural drugs molecular target identification, revealing and understanding of the novel mechanism of actions of curcumol is crucial for cancer prevention and treatment in nasopharynx cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

Performance of ASML YieldStar μDBO overlay targets for advanced lithography nodes C028 and C014 overlay process control

NASA Astrophysics Data System (ADS)

Blancquaert, Yoann; Dezauzier, Christophe; Depre, Jerome; Miqyass, Mohamed; Beltman, Jan

2013-04-01

Continued tightening of overlay control budget in semiconductor lithography drives the need for improved metrology capabilities. Aggressive improvements are needed for overlay metrology speed, accuracy and precision. This paper is dealing with the on product metrology results of a scatterometry based platform showing excellent production results on resolution, precision, and tool matching for overlay. We will demonstrate point to point matching between tool generations as well as between target sizes and types. Nowadays, for the advanced process nodes a lot of information is needed (Higher order process correction, Reticle fingerprint, wafer edge effects) to quantify process overlay. For that purpose various overlay sampling schemes are evaluated: ultra- dense, dense and production type. We will show DBO results from multiple target type and shape for on product overlay control for current and future node down to at least 14 nm node. As overlay requirements drive metrology needs, we will evaluate if the new metrology platform meets the overlay requirements.

Au and Pt nanoparticle supported catalysts tailored for H-2 production: From models to powder catalysts

DOE PAGES

T. D. Nguyen-Phan; Baber, A. E.; Rodriguez, J. A.; ...

2015-12-10

The use of metal nanoparticles (NPs), including Au and Pt, supported over oxides has been pivotal, and is ever increasing in enabling catalytic reactions which target the production of hydrogen. We review here the most recent works pertaining to the fundamental understanding of the structure, morphology, growth, characterization, and intrinsic phenomenological properties of Au– and Pt– based catalysts that influence the reactivity and selectivity to target hydrogen production. We draw on surface science and theoretical methods of model and powder catalysts using high resolution imaging, spectroscopy, scattering experiments, and theoretical studies. Based on these insights we identify key aspects ofmore » studies of supported metal nanoparticle (NP) catalysts for several reactions. The main focus of this review is on the intersection of catalytic chemistry related to the water-gas shift (WGS), oxygenate steam reforming (OSR), and solarassisted reactions (SAR).« less

Drug target identification in protozoan parasites.

PubMed

Müller, Joachim; Hemphill, Andrew

2016-08-01

Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses.

Proton irradiation of beryllium deposits on different candidate materials to be used as a neutron production target for accelerator-based BNCT

NASA Astrophysics Data System (ADS)

Gagetti, Leonardo; Anzorena, Manuel Suarez; Bertolo, Alma; del Grosso, Mariela; Kreiner, Andrés J.

2017-12-01

Thin Be targets for neutron production through Be(d,n) are produced and characterized. We improved and characterized the substrate surface, specifically the roughness, in order to achieve homogeneous and stable deposits. Once well bonded deposits were obtained, some of them were irradiated with a 150 keV proton beam and with a 1.45 MeV deuteron beam. Both deposits, pristine and irradiated, were characterized by profilometry, X-ray diffraction, scanning electron microscopy and electron probe microanalyzer.

Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

PubMed

Stegemann, Sven

2018-06-01

The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

The Variation of Work Productivity and Muscle Activities at Different Levels of Production Target

NASA Astrophysics Data System (ADS)

Nur, Nurhayati Mohd; Dawal, Siti Zawiah Md; Dahari, Mahidzal; Zuhairah Mahmud Zuhudi, Nurul

2017-10-01

This paper aims to investigate the variation of work productivity and muscle activities among workers performing industrial repetitive tasks at four different levels of production target. The work productivity and muscle activities data were recorded from twenty workers at four levels of production target corresponding to “participative (PS1)”, “normal (PS2)”, “high (PS3)” and “very high (PS4)”. The results showed that worker productivity was found to increase at higher production target and there was a significant change (p < 0.005) in work productivity across the four different production targets. The muscle activities were found to increase at higher production target and correspond to more discomfort and a higher rate of muscle fatigue. The results indicated that working with a higher production target results in higher worker productivity, but could lead to higher risk of WMSDs.

Polymerase chain reaction assay for verifying the labeling of meat and commercial meat products from game birds targeting specific sequences from the mitochondrial D-loop region.

PubMed

Rojas, M; González, I; Pavón, M A; Pegels, N; Hernández, P E; García, T; Martín, R

2010-05-01

A PCR assay was developed for the identification of meats and commercial meat products from quail (Coturnix coturnix), pheasant (Phasianus colchicus), partridge (Alectoris spp.), guinea fowl (Numida meleagris), pigeon (Columba spp.), Eurasian woodcock (Scolopax rusticola), and song thrush (Turdus philomelos) based on oligonucleotide primers targeting specific sequences from the mitochondrial D-loop region. The primers designed generated specific fragments of 96, 100, 104, 106, 147, 127, and 154 bp in length for quail, pheasant, partridge, guinea fowl, pigeon, Eurasian woodcock, and song thrush tissues, respectively. The specificity of each primer pair was tested against DNA from various game and domestic species. In this work, satisfactory amplification was accomplished in the analysis of experimentally pasteurized (72 degrees C for 30 min) and sterilized (121 degrees C for 20 min) meats, as well as in commercial meat products from the target species. The technique was also applied to raw and sterilized muscular binary mixtures, with a detection limit of 0.1% (wt/wt) for each of the targeted species. The proposed PCR assay represents a rapid and straightforward method for the detection of possible mislabeling in game bird meat products.

A systematic approach to identify therapeutic effects of natural products based on human metabolite information.

PubMed

Noh, Kyungrin; Yoo, Sunyong; Lee, Doheon

2018-06-13

Natural products have been widely investigated in the drug development field. Their traditional use cases as medicinal agents and their resemblance of our endogenous compounds show the possibility of new drug development. Many researchers have focused on identifying therapeutic effects of natural products, yet the resemblance of natural products and human metabolites has been rarely touched. We propose a novel method which predicts therapeutic effects of natural products based on their similarity with human metabolites. In this study, we compare the structure, target and phenotype similarities between natural products and human metabolites to capture molecular and phenotypic properties of both compounds. With the generated similarity features, we train support vector machine model to identify similar natural product and human metabolite pairs. The known functions of human metabolites are then mapped to the paired natural products to predict their therapeutic effects. With our selected three feature sets, structure, target and phenotype similarities, our trained model successfully paired similar natural products and human metabolites. When applied to the natural product derived drugs, we could successfully identify their indications with high specificity and sensitivity. We further validated the found therapeutic effects of natural products with the literature evidence. These results suggest that our model can match natural products to similar human metabolites and provide possible therapeutic effects of natural products. By utilizing the similar human metabolite information, we expect to find new indications of natural products which could not be covered by previous in silico methods.

Antibody Targeting of Caveolae in Breast Tumors

DTIC Science & Technology

2004-08-01

regulatory cofactor NHE-RF2; P2X7, " P2X purinergic receptor 7; Podo, podocalyxin; RAGE, receptor for advanced glycation end products; STR, seven...subtractive proteomics and molecular imaging in vivo." (San Diego, CA) 2004 Keystone Symposia, G-Protein-Coupled Receptors : Evolving Concepts and Drug...34 (Rochester, MN) 8 Schnitzer, Jan E., M.D. DAMD 1-02-1-0563 2004 Second International Conference on Vascular Targeting, Ligand Based Vascular Targeting

Degradable Magnetic Composites for Minimally Invasive Interventions: Device Fabrication, Targeted Drug Delivery, and Cytotoxicity Tests.

PubMed

Peters, Christian; Hoop, Marcus; Pané, Salvador; Nelson, Bradley J; Hierold, Christofer

2016-01-20

Superparamagnetic nanoparticles and a functional, degradable polymer matrix based on poly(ethylene glycol) are combined to enable fully degradable magnetic microdevices for minimally invasive biomedical applications. A bioinspired helical microrobot platform mimicking Escherichia coli bacteria is fabricated and actuated using weak rotating magnetic fields. Locomotion based on corkscrew propulsion, targeted drug delivery, and low-degradation-product cytotoxicity are demonstrated. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

One size does not fit all: how the tobacco industry has altered cigarette design to target consumer groups with specific psychological and psychosocial needs.

PubMed

Cook, Benjamin Lê; Wayne, Geoffrey Ferris; Keithly, Lois; Connolly, Gregory

2003-11-01

To identify whether the tobacco industry has targeted cigarette product design towards individuals with varying psychological/psychosocial needs. Internal industry documents were identified through searches of an online archival document research tool database using relevancy criteria of consumer segmentation and needs assessment. The industry segmented consumer markets based on psychological needs (stress relief, behavioral arousal, performance enhancement, obesity reduction) and psychosocial needs (social acceptance, personal image). Associations between these segments and smoking behaviors, brand and design preferences were used to create cigarette brands targeting individuals with these needs. Cigarette brands created to address the psychological/psychosocial needs of smokers may increase the likelihood of smoking initiation and addiction. Awareness of targeted product development will improve smoking cessation and prevention efforts.

Mitigation Strategies for Greenhouse Gas Emissions from Agriculture and Land-Use Change: Consequences for Food Prices.

PubMed

Stevanović, Miodrag; Popp, Alexander; Bodirsky, Benjamin Leon; Humpenöder, Florian; Müller, Christoph; Weindl, Isabelle; Dietrich, Jan Philipp; Lotze-Campen, Hermann; Kreidenweis, Ulrich; Rolinski, Susanne; Biewald, Anne; Wang, Xiaoxi

2017-01-03

The land use sector of agriculture, forestry, and other land use (AFOLU) plays a central role in ambitious climate change mitigation efforts. Yet, mitigation policies in agriculture may be in conflict with food security related targets. Using a global agro-economic model, we analyze the impacts on food prices under mitigation policies targeting either incentives for producers (e.g., through taxes) or consumer preferences (e.g., through education programs). Despite having a similar reduction potential of 43-44% in 2100, the two types of policy instruments result in opposite outcomes for food prices. Incentive-based mitigation, such as protecting carbon-rich forests or adopting low-emission production techniques, increase land scarcity and production costs and thereby food prices. Preference-based mitigation, such as reduced household waste or lower consumption of animal-based products, decreases land scarcity, prevents emissions leakage, and concentrates production on the most productive sites and consequently lowers food prices. Whereas agricultural emissions are further abated in the combination of these mitigation measures, the synergy of strategies fails to substantially lower food prices. Additionally, we demonstrate that the efficiency of agricultural emission abatement is stable across a range of greenhouse-gas (GHG) tax levels, while resulting food prices exhibit a disproportionally larger spread.

Toddler foods, children's foods: assessing sodium in packaged supermarket foods targeted at children.

PubMed

Elliott, Charlene D; Conlon, Martin J

2011-03-01

To critically examine child-oriented packaged food products sold in Canada for their sodium content, and to assess them light of intake recommendations, the current policy context and suggested targets. Baby/toddler foods (n 186) and child-oriented packaged foods (n 354) were coded for various attributes (including sodium). Summary statistics were created for sodium, then the children's food products were compared with the UK Food Standards Agency (FSA) 'targets' for sodium in packaged foods. Also assessed were the products' per-serving sodium levels were assessed in light of the US Institute of Medicine's dietary reference intakes and Canada's Food Guide. Calgary, Alberta, Canada. None. Twenty per cent of products could be classified as having high sodium levels. Certain sub-categories of food (i.e. toddler entrées, children's packaged lunches, soups and canned pastas) were problematic. Significantly, when scaled in according to Schedule M or viewed in light of the serving sizes on the Nutrition Facts table, the sodium level in various dry goods products generally fell within, and below, the Adequate Intake (AI)/Tolerable Upper Intake Level (UL) band for sodium. When scaled in accordance with the UK FSA targets, however, none of the (same) products met the targets. In light of AI/UL thresholds based on age and per-serving cut-offs, packaged foodstuffs for youngsters fare relatively well, with the exception of some problematic areas. 'Stealth sodium' and 'subtle sodium' are important considerations; so is use of the FSA's scaling method to evaluate sodium content, because it is highly sensitive to the difference between the reference amount and the actual real-world serving size for the product being considered.

Towards environmentally sustainable human behaviour: targeting non-conscious and conscious processes for effective and acceptable policies

NASA Astrophysics Data System (ADS)

Marteau, Theresa M.

2017-05-01

Meeting climate change targets to limit global warming to 2°C requires rapid and large reductions in demand for products that most contribute to greenhouse gas (GHG) emissions. These include production of bulk materials (e.g. steel and cement), energy supply (e.g. fossil fuels) and animal source foods (particularly ruminants and their products). Effective strategies to meet these targets require transformative changes in supply as well as demand, involving changes in economic, political and legal systems at local, national and international levels, building on evidence from many disciplines. This paper outlines contributions from behavioural science in reducing demand. Grounded in dual-process models of human behaviour (involving non-conscious and conscious processes) this paper considers first why interventions aimed at changing population values towards the environment are usually insufficient or unnecessary for reducing demand although they may be important in increasing public acceptability of policies that could reduce demand. It then outlines two sets of evidence from behavioural science towards effective systems-based strategies, to identify interventions likely to be effective at: (i) reducing demand for products that contribute most to GHG emissions, mainly targeting non-conscious processes and (ii) increasing public acceptability for policy changes to enable these interventions, targeting conscious processes. This article is part of the themed issue 'Material demand reduction'.

Towards environmentally sustainable human behaviour: targeting non-conscious and conscious processes for effective and acceptable policies.

PubMed

Marteau, Theresa M

2017-06-13

Meeting climate change targets to limit global warming to 2°C requires rapid and large reductions in demand for products that most contribute to greenhouse gas (GHG) emissions. These include production of bulk materials (e.g. steel and cement), energy supply (e.g. fossil fuels) and animal source foods (particularly ruminants and their products). Effective strategies to meet these targets require transformative changes in supply as well as demand, involving changes in economic, political and legal systems at local, national and international levels, building on evidence from many disciplines. This paper outlines contributions from behavioural science in reducing demand. Grounded in dual-process models of human behaviour (involving non-conscious and conscious processes) this paper considers first why interventions aimed at changing population values towards the environment are usually insufficient or unnecessary for reducing demand although they may be important in increasing public acceptability of policies that could reduce demand. It then outlines two sets of evidence from behavioural science towards effective systems-based strategies, to identify interventions likely to be effective at: (i) reducing demand for products that contribute most to GHG emissions, mainly targeting non-conscious processes and (ii) increasing public acceptability for policy changes to enable these interventions, targeting conscious processes.This article is part of the themed issue 'Material demand reduction'. © 2017 The Authors.

Towards environmentally sustainable human behaviour: targeting non-conscious and conscious processes for effective and acceptable policies

PubMed Central

2017-01-01

Meeting climate change targets to limit global warming to 2°C requires rapid and large reductions in demand for products that most contribute to greenhouse gas (GHG) emissions. These include production of bulk materials (e.g. steel and cement), energy supply (e.g. fossil fuels) and animal source foods (particularly ruminants and their products). Effective strategies to meet these targets require transformative changes in supply as well as demand, involving changes in economic, political and legal systems at local, national and international levels, building on evidence from many disciplines. This paper outlines contributions from behavioural science in reducing demand. Grounded in dual-process models of human behaviour (involving non-conscious and conscious processes) this paper considers first why interventions aimed at changing population values towards the environment are usually insufficient or unnecessary for reducing demand although they may be important in increasing public acceptability of policies that could reduce demand. It then outlines two sets of evidence from behavioural science towards effective systems-based strategies, to identify interventions likely to be effective at: (i) reducing demand for products that contribute most to GHG emissions, mainly targeting non-conscious processes and (ii) increasing public acceptability for policy changes to enable these interventions, targeting conscious processes. This article is part of the themed issue ‘Material demand reduction’. PMID:28461435

A Secure and Privacy-Preserving Targeted Ad-System

NASA Astrophysics Data System (ADS)

Androulaki, Elli; Bellovin, Steven M.

Thanks to its low product-promotion cost and its efficiency, targeted online advertising has become very popular. Unfortunately, being profile-based, online advertising methods violate consumers' privacy, which has engendered resistance to the ads. However, protecting privacy through anonymity seems to encourage click-fraud. In this paper, we define consumer's privacy and present a privacy-preserving, targeted ad system (PPOAd) which is resistant towards click fraud. Our scheme is structured to provide financial incentives to all entities involved.

MODIS 3km Aerosol Product: Algorithm and Global Perspective

NASA Technical Reports Server (NTRS)

Remer, L. A.; Mattoo, S.; Levy, R. C.; Munchak, L.

2013-01-01

After more than a decade of producing a nominal 10 km aerosol product based on the dark target method, the MODIS aerosol team will be releasing a nominal 3 km product as part of their Collection 6 release. The new product differs from the original 10 km product only in the manner in which reflectance pixels are ingested, organized and selected by the aerosol algorithm. Overall, the 3 km product closely mirrors the 10 km product. However, the finer resolution product is able to retrieve over ocean closer to islands and coastlines, and is better able to resolve fine aerosol features such as smoke plumes over both ocean and land. In some situations, it provides retrievals over entire regions that the 10 km product barely samples. In situations traditionally difficult for the dark target algorithm, such as over bright or urban surfaces the 3 km product introduces isolated spikes of artificially high aerosol optical depth (AOD) that the 10 km algorithm avoids. Over land, globally, the 3 km product appears to be 0.01 to 0.02 higher than the 10 km product, while over ocean, the 3 km algorithm is retrieving a proportionally greater number of very low aerosol loading situations. Based on collocations with ground-based observations for only six months, expected errors associated with the 3 km land product are determined to be greater than for the 10 km product: 0.05 0.25 AOD. Over ocean, the suggestion is for expected errors to be the same as the 10 km product: 0.03 0.05 AOD. The advantage of the product is on the local scale, which will require continued evaluation not addressed here. Nevertheless, the new 3 km product is expected to provide important information complementary to existing satellite-derived products and become an important tool for the aerosol community.

An efficient procedure for marker-free mutagenesis of S. coelicolor by site-specific recombination for secondary metabolite overproduction.

PubMed

Zhang, Bo; Zhang, Lin; Dai, Ruixue; Yu, Meiying; Zhao, Guoping; Ding, Xiaoming

2013-01-01

Streptomyces bacteria are known for producing important natural compounds by secondary metabolism, especially antibiotics with novel biological activities. Functional studies of antibiotic-biosynthesizing gene clusters are generally through homologous genomic recombination by gene-targeting vectors. Here, we present a rapid and efficient method for construction of gene-targeting vectors. This approach is based on Streptomyces phage φBT1 integrase-mediated multisite in vitro site-specific recombination. Four 'entry clones' were assembled into a circular plasmid to generate the destination gene-targeting vector by a one-step reaction. The four 'entry clones' contained two clones of the upstream and downstream flanks of the target gene, a selectable marker and an E. coli-Streptomyces shuttle vector. After targeted modification of the genome, the selectable markers were removed by φC31 integrase-mediated in vivo site-specific recombination between pre-placed attB and attP sites. Using this method, part of the calcium-dependent antibiotic (CDA) and actinorhodin (Act) biosynthetic gene clusters were deleted, and the rrdA encoding RrdA, a negative regulator of Red production, was also deleted. The final prodiginine production of the engineered strain was over five times that of the wild-type strain. This straightforward φBT1 and φC31 integrase-based strategy provides an alternative approach for rapid gene-targeting vector construction and marker removal in streptomycetes.

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

Nigg, D.W.; Mitchell, H.E.; Harker, Y.D.

Therapeutically-useful epithermal-neutron beams for BNCT are currently generated by nuclear reactors. Various accelerator-based neutron sources for BNCT have been proposed and some low intensity prototypes of such sources, generally featuring the use of proton beams and beryllium or lithium targets have been constructed. This paper describes an alternate approach to the realization of a clinically useful accelerator-based source of epithermal neutrons for BNCT that reconciles the often conflicting objectives of target cooling, neutron beam intensity, and neutron beam spectral purity via a two stage photoneutron production process.

Meeting the need for regenerative therapies I: target-based incidence and its relationship to U.S. spending, productivity, and innovation.

PubMed

Parenteau, Nancy; Hardin-Young, Janet; Shannon, William; Cantini, Patrick; Russell, Alan

2012-04-01

Regenerative therapies possess high theoretical potential for medical advance yet their success as commercial therapeutics is still open to debate. Appropriate data on target opportunities that provide perspective and enable strategic decision making is necessary for both efficient and effective translation. Up until now, this data have been out of reach to research scientists and many start-up companies-the very groups currently looked to for the critical advance of these therapies. The target-based estimate of opportunity presented in this report demonstrates its importance in evaluating medical need and technology feasibility. In addition, analysis of U.S. research spending, productivity, and innovation reveals that U.S. basic research in this field would benefit from greater interdisciplinarity. Overcoming the barriers that currently prevent translation into high value therapies that are quickly clinically adopted requires simultaneous integration of engineering, science, business, and clinical practice. Achieving this integration is nontrivial.

Identification of reliable gridded reference data for statistical downscaling methods in Alberta

NASA Astrophysics Data System (ADS)

Eum, H. I.; Gupta, A.

2017-12-01

Climate models provide essential information to assess impacts of climate change at regional and global scales. However, statistical downscaling methods have been applied to prepare climate model data for various applications such as hydrologic and ecologic modelling at a watershed scale. As the reliability and (spatial and temporal) resolution of statistically downscaled climate data mainly depend on a reference data, identifying the most reliable reference data is crucial for statistical downscaling. A growing number of gridded climate products are available for key climate variables which are main input data to regional modelling systems. However, inconsistencies in these climate products, for example, different combinations of climate variables, varying data domains and data lengths and data accuracy varying with physiographic characteristics of the landscape, have caused significant challenges in selecting the most suitable reference climate data for various environmental studies and modelling. Employing various observation-based daily gridded climate products available in public domain, i.e. thin plate spline regression products (ANUSPLIN and TPS), inverse distance method (Alberta Townships), and numerical climate model (North American Regional Reanalysis) and an optimum interpolation technique (Canadian Precipitation Analysis), this study evaluates the accuracy of the climate products at each grid point by comparing with the Adjusted and Homogenized Canadian Climate Data (AHCCD) observations for precipitation, minimum and maximum temperature over the province of Alberta. Based on the performance of climate products at AHCCD stations, we ranked the reliability of these publically available climate products corresponding to the elevations of stations discretized into several classes. According to the rank of climate products for each elevation class, we identified the most reliable climate products based on the elevation of target points. A web-based system was developed to allow users to easily select the most reliable reference climate data at each target point based on the elevation of grid cell. By constructing the best combination of reference data for the study domain, the accurate and reliable statistically downscaled climate projections could be significantly improved.

Optical design for consumer products

NASA Astrophysics Data System (ADS)

Gupta, Anurag

2014-10-01

Optical engineers often limit their focus on meeting the provided targets on performance and geometry and assume that the specifications are largely non-negotiable. Such approach ignores the value proposition behind the product and the challenges associated with overall product design, manufacturing, business development and legal issues. As a result, the design effort can be expensive, time consuming and can result in product failure. We discuss a product based systems engineering approach that leads to an application specific optical design that is more effective and efficient to implement.

Form gene clustering method about pan-ethnic-group products based on emotional semantic

NASA Astrophysics Data System (ADS)

Chen, Dengkai; Ding, Jingjing; Gao, Minzhuo; Ma, Danping; Liu, Donghui

2016-09-01

The use of pan-ethnic-group products form knowledge primarily depends on a designer's subjective experience without user participation. The majority of studies primarily focus on the detection of the perceptual demands of consumers from the target product category. A pan-ethnic-group products form gene clustering method based on emotional semantic is constructed. Consumers' perceptual images of the pan-ethnic-group products are obtained by means of product form gene extraction and coding and computer aided product form clustering technology. A case of form gene clustering about the typical pan-ethnic-group products is investigated which indicates that the method is feasible. This paper opens up a new direction for the future development of product form design which improves the agility of product design process in the era of Industry 4.0.

Composite uranium carbide targets at TRIUMF: Development and characterization with SEM, XRD, XRF and L-edge densitometry

NASA Astrophysics Data System (ADS)

Kunz, Peter; Bricault, Pierre; Dombsky, Marik; Erdmann, Nicole; Hanemaayer, Vicky; Wong, John; Lützenkirchen, Klaus

2013-09-01

The production of radioactive ion beams (RIB) from spallation targets by irradiation with a continuous 500 MeV proton beam, has been routine at TRIUMF for several years. Based on the experience with composite refractory carbide targets a procedure for the fabrication of UC2/C targets was developed. It includes the preparation of UC2 by carbothermal reduction of UO2, the slip-casting of fine-grained UC2/C slurry on graphite foil under inert gas atmosphere and the cutting of composite target discs which are stacked up to a lamellar structure. The thermal properties of such an arrangement are adequate to withstand the high power deposition of an intense, continuous proton beam and also beneficial for the fast release of short-lived radioactive isotopes. Molecular structure, particle size and the impact of sintering of the target discs were investigated via XRD and SEM. Thickness and mass distribution were measured with position-sensitive LIII-edge densitometry. The results confirm that the properties of the UC2/C target material are well suited for RIB production at TRIUMF while there is still room for improvement with regard to uniformity of mass distribution in target disc thickness.

Bioactive Natural Products Prioritization Using Massive Multi-informational Molecular Networks.

PubMed

Olivon, Florent; Allard, Pierre-Marie; Koval, Alexey; Righi, Davide; Genta-Jouve, Gregory; Neyts, Johan; Apel, Cécile; Pannecouque, Christophe; Nothias, Louis-Félix; Cachet, Xavier; Marcourt, Laurence; Roussi, Fanny; Katanaev, Vladimir L; Touboul, David; Wolfender, Jean-Luc; Litaudon, Marc

2017-10-20

Natural products represent an inexhaustible source of novel therapeutic agents. Their complex and constrained three-dimensional structures endow these molecules with exceptional biological properties, thereby giving them a major role in drug discovery programs. However, the search for new bioactive metabolites is hampered by the chemical complexity of the biological matrices in which they are found. The purification of single constituents from such matrices requires such a significant amount of work that it should be ideally performed only on molecules of high potential value (i.e., chemical novelty and biological activity). Recent bioinformatics approaches based on mass spectrometry metabolite profiling methods are beginning to address the complex task of compound identification within complex mixtures. However, in parallel to these developments, methods providing information on the bioactivity potential of natural products prior to their isolation are still lacking and are of key interest to target the isolation of valuable natural products only. In the present investigation, we propose an integrated analysis strategy for bioactive natural products prioritization. Our approach uses massive molecular networks embedding various informational layers (bioactivity and taxonomical data) to highlight potentially bioactive scaffolds within the chemical diversity of crude extracts collections. We exemplify this workflow by targeting the isolation of predicted active and nonactive metabolites from two botanical sources (Bocquillonia nervosa and Neoguillauminia cleopatra) against two biological targets (Wnt signaling pathway and chikungunya virus replication). Eventually, the detection and isolation processes of a daphnane diterpene orthoester and four 12-deoxyphorbols inhibiting the Wnt signaling pathway and exhibiting potent antiviral activities against the CHIKV virus are detailed. Combined with efficient metabolite annotation tools, this bioactive natural products prioritization pipeline proves to be efficient. Implementation of this approach in drug discovery programs based on natural extract screening should speed up and rationalize the isolation of bioactive natural products.

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

Youker, Amanda J.; Krebs, John F.; Quigley, Kevin J.

With funding from the National Nuclear Security Administrations Material Management and Minimization Office, Argonne National Laboratory (Argonne) is providing technical assistance to help accelerate the U.S. production of Mo-99 using a non-highly enriched uranium (non-HEU) source. A potential Mo-99 production pathway is by accelerator-initiated fissioning in a subcritical uranyl sulfate solution containing low enriched uranium (LEU). As part of the Argonne development effort, we are undertaking the AMORE (Argonne Molybdenum Research Experiment) project, which is essentially a pilot facility for all phases of Mo-99 production, recovery, and purification. Production of Mo-99 and other fission products in the subcritical target solutionmore » is initiated by putting an electron beam on a depleted uranium (DU) target; the fast neutrons produced in the DU target are thermalized and lead to fissioning of U-235. At the end of irradiation, Mo is recovered from the target solution and separated from uranium and most of the fission products by using a titania column. The Mo is stripped from the column with an alkaline solution. After acidification of the Mo product solution from the recovery column, the Mo is concentrated (and further purified) in a second titania column. The strip solution from the concentration column is then purified with the LEU Modified Cintichem process. A full description of the process can be found elsewhere [1–3]. The initial commissioning steps for the AMORE project include performing a Mo-99 spike test with pH 1 sulfuric acid in the target vessel without a beam on the target to demonstrate the initial Mo separation-and-recovery process, followed by the concentration column process. All glovebox operations were tested with cold solutions prior to performing the Mo-99 spike tests. Two Mo-99 spike tests with pH 1 sulfuric acid have been performed to date. Figure 1 shows the flow diagram for the remotely operated Mo-recovery system for the AMORE project. There are two separate pumps and flow paths for the acid and base operations. The system contains three sample ladders with eight sample loops per ladder for target mixing; column loading, including acid and water washes; and column stripping, including the final water wash.« less

Gadolinium-148 and other spallation production cross section measurements for accelerator target facilities

NASA Astrophysics Data System (ADS)

Kelley, Karen Corzine

At the Los Alamos Neutron Science Center accelerator complex, protons are accelerated to 800 MeV and directed to two tungsten targets, Target 4 at the Weapons Neutron Research facility and the 1L target at the Lujan Center. The Department of Energy requires hazard classification analyses to be performed on these targets and places limits on certain radionuclide inventories in the targets to avoid characterizing the facilities as "nuclear facilities." Gadolinium-148 is a radionuclide created from the spallation of tungsten. Allowed isotopic inventories are particularly low for this isotope because it is an alpha-particle emitter with a 75-year half-life. The activity level of Gadolinium-148 is low, but it encompasses almost two-thirds of the total dose burden for the two tungsten targets based on present yield estimates. From a hazard classification standpoint, this severely limits the lifetime of these tungsten targets. The cross section is not well-established experimentally and this is the motivation for measuring the Gadolinium-148 production cross section from tungsten. In a series of experiments at the Weapons Neutron Research facility, Gadolinium-148 production was measured for 600- and 800-MeV protons on tungsten, tantalum, and gold. These experiments used 3 mum thin tungsten, tantalum, and gold foils and 10 mum thin aluminum activation foils. In addition, spallation yields were determined for many short-lived and long-lived spallation products with these foils using gamma and alpha spectroscopy and compared with predictions of the Los Alamos National Laboratory codes CEM2k+GEM2 and MCNPX. The cumulative Gadolinium-148 production cross section measured from tantalum, tungsten, and gold for incident 600-MeV protons were 15.2 +/- 4.0, 8.31 +/- 0.92, and 0.591 +/- 0.155, respectively. The average production cross sections measured at 800 MeV were 28.6 +/- 3.5, 19.4 +/- 1.8, and 3.69 +/- 0.50 for tantalum, tungsten, and gold, respectively. These cumulative measurements compared best with Bertini and were within a factor of two to three of CEM2k+GEM2.

Production and separation of 43Sc for radiopharmaceutical purposes.

PubMed

Domnanich, Katharina A; Eichler, Robert; Müller, Cristina; Jordi, Sara; Yakusheva, Vera; Braccini, Saverio; Behe, Martin; Schibli, Roger; Türler, Andreas; van der Meulen, Nicholas P

2017-01-01

The favorable decay properties of 43 Sc and 44 Sc for PET make them promising candidates for future applications in nuclear medicine. An advantage 43 Sc (T 1/2 = 3.89 h, Eβ + av = 476 keV [88%]) exhibits over 44 Sc, however, is the absence of co-emitted high energy γ-rays. While the production and application of 44 Sc has been comprehensively discussed, research concerning 43 Sc is still in its infancy. This study aimed at developing two different production routes for 43 Sc, based on proton irradiation of enriched 46 Ti and 43 Ca target material. 43 Sc was produced via the 46 Ti(p,α) 43 Sc and 43 Ca(p,n) 43 Sc nuclear reactions, yielding activities of up to 225 MBq and 480 MBq, respectively. 43 Sc was chemically separated from enriched metallic 46 Ti (97.0%) and 43 CaCO 3 (57.9%) targets, using extraction chromatography. In both cases, ~90% of the final activity was eluted in a small volume of 700 μL, thereby, making it suitable for direct radiolabeling. The prepared products were of high radionuclidic purity, i.e. 98.2% 43 Sc were achieved from the irradiation of 46 Ti, whereas the product isolated from irradiated 43 Ca consisted of 66.2% 43 Sc and 33.3% 44 Sc. A PET phantom study performed with 43 Sc, via both nuclear reactions, revealed slightly improved resolution over 44 Sc. In order to assess the chemical purity of the separated 43 Sc, radiolabeling experiments were performed with DOTANOC, attaining specific activities of 5-8 MBq/nmol, respectively, with a radiochemical yield of >96%. It was determined that higher 43 Sc activities were accessible via the 43 Ca production route, with a comparatively less complex target preparation and separation procedure. The product isolated from irradiated 46 Ti, however, revealed purer 43 Sc with minor radionuclidic impurities. Based on the results obtained herein, the 43 Ca route features some advantages (such as higher yields and direct usage of the purchased target material) over the 46 Ti path when aiming at 43 Sc production on a routine basis.

[Research on the marketing status of antimicrobial products and the use of antimicrobial agents indicated on product labels from 1991 through 2005].

PubMed

Nakashima, Harunobu; Miyano, Naoko; Matsunaga, Ichiro; Nakashima, Naomi; Kaniwa, Masa-aki

2007-05-01

To clarify the marketing status of antimicrobial products, descriptions on the labels of commercially available antimicrobial products were investigated from 1991 through 2005, and the results were analyzed using a database system on antimicrobial deodorant agents. A classification table of household antimicrobial products was prepared and revised, based on which target products were reviewed for any changes in the product type. The number of antimicrobial products markedly increased over 3 years starting from 1996, among which there were many products apparently not requiring antimicrobial processing. More recently, in the 2002 and 2004 surveys, while sales of kitchenware and daily necessities decreased, chemical products, baby articles, and articles for pets increased; this poses new problems. To clarify the use of antimicrobial agents in the target products, a 3-step (large, intermediate, small) classification table of antimicrobial agents was also prepared, based on which antimicrobial agents indicated on the product labels were checked. The rate of identifying the agents increased. However, this is because of the increase of chemical products and baby articles, both of which more frequently indicated the ingredient agents on the labels, and the decrease of kitchenware and daily necessities, which less frequently indicated them on the labels. Therefore there has been little change in the actual identification rate. The agents used are characterized by product types: quaternary ammonium salts, metal salts, and organic antimicrobials are commonly used in textiles, plastics, and chemical products, respectively. Since the use of natural organic agents has recently increased, the safety of these agents should be evaluated.

Studies for aluminum photoionization in hot cavity for the selective production of exotic species projecta)

NASA Astrophysics Data System (ADS)

Scarpa, D.; Vasquez, J.; Tomaselli, A.; Grassi, D.; Biasetto, L.; Cavazza, A.; Corradetti, S.; Manzolaro, M.; Montano, J.; Andrighetto, A.; Prete, G.

2012-02-01

Selective production of exotic species (SPES) is an ISOL-based accelerator facility that will be built in the Legnaro INFN Laboratory (Italy), intended to provide an intense neutron-rich radioactive ion beams obtained by proton induced fission of an uranium carbide target. Beside this main target, a silicon carbide (SiC) target will the first to be used to deliver some p-rich beams. This target will validate also the functionality of the SPES facility with aluminum beam as result of hitting SiC target with protons. In the past off-line studies on laser photoionization of aluminum have performed in Pavia Spectroscopy Laboratory and in Laboratori Nazionali di Legnaro where, recently, a XeCl excimer laser was installed in order to test the laser ionization in the SPES hot cavity. Results are promising to justify further studies with this technique, aiming a better characterization of the SPES ion extraction capability under laser photoionization.

Integration of systems biology with bioprocess engineering: L: -threonine production by systems metabolic engineering of Escherichia coli.

PubMed

Lee, Sang Yup; Park, Jin Hwan

2010-01-01

Random mutation and selection or targeted metabolic engineering without consideration of its impact on the entire metabolic and regulatory networks can unintentionally cause genetic alterations in the region, which is not directly related to the target metabolite. This is one of the reasons why strategies for developing industrial strains are now shifted towards targeted metabolic engineering based on systems biology, which is termed systems metabolic engineering. Using systems metabolic engineering strategies, all the metabolic engineering works are conducted in systems biology framework, whereby entire metabolic and regulatory networks are thoroughly considered in an integrated manner. The targets for purposeful engineering are selected after all possible effects on the entire metabolic and regulatory networks are thoroughly considered. Finally, the strain, which is capable of producing the target metabolite to a high level close to the theoretical maximum value, can be constructed. Here we review strategies and applications of systems biology successfully implemented on bioprocess engineering, with particular focus on developing L: -threonine production strains of Escherichia coli.

Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase.

PubMed

Keohane, Colleen E; Steele, Andrew D; Fetzer, Christian; Khowsathit, Jittasak; Van Tyne, Daria; Moynié, Lucile; Gilmore, Michael S; Karanicolas, John; Sieber, Stephan A; Wuest, William M

2018-02-07

Natural products have served as an inspiration to scientists both for their complex three-dimensional architecture and exquisite biological activity. Promysalin is one such Pseudomonad secondary metabolite that exhibits narrow-spectrum antibacterial activity, originally isolated from the rhizosphere. We herein utilize affinity-based protein profiling (AfBPP) to identify succinate dehydrogenase (Sdh) as the biological target of the natural product. The target was further validated in silico, in vitro, in vivo, and through the selection, and sequencing, of a resistant mutant. Succinate dehydrogenase plays an essential role in primary metabolism of Pseudomonas aeruginosa as the only enzyme that is involved both in the tricarboxylic acid cycle (TCA) and in respiration via the electron transport chain. These findings add credence to other studies that suggest that the TCA cycle is an understudied target in the development of novel therapeutics to combat P. aeruginosa, a significant pathogen in clinical settings.

Target identification by image analysis.

PubMed

Fetz, V; Prochnow, H; Brönstrup, M; Sasse, F

2016-05-04

Covering: 1997 to the end of 2015Each biologically active compound induces phenotypic changes in target cells that are characteristic for its mode of action. These phenotypic alterations can be directly observed under the microscope or made visible by labelling structural elements or selected proteins of the cells with dyes. A comparison of the cellular phenotype induced by a compound of interest with the phenotypes of reference compounds with known cellular targets allows predicting its mode of action. While this approach has been successfully applied to the characterization of natural products based on a visual inspection of images, recent studies used automated microscopy and analysis software to increase speed and to reduce subjective interpretation. In this review, we give a general outline of the workflow for manual and automated image analysis, and we highlight natural products whose bacterial and eucaryotic targets could be identified through such approaches.

Development and application of novel SNP-based serotyping assays in targeting Salmonella enterica within the poultry production and processing continuum.

USDA-ARS?s Scientific Manuscript database

Salmonella enterica subsp. enterica serotype Enteriditis (S. Enteriditis) is the leading cause of salmonellosis worldwide. While some S. enterica serotypes are specific to birds, many represent human zoonotic pathogens, thus their presence and survival throughout the continuum of poultry production...

Morphosyntactic Production and Verbal Working Memory: Evidence from Greek Aphasia and Healthy Aging

ERIC Educational Resources Information Center

Fyndanis, Valantis; Arcara, Giorgio; Christidou, Paraskevi; Caplan, David

2018-01-01

Purpose: The present work investigated whether verbal working memory (WM) affects morphosyntactic production in configurations that do not involve or favor similarity-based interference and whether WM interacts with verb-related morphosyntactic categories and/or cue-target distance (locality). It also explored whether the findings related to the…

Integration of parallel 13 C-labeling experiments and in silico pathway analysis for enhanced production of ascomycin.

PubMed

Qi, Haishan; Lv, Mengmeng; Song, Kejing; Wen, Jianping

2017-05-01

Herein, the hyper-producing strain for ascomycin was engineered based on 13 C-labeling experiments and elementary flux modes analysis (EFMA). First, the metabolism of non-model organism Streptomyces hygroscopicus var. ascomyceticus SA68 was investigated and an updated network model was reconstructed using 13 C- metabolic flux analysis. Based on the precise model, EFMA was further employed to predict genetic targets for higher ascomycin production. Chorismatase (FkbO) and pyruvate carboxylase (Pyc) were predicted as the promising overexpression and deletion targets, respectively. The corresponding mutant TD-FkbO and TD-ΔPyc exhibited the consistency effects between model prediction and experimental results. Finally, the combined genetic manipulations were performed, achieving a high-yield ascomycin engineering strain TD-ΔPyc-FkbO with production up to 610 mg/L, 84.8% improvement compared with the parent strain SA68. These results manifested that the integration of 13 C-labeling experiments and in silico pathway analysis could serve as a promising concept to enhance ascomycin production, as well as other valuable products. Biotechnol. Bioeng. 2017;114: 1036-1044. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Children's Food and Beverage Promotion on Television to Parents.

PubMed

Emond, Jennifer A; Smith, Marietta E; Mathur, Suman J; Sargent, James D; Gilbert-Diamond, Diane

2015-12-01

Nutritionally poor foods are heavily advertised to children on television. Whether those same products are also advertised to parents on television has not been systematically examined. This study is a content analysis of advertisements for children's packaged foods and beverages aired over US network, cable, and syndicated television for 1 year (2012 to 2013). The target audience of each advertisement was defined as children or parents based on advertisement content, where parent-directed advertisements included emotional appeals related to family bonding and love. Advertisement characteristics and patterns of airtime were compared across target audience, and the proportion of total airtime devoted to advertisements targeting parents was computed. Fifty-one children's food or beverage products were advertised over the study year, 25 (49%) of which were advertised directly to parents. Parent-directed advertisements more often featured nutrition and health messaging and an active lifestyle than child-directed advertisements, whereas child-directed advertisements more frequently highlighted fun and product taste. Over all products, 42.4% of total airtime was devoted to advertisements that targeted parents. The products with the most amount of airtime over the study year were ready-to-eat cereals, sugar-sweetened beverages, and children's yogurt, and the proportion of total advertisement airtime for those products devoted to parents was 24.4%, 72.8%, and 25.8%, respectively. Television advertisements for children's packaged foods and beverages frequently targeted parents with emotional appeals and messaging related to nutrition and health. Findings are of concern if exposure to such advertisements among parents may shape their beliefs about the appropriateness of nutritionally questionable children's foods and beverages. Copyright © 2015 by the American Academy of Pediatrics.

Children’s Food and Beverage Promotion on Television to Parents

PubMed Central

Smith, Marietta E.; Mathur, Suman J.; Sargent, James D.; Gilbert-Diamond, Diane

2015-01-01

BACKGROUND: Nutritionally poor foods are heavily advertised to children on television. Whether those same products are also advertised to parents on television has not been systematically examined. METHODS: This study is a content analysis of advertisements for children’s packaged foods and beverages aired over US network, cable, and syndicated television for 1 year (2012 to 2013). The target audience of each advertisement was defined as children or parents based on advertisement content, where parent-directed advertisements included emotional appeals related to family bonding and love. Advertisement characteristics and patterns of airtime were compared across target audience, and the proportion of total airtime devoted to advertisements targeting parents was computed. RESULTS: Fifty-one children’s food or beverage products were advertised over the study year, 25 (49%) of which were advertised directly to parents. Parent-directed advertisements more often featured nutrition and health messaging and an active lifestyle than child-directed advertisements, whereas child-directed advertisements more frequently highlighted fun and product taste. Over all products, 42.4% of total airtime was devoted to advertisements that targeted parents. The products with the most amount of airtime over the study year were ready-to-eat cereals, sugar-sweetened beverages, and children’s yogurt, and the proportion of total advertisement airtime for those products devoted to parents was 24.4%, 72.8%, and 25.8%, respectively. DISCUSSION: Television advertisements for children’s packaged foods and beverages frequently targeted parents with emotional appeals and messaging related to nutrition and health. Findings are of concern if exposure to such advertisements among parents may shape their beliefs about the appropriateness of nutritionally questionable children’s foods and beverages. PMID:26553181

Improving health visitor emollient prescribing using a CQUIN-based approach.

PubMed

Brooks, Christina; Khatau, Tejas

2015-12-01

Prescribing is an essential element of health visiting practice. This initiative used the payment framework of Commissioning for Quality and Innovation (CQUIN) to develop health visiting practice across a large health visiting workforce in the East Midlands. A focus on emollient prescribing practice was agreed and a guidance booklet regarding preferred emollient products was produced, based on the local formulary Each health visitor benefitted from receiving additional training and was given a guidance booklet to inform their practice. Targets were set for each quarter to demonstrate an improved prescribing adherence to the preferred product list.The targets were achieved for each quarter. Prescribing rates and confidence improved across the service. Therefore, it was demonstrated that specific guidance and ongoing support can improve prescribing practice within the health visiting service.

Drug target identification in protozoan parasites

PubMed Central

Müller, Joachim; Hemphill, Andrew

2016-01-01

Introduction Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Areas covered Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Expert opinion Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses. PMID:27238605

Dubbing Projects for the Language Learner: A Framework for Integrating Audiovisual Translation into Task-Based Instruction

ERIC Educational Resources Information Center

Danan, Martine

2010-01-01

This article describes a series of exploratory L1 to L2 dubbing projects for which students translated and used editing software to dub short American film and TV clips into their target language. Translating and dubbing into the target language involve students in multifaceted, high-level language production tasks that lead to enhanced vocabulary…

Implementing Project Based Learning Approach to Graphic Design Course

ERIC Educational Resources Information Center

Riyanti, Menul Teguh; Erwin, Tuti Nuriah; Suriani, S. H.

2017-01-01

The purpose of this study was to develop a learning model based Commercial Graphic Design Drafting project-based learning approach, was chosen as a strategy in the learning product development research. University students as the target audience of this model are the students of the fifth semester Visual Communications Design Studies Program…

Cyclotron production of Ga-68 for human use from liquid targets: From theory to practice

NASA Astrophysics Data System (ADS)

Alves, F.; Alves, V. H.; Neves, A. C. B.; do Carmo, S. J. C.; Nactergal, B.; Hellas, V.; Kral, E.; Gonçalves-Gameiro, C.; Abrunhosa, A. J.

2017-05-01

A fully automated system for the production of 68Ga based on commercially available cyclotron liquid target and synthesis modules is described. A solution containing enriched 68Zn dissolved in a nitric solution is irradiated in a Cyclone 18/9 IBA cyclotron leading to the production of up to about 25 GBq of 68Ga. The irradiated solution is transferred to a Synthera synthesis module in which 68Ga is separated and purified with a yield superior to 85 % and where further labelling is achieved with yields no inferior to 70 %. The developed and implemented method presents an improved approach for the production of 68Ga-radiopharmaceuticals suitable for human use, in a process that takes less than 2 hours. This technique represents an economically viable alternative to 68Ge/68Ga generators with improved characteristics.

Efficient Generation of Somatic Cell Nuclear Transfer-Competent Porcine Cells with Mutated Alleles at Multiple Target Loci by Using CRISPR/Cas9 Combined with Targeted Toxin-Based Selection System.

PubMed

Sato, Masahiro; Miyoshi, Kazuchika; Nakamura, Shingo; Ohtsuka, Masato; Sakurai, Takayuki; Watanabe, Satoshi; Kawaguchi, Hiroaki; Tanimoto, Akihide

2017-12-04

The recent advancement in genome editing such a CRISPR/Cas9 system has enabled isolation of cells with knocked multiple alleles through a one-step transfection. Somatic cell nuclear transfer (SCNT) has been frequently employed as one of the efficient tools for the production of genetically modified (GM) animals. To use GM cells as SCNT donor, efficient isolation of transfectants with mutations at multiple target loci is often required. The methods for the isolation of such GM cells largely rely on the use of drug selection-based approach using selectable genes; however, it is often difficult to isolate cells with mutations at multiple target loci. In this study, we used a novel approach for the efficient isolation of porcine cells with at least two target loci mutations by one-step introduction of CRISPR/Cas9-related components. A single guide (sg) RNA targeted to GGTA1 gene, involved in the synthesis of cell-surface α-Gal epitope (known as xenogenic antigen), is always a prerequisite. When the transfected cells were reacted with toxin-labeled BS-I-B₄ isolectin for 2 h at 37 C to eliminate α-Gal epitope-expressing cells, the surviving clones lacked α-Gal epitope expression and were highly expected to exhibit induced mutations at another target loci. Analysis of these α-Gal epitope-negative surviving cells demonstrated a 100% occurrence of genome editing at target loci. SCNT using these cells as donors resulted in the production of cloned blastocysts with the genotype similar to that of the donor cells used. Thus, this novel system will be useful for SCNT-mediated acquisition of GM cloned piglets, in which multiple target loci may be mutated.

Micro-channel-based high specific power lithium target

NASA Astrophysics Data System (ADS)

Mastinu, P.; Martın-Hernández, G.; Praena, J.; Gramegna, F.; Prete, G.; Agostini, P.; Aiello, A.; Phoenix, B.

2016-11-01

A micro-channel-based heat sink has been produced and tested. The device has been developed to be used as a Lithium target for the LENOS (Legnaro Neutron Source) facility and for the production of radioisotope. Nevertheless, applications of such device can span on many areas: cooling of electronic devices, diode laser array, automotive applications etc. The target has been tested using a proton beam of 2.8MeV energy and delivering total power shots from 100W to 1500W with beam spots varying from 5mm2 to 19mm2. Since the target has been designed to be used with a thin deposit of lithium and since lithium is a low-melting-point material, we have measured that, for such application, a specific power of about 3kW/cm2 can be delivered to the target, keeping the maximum surface temperature not exceeding 150° C.

Manipulation of the carbon storage regulator system for metabolite remodeling and biofuel production in Escherichia coli

PubMed Central

2012-01-01

Background Microbial engineering strategies that elicit global metabolic perturbations have the capacity to increase organism robustness for targeted metabolite production. In particular, perturbations to regulators of cellular systems that impact glycolysis and amino acid production while simultaneously decreasing fermentation by-products such as acetate and CO2 make ideal targets. Intriguingly, perturbation of the Carbon Storage Regulator (Csr) system has been previously implicated in large changes in central carbon metabolism in E. coli. Therefore, we hypothesized that perturbation of the Csr system through the CsrA-CsrB ribonucleoprotein complex might increase production of biofuels and their intermediates from heterologous pathways. Results We engaged the CsrA-CsrB ribonucleoprotein complex of E. coli via overexpression of CsrB. CsrB is a 350-nucleotide non-coding RNA that antagonizes CsrA, an RNA-binding protein that regulates translation of specific mRNA targets. By using shotgun proteomics and targeted metabolomics we established that elevation of CsrB levels leads to alterations in metabolite and protein levels in glycolysis, the TCA cycle and amino acid levels. Consequently, we show that such changes can be suitably applied to improve the production of desired compounds through the native fatty acid and heterologous n-butanol and isoprenoid pathways by up to two-fold. We also observed concomitant decreases in undesirable fermentation by-products such as acetate and CO2. Conclusions We have demonstrated that simple engineering of the RNA-based Csr global regulatory system constitutes a novel approach to obtaining pathway-independent improvements within engineered hosts. Additionally, since Csr is conserved across most prokaryotic species, this approach may also be amenable to a wide variety of production hosts. PMID:22694848

Manipulation of the carbon storage regulator system for metabolite remodeling and biofuel production in Escherichia coli.

PubMed

McKee, Adrienne E; Rutherford, Becky J; Chivian, Dylan C; Baidoo, Edward K; Juminaga, Darmawi; Kuo, Dwight; Benke, Peter I; Dietrich, Jeffrey A; Ma, Suzanne M; Arkin, Adam P; Petzold, Christopher J; Adams, Paul D; Keasling, Jay D; Chhabra, Swapnil R

2012-06-13

Microbial engineering strategies that elicit global metabolic perturbations have the capacity to increase organism robustness for targeted metabolite production. In particular, perturbations to regulators of cellular systems that impact glycolysis and amino acid production while simultaneously decreasing fermentation by-products such as acetate and CO(2) make ideal targets. Intriguingly, perturbation of the Carbon Storage Regulator (Csr) system has been previously implicated in large changes in central carbon metabolism in E. coli. Therefore, we hypothesized that perturbation of the Csr system through the CsrA-CsrB ribonucleoprotein complex might increase production of biofuels and their intermediates from heterologous pathways. We engaged the CsrA-CsrB ribonucleoprotein complex of E. coli via overexpression of CsrB. CsrB is a 350-nucleotide non-coding RNA that antagonizes CsrA, an RNA-binding protein that regulates translation of specific mRNA targets. By using shotgun proteomics and targeted metabolomics we established that elevation of CsrB levels leads to alterations in metabolite and protein levels in glycolysis, the TCA cycle and amino acid levels. Consequently, we show that such changes can be suitably applied to improve the production of desired compounds through the native fatty acid and heterologous n-butanol and isoprenoid pathways by up to two-fold. We also observed concomitant decreases in undesirable fermentation by-products such as acetate and CO(2). We have demonstrated that simple engineering of the RNA-based Csr global regulatory system constitutes a novel approach to obtaining pathway-independent improvements within engineered hosts. Additionally, since Csr is conserved across most prokaryotic species, this approach may also be amenable to a wide variety of production hosts.

Adaptive bi-level programming for optimal gene knockouts for targeted overproduction under phenotypic constraints

PubMed Central

2013-01-01

Background Optimization procedures to identify gene knockouts for targeted biochemical overproduction have been widely in use in modern metabolic engineering. Flux balance analysis (FBA) framework has provided conceptual simplifications for genome-scale dynamic analysis at steady states. Based on FBA, many current optimization methods for targeted bio-productions have been developed under the maximum cell growth assumption. The optimization problem to derive gene knockout strategies recently has been formulated as a bi-level programming problem in OptKnock for maximum targeted bio-productions with maximum growth rates. However, it has been shown that knockout mutants in fact reach the steady states with the minimization of metabolic adjustment (MOMA) from the corresponding wild-type strains instead of having maximal growth rates after genetic or metabolic intervention. In this work, we propose a new bi-level computational framework--MOMAKnock--which can derive robust knockout strategies under the MOMA flux distribution approximation. Methods In this new bi-level optimization framework, we aim to maximize the production of targeted chemicals by identifying candidate knockout genes or reactions under phenotypic constraints approximated by the MOMA assumption. Hence, the targeted chemical production is the primary objective of MOMAKnock while the MOMA assumption is formulated as the inner problem of constraining the knockout metabolic flux to be as close as possible to the steady-state phenotypes of wide-type strains. As this new inner problem becomes a quadratic programming problem, a novel adaptive piecewise linearization algorithm is developed in this paper to obtain the exact optimal solution to this new bi-level integer quadratic programming problem for MOMAKnock. Results Our new MOMAKnock model and the adaptive piecewise linearization solution algorithm are tested with a small E. coli core metabolic network and a large-scale iAF1260 E. coli metabolic network. The derived knockout strategies are compared with those from OptKnock. Our preliminary experimental results show that MOMAKnock can provide improved targeted productions with more robust knockout strategies. PMID:23368729

Adaptive bi-level programming for optimal gene knockouts for targeted overproduction under phenotypic constraints.

PubMed

Ren, Shaogang; Zeng, Bo; Qian, Xiaoning

2013-01-01

Optimization procedures to identify gene knockouts for targeted biochemical overproduction have been widely in use in modern metabolic engineering. Flux balance analysis (FBA) framework has provided conceptual simplifications for genome-scale dynamic analysis at steady states. Based on FBA, many current optimization methods for targeted bio-productions have been developed under the maximum cell growth assumption. The optimization problem to derive gene knockout strategies recently has been formulated as a bi-level programming problem in OptKnock for maximum targeted bio-productions with maximum growth rates. However, it has been shown that knockout mutants in fact reach the steady states with the minimization of metabolic adjustment (MOMA) from the corresponding wild-type strains instead of having maximal growth rates after genetic or metabolic intervention. In this work, we propose a new bi-level computational framework--MOMAKnock--which can derive robust knockout strategies under the MOMA flux distribution approximation. In this new bi-level optimization framework, we aim to maximize the production of targeted chemicals by identifying candidate knockout genes or reactions under phenotypic constraints approximated by the MOMA assumption. Hence, the targeted chemical production is the primary objective of MOMAKnock while the MOMA assumption is formulated as the inner problem of constraining the knockout metabolic flux to be as close as possible to the steady-state phenotypes of wide-type strains. As this new inner problem becomes a quadratic programming problem, a novel adaptive piecewise linearization algorithm is developed in this paper to obtain the exact optimal solution to this new bi-level integer quadratic programming problem for MOMAKnock. Our new MOMAKnock model and the adaptive piecewise linearization solution algorithm are tested with a small E. coli core metabolic network and a large-scale iAF1260 E. coli metabolic network. The derived knockout strategies are compared with those from OptKnock. Our preliminary experimental results show that MOMAKnock can provide improved targeted productions with more robust knockout strategies.

Scalable total synthesis and comprehensive structure-activity relationship studies of the phytotoxin coronatine.

PubMed

Littleson, Mairi M; Baker, Christopher M; Dalençon, Anne J; Frye, Elizabeth C; Jamieson, Craig; Kennedy, Alan R; Ling, Kenneth B; McLachlan, Matthew M; Montgomery, Mark G; Russell, Claire J; Watson, Allan J B

2018-03-16

Natural phytotoxins are valuable starting points for agrochemical design. Acting as a jasmonate agonist, coronatine represents an attractive herbicidal lead with novel mode of action, and has been an important synthetic target for agrochemical development. However, both restricted access to quantities of coronatine and a lack of a suitably scalable and flexible synthetic approach to its constituent natural product components, coronafacic and coronamic acids, has frustrated development of this target. Here, we report gram-scale production of coronafacic acid that allows a comprehensive structure-activity relationship study of this target. Biological assessment of a >120 member library combined with computational studies have revealed the key determinants of potency, rationalising hypotheses held for decades, and allowing future rational design of new herbicidal leads based on this template.

Assessment of Laser-Driven Pulsed Neutron Sources for Poolside Neutron-based Advanced NDE – A Pathway to LANSCE-like Characterization at INL

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

Roth, Markus; Vogel, Sven C.; Bourke, Mark Andrew M.

A variety of opportunities for characterization of fresh nuclear fuels using thermal (~25meV) and epithermal (~10eV) neutrons have been documented at Los Alamos National Laboratory. They include spatially resolved non-destructive characterization of features, isotopic enrichment, chemical heterogeneity and stoichiometry. The LANSCE spallation neutron source is well suited in neutron fluence and temporal characteristics for studies of fuels. However, recent advances in high power short pulse lasers suggest that compact neutron sources might, over the next decade, become viable at a price point that would permit their consideration for poolside characterization on site at irradiation facilities. In a laser-driven neutron sourcemore » the laser is used to accelerate deuterium ions into a beryllium target where neutrons are produced. At this time, the technology is new and their total neutron production is approximately four orders of magnitude less than a facility like LANSCE. However, recent measurements on a sub-optimized system demonstrated >10 10 neutrons in sub-nanosecond pulses in predominantly forward direction. The compactness of the target system compared to a spallation target may allow exchanging the target during a measurement to e.g. characterize a highly radioactive sample with thermal, epithermal, and fast neutrons as well as hard X-rays, thus avoiding sample handling. At this time several groups are working on laser-driven neutron production and are advancing concepts for lasers, laser targets, and optimized neutron target/moderator systems. Advances in performance sufficient to enable poolside fuels characterization with LANSCE-like fluence on sample within a decade may be possible. This report describes the underlying physics and state-of-the-art of the laser-driven neutron production process from the perspective of the DOE/NE mission. It also discusses the development and understanding that will be necessary to provide customized capability for characterization of irradiated fuels. Potential operational advantages compared to a spallation neutron source include reduced shielding complexity, reduced energy requirements, and a production target free of fission products. Contributors to this report include experts in laser-driven neutron production (Roth, Fernandez), laser design (Haefner, Siders, Leemans), laser target design (Glenzer), spallation target/moderator design (Mocko), neutron instrumentation and characterization applications (Vogel, Bourke).« less

Cryogenci DT and D2 Targets for Inertial Confinement Fusion

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

Sangster, T.C.; Betti, R.; Craxton, R.S.

Ignition target designs for inertial confinement fusion on the National Ignition Facility (NIF) are based on a spherical ablator containing a solid, cryogenic-fuel layer of deuterium and tritium. The need for solid-fuel layers was recognized more than 30 years ago and considerable effort has resulted in the production of cryogenic targets that meet most of the critical fabrication tolerances for ignition on the NIf. Significant progress with the formation and characterization of cryogenic targets for both direct and x-ray drive will be described. Results from recent cryogenic implosions will also be presented.

Image-based overlay measurement using subsurface ultrasonic resonance force microscopy

NASA Astrophysics Data System (ADS)

Tamer, M. S.; van der Lans, M. J.; Sadeghian, H.

2018-03-01

Image Based Overlay (IBO) measurement is one of the most common techniques used in Integrated Circuit (IC) manufacturing to extract the overlay error values. The overlay error is measured using dedicated overlay targets which are optimized to increase the accuracy and the resolution, but these features are much larger than the IC feature size. IBO measurements are realized on the dedicated targets instead of product features, because the current overlay metrology solutions, mainly based on optics, cannot provide sufficient resolution on product features. However, considering the fact that the overlay error tolerance is approaching 2 nm, the overlay error measurement on product features becomes a need for the industry. For sub-nanometer resolution metrology, Scanning Probe Microscopy (SPM) is widely used, though at the cost of very low throughput. The semiconductor industry is interested in non-destructive imaging of buried structures under one or more layers for the application of overlay and wafer alignment, specifically through optically opaque media. Recently an SPM technique has been developed for imaging subsurface features which can be potentially considered as a solution for overlay metrology. In this paper we present the use of Subsurface Ultrasonic Resonance Force Microscopy (SSURFM) used for IBO measurement. We used SSURFM for imaging the most commonly used overlay targets on a silicon substrate and photoresist. As a proof of concept we have imaged surface and subsurface structures simultaneously. The surface and subsurface features of the overlay targets are fabricated with programmed overlay errors of +/-40 nm, +/-20 nm, and 0 nm. The top layer thickness changes between 30 nm and 80 nm. Using SSURFM the surface and subsurface features were successfully imaged and the overlay errors were extracted, via a rudimentary image processing algorithm. The measurement results are in agreement with the nominal values of the programmed overlay errors.

Pion emission in α-particle interactions with various targets of nuclear emulsion detector

NASA Astrophysics Data System (ADS)

Abdelsalam, A.; Abou-Moussa, Z.; Rashed, N.; M. Badawy, B.; A. Amer, H.; Osman, W.; M. El-Ashmawy, M.; Abdallah, N.

2015-09-01

The behavior of relativistic hadron multiplicity for 4He-nucleus interactions is investigated. The experiment is carried out at 2.1 A and 3.7 A GeV (Dubna energy) to search for the incident energy effect on the interactions inside different emulsion target nuclei. Data are presented in terms of the number of emitted relativistic hadrons in both forward and backward angular zones. The dependence on the target size is presented. For this purpose the statistical events are discriminated into groups according to the interactions with H, CNO, Em, and AgBr target nuclei. The separation of events, into the mentioned groups, is executed based on Glauber's multiple scattering theory approach. Features suggestive of a decay mechanism seem to be a characteristic of the backward emission of relativistic hadrons. The results strongly support the assumption that the relativistic hadrons may already be emitted during the de-excitation of the excited target nucleus, in a behavior like that of compound-nucleus disintegration. Regarding the limiting fragmentation hypothesis beyond 1 A GeV, the target size is the main parameter affecting the backward production of the relativistic hadron. The incident energy is a principal factor responsible for the forward relativistic hadron production, implying that this system of particle production is a creation system. However, the target size is an effective parameter as well as the projectile size considering the geometrical concept regarded in the nuclear fireball model. The data are analyzed in the framework of the FRITIOF model.

Present status of Accelerator-Based BNCT.

PubMed

Kreiner, Andres Juan; Bergueiro, Javier; Cartelli, Daniel; Baldo, Matias; Castell, Walter; Asoia, Javier Gomez; Padulo, Javier; Suárez Sandín, Juan Carlos; Igarzabal, Marcelo; Erhardt, Julian; Mercuri, Daniel; Valda, Alejandro A; Minsky, Daniel M; Debray, Mario E; Somacal, Hector R; Capoulat, María Eugenia; Herrera, María S; Del Grosso, Mariela F; Gagetti, Leonardo; Anzorena, Manuel Suarez; Canepa, Nicolas; Real, Nicolas; Gun, Marcelo; Tacca, Hernán

2016-01-01

This work aims at giving an updated report of the worldwide status of Accelerator-Based BNCT (AB-BNCT). There is a generalized perception that the availability of accelerators installed in hospitals, as neutron sources, may be crucial for the advancement of BNCT. Accordingly, in recent years a significant effort has started to develop such machines. A variety of possible charged-particle induced nuclear reactions and the characteristics of the resulting neutron spectra are discussed along with the worldwide activity in suitable accelerator development. Endothermic (7)Li(p,n)(7)Be and (9)Be(p,n)(9)B and exothermic (9)Be(d,n)(10)B are compared. In addition to having much better thermo-mechanical properties than Li, Be as a target leads to stable products. This is a significant advantage for a hospital-based facility. (9)Be(p,n)(9)B needs at least 4-5 MeV bombarding energy to have a sufficient yield, while (9)Be(d,n)(10)B can be utilized at about 1.4 MeV, implying the smallest possible accelerator. This reaction operating with a thin target can produce a sufficiently soft spectrum to be viable for AB-BNCT. The machines considered are electrostatic single ended or tandem accelerators or radiofrequency quadrupoles plus drift tube Linacs. (7)Li(p,n)(7)Be provides one of the best solutions for the production of epithermal neutron beams for deep-seated tumors. However, a Li-based target poses significant technological challenges. Hence, Be has been considered as an alternative target, both in combination with (p,n) and (d,n) reactions. (9)Be(d,n)(10)B at 1.4 MeV, with a thin target has been shown to be a realistic option for the treatment of deep-seated lesions.

Experiencing production ramp-up education for engineers

NASA Astrophysics Data System (ADS)

Bassetto, S.; Fiegenwald, V.; Cholez, C.; Mangione, F.

2011-08-01

This paper presents a game of industrialisation, based on a paper airplane, that mimics real world production ramp-up and blends classical engineering courses together. It is based on a low cost product so that it can be mass produced. The game targets graduate students and practitioners in engineering fields. For students, it offers an experiment in which methods learned in separate courses can be applied. For practitioners, it affords an opportunity to engage in reflexive practices related to industrialisation. Both students and practitioners are able to experience integrated management, required by industrialisation, in a controlled environment: the laboratory.

A new approach to data evaluation in the non-target screening of organic trace substances in water analysis.

PubMed

Müller, Alexander; Schulz, Wolfgang; Ruck, Wolfgang K L; Weber, Walter H

2011-11-01

Non-target screening via high performance liquid chromatography-mass spectrometry (HPLC-MS) has gained increasingly in importance for monitoring organic trace substances in water resources targeted for the production of drinking water. In this article a new approach for evaluating the data from non-target HPLC-MS screening in water is introduced and its advantages are demonstrated using the supply of drinking water as an example. The crucial difference between this and other approaches is the comparison of samples based on compounds (features) determined by their full scan data. In so doing, we take advantage of the temporal, spatial, or process-based relationships among the samples by applying the set operators, UNION, INTERSECT, and COMPLEMENT to the features of each sample. This approach regards all compounds, detectable by the used analytical method. That is the fundamental meaning of non-target screening, which includes all analytical information from the applied technique for further data evaluation. In the given example, in just one step, all detected features (1729) of a landfill leachate sample could be examined for their relevant influences on water purification respectively drinking water. This study shows that 1721 out of 1729 features were not relevant for the water purification. Only eight features could be determined in the untreated water and three of them were found in the final drinking water after ozonation. In so doing, it was possible to identify 1-adamantylamine as contamination of the landfill in the drinking water at a concentration in the range of 20 ng L(-1). To support the identification of relevant compounds and their transformation products, the DAIOS database (Database-Assisted Identification of Organic Substances) was used. This database concept includes some functions such as product ion search to increase the efficiency of the database query after the screening. To identify related transformation products the database function "transformation tree" was used. Copyright © 2011 Elsevier Ltd. All rights reserved.

Optimizing productivity, herd structure, environmental performance, and profitability of dairy cattle herds.

PubMed

Liang, D; Cabrera, V E

2015-04-01

This study used the Integrated Farm System Model to simulate the whole farm performance of a representative Wisconsin dairy farm and predict its economic and environmental outputs based on 25 yr of daily local weather data (1986 to 2010). The studied farm, located in southern Wisconsin, had 100 milking cows and 100 ha of cropland with no replacement heifers kept on the farm. Sensitivity analyses were conducted to test the effect of management strategies on energy-corrected milk production (ECM; 4.0% fat and 3.5% protein), net return to management, and greenhouse gas (GHG; including biogenic CO2) emission. The management strategies included (1) target milk production, for which the model optimized available resources to attain, and (2) herd structure, represented by the percentage of first-lactation cows. Weather conditions affected the outputs by changing the farm quantity and the quality of produced feed resources. As expected, when target milk production increased, the ECM increased positively and linearly to a certain level, and then it increased nonlinearly at a decreasing rate, constrained by available feed nutrients. Thereafter, the ECM reached the maximum potential milk production and remained flat regardless of higher target milk production input. Greenhouse gas emissions decreased between 3.4 and 7.3% at different first-lactation cow percentages. As the first-lactation cow percent increased from 15 to 45% in 5% intervals, GHG increased between 9.4 and 11.3% at different levels of target milk production. A high percentage of first-lactation cows reduced the maximum potential milk production. Net return to management had a similar changing trend as ECM. As the target milk production increased from 9,979 to 11,793 kg, the net return to management increased between 31 and 46% at different first-lactation cow percentages. Results revealed a win-win situation when increasing milk production or improving herd structure, which concurrently increased farm net return to management and decreased GHG emissions. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of oncoming target velocities on rapid force production and accuracy of force production intensity and timing.

PubMed

Ohta, Yoichi

2017-12-01

The present study aimed to clarify the effects of oncoming target velocities on the ability of rapid force production and accuracy and variability of simultaneous control of both force production intensity and timing. Twenty male participants (age: 21.0 ± 1.4 years) performed rapid gripping with a handgrip dynamometer to coincide with the arrival of an oncoming target by using a horizontal electronic trackway. The oncoming target velocities were 4, 8, and 12 m · s -1 , which were randomly produced. The grip force required was 30% of the maximal voluntary contraction. Although the peak force (Pf) and rate of force development (RFD) increased with increasing target velocity, the value of the RFD to Pf ratio was constant across the 3 target velocities. The accuracy of both force production intensity and timing decreased at higher target velocities. Moreover, the intrapersonal variability in temporal parameters was lower in the fast target velocity condition, but constant variability in 3 target velocities was observed in force intensity parameters. These results suggest that oncoming target velocity does not intrinsically affect the ability for rapid force production. However, the oncoming target velocity affects accuracy and variability of force production intensity and timing during rapid force production.

Large-scale production of diesel-like biofuels - process design as an inherent part of microorganism development.

PubMed

Cuellar, Maria C; Heijnen, Joseph J; van der Wielen, Luuk A M

2013-06-01

Industrial biotechnology is playing an important role in the transition to a bio-based economy. Currently, however, industrial implementation is still modest, despite the advances made in microorganism development. Given that the fuels and commodity chemicals sectors are characterized by tight economic margins, we propose to address overall process design and efficiency at the start of bioprocess development. While current microorganism development is targeted at product formation and product yield, addressing process design at the start of bioprocess development means that microorganism selection can also be extended to other critical targets for process technology and process scale implementation, such as enhancing cell separation or increasing cell robustness at operating conditions that favor the overall process. In this paper we follow this approach for the microbial production of diesel-like biofuels. We review current microbial routes with both oleaginous and engineered microorganisms. For the routes leading to extracellular production, we identify the process conditions for large scale operation. The process conditions identified are finally translated to microorganism development targets. We show that microorganism development should be directed at anaerobic production, increasing robustness at extreme process conditions and tailoring cell surface properties. All the same time, novel process configurations integrating fermentation and product recovery, cell reuse and low-cost technologies for product separation are mandatory. This review provides a state-of-the-art summary of the latest challenges in large-scale production of diesel-like biofuels. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

GlobPermafrost- How Space-BasedEarth Observation Supports Understanding of Permafrost

NASA Astrophysics Data System (ADS)

Bartsch, Annett; Grosse, Guido; Kaab, Andreas; Westermann, Sebastian; Strozzi, Tazio; Wiesmann, Andreas; Duguay, Claude; Seifert, Frank Martin; Obu, Jaroslav; Goler, Robert

2016-08-01

The GlobPermafrost project develops, validates and implements Earth Observation (EO) products to support research communities and international organisations in their work on better understanding permafrost characteristics and dynamics. To facilitate usability of these products by the target audience, user requirements with respect to the planned products have been requested and collected through an online community survey as well as by interview. This paper provides an overview on the planned thematic EO products as well as results of the user requirement survey.

Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production.

PubMed

George, Kevin W; Chen, Amy; Jain, Aakriti; Batth, Tanveer S; Baidoo, Edward E K; Wang, George; Adams, Paul D; Petzold, Christopher J; Keasling, Jay D; Lee, Taek Soon

2014-08-01

The ability to rapidly assess and optimize heterologous pathway function is critical for effective metabolic engineering. Here, we develop a systematic approach to pathway analysis based on correlations between targeted proteins and metabolites and apply it to the microbial production of isopentenol, a promising biofuel. Starting with a seven-gene pathway, we performed a correlation analysis to reduce pathway complexity and identified two pathway proteins as the primary determinants of efficient isopentenol production. Aided by the targeted quantification of relevant pathway intermediates, we constructed and subsequently validated a conceptual model of isopentenol pathway function. Informed by our analysis, we assembled a strain which produced isopentenol at a titer 1.5 g/L, or 46% of theoretical yield. Our engineering approach allowed us to accurately identify bottlenecks and determine appropriate pathway balance. Paired with high-throughput cloning techniques and analytics, this strategy should prove useful for the analysis and optimization of increasingly complex heterologous pathways. © 2014 Wiley Periodicals, Inc.

Validation approach for a fast and simple targeted screening method for 75 antibiotics in meat and aquaculture products using LC-MS/MS.

PubMed

Dubreil, Estelle; Gautier, Sophie; Fourmond, Marie-Pierre; Bessiral, Mélaine; Gaugain, Murielle; Verdon, Eric; Pessel, Dominique

2017-04-01

An approach is described to validate a fast and simple targeted screening method for antibiotic analysis in meat and aquaculture products by LC-MS/MS. The strategy of validation was applied for a panel of 75 antibiotics belonging to different families, i.e., penicillins, cephalosporins, sulfonamides, macrolides, quinolones and phenicols. The samples were extracted once with acetonitrile, concentrated by evaporation and injected into the LC-MS/MS system. The approach chosen for the validation was based on the Community Reference Laboratory (CRL) guidelines for the validation of screening qualitative methods. The aim of the validation was to prove sufficient sensitivity of the method to detect all the targeted antibiotics at the level of interest, generally the maximum residue limit (MRL). A robustness study was also performed to test the influence of different factors. The validation showed that the method is valid to detect and identify 73 antibiotics of the 75 antibiotics studied in meat and aquaculture products at the validation levels.

75 FR 13489 - Natural Bristle Paint Brushes and Brush Heads from the People's Republic of China: Final Results...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... Animal By-Products Import/Export Corp......... 351.92 Hunan Provincial Native Produce and Animal 351.92 By-Products Import/Export Corp Peace Target, Inc 351.92 PRC-Wide Entity 351.92 Notification Regarding..., 1986) (``Order''). Based on the notice of intent to participate and adequate response filed by the...

Exploiting nature's rich source of proteasome inhibitors as starting points in drug development.

PubMed

Gräwert, Melissa Ann; Groll, Michael

2012-02-01

Cancer is the No. 2 cause of death in the Western world and one of the most expensive diseases to treat. Thus, it is not surprising, that every major pharmaceutical and biotechnology company has a blockbuster oncology product. In 2003, Millennium Pharmaceuticals entered the race with Velcade®, a first-in-class proteasome inhibitor that has been approved by the FDA for treatment of multiple myeloma and its sales have passed the billion dollar mark. Velcade®'s extremely toxic boronic acid pharmacophore, however, contributes to a number of severe side effects. Nevertheless, the launching of this product has validated the proteasome as a target in fighting cancer and further proteasome inhibitors have entered the market as anti-cancer drugs. Additionally, proteasome inhibitors have found application as crop protection agents, anti-parasitics, immunosuppressives, as well as in new therapies for muscular dystrophies and inflammation. Many of these compounds are based on microbial metabolites. In this review, we emphasize the important role of the structural elucidation of the various unique binding mechanisms of these compounds that have been optimized throughout evolution to target the proteasome. Based on this knowledge, medicinal chemists have further optimized these natural products, resulting in potential drugs with reduced off-target activities. This journal is © The Royal Society of Chemistry 2012

Enhanced DNA Sensing via Catalytic Aggregation of Gold Nanoparticles

PubMed Central

Huttanus, Herbert M.; Graugnard, Elton; Yurke, Bernard; Knowlton, William B.; Kuang, Wan; Hughes, William L.; Lee, Jeunghoon

2014-01-01

A catalytic colorimetric detection scheme that incorporates a DNA-based hybridization chain reaction into gold nanoparticles was designed and tested. While direct aggregation forms an inter-particle linkage from only ones target DNA strand, the catalytic aggregation forms multiple linkages from a single target DNA strand. Gold nanoparticles were functionalized with thiol-modified DNA strands capable of undergoing hybridization chain reactions. The changes in their absorption spectra were measured at different times and target concentrations and compared against direct aggregation. Catalytic aggregation showed a multifold increase in sensitivity at low target concentrations when compared to direct aggregation. Gel electrophoresis was performed to compare DNA hybridization reactions in catalytic and direct aggregation schemes, and the product formation was confirmed in the catalytic aggregation scheme at low levels of target concentrations. The catalytic aggregation scheme also showed high target specificity. This application of a DNA reaction network to gold nanoparticle-based colorimetric detection enables highly-sensitive, field-deployable, colorimetric readout systems capable of detecting a variety of biomolecules. PMID:23891867

Feedstock Supply System Design and Economics for Conversion of Lignocellulosic Biomass to Hydrocarbon Fuels: Conversion Pathway: Biological Conversion of Sugars to Hydrocarbons The 2017 Design Case

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

Kevin Kenney; Kara G. Cafferty; Jacob J. Jacobson

The U.S. Department of Energy promotes the production of a range of liquid fuels and fuel blendstocks from lignocellulosic biomass feedstocks by funding fundamental and applied research that advances the state of technology in biomass collection, conversion, and sustainability. As part of its involvement in this program, the Idaho National Laboratory (INL) investigates the feedstock logistics economics and sustainability of these fuels. Between 2000 and 2012, INL conducted a campaign to quantify the economics and sustainability of moving biomass from standing in the field or stand to the throat of the biomass conversion process. The goal of this program wasmore » to establish the current costs based on conventional equipment and processes, design improvements to the current system, and to mark annual improvements based on higher efficiencies or better designs. The 2012 programmatic target was to demonstrate a delivered biomass logistics cost of $35/dry ton. This goal was successfully achieved in 2012 by implementing field and process demonstration unit-scale data from harvest, collection, storage, preprocessing, handling, and transportation operations into INL’s biomass logistics model. Looking forward to 2017, the programmatic target is to supply biomass to the conversion facilities at a total cost of $80/dry ton and on specification with in-feed requirements. The goal of the 2017 Design Case is to enable expansion of biofuels production beyond highly productive resource areas by breaking the reliance of cost-competitive biofuel production on a single, abundant, low-cost feedstock. If this goal is not achieved, biofuel plants are destined to be small and/or clustered in select regions of the country that have a lock on low-cost feedstock. To put the 2017 cost target into perspective of past accomplishments of the cellulosic ethanol pathway, the $80 target encompasses total delivered feedstock cost, including both grower payment and logistics costs, while meeting all conversion in-feed quality targets. The 2012 $35 programmatic target included only logistics costs with a limited focus on biomass quality« less

A novel 9 × 9 map-based solvent selection strategy for targeted counter-current chromatography isolation of natural products.

PubMed

Liang, Junling; Meng, Jie; Wu, Dingfang; Guo, Mengzhe; Wu, Shihua

2015-06-26

Counter-current chromatography (CCC) is an efficient liquid-liquid chromatography technique for separation and purification of complex mixtures like natural products extracts and synthetic chemicals. However, CCC is still a challenging process requiring some special technical knowledge especially in the selection of appropriated solvent systems. In this work, we introduced a new 9 × 9 map-based solvent selection strategy for CCC isolation of targets, which permit more than 60 hexane-ethyl acetate-methanol-water (HEMWat) solvent systems as the start candidates for the selection of solvent systems. Among these solvent systems, there are clear linear correlations between partition coefficient (K) and the system numbers. Thus, an appropriate CCC solvent system (i.e., sweet spot for K = 1) may be hit by measurement of k values of the target only in two random solvent systems. Besides this, surprisingly, we found that through two sweet spots, we could get a line ("Sweet line") where there are infinite sweet solvent systems being suitable for CCC separation. In these sweet solvent systems, the target has the same partition coefficient (K) but different solubilities. Thus, the better sweet solvent system with higher sample solubility can be obtained for high capacity CCC preparation. Furthermore, we found that there is a zone ("Sweet zone") where all solvent systems have their own sweet partition coefficients values for the target in range of 0.4 < K< 2.5 or extended range of 0.25 < K < 16. All results were validated by using 14 pure GUESSmix mimic natural products as standards and further confirmed by isolation of several targets including honokiol and magnolol from the extracts of Magnolia officinalis Rehd. Et Wils and tanshinone IIA from Salvia miltiorrhiza Bunge. In practice, it is much easier to get a suitable solvent system only by making a simple screening two to four HEMWat two-phase solvent systems to obtain the sweet line or sweet zone without special knowledge or comprehensive standards as references. This is an important advancement for solvent system selection and also will be very useful for isolation of current natural products including Traditional Chinese Medicines. Copyright © 2015 Elsevier B.V. All rights reserved.

Improving the Nutritional Resource Environment for Healthy Living Through Community-based Participatory Research

PubMed Central

Sloane, David C; Diamant, Allison L; Lewis, LaVonna B; Yancey, Antronette K; Flynn, Gwendolyn; Nascimento, Lori Miller; McCarthy, William J; Guinyard, Joyce Jones; Cousineau, Michael R

2003-01-01

OBJECTIVES To build health promotion capacity among community residents through a community-based participatory model, and to apply this model to study the nutritional environment of an urban area to better understand the role of such resources in residents' efforts to live a healthy life. DESIGN A multiphase collaborative study that inventoried selected markets in targeted areas of high African-American concentration in comparison with markets in a contrasting wealthier area with fewer African Americans. SETTING A community study set in the Los Angeles metropolitan area. PARTICIPANTS African-American community organizations and community residents in the target areas. INTERVENTIONS Two surveys of market inventories were conducted. The first was a single-sheet form profiling store conditions and the availability of a small selection of healthy foods. The second provided detailed information on whether the store offered fruit, vegetables, low-fat dairy products, dried goods and other items necessary for residents to consume a nutritious diet. RESULTS The targeted areas were significantly less likely to have important items for living a healthier life. The variety and quality of fresh fruit and vegetable produce was significantly lower in the target areas. Such products as 1% milk, skim milk, low-fat and nonfat cheese, soy milk, tofu, whole grain pasta and breads, and low-fat meat and poultry items were sig-nificantly less available. CONCLUSIONS Healthy food products were significantly less available in the target areas. The authors conclude from these results that the health disparities experienced by African-American communities have origins that extend beyond the health delivery system and individual behaviors inasmuch as adherence to the healthy lifestyle associated with low chronic disease risk is more difficult in resource-poor neighborhoods than in resource-rich ones. PMID:12848840

Climate change increases the risk of herbicide-resistant weeds due to enhanced detoxification.

PubMed

Matzrafi, Maor; Seiwert, Bettina; Reemtsma, Thorsten; Rubin, Baruch; Peleg, Zvi

2016-12-01

Global warming will increase the incidence of metabolism-based reduced herbicide efficacy on weeds and, therefore, the risk for evolution of non-target site herbicide resistance. Climate changes affect food security both directly and indirectly. Weeds are the major biotic factor limiting crop production worldwide, and herbicides are the most cost-effective way for weed management. Processes associated with climatic changes, such as elevated temperatures, can strongly affect weed control efficiency. Responses of several grass weed populations to herbicides that inhibit acetyl-CoA carboxylase (ACCase) were examined under different temperature regimes. We characterized the mechanism of temperature-dependent sensitivity and the kinetics of pinoxaden detoxification. The products of pinoxaden detoxification were quantified. Decreased sensitivity to ACCase inhibitors was observed under elevated temperatures. Pre-treatment with the cytochrome-P450 inhibitor malathion supports a non-target site metabolism-based mechanism of herbicide resistance. The first 48 h after herbicide application were crucial for pinoxaden detoxification. The levels of the inactive glucose-conjugated pinoxaden product (M5) were found significantly higher under high- than low-temperature regime. Under high temperature, a rapid elevation in the level of the intermediate metabolite (M4) was found only in pinoxaden-resistant plants. Our results highlight the quantitative nature of non-target-site resistance. To the best of our knowledge, this is the first experimental evidence for temperature-dependent herbicide sensitivity based on metabolic detoxification. These findings suggest an increased risk for the evolution of herbicide-resistant weeds under predicted climatic conditions.

Is the risk for soil arthropods covered by new data requirements under the EU PPP Regulation No. 1107/2009?

PubMed

Kohlschmid, E; Ruf, D

2016-12-01

Testing of effects on earthworms and non-target foliar arthropods is an integral part of the ecotoxicological risk assessment for the authorization of plant protection products. According to the new data requirements, which came into force in 2014 for active substances and in 2016 for plant protection products, the chronic earthworm toxicity test with Eisenia fetida based on reproductive, growth, and behavioral effects instead of the acute earthworm toxicity test based on mortality, has to be conducted routinely. Additional testing of effects on soil arthropods (Folsomia candida, Hyposaspis aculeifer) is required if the risk assessment of foliar applications raises concerns regarding non-target foliar arthropods (Aphidius rhopalosiphi, Typhlodromus pyri) or if the product is applied directly on or into the soil. Thus, it was investigated whether the sublethal earthworm endpoint is more sensitive than the sublethal soil arthropod endpoint for different types of pesticides and whether the risk assessment for non-target arthropods would trigger the testing of effects on soil arthropods in the cases where soil arthropods are more sensitive than earthworms. Toxicity data were obtained from Swiss ecotoxicological database, EFSA Conclusions and scientific literature. For insecticides and herbicides, no general conclusion regarding differences in sensitivity of either earthworms or soil arthropods based on sublethal endpoints were possible. For fungicides, the data indicated that in general, earthworms seemed to be more sensitive than soil arthropods. In total, the sublethal F. candida or H. aculeifer endpoint was lower than the sublethal E. fetida endpoint for 23 (34 %) out of 68 active substances. For 26 % of these 23 active substances, testing of soil arthropods would not have been triggered due to the new data requirement. These results based on sublethal endpoints show that earthworms and soil arthropods differ in sensitivity toward certain active substances and that the risk assessment for non-target foliar arthropods did not always trigger soil arthropod testing in the cases where soil arthropods were more sensitive than earthworms.

Development of loop-mediated isothermal amplification (LAMP) assay for the rapid detection of Penicillium nordicum in dry-cured meat products.

PubMed

Ferrara, M; Perrone, G; Gallo, A; Epifani, F; Visconti, A; Susca, A

2015-06-02

The need of powerful diagnostic tools for rapid, simple, and cost-effective detection of food-borne fungi has become very important in the area of food safety. Currently, several isothermal nucleic acid amplification methods have been developed as an alternative to PCR-based analyses. Loop-mediated isothermal amplification (LAMP) is one of these innovative methods; it requires neither gel electrophoresis to separate and visualize the products nor expensive laboratory equipment and it has been applied already for detection of pathogenic organisms. In the current study, we developed a LAMP assay for the specific detection of Penicillium nordicum, the major causative agent of ochratoxin A contamination in protein-rich food, especially dry-cured meat products. The assay was based on targeting otapksPN gene, a key gene in the biosynthesis of ochratoxin A (OTA) in P. nordicum. Amplification of DNA during the reaction was detected directly in-tube by color transition of hydroxynaphthol blue from violet to sky blue, visible to the naked eye, avoiding further post amplification analyses. Only DNAs isolated from several P. nordicum strains led to positive results and no amplification was observed from non-target OTA and non OTA-producing strains. The assay was able to detect down to 100 fg of purified targeted genomic DNA or 10(2) conidia/reaction within 60 min. The LAMP assay for detection and identification of P. nordicum was combined with a rapid DNA extraction method set up on serially diluted conidia, providing an alternative rapid, specific and sensitive DNA-based method suitable for application directly "on-site", notably in key steps of dry-cured meat production. Copyright © 2015 Elsevier B.V. All rights reserved.

Limitation of Biofuel Production in Europe from the Forest Market

NASA Astrophysics Data System (ADS)

Leduc, Sylvain; Wetterlund, Elisabeth; Dotzauer, Erik; Kindermann, Georg

2013-04-01

The European Union has set a 10% target for the share of biofuel in the transportation sector to be met by 2020. To reach this target, second generation biofuel is expected to replace 3 to 5% of the transport fossil fuel consumption. But the competition on the feedstock is an issue and makes the planning for the second generation biofuel plant a challenge. Moreover, no commercial second generation biofuel production plant is under operation, but if reaching commercial status, this type of production plants are expected to become very large. In order to minimize the tranportation costs and to takle the competetion for the feedstock against the existing woody based industries, the geographical location of biofuel production plants becomes an issue. This study investigates the potential of second generation biofuel economically feasible in Europe by 2020 in regards with the competition for the feedsstock with the existing woody biomass based industries (CHP, pulp and paper mills, sawmills...). To assess the biofuel potential in Europe, a techno-economic, geographically explicit model, BeWhere, is used. It determines the optimal locations of bio-energy production plants by minimizing the costs and CO2 emissions of the entire supply chain. The existing woody based industries have to first meet their wood demand, and if the amount of wood that remains is suficiant, new bio-energy production plants if any can be set up. Preliminary results show that CHP plants are preferably chosen over biofuel production plants. Strong biofuel policy support is needed in order to consequently increase the biofuel production in Europe. The carbon tax influences the emission reduction to a higher degree than the biofuel support. And the potential of second generation biofuel would at most reach 3% of the European transport fuel if the wood demand does not increase from 2010.

Flavored alcoholic beverages: an international marketing campaign that targets youth.

PubMed

Mosher, James F; Johnsson, Diane

2005-09-01

Flavored alcoholic beverages (FABs) were first introduced into the alcohol market in the early I980s in the form of wine coolers. FABs are sweet, relatively low alcohol content beverages that are designed for "entry-level" drinkers. The alcohol industry has introduced new products and production methods to expand the category's popularity. Research suggests that they are popular with underage drinkers, particularly teenage girls, and that the industry uses marketing practices that appear to target youth. FABs are now marketed globally, and their production and marketing vary by country based on national regulatory restraints. In the United States, industry representations that the products are malt beverages for regulatory purposes appears to violate many state laws because the alcohol in the FABs is derived from distilled spirits. Recommendations for regulatory reform, including new legal definitions of FABs, increased taxes, and restrictions on availability, are applicable at both national and state levels.

Real-time observation of DNA target interrogation and product release by the RNA-guided endonuclease CRISPR Cpf1 (Cas12a).

PubMed

Singh, Digvijay; Mallon, John; Poddar, Anustup; Wang, Yanbo; Tippana, Ramreddy; Yang, Olivia; Bailey, Scott; Ha, Taekjip

2018-05-22

CRISPR-Cas9, which imparts adaptive immunity against foreign genomic invaders in certain prokaryotes, has been repurposed for genome-engineering applications. More recently, another RNA-guided CRISPR endonuclease called Cpf1 (also known as Cas12a) was identified and is also being repurposed. Little is known about the kinetics and mechanism of Cpf1 DNA interaction and how sequence mismatches between the DNA target and guide-RNA influence this interaction. We used single-molecule fluorescence analysis and biochemical assays to characterize DNA interrogation, cleavage, and product release by three Cpf1 orthologs. Our Cpf1 data are consistent with the DNA interrogation mechanism proposed for Cas9. They both bind any DNA in search of protospacer-adjacent motif (PAM) sequences, verify the target sequence directionally from the PAM-proximal end, and rapidly reject any targets that lack a PAM or that are poorly matched with the guide-RNA. Unlike Cas9, which requires 9 bp for stable binding and ∼16 bp for cleavage, Cpf1 requires an ∼17-bp sequence match for both stable binding and cleavage. Unlike Cas9, which does not release the DNA cleavage products, Cpf1 rapidly releases the PAM-distal cleavage product, but not the PAM-proximal product. Solution pH, reducing conditions, and 5' guanine in guide-RNA differentially affected different Cpf1 orthologs. Our findings have important implications on Cpf1-based genome engineering and manipulation applications.

[Preparation, quality control and thyroid molecule imaging of solid-target based radionuclide ioine-124].

PubMed

Zhu, H; Wang, F; Guo, X Y; Li, L Q; Duan, D B; Liu, Z B; Yang, Z

2018-04-18

To provide useful information for the further production and application of this novel radio-nuclide for potential clinical application. 124 Te (p,n) 124 I nuclide reaction was used for the 124 I production. Firstly, the target material, 124 TeO 2 (200 mg) and Al2O3 (30 mg) mixture, were compressed into the round platinum based solid target by tablet device. HM-20 medical cyclotron was applied to irradiate the solid target slice for 6-10 h with helium and water cooling. Then, the radiated solid target was placed for 12 h (overnight) to decay the radioactive impurity; finally, 124 I was be purified by dry distillation using 1 mL/min nitrogen for about 6 hours and radiochemical separation methods. Micro-PET imaging studies were performed to investigate the metabolism properties and thyroid imaging ability of 124 I.After 740 kBq 124 I was injected intravenously into the tail vein of the normal mice, the animals were imaged with micro-PET and infused with CT. The micro-PET/CT infusion imaging revealed actual state 124 I's metabolism in the mice. It was been successfully applied for 200 mg 124 TeO 2 plating by the tablet device on the surface of platinum. It showed smooth, dense surface and without obviously pits and cracks. The enriched 124 Te target was irradiated for 6 to 10 hours at about 12.0 MeV with 20 μA current on HM-20 cyclotron. Then 370-1 110 MBq 124 I could be produced on the solid target after irradiation and 370-740 MBq high specific activity could be collected afterdry distillation separation and radio-chemical purification. 124 I product was finally dissolved in 0.01 mol/L NaOH for the future distribution. The gamma spectrum of the produced 124 I-solution showed that radionuclide purity was over 80.0%. The micro-PET imaging of 124 I in the normal mice exhibited the thyroid and stomach accumulations and kidney metabolism, the bladder could also be clearly visible, which was in accordance with what was previously reported. To the best of our knowledge, it was the first production of 124 I report in China. In this study, the preparation of 124 TeO 2 solid target was successfully carried out by using the tablet device. After irradiation of the 124 TeO 2 solid target and radio-chemical purification, we successfully produced 370-740 MBq high specific activity 124 I by a cyclotron for biomedical application, and micro-PET imaging of 124 I in normal mice exhibited the thyroid accumulations. Also, slight uptake in stomach were also monitored with almost nonuptake in other organs in the micro-PET imaging. The production of 124 I is expected to provide a new solid target radionuclide for the scientific research and potential clinical application of our country.

Neutron Detection in the A2 Collaboration Experiment on Neutral Pion Photo-production on Neutron

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

Bulychjov, S. A.; Kudryavtsev, A. E.; Kulikov, V. V.

Neutron detection is of crucial importance for the neutral pion photo-production study on a neutron target that now is in progress at MAMI. Two electro-magnetic calorimeters, based on NaI and BaF 2 crystals, are used in the A2 experiment. While these calorimeters are optimized for pion decay photon detection, they have a reason able efficiency for neutron detection also. The paper describes the method, which has been used to measure this efficiency using the same data taken for pion photo-production study on deuterium target with tagged photon been of 800 MeV maximal energy. As a result, the detection efficiency ismore » a rising function of neutron momentum that reaches 40% near 1 GeV/c.« less

Neutron Detection in the A2 Collaboration Experiment on Neutral Pion Photo-production on Neutron

DOE PAGES

Bulychjov, S. A.; Kudryavtsev, A. E.; Kulikov, V. V.; ...

2018-04-09

Neutron detection is of crucial importance for the neutral pion photo-production study on a neutron target that now is in progress at MAMI. Two electro-magnetic calorimeters, based on NaI and BaF 2 crystals, are used in the A2 experiment. While these calorimeters are optimized for pion decay photon detection, they have a reason able efficiency for neutron detection also. The paper describes the method, which has been used to measure this efficiency using the same data taken for pion photo-production study on deuterium target with tagged photon been of 800 MeV maximal energy. As a result, the detection efficiency ismore » a rising function of neutron momentum that reaches 40% near 1 GeV/c.« less

[Techniques for rapid production of monoclonal antibodies for use with antibody technology].

PubMed

Kamada, Haruhiko

2012-01-01

A monoclonal antibody (Mab), due to its specific binding ability to a target protein, can potentially be one of the most useful tools for the functional analysis of proteins in recent proteomics-based research. However, the production of Mab is a very time-consuming and laborious process (i.e., preparation of recombinant antigens, immunization of animals, preparation of hybridomas), making it the rate-limiting step in using Mabs in high-throughput proteomics research, which heavily relies on comprehensive and rapid methods. Therefore, there is a great demand for new methods to efficiently generate Mabs against a group of proteins identified by proteome analysis. Here, we describe a useful method called "Antibody proteomic technique" for the rapid generations of Mabs to pharmaceutical target, which were identified by proteomic analyses of disease samples (ex. tumor tissue, etc.). We also introduce another method to find profitable targets on vasculature, which is called "Vascular proteomic technique". Our results suggest that this method for the rapid generation of Mabs to proteins may be very useful in proteomics-based research as well as in clinical applications.

Application of advanced diffraction based optical metrology overlay capabilities for high-volume manufacturing

NASA Astrophysics Data System (ADS)

Chen, Kai-Hsiung; Huang, Guo-Tsai; Hsieh, Hung-Chih; Ni, Wei-Feng; Chuang, S. M.; Chuang, T. K.; Ke, Chih-Ming; Huang, Jacky; Rao, Shiuan-An; Cumurcu Gysen, Aysegul; d'Alfonso, Maxime; Yueh, Jenny; Izikson, Pavel; Soco, Aileen; Wu, Jon; Nooitgedagt, Tjitte; Ottens, Jeroen; Kim, Yong Ho; Ebert, Martin

2017-03-01

On-product overlay requirements are becoming more challenging with every next technology node due to the continued decrease of the device dimensions and process tolerances. Therefore, current and future technology nodes require demanding metrology capabilities such as target designs that are robust towards process variations and high overlay measurement density (e.g. for higher order process corrections) to enable advanced process control solutions. The impact of advanced control solutions based on YieldStar overlay data is being presented in this paper. Multi patterning techniques are applied for critical layers and leading to additional overlay measurement demands. The use of 1D process steps results in the need of overlay measurements relative to more than one layer. Dealing with the increased number of overlay measurements while keeping the high measurement density and metrology accuracy at the same time presents a challenge for high volume manufacturing (HVM). These challenges are addressed by the capability to measure multi-layer targets with the recently introduced YieldStar metrology tool, YS350. On-product overlay results of such multi-layers and standard targets are presented including measurement stability performance.

Thin-film filament-based solar cells and modules

NASA Astrophysics Data System (ADS)

Tuttle, J. R.; Cole, E. D.; Berens, T. A.; Alleman, J.; Keane, J.

1997-04-01

This concept paper describes a patented, novel photovoltaic (PV) technology that is capable of achieving near-term commercialization and profitability based upon design features that maximize product performance while minimizing initial and future manufacturing costs. DayStar Technologies plans to exploit these features and introduce a product to the market based upon these differential positions. The technology combines the demonstrated performance and reliability of existing thin-film PV product with a cell and module geometry that cuts material usage by a factor of 5, and enhances performance and manufacturability relative to standard flat-plate designs. The target product introduction price is 1.50/Watt-peak (Wp). This is approximately one-half the cost of the presently available PV product. Additional features include: increased efficiency through low-level concentration, no scribe or grid loss, simple series interconnect, high voltage, light weight, high-throughput manufacturing, large area immediate demonstration, flexibility, modularity.

A prototype for automation of land-cover products from Landsat Surface Reflectance Data Records

NASA Astrophysics Data System (ADS)

Rover, J.; Goldhaber, M. B.; Steinwand, D.; Nelson, K.; Coan, M.; Wylie, B. K.; Dahal, D.; Wika, S.; Quenzer, R.

2014-12-01

Landsat data records of surface reflectance provide a three-decade history of land surface processes. Due to the vast number of these archived records, development of innovative approaches for automated data mining and information retrieval were necessary. Recently, we created a prototype utilizing open source software libraries for automatically generating annual Anderson Level 1 land cover maps and information products from data acquired by the Landsat Mission for the years 1984 to 2013. The automated prototype was applied to two target areas in northwestern and east-central North Dakota, USA. The approach required the National Land Cover Database (NLCD) and two user-input target acquisition year-days. The Landsat archive was mined for scenes acquired within a 100-day window surrounding these target dates, and then cloud-free pixels where chosen closest to the specified target acquisition dates. The selected pixels were then composited before completing an unsupervised classification using the NLCD. Pixels unchanged in pairs of the NLCD were used for training decision tree models in an iterative process refined with model confidence measures. The decision tree models were applied to the Landsat composites to generate a yearly land cover map and related information products. Results for the target areas captured changes associated with the recent expansion of oil shale production and agriculture driven by economics and policy, such as the increase in biofuel production and reduction in Conservation Reserve Program. Changes in agriculture, grasslands, and surface water reflect the local hydrological conditions that occurred during the 29-year span. Future enhancements considered for this prototype include a web-based client, ancillary spatial datasets, trends and clustering algorithms, and the forecasting of future land cover.

Technology CAD for integrated circuit fabrication technology development and technology transfer

NASA Astrophysics Data System (ADS)

Saha, Samar

2003-07-01

In this paper systematic simulation-based methodologies for integrated circuit (IC) manufacturing technology development and technology transfer are presented. In technology development, technology computer-aided design (TCAD) tools are used to optimize the device and process parameters to develop a new generation of IC manufacturing technology by reverse engineering from the target product specifications. While in technology transfer to manufacturing co-location, TCAD is used for process centering with respect to high-volume manufacturing equipment of the target manufacturing equipment of the target manufacturing facility. A quantitative model is developed to demonstrate the potential benefits of the simulation-based methodology in reducing the cycle time and cost of typical technology development and technology transfer projects over the traditional practices. The strategy for predictive simulation to improve the effectiveness of a TCAD-based project, is also discussed.

Emerging engineering principles for yield improvement in microbial cell design.

PubMed

Comba, Santiago; Arabolaza, Ana; Gramajo, Hugo

2012-01-01

Metabolic Engineering has undertaken a rapid transformation in the last ten years making real progress towards the production of a wide range of molecules and fine chemicals using a designed cellular host. However, the maximization of product yields through pathway optimization is a constant and central challenge of this field. Traditional methods used to improve the production of target compounds from engineered biosynthetic pathways in non-native hosts include: codon usage optimization, elimination of the accumulation of toxic intermediates or byproducts, enhanced production of rate-limiting enzymes, selection of appropriate promoter and ribosome binding sites, application of directed evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to be specific for each engineering project rather than a systematic practice based on a more generalizable strategy. In this mini-review, we highlight some novel and extensive approaches and tools intended to address the improvement of a target product formation, founded in sophisticated principles such as dynamic control, pathway genes modularization, and flux modeling.

Emerging engineering principles for yield improvement in microbial cell design

PubMed Central

Comba, Santiago; Arabolaza, Ana; Gramajo, Hugo

2012-01-01

Metabolic Engineering has undertaken a rapid transformation in the last ten years making real progress towards the production of a wide range of molecules and fine chemicals using a designed cellular host. However, the maximization of product yields through pathway optimization is a constant and central challenge of this field. Traditional methods used to improve the production of target compounds from engineered biosynthetic pathways in non-native hosts include: codon usage optimization, elimination of the accumulation of toxic intermediates or byproducts, enhanced production of rate-limiting enzymes, selection of appropriate promoter and ribosome binding sites, application of directed evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to be specific for each engineering project rather than a systematic practice based on a more generalizable strategy. In this mini-review, we highlight some novel and extensive approaches and tools intended to address the improvement of a target product formation, founded in sophisticated principles such as dynamic control, pathway genes modularization, and flux modeling. PMID:24688676

PCR-free quantitative detection of genetically modified organism from raw materials – A novel electrochemiluminescence-based bio-barcode method

PubMed Central

Zhu, Debin; Tang, Yabing; Xing, Da; Chen, Wei R.

2018-01-01

Bio-barcode assay based on oligonucleotide-modified gold nanoparticles (Au-NPs) provides a PCR-free method for quantitative detection of nucleic acid targets. However, the current bio-barcode assay requires lengthy experimental procedures including the preparation and release of barcode DNA probes from the target-nanoparticle complex, and immobilization and hybridization of the probes for quantification. Herein, we report a novel PCR-free electrochemiluminescence (ECL)-based bio-barcode assay for the quantitative detection of genetically modified organism (GMO) from raw materials. It consists of tris-(2’2’-bipyridyl) ruthenium (TBR)-labele barcode DNA, nucleic acid hybridization using Au-NPs and biotin-labeled probes, and selective capture of the hybridization complex by streptavidin-coated paramagnetic beads. The detection of target DNA is realized by direct measurement of ECL emission of TBR. It can quantitatively detect target nucleic acids with high speed and sensitivity. This method can be used to quantitatively detect GMO fragments from real GMO products. PMID:18386909

PCR-free quantitative detection of genetically modified organism from raw materials. An electrochemiluminescence-based bio bar code method.

PubMed

Zhu, Debin; Tang, Yabing; Xing, Da; Chen, Wei R

2008-05-15

A bio bar code assay based on oligonucleotide-modified gold nanoparticles (Au-NPs) provides a PCR-free method for quantitative detection of nucleic acid targets. However, the current bio bar code assay requires lengthy experimental procedures including the preparation and release of bar code DNA probes from the target-nanoparticle complex and immobilization and hybridization of the probes for quantification. Herein, we report a novel PCR-free electrochemiluminescence (ECL)-based bio bar code assay for the quantitative detection of genetically modified organism (GMO) from raw materials. It consists of tris-(2,2'-bipyridyl) ruthenium (TBR)-labeled bar code DNA, nucleic acid hybridization using Au-NPs and biotin-labeled probes, and selective capture of the hybridization complex by streptavidin-coated paramagnetic beads. The detection of target DNA is realized by direct measurement of ECL emission of TBR. It can quantitatively detect target nucleic acids with high speed and sensitivity. This method can be used to quantitatively detect GMO fragments from real GMO products.

Identification of unwanted photoproducts of cosmetic preservatives in personal care products under ultraviolet-light using solid-phase microextraction and micro-matrix solid-phase dispersion.

PubMed

Alvarez-Rivera, Gerardo; Llompart, Maria; Garcia-Jares, Carmen; Lores, Marta

2015-04-17

The photochemical transformation of widely used cosmetic preservatives including benzoates, parabens, BHA, BHT and triclosan has been investigated in this work applying an innovative double-approach strategy: identification of transformation products in aqueous photodegradation experiments (UV-light, 254nm), followed by targeted screening analysis of such photoproducts in UV-irradiated cosmetic samples. Solid-phase microextraction (SPME) was applied, using different fiber coatings, in order to widen the range of detectable photoproducts in water, whereas UV-irradiated personal care products (PCPs) containing the target preservatives were extracted by micro-matrix solid-phase dispersion (micro-MSPD). Both SPME and micro-MSPD-based methodologies were successfully optimized and validated. Degradation kinetics of parent species, and photoformation of their transformation by-products were monitored by gas chromatography coupled to mass spectrometry (GC-MS). Thirty nine photoproducts were detected in aqueous photodegradation experiments, being tentatively identified based on their mass spectra. Transformation pathways between structurally related by-products, consistent with their kinetic behavior were postulated. The photoformation of unexpected photoproducts such as 2- and 4-hydroxybenzophenones, and 2,8-dichlorodibenzo-p-dioxin in PCPs are reported in this work for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.

Touch the Page and Mimic Me: Evaluation of a Talking-Pen Learning Tool

ERIC Educational Resources Information Center

Odakura, Abigail

2013-01-01

The purpose of this paper is to evaluate the talking-pen device called the Mimic Me, an educational technology product of a large English conversation school in Japan, as an educational learning tool. The product will be reviewed in terms of its developmental appropriateness for the target audience based on current research. Although the Mimic Me…

Remilling of salvaged wood siding coated with lead-based paint. Part 2, Wood product yield

Treesearch

John J. Janowiak; Robert H. Falk; Brian W. Beakler; Richard G. Lampo; Thomas R. Napier

2005-01-01

Many U.S. military buildings being targeted for removal contain large quantities of potentially reusable wood materials. In this study, we evaluated approximately 2180 m (7,152 ft) of painted Douglas-fir siding salvaged from U.S. Army barracks. Utilizing a conventional woodworking molder, we evaluated the feasibility of producing several standardized wood product...

The Economic Gains of Achieving Reduced Alcohol Consumption Targets for Australia

PubMed Central

Magnus, Anne; Cadilhac, Dominique; Sheppard, Lauren; Cumming, Toby; Pearce, Dora; Carter, Rob

2012-01-01

Objectives. To inform prevention policy, we estimated the economic benefits to health, production, and leisure in the 2008 Australian population of a realistic target reduction in per capita annual adult alcohol consumption. Methods. We chose a target of 6.4 liters annually per capita on average. We modeled lifetime health benefits as fewer incident cases of alcohol-related disease, deaths, and disability adjusted life years. We estimated production gains with surveyed participation and absenteeism rates. We valued gains with friction cost and human capital methods. We estimated and valued household production and leisure gains from time-use surveys. Results. A reduction of 3.4 liters of alcohol consumed annually per capita would result in one third fewer incident cases of disease (98 000), deaths (380), working days lost (5 million), days of home-based production lost (54 000), and a A$ 789-million health sector cost reduction. Workforce production had a A$ 427 million gain when we used the friction cost method. By contrast, we estimated a loss of 28 000 leisure days and 1000 additional early retirements. Conclusions. Economic savings and health benefits from reduced alcohol consumption may be substantial—particularly in the health sector with reduced alcohol-related disease and injury. PMID:22594720

Gene targeting in mosquito cells: a demonstration of 'knockout' technology in extrachromosomal gene arrays

PubMed Central

Eggleston, Paul; Zhao, Yuguang

2001-01-01

Background Gene targeting would offer a number of advantages over current transposon-based strategies for insect transformation. These include freedom from both position effects associated with quasi-random integration and concerns over transgene instability mediated by endogenous transposases, independence from phylogenetic restrictions on transposon mobility and the ability to generate gene knockouts. Results We describe here our initial investigations of gene targeting in the mosquito. The target site was a hygromycin resistance gene, stably maintained as part of an extrachromosomal array. Using a promoter-trap strategy to enrich for targeted events, a neomycin resistance gene was integrated into the target site. This resulted in knockout of hygromycin resistance concurrent with the expression of high levels of neomycin resistance from the resident promoter. PCR amplification of the targeted site generated a product that was specific to the targeted cell line and consistent with precise integration of the neomycin resistance gene into the 5' end of the hygromycin resistance gene. Sequencing of the PCR product and Southern analysis of cellular DNA subsequently confirmed this molecular structure. Conclusions These experiments provide the first demonstration of gene targeting in mosquito tissue and show that mosquito cells possess the necessary machinery to bring about precise integration of exogenous sequences through homologous recombination. Further development of these procedures and their extension to chromosomally located targets hold much promise for the exploitation of gene targeting in a wide range of medically and economically important insect species. PMID:11513755

Cryogenic hydrogen fuel for controlled inertial confinement fusion (formation of reactor-scale cryogenic targets)

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

Aleksandrova, I. V.; Koresheva, E. R., E-mail: elena.koresheva@gmail.com; Krokhin, O. N.

2016-12-15

In inertial fusion energy research, considerable attention has recently been focused on low-cost fabrication of a large number of targets by developing a specialized layering module of repeatable operation. The targets must be free-standing, or unmounted. Therefore, the development of a target factory for inertial confinement fusion (ICF) is based on methods that can ensure a cost-effective target production with high repeatability. Minimization of the amount of tritium (i.e., minimization of time and space at all production stages) is a necessary condition as well. Additionally, the cryogenic hydrogen fuel inside the targets must have a structure (ultrafine layers—the grain sizemore » should be scaled back to the nanometer range) that supports the fuel layer survivability under target injection and transport through the reactor chamber. To meet the above requirements, significant progress has been made at the Lebedev Physical Institute (LPI) in the technology developed on the basis of rapid fuel layering inside moving free-standing targets (FST), also referred to as the FST layering method. Owing to the research carried out at LPI, unique experience has been gained in the development of the FST-layering module for target fabrication with an ultrafine fuel layer, including a reactor- scale target design. This experience can be used for the development of the next-generation FST-layering module for construction of a prototype of a target factory for power laser facilities and inertial fusion power plants.« less

Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

PubMed

Malayandi, Rajkumar; Kondamudi, Phani Krishna; Ruby, P K; Aggarwal, Deepika

2014-04-01

Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin.

PubMed

Menchon, Grégory; Prota, Andrea E; Lucena-Agell, Daniel; Bucher, Pascal; Jansen, Rolf; Irschik, Herbert; Müller, Rolf; Paterson, Ian; Díaz, J Fernando; Altmann, Karl-Heinz; Steinmetz, Michel O

2018-05-29

Microtubule-targeting agents (MTAs) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered maytansine site of tubulin. Using this assay, we have determined the dissociation constants of known maytansine site ligands, including the pharmacologically active degradation product of the clinical antibody-drug conjugate trastuzumab emtansine. In addition, we discovered that the two natural products spongistatin-1 and disorazole Z with established cellular potency bind to the maytansine site on β-tubulin. The high-resolution crystal structures of spongistatin-1 and disorazole Z in complex with tubulin allowed the definition of an additional sub-site adjacent to the pocket shared by all maytansine-site ligands, which could be exploitable as a distinct, separate target site for small molecules. Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer.

Photo-ionization of aluminum in a hot cavity for the selective production of exotic species project

NASA Astrophysics Data System (ADS)

Scarpa, D.; Makhathini, L.; Tomaselli, A.; Grassi, D.; Corradetti, S.; Manzolaro, M.; Vasquez, J.; Calderolla, M.; Rossignoli, M.; Monetti, A.; Andrighetto, A.; Prete, G.

2014-02-01

SPES (Selective Production of Exotic Species) is an Isotope Separation On-Line (ISOL) based accelerator facility that will be built in the Legnaro-Istituto Nazionale di Fisica Nucleare (INFN) Laboratory (Italy), intended to provide intense neutron-rich radioactive ion beams obtained by proton-induced fission of a uranium carbide (UCx) target. Besides this main target material, silicon carbide (SiC) will be the first to be used to deliver p-rich beams. This target will also validate the functionality of the SPES facility with aluminum beam as result of impinging SiC target with proton beam. In the past, off line studies on laser photoionization of aluminum have been performed in Pavia Spectroscopy Laboratory and in Laboratori Nazionali di Legnaro; a XeCl excimer laser was installed in order to test the laser ionization in the SPES hot cavity. With the new Wien filter installed a better characterization of the ionization process in terms of efficiency was performed and results are discussed.

The roles of word-form frequency and phonological neighbourhood density in the acquisition of Lithuanian noun morphology.

PubMed

Savičiūtė, Eglė; Ambridge, Ben; Pine, Julian M

2018-05-01

Four- and five-year-old children took part in an elicited familiar and novel Lithuanian noun production task to test predictions of input-based accounts of the acquisition of inflectional morphology. Two major findings emerged. First, as predicted by input-based accounts, correct production rates were correlated with the input frequency of the target form, and with the phonological neighbourhood density of the noun. Second, the error patterns were not compatible with the systematic substitution of target forms by either (a) the most frequent form of that noun or (b) a single morphosyntactic default form, as might be predicted by naive versions of a constructivist and generativist account, respectively. Rather, most errors reflected near-miss substitutions of singular for plural, masculine for feminine, or nominative/accusative for a less frequent case. Together, these findings provide support for an input-based approach to morphological acquisition, but are not adequately explained by any single account in its current form.

Engineering nucleases for gene targeting: safety and regulatory considerations.

PubMed

Pauwels, Katia; Podevin, Nancy; Breyer, Didier; Carroll, Dana; Herman, Philippe

2014-01-25

Nuclease-based gene targeting (NBGT) represents a significant breakthrough in targeted genome editing since it is applicable from single-celled protozoa to human, including several species of economic importance. Along with the fast progress in NBGT and the increasing availability of customized nucleases, more data are available about off-target effects associated with the use of this approach. We discuss how NBGT may offer a new perspective for genetic modification, we address some aspects crucial for a safety improvement of the corresponding techniques and we also briefly relate the use of NBGT applications and products to the regulatory oversight. Copyright © 2013 Elsevier B.V. All rights reserved.

Defining the Needs for Next Generation Assays for Tuberculosis

PubMed Central

Denkinger, Claudia M.; Kik, Sandra V.; Cirillo, Daniela Maria; Casenghi, Martina; Shinnick, Thomas; Weyer, Karin; Gilpin, Chris; Boehme, Catharina C.; Schito, Marco; Kimerling, Michael; Pai, Madhukar

2015-01-01

To accelerate the fight against tuberculosis, major diagnostic challenges need to be addressed urgently. Post-2015 targets are unlikely to be met without the use of novel diagnostics that are more accurate and can be used closer to where patients first seek care in affordable diagnostic algorithms. This article describes the efforts by the stakeholder community that led to the identification of the high-priority diagnostic needs in tuberculosis. Subsequently target product profiles for the high-priority diagnostic needs were developed and reviewed in a World Health Organization (WHO)-led consensus meeting. The high-priority diagnostic needs included (1) a sputum-based replacement test for smear-microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis, ideally suitable for use at levels below microscopy centers; (3) a simple, low cost triage test for use by first-contact care providers as a rule-out test, ideally suitable for use by community health workers; and (4) a rapid drug susceptibility test for use at the microscopy center level. The developed target product profiles, along with complimentary work presented in this supplement, will help to facilitate the interaction between the tuberculosis community and the diagnostics industry with the goal to lead the way toward the post-2015 global tuberculosis targets. PMID:25765104

Process Design and Economics for the Production of Algal Biomass: Algal Biomass Production in Open Pond Systems and Processing Through Dewatering for Downstream Conversion

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

Davis, Ryan; Markham, Jennifer; Kinchin, Christopher

2016-02-17

This report describes in detail a set of aspirational design and process targets to better understand the realistic economic potential for the production of algal biomass for subsequent conversion to biofuels and/or coproducts, based on the use of open pond cultivation systems and a series of dewatering operations to concentrate the biomass up to 20 wt% solids (ash-free dry weight basis).

Production and Evaluation of 236gNp and Reference Materials for Naturally Occurring Radioactive Materials

NASA Astrophysics Data System (ADS)

Larijani, Cyrus Kouroush

This thesis is based on the development of a radiochemical separation scheme capable of separating both 236gNp and 236Pu from a uranium target of natural isotopic composition ( 1 g uranium) and 200 MBq of fission decay products. The isobaric distribution of fission residues produced following the bombardment of a natural uranium target with a beam of 25 MeV protons has been evaluated. Decay analysis of thirteen isobarically distinct fission residues were carried out using high-resolution gamma-ray spectrometry at the UK National Physical Laboratory. Stoichiometric abundances were calculated via the determination of absolute activity concentrations associated with the longest-lived members of each isobaric chain. This technique was validated by computational modelling of likely sequential decay processes through an isobaric decay chain. The results were largely in agreement with previously published values for neutron bombardments on natural uranium at energies of 14 MeV. Higher relative yields of products with mass numbers A 110-130 were found, consistent with the increasing yield of these radionuclides as the bombarding energy is increased. Using literature values for the production cross-section for fusion of protons with uranium targets, it is estimated that an upper limit of approximately 250 Bq of activity from the 236Np ground state was produced in this experiment. Using a radiochemical separation scheme, Np and Pu fractions were separated from the produced fission decay products, with analyses of the target-based final reaction products made using Inductively Couple Plasma Mass Spectrometry (ICP-MS) and high-resolution alpha and gamma-ray spectrometry. In a separate research theme, reliable measurement of Naturally Occurring Radioactive Materials is of significance in order to comply with environmental regulations and for radiological protection purposes. The thesis describes the standardisation of three reference materials, namely Sand, Tuff and TiO2 which can serve as quality control materials to achieve traceability, method validation and instrument calibration. The sample preparation, material characterization via gamma, alpha and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and the assignment of values for both the 4n Thorium and 4n + 2 Uranium decay series are presented.

Alignment of microbial fitness with engineered product formation: obligatory coupling between acetate production and photoautotrophic growth.

PubMed

Du, Wei; Jongbloets, Joeri A; van Boxtel, Coco; Pineda Hernández, Hugo; Lips, David; Oliver, Brett G; Hellingwerf, Klaas J; Branco Dos Santos, Filipe

2018-01-01

Microbial bioengineering has the potential to become a key contributor to the future development of human society by providing sustainable, novel, and cost-effective production pipelines. However, the sustained productivity of genetically engineered strains is often a challenge, as spontaneous non-producing mutants tend to grow faster and take over the population. Novel strategies to prevent this issue of strain instability are urgently needed. In this study, we propose a novel strategy applicable to all microbial production systems for which a genome-scale metabolic model is available that aligns the production of native metabolites to the formation of biomass. Based on well-established constraint-based analysis techniques such as OptKnock and FVA, we developed an in silico pipeline-FRUITS-that specifically 'Finds Reactions Usable in Tapping Side-products'. It analyses a metabolic network to identify compounds produced in anabolism that are suitable to be coupled to growth by deletion of their re-utilization pathway(s), and computes their respective biomass and product formation rates. When applied to Synechocystis sp. PCC6803, a model cyanobacterium explored for sustainable bioproduction, a total of nine target metabolites were identified. We tested our approach for one of these compounds, acetate, which is used in a wide range of industrial applications. The model-guided engineered strain shows an obligatory coupling between acetate production and photoautotrophic growth as predicted. Furthermore, the stability of acetate productivity in this strain was confirmed by performing prolonged turbidostat cultivations. This work demonstrates a novel approach to stabilize the production of target compounds in cyanobacteria that culminated in the first report of a photoautotrophic growth-coupled cell factory. The method developed is generic and can easily be extended to any other modeled microbial production system.

The Army Budget Amended Fiscal Year 1990-91

DTIC Science & Technology

1989-05-01

Station -PERS: Personnel -PGTS: Precision Gunnery Target System -PHIL: Phillipines -PIP: Product Improvement Program -PL: Public Law -PM TRADE : Program...COMANDS 24.174 24.884 27,092 37,280 FOREIGN CURRECY FLUCTUATION 453,848 73,260 0 0 009 BASE INFORMATION MANAGEMENT 72,028 68.967 78,953 80,323 056 BASE

Leucine zipper-mediated targeting of multi-enzyme cascade reactions to inclusion bodies in Escherichia coli for enhanced production of 1-butanol.

PubMed

Han, Gui Hwan; Seong, Wonjae; Fu, Yaoyao; Yoon, Paul K; Kim, Seong Keun; Yeom, Soo-Jin; Lee, Dae-Hee; Lee, Seung-Goo

2017-03-01

Metabolons in nature have evolved to facilitate more efficient catalysis of multistep reactions through the co-localization of functionally related enzymes to cellular organelles or membrane structures. To mimic the natural metabolon architecture, we present a novel artificial metabolon that was created by targeting multi-enzyme cascade reactions onto inclusion body (IB) in Escherichia coli. The utility of this system was examined by co-localizing four heterologous enzymes of the 1-butanol pathway onto an IB that was formed in E. coli through overexpression of the cellulose binding domain (CBD) of Cellulomonas fimi exoglucanase. To target the 1-butanol pathway enzymes to the CBD IB, we utilized a peptide-peptide interaction between leucine zipper (LZ) peptides. We genetically fused the LZ peptide to the N-termini of four heterologous genes involved in the synthetic 1-butanol pathway, whereas an antiparallel LZ peptide was fused to the CBD gene. The in vivo activity of the CBD IB-based metabolon was examined through the determination of 1-butanol synthesis using E. coli transformed with two plasmids containing the LZ-fused CBD and LZ-fused 1-butanol pathway genes, respectively. In vivo synthesis of 1-butanol using the engineered E. coli yielded 1.98g/L of 1-butanol from glucose, representing a 1.5-fold increase over that obtained from E. coli expressing the LZ-fused 1-butanol pathway genes alone. In an attempt to examine the in vitro 1-butanol productivity, we reconstituted CBD IB-based metabolon using CBD IB and individual enzymes of 1-butanol pathway. The 1-butanol productivity of in vitro reconstituted CBD IB-based metabolon using acetoacetyl-CoA as the starting material was 2.29mg/L/h, 7.9-fold higher than that obtained from metabolon-free enzymes of 1-butanol pathway. Therefore, this novel CBD-based artificial metabolon may prove useful in metabolic engineering both in vivo and in vitro for the efficient production of desired products. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Tomato-based food products for prostate cancer prevention: what have we learned?

PubMed

Tan, Hsueh-Li; Thomas-Ahner, Jennifer M; Grainger, Elizabeth M; Wan, Lei; Francis, David M; Schwartz, Steven J; Erdman, John W; Clinton, Steven K

2010-09-01

Evidence derived from a vast array of laboratory studies and epidemiological investigations have implicated diets rich in fruits and vegetables with a reduced risk of certain cancers. However, these approaches cannot demonstrate causal relationships and there is a paucity of randomized, controlled trials due to the difficulties involved with executing studies of food and behavioral change. Rather than pursuing the definitive intervention trials that are necessary, the thrust of research in recent decades has been driven by a reductionist approach focusing upon the identification of bioactive components in fruits and vegetables with the subsequent development of single agents using a pharmacologic approach. At this point in time, there are no chemopreventive strategies that are standard of care in medical practice that have resulted from this approach. This review describes an alternative approach focusing upon development of tomato-based food products for human clinical trials targeting cancer prevention and as an adjunct to therapy. Tomatoes are a source of bioactive phytochemicals and are widely consumed. The phytochemical pattern of tomato products can be manipulated to optimize anticancer activity through genetics, horticultural techniques, and food processing. The opportunity to develop a highly consistent tomato-based food product rich in anticancer phytochemicals for clinical trials targeting specific cancers, particularly the prostate, necessitates the interactive transdisciplinary research efforts of horticulturalists, food technologists, cancer biologists, and clinical translational investigators.

Tomato-based food products for prostate cancer prevention: what have we learned?

PubMed Central

Tan, Hsueh-Li; Thomas-Ahner, Jennifer M.; Grainger, Elizabeth M.; Wan, Lei; Francis, David M.; Schwartz, Steven J.; Erdman, John W.

2013-01-01

Evidence derived from a vast array of laboratory studies and epidemiological investigations have implicated diets rich in fruits and vegetables with a reduced risk of certain cancers. However, these approaches cannot demonstrate causal relationships and there is a paucity of randomized, controlled trials due to the difficulties involved with executing studies of food and behavioral change. Rather than pursuing the definitive intervention trials that are necessary, the thrust of research in recent decades has been driven by a reductionist approach focusing upon the identification of bioactive components in fruits and vegetables with the subsequent development of single agents using a pharmacologic approach. At this point in time, there are no chemopreventive strategies that are standard of care in medical practice that have resulted from this approach. This review describes an alternative approach focusing upon development of tomato-based food products for human clinical trials targeting cancer prevention and as an adjunct to therapy. Tomatoes are a source of bioactive phytochemicals and are widely consumed. The phytochemical pattern of tomato products can be manipulated to optimize anticancer activity through genetics, horticultural techniques, and food processing. The opportunity to develop a highly consistent tomato-based food product rich in anticancer phytochemicals for clinical trials targeting specific cancers, particularly the prostate, necessitates the interactive transdisciplinary research efforts of horticulturalists, food technologists, cancer biologists, and clinical translational investigators. PMID:20803054

Potential impact of Thailand's alcohol program on production, consumption, and trade of cassava, sugarcane, and corn

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

Boonserm, P.

1985-01-01

On the first of May 1980, Thailand's fuel-alcohol program was announced by the Thai government. According to the program, a target of 147 million liters of ethanol would be produced in 1981, from cassava, sugarcane, and other biomasses. Projecting increases in output each year, the target level of ethanol produciton was set at 482 million liters of ethanol for 1986. The proposed amount of ethanol production could create a major shift up in the demand schedule of energy crops such as cassava, sugarcane, and corn. The extent of the adjustments in price, production, consumption, and exports for these energy cropsmore » need to be evaluated. The purpose of this study is to assess the potential impact of Thailand's fuel-alcohol program on price, production, consumption, and exports of three potential energy crops: cassava, sugarcane, and corn. Econometric commodity models of cassava, sugarcane, and corn are constructed and used as a method of assessment. The overall results of the forecasting simulations of the models indicate that the fuel-alcohol program proposed by the Thai government will cause the price, production, and total consumption of cassava, sugarcane, and corn to increase; on the other hand, it will cause exports to decline. In addition, based on the relative prices and the technical coefficients of ethanol production of these three energy crops, this study concludes that only cassava should be used to produce the proposed target of ethanol production.« less

Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions

PubMed Central

Kagan, Valerian E.; Wipf, Peter; Stoyanovsky, Detcho; Greenberger, Joel S.; Borisenko, Grigory; Belikova, Natalia A.; Yanamala, Naveena; Samhan Arias, Alejandro K.; Tungekar, Muhammad A.; Jiang, Jianfei; Tyurina, Yulia Y.; Ji, Jing; Klein-Seetharaman, Judith; Pitt, Bruce R.; Shvedova, Anna A; Bayır, Hülya

2009-01-01

Effective regulation of highly compartmentalized production of reactive oxygen species and peroxidation reactions in mitochondria requires targeting of small molecule antioxidants and antioxidant enzymes into the organelles. This review describes recently developed approaches to mitochondrial targeting of small biologically active molecules based on: (i) preferential accumulation in mitochondria because of their hydrophobicity and positive charge (hydrophobic cations), (ii) binding with high affinity to an intra-mitochondrial constituent, and (iii) metabolic conversions by specific mitochondrial enzymes to reveal an active entity. In addition, targeted delivery of antioxidant enzymes via expression of leader-sequences directing the proteins into mitochondria is considered. Examples of successful antioxidant and anti-apoptotic protection based on the ability of targeted cargoes to inhibit cytochrome c-catalyzed peroxidation of a mitochondria-specific phospholipid cardiolipin, in vitro and in vivo are presented. Particular emphasis is placed on the employment of triphenylphosphonium- and hemi-gramicidin S-moieties as two effective vehicles for mitochondrial delivery of antioxidants. PMID:19716396

Development and validation of a 48-target analytical method for high-throughput monitoring of genetically modified organisms.

PubMed

Li, Xiaofei; Wu, Yuhua; Li, Jun; Li, Yunjing; Long, Likun; Li, Feiwu; Wu, Gang

2015-01-05

The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection.

Development and Validation of A 48-Target Analytical Method for High-throughput Monitoring of Genetically Modified Organisms

PubMed Central

Li, Xiaofei; Wu, Yuhua; Li, Jun; Li, Yunjing; Long, Likun; Li, Feiwu; Wu, Gang

2015-01-01

The rapid increase in the number of genetically modified (GM) varieties has led to a demand for high-throughput methods to detect genetically modified organisms (GMOs). We describe a new dynamic array-based high throughput method to simultaneously detect 48 targets in 48 samples on a Fludigm system. The test targets included species-specific genes, common screening elements, most of the Chinese-approved GM events, and several unapproved events. The 48 TaqMan assays successfully amplified products from both single-event samples and complex samples with a GMO DNA amount of 0.05 ng, and displayed high specificity. To improve the sensitivity of detection, a preamplification step for 48 pooled targets was added to enrich the amount of template before performing dynamic chip assays. This dynamic chip-based method allowed the synchronous high-throughput detection of multiple targets in multiple samples. Thus, it represents an efficient, qualitative method for GMO multi-detection. PMID:25556930

Tracking of buried layers during plasma-assisted femtosecond laser drilling of compound targets

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

Zhvaniya, I. A., E-mail: irina.zhvaniya@physics.msu.ru; Garmatina, A. A.; Makarov, I. A.

It was shown that drilling of multi-layered target placed in the air by tightly focused femtosecond laser radiation with high fluence (up to 1000 J/cm{sup 2}) can be monitored online using plasma-induced X-ray emission and second harmonic of incident laser radiation. The technique based on X-rays registration is appeared to be more flexible than the method based on detection of second harmonic since its accuracy depends crucially on the target type. We demonstrated that the X-ray signal clearly indicates the transition from one layer to another during the microdrilling of targets consisting of 2–4 layers of titanium foil when a lasermore » beam is focused beneath the target surface at a depth comparable to the layer thickness. The diagnostics of microchannel production in the chicken eggshell was performed for the first time. It was found that the presence of albumen beneath the shell accounts for longtime generation of X-ray pulses.« less

Target biomarker profile for the clinical management of paracetamol overdose

PubMed Central

Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

2015-01-01

Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

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

Sun, Zhen; Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058; Xiang, Wenqing

Highlights: {yields} LNA-modified oligonucleotides can pass through the plasma membrane of cultured cells even without using transfection machinery. {yields} LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. {yields} LNA-oligonucleotide designed to target nuclear HBV DNA efficiently suppresses HBV replication and transcription in cultured hepatic cells. -- Abstract: Silencing target genes with small regulatory RNAs is widely used to investigate gene function and therapeutic drug development. Recently, triplex-based approaches have provided another attractive means to achieve targeted gene regulation and gene manipulation at the molecular and cellular levels. Nuclear entry ofmore » oligonucleotides and enhancement of their affinity to the DNA targets are key points of such approaches. In this study, we developed lipid-based transport of a locked-nucleic-acid (LNA)-modified oligonucleotide for hepatitis B virus (HBV) DNA interference in human hepatocytes expressing HBV genomic DNA. In these cells, the LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. The oligonucleotide specifically targeting HBV DNA clearly interfered with HBV DNA transcription as shown by a block in pregenomic RNA (pgRNA) production. The HBV DNA-targeted oligonucleotide suppressed HBV DNA replication and HBV protein production more efficiently than small interfering RNAs directed to the pgRNA. These results demonstrate that fusion with lipid can carry LNA-modified oligonucleotides to the nucleus where they regulate gene expression. Interfering with HBV DNA transcription by LNA-modified oligonucleotides has strong potential as a new strategy for HBV inhibition.« less

Industrial recovered-materials-utilization targets for the textile-mill-products industry

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

None

1979-01-01

The Congress, in the National Energy Conservation and Policy Act of 1978 (NECPA), directed the Department of Energy to establish materials recovery targets for the metals and metal products, paper and allied products, rubber, and textile-mill-products industries. The targets were developed to provide incentives for using energy-saving recorded materials and to provied a yardstick for measuring progress and improvement in this endeavor. The NECPA indicates that the targets should represent the maximum technically and economically feasible increase in the use of energy-saving recovered materials that each industry can achieve progressively by January 1, 1987. Materials affected by recovered-materials targets includemore » and are limited to aluminum, copper, lead, zinc, iron, steel, paper and associated products, textile-mill, products, and rubber. Using information gathered from the textile-mill-products industry and from other textile-relaed sources, DOE has developed recovered materials targets for that industry. This report presents those targets and their basis and justification. Following an overview of the textile industry, the chapters are: Textile-Mill-Products Industry Operations; Economic Analysis of the Textile-Mill-Products Industry; Governmental and Regulatory Influence on the US Textile Industry; Current Mill Use of Recovered Materials in the Textile-Mill-Products Industry; Limitations on the Use of Recovered Materials in the US Textile-Mill-Products Industry; Materials-Recovery Targets; and Government and Industry Actions That Could Increase the Use of Recovered Materials.« less

Design and engineering of a target for x-ray Thomson scattering measurements on matter at extreme densities and gigabar pressures

DOE PAGES

Boehm, K. -J.; Hash, N.; Barker, D.; ...

2016-06-24

Reconciling the experimental and system requirements during the development of a new target system is one of the most challenging tasks in the design and engineering of targets used in the National Ignition Facility. Targets for the GigaBar 3 campaign were meant to allow the detection of extremely weak Thomson scattering from matter at extreme densities in the face of very bright backlighter and laser entry hole plasma emissions. The problem was to shield the detector sufficiently while maintaining beamline and view clearances, and observing target mass restrictions. A new construction process, based on a rapid prototype frame structure, wasmore » used to develop this target. As a result, details of the design process for these targets are described, and lessons from this development for production and target assembly teams are discussed.« less

Improving Quality of Seal Leak Test Product using Six Sigma

NASA Astrophysics Data System (ADS)

Luthfi Malik, Abdullah; Akbar, Muhammad; Irianto, Dradjad

2016-02-01

Seal leak test part is a polyurethane material-based product. Based on past data, defect level of this product was 8%, higher than the target of 5%. Quality improvement effort was done using six sigma method that included phases of define, measure, analyse, improve, and control. In the design phase, a Delphi method was used to identify factors that were critical to quality. In the measure phase, stability and process capability was measured. Fault tree analysis (FTA) and failure mode and effect analysis (FMEA) were used in the next phase to analize the root cause and to determine the priority issues. Improve phase was done by compiling, selecting, and designing alternative repair. Some improvement efforts were identified, i.e. (i) making a checklist for maintenance schedules, (ii) making written reminder form, (iii) modifying the SOP more detail, and (iv) performing a major service to the vacuum machine. To ensure the continuity of improvement efforts, some control activities were executed, i.e. (i) controlling, monitoring, documenting, and setting target frequently, (ii) implementing reward and punishment system, (iii) adding cleaning tool, and (iv) building six sigma organizational structure.

Radiological Hazard of Spallation Products in Accelerator-Driven System

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

Saito, M.; Stankovskii, A.; Artisyuk, V.

The central issue underlying this paper is related to elucidating the hazard of radioactive spallation products that might be an important factor affecting the design option of accelerator-driven systems (ADSs). Hazard analysis based on the concept of Annual Limit on Intake identifies alpha-emitting isotopes of rare earths (REs) (dysprosium, gadolinium, and samarium) as the dominant contributors to the overall toxicity of traditional (W, Pb, Pb-Bi) targets. The matter is addressed from several points of view: code validation to simulate their yields, choice of material for the neutron producing targets, and challenging the beam type. The paper quantitatively determines the domainmore » in which the toxicity of REs exceeds that of polonium activation products broadly discussed now in connection with advertising lead-bismuth technology for the needs of ADSs.« less

Novel TaqMan real-time polymerase chain reaction assay for verifying the authenticity of meat and commercial meat products from game birds.

PubMed

Rojas, María; González, Isabel; Pavón, Miguel Angel; Pegels, Nicolette; Lago, Adriana; Hernández, Pablo E; García, Teresa; Martín, Rosario

2010-06-01

Species-specific real-time polymerase chain reaction (PCR) assays using TaqMan probes have been developed for verifying the labeling of meat and commercial meat products from game birds, including quail, pheasant, partridge, guinea fowl, pigeon, Eurasian woodcock and song thrush. The method combines the use of species-specific primers and TaqMan probes that amplify small fragments (amplicons <150 base pairs) of the mitochondrial 12S rRNA gene, and an endogenous control primer pair that amplifies a 141-bp fragment of the nuclear 18S rRNA gene from eukaryotic DNA. Analysis of experimental raw and heat-treated binary mixtures as well as of commercial meat products from the target species demonstrated the suitability of the assay for the detection of the target DNAs.

Fission-Fusion: A new reaction mechanism for nuclear astrophysics based on laser-ion acceleration

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

Thirolf, P. G.; Gross, M.; Allinger, K.

We propose to produce neutron-rich nuclei in the range of the astrophysical r-process around the waiting point N = 126 by fissioning a dense laser-accelerated thorium ion bunch in a thorium target (covered by a CH{sub 2} layer), where the light fission fragments of the beam fuse with the light fission fragments of the target. Via the 'hole-boring' mode of laser Radiation Pressure Acceleration using a high-intensity, short pulse laser, very efficiently bunches of {sup 232}Th with solid-state density can be generated from a Th target and a deuterated CD{sub 2} foil, both forming the production target assembly. Laser-accelerated Thmore » ions with about 7 MeV/u will pass through a thin CH{sub 2} layer placed in front of a thicker second Th foil (both forming the reaction target) closely behind the production target and disintegrate into light and heavy fission fragments. In addition, light ions (d,C) from the CD{sub 2} layer of the production target will be accelerated as well, inducing the fission process of {sup 232}Th also in the second Th layer. The laser-accelerated ion bunches with solid-state density, which are about 10{sup 14} times more dense than classically accelerated ion bunches, allow for a high probability that generated fission products can fuse again. The high ion beam density may lead to a strong collective modification of the stopping power, leading to significant range and thus yield enhancement. Using a high-intensity laser as envisaged for the ELI-Nuclear Physics project in Bucharest (ELI-NP), order-of-magnitude estimates promise a fusion yield of about 10{sup 3} ions per laser pulse in the mass range of A = 180-190, thus enabling to approach the r-process waiting point at N = 126.« less

Effect of advanced nanowire-based targets in nanosecond laser-matter interaction (invited)

NASA Astrophysics Data System (ADS)

Lanzalone, G.; Altana, C.; Mascali, D.; Muoio, A.; Malferrari, L.; Odorici, F.; Malandrino, G.; Tudisco, S.

2016-02-01

An experimental campaign aiming to investigate the effects of innovative nanostructured targets based on Ag nanowires on laser energy absorption in the ns time domain has been carried out at the Laser Energy for Nuclear Science laboratory of INFN-LNS in Catania. The tested targets were realized at INFN-Bologna by anodizing aluminium sheets in order to obtain layers of porous Al2O3 of different thicknesses, on which nanowires of various metals are grown by electro-deposition with different heights. Targets were then irradiated by using a Nd:YAG laser at different pumping energies. Advanced diagnostic tools were used for characterizing the plasma plume and ion production. As compared with targets of pure Al, a huge enhancement (of almost two order of magnitude) of the X-ray flux emitted by the plasma has been observed when using the nanostructured targets, with a corresponding decrease of the "optical range" signal, pointing out that the energetic content of the laser produced plasma was remarkably increased. This analysis was furthermore confirmed from time-of-flight spectra.

Effect of advanced nanowire-based targets in nanosecond laser-matter interaction (invited).

PubMed

Lanzalone, G; Altana, C; Mascali, D; Muoio, A; Malferrari, L; Odorici, F; Malandrino, G; Tudisco, S

2016-02-01

An experimental campaign aiming to investigate the effects of innovative nanostructured targets based on Ag nanowires on laser energy absorption in the ns time domain has been carried out at the Laser Energy for Nuclear Science laboratory of INFN-LNS in Catania. The tested targets were realized at INFN-Bologna by anodizing aluminium sheets in order to obtain layers of porous Al2O3 of different thicknesses, on which nanowires of various metals are grown by electro-deposition with different heights. Targets were then irradiated by using a Nd:YAG laser at different pumping energies. Advanced diagnostic tools were used for characterizing the plasma plume and ion production. As compared with targets of pure Al, a huge enhancement (of almost two order of magnitude) of the X-ray flux emitted by the plasma has been observed when using the nanostructured targets, with a corresponding decrease of the "optical range" signal, pointing out that the energetic content of the laser produced plasma was remarkably increased. This analysis was furthermore confirmed from time-of-flight spectra.

Effect of advanced nanowire-based targets in nanosecond laser-matter interaction (invited)

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

Lanzalone, G., E-mail: Gaetano.Lanzalone@ct.infn.it; Università degli Studi di Enna “Kore,” Via delle Olimpiadi, 94100 Enna; Altana, C.

2016-02-15

An experimental campaign aiming to investigate the effects of innovative nanostructured targets based on Ag nanowires on laser energy absorption in the ns time domain has been carried out at the Laser Energy for Nuclear Science laboratory of INFN-LNS in Catania. The tested targets were realized at INFN-Bologna by anodizing aluminium sheets in order to obtain layers of porous Al{sub 2}O{sub 3} of different thicknesses, on which nanowires of various metals are grown by electro-deposition with different heights. Targets were then irradiated by using a Nd:YAG laser at different pumping energies. Advanced diagnostic tools were used for characterizing the plasmamore » plume and ion production. As compared with targets of pure Al, a huge enhancement (of almost two order of magnitude) of the X-ray flux emitted by the plasma has been observed when using the nanostructured targets, with a corresponding decrease of the “optical range” signal, pointing out that the energetic content of the laser produced plasma was remarkably increased. This analysis was furthermore confirmed from time-of-flight spectra.« less

Thermochemical energy storage with ammonia: Aiming for the sunshot cost target

NASA Astrophysics Data System (ADS)

Lavine, Adrienne S.; Lovegrove, Keith M.; Jordan, Joshua; Anleu, Gabriela Bran; Chen, Chen; Aryafar, Hamarz; Sepulveda, Abdon

2016-05-01

Thermochemical energy storage has the potential to reduce the cost of concentrating solar thermal power. This paper presents recent advances in ammonia-based thermochemical energy storage (TCES), supported by an award from the U.S. Dept. of Energy SunShot program. Advances have been made in three areas: identification of promising approaches for underground containment of the gaseous products of the dissociation reaction, demonstration that ammonia synthesis can be used to generate steam for a supercritical-steam Rankine cycle, and a preliminary design for integration of the endothermic reactors within a tower receiver. Based on these advances, ammonia-based TCES shows promise to meet the 15/kWht SunShot cost target.

Natural toxins for use in pest management.

PubMed

Duke, Stephen O; Cantrell, Charles L; Meepagala, Kumudini M; Wedge, David E; Tabanca, Nurhayat; Schrader, Kevin K

2010-08-01

Natural toxins are a source of new chemical classes of pesticides, as well as environmentally and toxicologically safer molecules than many of the currently used pesticides. Furthermore, they often have molecular target sites that are not exploited by currently marketed pesticides. There are highly successful products based on natural compounds in the major pesticide classes. These include the herbicide glufosinate (synthetic phosphinothricin), the spinosad insecticides, and the strobilurin fungicides. These and other examples of currently marketed natural product-based pesticides, as well as natural toxins that show promise as pesticides from our own research are discussed.

Colorimetric detection of genetically modified organisms based on exonuclease III-assisted target recycling and hemin/G-quadruplex DNAzyme amplification.

PubMed

Zhang, Decai; Wang, Weijia; Dong, Qian; Huang, Yunxiu; Wen, Dongmei; Mu, Yuejing; Yuan, Yong

2017-12-21

An isothermal colorimetric method is described for amplified detection of the CaMV 35S promoter sequence in genetically modified organism (GMO). It is based on (a) target DNA-triggered unlabeled molecular beacon (UMB) termini binding, and (b) exonuclease III (Exo III)-assisted target recycling, and (c) hemin/G-quadruplex (DNAzyme) based signal amplification. The specific binding of target to the G-quadruplex sequence-locked UMB triggers the digestion of Exo III. This, in turn, releases an active G-quadruplex segment and target DNA for successive hybridization and cleavage. The Exo III impellent recycling of targets produces numerous G-quadruplex sequences. These further associate with hemin to form DNAzymes and hence will catalyze H 2 O 2 -mediated oxidation of the chromogenic enzyme substrate ABTS 2- causing the formation of a green colored product. This finding enables a sensitive colorimetric determination of GMO DNA (at an analytical wavelength of 420 nm) at concentrations as low as 0.23 nM. By taking advantage of isothermal incubation, this method does not require sophisticated equipment or complicated syntheses. Analyses can be performed within 90 min. The method also discriminates single base mismatches. In our perception, it has a wide scope in that it may be applied to the detection of many other GMOs. Graphical abstract An isothermal and sensitive colorimetric method is described for amplified detection of CaMV 35S promoter sequence in genetically modified organism (GMO). It is based on target DNA-triggered molecular beacon (UMB) termini-binding and exonuclease III assisted target recycling, and on hemin/G-quadruplex (DNAzyme) signal amplification.

Genome-Wide siRNA-Based Functional Genomics of Pigmentation Identifies Novel Genes and Pathways That Impact Melanogenesis in Human Cells

PubMed Central

Bodemann, Brian; Petersen, Sean; Aruri, Jayavani; Koshy, Shiney; Richardson, Zachary; Le, Lu Q.; Krasieva, Tatiana; Roth, Michael G.; Farmer, Pat; White, Michael A.

2008-01-01

Melanin protects the skin and eyes from the harmful effects of UV irradiation, protects neural cells from toxic insults, and is required for sound conduction in the inner ear. Aberrant regulation of melanogenesis underlies skin disorders (melasma and vitiligo), neurologic disorders (Parkinson's disease), auditory disorders (Waardenburg's syndrome), and opthalmologic disorders (age related macular degeneration). Much of the core synthetic machinery driving melanin production has been identified; however, the spectrum of gene products participating in melanogenesis in different physiological niches is poorly understood. Functional genomics based on RNA-mediated interference (RNAi) provides the opportunity to derive unbiased comprehensive collections of pharmaceutically tractable single gene targets supporting melanin production. In this study, we have combined a high-throughput, cell-based, one-well/one-gene screening platform with a genome-wide arrayed synthetic library of chemically synthesized, small interfering RNAs to identify novel biological pathways that govern melanin biogenesis in human melanocytes. Ninety-two novel genes that support pigment production were identified with a low false discovery rate. Secondary validation and preliminary mechanistic studies identified a large panel of targets that converge on tyrosinase expression and stability. Small molecule inhibition of a family of gene products in this class was sufficient to impair chronic tyrosinase expression in pigmented melanoma cells and UV-induced tyrosinase expression in primary melanocytes. Isolation of molecular machinery known to support autophagosome biosynthesis from this screen, together with in vitro and in vivo validation, exposed a close functional relationship between melanogenesis and autophagy. In summary, these studies illustrate the power of RNAi-based functional genomics to identify novel genes, pathways, and pharmacologic agents that impact a biological phenotype and operate outside of preconceived mechanistic relationships. PMID:19057677

New product development: A batik multifunctional chair

NASA Astrophysics Data System (ADS)

Indrawati, Sri; Sukmaningsih, Nias

2017-11-01

The biggest challenge facing by Batik industry in ASEAN Economic Community (AEC) era is the greater number of fashion competitors both domestically and internationally. Based on that condition, the development of new product variants by considering product performance and price is needed. This research was conducted to develop batik products with a new target market. Products that being developed is batik multifunctional chair using integrated value engineering and analytic hierarchy process methods. This research has been done in several stages, ie. Information stage, creative stage, value analysis and product prototyping. The results of this research shows that the batik multifunctional chair product criteria are aesthetic (29%), multifunctional (34%) and ergonomic (37%). There are three new product design alternatives that successfully being developed. Based on value analysis, the product design alternatives that have the highest value is alternative design 2, the value is 2,37. The production cost for this design is Rp. 500.000,-. Alternative design 2 specification are using Mahoni wood, Batik parang rusak pattern with natural coloring process, can be used as table and fit with customer's body anthropometry. Then a batik multifunctional chair prototype is developed based on the best alternative design.

Cosmogenic Production of Be-7 and Be-10 in Water Targets

NASA Technical Reports Server (NTRS)

Nishiizumi, K.; Finkel, R. C.; Klein, J.; Kohl, C. P.

1996-01-01

We have measured Be-10(t(sub 1/2) = 1.5 x 10(exp 6) years) and Be-7 (t(sub 1/2) = 53.28 days) concentrations in water targets exposed for 1 to 2 years at Echo Lake, Colorado (elevation = 3246 m) and at La Jolla, California (140 m). Neutron monitor data were used to normalize the measured concentrations in order to calculate production rates equivalent to the cosmic ray flux averaged over four solar cycles (43 years). The Be-7 production rates thus obtained correspond to 6.03 +/- 0.07 x 10(exp -6) atom/g.O/s at Echo Lake and 5.06 +/- 0.20 x 10(exp -7) atom/g.O/ s at La Jolla. The Be-10 production rates correspond to 3.14 +/- 0.18 x 10(exp -6) atom/g.O/s at Echo Lake and 2.68 +/- 0.47 x 10(exp -7) atom/g.O/s at La Jolla. When compared with Be-10 production rates determined in Be-10-saturated rocks from the Antarctic and with theoretical calculations based on meteorite and lunar sample data, we find that the million-year average production rate is about 14 - 17% greater than the present production rate averaged over the last four solar cycles. Comparison with production rates determined by measuring glacially polished rocks from the Sierra Nevada in California indicates that average production (based on a revised 13,000-year deglaciation age and a geographic latitude correction) is a about 11% greater than the average over the last four solar cycles. The measured Be-10/Be-7 production ratio in oxygen is 0.52 +/- 0.03 at Echo Lake and 0.55 +/- 0.07 at La Jolla.

Dynamic pricing of network goods with boundedly rational consumers.

PubMed

Radner, Roy; Radunskaya, Ami; Sundararajan, Arun

2014-01-07

We present a model of dynamic monopoly pricing for a good that displays network effects. In contrast with the standard notion of a rational-expectations equilibrium, we model consumers as boundedly rational and unable either to pay immediate attention to each price change or to make accurate forecasts of the adoption of the network good. Our analysis shows that the seller's optimal price trajectory has the following structure: The price is low when the user base is below a target level, is high when the user base is above the target, and is set to keep the user base stationary once the target level has been attained. We show that this pricing policy is robust to a number of extensions, which include the product's user base evolving over time and consumers basing their choices on a mixture of a myopic and a "stubborn" expectation of adoption. Our results differ significantly from those that would be predicted by a model based on rational-expectations equilibrium and are more consistent with the pricing of network goods observed in practice.

Feasibility study on the use of uranium in photoneutron target and BSA optimization for Linac based BNCT

NASA Astrophysics Data System (ADS)

Rahmani, Faezeh; Shahriari, Majid; Minoochehr, Abdolhamid; Nedaie, Hasan

2011-06-01

A hybrid photoneutron target including natural uranium has been studied for a 20 MeV linear electron accelerator (Linac) based Boron Neutron Capture Therapy (BNCT) facility. In this study the possibility of using uranium to increase the neutron intensity has been investigated by focusing on the time dependence behavior of the build-up and decay of the delayed gamma rays from fission fragments and activation products through photo-fission reactions in the BSA (Beam Shaping Assembly) configuration design. Delayed components of neutrons and photons were calculated. The obtained BSA parameters are in agreement with the IAEA recommendation and compared to the hybrid photoneutron target without U. The epithermal flux in the suggested design is 2.67E9 (n/cm 2s/mA).

The healthfulness and prominence of sugar in child-targeted breakfast cereals in Canada.

PubMed

Potvin Kent, Monique; Cameron, Cher; Philippe, Sarah

2017-09-01

The objective of this study was to compare the nutritional content and healthfulness of child-targeted and "not child-targeted" breakfast cereals and to assess the predominance of added sugar in these products. We collected data on the nutritional content of 262 unique breakfast cereals found in the five largest grocery store chains in Ottawa (Ontario) and Gatineau (Quebec). We noted the first five ingredients and the number of added sugars present in each cereal from the ingredients list. The various cereal brands were then classified as either "healthier" or "less healthy" using the UK Nutrient Profile Model. We assessed each cereal to determine if it was child-targeted or not, based on set criteria. Statistical comparisons were made between child and not child-targeted cereals. 19.8% of all breakfast cereals were child-targeted, and these were significantly lower in total and saturated fat. Child-targeted cereals were significantly higher in sodium and sugar and lower in fibre and protein, and were three times more likely to be classified as "less healthy" compared to not child-targeted cereals. No child-targeted cereals were sugar-free, and sugar was the second most common ingredient in 75% of cereals. Six breakfast cereal companies had child-targeted product lines that consisted entirely of "less healthy" cereals. There is a need for regulations that restrict food marketing to children and youth under the age of 17 on packaging to reduce their appeal to this age group. Children's breakfast cereals also need to be reformulated through government-set targets, or through regulation should compliance be deemed unacceptable.

Trained in Science-Base Field: Change of Specialization among Educated Women in Malaysia

ERIC Educational Resources Information Center

Amin, Suhaida Mohd; Satar, Nurulhuda Mohd; Yap, Su Fei

2015-01-01

The theoretical model for economic development states that development in science and technology is the key to increased productivity. Upon realizing this, the Malaysian government has targeted 60 to 40 per cent of students for Science to Arts field at the tertiary level of education. However the rate of participation in science-based programs…

Beauty and charm production at fixed-target experiments

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

Erik E. Gottschalk

Fixed-target experiments continue to provide insights into the physics of particle production in strong interactions. The experiments are performed with different types of beam particles of varying energies, and many different target materials. Studies of beauty and charm production are of particular interest, since experimental results can be compared to perturbative QCD calculations. It is in this context that recent results from fixed-target experiments on beauty and charm production will be reviewed.

MicroRNA-mediated gene regulation: potential applications for plant genetic engineering.

PubMed

Zhou, Man; Luo, Hong

2013-09-01

Food security is one of the most important issues challenging the world today. Any strategies to solve this problem must include increasing crop yields and quality. MicroRNA-based genetic modification technology (miRNA-based GM tech) can be one of the most promising solutions that contribute to agricultural productivity directly by developing superior crop cultivars with enhanced biotic and abiotic stress tolerance and increased biomass yields. Indirectly, the technology may increase usage of marginal soils and decrease pesticide use, among other benefits. This review highlights the most recent progress of transgenic studies utilizing various miRNAs and their targets for plant trait modifications, and analyzes the potential of miRNA-mediated gene regulation for use in crop improvement. Strategies for manipulating miRNAs and their targets in transgenic plants including constitutive, stress-induced, or tissue-specific expression of miRNAs or their targets, RNA interference, expressing miRNA-resistant target genes, artificial target mimic and artificial miRNAs were discussed. We also discussed potential risks of utilizing miRNA-based GM tech. In general, miRNAs and their targets not only provide an invaluable source of novel transgenes, but also inspire the development of several new GM strategies, allowing advances in breeding novel crop cultivars with agronomically useful characteristics.

800-MeV proton irradiation of thorium and depleted uranium targets

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

Russell, G.J.; Brun, T.O.; Pitcher, E.J.

As part of the Los Alamos Fertile-to-Fissile-Conversion (FERFICON) program in the late 1980`s, thick targets of the fertile materials thorium and depleted uranium were bombarded by 800-MeV protons to produce the fissile materials {sup 233}U and {sup 239}Pu, respectively. The amount of {sup 233}U made was determined by measuring the {sup 233}Pa activity, and the yield of {sup 239}Pu was deduced by measuring the activity of {sup 239}Np. For the thorium target, 4 spallation products and 34 fission products were also measured. For the depleted uranium target, 3 spallation products and 16 fission products were also measured. The number ofmore » fissions in each target was deduced from fission product mass-yield curves. In actuality, axial distributions of the products were measured, and the distributions were then integrated over the target volume to obtain the total number of products for each reaction.« less

Cost of unreliability method to estimate loss of revenue based on unreliability data: Case study of Printing Company

NASA Astrophysics Data System (ADS)

alhilman, Judi

2017-12-01

In the production line process of the printing office, the reliability of the printing machine plays a very important role, if the machine fail it can disrupt production target so that the company will suffer huge financial loss. One method to calculate the financial loss cause by machine failure is use the Cost of Unreliability(COUR) method. COUR method works based on down time machine and costs associated with unreliability data. Based on the calculation of COUR method, so the sum of cost due to unreliability printing machine during active repair time and downtime is 1003,747.00.

Fisk-based criteria to support validation of detection methods for drinking water and air.

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

MacDonell, M.; Bhattacharyya, M.; Finster, M.

2009-02-18

This report was prepared to support the validation of analytical methods for threat contaminants under the U.S. Environmental Protection Agency (EPA) National Homeland Security Research Center (NHSRC) program. It is designed to serve as a resource for certain applications of benchmark and fate information for homeland security threat contaminants. The report identifies risk-based criteria from existing health benchmarks for drinking water and air for potential use as validation targets. The focus is on benchmarks for chronic public exposures. The priority sources are standard EPA concentration limits for drinking water and air, along with oral and inhalation toxicity values. Many contaminantsmore » identified as homeland security threats to drinking water or air would convert to other chemicals within minutes to hours of being released. For this reason, a fate analysis has been performed to identify potential transformation products and removal half-lives in air and water so appropriate forms can be targeted for detection over time. The risk-based criteria presented in this report to frame method validation are expected to be lower than actual operational targets based on realistic exposures following a release. Note that many target criteria provided in this report are taken from available benchmarks without assessing the underlying toxicological details. That is, although the relevance of the chemical form and analogues are evaluated, the toxicological interpretations and extrapolations conducted by the authoring organizations are not. It is also important to emphasize that such targets in the current analysis are not health-based advisory levels to guide homeland security responses. This integrated evaluation of chronic public benchmarks and contaminant fate has identified more than 200 risk-based criteria as method validation targets across numerous contaminants and fate products in drinking water and air combined. The gap in directly applicable values is considerable across the full set of threat contaminants, so preliminary indicators were developed from other well-documented benchmarks to serve as a starting point for validation efforts. By this approach, at least preliminary context is available for water or air, and sometimes both, for all chemicals on the NHSRC list that was provided for this evaluation. This means that a number of concentrations presented in this report represent indirect measures derived from related benchmarks or surrogate chemicals, as described within the many results tables provided in this report.« less

Present status of Accelerator-Based BNCT

PubMed Central

Kreiner, Andres Juan; Bergueiro, Javier; Cartelli, Daniel; Baldo, Matias; Castell, Walter; Asoia, Javier Gomez; Padulo, Javier; Suárez Sandín, Juan Carlos; Igarzabal, Marcelo; Erhardt, Julian; Mercuri, Daniel; Valda, Alejandro A.; Minsky, Daniel M.; Debray, Mario E.; Somacal, Hector R.; Capoulat, María Eugenia; Herrera, María S.; del Grosso, Mariela F.; Gagetti, Leonardo; Anzorena, Manuel Suarez; Canepa, Nicolas; Real, Nicolas; Gun, Marcelo; Tacca, Hernán

2016-01-01

Aim This work aims at giving an updated report of the worldwide status of Accelerator-Based BNCT (AB-BNCT). Background There is a generalized perception that the availability of accelerators installed in hospitals, as neutron sources, may be crucial for the advancement of BNCT. Accordingly, in recent years a significant effort has started to develop such machines. Materials and methods A variety of possible charged-particle induced nuclear reactions and the characteristics of the resulting neutron spectra are discussed along with the worldwide activity in suitable accelerator development. Results Endothermic 7Li(p,n)7Be and 9Be(p,n)9B and exothermic 9Be(d,n)10B are compared. In addition to having much better thermo-mechanical properties than Li, Be as a target leads to stable products. This is a significant advantage for a hospital-based facility. 9Be(p,n)9B needs at least 4–5 MeV bombarding energy to have a sufficient yield, while 9Be(d,n)10B can be utilized at about 1.4 MeV, implying the smallest possible accelerator. This reaction operating with a thin target can produce a sufficiently soft spectrum to be viable for AB-BNCT. The machines considered are electrostatic single ended or tandem accelerators or radiofrequency quadrupoles plus drift tube Linacs. Conclusions 7Li(p,n)7Be provides one of the best solutions for the production of epithermal neutron beams for deep-seated tumors. However, a Li-based target poses significant technological challenges. Hence, Be has been considered as an alternative target, both in combination with (p,n) and (d,n) reactions. 9Be(d,n)10B at 1.4 MeV, with a thin target has been shown to be a realistic option for the treatment of deep-seated lesions. PMID:26933390

Plasma production in carbon-based materials

NASA Astrophysics Data System (ADS)

Giuffreda, E.; Delle Side, D.; Nassisi, V.; Krása, J.

2017-09-01

High intensity lasers can induce in solid targets a charge separation resulting in a time-dependent induced polarization. In this work, the characterization of a plastic target subjected to a laser irradiation has been analysed. A focus was particularly devoted to the interaction of the target with the whole grounded chamber, manipulated through the change of the target-holder surface ratio. The targets are thick samples (thickness >1 mm) of polymers arranged in discs according to the metallic holder shape. A possible correlation between the target current and the main features of the produced plasma was analyzed, in order to acquire a deeper knowledge on laser-matter interactions with the laser pulse on the nanosecond scale. Collected signals were analyzed to reconstruct the time evolution of key observables as well as the charge space distribution in the chamber. The experimental setting allowing the target current observation and the measurement procedure is discussed.

Marine natural products for multi-targeted cancer treatment: A future insight.

PubMed

Kumar, Maushmi S; Adki, Kaveri M

2018-05-30

Cancer is world's second largest alarming disease, which involves abnormal cell growth and have potential to spread to other parts of the body. Most of the available anticancer drugs are designed to act on specific targets by altering the activity of involved transporters and genes. As cancer cells exhibit complex cellular machinery, the regeneration of cancer tissues and chemo resistance towards the therapy has been the main obstacle in cancer treatment. This fact encourages the researchers to explore the multitargeted use of existing medicines to overcome the shortcomings of chemotherapy for alternative and safer treatment strategies. Recent developments in genomics-proteomics and an understanding of the molecular pharmacology of cancer have also challenged researchers to come up with target-based drugs. The literature supports the evidence of natural compounds exhibiting antioxidant, antimitotic, anti-inflammatory, antibiotic as well as anticancer activity. In this review, we have selected marine sponges as a prolific source of bioactive compounds which can be explored for their possible use in cancer and have tried to link their role in cancer pathway. To prove this, we revisited the literature for the selection of cancer genes for the multitargeted use of existing drugs and natural products. We used Cytoscape network analysis and Search tool for retrieval of interacting genes/ proteins (STRING) to study the possible interactions to show the links between the antioxidants, antibiotics, anti-inflammatory and antimitotic agents and their targets for their possible use in cancer. We included total 78 pathways, their genes and natural compounds from the above four pharmacological classes used in cancer treatment for multitargeted approach. Based on the Cytoscape network analysis results, we shortlist 22 genes based on their average shortest path length connecting one node to all other nodes in a network. These selected genes are CDKN2A, FH, VHL, STK11, SUFU, RB1, MEN1, HRPT2, EXT1, 2, CDK4, p14, p16, TSC1, 2, AXIN2, SDBH C, D, NF1, 2, BHD, PTCH, GPC3, CYLD and WT1. The selected genes were analysed using STRING for their protein-protein interactions. Based on the above findings, we propose the selected genes to be considered as major targets and are suggested to be studied for discovering marine natural products as drug lead in cancer treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Biosynthetic Potential-Based Strain Prioritization for Natural Product Discovery: A Showcase for Diterpenoid-Producing Actinomycetes

PubMed Central

2015-01-01

Natural products remain the best sources of drugs and drug leads and serve as outstanding small-molecule probes to dissect fundamental biological processes. A great challenge for the natural product community is to discover novel natural products efficiently and cost effectively. Here we report the development of a practical method to survey biosynthetic potential in microorganisms, thereby identifying the most promising strains and prioritizing them for natural product discovery. Central to our approach is the innovative preparation, by a two-tiered PCR method, of a pool of pathway-specific probes, thereby allowing the survey of all variants of the biosynthetic machineries for the targeted class of natural products. The utility of the method was demonstrated by surveying 100 strains, randomly selected from our actinomycete collection, for their biosynthetic potential of four classes of natural products, aromatic polyketides, reduced polyketides, nonribosomal peptides, and diterpenoids, identifying 16 talented strains. One of the talented strains, Streptomyces griseus CB00830, was finally chosen to showcase the discovery of the targeted classes of natural products, resulting in the isolation of three diterpenoids, six nonribosomal peptides and related metabolites, and three polyketides. Variations of this method should be applicable to the discovery of other classes of natural products. PMID:24484381

Evolution-guided optimization of biosynthetic pathways.

PubMed

Raman, Srivatsan; Rogers, Jameson K; Taylor, Noah D; Church, George M

2014-12-16

Engineering biosynthetic pathways for chemical production requires extensive optimization of the host cellular metabolic machinery. Because it is challenging to specify a priori an optimal design, metabolic engineers often need to construct and evaluate a large number of variants of the pathway. We report a general strategy that combines targeted genome-wide mutagenesis to generate pathway variants with evolution to enrich for rare high producers. We convert the intracellular presence of the target chemical into a fitness advantage for the cell by using a sensor domain responsive to the chemical to control a reporter gene necessary for survival under selective conditions. Because artificial selection tends to amplify unproductive cheaters, we devised a negative selection scheme to eliminate cheaters while preserving library diversity. This scheme allows us to perform multiple rounds of evolution (addressing ∼10(9) cells per round) with minimal carryover of cheaters after each round. Based on candidate genes identified by flux balance analysis, we used targeted genome-wide mutagenesis to vary the expression of pathway genes involved in the production of naringenin and glucaric acid. Through up to four rounds of evolution, we increased production of naringenin and glucaric acid by 36- and 22-fold, respectively. Naringenin production (61 mg/L) from glucose was more than double the previous highest titer reported. Whole-genome sequencing of evolved strains revealed additional untargeted mutations that likely benefit production, suggesting new routes for optimization.

Nutritional quality of packaged foods targeted at children in Brazil: which ones should be eligible to bear nutrient claims?

PubMed

Rodrigues, V M; Rayner, M; Fernandes, A C; de Oliveira, R C; Proença, R P C; Fiates, G M R

2017-01-01

This study aimed to assess the nutritional quality of food products marketed at children, with and without nutrient claims, using two different approaches. Analyses were performed based on a data set with food composition and labelling data from every packaged food marketed at children sold in a major Brazilian supermarket (n=535). Foods were classified as 'healthier' and 'less healthy' according to the UK/Ofcom nutrient profile model and to the NOVA classification based on the level of food processing. Pearson's χ 2 test was used to compare proportions between models. Agreement was assessed using Cohen's κ-statistic (P<0.05). The NOVA model was stricter than the UK/Ofcom model, classifying more products as 'less healthy' (91.4%) compared with the nutrient profile-based model (75.0%; P<0.001). Agreement between models was 79.4% (k=0.30), because 72.9% (n=390) of products were categorised as 'less healthy' by both models, and 6.5% (n=35) as 'healthier'. Half of the food products marketed at children from the database (270; 50.5%) bore nutrient claims. From these products with nutrient claims, 95.9% (92.8-98.0) were classified as 'less healthy' by the NOVA model, whereas this percentage was 74.1% (68.4-79.2) according to the UK/Ofcom model (P<0.05). The high number of foods with low nutritional quality being marketed at children via product packaging and nutrient claims should be of concern to policy makers wanting to improve children's diets and to tackle childhood obesity. The implementation of nutritional quality criteria to ensure that foods targeted at children should be eligible to bear nutrient claims on their labels could avoid a situation where claims mask the overall nutritional status of a food.

Review of sample preparation strategies for MS-based metabolomic studies in industrial biotechnology.

PubMed

Causon, Tim J; Hann, Stephan

2016-09-28

Fermentation and cell culture biotechnology in the form of so-called "cell factories" now play an increasingly significant role in production of both large (e.g. proteins, biopharmaceuticals) and small organic molecules for a wide variety of applications. However, associated metabolic engineering optimisation processes relying on genetic modification of organisms used in cell factories, or alteration of production conditions remain a challenging undertaking for improving the final yield and quality of cell factory products. In addition to genomic, transcriptomic and proteomic workflows, analytical metabolomics continues to play a critical role in studying detailed aspects of critical pathways (e.g. via targeted quantification of metabolites), identification of biosynthetic intermediates, and also for phenotype differentiation and the elucidation of previously unknown pathways (e.g. via non-targeted strategies). However, the diversity of primary and secondary metabolites and the broad concentration ranges encompassed during typical biotechnological processes means that simultaneous extraction and robust analytical determination of all parts of interest of the metabolome is effectively impossible. As the integration of metabolome data with transcriptome and proteome data is an essential goal of both targeted and non-targeted methods addressing production optimisation goals, additional sample preparation steps beyond necessary sampling, quenching and extraction protocols including clean-up, analyte enrichment, and derivatisation are important considerations for some classes of metabolites, especially those present in low concentrations or exhibiting poor stability. This contribution critically assesses the potential of current sample preparation strategies applied in metabolomic studies of industrially-relevant cell factory organisms using mass spectrometry-based platforms primarily coupled to liquid-phase sample introduction (i.e. flow injection, liquid chromatography, or capillary electrophoresis). Particular focus is placed on the selectivity and degree of enrichment attainable, as well as demands of speed, absolute quantification, robustness and, ultimately, consideration of fully-integrated bioanalytical solutions to optimise sample handling and throughput. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation.

PubMed

Pallagi, Edina; Ambrus, Rita; Szabó-Révész, Piroska; Csóka, Ildikó

2015-08-01

Regulatory science based pharmaceutical development and product manufacturing is highly recommended by the authorities nowadays. The aim of this study was to adapt regulatory science even in the nano-pharmaceutical early development. Authors applied the quality by design (QbD) concept in the early development phase of nano-systems, where the illustration material was meloxicam. The meloxicam nanoparticles produced by co-grinding method for nasal administration were studied according to the QbD policy and the QbD based risk assessment (RA) was performed. The steps were implemented according to the relevant regulatory guidelines (quality target product profile (QTPP) determination, selection of critical quality attributes (CQAs) and critical process parameters (CPPs)) and a special software (Lean QbD Software(®)) was used for the RA, which represents a novelty in this field. The RA was able to predict and identify theoretically the factors (e.g. sample composition, production method parameters, etc.) which have the highest impact on the desired meloxicam-product quality. The results of the practical research justified the theoretical prediction. This method can improve pharmaceutical nano-developments by achieving shorter development time, lower cost, saving human resource efforts and more effective target-orientation. It makes possible focusing the resources on the selected parameters and area during the practical product development. Copyright © 2015 Elsevier B.V. All rights reserved.

Critical product features' identification using an opinion analyzer.

PubMed

Shamim, Azra; Balakrishnan, Vimala; Tahir, Muhammad; Shiraz, Muhammad

2014-01-01

The increasing use and ubiquity of the Internet facilitate dissemination of word-of-mouth through blogs, online forums, newsgroups, and consumer's reviews. Online consumer's reviews present tremendous opportunities and challenges for consumers and marketers. One of the challenges is to develop interactive marketing practices for making connections with target consumers that capitalize consumer-to-consumer communications for generating product adoption. Opinion mining is employed in marketing to help consumers and enterprises in the analysis of online consumers' reviews by highlighting the strengths and weaknesses of the products. This paper describes an opinion mining system based on novel review and feature ranking methods to empower consumers and enterprises for identifying critical product features from enormous consumers' reviews. Consumers and business analysts are the main target group for the proposed system who want to explore consumers' feedback for determining purchase decisions and enterprise strategies. We evaluate the proposed system on real dataset. Results show that integration of review and feature-ranking methods improves the decision making processes significantly.

Critical Product Features' Identification Using an Opinion Analyzer

PubMed Central

Shamim, Azra; Balakrishnan, Vimala

2014-01-01

The increasing use and ubiquity of the Internet facilitate dissemination of word-of-mouth through blogs, online forums, newsgroups, and consumer's reviews. Online consumer's reviews present tremendous opportunities and challenges for consumers and marketers. One of the challenges is to develop interactive marketing practices for making connections with target consumers that capitalize consumer-to-consumer communications for generating product adoption. Opinion mining is employed in marketing to help consumers and enterprises in the analysis of online consumers' reviews by highlighting the strengths and weaknesses of the products. This paper describes an opinion mining system based on novel review and feature ranking methods to empower consumers and enterprises for identifying critical product features from enormous consumers' reviews. Consumers and business analysts are the main target group for the proposed system who want to explore consumers' feedback for determining purchase decisions and enterprise strategies. We evaluate the proposed system on real dataset. Results show that integration of review and feature-ranking methods improves the decision making processes significantly. PMID:25506612

Formulation Effects and the Off-target Transport of Pyrethroid Insecticides from Urban Hard Surfaces

PubMed Central

Jorgenson, Brant C.; Young, Thomas M.

2010-01-01

Controlled rainfall experiments utilizing drop forming rainfall simulators were conducted to study various factors contributing to off-target transport of off-the-shelf formulated pyrethroid insecticides from concrete surfaces. Factors evaluated included active ingredient, product formulation, time between application and rainfall (set time), and rainfall intensity. As much as 60% and as little as 0.8% of pyrethroid applied could be recovered in surface runoff depending primarily on product formulation, and to a lesser extent on product set time. Resulting wash-off profiles during one-hour storm simulations could be categorized based on formulation, with formulations utilizing emulsifying surfactants rather than organic solvents resulting in unique wash-off profiles with overall higher wash-off efficiency. These higher wash-off efficiency profiles were qualitatively replicated by applying formulation-free neat pyrethroid in the presence of independently applied linear alkyl benzene sulfonate (LAS) surfactant, suggesting that the surfactant component of some formulated products may be influential in pyrethroid wash-off from urban hard surfaces. PMID:20524665

ASDB: a resource for probing protein functions with small molecules.

PubMed

Liu, Zhihong; Ding, Peng; Yan, Xin; Zheng, Minghao; Zhou, Huihao; Xu, Yuehua; Du, Yunfei; Gu, Qiong; Xu, Jun

2016-06-01

: Identifying chemical probes or seeking scaffolds for a specific biological target is important for protein function studies. Therefore, we create the Annotated Scaffold Database (ASDB), a computer-readable and systematic target-annotated scaffold database, to serve such needs. The scaffolds in ASDB were derived from public databases including ChEMBL, DrugBank and TCMSP, with a scaffold-based classification approach. Each scaffold was assigned with an InChIKey as its unique identifier, energy-minimized 3D conformations, and other calculated properties. A scaffold is also associated with drugs, natural products, drug targets and medical indications. The database can be retrieved through text or structure query tools. ASDB collects 333 601 scaffolds, which are associated with 4368 targets. The scaffolds consist of 3032 scaffolds derived from drugs and 5163 scaffolds derived from natural products. For given scaffolds, scaffold-target networks can be generated from the database to demonstrate the relations of scaffolds and targets. ASDB is freely available at http://www.rcdd.org.cn/asdb/with the major web browsers. junxu@biochemomes.com or xujun9@mail.sysu.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Structure of Lmaj006129AAA, a hypothetical protein from Leishmania major

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

Arakaki, Tracy; Le Trong, Isolde; Structural Genomics of Pathogenic Protozoa

2006-03-01

The crystal structure of a conserved hypothetical protein from L. major, Pfam sequence family PF04543, structural genomics target ID Lmaj006129AAA, has been determined at a resolution of 1.6 Å. The gene product of structural genomics target Lmaj006129 from Leishmania major codes for a 164-residue protein of unknown function. When SeMet expression of the full-length gene product failed, several truncation variants were created with the aid of Ginzu, a domain-prediction method. 11 truncations were selected for expression, purification and crystallization based upon secondary-structure elements and disorder. The structure of one of these variants, Lmaj006129AAH, was solved by multiple-wavelength anomalous diffraction (MAD)more » using ELVES, an automatic protein crystal structure-determination system. This model was then successfully used as a molecular-replacement probe for the parent full-length target, Lmaj006129AAA. The final structure of Lmaj006129AAA was refined to an R value of 0.185 (R{sub free} = 0.229) at 1.60 Å resolution. Structure and sequence comparisons based on Lmaj006129AAA suggest that proteins belonging to Pfam sequence families PF04543 and PF01878 may share a common ligand-binding motif.« less

Current progress of targetron technology: development, improvement and application in metabolic engineering.

PubMed

Liu, Ya-Jun; Zhang, Jie; Cui, Gu-Zhen; Cui, Qiu

2015-06-01

Targetrons are mobile group II introns that can recognize their DNA target sites by base-pairing RNA-DNA interactions with the aid of site-specific binding reverse transcriptases. Targetron technology stands out from recently developed gene targeting methods because of the flexibility, feasibility, and efficiency, and is particularly suitable for the genetic engineering of difficult microorganisms, including cellulolytic bacteria that are considered promising candidates for biomass conversion via consolidated bioprocessing. Along with the development of the thermotargetron method for thermophiles, targetron technology becomes increasingly important for the metabolic engineering of industrial microorganisms aiming at biofuel/chemical production. To summarize the current progress of targetron technology and provide new insights on the use of the technology, this paper reviews the retrohoming mechanisms of both mesophilic and thermophilic targetron methods based on various group II introns, investigates the improvement of targetron tools for high target efficiency and specificity, and discusses the current applications in the metabolic engineering for bacterial producers. Although there are still intellectual property and technical restrictions in targetron applications, we propose that targetron technology will contribute to both biochemistry research and the metabolic engineering for industrial productions. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application of the MIDAS approach for analysis of lysine acetylation sites.

PubMed

Evans, Caroline A; Griffiths, John R; Unwin, Richard D; Whetton, Anthony D; Corfe, Bernard M

2013-01-01

Multiple Reaction Monitoring Initiated Detection and Sequencing (MIDAS™) is a mass spectrometry-based technique for the detection and characterization of specific post-translational modifications (Unwin et al. 4:1134-1144, 2005), for example acetylated lysine residues (Griffiths et al. 18:1423-1428, 2007). The MIDAS™ technique has application for discovery and analysis of acetylation sites. It is a hypothesis-driven approach that requires a priori knowledge of the primary sequence of the target protein and a proteolytic digest of this protein. MIDAS essentially performs a targeted search for the presence of modified, for example acetylated, peptides. The detection is based on the combination of the predicted molecular weight (measured as mass-charge ratio) of the acetylated proteolytic peptide and a diagnostic fragment (product ion of m/z 126.1), which is generated by specific fragmentation of acetylated peptides during collision induced dissociation performed in tandem mass spectrometry (MS) analysis. Sequence information is subsequently obtained which enables acetylation site assignment. The technique of MIDAS was later trademarked by ABSciex for targeted protein analysis where an MRM scan is combined with full MS/MS product ion scan to enable sequence confirmation.

U.S. Geographic Analysis of the Cost of Hydrogen from Electrolysis

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

Saur, G.; Ainscough, C.

2011-12-01

This report summarizes U.S. geographic analysis of the cost of hydrogen from electrolysis. Wind-based water electrolysis represents a viable path to renewably-produced hydrogen production. It might be used for hydrogen-based transportation fuels, energy storage to augment electricity grid services, or as a supplement for other industrial hydrogen uses. This analysis focuses on the levelized production, costs of producing green hydrogen, rather than market prices which would require more extensive knowledge of an hourly or daily hydrogen market. However, the costs of hydrogen presented here do include a small profit from an internal rate of return on the system. The costmore » of renewable wind-based hydrogen production is very sensitive to the cost of the wind electricity. Using differently priced grid electricity to supplement the system had only a small effect on the cost of hydrogen; because wind electricity was always used either directly or indirectly to fully generate the hydrogen. Wind classes 3-6 across the U.S. were examined and the costs of hydrogen ranged from $3.74kg to $5.86/kg. These costs do not quite meet the 2015 DOE targets for central or distributed hydrogen production ($3.10/kg and $3.70/kg, respectively), so more work is needed on reducing the cost of wind electricity and the electrolyzers. If the PTC and ITC are claimed, however, many of the sites will meet both targets. For a subset of distributed refueling stations where there is also inexpensive, open space nearby this could be an alternative to central hydrogen production and distribution.« less

SUSTAINABLE BIOFUEL SYSTEMS FOR UNDEVELOPED REGIONS

EPA Science Inventory

We evaluated our findings based on the level of integration of sustainable methods, feasibility of implementation within the target community, and the quantity of energy produced in relation to community needs. Particular emphasis was placed on development of a production meth...

Development of genome-based anti-virulence therapeutics to control HLB

USDA-ARS?s Scientific Manuscript database

Orthologous gene replacement technique has been developed to confirm functions of key virulence genes in 'Candidatus Liberibacters asiaticus'. These results facilitate the development of antivirulence drugs that specifically target functional domains of virulence gene products to disarm pathogenicit...

Comparison of bulk and pitcher-catcher targets for laser-driven neutron production

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

Willingale, L.; Maksimchuk, A.; Joglekar, A. S.

2011-08-15

Laser-driven d(d, n)-{sup 3}He beam-target fusion neutron production from bulk deuterated plastic (CD) targets is compared with a pitcher-catcher target scheme using an identical laser and detector arrangement. For laser intensities in the range of (1-3) x 10{sup 19} W cm{sup -2}, it was found that the bulk targets produced a high yield (5 x 10{sup 4} neutrons per steradian) beamed preferentially in the laser propagation direction. Numerical modeling shows the importance of considering the temperature adjusted stopping powers to correctly model the neutron production. The bulk CD targets have a high background target temperature leading to a reduced stoppingmore » power for the deuterons, which increases the probability of generating neutrons by fusion. Neutron production from the pitcher-catcher targets was not as efficient since it does not benefit from the reduced stopping power in the cold catcher target. Also, the inhibition of the deuteron acceleration by a proton rich contamination layer significantly reduces the pitcher-catcher neutron production.« less

Farming of Plant-Based Veterinary Vaccines and Their Applications for Disease Prevention in Animals

PubMed Central

Liew, Pit Sze; Hair-Bejo, Mohd

2015-01-01

Plants have been studied for the production of pharmaceutical compounds for more than two decades now. Ever since the plant-made poultry vaccine against Newcastle disease virus made a breakthrough and went all the way to obtain regulatory approval, research to use plants for expression and delivery of vaccine proteins for animals was intensified. Indeed, in view of the high production costs of veterinary vaccines, plants represent attractive biofactories and offer many promising advantages in the production of recombinant vaccine proteins. Furthermore, the possibility of conducting immunogenicity and challenge studies in target animals has greatly exaggerated the progress. Although there are no edible plant-produced animal vaccines in the market, plant-based vaccine technology has great potentials. In this review, development, uses, and advantages of plant-based recombinant protein production in various expression platforms are discussed. In addition, examples of plant-based veterinary vaccines showing strong indication in terms of efficacy in animal disease prevention are also described. PMID:26351454

Agile science: creating useful products for behavior change in the real world.

PubMed

Hekler, Eric B; Klasnja, Predrag; Riley, William T; Buman, Matthew P; Huberty, Jennifer; Rivera, Daniel E; Martin, Cesar A

2016-06-01

Evidence-based practice is important for behavioral interventions but there is debate on how best to support real-world behavior change. The purpose of this paper is to define products and a preliminary process for efficiently and adaptively creating and curating a knowledge base for behavior change for real-world implementation. We look to evidence-based practice suggestions and draw parallels to software development. We argue to target three products: (1) the smallest, meaningful, self-contained, and repurposable behavior change modules of an intervention; (2) "computational models" that define the interaction between modules, individuals, and context; and (3) "personalization" algorithms, which are decision rules for intervention adaptation. The "agile science" process includes a generation phase whereby contender operational definitions and constructs of the three products are created and assessed for feasibility and an evaluation phase, whereby effect size estimates/casual inferences are created. The process emphasizes early-and-often sharing. If correct, agile science could enable a more robust knowledge base for behavior change.

Cosmogenic production of tritium in dark matter detectors

NASA Astrophysics Data System (ADS)

Amaré, J.; Castel, J.; Cebrián, S.; Coarasa, I.; Cuesta, C.; Dafni, T.; Galán, J.; García, E.; Garza, J. G.; Iguaz, F. J.; Irastorza, I. G.; Luzón, G.; Martínez, M.; Mirallas, H.; Oliván, M. A.; Ortigoza, Y.; Ortiz de Solórzano, A.; Puimedón, J.; Ruiz-Chóliz, E.; Sarsa, M. L.; Villar, J. A.; Villar, P.

2018-01-01

The direct detection of dark matter particles requires ultra-low background conditions at energies below a few tens of keV. Radioactive isotopes are produced via cosmogenic activation in detectors and other materials and those isotopes constitute a background source which has to be under control. In particular, tritium is specially relevant due to its decay properties (very low endpoint energy and long half-life) when induced in the detector medium, and because it can be generated in any material as a spallation product. Quantification of cosmogenic production of tritium is not straightforward, neither experimentally nor by calculations. In this work, a method for the calculation of production rates at sea level has been developed and applied to some of the materials typically used as targets in dark matter detectors (germanium, sodium iodide, argon and neon); it is based on a selected description of tritium production cross sections over the entire energy range of cosmic nucleons. Results have been compared to available data in the literature, either based on other calculations or from measurements. The obtained tritium production rates, ranging from a few tens to a few hundreds of nuclei per kg and per day at sea level, point to a significant contribution to the background in dark matter experiments, requiring the application of specific protocols for target material purification, material storing underground and limiting the time the detector is on surface during the building process in order to minimize the exposure to the most dangerous cosmic ray components.

A flexible environmental reuse/recycle policy based on economic strength.

PubMed

Tsiliyannis, C A

2007-01-01

Environmental policies based on fixed recycling rates may lead to increased environmental impacts (e.g., landfilled wastes) during economic expansion. A rate policy is proposed, which is adjusted according to the overall strength or weakness of the economy, as reflected by overall packaging demand and consumption, production and imports-exports. During economic expansion featuring rising consumption, production or exports, the proposed flexible policy suggests a higher reuse/recycle rate. During economic slowdown a lower rate results in lower impacts. The flexible target rates are determined in terms of annual data, including consumption, imports-exports and production. Higher environmental gains can be achieved at lower cost if the flexible policy is applied to widely consumed packaging products and materials associated with low rates, or if cleaner recycling technology is adopted.

Structuring Formal Requirements Specifications for Reuse and Product Families

NASA Technical Reports Server (NTRS)

Heimdahl, Mats P. E.

2001-01-01

In this project we have investigated how formal specifications should be structured to allow for requirements reuse, product family engineering, and ease of requirements change, The contributions of this work include (1) a requirements specification methodology specifically targeted for critical avionics applications, (2) guidelines for how to structure state-based specifications to facilitate ease of change and reuse, and (3) examples from the avionics domain demonstrating the proposed approach.

Energy Production Demonstrator for Megawatt Proton Beams

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

Pronskikh, Vitaly S.; Mokhov, Nikolai V.; Novitski, Igor

2014-07-16

A preliminary study of the Energy Production Demonstrator (EPD) concept - a solid heavy metal target irradiated by GeV-range intense proton beams and producing more energy than consuming - is carried out. Neutron production, fission, energy deposition, energy gain, testing volume and helium production are simulated with the MARS15 code for tungsten, thorium, and natural uranium targets in the proton energy range 0.5 to 120 GeV. This study shows that the proton energy range of 2 to 4 GeV is optimal for both a natU EPD and the tungsten-based testing station that would be the most suitable for proton acceleratormore » facilities. Conservative estimates, not including breeding and fission of plutonium, based on the simulations suggest that the proton beam current of 1 mA will be sufficient to produce 1 GW of thermal output power with the natU EPD while supplying < 8% of that power to operate the accelerator. The thermal analysis shows that the concept considered has a problem due to a possible core meltdown; however, a number of approaches (a beam rastering, in first place) are suggested to mitigate the issue. The efficiency of the considered EPD as a Materials Test Station (MTS) is also evaluated in this study.« less

A potyvirus vector efficiently targets recombinant proteins to chloroplasts, mitochondria and nuclei in plant cells when expressed at the amino terminus of the polyprotein.

PubMed

Majer, Eszter; Navarro, José-Antonio; Daròs, José-Antonio

2015-09-01

Plant virus-based expression systems allow quick and efficient production of recombinant proteins in plant biofactories. Among them, a system derived from tobacco etch virus (TEV; genus potyvirus) permits coexpression of equimolar amounts of several recombinant proteins. This work analyzed how to target recombinant proteins to different subcellular localizations in the plant cell using this system. We constructed TEV clones in which green fluorescent protein (GFP), with a chloroplast transit peptide (cTP), a nuclear localization signal (NLS) or a mitochondrial targeting peptide (mTP) was expressed either as the most amino-terminal product or embedded in the viral polyprotein. Results showed that cTP and mTP mediated efficient translocation of GFP to the corresponding organelle only when present at the amino terminus of the viral polyprotein. In contrast, the NLS worked efficiently at both positions. Viruses expressing GFP in the amino terminus of the viral polyprotein produced milder symptoms. Untagged GFPs and cTP and NLS tagged amino-terminal GFPs accumulated to higher amounts in infected tissues. Finally, viral progeny from clones with internal GFPs maintained the extra gene better. These observations will help in the design of potyvirus-based vectors able to coexpress several proteins while targeting different subcellular localizations, as required in plant metabolic engineering. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly sensitive surface plasmon resonance biosensor for the detection of HIV-related DNA based on dynamic and structural DNA nanodevices.

PubMed

Diao, Wei; Tang, Min; Ding, Shijia; Li, Xinmin; Cheng, Wenbin; Mo, Fei; Yan, Xiaoyu; Ma, Hongmin; Yan, Yurong

2018-02-15

Early detection, diagnosis and treatment of human immune deficiency virus (HIV) infection is the key to reduce acquired immunodeficiency syndrome (AIDS) mortality. In our research, an innovative surface plasmon resonance (SPR) biosensing strategy has been developed for highly sensitive detection of HIV-related DNA based on entropy-driven strand displacement reactions (ESDRs) and double-layer DNA tetrahedrons (DDTs). ESDRs as enzyme-free and label-free signal amplification circuit can be specifically triggered by target DNA, leading to the cyclic utilization of target DNA and the formation of plentiful double-stranded DNA (dsDNA) products. Subsequently, the dsDNA products bind to the immobilized hairpin capture probes and further combine with DDTs nanostructures. Due to the high efficiency of ESDRs and large molecular weight of DDTs, the SPR response signal was enhanced dramatically. The proposed SPR biosensor could detect target DNA sensitively and specifically in a linear range from 1pM to 150nM with a detection limit of 48fM. In addition, the whole detecting process can be accomplished in 60min with high accuracy and duplicability. In particular, the developed SPR biosensor was successfully used to analyze target DNA in complex biological sample, indicating that the developed strategy is promising for rapid and early clinical diagnosis of HIV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of metabolic networks of Streptomyces leeuwenhoekii C34 by means of a genome scale model: Prediction of modifications that enhance the production of specialized metabolites.

PubMed

Razmilic, Valeria; Castro, Jean F; Andrews, Barbara; Asenjo, Juan A

2018-07-01

The first genome scale model (GSM) for Streptomyces leeuwenhoekii C34 was developed to study the biosynthesis pathways of specialized metabolites and to find metabolic engineering targets for enhancing their production. The model, iVR1007, consists of 1,722 reactions, 1,463 metabolites, and 1,007 genes, it includes the biosynthesis pathways of chaxamycins, chaxalactins, desferrioxamines, ectoine, and other specialized metabolites. iVR1007 was validated using experimental information of growth on 166 different sources of carbon, nitrogen and phosphorous, showing an 83.7% accuracy. The model was used to predict metabolic engineering targets for enhancing the biosynthesis of chaxamycins and chaxalactins. Gene knockouts, such as sle03600 (L-homoserine O-acetyltransferase), and sle39090 (trehalose-phosphate synthase), that enhance the production of the specialized metabolites by increasing the pool of precursors were identified. Using the algorithm of flux scanning based on enforced objective flux (FSEOF) implemented in python, 35 and 25 over-expression targets for increasing the production of chaxamycin A and chaxalactin A, respectively, that were not directly associated with their biosynthesis routes were identified. Nineteen over-expression targets that were common to the two specialized metabolites studied, like the over-expression of the acetyl carboxylase complex (sle47660 (accA) and any of the following genes: sle44630 (accA_1) or sle39830 (accA_2) or sle27560 (bccA) or sle59710) were identified. The predicted knockouts and over-expression targets will be used to perform metabolic engineering of S. leeuwenhoekii C34 and obtain overproducer strains. © 2018 Wiley Periodicals, Inc.

Neural evidence for phonologically based language production deficits in older adults: An fMRI investigation of age-related differences in picture-word interference.

PubMed

Rizio, Avery A; Moyer, Karlee J; Diaz, Michele T

2017-04-01

Older adults often show declines in phonological aspects of language production, particularly for low-frequency words, but maintain strong semantic systems. However, there are different theories about the mechanism that may underlie such age-related differences in language (e.g., age-related declines in transmission of activation or inhibition). This study used fMRI to investigate whether age-related differences in language production are associated with transmission deficits or inhibition deficits. We used the picture-word interference paradigm to examine age-related differences in picture naming as a function of both target frequency and the relationship between the target picture and distractor word. We found that the presence of a categorically related distractor led to greater semantic elaboration by older adults compared to younger adults, as evidenced by older adults' increased recruitment of regions including the left middle frontal gyrus and bilateral precuneus. When presented with a phonologically related distractor, patterns of neural activation are consistent with previously observed age deficits in phonological processing, including age-related reductions in the recruitment of regions such as the left middle temporal gyrus and right supramarginal gyrus. Lastly, older, but not younger, adults show increased brain activation of the pre- and postcentral gyri as a function of decreasing target frequency when target pictures are paired with a phonological distractor, suggesting that cuing the phonology of the target disproportionately aids production of low-frequency items. Overall, this pattern of results is generally consistent with the transmission deficit hypothesis, illustrating that links within the phonological system, but not the semantic system, are weakened with age.

RNAi revised--target mRNA-dependent enhancement of gene silencing.

PubMed

Dornseifer, Simon; Willkomm, Sarah; Far, Rosel Kretschmer-Kazemi; Liebschwager, Janine; Beltsiou, Foteini; Frank, Kirsten; Laufer, Sandra D; Martinetz, Thomas; Sczakiel, Georg; Claussen, Jens Christian; Restle, Tobias

2015-12-15

The discovery of RNA interference (RNAi) gave rise to the development of new nucleic acid-based technologies as powerful investigational tools and potential therapeutics. Mechanistic key details of RNAi in humans need to be deciphered yet, before such approaches take root in biomedicine and molecular therapy. We developed and validated an in silico-based model of siRNA-mediated RNAi in human cells in order to link in vitro-derived pre-steady state kinetic data with a quantitative and time-resolved understanding of RNAi on the cellular level. The observation that product release by Argonaute 2 is accelerated in the presence of an excess of target RNA in vitro inspired us to suggest an associative mechanism for the RNA slicer reaction where incoming target mRNAs actively promote dissociation of cleaved mRNA fragments. This novel associative model is compatible with high multiple turnover rates of RNAi-based gene silencing in living cells and accounts for target mRNA concentration-dependent enhancement of the RNAi machinery. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Seeking new anti-cancer agents from autophagy-regulating natural products.

PubMed

Hua, Fang; Shang, Shuang; Hu, Zhuo-Wei

2017-04-01

Natural products are an important original source of many widely used drugs, including anti-cancer drugs. Early research efforts for seeking anti-cancer therapy from the natural products are mainly focused on the compounds with cytotoxicity capability. The good examples include vinblastine, vincristine, the camptothecin derivatives; topotecan, irinotecan, epipodophyllotoxin derivatives and paclitaxel. In a recent decade, the fundamental progression has been made in the understanding of molecular and cellular mechanisms regarding tumor initiation, metastasis, therapeutic resistance, immune escape, and relapse, which provide a great opportunity for the development of new mechanism-based anticancer drugs, especially drugs against new molecular and cellular targets. Autophagy, a critical cell homeostasis mechanism and promising drug target involved in a verity of human diseases including cancer, can be modulated by many compounds derived from natural products. In this review, we'll give a short introduction of autophagy and discuss the roles of autophagy in the tumorigenesis and progression. And then, we summarize the accumulated evidences to show the anti-tumor effects of several compounds derived from natural products through modulation of autophagy activity.

Satellite aerosol retrieval using dark target algorithm by coupling BRDF effect over AERONET site

NASA Astrophysics Data System (ADS)

Yang, Leiku; Xue, Yong; Guang, Jie; Li, Chi

2012-11-01

For most satellite aerosol retrieval algorithms even for multi-angle instrument, the simple forward model (FM) based on Lambertian surface assumption is employed to simulate top of the atmosphere (TOA) spectral reflectance, which does not fully consider the surface bi-directional reflectance functions (BRDF) effect. The approximating forward model largely simplifies the radiative transfer model, reduces the size of the look-up tables, and creates faster algorithm. At the same time, it creates systematic biases in the aerosol optical depth (AOD) retrieval. AOD product from the Moderate Resolution Imaging Spectro-radiometer (MODIS) data based on the dark target algorithm is considered as one of accurate satellite aerosol products at present. Though it performs well at a global scale, uncertainties are still found on regional in a lot of studies. The Lambertian surface assumpiton employed in the retrieving algorithm may be one of the uncertain factors. In this study, we first use radiative transfer simulations over dark target to assess the uncertainty to what extent is introduced from the Lambertian surface assumption. The result shows that the uncertainties of AOD retrieval could reach up to ±0.3. Then the Lambertian FM (L_FM) and the BRDF FM (BRDF_FM) are respectively employed in AOD retrieval using dark target algorithm from MODARNSS (MODIS/Terra and MODIS/Aqua Atmosphere Aeronet Subsetting Product) data over Beijing AERONET site. The validation shows that accuracy in AOD retrieval has been improved by employing the BRDF_FM accounting for the surface BRDF effect, the regression slope of scatter plots with retrieved AOD against AEROENET AOD increases from 0.7163 (for L_FM) to 0.7776 (for BRDF_FM) and the intercept decreases from 0.0778 (for L_FM) to 0.0627 (for BRDF_FM).

MESSI: metabolic engineering target selection and best strain identification tool.

PubMed

Kang, Kang; Li, Jun; Lim, Boon Leong; Panagiotou, Gianni

2015-01-01

Metabolic engineering and synthetic biology are synergistically related fields for manipulating target pathways and designing microorganisms that can act as chemical factories. Saccharomyces cerevisiae's ideal bioprocessing traits make yeast a very attractive chemical factory for production of fuels, pharmaceuticals, nutraceuticals as well as a wide range of chemicals. However, future attempts of engineering S. cerevisiae's metabolism using synthetic biology need to move towards more integrative models that incorporate the high connectivity of metabolic pathways and regulatory processes and the interactions in genetic elements across those pathways and processes. To contribute in this direction, we have developed Metabolic Engineering target Selection and best Strain Identification tool (MESSI), a web server for predicting efficient chassis and regulatory components for yeast bio-based production. The server provides an integrative platform for users to analyse ready-to-use public high-throughput metabolomic data, which are transformed to metabolic pathway activities for identifying the most efficient S. cerevisiae strain for the production of a compound of interest. As input MESSI accepts metabolite KEGG IDs or pathway names. MESSI outputs a ranked list of S. cerevisiae strains based on aggregation algorithms. Furthermore, through a genome-wide association study of the metabolic pathway activities with the strains' natural variation, MESSI prioritizes genes and small variants as potential regulatory points and promising metabolic engineering targets. Users can choose various parameters in the whole process such as (i) weight and expectation of each metabolic pathway activity in the final ranking of the strains, (ii) Weighted AddScore Fuse or Weighted Borda Fuse aggregation algorithm, (iii) type of variants to be included, (iv) variant sets in different biological levels.Database URL: http://sbb.hku.hk/MESSI/. © The Author(s) 2015. Published by Oxford University Press.

Simultaneous quantification of protein phosphorylation sites using liquid chromatography-tandem mass spectrometry-based targeted proteomics: a linear algebra approach for isobaric phosphopeptides.

PubMed

Xu, Feifei; Yang, Ting; Sheng, Yuan; Zhong, Ting; Yang, Mi; Chen, Yun

2014-12-05

As one of the most studied post-translational modifications (PTM), protein phosphorylation plays an essential role in almost all cellular processes. Current methods are able to predict and determine thousands of phosphorylation sites, whereas stoichiometric quantification of these sites is still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics is emerging as a promising technique for site-specific quantification of protein phosphorylation using proteolytic peptides as surrogates of proteins. However, several issues may limit its application, one of which relates to the phosphopeptides with different phosphorylation sites and the same mass (i.e., isobaric phosphopeptides). While employment of site-specific product ions allows for these isobaric phosphopeptides to be distinguished and quantified, site-specific product ions are often absent or weak in tandem mass spectra. In this study, linear algebra algorithms were employed as an add-on to targeted proteomics to retrieve information on individual phosphopeptides from their common spectra. To achieve this simultaneous quantification, a LC-MS/MS-based targeted proteomics assay was first developed and validated for each phosphopeptide. Given the slope and intercept of calibration curves of phosphopeptides in each transition, linear algebraic equations were developed. Using a series of mock mixtures prepared with varying concentrations of each phosphopeptide, the reliability of the approach to quantify isobaric phosphopeptides containing multiple phosphorylation sites (≥ 2) was discussed. Finally, we applied this approach to determine the phosphorylation stoichiometry of heat shock protein 27 (HSP27) at Ser78 and Ser82 in breast cancer cells and tissue samples.

Ewing's Sarcoma: Development of RNA Interference-Based Therapy for Advanced Disease

PubMed Central

Simmons, Olivia; Maples, Phillip B.; Senzer, Neil; Nemunaitis, John

2012-01-01

Ewing's sarcoma tumors are associated with chromosomal translocation between the EWS gene and the ETS transcription factor gene. These unique target sequences provide opportunity for RNA interference(i)-based therapy. A summary of RNAi mechanism and therapeutically designed products including siRNA, shRNA and bi-shRNA are described. Comparison is made between each of these approaches. Systemic RNAi-based therapy, however, requires protected delivery to the Ewing's sarcoma tumor site for activity. Delivery systems which have been most effective in preclinical and clinical testing are reviewed, followed by preclinical assessment of various silencing strategies with demonstration of effectiveness to EWS/FLI-1 target sequences. It is concluded that RNAi-based therapeutics may have testable and achievable activity in management of Ewing's sarcoma. PMID:22523703

Strategic marketing in the UK tobacco industry.

PubMed

Anderson, Susan; Hastings, Gerard; MacFadyen, Lynn

2002-08-01

Tobacco-industry marketing has played a central part in the global spread of tobacco use and addiction. Although the absolute size of the tobacco market has dwindled, the industry is still immensely successful, largely due to sophisticated and manipulative marketing strategies. The UK tobacco industry identifies target groups and builds enduring relationships based on careful brand management. Potential customers are exposed to brands which are likely to appeal to them most. Tobacco companies tailor their products to target markets by altering the content of tar and nicotine, and by adding flavourings to produce a distinctive taste. Marketing strategies ensure that the products are promoted heavily at the point of sale, and directed advertising and sponsorship agreements are used to increase the visibility of the brand and strengthen its image. Tobacco companies also target non-consumer organisations such as retailers and policy makers with the aim of creating the best possible business environment for tobacco sales. We review published evidence, internal-advertising-agency documents, and observational data about tobacco promotion, and discuss the use of targeted marketing strategies in the UK.

High-intensity positron microprobe at Jefferson Lab

DOE PAGES

Golge, Serkan; Vlahovic, Branislav; Wojtsekhowski, Bogdan B.

2014-06-19

We present a conceptual design for a novel continuous wave electron-linac based high-intensity slow-positron production source with a projected intensity on the order of 10 10 e +/s. Reaching this intensity in our design relies on the transport of positrons (T + below 600 keV) from the electron-positron pair production converter target to a low-radiation and low-temperature area for moderation in a high-efficiency cryogenic rare gas moderator, solid Ne. The performance of the integrated beamline has been verified through computational studies. The computational results include Monte Carlo calculations of the optimized electron/positron beam energies, converter target thickness, synchronized raster system,more » transport of the beam from the converter target to the moderator, extraction of the beam from the channel, and moderation efficiency calculations. For the extraction of positrons from the magnetic channel a magnetic field terminator plug prototype has been built and experimental data on the effectiveness of this prototype are presented. The dissipation of the heat away from the converter target and radiation protection measures are also discussed.« less

Target-triggering multiple-cycle signal amplification strategy for ultrasensitive detection of DNA based on QCM and SPR.

PubMed

Song, Weiling; Yin, Wenshuo; Sun, Wenbo; Guo, Xiaoyan; He, Peng; Yang, Xiaoyan; Zhang, Xiaoru

2018-04-24

Detection of ultralow concentrations of nucleic acid sequences is a central challenge in the early diagnosis of genetic diseases. Herein, we developed a target-triggering cascade multiple cycle amplification for ultrasensitive DNA detection using quartz crystal microbalance (QCM) and surface plasmon resonance (SPR). It was based on the exonuclease Ⅲ (Exo Ⅲ)-assisted signal amplification and the hybridization chain reaction (HCR). The streptavidin-coated Au-NPs (Au-NPs-SA) were assembled on the HCR products as recognition element. Upon sensing of target DNA, the duplex DNA probe triggered the Exo Ⅲ cleavage process, accompanied by generating a new secondary target DNA and releasing target DNA. The released target DNA and the secondary target DNA were recycled. Simultaneously, numerous single strands were liberated and acted as the trigger of HCR to generate further signal amplification, resulting in the immobilization of abundant Au-NPs-SA on the gold substrate. The QCM sensor results were found to be comparable to that achieved using a SPR sensor platform. This method exhibited a high sensitivity toward target DNA with a detection limit of 0.70 fM. The high sensitivity and specificity make this method a great potential for detecting DNA with trace amounts in bioanalysis and clinical biomedicine. Copyright © 2018 Elsevier Inc. All rights reserved.

Production Of High Specific Activity Copper-67

DOEpatents

Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

2002-12-03

A process for the selective production and isolation of high specific activity cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

Production Of High Specific Activity Copper-67

DOEpatents

Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

2003-10-28

A process for the selective production and isolation of high specific activity Cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

Advances in large, transportable, highly spin-polarized, solid HD targets operable in the frozen-spin mode in a 1-4K temperature environment

NASA Astrophysics Data System (ADS)

Lewis, Aaron Paul

The development of large, portable highly spin-polarized solid HD targets has been in progress at Syracuse University for the past 5 years. These targets are scheduled for deployment at Brookhaven National Laboratory, bearing the acronym SPHICE (Spin-Polarized Hydrogen Ice), for studies of the electro-magnetic spin structure of the nucleus via scattering of polarized gammas from the HD polarized protons and deuterons. The target work has just reached the milestone demonstration of the complete system, including polarization of triple targets containing 4 moles of solid HD, aging of these targets so that they retain their polarization for months under storage at a temperature of 1.3K and in an 8 Tesla field, and for at least a week at operational conditions of 1.3K and 0.7 Tesla in an in-beam cryostat. Cold-transfers of the polarized targets to a storage cryostat have been successfully carried out, and the storage cryostat has been trucked from Syracuse to BNL with one polarized target, sufficient to test the in-beam operations there. The complete system is presented here, with emphasis on innovations for engagement and disengagement of multiple targets, a solution to the challenge of attaining sufficiently strong RF fields in the large volume probe coils at acceptable power dissipation in the cables, and the polarization production and monitoring in the highly inhomogeneous magnetic fields owing to the multiple targets and the large dimensions of the targets. In this first multiple target production and extraction-to-storage cycle, air-ice accumulation in the dilution refrigerator due to repetitive use of cold sliding o-ring seals resulted in a rupture of one of the inserted targets, and a consequent partial thermal short from a solid HD ice bridge. The o-ring fault was cured with double evacuatable o-ring seals, and the air-ice was successfully cleaned out. However, the refrigerator operating base temperature was substantially higher than that normally obtained and the proton polarizations were accordingly lower than the 48% previously obtained. Nevertheless, the targets passed all their production procedures and are still useful for a first experiment at BNL. We anticipate an era of important use of these now demonstrated specially advantageous polarized frozen-spin HD targets.

High impact technologies for natural products screening.

PubMed

Koehn, Frank E

2008-01-01

Natural products have historically been a rich source of lead molecules in drug discovery. However, natural products have been de-emphasized as high throughput screening resources in the recent past, in part because of difficulties in obtaining high quality natural products screening libraries, or in applying modern screening assays to these libraries. In addition, natural products programs based on screening of extract libraries, bioassay-guided isolation, structure elucidation and subsequent production scale-up are challenged to meet the rapid cycle times that are characteristic of the modern HTS approach. Fortunately, new technologies in mass spectrometry, NMR and other spectroscopic techniques can greatly facilitate the first components of the process - namely the efficient creation of high-quality natural products libraries, bimolecular target or cell-based screening, and early hit characterization. The success of any high throughput screening campaign is dependent on the quality of the chemical library. The construction and maintenance of a high quality natural products library, whether based on microbial, plant, marine or other sources is a costly endeavor. The library itself may be composed of samples that are themselves mixtures - such as crude extracts, semi-pure mixtures or single purified natural products. Each of these library designs carries with it distinctive advantages and disadvantages. Crude extract libraries have lower resource requirements for sample preparation, but high requirements for identification of the bioactive constituents. Pre-fractionated libraries can be an effective strategy to alleviate interferences encountered with crude libraries, and may shorten the time needed to identify the active principle. Purified natural product libraries require substantial resources for preparation, but offer the advantage that the hit detection process is reduced to that of synthetic single component libraries. Whether the natural products library consists of crude or partially fractionated mixtures, the library contents should be profiled to identify the known components present - a process known as dereplication. The use of mass spectrometry and HPLC-mass spectrometry together with spectral databases is a powerful tool in the chemometric profiling of bio-sources for natural product production. High throughput, high sensitivity flow NMR is an emerging tool in this area as well. Whether by cell based or biomolecular target based assays, screening of natural product extract libraries continues to furnish novel lead molecules for further drug development, despite challenges in the analysis and prioritization of natural products hits. Spectroscopic techniques are now being used to directly screen natural product and synthetic libraries. Mass spectrometry in the form of methods such as ESI-ICRFTMS, and FACS-MS as well as NMR methods such as SAR by NMR and STD-NMR have been utilized to effectively screen molecular libraries. Overall, emerging advances in mass spectrometry, NMR and other technologies are making it possible to overcome the challenges encountered in screening natural products libraries in today's drug discovery environment. As we apply these technologies and develop them even further, we can look forward to increased impact of natural products in the HTS based drug discovery.

Analysis of Operating Strategies Using Different Target Designs For 238Pu Production

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

Thomas, Tomcy; Sherman, Steven R; Sawhney, Dr. Rapinder

2017-01-01

An engineering effort is underway to re-establish capability to produce 238Pu oxide at the kilogram scale in the United States. A multi-step batch process is being developed to produce this important material. Recently, a portion of this process was studied using discrete-event simulation tools to determine whether the conceptual process might achieve its yearly production goal. The study showed the conceptual process can meet the yearly production goal under some circumstances, but process improvements would be needed to ensure greater likelihood of success. This study extends the work performed previously by examining the effects of changing the reactor target designmore » on the yearly process output. Two new reactor target configurations are considered an aluminum-clad reactor target containing 50% greater 237Np oxide content than the original target, and a zirconium alloy-clad target using no aluminum. The results indicate that use of the new aluminum-clad target configuration may allow the process to achieve the same yearly production goal in less time using fewer targets. If the zirconium alloy-clad target is used, then even fewer targets would be needed to reach the production goal, but some process changes would be required to handle the zirconium cladding. The number of days needed to process a target batch to completion, and the steady state 238Pu oxide production rate, for each configuration are compared to the results from the initial simulation study.« less

Disulfide-induced self-assembled targets: A novel strategy for the label free colorimetric detection of DNAs/RNAs via unmodified gold nanoparticles

NASA Astrophysics Data System (ADS)

Shokri, Ehsan; Hosseini, Morteza; Davari, Mehdi D.; Ganjali, Mohammad R.; Peppelenbosch, Maikel P.; Rezaee, Farhad

2017-04-01

A modified non-cross-linking gold-nanoparticles (Au-NPs) aggregation strategy has been developed for the label free colorimetric detection of DNAs/RNAs based on self-assembling target species in the presence of thiolated probes. Two complementary thiol- modified probes, each of which specifically binds at one half of the target introduced SH groups at both ends of dsDNA. Continuous disulfide bond formation at 3‧ and 5‧ terminals of targets leads to the self-assembly of dsDNAs into the sulfur- rich and flexible products with different lengths. These products have a high affinity for the surface of Au-NPs and efficiently protect the surface from salt induced aggregation. To evaluate the assay efficacy, a small part of the citrus tristeza virus (CTV) genome was targeted, leading to a detection limit of about 5 × 10-9 mol.L-1 over a linear ranged from 20 × 10-9 to 10 × 10-7 mol.L-1. This approach also exhibits good reproducibility and recovery levels in the presence of plant total RNA or human plasma total circulating RNA extracts. Self-assembled targets can be then sensitively distinguished from non-assembled or mismatched targets after gel electrophoresis. The disulfide reaction method and integrating self-assembled DNAs/RNAs targets with bare AuNPs as a sensitive indicator provide us a powerful and simple visual detection tool for a wide range of applications.

Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment

PubMed Central

Hill, Andrew; Gotham, Dzintars; Fortunak, Joseph; Meldrum, Jonathan; Erbacher, Isabelle; Martin, Manuel; Shoman, Haitham; Levi, Jacob; Powderly, William G; Bower, Mark

2016-01-01

Objective To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). Background TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. Methods Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. Results API costs per kg were $347–$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128–$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. Conclusions Mass generic production of several TKIs could achieve treatment prices in the range of $128–$4020 per person-year, versus current US prices of $75161–$139 138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients. PMID:26817636

Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining.

PubMed

Tang, Xiaoyu; Li, Jie; Millán-Aguiñaga, Natalie; Zhang, Jia Jia; O'Neill, Ellis C; Ugalde, Juan A; Jensen, Paul R; Mantovani, Simone M; Moore, Bradley S

2015-12-18

Recent genome sequencing efforts have led to the rapid accumulation of uncharacterized or "orphaned" secondary metabolic biosynthesis gene clusters (BGCs) in public databases. This increase in DNA-sequenced big data has given rise to significant challenges in the applied field of natural product genome mining, including (i) how to prioritize the characterization of orphan BGCs and (ii) how to rapidly connect genes to biosynthesized small molecules. Here, we show that by correlating putative antibiotic resistance genes that encode target-modified proteins with orphan BGCs, we predict the biological function of pathway specific small molecules before they have been revealed in a process we call target-directed genome mining. By querying the pan-genome of 86 Salinispora bacterial genomes for duplicated house-keeping genes colocalized with natural product BGCs, we prioritized an orphan polyketide synthase-nonribosomal peptide synthetase hybrid BGC (tlm) with a putative fatty acid synthase resistance gene. We employed a new synthetic double-stranded DNA-mediated cloning strategy based on transformation-associated recombination to efficiently capture tlm and the related ttm BGCs directly from genomic DNA and to heterologously express them in Streptomyces hosts. We show the production of a group of unusual thiotetronic acid natural products, including the well-known fatty acid synthase inhibitor thiolactomycin that was first described over 30 years ago, yet never at the genetic level in regards to biosynthesis and autoresistance. This finding not only validates the target-directed genome mining strategy for the discovery of antibiotic producing gene clusters without a priori knowledge of the molecule synthesized but also paves the way for the investigation of novel enzymology involved in thiotetronic acid natural product biosynthesis.

System Characterization Results for the QuickBird Sensor

NASA Technical Reports Server (NTRS)

Holekamp, Kara; Ross, Kenton; Blonski, Slawomir

2007-01-01

An overall system characterization was performed on several DigitalGlobe' QuickBird image products by the NASA Applied Research & Technology Project Office (formerly the Applied Sciences Directorate) at the John C. Stennis Space Center. This system characterization incorporated geopositional accuracy assessments, a spatial resolution assessment, and a radiometric calibration assessment. Geopositional assessments of standard georeferenced multispectral products were obtained using an array of accurately surveyed geodetic targets evenly spaced throughout a scene. Geopositional accuracy was calculated in terms of circular error. Spatial resolution of QuickBird panchromatic imagery was characterized based on edge response measurements using edge targets and the tilted-edge technique. Relative edge response was estimated as a geometric mean of normalized edge response differences measured in two directions of image pixels at points distanced from the edge by -0.5 and 0.5 of ground sample distance. A reflectance-based vicarious calibration approach, based on ground-based measurements and radiative transfer calculations, was used to estimate at-sensor radiance. These values were compared to those measured by the sensor to determine the sensor's radiometric accuracy. All imagery analyzed was acquired between fall 2005 and spring 2006. These characterization results were compared to previous years' results to identify any temporal drifts or trends.

An Informatics Approach to Evaluating Combined Chemical Exposures from Consumer Products: A Case Study of Asthma-Associated Chemicals and Potential Endocrine Disruptors.

PubMed

Gabb, Henry A; Blake, Catherine

2016-08-01

Simultaneous or sequential exposure to multiple environmental stressors can affect chemical toxicity. Cumulative risk assessments consider multiple stressors but it is impractical to test every chemical combination to which people are exposed. New methods are needed to prioritize chemical combinations based on their prevalence and possible health impacts. We introduce an informatics approach that uses publicly available data to identify chemicals that co-occur in consumer products, which account for a significant proportion of overall chemical load. Fifty-five asthma-associated and endocrine disrupting chemicals (target chemicals) were selected. A database of 38,975 distinct consumer products and 32,231 distinct ingredient names was created from online sources, and PubChem and the Unified Medical Language System were used to resolve synonymous ingredient names. Synonymous ingredient names are different names for the same chemical (e.g., vitamin E and tocopherol). Nearly one-third of the products (11,688 products, 30%) contained ≥ 1 target chemical and 5,229 products (13%) contained > 1. Of the 55 target chemicals, 31 (56%) appear in ≥ 1 product and 19 (35%) appear under more than one name. The most frequent three-way chemical combination (2-phenoxyethanol, methyl paraben, and ethyl paraben) appears in 1,059 products. Further work is needed to assess combined chemical exposures related to the use of multiple products. The informatics approach increased the number of products considered in a traditional analysis by two orders of magnitude, but missing/incomplete product labels can limit the effectiveness of this approach. Such an approach must resolve synonymy to ensure that chemicals of interest are not missed. Commonly occurring chemical combinations can be used to prioritize cumulative toxicology risk assessments. Gabb HA, Blake C. 2016. An informatics approach to evaluating combined chemical exposures from consumer products: a case study of asthma-associated chemicals and potential endocrine disruptors. Environ Health Perspect 124:1155-1165; http://dx.doi.org/10.1289/ehp.1510529.

Twin target self-amplification-based DNA machine for highly sensitive detection of cancer-related gene.

PubMed

Xu, Huo; Jiang, Yifan; Liu, Dengyou; Liu, Kai; Zhang, Yafeng; Yu, Suhong; Shen, Zhifa; Wu, Zai-Sheng

2018-06-29

The sensitive detection of cancer-related genes is of great significance for early diagnosis and treatment of human cancers, and previous isothermal amplification sensing systems were often based on the reuse of target DNA, the amplification of enzymatic products and the accumulation of reporting probes. However, no reporting probes are able to be transformed into target species and in turn initiate the signal of other probes. Herein we reported a simple, isothermal and highly sensitive homogeneous assay system for tumor suppressor p53 gene detection based on a new autonomous DNA machine, where the signaling probe, molecular beacon (MB), was able to execute the function similar to target DNA besides providing the common signal. In the presence of target p53 gene, the operation of DNA machine can be initiated, and cyclical nucleic acid strand-displacement polymerization (CNDP) and nicking/polymerization cyclical amplification (NPCA) occur, during which the MB was opened by target species and cleaved by restriction endonuclease. In turn, the cleaved fragments could activate the next signaling process as target DNA did. According to the functional similarity, the cleaved fragment was called twin target, and the corresponding fashion to amplify the signal was named twin target self-amplification. Utilizing this newly-proposed DNA machine, the target DNA could be detected down to 0.1 pM with a wide dynamic range (6 orders of magnitude) and single-base mismatched targets were discriminated, indicating a very high assay sensitivity and good specificity. In addition, the DNA machine was not only used to screen the p53 gene in complex biological matrix but also was capable of practically detecting genomic DNA p53 extracted from A549 cell line. This indicates that the proposed DNA machine holds the potential application in biomedical research and early clinical diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Natural product-based nanomedicine: recent advances and issues

PubMed Central

Watkins, Rebekah; Wu, Ling; Zhang, Chenming; Davis, Richey M; Xu, Bin

2015-01-01

Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds’ low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications. PMID:26451111

Finished with Menthol: An Evidence-Based Policy Option That Will Save Lives.

PubMed

Lester, Joelle M; Gagosian, Stacey Younger

2017-03-01

Smoking remains the leading cause of preventable disease and death in the United States, killing approximately 480,000 people each year. This crushing health burden falls disproportionately, and recent CDC data shows that large disparities in adult cigarette smoking remain. One factor in these disparities is the use of flavors. Menthol cigarettes and other flavored tobacco products are used at higher rates by vulnerable populations including youth and young adults, African Americans, women, Hispanics and Asian Americans. This is no accident; the tobacco industry has long targeted these same groups. Given FDA's failure to act to ban flavored tobacco products, states and municipalities are considering taking matters into their own hands to protect their communities from these dangerous products. The authors will explore state and local authority to restrict the sales of these products and review the evidence base indicating that removing flavored tobacco products - and menthol combustible products in particular - from the market would significantly reduce the toll of illness and death caused by these products.

Kepler Data Validation I—Architecture, Diagnostic Tests, and Data Products for Vetting Transiting Planet Candidates

NASA Astrophysics Data System (ADS)

Twicken, Joseph D.; Catanzarite, Joseph H.; Clarke, Bruce D.; Girouard, Forrest; Jenkins, Jon M.; Klaus, Todd C.; Li, Jie; McCauliff, Sean D.; Seader, Shawn E.; Tenenbaum, Peter; Wohler, Bill; Bryson, Stephen T.; Burke, Christopher J.; Caldwell, Douglas A.; Haas, Michael R.; Henze, Christopher E.; Sanderfer, Dwight T.

2018-06-01

The Kepler Mission was designed to identify and characterize transiting planets in the Kepler Field of View and to determine their occurrence rates. Emphasis was placed on identification of Earth-size planets orbiting in the Habitable Zone of their host stars. Science data were acquired for a period of four years. Long-cadence data with 29.4 min sampling were obtained for ∼200,000 individual stellar targets in at least one observing quarter in the primary Kepler Mission. Light curves for target stars are extracted in the Kepler Science Data Processing Pipeline, and are searched for transiting planet signatures. A Threshold Crossing Event is generated in the transit search for targets where the transit detection threshold is exceeded and transit consistency checks are satisfied. These targets are subjected to further scrutiny in the Data Validation (DV) component of the Pipeline. Transiting planet candidates are characterized in DV, and light curves are searched for additional planets after transit signatures are modeled and removed. A suite of diagnostic tests is performed on all candidates to aid in discrimination between genuine transiting planets and instrumental or astrophysical false positives. Data products are generated per target and planet candidate to document and display transiting planet model fit and diagnostic test results. These products are exported to the Exoplanet Archive at the NASA Exoplanet Science Institute, and are available to the community. We describe the DV architecture and diagnostic tests, and provide a brief overview of the data products. Transiting planet modeling and the search for multiple planets on individual targets are described in a companion paper. The final revision of the Kepler Pipeline code base is available to the general public through GitHub. The Kepler Pipeline has also been modified to support the Transiting Exoplanet Survey Satellite (TESS) Mission which is expected to commence in 2018.

Human Parainfluenza Virus-3 can be Targeted by Rapidly ex vivo Expanded T-Lymphocytes

PubMed Central

McLaughlin, Lauren P.; Lang, Haili; Williams, Elizabeth; Wright, Kaylor E.; Powell, Allison; Cruz, Conrad R; Colberg-Poley, Anamaris M.; Barese, Cecilia; Hanley, Patrick J.; Bollard, Catherine M.; Keller, Michael D.

2016-01-01

Background Human Parainfluenza virus-3 (HPIV) is a common cause of respiratory infection in immunocompromised patients, and presently has no effective therapies. Virus-specific T-cell therapy has been successful for the treatment or prevention of viral infections in immunocompromised patients, but requires determination of T-cell antigens on targeted viruses. Methods HPIV3-specific T cells were expanded from peripheral blood of healthy donors using a rapid generation protocol targeting four HPIV3 proteins. Immunophenotyping was performed by flow cytometry. Viral specificity was determined by IFN-γ ELISpot, intracellular cytokine staining, and cytokine measurements from culture supernatants by Luminex assay. Cytotoxic activity was tested by 51Cr release and CD107a mobilization assays. Virus-specific T-cells targeting 6 viruses were then produced by rapid protocol, and the phenotype of HPIV3-specific T-cells was determined by immunomagnetic sorting for IFN-γ producing cells. Results HPIV3-specific T cells were expanded from 13 healthy donors. HPIV3-specific T-cells showed a CD4+ predominance (mean CD4:CD8 ratio 2.89), and demonstrated specificity for multiple HPIV3 antigens. The expanded T-cells were polyfunctional based on cytokine production, but only had a minor cytotoxic component. T cells targeting six viruses in a single product similarly showed HPIV3 specificity, with a predominant effector memory phenotype (CD3+/CD45RA-/CCR7-) in responder cells. Discussion HPIV3-specific T cells can be produced using a rapid ex vivo protocol from healthy donors and are predominantly CD4+ T-cells with Th1 activity. HPIV3 epitopes can also be successfully targeted alongside multiple other viral epitopes in production of 6-virus T-cells, without loss of HPIV3 specificity. These products may be clinically beneficial to combat HPIV3 infections by adoptive T-cell therapy in immune compromised patients. PMID:27692559

Kepler Data Validation I: Architecture, Diagnostic Tests, and Data Products for Vetting Transiting Planet Candidates

NASA Technical Reports Server (NTRS)

Twicken, Joseph D.; Catanzarite, Joseph H.; Clarke, Bruce D.; Giroud, Forrest; Jenkins, Jon M.; Klaus, Todd C.; Li, Jie; McCauliff, Sean D.; Seader, Shawn E.; Tennenbaum, Peter;

12 CFR 1805.701 - Evaluation of applications.

Code of Federal Regulations, 2012 CFR

2012-01-01

... assistance from the Fund, expand its operations into a new Target Market, offer more products or services... Target Market, the extent of success in serving such Target Market); (2) Operational capacity and risk... designated Target Market, and the extent of demand within the Target Market for the Applicant's products and...

12 CFR 1805.701 - Evaluation of applications.

Code of Federal Regulations, 2014 CFR

2014-01-01

... assistance from the Fund, expand its operations into a new Target Market, offer more products or services... Target Market, the extent of success in serving such Target Market); (2) Operational capacity and risk... designated Target Market, and the extent of demand within the Target Market for the Applicant's products and...

12 CFR 1805.701 - Evaluation of applications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... assistance from the Fund, expand its operations into a new Target Market, offer more products or services... Target Market, the extent of success in serving such Target Market); (2) Operational capacity and risk... designated Target Market, and the extent of demand within the Target Market for the Applicant's products and...

12 CFR 1805.701 - Evaluation of applications.

Code of Federal Regulations, 2011 CFR

2011-01-01

... assistance from the Fund, expand its operations into a new Target Market, offer more products or services... Target Market, the extent of success in serving such Target Market); (2) Operational capacity and risk... designated Target Market, and the extent of demand within the Target Market for the Applicant's products and...

Evanescent acoustic waves: Production and scattering by resonant targets

NASA Astrophysics Data System (ADS)

Osterhoudt, Curtis F.

Small targets with acoustic resonances which may be excited by incident acoustic planewaves are shown to possess high-Q modes ("organ-pipe" modes) which may be suitable for ocean-based calibration and ranging purposes. The modes are modeled using a double point-source model; this, along with acoustic reciprocity and inversion symmetry, is shown to adequately model the backscattering form functions of the modes at low frequencies. The backscattering form-functions are extended to apply to any bistatic acoustic experiment using the targets when the target response is dominated by the modes in question. An interface between two fluids which each approximate an unbounded half-space has been produced in the laboratory. The fluids have different sound speeds. When sound is incident on this interface at beyond the critical angle from within the first fluid, the second fluid is made to evince a region dominated by evanescent acoustic energy. Such a system is shown to be an possible laboratory-based proxy for a flat sediment bottom in the ocean, or sloped (unrippled) bottom in littoral environments. The evanescent sound field is characterized and shown to have complicated features despite the simplicity of its production. Notable among these features is the presence of dips in the soundfield amplitude, or "quasi-nulls". These are proposed to be extremely important when considering the return from ocean-based experiments. The soundfield features are also shown to be accurately predicted and characterized by wavenumber-integration software. The targets which exhibit organ-pipe modes in the free-field are shown to also be excited by the evanescent waves, and may be used as soundfield probes when the target returns are well characterized. Alternately, if the soundfield is well-known, the target parameters may be extracted from back- or bistatic-scattering experiments in evanescent fields. It is shown that the spatial decay rate as measured by a probe directly in the evanescent field is half that as measured by backscattering experiments on horizontal and vertical cylinders driven at the fundamental mode, and it is demonstrated that this is explained by the principle of acoustic reciprocity.

Undesired Small RNAs Originate from an Artificial microRNA Precursor in Transgenic Petunia (Petunia hybrida)

PubMed Central

Guo, Yulong; Han, Yao; Ma, Jing; Wang, Huiping; Sang, Xianchun; Li, Mingyang

2014-01-01

Although artificial microRNA (amiRNA) technology has been used frequently in gene silencing in plants, little research has been devoted to investigating the accuracy of amiRNA precursor processing. In this work, amiRNAchs1 (amiRchs1), based on the Arabidopsis miR319a precursor, was expressed in order to suppress the expression of CHS genes in petunia. The transgenic plants showed the CHS gene-silencing phenotype. A modified 5′ RACE technique was used to map small-RNA-directed cleavage sites and to detect processing intermediates of the amiRchs1 precursor. The results showed that the target CHS mRNAs were cut at the expected sites and that the amiRchs1 precursor was processed from loop to base. The accumulation of small RNAs in amiRchs1 transgenic petunia petals was analyzed using the deep-sequencing technique. The results showed that, alongside the accumulation of the desired artificial microRNAs, additional small RNAs that originated from other regions of the amiRNA precursor were also accumulated at high frequency. Some of these had previously been found to be accumulated at low frequency in the products of ath-miR319a precursor processing and some of them were accompanied by 3′-tailing variant. Potential targets of the undesired small RNAs were discovered in petunia and other Solanaceae plants. The findings draw attention to the potential occurrence of undesired target silencing induced by such additional small RNAs when amiRNA technology is used. No appreciable production of secondary small RNAs occurred, despite the fact that amiRchs1 was designed to have perfect complementarity to its CHS-J target. This confirmed that perfect pairing between an amiRNA and its targets is not the trigger for secondary small RNA production. In conjunction with the observation that amiRNAs with perfect complementarity to their target genes show high efficiency and specificity in gene silencing, this finding has an important bearing on future applications of amiRNAs in gene silencing in plants. PMID:24897430

Undesired small RNAs originate from an artificial microRNA precursor in transgenic petunia (Petunia hybrida).

PubMed

Guo, Yulong; Han, Yao; Ma, Jing; Wang, Huiping; Sang, Xianchun; Li, Mingyang

2014-01-01

Although artificial microRNA (amiRNA) technology has been used frequently in gene silencing in plants, little research has been devoted to investigating the accuracy of amiRNA precursor processing. In this work, amiRNAchs1 (amiRchs1), based on the Arabidopsis miR319a precursor, was expressed in order to suppress the expression of CHS genes in petunia. The transgenic plants showed the CHS gene-silencing phenotype. A modified 5' RACE technique was used to map small-RNA-directed cleavage sites and to detect processing intermediates of the amiRchs1 precursor. The results showed that the target CHS mRNAs were cut at the expected sites and that the amiRchs1 precursor was processed from loop to base. The accumulation of small RNAs in amiRchs1 transgenic petunia petals was analyzed using the deep-sequencing technique. The results showed that, alongside the accumulation of the desired artificial microRNAs, additional small RNAs that originated from other regions of the amiRNA precursor were also accumulated at high frequency. Some of these had previously been found to be accumulated at low frequency in the products of ath-miR319a precursor processing and some of them were accompanied by 3'-tailing variant. Potential targets of the undesired small RNAs were discovered in petunia and other Solanaceae plants. The findings draw attention to the potential occurrence of undesired target silencing induced by such additional small RNAs when amiRNA technology is used. No appreciable production of secondary small RNAs occurred, despite the fact that amiRchs1 was designed to have perfect complementarity to its CHS-J target. This confirmed that perfect pairing between an amiRNA and its targets is not the trigger for secondary small RNA production. In conjunction with the observation that amiRNAs with perfect complementarity to their target genes show high efficiency and specificity in gene silencing, this finding has an important bearing on future applications of amiRNAs in gene silencing in plants.

Lab-on-a-chip-based PCR-RFLP assay for the confirmed detection of short-length feline DNA in food.

PubMed

Ali, Md Eaqub; Al Amin, Md; Hamid, Sharifah Bee Abd; Hossain, M A Motalib; Mustafa, Shuhaimi

2015-01-01

Wider availability but lack of legal market trades has given feline meat a high potential for use as an adulterant in common meat and meat products. However, mixing of feline meat or its derivatives in food is a sensitive issue, since it is a taboo in most countries and prohibited in certain religions such as Islam and Judaism. Cat meat also has potential for contamination with of severe acute respiratory syndrome, anthrax and hepatitis, and its consumption might lead to an allergic reaction. We developed a very short-amplicon-length (69 bp) PCR assay, authenticated the amplified PCR products by AluI-restriction digestion followed by its separation and detection on a lab-on-a-chip-based automated electrophoretic system, and proved its superiority over the existing long-amplicon-based assays. Although it has been assumed that longer DNA targets are susceptible to breakdown under compromised states, scientific evidence for this hypothesis has been rarely documented. Strong evidence showed that shorter targets are more stable than the longer ones. We confirmed feline-specificity by cross-challenging the primers against 10 different species of terrestrial, aquatic and plant origins in the presence of a 141-bp site of an 18S rRNA gene as a universal eukaryotic control. RFLP analysis separated 43- and 26-bp fragments of AluI-digest in both the gel-image and electropherograms, confirming the original products. The tested detection limit was 0.01% (w/w) feline meat in binary and ternary admixed as well as meatball matrices. Shorter target, better stability and higher sensitivity mean such an assay would be valid for feline identification even in degraded specimens.

Natural Toxins for Use in Pest Management

PubMed Central

Duke, Stephen O.; Cantrell, Charles L.; Meepagala, Kumudini M.; Wedge, David E.; Tabanca, Nurhayat; Schrader, Kevin K.

2010-01-01

Natural toxins are a source of new chemical classes of pesticides, as well as environmentally and toxicologically safer molecules than many of the currently used pesticides. Furthermore, they often have molecular target sites that are not exploited by currently marketed pesticides. There are highly successful products based on natural compounds in the major pesticide classes. These include the herbicide glufosinate (synthetic phosphinothricin), the spinosad insecticides, and the strobilurin fungicides. These and other examples of currently marketed natural product-based pesticides, as well as natural toxins that show promise as pesticides from our own research are discussed. PMID:22069667

[Physically-based model of pesticide application for risk assessment of agricultural workers].

PubMed

Rubino, F M; Mandic-Rajcevic, S; Vianello, G; Brambilla, G; Colosio, C

2012-01-01

Due to their unavoidable toxicity to non-target organisms, including man, the not of Plant Protection Products requires a thorough risk assessment to rationally advise safe use procedures and protection equipment by farmers. Most information on active substances and formulations, such as dermal absorption rates and exposure limits are available in the large body of regulatory data. Physically-based computational models can be used to forecast risk in real-life conditions (preventive assessment by 'exposure profiles'), to drive the cost-effective use of products and equipment and to understand the sources of unexpected exposure.

Hi-Plex for Simple, Accurate, and Cost-Effective Amplicon-based Targeted DNA Sequencing.

PubMed

Pope, Bernard J; Hammet, Fleur; Nguyen-Dumont, Tu; Park, Daniel J

2018-01-01

Hi-Plex is a suite of methods to enable simple, accurate, and cost-effective highly multiplex PCR-based targeted sequencing (Nguyen-Dumont et al., Biotechniques 58:33-36, 2015). At its core is the principle of using gene-specific primers (GSPs) to "seed" (or target) the reaction and universal primers to "drive" the majority of the reaction. In this manner, effects on amplification efficiencies across the target amplicons can, to a large extent, be restricted to early seeding cycles. Product sizes are defined within a relatively narrow range to enable high-specificity size selection, replication uniformity across target sites (including in the context of fragmented input DNA such as that derived from fixed tumor specimens (Nguyen-Dumont et al., Biotechniques 55:69-74, 2013; Nguyen-Dumont et al., Anal Biochem 470:48-51, 2015), and application of high-specificity genetic variant calling algorithms (Pope et al., Source Code Biol Med 9:3, 2014; Park et al., BMC Bioinformatics 17:165, 2016). Hi-Plex offers a streamlined workflow that is suitable for testing large numbers of specimens without the need for automation.

Targeted marketing and public health.

PubMed

Grier, Sonya A; Kumanyika, Shiriki

2010-01-01

Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies.

Energy release, beam attenuation radiation damage, gas production and accumulation of long-lived activity in Pb, Pb-Bi and Hg targets

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

Shubin, Yu.N.

1996-06-01

The calculation and analysis of the nuclei concentrations and long-lived residual radioactivity accumulated in Pb, Pb-Bi and Hg targets irradiated by 800 MeV, 30 mA proton beam have been performed. The dominating components to the total radioactivity of radionuclides resulting from fission and spallation reactions and radiative capture by both target nuclei and accumulated radioactive nuclei for various irradiation and cooling times were analyzed. The estimations of spectral component contributions of neutron and proton fluxes to the accumulated activity were carried out. The contributions of fission products to the targets activity and partial activities of main long-lived fission products tomore » the targets activity and partial activities of main long-lived fission products were evaluated. The accumulation of Po isotopes due to reactions induced by secondary alpha-particles were found to be important for the Pb target as compared with two-step radiative capture. The production of Tritium in the targets and its contribution to the total targets activity was considered in detail. It is found that total activities of both targets are close to one another.« less

Multiresidue determination and potential risks of emerging pesticides in aquatic products from Northeast China by LC-MS/MS.

PubMed

Fu, Lei; Lu, Xianbo; Tan, Jun; Wang, Longxing; Chen, Jiping

2018-01-01

A simple method for determining 33 pesticides with a wide polarity range (logK ow 0.6-4.5) in aquatic products was developed based on LC-MS/MS. The target analytes included three types of widely used pesticides: insecticides, fungicides and herbicides. Based on the optimization of ultrasonic assisted extraction and GPC clean-up procedures, the matrix effect, extraction recoveries and LOD were improved distinctively. LOQ of this method was below 0.5ng/g for all pesticides, which is superior to values in the literature, and the matrix effect was reduced effectively (-14.7% to 7.5%). The method was successfully applied to investigate the pesticide residue levels of twenty-five samples including seven common kinds of fishes from Northeast China. The results showed that all targeted pesticides were present in the fish samples; however, their levels were low, except for atrazine, linuron, ethoprophos, tetrachlorvinphos, acetochlor and fenthion. Atrazine and linuron caught our attention because the concentrations of atrazine in fish samples from Liaoning province were in the range of 0.5-8ng/g (w/w) with mean concentration of 2.3ng/g, which were far above those of other pesticides. The levels of linuron were in the range of 0.6-6ng/g (mean concentration 2.8ng/g), which were the highest among all targeted pesticides in the Inner Mongolia. This is the first systematic investigation on the characteristics and levels of these pesticides in aquatic products from northeast China. Considering their toxicity and bioaccumulation, the potential risk of atrazine and linuron from consuming aquatic products should be paid more attention. Copyright © 2017. Published by Elsevier B.V.

Discharge current modes of high power impulse magnetron sputtering

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

Wu, Zhongzhen, E-mail: wuzz@pkusz.edu.cn; Xiao, Shu; Ma, Zhengyong

2015-09-15

Based on the production and disappearance of ions and electrons in the high power impulse magnetron sputtering plasma near the target, the expression of the discharge current is derived. Depending on the slope, six possible modes are deduced for the discharge current and the feasibility of each mode is discussed. The discharge parameters and target properties are simplified into the discharge voltage, sputtering yield, and ionization energy which mainly affect the discharge plasma. The relationship between these factors and the discharge current modes is also investigated.

Porous silicon carbide and aluminum oxide with unidirectional open porosity as model target materials for radioisotope beam production

NASA Astrophysics Data System (ADS)

Czapski, M.; Stora, T.; Tardivat, C.; Deville, S.; Santos Augusto, R.; Leloup, J.; Bouville, F.; Fernandes Luis, R.

2013-12-01

New silicon carbide (SiC) and aluminum oxide (Al2O3) of a tailor-made microstructure were produced using the ice-templating technique, which permits controlled pore formation conditions within the material. These prototypes will serve to verify aging of the new advanced target materials under irradiation with proton beams. Before this, the evaluation of their mechanical integrity was made based on the energy deposition spectra produced by FLUKA codes.

High Efficiency Solar Thermochemical Reactor for Hydrogen Production.

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

McDaniel, Anthony H.

2017-09-30

This research and development project is focused on the advancement of a technology that produces hydrogen at a cost that is competitive with fossil-based fuels for transportation. A twostep, solar-driven WS thermochemical cycle is theoretically capable of achieving an STH conversion ratio that exceeds the DOE target of 26% at a scale large enough to support an industrialized economy [1]. The challenge is to transition this technology from the laboratory to the marketplace and produce hydrogen at a cost that meets or exceeds DOE targets.

The psychology of psychology: A thought experiment.

PubMed

Ceci, Stephen J; Williams, Wendy M

2015-01-01

In the target article, Duarte et al. allege that the lack of political diversity reduces research efficacy. We pose a thought experiment that could provide an empirical test by examining whether institutional review board (IRB) members, granting agencies, and journal reviewers filter scientific products based on political values, invoking scientific criteria (rigor, etc.) as their justification. When these same products are cast in terms highlighting opposite values, do these people shift their decisions?

A magnetic bead-based ligand binding assay to facilitate human kynurenine 3-monooxygenase drug discovery.

PubMed

Wilson, Kris; Mole, Damian J; Homer, Natalie Z M; Iredale, John P; Auer, Manfred; Webster, Scott P

2015-02-01

Human kynurenine 3-monooxygenase (KMO) is emerging as an important drug target enzyme in a number of inflammatory and neurodegenerative disease states. Recombinant protein production of KMO, and therefore discovery of KMO ligands, is challenging due to a large membrane targeting domain at the C-terminus of the enzyme that causes stability, solubility, and purification difficulties. The purpose of our investigation was to develop a suitable screening method for targeting human KMO and other similarly challenging drug targets. Here, we report the development of a magnetic bead-based binding assay using mass spectrometry detection for human KMO protein. The assay incorporates isolation of FLAG-tagged KMO enzyme on protein A magnetic beads. The protein-bound beads are incubated with potential binding compounds before specific cleavage of the protein-compound complexes from the beads. Mass spectrometry analysis is used to identify the compounds that demonstrate specific binding affinity for the target protein. The technique was validated using known inhibitors of KMO. This assay is a robust alternative to traditional ligand-binding assays for challenging protein targets, and it overcomes specific difficulties associated with isolating human KMO. © 2014 Society for Laboratory Automation and Screening.

Cyclotron Production of Radionuclides for Nuclear Medicine at Academic Centers

NASA Astrophysics Data System (ADS)

Lapi, Suzanne

2016-09-01

The increase in use of radioisotopes for medical imaging has led to the development of new accelerator targetry and separation techniques for isotope production. For example, the development of longer-lived position emitting radionuclides has been explored to allow for nuclear imaging agents based on peptides, antibodies and nanoparticles. These isotopes (64Cu, 89Zr, 86Y) are typically produced via irradiation of solid targets on smaller cyclotrons (10-25 MeV) at academic or hospital based facilities. Recent research has further expanded the toolbox of PET tracers to include additional isotopes such as 52Mn, 55Co, 76Br and others. The smaller scale of these types of facilities can enable the straightforward involvement of students, thus adding to the next generation of nuclear science leaders. Research pertaining to development of robust and larger scale production technologies including solid target systems and remote systems for transport and purification of these isotopes has enabled both preclinical and clinical imaging research for many diseases. In particular, our group has focused on the use of radiolabeled antibodies for imaging of receptor expression in preclinical models and in a clinical trial of metastatic breast cancer patients.

Radionuclide production and dose rate estimation during the commissioning of the W-Ta spallation target

NASA Astrophysics Data System (ADS)

Yu, Q. Z.; Liang, T. J.

2018-06-01

China Spallation Neutron Source (CSNS) is intended to begin operation in 2018. CSNS is an accelerator-base multidisciplinary user facility. The pulsed neutrons are produced by a 1.6GeV short-pulsed proton beam impinging on a W-Ta spallation target, at a beam power of100 kW and a repetition rate of 25 Hz. 20 neutron beam lines are extracted for the neutron scattering and neutron irradiation research. During the commissioning and maintenance scenarios, the gamma rays induced from the W-Ta target can cause the dose threat to the personal and the environment. In this paper, the gamma dose rate distributions for the W-Ta spallation are calculated, based on the engineering model of the target-moderator-reflector system. The shipping cask is analyzed to satisfy the dose rate limit that less than 2 mSv/h at the surface of the shipping cask. All calculations are performed by the Monte carlo code MCNPX2.5 and the activation code CINDER’90.

REVIEW: ASSESSING THE POTENTIAL TO INDUCE RESPIRATORY HYPERSENSITIVITY

EPA Science Inventory

The respiratory tract has been long recognized as an important target organ in the safety assessment of drugs and chemicals, as well as protein- or peptide-based products. Indeed, acute and repeat dose inhalation studies have been an important part of guideline studies throughou...

An 1H NMR-based metabolomic approach to compare the chemical profiling of retail samples of ground roasted and instant coffees.

PubMed

Villalón-López, Nayelli; Serrano-Contreras, José I; Téllez-Medina, Darío I; Gerardo Zepeda, L

2018-04-01

The present non-targeted 1 H NMR-based fingerprinting approach along with multivariate analysis established differences between representative aqueous extracts of commercial ground roasted coffee (GRC) and instant (soluble) coffee (IC) samples. The latter were prepared either by spray drying or freeze drying. When comparing a total of 33 compounds between GRC and IC, the latter product contained a remarkable increase in 5-(hydroxymethyl)furfural and carbohydrates, as well as a clear decrease in trigonelline, N-methylpyridinium, caffeine, caffeoylquinic acids and 2-furylmethanol. Furthermore, the current protocol was able to detect the subtle chemical differences between spray-dried and freeze-dried IC. The aforementioned metabolites could serve as target molecules in the attempt to preserve, as much as possible, the organoleptic and nutraceutical properties of GRC during the industrial drying processes used in the production of the two commercial types of IC. Copyright © 2018 Elsevier Ltd. All rights reserved.

PECAN: Library Free Peptide Detection for Data-Independent Acquisition Tandem Mass Spectrometry Data

PubMed Central

Ting, Ying S.; Egertson, Jarrett D.; Bollinger, James G.; Searle, Brian C.; Payne, Samuel H.; Noble, William Stafford; MacCoss, Michael J.

2017-01-01

In mass spectrometry-based shogun proteomics, data-independent acquisition (DIA) is an emerging technique for unbiased and reproducible measurement of protein mixtures. Without targeting a specific precursor ion, DIA MS/MS spectra are often highly multiplexed, containing product ions from multiple co-fragmenting precursors. Thus, detecting peptides directly from DIA data is challenging; most DIA data analyses require spectral libraries. Here we present a new library-free, peptide-centric tool PECAN that detects peptides directly from DIA data. PECAN reports evidence of detection based on product ion scoring, enabling detection of low abundance analytes with poor precursor ion signal. We benchmarked PECAN with chromatographic peak picking accuracy and peptide detection capability. We further validated PECAN detection with data-dependent acquisition and targeted analyses. Last, we used PECAN to build a library from DIA data and to query sequence variants. Together, these results show that PECAN detects peptides robustly and accurately from DIA data without using a library. PMID:28783153

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

PubMed

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

2015-11-01

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

Rate of introduction of a low pathogenic avian influenza virus infection in different poultry production sectors in the Netherlands

PubMed Central

Gonzales, Jose L.; Stegeman, Jan A.; Koch, Guus; de Wit, Sjaak J.; Elbers, Armin R. W.

2012-01-01

Please cite this paper as: Gonzales et al. (2012) Rate of introduction of a low pathogenic avian influenza virus infection in different poultry production sectors in the Netherlands. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00348.x. Background  Targeted risk‐based surveillance of poultry types (PT) with different risks of introduction of low pathogenic avian influenza virus (LPAIv) infection may improve the sensitivity of surveillance. Objective  To quantify the rate of introduction of LPAIv infections in different PT. Methods  Data from the Dutch LPAIv surveillance programme (2007–2010) were analysed using a generalised linear mixed and spatial model. Results  Outdoor‐layer, turkey, duck‐breeder and meat‐duck, farms had a 11, 8, 24 and 13 times higher rate of introduction of LPAIv than indoor‐layer farms, respectively. Conclusion  Differences in the rate of introduction of LPAIv could be used to (re)design a targeted risk‐based surveillance programme. PMID:22376126

New production systems at ISOLDE

NASA Astrophysics Data System (ADS)

Hagebø, E.; Hoff, P.; Jonsson, O. C.; Kugler, E.; Omtvedt, J. P.; Ravn, H. L.; Steffensen, K.

1992-08-01

New target systems for the ISOLDE on-line mass separator facility are presented. Targets of carbides, metal/graphite mixtures, foils of refractory metals, molten metals and oxides have been tested. Beams of high intensity of neutron-rich isotopes of a large number of elements are obtained from a uranium carbide target with a hot plasma-discharge ion source. A target of ZrO 2 has been shown to provide high intensity beams of neutron-deficient isotopes of Mn, Cu, Zn, Ga, Ge, As, Se, Br, Kr and Rb, while a SiC target with a hot plasma ion source gives intense beams of radioactive isotopes of a number of light elements. All these systems are rather chemically unselective. Chemically selective performance has been obtained for several systems, i.e.: the production of neutron-deficient Au from ( 3He, pχn) reactions on a Pt/graphite target with a hot plasma ion source; the production of neutron-deficient Lu and LuF + and Hf and HfF 3+ from a Ta-foil target with a hot plasma ion source under CF 4 addition; the production of neutron-deficient Sr as SrF + and Y as YF 2+ form a Nb-foil target with a W surface ionizer under CF 4 addition; the production of neutron-deficient Se as COSe + from a ZrO 2 target with a hot plasma ion source under O 2 addition; and the production of radioactive F from a SiC target with a hot plasma ion source operating in Al vapour.

Development of mini linac-based positron source and an efficient positronium convertor for positively charged antihydrogen production

NASA Astrophysics Data System (ADS)

Muranaka, T.; Debu, P.; Dupré, P.; Liszkay, L.; Mansoulie, B.; Pérez, P.; Rey, J. M.; Ruiz, N.; Sacquin, Y.; Crivelli, P.; Gendotti, U.; Rubbia, A.

2010-04-01

We have installed in Saclay a facility for an intense positron source in November 2008. It is based on a compact 5.5 MeV electron linac connected to a reaction chamber with a tungsten target inside to produce positrons via pair production. The expected production rate for fast positrons is 5·1011 per second. The study of moderation of fast positrons and the construction of a slow positron trap are underway. In parallel, we have investigated an efficient positron-positronium convertor using porous silica materials. These studies are parts of a project to produce positively charged antihydrogen ions aiming to demonstrate the feasibility of a free fall antigravity measurement of neutral antihydrogen.

RNA interference-based silencing of the alpha-amylase (amy1) gene in Aspergillus flavus decreases fungal growth and aflatoxin production in maize kernels.

PubMed

Gilbert, Matthew K; Majumdar, Rajtilak; Rajasekaran, Kanniah; Chen, Zhi-Yuan; Wei, Qijian; Sickler, Christine M; Lebar, Matthew D; Cary, Jeffrey W; Frame, Bronwyn R; Wang, Kan

2018-06-01

Expressing an RNAi construct in maize kernels that targets the gene for alpha-amylase in Aspergillus flavus resulted in suppression of alpha-amylase (amy1) gene expression and decreased fungal growth during in situ infection resulting in decreased aflatoxin production. Aspergillus flavus is a saprophytic fungus and pathogen to several important food and feed crops, including maize. Once the fungus colonizes lipid-rich seed tissues, it has the potential to produce toxic secondary metabolites, the most dangerous of which is aflatoxin. The pre-harvest control of A. flavus contamination and aflatoxin production is an area of intense research, which includes breeding strategies, biological control, and the use of genetically-modified crops. Host-induced gene silencing, whereby the host crop produces siRNA molecules targeting crucial genes in the invading fungus and targeting the gene for degradation, has shown to be promising in its ability to inhibit fungal growth and decrease aflatoxin contamination. Here, we demonstrate that maize inbred B104 expressing an RNAi construct targeting the A. flavus alpha-amylase gene amy1 effectively reduces amy1 gene expression resulting in decreased fungal colonization and aflatoxin accumulation in kernels. This work contributes to the development of a promising technology for reducing the negative economic and health impacts of A. flavus growth and aflatoxin contamination in food and feed crops.

Simultaneous identification and DNA barcoding of six Eimeria species infecting turkeys using PCR primers targeting the mitochondrial cytochrome c oxidase subunit I (mtCOI) locus.

PubMed

Hafeez, Mian A; Shivaramaiah, Srichaitanya; Dorsey, Kristi Moore; Ogedengbe, Mosun E; El-Sherry, Shiem; Whale, Julia; Cobean, Julie; Barta, John R

2015-05-01

Species-specific PCR primers targeting the mitochondrial cytochrome c oxidase subunit I (mtCOI) locus were generated that allow for the specific identification of the most common Eimeria species infecting turkeys (i.e., Eimeria adenoeides, Eimeria meleagrimitis, Eimeria gallopavonis, Eimeria meleagridis, Eimeria dispersa, and Eimeria innocua). PCR reaction chemistries were optimized with respect to divalent cation (MgCl2) and dNTP concentrations, as well as PCR cycling conditions (particularly anneal temperature for primers). Genomic DNA samples from single oocyst-derived lines of six Eimeria species were tested to establish specificity and sensitivity of these newly designed primer pairs. A mixed 60-ng total DNA sample containing 10 ng of each of the six Eimeria species was used as DNA template to demonstrate specific amplification of the correct product using each of the species-specific primer pairs. Ten nanograms of each of the five non-target Eimeria species was pooled to provide a non-target, control DNA sample suitable to test the specificity of each primer pair. The amplifications of the COI region with species-specific primer pairs from pooled samples yielded products of expected sizes (209 to 1,012 bp) and no amplification of non-target Eimeria sp. DNA was detected using the non-target, control DNA samples. These primer pairs specific for Eimeria spp. of turkeys did not amplify any of the seven Eimeria species infecting chickens. The newly developed PCR primers can be used as a diagnostic tool capable of specifically identifying six turkey Eimeria species; additionally, sequencing of the PCR amplification products yields sequence-based genotyping data suitable for identification and molecular phylogenetics.

Remote direct memory access

DOEpatents

Archer, Charles J.; Blocksome, Michael A.

2012-12-11

Methods, parallel computers, and computer program products are disclosed for remote direct memory access. Embodiments include transmitting, from an origin DMA engine on an origin compute node to a plurality target DMA engines on target compute nodes, a request to send message, the request to send message specifying a data to be transferred from the origin DMA engine to data storage on each target compute node; receiving, by each target DMA engine on each target compute node, the request to send message; preparing, by each target DMA engine, to store data according to the data storage reference and the data length, including assigning a base storage address for the data storage reference; sending, by one or more of the target DMA engines, an acknowledgment message acknowledging that all the target DMA engines are prepared to receive a data transmission from the origin DMA engine; receiving, by the origin DMA engine, the acknowledgement message from the one or more of the target DMA engines; and transferring, by the origin DMA engine, data to data storage on each of the target compute nodes according to the data storage reference using a single direct put operation.

NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening.

PubMed

Thornburg, Christopher C; Britt, John R; Evans, Jason R; Akee, Rhone K; Whitt, James A; Trinh, Spencer K; Harris, Matthew J; Thompson, Jerell R; Ewing, Teresa L; Shipley, Suzanne M; Grothaus, Paul G; Newman, David J; Schneider, Joel P; Grkovic, Tanja; O'Keefe, Barry R

2018-06-13

The US National Cancer Institute's (NCI) Natural Product Repository is one of the world's largest, most diverse collections of natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected from biodiverse regions throughout the world. Importantly, this national resource is available to the research community for the screening of extracts and the isolation of bioactive natural products. However, despite the success of natural products in drug discovery, compatibility issues that make extracts challenging for liquid handling systems, extended timelines that complicate natural product-based drug discovery efforts and the presence of pan-assay interfering compounds have reduced enthusiasm for the high-throughput screening (HTS) of crude natural product extract libraries in targeted assay systems. To address these limitations, the NCI Program for Natural Product Discovery (NPNPD), a newly launched, national program to advance natural product discovery technologies and facilitate the discovery of structurally defined, validated lead molecules ready for translation will create a prefractionated library from over 125,000 natural product extracts with the aim of producing a publicly-accessible, HTS-amenable library of >1,000,000 fractions. This library, representing perhaps the largest accumulation of natural-product based fractions in the world, will be made available free of charge in 384-well plates for screening against all disease states in an effort to reinvigorate natural product-based drug discovery.

Canadian regulatory requirements for recombinant fish vaccines.

PubMed

Sethi, M S; Gifford, G A; Samagh, B S

1997-01-01

In Canada, veterinary biological products derived by using conventional and new techniques of biotechnology are licensed and regulated under the Health of Animals Act and Regulations. Biological products include vaccines, bacterins, bacterin-toxoids and diagnostic kits which are used for the prevention, treatment or diagnosis of infectious diseases in all species of animals, including fish. Veterinary biologicals are licensed on the basis of fulfillment of four criteria: purity, potency, safety and efficacy. A risk-based approach is used to evaluate the safety of the product in target species, as well as non-target species, humans and the environment. On the basis of biological characteristics, biotechnology derived veterinary biologicals have been divided into two broad categories, high and low risk products. The paper describes the regulatory framework for the licensing of veterinary biologicals in Canada, with emphasis on the regulatory considerations for recombinant fish vaccines. Stages of movement of the product from research in a contained laboratory facility to a fully licensed product for free sale are discussed. The requirements for field testing and environmental assessment involved in these stages are highlighted. Manufacturers and researchers who intend to commercialize experimental vaccines are encouraged to consult with the Veterinary Biologics and Biotechnology Section early in the product development process so that the research data and quality assurance documentation are consistent with regulatory requirements.

FRET-based genetically-encoded sensors for quantitative monitoring of metabolites.

PubMed

Mohsin, Mohd; Ahmad, Altaf; Iqbal, Muhammad

2015-10-01

Neighboring cells in the same tissue can exist in different states of dynamic activities. After genomics, proteomics and metabolomics, fluxomics is now equally important for generating accurate quantitative information on the cellular and sub-cellular dynamics of ions and metabolite, which is critical for functional understanding of organisms. Various spectrometry techniques are used for monitoring ions and metabolites, although their temporal and spatial resolutions are limited. Discovery of the fluorescent proteins and their variants has revolutionized cell biology. Therefore, novel tools and methods targeting sub-cellular compartments need to be deployed in specific cells and targeted to sub-cellular compartments in order to quantify the target-molecule dynamics directly. We require tools that can measure cellular activities and protein dynamics with sub-cellular resolution. Biosensors based on fluorescence resonance energy transfer (FRET) are genetically encoded and hence can specifically target sub-cellular organelles by fusion to proteins or targetted sequences. Since last decade, FRET-based genetically encoded sensors for molecules involved in energy production, reactive oxygen species and secondary messengers have helped to unravel key aspects of cellular physiology. This review, describing the design and principles of sensors, presents a database of sensors for different analytes/processes, and illustrate examples of application in quantitative live cell imaging.

Impacts of drug reimbursement reductions on utilization and expenditures of oral antidiabetic medications in Taiwan: an interrupted time series study.

PubMed

Hsu, Jason C; Lu, Christine Y; Wagner, Anita K; Chan, K Arnold; Lai, Mei-Shu; Ross-Degnan, Dennis

2014-06-01

To control increasing pharmaceutical expenditures, Taiwan's National Health Insurance has implemented a series of drug reimbursement price reductions since 2000. This study examined changes in use and expenditures of oral antidiabetic medications following the price regulation in November 2006. We obtained claims data between January 2006 and August 2007 from Taiwan's National Health Insurance Research Database. We categorized oral antidiabetic products as affected by the reimbursement reduction ("targeted") or not ("non-targeted"), by level of relative price reduction, and by manufacturer type (international vs. local manufacturers). We used an interrupted time series design and segmented regression models to estimate changes in monthly per capita prescribing rate, volume, and insurance reimbursement expenditures following the policy. The majority (129/178; 72.5%) of oral antidiabetic products were targeted by this round of price reductions. There was a relative reduction of 9.5% [95%CI: -12.68, -6.32] in total expenditures at ten months post-policy compared to expected rates. For targeted products, there were 2.04% [95%CI: -4.15, 0.07] and 13.26% [95%CI: -16.64, -9.87] relative reductions in prescribing rate and expenditures, respectively, at ten months post-policy. Non-targeted products increased significantly (22% [95%CI: 10.49, 33.51] and 22.85% [95%CI: 11.69, 34.01] relative increases in prescribing rate and expenditures respectively). Larger reimbursement cuts led to greater reductions in prescribing rate, volume, and insurance reimbursement expenditures of targeted products. Prescribing rates of both targeted and non-targeted products by international manufacturers declined after the policy while rates of prescribing non-targeted products by local manufacturers increased. While total government expenditures for oral antidiabetic medications were contained by the policy, our results indicate that prescribing shifted at the margin from targeted to non-targeted products and from international to local products. Further research is warranted to understand how changes in medication use due to price regulation policies affect medication adherence and patient health outcomes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

On Improving CRISPR for Editing Plant Genes: Ribozyme-Mediated Guide RNA Production and Fluorescence-Based Technology for Isolating Transgene-Free Mutants Generated by CRISPR.

PubMed

He, Yubing; Wang, Rongchen; Dai, Xinhua; Zhao, Yunde

2017-01-01

CRISPR/Cas9-mediated genome editing technology has been used to successfully edit numerous genes in various organisms including plants. There are still two major challenges in using CRISPR/Cas9 technology for gene editing in plants. First, there are very limited choices of promoters that are suitable for in vivo production of single-guide RNAs (sgRNAs), which is complementary to the target sequence and which guides Cas9 to generate double-strand breaks at the target site. It is especially difficult to produce sgRNA molecules with temporal and spatial precision. Second, there is a lack of efficient methods for identifying plants that (1) contain heritable and stable mutations generated by CRISPR/Cas9, and (2) no longer harbor the CRISPR/Cas9 construct and other transgenes. In this chapter, we describe the development of a ribozyme-based strategy that enables the production of sgRNA molecules from any chosen promoter. More importantly, the ribozyme-based technology makes it feasible to produce sgRNAs with temporal and spatial precision, greatly expanding the scope and applications of CRISPR/Cas9 technology. We also developed a fluorescence-based technology that allows us to efficiently and reliably isolate Cas9-free stable Arabidopsis mutants. Thus, we provide effective protocols to overcome two important obstacles in using CRISPR/Cas9 for editing genes in plants. © 2017 Elsevier Inc. All rights reserved.

Dereplication of plant phenolics using a mass-spectrometry database independent method.

PubMed

Borges, Ricardo M; Taujale, Rahil; de Souza, Juliana Santana; de Andrade Bezerra, Thaís; Silva, Eder Lana E; Herzog, Ronny; Ponce, Francesca V; Wolfender, Jean-Luc; Edison, Arthur S

2018-05-29

Dereplication, an approach to sidestep the efforts involved in the isolation of known compounds, is generally accepted as being the first stage of novel discoveries in natural product research. It is based on metabolite profiling analysis of complex natural extracts. To present the application of LipidXplorer for automatic targeted dereplication of phenolics in plant crude extracts based on direct infusion high-resolution tandem mass spectrometry data. LipidXplorer uses a user-defined molecular fragmentation query language (MFQL) to search for specific characteristic fragmentation patterns in large data sets and highlight the corresponding metabolites. To this end, MFQL files were written to dereplicate common phenolics occurring in plant extracts. Complementary MFQL files were used for validation purposes. New MFQL files with molecular formula restrictions for common classes of phenolic natural products were generated for the metabolite profiling of different representative crude plant extracts. This method was evaluated against an open-source software for mass-spectrometry data processing (MZMine®) and against manual annotation based on published data. The targeted LipidXplorer method implemented using common phenolic fragmentation patterns, was found to be able to annotate more phenolics than MZMine® that is based on automated queries on the available databases. Additionally, screening for ascarosides, natural products with unrelated structures to plant phenolics collected from the nematode Caenorhabditis elegans, demonstrated the specificity of this method by cross-testing both groups of chemicals in both plants and nematodes. Copyright © 2018 John Wiley & Sons, Ltd.

The use of sports references in marketing of food and beverage products in supermarkets.

PubMed

Bragg, Marie A; Liu, Peggy J; Roberto, Christina A; Sarda, Vishnu; Harris, Jennifer L; Brownell, Kelly D

2013-04-01

Food marketing has been identified as a significant driver of the childhood obesity epidemic. The purpose of the present study was to (i) conduct a content analysis of the types of sports references that appear on supermarket food and beverage products and (ii) assess each product's nutritional and marketing profile. This was a descriptive study. Every product featuring sports references on the packaging was purchased in two major supermarkets during 2010. A content analysis was conducted and nutritional evaluations were made based on the Nutrient Profile Model, a validated nutrition model. Marketing data were obtained from The Nielsen Company. Two major supermarkets in Connecticut, USA. Food and beverage products (n 102) were selected from two supermarkets. The 102 products (fifty-three foods and forty-nine beverages) had sports references as part of their packaging: 72·5 % featured a character exercising, 42·2 % were endorsed by a professional sports entity and 34·0 % were child-targeted. The median nutrition score for food products was 36 (1 = unhealthiest and 100 = healthiest; scores of ≥63 are considered healthy according to this model). More than two-thirds of beverages (69·4 %) were 100 % sugar-sweetened. Children saw significantly more commercials for these products than adults. Companies place sports figures on food and beverage products that are child-targeted and unhealthy.

Fine-Tuning of the Fatty Acid Pathway by Synthetic Antisense RNA for Enhanced (2S)-Naringenin Production from l-Tyrosine in Escherichia coli

PubMed Central

Wu, Junjun; Yu, Oliver; Du, Guocheng

2014-01-01

Malonyl coenzyme A (malonyl-CoA) is an important precursor for the synthesis of natural products, such as polyketides and flavonoids. The majority of this cofactor often is consumed for producing fatty acids and phospholipids, leaving only a small amount of cellular malonyl-CoA available for producing the target compound. The tuning of malonyl-CoA into heterologous pathways yields significant phenotypic effects, such as growth retardation and even cell death. In this study, fine-tuning of the fatty acid pathway in Escherichia coli with antisense RNA (asRNA) to balance the demands on malonyl-CoA for target-product synthesis and cell health was proposed. To establish an efficient asRNA system, the relationship between sequence and function for asRNA was explored. It was demonstrated that the gene-silencing effect of asRNA could be tuned by directing asRNA to different positions in the 5′-UTR (untranslated region) of the target gene. Based on this principle, the activity of asRNA was quantitatively tailored to balance the need for malonyl-CoA in cell growth and the production of the main flavonoid precursor, (2S)-naringenin. Appropriate inhibitory efficiency of the anti-fabB/fabF asRNA improved the production titer by 431% (391 mg/liter). Therefore, the strategy presented in this study provided a useful tool for the fine-tuning of endogenous gene expression in bacteria. PMID:25239896

Informatic search strategies to discover analogues and variants of natural product archetypes.

PubMed

Johnston, Chad W; Connaty, Alex D; Skinnider, Michael A; Li, Yong; Grunwald, Alyssa; Wyatt, Morgan A; Kerr, Russell G; Magarvey, Nathan A

2016-03-01

Natural products are a crucial source of antimicrobial agents, but reliance on low-resolution bioactivity-guided approaches has led to diminishing interest in discovery programmes. Here, we demonstrate that two in-house automated informatic platforms can be used to target classes of biologically active natural products, specifically, peptaibols. We demonstrate that mass spectrometry-based informatic approaches can be used to detect natural products with high sensitivity, identifying desired agents present in complex microbial extracts. Using our specialised software packages, we could elaborate specific branches of chemical space, uncovering new variants of trichopolyn and demonstrating a way forward in mining natural products as a valuable source of potential pharmaceutical agents.

A National-Scale Comparison of Resource and Nutrient Demands for Algae-Based Biofuel Production by Lipid Extraction and Hydrothermal Liquefaction

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

Venteris, Erik R.; Skaggs, Richard; Wigmosta, Mark S.

Algae’s high productivity provides potential resource advantages over other fuel crops. However, demand for land, water, and nutrients must be minimized to avoid impacts on food production. We apply our national-scale, open-pond, growth and resource models to assess several biomass to fuel technological pathways based on Chlorella. We compare resource demands between hydrothermal liquefaction (HTL) and lipid extraction (LE) to meet 1.89E+10 and 7.95E+10 L yr-1 biofuel targets. We estimate nutrient demands where post-fuel biomass is consumed as co-products and recycling by anaerobic digestion (AD) or catalytic hydrothermal gasification (CHG). Sites are selected through prioritization based on fuel value relativemore » to a set of site-specific resource costs. The highest priority sites are located along the Gulf of Mexico coast, but potential sites exist nationwide. We find that HTL reduces land and freshwater consumption by up to 46% and saline groundwater by around 70%. Without recycling, nitrogen (N) and phosphorous (P) demand is reduced 33%, but is large relative to current U.S. agricultural consumption. The most nutrient-efficient pathways are LE+CHG for N and HTL+CHG for P (by 42%). Resource gains for HTL+CHG are offset by a 344% increase in N consumption relative to LE+CHG (with potential for further recycling). Nutrient recycling is essential to effective use of alternative nutrient sources. Modeling of utilization availability and costs remains, but we find that for HTL+CHG at the 7.95E+10 L yr-1 production target, municipal sources can offset 17% of N and 40% of P demand and animal manures can generally meet demands.« less

Review of photorejuvenation: devices, cosmeceuticals, or both?

PubMed

Rokhsar, Cameron K; Lee, Sandra; Fitzpatrick, Richard E

2005-09-01

Both the public and the medical profession have placed a lot of attention on reversal of signs of aging and photodamage, resulting in numerous cosmeceutical products and nonablative laser techniques designed to achieve these results. The purpose of this report is to briefly review both the cosmeceutical products and nonablative laser techniques that appear to be most promising based on published studies. After this review, recommendations for potential enhancement of benefits by combining cosmeceuticals and laser treatments will be explored. Pulsed dye lasers targeting microvessels, intense pulsed light targeting both melanin and microvessels, and midinfrared lasers targeting dermal water and collagen all appear to have some ability to improve skin texture, color, and wrinkling. Retinoids, vitamin C, alpha-hydroxy acids, and topical growth factors may also stimulate repair mechanisms that result in similar improvements in photodamaged skin. Although supported only by theoretic considerations and anecdotal reports, it seems logical that the concurrent use of appropriate cosmeceuticals with nonablative laser photorejuvenation should result in enhanced benefits.

Retroviral DNA Integration Directed by HIV Integration Protein in Vitro

NASA Astrophysics Data System (ADS)

Bushman, Frederic D.; Fujiwara, Tamio; Craigie, Robert

1990-09-01

Efficient retroviral growth requires integration of a DNA copy of the viral RNA genome into a chromosome of the host. As a first step in analyzing the mechanism of integration of human immunodeficiency virus (HIV) DNA, a cell-free system was established that models the integration reaction. The in vitro system depends on the HIV integration (IN) protein, which was partially purified from insect cells engineered to express IN protein in large quantities. Integration was detected in a biological assay that scores the insertion of a linear DNA containing HIV terminal sequences into a λ DNA target. Some integration products generated in this assay contained five-base pair duplications of the target DNA at the recombination junctions, a characteristic of HIV integration in vivo; the remaining products contained aberrant junctional sequences that may have been produced in a variation of the normal reaction. These results indicate that HIV IN protein is the only viral protein required to insert model HIV DNA sequences into a target DNA in vitro.

STK Integrated Message Production List Editor (SIMPLE) for CEO Operations

NASA Technical Reports Server (NTRS)

Trenchard, Mike; Heydorn, James

2014-01-01

Late in fiscal year 2011, the Crew Earth Observations (CEO) team was tasked to upgrade and replace its mission planning and mission operations software systems, which were developed in the Space Shuttle era of the 1980s and 1990s. The impetuses for this change were the planned transition of all workstations to the Windows 7 64-bit operating system and the desire for more efficient and effective use of Satellite Tool Kit (STK) software required for reliable International Space Station (ISS) Earth location tracking. An additional requirement of this new system was the use of the same SQL database of CEO science sites from the SMMS, which was also being developed. STK Integrated Message Production List Editor (SIMPLE) is the essential, all-in-one tool now used by CEO staff to perform daily ISS mission planning to meet its requirement to acquire astronaut photography of specific sites on Earth. The sites are part of a managed, long-term database that has been defined and developed for scientific, educational, and public interest. SIMPLE's end product is a set of basic time and location data computed for an operator-selected set of targets that the ISS crew will be asked to photograph (photography is typically planned 12 to 36 hours out). The CEO operator uses SIMPLE to (a) specify a payload operations planning period; (b) acquire and validate the best available ephemeris data (vectors) for the ISS during the planning period; (c) ingest and display mission-specific site information from the CEO database; (d) identify and display potential current dynamic event targets as map features; (e) compute and display time and location information for each target; (f) screen and select targets based on known crew availability constraints, obliquity constraints, and real-time evaluated constraints to target visibility due to illumination (sun elevation) and atmospheric conditions (weather); and finally (g) incorporate basic, computed time and location information for each selected target into the daily CEO Target List product (message) for submission to ISS payload planning and integration teams for their review and approval prior to uplink. SIMPLE requires and uses the following resources: an ISS mission planning period Greenwich Mean Time start date/time and end date/time), the best available ISS mission ephemeris data (vectors) for that planning period, the STK software package configured for the ISS, and an ISS mission-specific subset of the CEO sites database. The primary advantages realized by the development and implementation of SIMPLE into the CEO payload operations support activity are a smooth transition to the Windows 7 operating system upon scheduled workstation refresh; streamlining of the input and verification of the current ISS ephemeris (vector data); seamless incorporation of selected contents of the SQL database of science sites; the ability to tag and display potential dynamic event opportunities on orbit track maps; simplification of the display and selection of encountered sites based on crew availability, illumination, obliquity, and weather constraints; the incorporation of high-quality mapping of the Earth with various satellite-based datasets for use in describing targets; and the ability to encapsulate and export the essential selected target elements in XML format for use by onboard Earth-location systems, such as Worldmap. SIMPLE is a carefully designed and crafted in-house software package that includes detailed help files for the user and meticulous internal documentation for future modifications. It was delivered in February 2012 for test and evaluation. Following acceptance, it was implemented for CEO mission operations support in May 2012.

The healthfulness and prominence of sugar in child-targeted breakfast cereals in Canada

PubMed Central

Monique, Potvin Kent; Cher, Cameron; Sarah, Philippe

2017-01-01

Abstract Introduction: The objective of this study was to compare the nutritional content and healthfulness of child-targeted and “not child-targeted” breakfast cereals and to assess the predominance of added sugar in these products. Methods: We collected data on the nutritional content of 262 unique breakfast cereals found in the five largest grocery store chains in Ottawa (Ontario) and Gatineau (Quebec). We noted the first five ingredients and the number of added sugars present in each cereal from the ingredients list. The various cereal brands were then classified as either “healthier” or “less healthy” using the UK Nutrient Profile Model. We assessed each cereal to determine if it was child-targeted or not, based on set criteria. Statistical comparisons were made between child and not child-targeted cereals. Results: 19.8% of all breakfast cereals were child-targeted, and these were significantly lower in total and saturated fat. Child-targeted cereals were significantly higher in sodium and sugar and lower in fibre and protein, and were three times more likely to be classified as “less healthy” compared to not child-targeted cereals. No child-targeted cereals were sugar-free, and sugar was the second most common ingredient in 75% of cereals. Six breakfast cereal companies had child-targeted product lines that consisted entirely of “less healthy” cereals. Conclusion: There is a need for regulations that restrict food marketing to children and youth under the age of 17 on packaging to reduce their appeal to this age group. Children’s breakfast cereals also need to be reformulated through government-set targets, or through regulation should compliance be deemed unacceptable. PMID:28902476

75 FR 55808 - Prospective Grant of Exclusive License: Development of AAV5 Based Therapeutics To Treat Human...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-14

.... Patent 6, 855, 314 entitled ``AAV5 Vector for Transducing Brain Cells and Lung Cells'' [HHS Ref. No. E... sale of AAV5 based therapeutic products to be delivered to the brain, eyes and liver for treatment of... vectors and particles. The specific brain cells that are targeted by AAV5 belong to both non-neuronal...

Functional Reconstitution of a Fungal Natural Product Gene Cluster by Advanced Genome Editing.

PubMed

Weber, Jakob; Valiante, Vito; Nødvig, Christina S; Mattern, Derek J; Slotkowski, Rebecca A; Mortensen, Uffe H; Brakhage, Axel A

2017-01-20

Filamentous fungi produce varieties of natural products even in a strain dependent manner. However, the genetic basis of chemical speciation between strains is still widely unknown. One example is trypacidin, a natural product of the opportunistic human pathogen Aspergillus fumigatus, which is not produced among different isolates. Combining computational analysis with targeted gene editing, we could link a single nucleotide insertion in the polyketide synthase of the trypacidin biosynthetic pathway and reconstitute its production in a nonproducing strain. Thus, we present a CRISPR/Cas9-based tool for advanced molecular genetic studies in filamentous fungi, exploiting selectable markers separated from the edited locus.

Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment.

PubMed

Hill, Andrew; Gotham, Dzintars; Fortunak, Joseph; Meldrum, Jonathan; Erbacher, Isabelle; Martin, Manuel; Shoman, Haitham; Levi, Jacob; Powderly, William G; Bower, Mark

2016-01-27

To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. API costs per kg were $347-$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128-$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. Mass generic production of several TKIs could achieve treatment prices in the range of $128-$4020 per person-year, versus current US prices of $75161-$139,138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Improved photobio-H2 production regulated by artificial miRNA targeting psbA in green microalga Chlamydomonas reinhardtii.

PubMed

Li, Hui; Liu, Yanmei; Wang, Yuting; Chen, Meirong; Zhuang, Xiaoshan; Wang, Chaogang; Wang, Jiangxin; Hu, Zhangli

2018-01-01

Sulfur-deprived cultivation of Chlamydomonas reinhardtii , referred as "two-stage culture" transferring the cells from regular algal medium to sulfur-deplete one, has been extensively studied to improve photobio-H 2 production in this green microalga. During sulfur-deprivation treatment, the synthesis of a key component of photosystem II complex, D1 protein, was inhibited and improved photobio-H 2 production could be established in C. reinhardtii . However, separation of algal cells from a regular liquid culture medium to a sulfur-deprived one is not only a discontinuous process, but also a cost- and time-consuming operation. More applicable and economic alternatives for sustained H 2 production by C. reinhardtii are still highly required. In the present study, a significant improvement in photobio-H 2 production was observed in the transgenic green microalga C. reinhardtii , which employed a newly designed strategy based on a heat-inducible artificial miRNA (amiRNA) expression system targeting D1-encoded gene, psbA . A transgenic algal strain referred as "amiRNA-D1" has been successfully obtained by transforming the expression vector containing a heat-inducible promoter. After heat shock conducted in the same algal cultures, the expression of amiRNA-D1 was detected increased 15-fold accompanied with a 73% decrease of target gene psbA . More interestingly, this transgenic alga accumulated about 60% more H 2 content than the wild-type strain CC-849 at the end of 7-day cultivation. The photobio-H 2 production in the engineered transgenic alga was significantly improved. Without imposing any nutrient-deprived stress, this novel strategy provided a convenient and efficient way for regulation of photobio-H 2 production in green microalga by simply "turn on" the expression of a designed amiRNA.

Method for fabricating .sup.99 Mo production targets using low enriched uranium, .sup.99 Mo production targets comprising low enriched uranium

DOEpatents

Wiencek, Thomas C.; Matos, James E.; Hofman, Gerard L.

1997-01-01

A radioisotope production target and a method for fabricating a radioisotope production target is provided, wherein the target comprises an inner cylinder, a foil of fissionable material circumferentially contacting the outer surface of the inner cylinder, and an outer hollow cylinder adapted to receive the substantially foil-covered inner cylinder and compress tightly against the foil to provide good mechanical contact therewith. The method for fabricating a primary target for the production of fission products comprises preparing a first substrate to receive a foil of fissionable material so as to allow for later removal of the foil from the first substrate, preparing a second substrate to receive the foil so as to allow for later removal of the foil from the second substrate; attaching the first substrate to the second substrate such that the foil is sandwiched between the first substrate and second substrate to prevent foil exposure to ambient atmosphere, and compressing the exposed surfaces of the first and second substrate to assure snug mechanical contact between the foil, the first substrate and the second substrate.

Method for fabricating .sup.99 Mo production targets using low enriched uranium, .sup.99 Mo production targets comprising low enriched uranium

DOEpatents

Wiencek, Thomas C [Orland Park, IL; Matos, James E [Oak Park, IL; Hofman, Gerard L [Downers Grove, IL

2000-12-12

A radioisotope production target and a method for fabricating a radioisotope production target is provided, wherein the target comprises an inner cylinder, a foil of fissionable material circumferentially contacting the outer surface of the inner cylinder, and an outer hollow cylinder adapted to receive the substantially foil-covered inner cylinder and compress tightly against the foil to provide good mechanical contact therewith. The method for fabricating a primary target for the production of fission products comprises preparing a first substrate to receive a foil of fissionable material so as to allow for later removal of the foil from the first substrate, preparing a second substrate to receive the foil so as to allow for later removal of the foil from the second substrate; attaching the first substrate to the second substrate such that the foil is sandwiched between the first substrate and second substrate to prevent foil exposure to ambient atmosphere, and compressing the exposed surfaces of the first and second substrate to assure snug mechanical contact between the foil, the first substrate and the second substrate.

Random Splicing of Several Exons Caused by a Single Base Change in the Target Exon of CRISPR/Cas9 Mediated Gene Knockout.

PubMed

Kapahnke, Marcel; Banning, Antje; Tikkanen, Ritva

2016-12-14

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated sequence 9 (CRISPR/Cas9) system is widely used for genome editing purposes as it facilitates an efficient knockout of a specific gene in, e.g. cultured cells. Targeted double-strand breaks are introduced to the target sequence of the guide RNAs, which activates the cellular DNA repair mechanism for non-homologous-end-joining, resulting in unprecise repair and introduction of small deletions or insertions. Due to this, sequence alterations in the coding region of the target gene frequently cause frame-shift mutations, facilitating degradation of the mRNA. We here show that such CRISPR/Cas9-mediated alterations in the target exon may also result in altered splicing of the respective pre-mRNA, most likely due to mutations of splice-regulatory sequences. Using the human FLOT-1 gene as an example, we demonstrate that such altered splicing products also give rise to aberrant protein products. These may potentially function as dominant-negative proteins and thus interfere with the interpretation of the data generated with these cell lines. Since most researchers only control the consequences of CRISPR knockout at genomic and protein level, our data should encourage to also check the alterations at the mRNA level.

The tunable pReX expression vector enables optimizing the T7-based production of membrane and secretory proteins in E. coli.

PubMed

Kuipers, Grietje; Karyolaimos, Alexandros; Zhang, Zhe; Ismail, Nurzian; Trinco, Gianluca; Vikström, David; Slotboom, Dirk Jan; de Gier, Jan-Willem

2017-12-16

To optimize the production of membrane and secretory proteins in Escherichia coli, it is critical to harmonize the expression rates of the genes encoding these proteins with the capacity of their biogenesis machineries. Therefore, we engineered the Lemo21(DE3) strain, which is derived from the T7 RNA polymerase-based BL21(DE3) protein production strain. In Lemo21(DE3), the T7 RNA polymerase activity can be modulated by the controlled co-production of its natural inhibitor T7 lysozyme. This setup enables to precisely tune target gene expression rates in Lemo21(DE3). The t7lys gene is expressed from the pLemo plasmid using the titratable rhamnose promoter. A disadvantage of the Lemo21(DE3) setup is that the system is based on two plasmids, a T7 expression vector and pLemo. The aim of this study was to simplify the Lemo21(DE3) setup by incorporating the key elements of pLemo in a standard T7-based expression vector. By incorporating the gene encoding the T7 lysozyme under control of the rhamnose promoter in a standard T7-based expression vector, pReX was created (ReX stands for Regulated gene eXpression). For two model membrane proteins and a model secretory protein we show that the optimized production yields obtained with the pReX expression vector in BL21(DE3) are similar to the ones obtained with Lemo21(DE3) using a standard T7 expression vector. For another secretory protein, a c-type cytochrome, we show that pReX, in contrast to Lemo21(DE3), enables the use of a helper plasmid that is required for the maturation and hence the production of this heme c protein. Here, we created pReX, a T7-based expression vector that contains the gene encoding the T7 lysozyme under control of the rhamnose promoter. pReX enables regulated T7-based target gene expression using only one plasmid. We show that with pReX the production of membrane and secretory proteins can be readily optimized. Importantly, pReX facilitates the use of helper plasmids. Furthermore, the use of pReX is not restricted to BL21(DE3), but it can in principle be used in any T7 RNAP-based strain. Thus, pReX is a versatile alternative to Lemo21(DE3).

The Biogeography of Putative Microbial Antibiotic Production

PubMed Central

Bryant, Jessica A.; Charkoudian, Louise K.; Docherty, Kathryn M.; Jones, Evan; Kembel, Steven W.; Green, Jessica L.; Bohannan, Brendan J. M.

2015-01-01

Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics. PMID:26102275

Target geometry and rigidity determines laser-induced cavitation bubble transport and nanoparticle productivity - a high-speed videography study.

PubMed

Kohsakowski, Sebastian; Gökce, Bilal; Tanabe, Rie; Wagener, Philipp; Plech, Anton; Ito, Yoshiro; Barcikowski, Stephan

2016-06-28

Laser-induced cavitation has mostly been studied in bulk liquid or at a two-dimensional wall, although target shapes for the particle synthesis may strongly affect bubble dynamics and interfere with particle productivity. We investigated the dynamics of the cavitation bubble induced by pulsed-laser ablation in liquid for different target geometries with high-speed laser microsecond videography and focus on the collapse behaviour. This method enables us observations in a high time resolution (intervals of 1 μs) and single-pulse experiments. Further, we analyzed the nanoparticle productivity, the sizes of the synthesized nanoparticles and the evolution of the bubble volume for each different target shape and geometry. For the ablation of metal (Ag, Cu, Ni) wire tips a springboard-like behaviour after the first collapse is observed which can be correlated with vertical projectile motion. Its turbulent friction in the liquid causes a very efficient transport and movement of the bubble and ablated material into the bulk liquid and prevents particle redeposition. This effect is influenced by the degree of freedom of the wire as well as the material properties and dimensions, especially the Young's modulus. The most efficient and largest bubble movement away from the wire was observed for a thin (500 μm) silver wire with velocities up to 19.8 m s(-1) and for materials with a small Young's modulus and flexural rigidity. We suggest that these observations may contribute to upscaling strategies and increase of particle yield towards large synthesis of colloids based on targets that may continuously be fed.

Segmented beryllium target for a 2 MW super beam facility

DOE PAGES

Davenne, T.; Caretta, O.; Densham, C.; ...

2015-09-14

The Long Baseline Neutrino Facility (LBNF, formerly the Long Baseline Neutrino Experiment) is under design as a next generation neutrino oscillation experiment, with primary objectives to search for CP violation in the leptonic sector, to determine the neutrino mass hierarchy and to provide a precise measurement of θ 23. The facility will generate a neutrino beam at Fermilab by the interaction of a proton beam with a target material. At the ultimate anticipated proton beam power of 2.3 MW the target material must dissipate a heat load of between 10 and 25 kW depending on the target size. This paper presents amore » target concept based on an array of spheres and compares it to a cylindrical monolithic target such as that which currently operates at the T2K facility. Thus simulation results show that the proposed technology offers efficient cooling and lower stresses whilst delivering a neutrino production comparable with that of a conventional solid cylindrical target.« less

Defining the needs for next generation assays for tuberculosis.

PubMed

Denkinger, Claudia M; Kik, Sandra V; Cirillo, Daniela Maria; Casenghi, Martina; Shinnick, Thomas; Weyer, Karin; Gilpin, Chris; Boehme, Catharina C; Schito, Marco; Kimerling, Michael; Pai, Madhukar

2015-04-01

To accelerate the fight against tuberculosis, major diagnostic challenges need to be addressed urgently. Post-2015 targets are unlikely to be met without the use of novel diagnostics that are more accurate and can be used closer to where patients first seek care in affordable diagnostic algorithms. This article describes the efforts by the stakeholder community that led to the identification of the high-priority diagnostic needs in tuberculosis. Subsequently target product profiles for the high-priority diagnostic needs were developed and reviewed in a World Health Organization (WHO)-led consensus meeting. The high-priority diagnostic needs included (1) a sputum-based replacement test for smear-microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis, ideally suitable for use at levels below microscopy centers; (3) a simple, low cost triage test for use by first-contact care providers as a rule-out test, ideally suitable for use by community health workers; and (4) a rapid drug susceptibility test for use at the microscopy center level. The developed target product profiles, along with complimentary work presented in this supplement, will help to facilitate the interaction between the tuberculosis community and the diagnostics industry with the goal to lead the way toward the post-2015 global tuberculosis targets. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Application of multi-target phytotherapeutic concept in malaria drug discovery: a systems biology approach in biomarker identification.

PubMed

Tarkang, Protus Arrey; Appiah-Opong, Regina; Ofori, Michael F; Ayong, Lawrence S; Nyarko, Alexander K

2016-01-01

There is an urgent need for new anti-malaria drugs with broad therapeutic potential and novel mode of action, for effective treatment and to overcome emerging drug resistance. Plant-derived anti-malarials remain a significant source of bioactive molecules in this regard. The multicomponent formulation forms the basis of phytotherapy. Mechanistic reasons for the poly-pharmacological effects of plants constitute increased bioavailability, interference with cellular transport processes, activation of pro-drugs/deactivation of active compounds to inactive metabolites and action of synergistic partners at different points of the same signaling cascade. These effects are known as the multi-target concept. However, due to the intrinsic complexity of natural products-based drug discovery, there is need to rethink the approaches toward understanding their therapeutic effect. This review discusses the multi-target phytotherapeutic concept and its application in biomarker identification using the modified reverse pharmacology - systems biology approach. Considerations include the generation of a product library, high throughput screening (HTS) techniques for efficacy and interaction assessment, High Performance Liquid Chromatography (HPLC)-based anti-malarial profiling and animal pharmacology. This approach is an integrated interdisciplinary implementation of tailored technology platforms coupled to miniaturized biological assays, to track and characterize the multi-target bioactive components of botanicals as well as identify potential biomarkers. While preserving biodiversity, this will serve as a primary step towards the development of standardized phytomedicines, as well as facilitate lead discovery for chemical prioritization and downstream clinical development.

EO based Agro-ecosystem approach for climate change adaptation in enhancing the crop production efficiency in the Indo-gangetic plains of India

NASA Astrophysics Data System (ADS)

Pandey, Suraj

This study develops a spatial mapping of agro-ecological zones based on earth observation model using MODIS regional dataset as a tool to guide key areas of cropping system and targeting to climate change strategies. This tool applies to the Indo-gangetic Plains of north India to target the domains of bio-physical characteristics and socio-economics with respect to changing climate in the region. It derive on secondary data for spatially-explicit variables at the state/district level, which serve as indicators of climate variability based on sustainable livelihood approach, natural, social and human. The study details the methodology used and generates the spatial climate risk maps for composite indicators of livelihood and vulnerability index in the region.

Production of 64Cu and 67Cu radiopharmaceuticals using zinc target irradiated with accelerator neutrons

NASA Astrophysics Data System (ADS)

Kawabata, Masako; Hashimoto, Kazuyuki; Saeki, Hideya; Sato, Nozomi; Motoishi, Shoji; Nagai, Yasuki

2014-09-01

Copper radioisotopes have gained a lot of attention in radiopharmaceuticals owing to their unique decay characteristics. The longest half-life β emitter, 67Cu, is thought to be suitable for targeted radio-immunotherapy. Adequate production of 67Cu to meet the demands of clinical studies has not been fully established. Another attractive copper isotope, 64Cu has possible applications as a diagnostic imaging tracer combined with a therapeutic effect. This work proposes a production method using accelerator neutrons in which two copper radioisotopes can be produced: 1) 68Zn(n,x)67Cu and 2) 64Zn(n,p)64Cu using ~14 MeV neutrons generated by natC(d, n) reaction, both from natural or enriched zinc oxides. The generated 64,67Cu were separated from the target zinc oxide using a chelating and an anion exchange columns and were labelled with two widely studied chelators where the labelling efficiency was found to be acceptably good. The major advantage of this method is that a significant amount of 64,67Cu with a very few impurity radionuclides are produced which also makes the separation procedure simple. Provided an accelerator supplying an Ed = ~ 40 MeV, a wide application of 64,67Cu based drugs in nuclear medicine is feasible in the near future. We will present the characteristics of this production method using accelerator neutrons including the chemical separation processes.

Clinical Development of Cell Therapies: Setting the Stage for Academic Success.

PubMed

Abou-El-Enein, M; Volk, H-D; Reinke, P

2017-01-01

Cellular therapies have potential to treat a wide range of diseases with autologous immunotherapies showing unprecedented therapeutic promise in clinical trials. Such therapies are mainly developed by academic researchers applying small-scale production, targeting rare and unmet medical needs. Here, we highlight the clinical translation of immunotherapy product in an academic setting, which may serve as a success model for early academic development of cell-based therapeutics. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Development of Water Target for Radioisotope Production

NASA Astrophysics Data System (ADS)

Tripp, Nathan

2011-10-01

Ongoing studies of plant physiology at TUNL require a supply of nitrogen-13 for use as a radiotracer. Production of nitrogen-13 using a water target and a proton beam follows the nuclear reaction 16-O(p,a)13-N. Unfortunately the irradiation of trace amounts of oxygen-18 within a natural water target produces fluorine-18 by the reaction 18-O(p, n)18-F. The presence of this second radioisotope reduces the efficacy of nitrogen-13 as a radiotracer. Designing a natural water target for nitrogen-13 production at TUNL required the design of several new systems to address the problems inherent in nitrogen-13 production. A heat exchanger cools the target water after irradiation within the target cell. The resulting improved thermal regulation of the target water prevents the system from overheating and minimizes the effect of the cavitations occurring within the target. Alumina pellets within a scrubbing unit remove the fluorine-18 contamination from the irradiated water. The modular design of the water target apparatus makes the system highly adaptable, allowing for easy reuse and adaptation of the different components into future projects. The newly designed and constructed water target should meet the current and future needs of TUNL researchers in the production of nitrogen-13. This TUNL REU project was funded in part by a grant from the National Science Foundation (NSF) NSF-PHY-08-51813.

Simulation of cosmic irradiation conditions in thick target arrangements

NASA Technical Reports Server (NTRS)

Theis, S.; Englert, P.; Reedy, R. C.; Arnold, J. R.

1986-01-01

One approach to simulate 2-pi irradiation conditions of planetary surfaces which has been widely applied in the past are bombardments of so called thick targets. A very large thick target was exposed recently to 2.1 GeV protons at the Bevatron-Bevalac in Berkeley. In a 100x100x180 cm steel-surrounded granodiorite target radioactive medium and high energy spallation products of the incident primary and of secondary particles were analyzed along the beam axis down to depths of 140 g/cm(2) in targets such as Cu, Ni, Co, Fe, T, Si, SiO2 and Al. Activities of these nuclides were exclusively determined via instrumental gamma-ray spectroscopy. Relative yields of neutron capture and spallation products induced in Co and Cu targets during the thick target bombardment are shown as a function of depth. The majority of the medium energy products such as Co-58 from Co targets exhibit a maximum at shallow depths of 40-60 g/cm(2) and then decrease exponentially. In a comparable 600 MeV proton bombarded thick target such a slight maximum for medium energy products was not observed. Rather, Co-58 activities in Co decreased steadily with the highest activity at the surface. The activities of the n-capture product Co-60 increase steadily starting at the surface. This indicates the rapidly growing flux of low energy neutrons within the target.

Octreotide-functionalized and resveratrol-loaded unimolecular micelles for targeted neuroendocrine cancer therapy

NASA Astrophysics Data System (ADS)

Xu, Wenjin; Burke, Jocelyn F.; Pilla, Srikanth; Chen, Herbert; Jaskula-Sztul, Renata; Gong, Shaoqin

2013-09-01

Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) that is often resistant to standard therapies. Resveratrol suppresses MTC growth in vitro, but it has low bioavailability in vivo due to its poor water solubility and rapid metabolic breakdown, as well as lack of tumor-targeting ability. A novel unimolecular micelle based on a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for NET-targeted delivery. The hyperbranched amphiphilic block copolymer consisted of a dendritic Boltorn® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell, and a hydrophilic poly(ethylene glycol) (PEG) outer shell. Octreotide (OCT), a peptide that shows strong binding affinity to somatostatin receptors, which are overexpressed on NET cells, was used as the targeting ligand. Resveratrol was physically encapsulated by the micelle with a drug loading content of 12.1%. The unimolecular micelles exhibited a uniform size distribution and spherical morphology, which were determined by both transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cellular uptake, cellular proliferation, and Western blot analyses demonstrated that the resveratrol-loaded OCT-targeted micelles suppressed growth more effectively than non-targeted micelles. Moreover, resveratrol-loaded NET-targeted micelles affected MTC cells similarly to free resveratrol in vitro, with equal growth suppression and reduction in NET marker production. These results suggest that the H40-based unimolecular micelle may offer a promising approach for targeted NET therapy.

Component analysis and target cell-based neuroactivity screening of Panax ginseng by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

PubMed

Yuan, Jinbin; Chen, Yang; Liang, Jian; Wang, Chong-Zhi; Liu, Xiaofei; Yan, Zhihong; Tang, Yi; Li, Jiankang; Yuan, Chun-Su

2016-12-01

Ginseng is one of the most widely used natural medicines in the world. Recent studies have suggested Panax ginseng has a wide range of beneficial effects on aging, central nervous system disorders, and neurodegenerative diseases. However, knowledge about the specific bioactive components of ginseng is still limited. This work aimed to screen for the bioactive components in Panax ginseng that act against neurodegenerative diseases, using the target cell-based bioactivity screening method. Firstly, component analysis of Panax ginseng extracts was performed by UPLC-QTOF-MS, and a total of 54 compounds in white ginseng were characterized and identified according to the retention behaviors, accurate MW, MS characteristics, parent nucleus, aglycones, side chains, and literature data. Then target cell-based bioactivity screening method was developed to predict the candidate compounds in ginseng with SH-SY5Y cells. Four ginsenosides, Rg 2 , Rh 1 , Ro, and Rd, were observed to be active. The target cell-based bioactivity screening method coupled with UPLC-QTOF-MS technique has suitable sensitivity and it can be used as a screening tool for low content bioactive constituents in natural products. Copyright © 2016 Elsevier B.V. All rights reserved.

River Food Web Response to Large-Scale Riparian Zone Manipulations

PubMed Central

Wootton, J. Timothy

2012-01-01

Conservation programs often focus on select species, leading to management plans based on the autecology of the focal species, but multiple ecosystem components can be affected both by the environmental factors impacting, and the management targeting, focal species. These broader effects can have indirect impacts on target species through the web of interactions within ecosystems. For example, human activity can strongly alter riparian vegetation, potentially impacting both economically-important salmonids and their associated river food web. In an Olympic Peninsula river, Washington state, USA, replicated large-scale riparian vegetation manipulations implemented with the long-term (>40 yr) goal of improving salmon habitat did not affect water temperature, nutrient limitation or habitat characteristics, but reduced canopy cover, causing reduced energy input via leaf litter, increased incident solar radiation (UV and PAR) and increased algal production compared to controls. In response, benthic algae, most insect taxa, and juvenile salmonids increased in manipulated areas. Stable isotope analysis revealed a predominant contribution of algal-derived energy to salmonid diets in manipulated reaches. The experiment demonstrates that riparian management targeting salmonids strongly affects river food webs via changes in the energy base, illustrates how species-based management strategies can have unanticipated indirect effects on the target species via the associated food web, and supports ecosystem-based management approaches for restoring depleted salmonid stocks. PMID:23284786

Microbial production of 1-octanol: A naturally excreted biofuel with diesel-like properties

PubMed Central

Akhtar, M. Kalim; Dandapani, Hariharan; Thiel, Kati; Jones, Patrik R.

2014-01-01

The development of sustainable, bio-based technologies to convert solar energy and carbon dioxide into fuels is a grand challenge. A core part of this challenge is to produce a fuel that is compatible with the existing transportation infrastructure. This task is further compounded by the commercial desire to separate the fuel from the biotechnological host. Based on its fuel characteristics, 1-octanol was identified as an attractive metabolic target with diesel-like properties. We therefore engineered a synthetic pathway specifically for the biosynthesis of 1-octanol in Escherichia coli BL21(DE3) by over-expression of three enzymes (thioesterase, carboxylic acid reductase and aldehyde reductase) and one maturation factor (phosphopantetheinyl transferase). Induction of this pathway in a shake flask resulted in 4.4 mg 1-octanol L−1 h−1 which exceeded the productivity of previously engineered strains. Furthermore, the majority (73%) of the fatty alcohol was localised within the media without the addition of detergent or solvent overlay. The deletion of acrA reduced the production and excretion of 1-octanol by 3-fold relative to the wild-type, suggesting that the AcrAB–TolC complex may be responsible for the majority of product efflux. This study presents 1-octanol as a potential fuel target that can be synthesised and naturally accumulated within the media using engineered microbes. PMID:27066394

Proton-induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/44Sc generator development.

PubMed

Radchenko, Valery; Engle, Jonathan W; Medvedev, Dmitri G; Maassen, Joel M; Naranjo, Cleo M; Unc, George A; Meyer, Catherine A L; Mastren, Tara; Brugh, Mark; Mausner, Leonard; Cutler, Cathy S; Birnbaum, Eva R; John, Kevin D; Nortier, F Meiring; Fassbender, Michael E

2017-07-01

Scandium-44g (half-life 3.97h) shows promise for application in positron emission tomography (PET), due to favorable decay parameters. One of the sources of 44g Sc is the 44 Ti/ 44g Sc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn, can be obtained via proton irradiation of scandium metal targets. A substantial 44 Ti product batch, however, requires high beam currents, long irradiation times and an elaborate chemical procedure for 44 Ti isolation and purification. This study describes the production of a combined 175MBq (4.7mCi) batch yield of 44 Ti in week long proton irradiations at the Los Alamos Isotope Production Facility (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion exchange chromatography based chemical separation method is introduced: first, a coarse separation of 44 Ti via anion exchange sorption in concentrated HCl results in a 44 Tc/Sc separation factor of 10 2 -10 3 . A second, cation exchange based step in HCl media is then applied for 44 Ti fine purification from residual Sc mass. In summary, this method yields a 90-97% 44 Ti recovery with an overall Ti/Sc separation factor of ≥10 6 . Copyright © 2017 Elsevier Inc. All rights reserved.

Proton induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/ 44Sc generator development

DOE PAGES

Radchenko, Valery; Engle, Jonathan Ward; Medvedev, Dmitri G.; ...

2017-04-07

Scandium-44 g (half-life 3.97 h) shows promise for application in positron emission tomography (PET), due to favorable decay parameters. One of the sources of 44gSc is the 44Ti/ 44gSc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn, can be obtained via proton irradiation of scandium metal targets. A substantial 44Ti product batch, however, requires high beam currents, long irradiation times and an elaborate chemical procedure for 44Ti isolation and purification. This study describes the production of a combined 175 MBq (4.7 mCi) batch yield of 44Ti inmore » week long proton irradiations at the Los Alamos Isotope Production Facility (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion exchange chromatography based chemical separation method is introduced: first, a coarse separation of 44Ti via anion exchange sorption in concentrated HCl results in a 44Tc/Sc separation factor of 10 2–10 3. A second, cation exchange based step in HCl media is then applied for 44Ti fine purification from residual Sc mass. In conclusion, this method yields a 90–97% 44Ti recovery with an overall Ti/Sc separation factor of ≥10 6.« less

Microbial production of 1-octanol: A naturally excreted biofuel with diesel-like properties.

PubMed

Akhtar, M Kalim; Dandapani, Hariharan; Thiel, Kati; Jones, Patrik R

2015-12-01

The development of sustainable, bio-based technologies to convert solar energy and carbon dioxide into fuels is a grand challenge. A core part of this challenge is to produce a fuel that is compatible with the existing transportation infrastructure. This task is further compounded by the commercial desire to separate the fuel from the biotechnological host. Based on its fuel characteristics, 1-octanol was identified as an attractive metabolic target with diesel-like properties. We therefore engineered a synthetic pathway specifically for the biosynthesis of 1-octanol in Escherichia coli BL21(DE3) by over-expression of three enzymes (thioesterase, carboxylic acid reductase and aldehyde reductase) and one maturation factor (phosphopantetheinyl transferase). Induction of this pathway in a shake flask resulted in 4.4 mg 1-octanol L -1  h -1 which exceeded the productivity of previously engineered strains. Furthermore, the majority (73%) of the fatty alcohol was localised within the media without the addition of detergent or solvent overlay. The deletion of acrA reduced the production and excretion of 1-octanol by 3-fold relative to the wild-type, suggesting that the AcrAB-TolC complex may be responsible for the majority of product efflux. This study presents 1-octanol as a potential fuel target that can be synthesised and naturally accumulated within the media using engineered microbes.

A novel multimodal chromatography based single step purification process for efficient manufacturing of an E. coli based biotherapeutic protein product.

PubMed

Bhambure, Rahul; Gupta, Darpan; Rathore, Anurag S

2013-11-01

Methionine oxidized, reduced and fMet forms of a native recombinant protein product are often the critical product variants which are associated with proteins expressed as bacterial inclusion bodies in E. coli. Such product variants differ from native protein in their structural and functional aspects, and may lead to loss of biological activity and immunogenic response in patients. This investigation focuses on evaluation of multimodal chromatography for selective removal of these product variants using recombinant human granulocyte colony stimulating factor (GCSF) as the model protein. Unique selectivity in separation of closely related product variants was obtained using combined pH and salt based elution gradients in hydrophobic charge induction chromatography. Simultaneous removal of process related impurities was also achieved in flow-through leading to single step purification process for the GCSF. Results indicate that the product recovery of up to 90.0% can be obtained with purity levels of greater than 99.0%. Binding the target protein at pH

Assessment of New Approaches in Geothermal Exploration Decision Making: Preprint

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

Akar, S.; Young, K. R.

Geothermal exploration projects have significant amount of risk associated with uncertainties encountered in the discovery of the geothermal resource. Understanding when and how to proceed in an exploration program, and when to walk away from a site, are two of the largest challenges for increased geothermal deployment. Current methodologies for exploration decision making is left to subjective by subjective expert opinion which can be incorrectly biased by expertise (e.g. geochemistry, geophysics), geographic location of focus, and the assumed conceptual model. The aim of this project is to develop a methodology for more objective geothermal exploration decision making at a givenmore » location, including go-no-go decision points to help developers and investors decide when to give up on a location. In this scope, two different approaches are investigated: 1) value of information analysis (VOIA) which is used for evaluating and quantifying the value of a data before they are purchased, and 2) enthalpy-based exploration targeting based on reservoir size, temperature gradient estimates, and internal rate of return (IRR). The first approach, VOIA, aims to identify the value of a particular data when making decisions with an uncertain outcome. This approach targets the pre-drilling phase of exploration. These estimated VOIs are highly affected by the size of the project and still have a high degree of subjectivity in assignment of probabilities. The second approach, exploration targeting, is focused on decision making during the drilling phase. It starts with a basic geothermal project definition that includes target and minimum required production capacity and initial budgeting for exploration phases. Then, it uses average temperature gradient, reservoir temperature estimates, and production capacity to define targets and go/no-go limits. The decision analysis in this approach is based on achieving a minimum IRR at each phase of the project. This second approach was determined to be less subjective, since it requires less subjectivity in the input values.« less

Evidence for Personal Protective Measures to Reduce Human Contact With Blacklegged Ticks and for Environmentally Based Control Methods to Suppress Host-Seeking Blacklegged Ticks and Reduce Infection with Lyme Disease Spirochetes in Tick Vectors and Rodent Reservoirs

PubMed Central

Eisen, Lars; Dolan, Marc C.

2018-01-01

In the 1980s, the blacklegged tick, Ixodes scapularis Say, and rodents were recognized as the principal vector and reservoir hosts of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, and deer were incriminated as principal hosts for I. scapularis adults. These realizations led to pioneering studies aiming to reduce the risk for transmission of B. burgdorferi to humans by attacking host-seeking ticks with acaricides, interrupting the enzootic transmission cycle by killing immatures infesting rodent reservoirs by means of acaricide-treated nesting material, or reducing deer abundance to suppress tick numbers. We review the progress over the past three decades in the fields of: 1) prevention of human–tick contact with repellents and permethrin-treated clothing, and 2) suppression of I. scapularis and disruption of enzootic B. burgdorferi transmission with environmentally based control methods. Personal protective measures include synthetic and natural product-based repellents that can be applied to skin and clothing, permethrin sprays for clothing and gear, and permethrin-treated clothing. A wide variety of approaches and products to suppress I. scapularis or disrupt enzootic B. burgdorferi transmission have emerged and been evaluated in field trials. Application of synthetic chemical acaricides is a robust method to suppress host-seeking I. scapularis ticks within a treated area for at least 6–8 wk. Natural product-based acaricides or entomopathogenic fungi have emerged as alternatives to kill host-seeking ticks for homeowners who are unwilling to use synthetic chemical acaricides. However, as compared with synthetic chemical acaricides, these approaches appear less robust in terms of both their killing efficacy and persistence. Use of rodent-targeted topical acaricides represents an alternative for homeowners opposed to open distribution of acaricides to the ground and vegetation on their properties. This host-targeted approach also provides the benefit of the intervention impacting the entire rodent home range. Rodent-targeted oral vaccines against B. burgdorferi and a rodent-targeted antibiotic bait have been evaluated in laboratory and field trials but are not yet commercially available. Targeting of deer—via deer reduction or treatment of deer with topical acaricides—can provide area-wide suppression of host-seeking I. scapularis. These two deer-targeted approaches combine great potential for protection that impacts the entire landscape with severe problems relating to public acceptance or implementation logistics. Integrated use of two or more methods has unfortunately been evaluated in very few published studies, but additional field evaluations of integrated tick and pathogen strategies are underway. PMID:27439616

Component extraction on CT volumes of assembled products using geometric template matching

NASA Astrophysics Data System (ADS)

Muramatsu, Katsutoshi; Ohtake, Yutaka; Suzuki, Hiromasa; Nagai, Yukie

2017-03-01

As a method of non-destructive internal inspection, X-ray computed tomography (CT) is used not only in medical applications but also for product inspection. Some assembled products can be divided into separate components based on density, which is known to be approximately proportional to CT values. However, components whose densities are similar cannot be distinguished using the CT value driven approach. In this study, we proposed a new component extraction algorithm from the CT volume, using a set of voxels with an assigned CT value with the surface mesh as the template rather than the density. The method has two main stages: rough matching and fine matching. At the rough matching stage, the position of candidate targets is identified roughly from the CT volume, using the template of the target component. At the fine matching stage, these candidates are precisely matched with the templates, allowing the correct position of the components to be detected from the CT volume. The results of two computational experiments showed that the proposed algorithm is able to extract components with similar density within the assembled products on CT volumes.

Postgenomic strategies in antibacterial drug discovery.

PubMed

Brötz-Oesterhelt, Heike; Sass, Peter

2010-10-01

During the last decade the field of antibacterial drug discovery has changed in many aspects including bacterial organisms of primary interest, discovery strategies applied and pharmaceutical companies involved. Target-based high-throughput screening had been disappointingly unsuccessful for antibiotic research. Understanding of this lack of success has increased substantially and the lessons learned refer to characteristics of targets, screening libraries and screening strategies. The 'genomics' approach was replaced by a diverse array of discovery strategies, for example, searching for new natural product leads among previously abandoned compounds or new microbial sources, screening for synthetic inhibitors by targeted approaches including structure-based design and analyses of focused libraries and designing resistance-breaking properties into antibiotics of established classes. Furthermore, alternative treatment options are being pursued including anti-virulence strategies and immunotherapeutic approaches. This article summarizes the lessons learned from the genomics era and describes discovery strategies resulting from that knowledge.

Market surveillance on non-halal additives incorporated in surimi based products using polymerase chain reaction (PCR)-southern hybridization analysis

NASA Astrophysics Data System (ADS)

Aravindran, S.; Sahilah, A. M.; Aminah, A.

2014-09-01

Halal surveillance on halal ingredients incorporated in surimi based products were studied using polymerase chain reaction (PCR)-southern hybridization on chip analysis. The primers used in this technique were targeted on mitochondria DNA (mtDNA) of cytochrome b (cyt b) gene sequence which able to differentiate 7 type (beef, chicken, duck, goat, buffalo, lamb and pork) of species on a single chip. 17 (n = 17*3) different brands of surimi-based product were purchased randomly from Selangor local market in January 2013. Of 17 brands, 3 (n = 3*3) brands were positive for chicken DNA, 1 (n = 1*3) brand was positive for goat DNA, and the remainder 13 brands (n = 13*3) have no DNA species detected. The sensitivity of PCR-southern hybridization primers to detect each meat species was 0.1 ng. In the present study, it is evidence that PCR-Southern Hybridization analysis offered a reliable result due to its highly specific and sensitive properties in detecting non-halal additive such as plasma protein incorporation in surimi-based product.

NAIMA: target amplification strategy allowing quantitative on-chip detection of GMOs.

PubMed

Morisset, Dany; Dobnik, David; Hamels, Sandrine; Zel, Jana; Gruden, Kristina

2008-10-01

We have developed a novel multiplex quantitative DNA-based target amplification method suitable for sensitive, specific and quantitative detection on microarray. This new method named NASBA Implemented Microarray Analysis (NAIMA) was applied to GMO detection in food and feed, but its application can be extended to all fields of biology requiring simultaneous detection of low copy number DNA targets. In a first step, the use of tailed primers allows the multiplex synthesis of template DNAs in a primer extension reaction. A second step of the procedure consists of transcription-based amplification using universal primers. The cRNA product is further on directly ligated to fluorescent dyes labelled 3DNA dendrimers allowing signal amplification and hybridized without further purification on an oligonucleotide probe-based microarray for multiplex detection. Two triplex systems have been applied to test maize samples containing several transgenic lines, and NAIMA has shown to be sensitive down to two target copies and to provide quantitative data on the transgenic contents in a range of 0.1-25%. Performances of NAIMA are comparable to singleplex quantitative real-time PCR. In addition, NAIMA amplification is faster since 20 min are sufficient to achieve full amplification.

NAIMA: target amplification strategy allowing quantitative on-chip detection of GMOs

PubMed Central

Morisset, Dany; Dobnik, David; Hamels, Sandrine; Žel, Jana; Gruden, Kristina

2008-01-01

We have developed a novel multiplex quantitative DNA-based target amplification method suitable for sensitive, specific and quantitative detection on microarray. This new method named NASBA Implemented Microarray Analysis (NAIMA) was applied to GMO detection in food and feed, but its application can be extended to all fields of biology requiring simultaneous detection of low copy number DNA targets. In a first step, the use of tailed primers allows the multiplex synthesis of template DNAs in a primer extension reaction. A second step of the procedure consists of transcription-based amplification using universal primers. The cRNA product is further on directly ligated to fluorescent dyes labelled 3DNA dendrimers allowing signal amplification and hybridized without further purification on an oligonucleotide probe-based microarray for multiplex detection. Two triplex systems have been applied to test maize samples containing several transgenic lines, and NAIMA has shown to be sensitive down to two target copies and to provide quantitative data on the transgenic contents in a range of 0.1–25%. Performances of NAIMA are comparable to singleplex quantitative real-time PCR. In addition, NAIMA amplification is faster since 20 min are sufficient to achieve full amplification. PMID:18710880

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

Milostan, Catharina; Levin, Todd; Muehleisen, Ralph T.

Many electric utilities operate energy efficiency incentive programs that encourage increased dissemination and use of energy-efficient (EE) products in their service territories. The programs can be segmented into three broad categories—downstream incentive programs target product end users, midstream programs target product distributors, and upstream programs target product manufacturers. Traditional downstream programs have had difficulty engaging Small Business/Small Portfolio (SBSP) audiences, and an opportunity exists to expand Commercial Midstream Incentive Programs (CMIPs) to reach this market segment instead.

Model-based assist feature insertion for sub-40nm memory device

NASA Astrophysics Data System (ADS)

Suh, Sungsoo; Lee, Suk-joo; Choi, Seong-woon; Lee, Sung-Woo; Park, Chan-hoon

2009-04-01

Many issues need to be resolved for a production-worthy model based assist feature insertion flow for single and double exposure patterning process to extend low k1 process at 193 nm immersion technology. Model based assist feature insertion is not trivial to implement either for single and double exposure patterning compared to rule based methods. As shown in Fig. 1, pixel based mask inversion technology in itself has difficulties in mask writing and inspection although it presents as one of key technology to extend single exposure for contact layer. Thus far, inversion technology is tried as a cooptimization of target mask to simultaneously generate optimized main and sub-resolution assists features for a desired process window. Alternatively, its technology can also be used to optimize for a target feature after an assist feature types are inserted in order to simplify the mask complexity. Simplification of inversion mask is one of major issue with applying inversion technology to device development even if a smaller mask feature can be fabricated since the mask writing time is also a major factor. As shown in Figure 2, mask writing time may be a limiting factor in determining whether or not an inversion solution is viable. It can be reasoned that increased number of shot counts relates to increase in margin for inversion methodology. On the other hand, there is a limit on how complex a mask can be in order to be production worthy. There is also source and mask co-optimization which influences the final mask patterns and assist feature sizes and positions for a given target. In this study, we will discuss assist feature insertion methods for sub 40-nm technology.

Specificity in the interaction of natural products with their target proteins--a biochemical and structural insight.

PubMed

Venkatraman, Prasanna

2010-06-01

Natural products are an abundant source of anti cancer agents. They act as cytotoxic drugs, and inhibitors of apoptosis, transcription, cell proliferation and angiogenesis. While pathways targeted by natural products have been well studied, there is paucity of information about the in vivo molecular target/s of these compounds. This review summarizes some of the natural compounds for which the molecular targets, mechanism of action and structural basis of specificity have been well documented. These examples illustrate that 'off target' binding can be explained on the basis of diversity inherent to biomolecular interactions. There is enough evidence to suggest that natural compounds are potent and versatile warheads that can be optimized for a multi targeted therapeutic intervention in cancer.

Diffraction based overlay re-assessed

NASA Astrophysics Data System (ADS)

Leray, Philippe; Laidler, David; D'havé, Koen; Cheng, Shaunee

2011-03-01

In recent years, numerous authors have reported the advantages of Diffraction Based Overlay (DBO) over Image Based Overlay (IBO), mainly by comparison of metrology figures of merit such as TIS and TMU. Some have even gone as far as to say that DBO is the only viable overlay metrology technique for advanced technology nodes; 22nm and beyond. Typically the only reported drawback of DBO is the size of the required targets. This severely limits its effective use, when all critical layers of a product, including double patterned layers need to be measured, and in-die overlay measurements are required. In this paper we ask whether target size is the only limitation to the adoption of DBO for overlay characterization and control, or are there other metrics, which need to be considered. For example, overlay accuracy with respect to scanner baseline or on-product process overlay control? In this work, we critically re-assess the strengths and weaknesses of DBO for the applications of scanner baseline and on-product process layer overlay control. A comprehensive comparison is made to IBO. For on product process layer control we compare the performance on critical process layers; Gate, Contact and Metal. In particularly we focus on the response of the scanner to the corrections determined by each metrology technique for each process layer, as a measure of the accuracy. Our results show that to characterize an overlay metrology technique that is suitable for use in advanced technology nodes requires much more than just evaluating the conventional metrology metrics of TIS and TMU.

Non-hormonal male contraception: A review and development of an Eppin based contraceptive.

PubMed

O'Rand, Michael G; Silva, Erick J R; Hamil, Katherine G

2016-01-01

Developing a non-hormonal male contraceptive requires identifying and characterizing an appropriate target and demonstrating its essential role in reproduction. Here we review the development of male contraceptive targets and the current therapeutic agents under consideration. In addition, the development of EPPIN as a target for contraception is reviewed. EPPIN is a well characterized surface protein on human spermatozoa that has an essential function in primate reproduction. EPPIN is discussed as an example of target development, testing in non-human primates, and the search for small organic compounds that mimic contraceptive antibodies; binding EPPIN and blocking sperm motility. Although many hurdles remain before the success of a non-hormonal male contraceptive, continued persistence should yield a marketable product. Copyright © 2015 Elsevier Inc. All rights reserved.

Microjet formation and hard x-ray production from a liquid metal target irradiated by intense femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Lar'kin, A.; Uryupina, D.; Ivanov, K.; Savel'ev, A.; Bonnet, T.; Gobet, F.; Hannachi, F.; Tarisien, M.; Versteegen, M.; Spohr, K.; Breil, J.; Chimier, B.; Dorchies, F.; Fourment, C.; Leguay, P.-M.; Tikhonchuk, V. T.

2014-09-01

By using a liquid metal as a target one may significantly enhance the yield of hard x-rays with a sequence of two intense femtosecond laser pulses. The influence of the time delay between the two pulses is studied experimentally and interpreted with numerical simulations. It was suggested that the first arbitrary weak pulse produces microjets from the target surface, while the second intense pulse provides an efficient electron heating and acceleration along the jet surface. These energetic electrons are the source of x-ray emission while striking the target surface. The microjet formation is explained based on the results given by both optical diagnostics and hydrodynamic modeling by a collision of shocks originated from two distinct zones of laser energy deposition.

Aerodynamic design and optimization of high altitude environment simulation system based on CFD

NASA Astrophysics Data System (ADS)

Ma, Pingchang; Yan, Lutao; Li, Hong

2017-05-01

High altitude environment simulation system (HAES) is built to provide a true flight environment for subsonic vehicles, with low density, high speed, and short time characteristics. Normally, wind tunnel experiments are based on similar principal, such as parameters of Re or Ma, in order to shorten test product size. However, the test products in HAES are trim size, so more attention is put on the true flight environment simulation. It includes real flight environment pressure, destiny and real flight velocity, and its type velocity is Ma=0.8. In this paper, the aerodynamic design of HAES is introduced and its rationality is explained according to CFD calculation based on Fluent. Besides, the initial pressure of vacuum tank in HAES is optimized, which is not only to meet the economic requirements, but also to decrease the effect of additional stress on the test product in the process of the establishment of the target flow field.

A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design.

PubMed

Li, Shiliang; Song, Yuwei; Liu, Xiaofeng; Li, Honglin

2016-01-01

The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly exploited to maximize hit rate and improve efficiency at the beginning of the drug discovery and drug development pipeline. This paper presented a valid methodology for fast target-focused combinatorial library design in both reaction-based and production-based ways with the library creating rates of approximately 70,000 molecules per second. Simple, quick and convenient operating procedures are the specific features of the method. SHAFTS, a hybrid 3D similarity calculation software, was embedded to help refine the size of the libraries and improve hit rates. Two target-focused (p38-focused and COX2-focused) libraries were constructed efficiently in this study. This rapid library enumeration method is portable and applicable to any other targets for good chemical starting points identification collaborated with either structure-based or ligand-based virtual screening.

Prostate-specific membrane antigen as a target for cancer imaging and therapy

PubMed Central

KIESS, A. P.; BANERJEE, S. R.; MEASE, R. C.; ROWE, S. P.; RAO, A.; FOSS, C. A.; CHEN, Y.; YANG, X.; CHO, S. Y.; NIMMAGADDA, S.; POMPER, M. G.

2016-01-01

The prostate-specific membrane antigen (PSMA) is a molecular target whose use has resulted in some of the most productive work toward imaging and treating prostate cancer over the past two decades. A wide variety of imaging agents extending from intact antibodies to low-molecular-weight compounds permeate the literature. In parallel there is a rapidly expanding pool of antibody-drug conjugates, radiopharmaceutical therapeutics, small-molecule drug conjugates, theranostics and nanomedicines targeting PSMA. Such productivity is motivated by the abundant expression of PSMA on the surface of prostate cancer cells and within the neovasculature of other solid tumors, with limited expression in most normal tissues. Animating the field is a variety of small-molecule scaffolds upon which the radionuclides, drugs, MR-detectable species and nanoparticles can be placed with relative ease. Among those, the urea-based agents have been most extensively leveraged, with expanding clinical use for detection and more recently for radiopharmaceutical therapy of prostate cancer, with surprisingly little toxicity. PSMA imaging of other cancers is also appearing in the clinical literature, and may overtake FDG for certain indications. Targeting PSMA may provide a viable alternative or first-line approach to managing prostate and other cancers. PMID:26213140

CHLOROACETONITRILE (CAN) INDUCES GLUTATHIONE DEPLETION AND 8-HYDROXYLATION OF GUANINE BASES IN RAT GASTRIC MUCOSA. (R825955)

EPA Science Inventory

Chloroacetonitrile (CAN) is detected in drinking-water supplies as a by-product of the chlorination process. Gastroesophageal tissues are potential target sites of acute and chronic toxicity by haloacetonitriles (HAN). To examine the mechanism of CAN toxicity, we studied its effe...

Severe Speech Sound Disorders: An Integrated Multimodal Intervention

ERIC Educational Resources Information Center

King, Amie M.; Hengst, Julie A.; DeThorne, Laura S.

2013-01-01

Purpose: This study introduces an integrated multimodal intervention (IMI) and examines its effectiveness for the treatment of persistent and severe speech sound disorders (SSD) in young children. The IMI is an activity-based intervention that focuses simultaneously on increasing the "quantity" of a child's meaningful productions of target words…

In Vivo Production of Agrotis ipsilon Nucleopolyhedrovirus for Quantity and Quality

USDA-ARS?s Scientific Manuscript database

The black cutworm, Agrotis ipsilon (Hüfnagel), is a pest causing damage to a variety plants from urban turf environments to farming row crops. A recently discovered baculovirus has the potential to be developed as a microbial-based biological pesticide to provide targeted control of this insect pest...

Development of Thixomolded{reg_sign} magnesium products

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

Ghosh, D.; Fan, R.; Kang, K.

1995-10-01

Thixomolding{reg_sign} is a racial new process which merges the technologies of die-casting and plastic injection molding for the net shape molding of magnesium based alloys. Properties of Thixomolded{reg_sign} magnesium alloys are discussed and compared with those of traditional die casting. Magnesium alloys are of great interest to automobile manufacturers because of the potential weight savings and corresponding energy savings due to increased fuel economy. For this reason, one of the first target markets for Thixomolded{reg_sign} products is the automotive industry. The use of Thixomolding{reg_sign} in the production of an automobile part is examined.

A biosensor generated via high throughput screening quantifies cell edge Src dynamics

PubMed Central

Gulyani, Akash; Vitriol, Eric; Allen, Richard; Wu, Jianrong; Gremyachinskiy, Dmitriy; Lewis, Steven; Dewar, Brian; Graves, Lee M.; Kay, Brian K.; Kuhlman, Brian; Elston, Tim; Hahn, Klaus M.

2011-01-01

Fluorescent biosensors for living cells currently require laborious optimization and a unique design for each target. They are limited by the availability of naturally occurring ligands with appropriate target specificity. Here we describe a biosensor based on an engineered fibronectin monobody scaffold that can be tailored to bind different targets via high throughput screening. This Src family kinase (SFK) biosensor was made by derivatizing a monobody specific for activated SFK with a bright dye whose fluorescence increases upon target binding. We identified sites for dye attachment and alterations to eliminate vesiculation in living cells, providing a generalizable scaffold for biosensor production. This approach minimizes cell perturbation because it senses endogenous, unmodified target, and because sensitivity is enhanced by direct dye excitation. Automated correlation of cell velocities and SFK activity revealed that SFK are activated specifically during protrusion. Activity correlates with velocity, and peaks 1–2 microns from the leading edge. PMID:21666688

Drug delivery technologies for autoimmune disease.

PubMed

Phillips, Brett E; Giannoukakis, Nick

2010-11-01

Targeting autoimmune disease poses two main challenges. The first is to identify unique targets to suppress directly or indirectly autoreactive cells exclusively. The second is to penetrate target tissues to deliver specifically drugs to desired cells that can achieve a therapeutic outcome. Herein, the range of drug delivery methods available and under development and how they can be useful to treat autoimmune diseases are discussed. Polymer delivery methods, as well as biological methods that include fusion proteins, targeted antibodies, recombinant viruses and cell products are compared. Readers will gain insight into the progression of clinical trials for different technologies and drug delivery methods useful for targeting and modulating the function of autoreactive immune cells. Several tissue-specific polymer-based and biologic drug delivery systems are now in Phase II/III clinical trials. Although these trials are focused mainly on cancer treatment, lessons from these trials can guide the use of the same agents for autoimmunity therapeutics.

Generating gene knockout rats by homologous recombination in embryonic stem cells

PubMed Central

Tong, Chang; Huang, Guanyi; Ashton, Charles; Li, Ping; Ying, Qi-Long

2013-01-01

We describe here a detailed protocol for generating gene knockout rats by homologous recombination in embryonic stem (ES) cells. This protocol comprises the following procedures: derivation and expansion of rat ES cells, construction of gene-targeting vectors, generation of gene-targeted rat ES cells and, finally, production of gene-targeted rats. The major differences between this protocol and the classical mouse gene-targeting protocol include ES cell culture methods, drug selection scheme, colony picking and screening strategies. This ES cell–based gene-targeting technique allows sophisticated genetic modifications to be performed in the rat, as many laboratories have been doing in the mouse for the past two decades. Recently we used this protocol to generate Tp53 (also known as p53) gene knockout rats. The entire process requires ~1 year to complete, from derivation of ES cells to generation of knockout rats. PMID:21637202

Interactive learning media based on flash for basic electronic engineering development for SMK Negeri 1 Driyorejo - Gresik

NASA Astrophysics Data System (ADS)

Mandigo Anggana Raras, Gustav

2018-04-01

This research aims to produce a product in the form of flash based interactive learning media on a basic electronic engineering subject that reliable to be used and to know students’ responses about the media. The target of this research is X-TEI 1 class at SMK Negeri 1 Driyorejo – Gresik. The method used in this study is R&D that has been limited into seven stages only (1) potential and problems, (2) data collection, (3) product design, (4) product validation, (5) product revision, (6) field test, and (7) analysis and writing. The obtained result is interactive learning media named MELDASH. Validation process used to produce a valid interactive learning media. The result of media validation state that the interactive learning media has a 90.83% rating. Students’ responses to this interactive learning media is really good with 88.89% rating.

Predictive acute toxicity tests with pesticides.

PubMed

Brown, V K

1983-01-01

By definition pesticides are biocidal products and this implies a probability that pesticides may be acutely toxic to species other than the designated target species. The ways in which pesticides are manufactured, formulated, packaged, distributed and used necessitates a potential for the exposure of non-target species although the technology exists to minimize adventitious exposure. The occurrence of deliberate exposure of non-target species due to the misuse of pesticides is known to happen. The array of predictive acute toxicity tests carried out on pesticides and involving the use of laboratory animals can be justified as providing data on which hazard assessment can be based. This paper addresses the justification and rationale of this statement.

A real-time articulatory visual feedback approach with target presentation for second language pronunciation learning.

PubMed

Suemitsu, Atsuo; Dang, Jianwu; Ito, Takayuki; Tiede, Mark

2015-10-01

Articulatory information can support learning or remediating pronunciation of a second language (L2). This paper describes an electromagnetic articulometer-based visual-feedback approach using an articulatory target presented in real-time to facilitate L2 pronunciation learning. This approach trains learners to adjust articulatory positions to match targets for a L2 vowel estimated from productions of vowels that overlap in both L1 and L2. Training of Japanese learners for the American English vowel /æ/ that included visual training improved its pronunciation regardless of whether audio training was also included. Articulatory visual feedback is shown to be an effective method for facilitating L2 pronunciation learning.

Note: Proton irradiation at kilowatt-power and neutron production from a free-surface liquid-lithium target

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

Halfon, S.; Feinberg, G.; Racah Institute of Physics, Hebrew University, Jerusalem 91904

2014-05-15

The free-surface Liquid-Lithium Target, recently developed at Soreq Applied Research Accelerator Facility (SARAF), was successfully used with a 1.9 MeV, 1.2 mA (2.3 kW) continuous-wave proton beam. Neutrons (∼2 × 10{sup 10} n/s having a peak energy of ∼27 keV) from the {sup 7}Li(p,n){sup 7}Be reaction were detected with a fission-chamber detector and by gold activation targets positioned in the forward direction. The setup is being used for nuclear astrophysics experiments to study neutron-induced reactions at stellar energies and to demonstrate the feasibility of accelerator-based boron neutron capture therapy.

Fabrication of light water reactor tritium targets

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

Pilger, J.P.

1991-11-01

The mission of the Fabrication Development Task of the Tritium Target Development Project is: to produce a documented technology basis, including specifications and procedures for target rod fabrication; to demonstrate that light water tritium targets can be manufactured at a rate consistent with tritium production requirements; and to develop quality control methods to evaluate target rod components and assemblies, and establish correlations between evaluated characteristics and target rod performance. Many of the target rod components: cladding tubes, end caps, plenum springs, etc., have similar counterparts in LWR fuel rods. High production rate manufacture and inspection of these components has beenmore » adequately demonstrated by nuclear fuel rod manufacturers. This summary describes the more non-conventional manufacturing processes and inspection techniques developed to fabricate target rod components whose manufacturability at required production rates had not been previously demonstrated.« less

Radiometric evaluation of diglycolamide resins for the chromatographic separation of actinium from fission product lanthanides

DOE PAGES

Radchenko, Valery; Mastren, Tara; Meyer, Catherine A. L.; ...

2017-07-20

Actinium-225 is a potential Targeted Alpha Therapy (TAT) isotope. It can be generated with high energy (≥ 100 MeV) proton irradiation of thorium targets. The main challenge in the chemical recovery of 225Ac lies in the separation from thorium and many fission by-products most importantly radiolanthanides. We recently developed a separation strategy based on a combination of cation exchange and extraction chromatography to isolate and purify 225Ac. In this study, actinium and lanthanide equilibrium distribution coefficients and column elution behavior for both TODGA (N,N,N',N'-tetra- n-octyldiglycolamide) and TEHDGA (N,N,N',N'-tetrakis-2-ethylhexyldiglycolamide) were determined. Density functional theory (DFT) calculations were performed and were inmore » agreement with experimental observations providing the foundation for understanding of the selectivity for Ac and lanthanides on different DGA (diglycolamide) based resins. The results of Gibbs energy (ΔG aq) calculations confirm significantly higher selectivity of DGA based resins for Ln III over Ac III in the presence of nitrate. As a result, DFT calculations and experimental results reveal that Ac chemistry cannot be predicted from lanthanide behavior under comparable circumstances.« less

Radiometric evaluation of diglycolamide resins for the chromatographic separation of actinium from fission product lanthanides

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

Radchenko, Valery; Mastren, Tara; Meyer, Catherine A. L.

Actinium-225 is a potential Targeted Alpha Therapy (TAT) isotope. It can be generated with high energy (≥ 100 MeV) proton irradiation of thorium targets. The main challenge in the chemical recovery of 225Ac lies in the separation from thorium and many fission by-products most importantly radiolanthanides. We recently developed a separation strategy based on a combination of cation exchange and extraction chromatography to isolate and purify 225Ac. In this study, actinium and lanthanide equilibrium distribution coefficients and column elution behavior for both TODGA (N,N,N',N'-tetra- n-octyldiglycolamide) and TEHDGA (N,N,N',N'-tetrakis-2-ethylhexyldiglycolamide) were determined. Density functional theory (DFT) calculations were performed and were inmore » agreement with experimental observations providing the foundation for understanding of the selectivity for Ac and lanthanides on different DGA (diglycolamide) based resins. The results of Gibbs energy (ΔG aq) calculations confirm significantly higher selectivity of DGA based resins for Ln III over Ac III in the presence of nitrate. As a result, DFT calculations and experimental results reveal that Ac chemistry cannot be predicted from lanthanide behavior under comparable circumstances.« less

Marketing information system online design for craftsmen small medium enterprises (case study: craftsmen ac)

NASA Astrophysics Data System (ADS)

Fitriana, Rina; Kurniawan, Wawan; Barlianto, Anung; Adriansyah Putra, Rizki

2016-02-01

AC is small and medium enterprises which is engaged in the field of crafts. This SME (Small Medium Enterprise) didn't have an integrated information system for managing sales. This research aims to design a marketing Information system online as applications that built as web base. The integrated system is made to manage sales and expand its market share. This study uses a structured analysis and design in its approach to build systems and also implemented a marketing framework of STP (Segmentation, Targeting, Positioning) and 4P (Price, Product, Place, Promotion) to obtain market analysis. The main market target customer craftsmen AC is women aged 13 years to 35 years. The products produced by AC are shoes, brooch, that are typical of the archipelago. The prices is range from Rp. 2000 until Rp. 400.000. Marketing information system online can be used as a sales transaction document, promoting the goods, and for customer booking products.

Alpha particle induced reactions on natCr up to 39 MeV: Experimental cross-sections, comparison with theoretical calculations and thick target yields for medically relevant 52gFe production

NASA Astrophysics Data System (ADS)

Hermanne, A.; Adam Rebeles, R.; Tárkányi, F.; Takács, S.

2015-08-01

Thin natCr targets were obtained by electroplating, using 23.75 μm Cu foils as backings. In five stacked foil irradiations, followed by high resolution gamma spectroscopy, the cross sections for production of 52gFe, 49,51cumCr, 52cum,54,56cumMn and 48cumV in Cr and 61Cu,68Ga in Cu were measured up to 39 MeV incident α-particle energy. Reduced uncertainty is obtained by simultaneous remeasurement of the natCu(α,x)67,66Ga monitor reactions over the whole energy range. Comparisons with the scarce literature values and results from the TENDL-2013 on-line library, based on the theoretical code family TALYS-1.6, were made. A discussion of the production routes for 52gFe with achievable yields and contamination rates was made.

Is handwriting constrained by phonology? Evidence from Stroop tasks with written responses and Chinese characters

PubMed Central

Damian, Markus F.; Qu, Qingqing

2013-01-01

To what extent is handwritten word production based on phonological codes? A few studies conducted in Western languages have recently provided evidence showing that phonology contributes to the retrieval of graphemic properties in written output tasks. Less is known about how orthographic production works in languages with non-alphabetic scripts such as written Chinese. We report a Stroop study in which Chinese participants wrote the color of characters on a digital graphic tablet; characters were either neutral, or homophonic to the target (congruent), or homophonic to an alternative (incongruent). Facilitation was found from congruent homophonic distractors, but only when the homophone shared the same tone with the target. This finding suggests a contribution of phonology to written word production. A second experiment served as a control experiment to exclude the possibility that the effect in Experiment 1 had an exclusively semantic locus. Overall, the findings offer new insight into the relative contribution of phonology to handwriting, particularly in non-Western languages. PMID:24146660

A Comparison of Word Learning in 3-Year-Old Children At-Risk for Language and Literacy Difficulties in Two Conditions: Dialogic Reading and Activity-Based Intervention

ERIC Educational Resources Information Center

Rahn, Naomi L.

2013-01-01

Existing research suggests a need for an intervention that can accelerate vocabulary acquisition for young children at-risk due to poverty. An adapted alternating treatments design was used to examine the effects of Dialogic Reading and Activity-Based Intervention (ABI) on participants' production of target words. Participants were three…

Imaging study of using radiopharmaceuticals labeled with cyclotron-produced 99mTc.

PubMed

Hou, X; Tanguay, J; Vuckovic, M; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2016-12-07

Cyclotron-produced 99m Tc (CPTc) has been recognized as an attractive and practical substitution of reactor/generator based 99m Tc. However, the small amount of 92-98 Mo in the irradiation of enriched 100 Mo could lead to the production of other radioactive technetium isotopes (Tc-impurities) which cannot be chemically separated. Thus, these impurities could contribute to patient dose and affect image quality. The potential radiation dose caused by these Tc-impurities produced using different targets, irradiation conditions, and corresponding to different injection times have been investigated, leading us to create dose-based limits of these parameters for producing clinically acceptable CPTc. However, image quality has been not considered. The aim of the present work is to provide a comprehensive and quantitative analysis of image quality for CPTc. The impact of Tc-impurities in CPTc on image resolution, background noise, and contrast is investigated by performing both Monte-Carlo simulations and phantom experiments. Various targets, irradiation, and acquisition conditions are employed for investigating the image-based limits of CPTc production parameters. Additionally, the relationship between patient dose and image quality of CPTc samples is studied. Only those samples which meet both dose- and image-based limits should be accepted in future clinical studies.

Imaging study of using radiopharmaceuticals labeled with cyclotron-produced 99mTc

NASA Astrophysics Data System (ADS)

Hou, X.; Tanguay, J.; Vuckovic, M.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2016-12-01

Cyclotron-produced 99mTc (CPTc) has been recognized as an attractive and practical substitution of reactor/generator based 99mTc. However, the small amount of 92-98Mo in the irradiation of enriched 100Mo could lead to the production of other radioactive technetium isotopes (Tc-impurities) which cannot be chemically separated. Thus, these impurities could contribute to patient dose and affect image quality. The potential radiation dose caused by these Tc-impurities produced using different targets, irradiation conditions, and corresponding to different injection times have been investigated, leading us to create dose-based limits of these parameters for producing clinically acceptable CPTc. However, image quality has been not considered. The aim of the present work is to provide a comprehensive and quantitative analysis of image quality for CPTc. The impact of Tc-impurities in CPTc on image resolution, background noise, and contrast is investigated by performing both Monte-Carlo simulations and phantom experiments. Various targets, irradiation, and acquisition conditions are employed for investigating the image-based limits of CPTc production parameters. Additionally, the relationship between patient dose and image quality of CPTc samples is studied. Only those samples which meet both dose- and image-based limits should be accepted in future clinical studies.

On-Orbit MTF Measurement and Product Quality Monitoring for Commercial Remote Sensing Systems

NASA Technical Reports Server (NTRS)

Person, Steven

2007-01-01

Initialization and opportunistic targets are chosen that represent the MTF on the spatial domain. Ideal targets have simple mathematical relationships. Determine the MTF of an on-orbit satellite using in-scene targets: Slant-Edge, Line Source, point Source, and Radial Target. Attempt to facilitate the MTF calculation by automatically locating targets of opportunity. Incorporate MTF results into a product quality monitoring architecture.

Method for fabricating {sup 99}Mo production targets using low enriched uranium, {sup 99}Mo production targets comprising low enriched uranium

DOEpatents

Wiencek, T.C.; Matos, J.E.; Hofman, G.L.

1997-03-25

A radioisotope production target and a method for fabricating a radioisotope production target is provided, wherein the target comprises an inner cylinder, a foil of fissionable material circumferentially contacting the outer surface of the inner cylinder, and an outer hollow cylinder adapted to receive the substantially foil-covered inner cylinder and compress tightly against the foil to provide good mechanical contact therewith. The method for fabricating a primary target for the production of fission products comprises preparing a first substrate to receive a foil of fissionable material so as to allow for later removal of the foil from the first substrate, preparing a second substrate to receive the foil so as to allow for later removal of the foil from the second substrate; attaching the first substrate to the second substrate such that the foil is sandwiched between the first substrate and second substrate to prevent foil exposure to ambient atmosphere, and compressing the exposed surfaces of the first and second substrate to assure snug mechanical contact between the foil, the first substrate and the second substrate. 3 figs.

Spot-welding solid targets for high current cyclotron irradiation

PubMed Central

Ellison, Paul A.; Valdovinos, Hector F.; Graves, Stephen A.; Barnhart, Todd E.; Nickles, Robert J.

2016-01-01

Zirconium-89 finds broad application for use in positron emission tomography. Its cyclotron production has been limited by the heat transfer from yttrium targets at high beam currents. A spot welding technique allows a three-fold increase in beam current, without affecting 89Zr quality. An yttrium foil, welded to a jet-cooled tantalum support base accommodates a 50 μA proton beam degraded to 14 MeV. The resulting activity yield of 48 ± 4 MBq/(μA·hr) now extends the outreach of 89Zr for a broader distribution. PMID:27771445

PCR Amplicon Prediction from Multiplex Degenerate Primer and Probe Sets

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

Gardner, S. N.

2013-08-08

Assessing primer specificity and predicting both desired and off-target amplification products is an essential step for robust PCR assay design. Code is described to predict potential polymerase chain reaction (PCR) amplicons in a large sequence database such as NCBI nt from either singleplex or a large multiplexed set of primers, allowing degenerate primer and probe bases, with target mismatch annotates amplicons with gene information automatically downloaded from NCBI, and optionally it can predict whether there are also TaqMan/Luminex probe matches within predicted amplicons.

Standardization of protein biomarker measurements: is it feasible?

PubMed

Schimmel, Heinz; Zegers, Ingrid; Emons, Hendrik

2010-01-01

The standardisation of measurements of protein biomarkers, which are potentially heterogeneous in terms of fragmentation, modification, substitution, primary, secondary, tertiary and quaternary structure, is a demanding task. However, they are a prime target for standardisation efforts due to the importance of protein biomarkers in diagnostics and health care and the typically observed significant discrepancies in measurement results obtained with non-standardized platforms. Based on the experience gathered during successfully completed projects for the production of reference materials, pragmatic approaches are described how standardisation could become feasible despite the fuzziness of the target analytes.

Plume Image Profiling of UV Laser Desorbed Biomolecules

NASA Astrophysics Data System (ADS)

Merrigan, T. L.; Hunniford, C. A.; Timson, D. J.; Catney, M.; McCullough, R. W.

2008-12-01

An experimental system, based upon the techniques of UV and IR laser desorption with time of flight mass spectrometry, has been constructed to enable the production and characterization of neutral biomolecular targets. The feasibility of the laser desorption technique for the purpose of radiation interaction experiments is investigated here. Fluorescent dye tagging and laser induced fluorescence imaging has been used to help characterize the laser produced plumes of biomolecules revealing their spatial density profiles and temporal evolution. Peak target thicknesses of 2×1012 molecules cm-2 were obtained 30 μs after laser desorption.

Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer

DTIC Science & Technology

2017-12-01

at cis-regulatory elements such as enhancers to facilitate gene transcription. CRISPR /Cas9- mediated ablation of a putative Meis1 enhancer carrying...Tables S4 and S5. 10 Cancer Cell 30, 1–16, July 11, 2016the CRISPR /Cas9-based genomic editing technology. Cas9 and a pair of single guide RNAs (sgRNA... CRISPR /Cas9-mediated deletio sgMeis1, a pair of sgRNAs that target the DMR boundaries. (N) Sequencing of the genomic PCR products from F2/R2 primers shows

Quantitative analysis of relationships between irradiation parameters and the reproducibility of cyclotron-produced (99m)Tc yields.

PubMed

Tanguay, J; Hou, X; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2015-05-21

Cyclotron production of (99m)Tc through the (100)Mo(p,2n) (99m)Tc reaction channel is actively being investigated as an alternative to reactor-based (99)Mo generation by nuclear fission of (235)U. An exciting aspect of this approach is that it can be implemented using currently-existing cyclotron infrastructure to supplement, or potentially replace, conventional (99m)Tc production methods that are based on aging and increasingly unreliable nuclear reactors. Successful implementation will require consistent production of large quantities of high-radionuclidic-purity (99m)Tc. However, variations in proton beam currents and the thickness and isotopic composition of enriched (100)Mo targets, in addition to other irradiation parameters, may degrade reproducibility of both radionuclidic purity and absolute (99m)Tc yields. The purpose of this article is to present a method for quantifying relationships between random variations in production parameters, including (100)Mo target thicknesses and proton beam currents, and reproducibility of absolute (99m)Tc yields (defined as the end of bombardment (EOB) (99m)Tc activity). Using the concepts of linear error propagation and the theory of stochastic point processes, we derive a mathematical expression that quantifies the influence of variations in various irradiation parameters on yield reproducibility, quantified in terms of the coefficient of variation of the EOB (99m)Tc activity. The utility of the developed formalism is demonstrated with an example. We show that achieving less than 20% variability in (99m)Tc yields will require highly-reproducible target thicknesses and proton currents. These results are related to the service rate which is defined as the percentage of (99m)Tc production runs that meet the minimum daily requirement of one (or many) nuclear medicine departments. For example, we show that achieving service rates of 84.0%, 97.5% and 99.9% with 20% variations in target thicknesses requires producing on average 1.2, 1.5 and 1.9 times the minimum daily activity requirement. The irradiation parameters that would be required to achieve these service rates are described. We believe the developed formalism will aid in the development of quality-control criteria required to ensure consistent supply of large quantities of high-radionuclidic-purity cyclotron-produced (99m)Tc.

Quantitative analysis of relationships between irradiation parameters and the reproducibility of cyclotron-produced 99mTc yields

NASA Astrophysics Data System (ADS)

Tanguay, J.; Hou, X.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2015-05-01

Cyclotron production of 99mTc through the 100Mo(p,2n) 99mTc reaction channel is actively being investigated as an alternative to reactor-based 99Mo generation by nuclear fission of 235U. An exciting aspect of this approach is that it can be implemented using currently-existing cyclotron infrastructure to supplement, or potentially replace, conventional 99mTc production methods that are based on aging and increasingly unreliable nuclear reactors. Successful implementation will require consistent production of large quantities of high-radionuclidic-purity 99mTc. However, variations in proton beam currents and the thickness and isotopic composition of enriched 100Mo targets, in addition to other irradiation parameters, may degrade reproducibility of both radionuclidic purity and absolute 99mTc yields. The purpose of this article is to present a method for quantifying relationships between random variations in production parameters, including 100Mo target thicknesses and proton beam currents, and reproducibility of absolute 99mTc yields (defined as the end of bombardment (EOB) 99mTc activity). Using the concepts of linear error propagation and the theory of stochastic point processes, we derive a mathematical expression that quantifies the influence of variations in various irradiation parameters on yield reproducibility, quantified in terms of the coefficient of variation of the EOB 99mTc activity. The utility of the developed formalism is demonstrated with an example. We show that achieving less than 20% variability in 99mTc yields will require highly-reproducible target thicknesses and proton currents. These results are related to the service rate which is defined as the percentage of 99mTc production runs that meet the minimum daily requirement of one (or many) nuclear medicine departments. For example, we show that achieving service rates of 84.0%, 97.5% and 99.9% with 20% variations in target thicknesses requires producing on average 1.2, 1.5 and 1.9 times the minimum daily activity requirement. The irradiation parameters that would be required to achieve these service rates are described. We believe the developed formalism will aid in the development of quality-control criteria required to ensure consistent supply of large quantities of high-radionuclidic-purity cyclotron-produced 99mTc.

Lithium target performance evaluation for low-energy accelerator-based in vivo measurements using gamma spectroscopy.

PubMed

Aslam; Prestwich, W V; McNeill, F E

2003-03-01

The operating conditions at McMaster KN Van de Graaf accelerator have been optimized to produce neutrons via the (7)Li(p, n)(7)Be reaction for in vivo neutron activation analysis. In a number of earlier studies (development of an accelerator based system for in vivo neutron activation analysis measurements of manganese in humans, Ph.D. Thesis, McMaster University, Hamilton, ON, Canada; Appl. Radiat. Isot. 53 (2000) 657; in vivo measurement of some trace elements in human Bone, Ph.D. Thesis. McMaster University, Hamilton, ON, Canada), a significant discrepancy between the experimental and the calculated neutron doses has been pointed out. The hypotheses formulated in the above references to explain the deviation of the experimental results from analytical calculations, have been tested experimentally. The performance of the lithium target for neutron production has been evaluated by measuring the (7)Be activity produced as a result of (p, n) interaction with (7)Li. In contradiction to the formulated hypotheses, lithium target performance was found to be mainly affected by inefficient target cooling and the presence of oxides layer on target surface. An appropriate choice of these parameters resulted in neutron yields same as predicated by analytical calculations.

A surface-confined DNA assembly amplification strategy on DNA nanostructural scaffold for electrochemiluminescence biosensing.

PubMed

Feng, Qiu-Mei; Guo, Yue-Hua; Xu, Jing-Juan; Chen, Hong-Yuan

2018-02-15

A critical challenge in surface-based DNA assembly amplification is the reduced accessibility of DNA strands arranged on a heterogeneous surface compared to that in homogeneous solution. Here, a novel in situ surface-confined DNA assembly amplification electrochemiluminescence (ECL) biosensor based on DNA nanostructural scaffold was presented. In this design, a stem-loop structural DNA segment (Hairpin 1) was constructed on the vertex of DNA nanostructural scaffold as recognition probe. In the present of target DNA, the hairpin structure changed to rod-like through complementary hybridization with target DNA, resulting in the formation of Hairpin 1:target DNA. When the obtained Hairpin 1:target DNA met Hairpin 2 labeled with glucose oxidase (GOD), the DNA cyclic amplification was activated, releasing target DNA into homogeneous solution for the next recycling. Thus, the ECL signal of Ru(bpy) 3 2+ -TPrA system was quenched by H 2 O 2 , the product of GOD catalyzing glucose. As a result, this proposed method achieved a linear range response from 50 aM to 10 pM with lower detection limit of 20 aM. Copyright © 2017 Elsevier B.V. All rights reserved.

Bacteriophages and phage-inspired nanocarriers for targeted delivery of therapeutic cargos.

PubMed

Karimi, Mahdi; Mirshekari, Hamed; Moosavi Basri, Seyed Masoud; Bahrami, Sajad; Moghoofei, Mohsen; Hamblin, Michael R

2016-11-15

The main goal of drug delivery systems is to target therapeutic cargoes to desired cells and to ensure their efficient uptake. Recently a number of studies have focused on designing bio-inspired nanocarriers, such as bacteriophages, and synthetic carriers based on the bacteriophage structure. Bacteriophages are viruses that specifically recognize their bacterial hosts. They can replicate only inside their host cell and can act as natural gene carriers. Each type of phage has a particular shape, a different capacity for loading cargo, a specific production time, and their own mechanisms of supramolecular assembly, that have enabled them to act as tunable carriers. New phage-based technologies have led to the construction of different peptide libraries, and recognition abilities provided by novel targeting ligands. Phage hybridization with non-organic compounds introduces new properties to phages and could be a suitable strategy for construction of bio-inorganic carriers. In this review we try to cover the major phage species that have been used in drug and gene delivery systems, and the biological application of phages as novel targeting ligands and targeted therapeutics. Copyright © 2016 Elsevier B.V. All rights reserved.

Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice.

PubMed

Judge, Adam D; Robbins, Marjorie; Tavakoli, Iran; Levi, Jasna; Hu, Lina; Fronda, Anna; Ambegia, Ellen; McClintock, Kevin; MacLachlan, Ian

2009-03-01

siRNAs that specifically silence the expression of cancer-related genes offer a therapeutic approach in oncology. However, it remains critical to determine the true mechanism of their therapeutic effects. Here, we describe the preclinical development of chemically modified siRNA targeting the essential cell-cycle proteins polo-like kinase 1 (PLK1) and kinesin spindle protein (KSP) in mice. siRNA formulated in stable nucleic acid lipid particles (SNALP) displayed potent antitumor efficacy in both hepatic and subcutaneous tumor models. This was correlated with target gene silencing following a single intravenous administration that was sufficient to cause extensive mitotic disruption and tumor cell apoptosis. Our siRNA formulations induced no measurable immune response, minimizing the potential for nonspecific effects. Additionally, RNAi-specific mRNA cleavage products were found in tumor cells, and their presence correlated with the duration of target mRNA silencing. Histological biomarkers confirmed that RNAi-mediated gene silencing effectively inhibited the target's biological activity. This report supports an RNAi-mediated mechanism of action for siRNA antitumor effects, suggesting a new methodology for targeting other key genes in cancer development with siRNA-based therapeutics.

Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma

NASA Astrophysics Data System (ADS)

Azevedo, Hátylas; Moreira-Filho, Carlos Alberto

2015-11-01

Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy, and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks’ robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance.

Modifying Yeast Tolerance to Inhibitory Conditions of Ethanol Production Processes

PubMed Central

Caspeta, Luis; Castillo, Tania; Nielsen, Jens

2015-01-01

Saccharomyces cerevisiae strains having a broad range of substrate utilization, rapid substrate consumption, and conversion to ethanol, as well as good tolerance to inhibitory conditions are ideal for cost-competitive ethanol production from lignocellulose. A major drawback to directly design S. cerevisiae tolerance to inhibitory conditions of lignocellulosic ethanol production processes is the lack of knowledge about basic aspects of its cellular signaling network in response to stress. Here, we highlight the inhibitory conditions found in ethanol production processes, the targeted cellular functions, the key contributions of integrated -omics analysis to reveal cellular stress responses according to these inhibitors, and current status on design-based engineering of tolerant and efficient S. cerevisiae strains for ethanol production from lignocellulose. PMID:26618154

On-product overlay enhancement using advanced litho-cluster control based on integrated metrology, ultra-small DBO targets and novel corrections

NASA Astrophysics Data System (ADS)

Bhattacharyya, Kaustuve; Ke, Chih-Ming; Huang, Guo-Tsai; Chen, Kai-Hsiung; Smilde, Henk-Jan H.; Fuchs, Andreas; Jak, Martin; van Schijndel, Mark; Bozkurt, Murat; van der Schaar, Maurits; Meyer, Steffen; Un, Miranda; Morgan, Stephen; Wu, Jon; Tsai, Vincent; Liang, Frida; den Boef, Arie; ten Berge, Peter; Kubis, Michael; Wang, Cathy; Fouquet, Christophe; Terng, L. G.; Hwang, David; Cheng, Kevin; Gau, TS; Ku, Y. C.

2013-04-01

Aggressive on-product overlay requirements in advanced nodes are setting a superior challenge for the semiconductor industry. This forces the industry to look beyond the traditional way-of-working and invest in several new technologies. Integrated metrology2, in-chip overlay control, advanced sampling and process correction-mechanism (using the highest order of correction possible with scanner interface today), are a few of such technologies considered in this publication.

Tetraspecific scFv construct provides NK cell mediated ADCC and self-sustaining stimuli via insertion of IL-15 as a cross-linker

PubMed Central

Schmohl, Joerg U.; Felices, Martin; Todhunter, Deborah; Taras, Elizabeth; Miller, Jeffrey S.; Vallera, Daniel A.

2016-01-01

Background The design of a highly effective anti-cancer immune-engager would include targeting of highly drug refractory cancer stem cells (CSC). The design would promote effective antibody-dependent cell-mediated cytotoxicity (ADCC) and simultaneously promote costimulation to expand and self-sustain the effector NK cell population. Based on our bispecific NK cell engager platform we constructed a tetraspecific killer engager (TetraKE) comprising single-chain variable fragments (scFvs) binding FcγRIII (CD16) on NK cells, EpCAM on carcinoma cells and CD133 on cancer stem cells in order to promote ADCC. Furthermore, an Interleukin (IL)-15-crosslinker enhanced NK cell related proliferation resulting in a highly active drug termed 1615EpCAM133. Results Proliferation assays showed TetraKE promoted proliferation and enhanced NK cell survival. Drug-target binding, NK cell related degranulation, and IFN-γ production was specific for both tumor related antigens in EpCAM and CD133 bearing cancer cell lines. The TetraKE showed higher killing activity and superior dose dependent degranulation. Cytokine profiling showed a moderately enhanced IFN-γ production, enhanced GM-CSF production, but no evidence of induction of excessive cytokine release. Methods Assembly and synthesis of hybrid genes encoding the TetraKE were performed using DNA shuffling and ligation. The TetraKE was tested for efficacy, specificity, proliferation, survival, and cytokine production using carcinoma cell lines and functional assays measuring NK cell activity. Conclusion 1615EpCAM133 combines improved induction of ADCC with enhanced proliferation, limited cytokine response, and prolonged survival and proliferation of NK cells. By linking scFv-related targeting of carcinoma and CSCs with a sustaining IL-15 signal, our new construct shows great promise to target cancer and CSCs. PMID:27650544

Measurements of production cross sections of 10Be and 26Al by 120 GeV and 392 MeV proton bombardment of 89Y, 159Tb, and natCu targets

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

Sekimoto, S.; Okumura, S.; Yashima, H.

2015-08-12

The production cross sections of 10Be and 26Al were measured by accelerator mass spectrometry using 89Y, 159Tb, and natCu targets bombarded by protons with energies E p of 120 GeV and 392 MeV. The production cross sections obtained for 10Be and 26Al were compared with those previously reported using E p = 50 MeV–24 GeV and various targets. It was found that the production cross sections of 10Be monotonically increased with increasing target mass number when the proton energy was greater than a few GeV. On the other hand, it was also found that the production cross sections of 10Bemore » decreased as the target mass number increased from that of carbon to those near the mass numbers of nickel and zinc when the proton energy was below approximately 1 GeV. They also increased as the target mass number increased from near those of nickel and zinc to that of bismuth, in the same proton energy range. Similar results were observed in the production cross sections of 26Al, though the absolute values were quite different between 10Be and 26Al. As a result, the difference between these production cross sections may depend on the impact parameter (nuclear radius) and/or the target nucleus stiffness.« less

False Positivity of Non-Targeted Infections in Malaria Rapid Diagnostic Tests: The Case of Human African Trypanosomiasis

PubMed Central

Gillet, Philippe; Mumba Ngoyi, Dieudonné; Lukuka, Albert; Kande, Viktor; Atua, Benjamin; van Griensven, Johan; Muyembe, Jean-Jacques; Jacobs, Jan; Lejon, Veerle

2013-01-01

Background In endemic settings, diagnosis of malaria increasingly relies on the use of rapid diagnostic tests (RDTs). False positivity of such RDTs is poorly documented, although it is especially relevant in those infections that resemble malaria, such as human African trypanosomiasis (HAT). We therefore examined specificity of malaria RDT products among patients infected with Trypanosoma brucei gambiense. Methodology/Principal Findings Blood samples of 117 HAT patients and 117 matched non-HAT controls were prospectively collected in the Democratic Republic of the Congo. Reference malaria diagnosis was based on real-time PCR. Ten commonly used malaria RDT products were assessed including three two-band and seven three-band products, targeting HRP-2, Pf-pLDH and/or pan-pLDH antigens. Rheumatoid factor was determined in PCR negative subjects. Specificity of the 10 malaria RDT products varied between 79.5 and 100% in HAT-negative controls and between 11.3 and 98.8% in HAT patients. For seven RDT products, specificity was significantly lower in HAT patients compared to controls. False positive reactions in HAT were mainly observed for pan-pLDH test lines (specificities between 13.8 and 97.5%), but also occurred frequently for the HRP-2 test line (specificities between 67.9 and 98.8%). The Pf-pLDH test line was not affected by false-positive lines in HAT patients (specificities between 97.5 and 100%). False positivity was not associated to rheumatoid factor, detected in 7.6% of controls and 1.2% of HAT patients. Conclusions/Significance Specificity of some malaria RDT products in HAT was surprisingly low, and constitutes a risk for misdiagnosis of a fatal but treatable infection. Our results show the importance to assess RDT specificity in non-targeted infections when evaluating diagnostic tests. PMID:23638201

Synthesis of most polyene natural product motifs using just twelve building blocks and one coupling reaction

PubMed Central

Woerly, Eric M.; Roy, Jahnabi; Burke, Martin D.

2014-01-01

The inherent modularity of polypeptides, oligonucleotides, and oligosaccharides has been harnessed to achieve generalized building block-based synthesis platforms. Importantly, like these other targets, most small molecule natural products are biosynthesized via iterative coupling of bifunctional building blocks. This suggests that many small molecules also possess inherent modularity commensurate with systematic building block-based construction. Supporting this hypothesis, here we report that the polyene motifs found in >75% of all known polyene natural products can be synthesized using just 12 building blocks and one coupling reaction. Using the same general retrosynthetic algorithm and reaction conditions, this platform enabled the synthesis of a wide range of polyene frameworks covering all of this natural product chemical space, and first total syntheses of the polyene natural products asnipyrone B, physarigin A, and neurosporaxanthin β-D-glucopyranoside. Collectively, these results suggest the potential for a more generalized approach for making small molecules in the laboratory. PMID:24848233

An Informatics Approach to Evaluating Combined Chemical Exposures from Consumer Products: A Case Study of Asthma-Associated Chemicals and Potential Endocrine Disruptors

PubMed Central

Gabb, Henry A.; Blake, Catherine

2016-01-01

Background: Simultaneous or sequential exposure to multiple environmental stressors can affect chemical toxicity. Cumulative risk assessments consider multiple stressors but it is impractical to test every chemical combination to which people are exposed. New methods are needed to prioritize chemical combinations based on their prevalence and possible health impacts. Objectives: We introduce an informatics approach that uses publicly available data to identify chemicals that co-occur in consumer products, which account for a significant proportion of overall chemical load. Methods: Fifty-five asthma-associated and endocrine disrupting chemicals (target chemicals) were selected. A database of 38,975 distinct consumer products and 32,231 distinct ingredient names was created from online sources, and PubChem and the Unified Medical Language System were used to resolve synonymous ingredient names. Synonymous ingredient names are different names for the same chemical (e.g., vitamin E and tocopherol). Results: Nearly one-third of the products (11,688 products, 30%) contained ≥ 1 target chemical and 5,229 products (13%) contained > 1. Of the 55 target chemicals, 31 (56%) appear in ≥ 1 product and 19 (35%) appear under more than one name. The most frequent three-way chemical combination (2-phenoxyethanol, methyl paraben, and ethyl paraben) appears in 1,059 products. Further work is needed to assess combined chemical exposures related to the use of multiple products. Conclusions: The informatics approach increased the number of products considered in a traditional analysis by two orders of magnitude, but missing/incomplete product labels can limit the effectiveness of this approach. Such an approach must resolve synonymy to ensure that chemicals of interest are not missed. Commonly occurring chemical combinations can be used to prioritize cumulative toxicology risk assessments. Citation: Gabb HA, Blake C. 2016. An informatics approach to evaluating combined chemical exposures from consumer products: a case study of asthma-associated chemicals and potential endocrine disruptors. Environ Health Perspect 124:1155–1165; http://dx.doi.org/10.1289/ehp.1510529 PMID:26955064

Covalent Ligand Discovery against Druggable Hotspots Targeted by Anti-cancer Natural Products.

PubMed

Grossman, Elizabeth A; Ward, Carl C; Spradlin, Jessica N; Bateman, Leslie A; Huffman, Tucker R; Miyamoto, David K; Kleinman, Jordan I; Nomura, Daniel K

2017-11-16

Many natural products that show therapeutic activities are often difficult to synthesize or isolate and have unknown targets, hindering their development as drugs. Identifying druggable hotspots targeted by covalently acting anti-cancer natural products can enable pharmacological interrogation of these sites with more synthetically tractable compounds. Here, we used chemoproteomic platforms to discover that the anti-cancer natural product withaferin A targets C377 on the regulatory subunit PPP2R1A of the tumor-suppressor protein phosphatase 2A (PP2A) complex leading to activation of PP2A activity, inactivation of AKT, and impaired breast cancer cell proliferation. We developed a more synthetically tractable cysteine-reactive covalent ligand, JNS 1-40, that selectively targets C377 of PPP2R1A to impair breast cancer signaling, proliferation, and in vivo tumor growth. Our study highlights the utility of using chemoproteomics to map druggable hotspots targeted by complex natural products and subsequently interrogating these sites with more synthetically tractable covalent ligands for cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Toxicity assessment of chlorpyrifos-degrading fungal bio-composites and their environmental risks.

PubMed

Liu, Jie; Zhang, Xiaoying; Yang, Mengran; Hu, Meiying; Zhong, Guohua

2018-02-01

Bioremediation techniques coupling with functional microorganisms have emerged as the most promising approaches for in-situ elimination of pesticide residue. However, the environmental safety of bio-products based on microorganisms or engineered enzymes was rarely known. Here, we described the toxicity assessment of two previously fabricated fungal bio-composites which were used for the biodegradation of chlorpyrifos, to clarify their potential risks on the environment and non-target organisms. Firstly, the acute and chronic toxicity of prepared bio-composites were evaluated using mice and rabbits, indicating neither acute nor chronic effect was induced via short-term or continuous exposure. Then, the acute mortality on zebrafish was investigated, which implied the application of fungal bio-composites had no lethal risk on aquatic organisms. Meanwhile, the assessment on soil organic matters suggested that no threat was posed to soil quality. Finally, by monitoring, the germination of cabbage was not affected by the exposure to two bio-products. Therefore, the application of fungal bio-composites for chlorpyrifos elimination cannot induce toxic risk to the environment and non-target organisms, which insured the safety of these engineered bio-products for realistic management of pesticide residue, and provided new insights for further development of bioremediation techniques based on functional microorganisms.

Maximizing Impact: Pairing interactive web visualizations with traditional print media

NASA Astrophysics Data System (ADS)

Read, E. K.; Appling, A.; Carr, L.; De Cicco, L.; Read, J. S.; Walker, J. I.; Winslow, L. A.

2016-12-01

Our Nation's rapidly growing store of environmental data makes new demands on researchers: to take on increasingly broad-scale, societally relevant analyses and to rapidly communicate findings to the public. Interactive web-based data visualizations now commonly supplement or comprise journalism, and science journalism has followed suit. To maximize the impact of US Geological Survey (USGS) science, the USGS Office of Water Information Data Science team builds tools and products that combine traditional static research products (e.g., print journal articles) with web-based, interactive data visualizations that target non-scientific audiences. We developed a lightweight, open-source framework for web visualizations to reduce time to production. The framework provides templates for a data visualization workflow and the packaging of text, interactive figures, and images into an appealing web interface with standardized look and feel, usage tracking, and responsiveness. By partnering with subject matter experts to focus on timely, societally relevant issues, we use these tools to produce appealing visual stories targeting specific audiences, including managers, the general public, and scientists, on diverse topics including drought, microplastic pollution, and fisheries response to climate change. We will describe the collaborative and technical methodologies used; describe some examples of how it's worked; and challenges and opportunities for the future.

Targeted delivery of TLR ligands to human and mouse dendritic cells strongly enhances adjuvanticity.

PubMed

Tacken, Paul J; Zeelenberg, Ingrid S; Cruz, Luis J; van Hout-Kuijer, Maaike A; van de Glind, Gerline; Fokkink, Remco G; Lambeck, Annechien J A; Figdor, Carl G

2011-12-22

Effective vaccines consist of 2 components: immunodominant antigens and effective adjuvants. Whereas it has been demonstrated that targeted delivery of antigens to dendritic cells (DCs) improves vaccine efficacy, we report here that co-targeting of TLR ligands (TLRLs) to DCs strongly enhances adjuvanticity and immunity. We encapsulated ligands for intracellular TLRs within biodegradable nanoparticles coated with Abs recognizing DC-specific receptors. Targeted delivery of TLRLs to human DCs enhanced the maturation and production of immune stimulatory cytokines and the Ag-specific activation of naive CD8(+) T cells. In vivo studies demonstrated that nanoparticles carrying Ag induced cytotoxic T-lymphocyte responses at 100-fold lower adjuvant dose when TLRLs were co-encapsulated instead of administered in soluble form. Moreover, the efficacy of these targeted TLRLs reduced the serum cytokine storm and related toxicity that is associated with administration of soluble TLRLs. We conclude that the targeted delivery of adjuvants may improve the efficacy and safety of DC-based vaccines.

Chasing helminths and their economic impact on farmed ruminants.

PubMed

Charlier, Johannes; van der Voort, Mariska; Kenyon, Fiona; Skuce, Philip; Vercruysse, Jozef

2014-07-01

Global agriculture will be required to intensify production from a shrinking natural resource base. Helminth infections of ruminants are a major constraint on efficient livestock production. The current challenge is to develop diagnostic methods that detect the production impact of helminth infections on farms in order to target control measures and contribute to the global challenge of preserving food security. We review here our understanding of the effects of helminth infections and control practices on productivity and the diagnostic tools that can inform on this. By combining advances in helminth laboratory diagnostics and animal health economics, sustainable management of helminth infections can be integrated into the whole-farm economic context. Copyright © 2014 Elsevier Ltd. All rights reserved.

Integrated process design for biocatalytic synthesis by a Leloir Glycosyltransferase: UDP-glucose production with sucrose synthase.

PubMed

Schmölzer, Katharina; Lemmerer, Martin; Gutmann, Alexander; Nidetzky, Bernd

2017-04-01

Nucleotide sugar-dependent ("Leloir") glycosyltransferases (GTs), represent a new paradigm for the application of biocatalytic glycosylations to the production of fine chemicals. However, it remains to be shown that GT processes meet the high efficiency targets of industrial biotransformations. We demonstrate in this study of uridine-5'-diphosphate glucose (UDP-glc) production by sucrose synthase (from Acidithiobacillus caldus) that a holistic process design, involving coordinated development of biocatalyst production, biotransformation, and downstream processing (DSP) was vital for target achievement at ∼100 g scale synthesis. Constitutive expression in Escherichia coli shifted the recombinant protein production mainly to the stationary phase and enhanced the specific enzyme activity to a level (∼480 U/g cell dry weight ) suitable for whole-cell biotransformation. The UDP-glc production had excellent performance metrics of ∼100 g product /L, 86% yield (based on UDP), and a total turnover number of 103 g UDP-glc /g cell dry weight at a space-time yield of 10 g/L/h. Using efficient chromatography-free DSP, the UDP-glc was isolated in a single batch with ≥90% purity and in 73% isolated yield. Overall, the process would allow production of ∼0.7 kg of isolated product/L E. coli bioreactor culture, thus demonstrating how integrated process design promotes the practical use of a GT conversion. Biotechnol. Bioeng. 2017;114: 924-928. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fine-Tuning of the Fatty Acid Pathway by Synthetic Antisense RNA for Enhanced (2S)-Naringenin Production from l-Tyrosine in Escherichia coli.

PubMed

Wu, Junjun; Yu, Oliver; Du, Guocheng; Zhou, Jingwen; Chen, Jian

2014-12-01

Malonyl coenzyme A (malonyl-CoA) is an important precursor for the synthesis of natural products, such as polyketides and flavonoids. The majority of this cofactor often is consumed for producing fatty acids and phospholipids, leaving only a small amount of cellular malonyl-CoA available for producing the target compound. The tuning of malonyl-CoA into heterologous pathways yields significant phenotypic effects, such as growth retardation and even cell death. In this study, fine-tuning of the fatty acid pathway in Escherichia coli with antisense RNA (asRNA) to balance the demands on malonyl-CoA for target-product synthesis and cell health was proposed. To establish an efficient asRNA system, the relationship between sequence and function for asRNA was explored. It was demonstrated that the gene-silencing effect of asRNA could be tuned by directing asRNA to different positions in the 5'-UTR (untranslated region) of the target gene. Based on this principle, the activity of asRNA was quantitatively tailored to balance the need for malonyl-CoA in cell growth and the production of the main flavonoid precursor, (2S)-naringenin. Appropriate inhibitory efficiency of the anti-fabB/fabF asRNA improved the production titer by 431% (391 mg/liter). Therefore, the strategy presented in this study provided a useful tool for the fine-tuning of endogenous gene expression in bacteria. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Low-Cost Bio-Based Carbon Fibers for High Temperature Processing

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

Paul, Ryan Michael; Naskar, Amit

GrafTech International Holdings Inc. (GTI), under Award No. DE-EE0005779, worked with Oak Ridge National Laboratory (ORNL) under CRADA No. NFE-15-05807 to develop lignin-based carbon fiber (LBCF) technology and to demonstrate LBCF performance in high-temperature products and applications. This work was unique and different from other reported LBCF work in that this study was application-focused and scalability-focused. Accordingly, the executed work was based on meeting criteria based on technology development, cost, and application suitability. High-temperature carbon fiber based insulation is used in energy intensive industries, such as metal heat treating and ceramic and semiconductor material production. Insulation plays a critical rolemore » in achieving high thermal and process efficiency, which is directly related to energy usage, cost, and product competitiveness. Current high temperature insulation is made with petroleum based carbon fibers, and one goal of this protect was to develop and demonstrate an alternative lignin (biomass) based carbon fiber that would achieve lower cost, CO2 emissions, and energy consumption and result in insulation that met or exceeded the thermal efficiency of current commercial insulation. In addition, other products were targeted to be evaluated with LBCF. As the project was designed to proceed in stages, the initial focus of this work was to demonstrate lab-scale LBCF from at least 4 different lignin precursor feedstock sources that could meet the estimated production cost of $5.00/pound and have ash level of less than 500 ppm in the carbonized insulation-grade fiber. Accordingly, a preliminary cost model was developed based on publicly available information. The team demonstrated that 4 lignin samples met the cost criteria. In addition, the ash level for the 4 carbonized lignin samples was below 500 ppm. Processing as-received lignin to produce a high purity lignin fiber was a significant accomplishment in that most industrial lignin, prior to purification, had greater than 4X the ash level needed for this project, and prior to this work there was not a clear path of how to achieve the purity target. The lab scale development of LBCF was performed with a specific functional application in mind, specifically for high temperature rigid insulation. GTI is a consumer of foreign-sourced pitch and rayon based carbon fibers for use in its high temperature insulation products, and the motivation was that LBCF had potential to decrease costs and increase product competitiveness in the marketplace through lowered raw material costs, lowered energy costs, and decreased environmental footprint. At the end of this project, the Technology Readiness Level (TRL) remained at 5 for LBCF in high temperature insulation.« less

Diversification of 99Mo/99mTc separation: non–fission reactor production of 99Mo as a strategy for enhancing 99mTc availability.

PubMed

Pillai, Maroor R A; Dash, Ashutosh; Knapp, Furn F Russ

2015-01-01

This paper discusses the benefits of obtaining (99m)Tc from non-fission reactor-produced low-specific-activity (99)Mo. This scenario is based on establishing a diversified chain of facilities for the distribution of (99m)Tc separated from reactor-produced (99)Mo by (n,γ) activation of natural or enriched Mo. Such facilities have expected lower investments than required for the proposed chain of cyclotrons for the production of (99m)Tc. Facilities can receive and process reactor-irradiated Mo targets then used for extraction of (99m)Tc over a period of 2 wk, with 3 extractions on the same day. Estimates suggest that a center receiving 1.85 TBq (50 Ci) of (99)Mo once every 4 d can provide 1.48-3.33 TBq (40-90 Ci) of (99m)Tc daily. This model can use research reactors operating in the United States to supply current (99)Mo needs by applying natural (nat)Mo targets. (99)Mo production capacity can be enhanced by using (98)Mo-enriched targets. The proposed model reduces the loss of (99)Mo by decay and avoids proliferation as well as waste management issues associated with fission-produced (99)Mo.

Design and synthesis of a biotinylated chemical probe for detecting the molecular targets of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin.

PubMed

Baker, Ysobel R; Galloway, Warren R J D; Hodgkinson, James T; Spring, David R

2013-09-25

Pseudomonas aeruginosa is a human pathogen associated with a variety of life-threatening nosocomial infections. This organism produces a range of virulence factors which actively cause damage to host tissues. One such virulence factor is pyocyanin, known to play a crucial role in the pathogenesis of P. aeruginosa infections. Previous studies had identified a novel compound capable of strongly inhibiting the production of pyocyanin. It was postulated that this inhibition results from modulation of an intercellular communication system termed quorum sensing, via direct binding of the compound with the LasR protein receptor. This raised the possibility that the compound could be an antagonist of quorum sensing in P. aeruginosa, which could have important implications as this intercellular signaling mechanism is known to regulate many additional facets of P. aeruginosa pathogenicity. However, there was no direct evidence for the binding of the active compound to LasR (or any other targets). Herein we describe the design and synthesis of a biotin-tagged version of the active compound. This could potentially be used as an affinity-based chemical probe to ascertain, in a direct fashion, the active compound's macromolecular biological targets, and thus better delineate the mechanism by which it reduces the level of pyocyanin production.

Low-enriched uranium high-density target project. Compendium report

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

Vandegrift, George; Brown, M. Alex; Jerden, James L.

2016-09-01

At present, most 99Mo is produced in research, test, or isotope production reactors by irradiation of highly enriched uranium targets. To achieve the denser form of uranium needed for switching from high to low enriched uranium (LEU), targets in the form of a metal foil (~125-150 µm thick) are being developed. The LEU High Density Target Project successfully demonstrated several iterations of an LEU-fission-based Mo-99 technology that has the potential to provide the world’s supply of Mo-99, should major producers choose to utilize the technology. Over 50 annular high density targets have been successfully tested, and the assembly and disassemblymore » of targets have been improved and optimized. Two target front-end processes (acidic and electrochemical) have been scaled up and demonstrated to allow for the high-density target technology to mate up to the existing producer technology for target processing. In the event that a new target processing line is started, the chemical processing of the targets is greatly simplified. Extensive modeling and safety analysis has been conducted, and the target has been qualified to be inserted into the High Flux Isotope Reactor, which is considered above and beyond the requirements for the typical use of this target due to high fluence and irradiation duration.« less

Systems metabolic engineering of Escherichia coli for production of the antitumor drugs violacein and deoxyviolacein.

PubMed

Rodrigues, André L; Trachtmann, Nathalie; Becker, Judith; Lohanatha, Ananta F; Blotenberg, Jana; Bolten, Christoph J; Korneli, Claudia; de Souza Lima, André O; Porto, Luismar M; Sprenger, Georg A; Wittmann, Christoph

2013-11-01

Violacein and deoxyviolacein are interesting therapeutics against pathogenic bacteria and viruses as well as tumor cells. In the present work, systems-wide metabolic engineering was applied to target Escherichia coli, a widely accepted recombinant host in pharmaceutical biotechnology, for production of these high-value products. The basic producer, E. coli dVio-1, that expressed the vioABCE cluster from Chromobacterium violaceum under control of the inducible araC system, accumulated 180 mg L(-1) of deoxyviolacein. Targeted intracellular metabolite analysis then identified bottlenecks in tryptophan supporting pathways, the major product building block. This was used for comprehensive engineering of serine, chorismate and tryptophan biosynthesis and the non-oxidative pentose-phosphate pathway. The final strain, E. coli dVio-6, accumulated 320 mg L(-1) deoxyviolacein in shake flask cultures. The created chassis of a high-flux tryptophan pathway was complemented by genomic integration of the vioD gene of Janthinobacterium lividum, which enabled exclusive production of violacein. In a fed-batch process, the resulting producer E. coli Vio-4 accumulated 710 mg L(-1) of the desired product. With straightforward broth extraction and subsequent crystallization, violacein could be obtained with 99.8% purity. This demonstrates the potential of E. coli as a platform for production of tryptophan based therapeutics. Copyright © 2013 Elsevier Inc. All rights reserved.

Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions.

PubMed

Lipinski, Christopher A

2016-06-01

The rule of five (Ro5), based on physicochemical profiles of phase II drugs, is consistent with structural limitations in protein targets and the drug target ligands. Three of four parameters in Ro5 are fundamental to the structure of both target and drug binding sites. The chemical structure of the drug ligand depends on the ligand chemistry and design philosophy. Two extremes of chemical structure and design philosophy exist; ligands constructed in the medicinal chemistry synthesis laboratory without input from natural selection and natural product (NP) metabolites biosynthesized based on evolutionary selection. Exceptions to Ro5 are found mostly among NPs. Chemistry chameleon-like behavior of some NPs due to intra-molecular hydrogen bonding as exemplified by cyclosporine A is a strong contributor to NP Ro5 outliers. The fragment derived, drug Navitoclax is an example of the extensive expertise, resources, time and key decisions required for the rare discovery of a non-NP Ro5 outlier. Copyright © 2016 Elsevier B.V. All rights reserved.

Regional price targets appropriate for advanced coal extraction

NASA Technical Reports Server (NTRS)

Terasawa, K. L.; Whipple, D. M.

1980-01-01

A methodology is presented for predicting coal prices in regional markets for the target time frames 1985 and 2000 that could subsequently be used to guide the development of an advanced coal extraction system. The model constructed is a supply and demand model that focuses on underground mining since the advanced technology is expected to be developed for these reserves by the target years. Coal reserve data and the cost of operating a mine are used to obtain the minimum acceptable selling price that would induce the producer to bring the mine into production. Based on this information, market supply curves can be generated. Demand by region is calculated based on an EEA methodology that emphasizes demand by electric utilities and demand by industry. The demand and supply curves are then used to obtain the price targets. The results show a growth in the size of the markets for compliance and low sulphur coal regions. A significant rise in the real price of coal is not expected even by the year 2000. The model predicts heavy reliance on mines with thick seams, larger block size and deep overburden.

Studies of Positron Generation from Ultraintense Laser-Matter Interactions

NASA Astrophysics Data System (ADS)

Williams, Gerald Jackson

Laser-produced pair jets possess unique characteristics that offer great potential for their use in laboratory-astrophysics experiments to study energetic phenomenon such as relativistic shock accelerations. High-flux, high-energy positron sources may also be used to study relativistic pair plasmas and useful as novel diagnostic tools for high energy density conditions. Copious amounts of positrons are produced with MeV energies from directly irradiating targets with ultraintense lasers where relativistic electrons, accelerated by the laser field, drive positron-electron pair production. Alternatively, laser wakefield accelerated electrons can produce pairs by the same mechanisms inside a secondary converter target. This dissertation describes a series of novel experiments that investigate the characteristics and scaling of pair production from ultraintense lasers, which are designed to establish a robust platform for laboratory-based relativistic pair plasmas. Results include a simple power-law scaling to estimate the effective positron yield for elemental targets for any Maxwellian electron source, typical of direct laser-target interactions. To facilitate these measurements, a solenoid electromagnetic coil was constructed to focus emitted particles, increasing the effective collection angle of the detector and enabling the investigation of pair production from thin targets and low-Z materials. Laser wakefield electron sources were also explored as a compact, high repetition rate platform for the production of high energy pairs with potential applications to the creation of charge-neutral relativistic pair plasmas. Plasma accelerators can produce low-divergence electron beams with energies approaching a GeV at Hz frequencies. It was found that, even for high-energy positrons, energy loss and scattering mechanisms in the target create a fundamental limit to the divergence and energy spectrum of the emitted positrons. The potential future application of laser-generated pairs was considered by exploring the feasibility of radiographing an imploding inertial confinement fusion capsule at ignition- relevant conditions. For an in-flight areal density of 0.02-0.2 g/cm2, currently available positron sources can make density and spatial measurements of deuterium-tritium fuel cores where additional complications of full-scale experiments are expected to reduce the measurement sensitivity.

Deuteron irradiation of W and WO 3 for production of high specific activity 186Re: Challenges associated with thick target preparation

DOE PAGES

Balkin, Ethan R.; Gagnon, Katherine; Strong, Kevin T.; ...

2016-06-28

This investigation evaluated target fabrication and beam parameters for scale-up production of high specific activity 186Re using deuteron irradiation of enriched 186W via the 186W(d,2n) 186Re reaction. Thick W and WO 3 targets were prepared, characterized and evaluated in deuteron irradiations. Full-thickness targets, as determined using SRIM, were prepared by uniaxi-ally pressing powdered natural abundance W and WO 3, or 96.86% enriched 186W, into Al target supports. Alternatively, thick targets were prepared by pressing 186W between two layers of graphite powder or by placing pre-sintered (1105°C, 12 hours) natural abundance WO 3 pellets into an Al target support. Assessments ofmore » structural integrity were made on each target pre-pared. Prior to irradiation, material composition analyses were conducted using SEM, XRD, and Raman spectroscopy. With-in a minimum of 24 hours post irradiation, gamma-ray spectroscopy was performed on all targets to assess production yields and radionuclidic byproducts. Problems were encountered with the structural integrity of some pressed W and WO 3 pellets before and during irradiation, and target material characterization results could be correlated with the structural integrity of the pressed target pellets. Under the conditions studied, the findings suggest that all WO 3 targets prepared and studied were unacceptable. By contrast, 186W metal was found to be a viable target material for 186Re production. Lastly, thick targets prepared with powdered 186W pressed between layers of graphite provided a particularly robust target configuration.« less

Deuteron irradiation of W and WO3 for production of high specific activity (186)Re: Challenges associated with thick target preparation.

PubMed

Balkin, Ethan R; Gagnon, Katherine; Strong, Kevin T; Smith, Bennett E; Dorman, Eric F; Emery, Robert C; Pauzauskie, Peter J; Fassbender, Michael E; Cutler, Cathy S; Ketring, Alan R; Jurisson, Silvia S; Wilbur, D Scott

2016-09-01

This investigation evaluated target fabrication and beam parameters for scale-up production of high specific activity (186)Re using deuteron irradiation of enriched (186)W via the (186)W(d,2n)(186)Re reaction. Thick W and WO3 targets were prepared, characterized and evaluated in deuteron irradiations. Full-thickness targets, as determined using SRIM, were prepared by uniaxially pressing powdered natural abundance W and WO3, or 96.86% enriched (186)W, into Al target supports. Alternatively, thick targets were prepared by pressing (186)W between two layers of graphite powder or by placing pre-sintered (1105°C, 12h) natural abundance WO3 pellets into an Al target support. Assessments of structural integrity were made on each target prepared. Prior to irradiation, material composition analyses were conducted using SEM, XRD, and Raman spectroscopy. Within a minimum of 24h post irradiation, gamma-ray spectroscopy was performed on all targets to assess production yields and radionuclidic byproducts. Problems were encountered with the structural integrity of some pressed W and WO3 pellets before and during irradiation, and target material characterization results could be correlated with the structural integrity of the pressed target pellets. Under the conditions studied, the findings suggest that all WO3 targets prepared and studied were unacceptable. By contrast, (186)W metal was found to be a viable target material for (186)Re production. Thick targets prepared with powdered (186)W pressed between layers of graphite provided a particularly robust target configuration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biosurfactants' Production from Renewable Natural Resources: Example of Innovativeand Smart Technology in Circular Bioeconomy

NASA Astrophysics Data System (ADS)

Satpute, Surekha K.; Płaza, Grażyna A.; Banpurkar, Arun G.

2017-03-01

A strong developed bio-based industrial sector will significantly reduce dependency on fossil resources, help the countries meet climate change targets, and lead to greener and more environmental friendly growth. The key is to develop new technologies to sustainably transform renewable natural resources into bio-based products and biofuels. Biomass is a valuable resource and many parameters need to be taken in to account when assessing its use and the products made from its. The bioeconomy encompass the production of renewable biological resources and their conversion into food, feed and bio-based products (chemicals, materials and fuels) via innovative and efficient technologies provided by industrial biotechnology. The paper presents the smart and efficient way to use the agro-industrial, dairy and food processing wastes for biosurfactant's production. Clarification processes are mandatory to use the raw substrates for microbial growth as well as biosurfactant production for commercial purposes. At the same time it is very essential to retain the nutritional values of those cheap substrates. Broad industrial perspectives can be achieved when quality as well as the quantity of the biosurfactant is considered in great depth. Since substrates resulting from food processing, dairy, animal fat industries are not explored in great details; and hence are potential areas which can be explored thoroughly.

Reinforcing Productivity in a Job-Skills Training Program for Unemployed Substance-Abusing Adults.

PubMed

Subramaniam, Shrinidhi; Everly, Jeffrey J; Silverman, Kenneth

2017-05-01

Chronically unemployed adults may benefit from intensive job-skills training; however, training programs do not always reliably engage participants in mastering skills. This study examined effects of voucher reinforcement for performance on a job-skills training program in the therapeutic workplace. Participants were four unemployed, substance abusing adults who earned monetary vouchers for working on programs targeting typing skills. Participants were exposed to two payment conditions that differed in whether or not pay was dependent on performance in a within-subject reversal design. In the productivity-pay condition, participants earned $8.00 per hour for attending the workplace plus a bonus for performance. In the base-pay condition, participants were paid an hourly wage that was equivalent to the total hourly earnings from the previous productivity-pay condition. Participants completed less work on the typing programs in the base- than the productivity-pay condition, but the amount of time spent in the workroom and the accuracy and rate of typing were not affected by the pay manipulation. All participants reported preferring base pay over productivity pay. Explicit reinforcement of productivity maintains consistent work in training programs, but more aspects of productivity pay need to be refined for effective, efficient, and socially valid implementation with unemployed, substance-abusing adults.

Reinforcing Productivity in a Job-Skills Training Program for Unemployed Substance-Abusing Adults

PubMed Central

Subramaniam, Shrinidhi; Everly, Jeffrey J.; Silverman, Kenneth

2017-01-01

Chronically unemployed adults may benefit from intensive job-skills training; however, training programs do not always reliably engage participants in mastering skills. This study examined effects of voucher reinforcement for performance on a job-skills training program in the therapeutic workplace. Participants were four unemployed, substance abusing adults who earned monetary vouchers for working on programs targeting typing skills. Participants were exposed to two payment conditions that differed in whether or not pay was dependent on performance in a within-subject reversal design. In the productivity-pay condition, participants earned $8.00 per hour for attending the workplace plus a bonus for performance. In the base-pay condition, participants were paid an hourly wage that was equivalent to the total hourly earnings from the previous productivity-pay condition. Participants completed less work on the typing programs in the base- than the productivity-pay condition, but the amount of time spent in the workroom and the accuracy and rate of typing were not affected by the pay manipulation. All participants reported preferring base pay over productivity pay. Explicit reinforcement of productivity maintains consistent work in training programs, but more aspects of productivity pay need to be refined for effective, efficient, and socially valid implementation with unemployed, substance-abusing adults. PMID:28824954

Systems metabolic engineering: the creation of microbial cell factories by rational metabolic design and evolution.

PubMed

Furusawa, Chikara; Horinouchi, Takaaki; Hirasawa, Takashi; Shimizu, Hiroshi

2013-01-01

It is widely acknowledged that in order to establish sustainable societies, production processes should shift from petrochemical-based processes to bioprocesses. Because bioconversion technologies, in which biomass resources are converted to valuable materials, are preferable to processes dependent on fossil resources, the former should be further developed. The following two approaches can be adopted to improve cellular properties and obtain high productivity and production yield of target products: (1) optimization of cellular metabolic pathways involved in various bioprocesses and (2) creation of stress-tolerant cells that can be active even under severe stress conditions in the bioprocesses. Recent progress in omics analyses has facilitated the analysis of microorganisms based on bioinformatics data for molecular breeding and bioprocess development. Systems metabolic engineering is a new area of study, and it has been defined as a methodology in which metabolic engineering and systems biology are integrated to upgrade the designability of industrially useful microorganisms. This chapter discusses multi-omics analyses and rational design methods for molecular breeding. The first is an example of the rational design of metabolic networks for target production by flux balance analysis using genome-scale metabolic models. Recent progress in the development of genome-scale metabolic models and the application of these models to the design of desirable metabolic networks is also described in this example. The second is an example of evolution engineering with omics analyses for the creation of stress-tolerant microorganisms. Long-term culture experiments to obtain the desired phenotypes and omics analyses to identify the phenotypic changes are described here.

A fungal biofilm reactor based on metal structured packing improves the quality of a Gla::GFP fusion protein produced by Aspergillus oryzae.

PubMed

Zune, Q; Delepierre, A; Gofflot, S; Bauwens, J; Twizere, J C; Punt, P J; Francis, F; Toye, D; Bawin, T; Delvigne, F

2015-08-01

Fungal biofilm is known to promote the excretion of secondary metabolites in accordance with solid-state-related physiological mechanisms. This work is based on the comparative analysis of classical submerged fermentation with a fungal biofilm reactor for the production of a Gla::green fluorescent protein (GFP) fusion protein by Aspergillus oryzae. The biofilm reactor comprises a metal structured packing allowing the attachment of the fungal biomass. Since the production of the target protein is under the control of the promoter glaB, specifically induced in solid-state fermentation, the biofilm mode of culture is expected to enhance the global productivity. Although production of the target protein was enhanced by using the biofilm mode of culture, we also found that fusion protein production is also significant when the submerged mode of culture is used. This result is related to high shear stress leading to biomass autolysis and leakage of intracellular fusion protein into the extracellular medium. Moreover, 2-D gel electrophoresis highlights the preservation of fusion protein integrity produced in biofilm conditions. Two fungal biofilm reactor designs were then investigated further, i.e. with full immersion of the packing or with medium recirculation on the packing, and the scale-up potentialities were evaluated. In this context, it has been shown that full immersion of the metal packing in the liquid medium during cultivation allows for a uniform colonization of the packing by the fungal biomass and leads to a better quality of the fusion protein.

New Fragment Separation Technology for Superheavy Element Research

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

Shaughnessy, D A; Moody, K J; Henderson, R A

2008-01-28

This project consisted of three major research areas: (1) development of a solid Pu ceramic target for the MASHA separator, (2) chemical separation of nuclear decay products, and (3) production of new isotopes and elements through nuclear reactions. There have been 16 publications as a result of this project, and this collection of papers summarizes our accomplishments in each of the three areas of research listed above. The MASHA (Mass Analyzer for Super-Heavy Atoms) separator is being constructed at the U400 Cyclotron at the Flerov Laboratory of Nuclear Reactions in Dubna, Russia. The purpose of the separator is to physicallymore » separate the products from nuclear reactions based on their isotopic masses rather than their decay characteristics. The separator was designed to have a separation between isotopic masses of {+-}0.25 amu, which would enable the mass of element 114 isotopes to be measured with outstanding resolution, thereby confirming their discovery. In order to increase the production rate of element 114 nuclides produced via the {sup 244}Pu+{sup 48}Ca reaction, a new target technology was required. Instead of a traditional thin actinide target, the MASHA separator required a thick, ceramic-based Pu target that was thick enough to increase element 114 production while still being porous enough to allow reaction products to migrate out of the target and travel through the separator to the detector array located at the back end. In collaboration with UNLV, we began work on development of the Pu target for MASHA. Using waste-form synthesis technology, we began by creating zirconia-based matrices that would form a ceramic with plutonium oxide. We used samarium oxide as a surrogate for Pu and created ceramics that had varying amounts of the starting materials in order to establish trends in material density and porosity. The results from this work are described in more detail in Refs. [1,4,10]. Unfortunately, work on MASHA was delayed in Russia because it was found that the efficiency of transporting products from the target chamber to the detector array was much too low for applications in heavy element experiments where production rates are on the order of one atom per day or less. Work continues on the MASHA separator, and once the efficiency has been improved, we plan to continue our work on the Pu target for future element 114 experiments. Due to the delays of the MASHA separator, work on establishing the identity of heavy element species produced through nuclear reactions focused instead on chemical separations. In particular, element 115 decays through a series of alpha decays, terminating with an element 105 isotope with a long half-life ({approx} 1 day). By chemically separating the element 105 daughter and observing its subsequent fission decay, the identity of the original parent nucleus can be established through the genetic correlation of the initial series of alpha decays. Chemical separations of element 105 were developed in Switzerland, Russia, and at LLNL. Over the course of two experiments, reaction products from the {sup 243}Am+{sup 48}Ca reaction were collected in a copper block and subsequently processed for chemical separation of the Group Five elements [8,9,13,15]. The Group Five elements were initially separated from the Group Four species, and then the samples were sub-divided into tantalum and niobium fractions. All of the fission events were observed in the tantalum fractions, which implied that element 105 behaved more like tantalum under the chemical conditions of these experiments. These experiments were very successful, and not only demonstrated that chemical separation could be performed on single atoms of interest, but also lent proof to the identity of the parent nucleus as element 115. Subsequent analysis of the alpha spectra taken during the experiment further prove that the fission events observed during the two experiments came from element 105 as the decay daughter of element 115 and could not attributed to interference from other background species [16]. The final aspect of this project was the production of new isotopes and elements. All of the experiments were performed in Dubna at the U400 Cyclotron and the results are described in more detail in Refs. [2,3,5-8,11,12,14]. The first experiments were designed to establish the decay properties of isotopes of elements 112, 114, and 116 [5]. Because these isotopic signatures were established through these initial experiments, the discovery of element 118 [11] was possible, since the 118 nuclides decayed into these previously studied isotopes. This was the first successful report of the discovery of element 118, which was reported by the media to a large extent. The last experiment that was performed for this project was the production and detection of a new isotope of element 113 [14].« less

Emerging therapeutic delivery capabilities and challenges utilizing enzyme/protein packaged bacterial vesicles.

PubMed

Alves, Nathan J; Turner, Kendrick B; Medintz, Igor L; Walper, Scott A

2015-07-01

Nanoparticle-based therapeutics are poised to play a critical role in treating disease. These complex multifunctional drug delivery vehicles provide for the passive and active targeted delivery of numerous small molecule, peptide and protein-derived pharmaceuticals. This article will first discuss some of the current state of the art nanoparticle classes (dendrimers, lipid-based, polymeric and inorganic), highlighting benefits/drawbacks associated with their implementation. We will then discuss an emerging class of nanoparticle therapeutics, bacterial outer membrane vesicles, that can provide many of the nanoparticle benefits while simplifying assembly. Through molecular biology techniques; outer membrane vesicle hijacking potentially allows for stringent control over nanoparticle production allowing for targeted protein packaged nanoparticles to be fully synthesized by bacteria.

A study of swing-curve physics in diffraction-based overlay

NASA Astrophysics Data System (ADS)

Bhattacharyya, Kaustuve; den Boef, Arie; Storms, Greet; van Heijst, Joost; Noot, Marc; An, Kevin; Park, Noh-Kyoung; Jeon, Se-Ra; Oh, Nang-Lyeom; McNamara, Elliott; van de Mast, Frank; Oh, SeungHwa; Lee, Seung Yoon; Hwang, Chan; Lee, Kuntack

2016-03-01

With the increase of process complexity in advanced nodes, the requirements of process robustness in overlay metrology continues to tighten. Especially with the introduction of newer materials in the film-stack along with typical stack variations (thickness, optical properties, profile asymmetry etc.), the signal formation physics in diffraction-based overlay (DBO) becomes an important aspect to apply in overlay metrology target and recipe selection. In order to address the signal formation physics, an effort is made towards studying the swing-curve phenomena through wavelength and polarizations on production stacks using simulations as well as experimental technique using DBO. The results provide a wealth of information on target and recipe selection for robustness. Details from simulation and measurements will be reported in this technical publication.

Optical model calculations of heavy-ion target fragmentation

NASA Technical Reports Server (NTRS)

Townsend, L. W.; Wilson, J. W.; Cucinotta, F. A.; Norbury, J. W.

1986-01-01

The fragmentation of target nuclei by relativistic protons and heavy ions is described within the context of a simple abrasion-ablation-final-state interaction model. Abrasion is described by a quantum mechanical formalism utilizing an optical model potential approximation. Nuclear charge distributions of the excited prefragments are calculated by both a hypergeometric distribution and a method based upon the zero-point oscillations of the giant dipole resonance. Excitation energies are estimated from the excess surface energy resulting from the abrasion process and the additional energy deposited by frictional spectator interactions of the abraded nucleons. The ablation probabilities are obtained from the EVA-3 computer program. Isotope production cross sections for the spallation of copper targets by relativistic protons and for the fragmenting of carbon targets by relativistic carbon, neon, and iron projectiles are calculated and compared with available experimental data.

Development and Validation of a Qualitative Method for Target Screening of 448 Pesticide Residues in Fruits and Vegetables Using UHPLC/ESI Q-Orbitrap Based on Data-Independent Acquisition and Compound Database.

PubMed

Wang, Jian; Chow, Willis; Chang, James; Wong, Jon W

2017-01-18

A semiautomated qualitative method for target screening of 448 pesticide residues in fruits and vegetables was developed and validated using ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC/ESI Q-Orbitrap). The Q-Orbitrap Full MS/dd-MS 2 (data dependent acquisition) was used to acquire product-ion spectra of individual pesticides to build a compound database or an MS library, while its Full MS/DIA (data independent acquisition) was utilized for sample data acquisition from fruit and vegetable matrices fortified with pesticides at 10 and 100 μg/kg for target screening purpose. Accurate mass, retention time and response threshold were three key parameters in a compound database that were used to detect incurred pesticide residues in samples. The concepts and practical aspects of in-spectrum mass correction or solvent background lock-mass correction, retention time alignment and response threshold adjustment are discussed while building a functional and working compound database for target screening. The validated target screening method is capable of screening at least 94% and 99% of 448 pesticides at 10 and 100 μg/kg, respectively, in fruits and vegetables without having to evaluate every compound manually during data processing, which significantly reduced the workload in routine practice.

Method to amplify variable sequences without imposing primer sequences

DOEpatents

Bradbury, Andrew M.; Zeytun, Ahmet

2006-11-14

The present invention provides methods of amplifying target sequences without including regions flanking the target sequence in the amplified product or imposing amplification primer sequences on the amplified product. Also provided are methods of preparing a library from such amplified target sequences.

Enrichment Clusters: A Practical Plan for Real-World, Student-Driven Learning.

ERIC Educational Resources Information Center

Renzulli, Joseph S.; Gentry, Marcia; Reis, Sally M.

This guidebook provides a rationale and guidelines for implementing a student-driven learning approach using enrichment clusters. Enrichment clusters allow students who share a common interest to meet each week to produce a product, performance, or targeted service based on that common interest. Chapter 1 discusses different models of learning.…

Linking Air Land & Water to Examine the Vulnerability of Groundwater Nitrate Contamination from Increased Corn Production

EPA Science Inventory

The Renewable Fuel Standard (RFS) requires oil refiners to reach a target of 15 billion gallons of corn-based ethanol by 2022. However, there are concerns that the broad-scale use of corn as a source of ethanol may lead to unintended economic and environmental consequences. Thi...

The Role of Metaphorical Thinking in the Creativity of Scientific Discourse

ERIC Educational Resources Information Center

Sanchez-Ruiz, Maria-Jose; Santos, Manuela Romo; Jiménez, Juan Jiménez

2013-01-01

This article critically reviews the extant literature on scientific creativity and metaphorical thinking. Metaphorical thinking is based on a conceptual transfer of relationships or mapping, from a well-known source domain to a poorly known target domain, which could result in creative outcomes in sciences. Creativity leads to products that are…

Evaluation of agronomic and economic benefits of using RTK-GPS-based auto-steer guidance systems for peanut digging operations

USDA-ARS?s Scientific Manuscript database

Increasing the peanut (Arachis hypogea L.) digger efficiency by accurate placement over the target rows could minimize damaged pods and yield losses. Producers have traditionally relied solely on tractor operator skills to harvest peanuts. However, as peanut production has shifted to new growing reg...

Promotional Video Production in a Foreign Language Course.

ERIC Educational Resources Information Center

Fukushima, Tatsuya

2002-01-01

Discusses a technology-based project as a requirement for a traditional intermediate Japanese course at the University of Arkansas in which students worked in a small group to produce the university's promotional video in the target language, thus enhancing their Japanese language skills and promoting the program to the public. (Author/VWL)

Differences in Characteristics of Online versus Traditional Students: Implications for Target Marketing

ERIC Educational Resources Information Center

Pentina, Iryna; Neeley, Concha

2007-01-01

This study provides insight for educators and administrators into differences between students enrolled in Web-based and traditional classes as online learning enters the growth stage of its product life cycle. We identify characteristics that differentiate online students from those who prefer traditional education methods in order to offer more…

[On-Orbit Multispectral Sensor Characterization Based on Spectral Tarps].

PubMed

Li, Xin; Zhang, Li-ming; Chen, Hong-yao; Xu, Wei-wei

2016-03-01

The multispectral remote sensing technology has been a primary means in the research of biomass monitoring, climate change, disaster prediction and etc. The spectral sensitivity is essential in the quantitative analysis of remote sensing data. When the sensor is running in the space, it will be influenced by cosmic radiation, severe change of temperature, chemical molecular contamination, cosmic dust and etc. As a result, the spectral sensitivity will degrade by time, which has great implication on the accuracy and consistency of the physical measurements. This paper presents a characterization method of the degradation based on man-made spectral targets. Firstly, a degradation model is established in the paper. Then, combined with equivalent reflectance of spectral targets measured and inverted from image, the degradation characterization can be achieved. The simulation and on orbit experiment results showed that, using the proposed method, the change of center wavelength and band width can be monotored. The method proposed in the paper has great significance for improving the accuracy of long time series remote sensing data product and comprehensive utilization level of multi sensor data products.

Comparing extraction rates of fossil fuel producers against global climate goals

NASA Astrophysics Data System (ADS)

Rekker, Saphira A. C.; O'Brien, Katherine R.; Humphrey, Jacquelyn E.; Pascale, Andrew C.

2018-06-01

Meeting global and national climate goals requires action and cooperation from a multitude of actors1,2. Current methods to define greenhouse gas emission targets for companies fail to acknowledge the unique influence of fossil fuel producers: combustion of reported fossil fuel reserves has the potential to push global warming above 2 °C by 2050, regardless of other efforts to mitigate climate change3. Here, we introduce a method to compare the extraction rates of individual fossil fuel producers against global climate targets, using two different approaches to quantify a burnable fossil fuel allowance (BFFA). BFFAs are calculated and compared with cumulative extraction since 2010 for the world's ten largest investor-owned companies and ten largest state-owned entities (SOEs), for oil and for gas, which together account for the majority of global oil and gas reserves and production. The results are strongly influenced by how BFFAs are quantified; allocating based on reserves favours SOEs over investor-owned companies, while allocating based on production would require most reduction to come from SOEs. Future research could refine the BFFA to account for equity, cost-effectiveness and emissions intensity.

MaRiMba: a software application for spectral library-based MRM transition list assembly.

PubMed

Sherwood, Carly A; Eastham, Ashley; Lee, Lik Wee; Peterson, Amelia; Eng, Jimmy K; Shteynberg, David; Mendoza, Luis; Deutsch, Eric W; Risler, Jenni; Tasman, Natalie; Aebersold, Ruedi; Lam, Henry; Martin, Daniel B

2009-10-01

Multiple reaction monitoring mass spectrometry (MRM-MS) is a targeted analysis method that has been increasingly viewed as an avenue to explore proteomes with unprecedented sensitivity and throughput. We have developed a software tool, called MaRiMba, to automate the creation of explicitly defined MRM transition lists required to program triple quadrupole mass spectrometers in such analyses. MaRiMba creates MRM transition lists from downloaded or custom-built spectral libraries, restricts output to specified proteins or peptides, and filters based on precursor peptide and product ion properties. MaRiMba can also create MRM lists containing corresponding transitions for isotopically heavy peptides, for which the precursor and product ions are adjusted according to user specifications. This open-source application is operated through a graphical user interface incorporated into the Trans-Proteomic Pipeline, and it outputs the final MRM list to a text file for upload to MS instruments. To illustrate the use of MaRiMba, we used the tool to design and execute an MRM-MS experiment in which we targeted the proteins of a well-defined and previously published standard mixture.

Quantitative competitive (QC) PCR for quantification of porcine DNA.

PubMed

Wolf, C; Lüthy, J

2001-02-01

Many meat products nowadays may contain several species in different proportions. To protect consumers from fraud and misdeclarations, not only a qualitative but also a quantitative monitoring of ingredients of complex food products is necessary. DNA based techniques like the polymerase chain reaction (PCR) are widely used for identification of species but no answer to the proportional amount of a certain species could be given using current techniques. In this study we report the development and evaluation of a quantitative competitive polymerase chain reaction (QC-PCR) for detection and quantification of porcine DNA using a new porcine specific PCR system based on the growth hormone gene of sus scrofa. A DNA competitor differing by 30 bp in length from the porcine target sequence was constructed and used for PCR together with the target DNA. Specificity of the new primers was evaluated with DNA from cattle, sheep, chicken and turkey. The competitor concentration was adjusted to porcine DNA contents of 2 or 20% by coamplification of mixtures containing porcine and corresponding amounts of bovine DNA in defined ratios.

Calculations of high-power production target and beamdump for the GSI future Super-FRS for a fast extraction scheme at the FAIR Facility

NASA Astrophysics Data System (ADS)

Tahir, N. A.; Weick, H.; Iwase, H.; Geissel, H.; Hoffmann, D. H. H.; Kindler, B.; Lommel, B.; Radon, T.; Münzenberg, G.; Shutov, A.; Sümmerer, K.; Winkler, M.

2005-06-01

A superconducting fragment separator (Super-FRS) is being designed for the production and separation of radioactive isotopes at the future FAIR (Facility for Antiprotons and Ion Research) facility at Darmstadt. This paper discusses various aspects and requirements for the high-power production target that will be used in the Super-FRS experiments. The production target must survive over an extended period of time as it will be used during the course of many experiments. The specific power deposited by the high intensity beam that will be generated at the future FAIR facility will be high enough to destroy the target in most of the cases as a result of a single shot from the new heavy ion synchrotrons SIS100/300. By using an appropriate beam intensity and focal spot parameters, the target would survive after being irradiated once. However, the heat should be dissipated efficiently before the same target area is irradiated again. We have considered a wheel shaped solid carbon target that rotates around its axis so that different areas of the target are irradiated successively. This allows for cooling of the beam heated region by thermal conduction before the same part of the target is irradiated a second time. Another attractive option is to use a liquid jet target at the Super-FRS. First calculations of a possible liquid lithium target are also presented in this paper. One of the advantages of using lithium as a target is that it will survive even if one uses a smaller focal spot, which has half the area of that used for a solid carbon target. This will significantly improve the isotope resolution. A similar problem associated with these experiments will be safe deposition of the beam energy in a beamdump after its interaction with the production target. We also present calculations to study the suitability of a proposed beamdump.

Trends in greenhouse gas emissions from consumption and production of animal food products - implications for long-term climate targets.

PubMed

Cederberg, C; Hedenus, F; Wirsenius, S; Sonesson, U

2013-02-01

To analyse trends in greenhouse gas (GHG) emissions from production and consumption of animal products in Sweden, life cycle emissions were calculated for the average production of pork, chicken meat, beef, dairy and eggs in 1990 and 2005. The calculated average emissions were used together with food consumption statistics and literature data on imported products to estimate trends in per capita emissions from animal food consumption. Total life cycle emissions from the Swedish livestock production were around 8.5 Mt carbon dioxide equivalents (CO2e) in 1990 and emissions decreased to 7.3 Mt CO2e in 2005 (14% reduction). Around two-thirds of the emission cut was explained by more efficient production (less GHG emission per product unit) and one-third was due to a reduced animal production. The average GHG emissions per product unit until the farm-gate were reduced by 20% for dairy, 15% for pork and 23% for chicken meat, unchanged for eggs and increased by 10% for beef. A larger share of the average beef was produced from suckler cows in cow-calf systems in 2005 due to the decreasing dairy cow herd, which explains the increased emissions for the average beef in 2005. The overall emission cuts from the livestock sector were a result of several measures taken in farm production, for example increased milk yield per cow, lowered use of synthetic nitrogen fertilisers in grasslands, reduced losses of ammonia from manure and a switch to biofuels for heating in chicken houses. In contrast to production, total GHG emissions from the Swedish consumption of animal products increased by around 22% between 1990 and 2005. This was explained by strong growth in meat consumption based mainly on imports, where growth in beef consumption especially was responsible for most emission increase over the 15-year period. Swedish GHG emissions caused by consumption of animal products reached around 1.1 t CO2e per capita in 2005. The emission cuts necessary for meeting a global temperature-increase target of 2° might imply a severe constraint on the long-term global consumption of animal food. Due to the relatively limited potential for reducing food-related emissions by higher productivity and technological means, structural changes in food consumption towards less emission-intensive food might be required for meeting the 2° target.

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

Hurt, Christopher J.; Freels, James D.; Hobbs, Randy W.

There has been a considerable effort over the previous few years to demonstrate and optimize the production of plutonium-238 ( 238Pu) at the High Flux Isotope Reactor (HFIR). This effort has involved resources from multiple divisions and facilities at the Oak Ridge National Laboratory (ORNL) to demonstrate the fabrication, irradiation, and chemical processing of targets containing neptunium-237 ( 237Np) dioxide (NpO 2)/aluminum (Al) cermet pellets. A critical preliminary step to irradiation at the HFIR is to demonstrate the safety of the target under irradiation via documented experiment safety analyses. The steady-state thermal safety analyses of the target are simulated inmore » a finite element model with the COMSOL Multiphysics code that determines, among other crucial parameters, the limiting maximum temperature in the target. Safety analysis efforts for this model discussed in the present report include: (1) initial modeling of single and reduced-length pellet capsules in order to generate an experimental knowledge base that incorporate initial non-linear contact heat transfer and fission gas equations, (2) modeling efforts for prototypical designs of partially loaded and fully loaded targets using limited available knowledge of fabrication and irradiation characteristics, and (3) the most recent and comprehensive modeling effort of a fully coupled thermo-mechanical approach over the entire fully loaded target domain incorporating burn-up dependent irradiation behavior and measured target and pellet properties, hereafter referred to as the production model. These models are used to conservatively determine several important steady-state parameters including target stresses and temperatures, the limiting condition of which is the maximum temperature with respect to the melting point. The single pellet model results provide a basis for the safety of the irradiations, followed by parametric analyses in the initial prototypical designs that were necessary due to the limiting fabrication and irradiation data available. The calculated parameters in the final production target model are the most accurate and comprehensive, while still conservative. Over 210 permutations in irradiation time and position were evaluated, and are supported by the most recent inputs and highest fidelity methodology. The results of these analyses show that the models presented in this report provide a robust and reliable basis for previous, current and future experiment safety analyses. In addition, they reveal an evolving knowledge of the steady-state behavior of the NpO 2/Al pellets under irradiation for a variety of target encapsulations and potential conditions.« less

[Status of traditional Chinese medicine materials seed and seedling breeding bases].

PubMed

Li, Ying; Huang, Lu-Qi; Zhang, Xiao-Bo; Wang, Hui; Cheng, Meng; Zhang, Tian; Yang, Guang

2017-11-01

Seeds and seedlings are the material basis of traditional Chinese medicine materials production, and the construction of traditional Chinese medicine materials seed and seedling breeding bases is beneficial to the production of high-quality traditional Chinese medicine materials. The construction of traditional Chinese medicine materials seed and seedling breeding bases is one of the major topics of Chinese medica resources census pilot. Targets, tasks of traditional Chinese medicine materials seed and seedling breeding bases based on Chinese medica resources census pilot were expounded.Construction progress including hardware construction, germplasm conservation and breeding, procedures and standardsestablishment, social servicesare presented. Development counter measures were proposed for the next step: perfect the standard and system, maintain and strengthen the breeding function, strengthen the cultivation of multi-level talents, explore market development model, joint efforts to deepen services and development. Copyright© by the Chinese Pharmaceutical Association.

Underexplored Opportunities for Natural Products in Drug Discovery.

PubMed

DeCorte, Bart L

2016-10-27

The importance of natural products in the treatment of human disease is well documented. While natural products continue to have a profound impact on human health, chemists have succeeded in generating semisynthetic analogues that sometimes overshadow the original natural product in terms of clinical significance. Synthetic efforts based on natural products have primarily focused on improving their drug-like features while targeting utility in the same biological space. A less documented phenomenon is that natural products can serve as powerful starting materials to generate drug substances with novel therapeutic utility that is unrelated to the biological space of the natural product starting material. In this Perspective, examples of natural product derived marketed drugs with therapeutic utility in clinical space that is different from the biological profile of the starting material are presented, demonstrating that this is not merely a theoretical concept but both a clinical reality and an underexplored opportunity.

An enzyme-free and label-free surface plasmon resonance biosensor for ultrasensitive detection of fusion gene based on DNA self-assembly hydrogel with streptavidin encapsulation.

PubMed

Guo, Bin; Wen, Bo; Cheng, Wei; Zhou, Xiaoyan; Duan, Xiaolei; Zhao, Min; Xia, Qianfeng; Ding, Shijia

2018-07-30

In this research, an enzyme-free and label-free surface plasmon resonance (SPR) biosensing strategy has been developed for ultrasensitive detection of fusion gene based on the heterogeneous target-triggered DNA self-assembly aptamer-based hydrogel with streptavidin (SA) encapsulation. In the presence of target, the capture probes (Cp) immobilized on the chip surface can capture the PML/RARα, forming a Cp-PML/RARα duplex. After that, the aptamer-based network hydrogel nanostructure is formed on the gold surface via target-triggered self-assembly of X shaped polymers. Subsequently, the SA can be encapsulated into hydrogel by the specific binding of SA aptamer, forming the complex with super molecular weight. Thus, the developed strategy achieves dramatic enhancement of the SPR signal. Using PML/RARα "S" subtype as model analyte, the developed biosensing method can detect target down to 45.22 fM with a wide linear range from 100 fM to 10 nM. Moreover, the high efficiency biosensing method shows excellent practical ability to identify the clinical PCR products of PML/RARα. Thus, this proposed strategy presents a powerful platform for ultrasensitive detection of fusion gene and early diagnosis and monitoring of disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Pharmaceutical product development: A quality by design approach

PubMed Central

Pramod, Kannissery; Tahir, M. Abu; Charoo, Naseem A.; Ansari, Shahid H.; Ali, Javed

2016-01-01

The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development. PMID:27606256

Pharmaceutical product development: A quality by design approach.

PubMed

Pramod, Kannissery; Tahir, M Abu; Charoo, Naseem A; Ansari, Shahid H; Ali, Javed

2016-01-01

The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development.

High-intensity positron microprobe at the Thomas Jefferson National Accelerator Facility

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

Golge, S., E-mail: serkan.golge@nasa.gov; Vlahovic, B.; Wojtsekhowski, B.

We present a conceptual design for a novel continuous wave electron-linac based high-intensity high-brightness slow-positron production source with a projected intensity on the order of 10{sup 10 }e{sup +}/s. Reaching this intensity in our design relies on the transport of positrons (T{sub +} below 600 keV) from the electron-positron pair production converter target to a low-radiation and low-temperature area for moderation in a high-efficiency cryogenic rare gas moderator, solid Ne. This design progressed through Monte Carlo optimizations of: electron/positron beam energies and converter target thickness, transport of the e{sup +} beam from the converter to the moderator, extraction of the e{sup +}more » beam from the magnetic channel, a synchronized raster system, and moderator efficiency calculations. For the extraction of e{sup +} from the magnetic channel, a magnetic field terminator plug prototype has been built and experimental results on the effectiveness of the prototype are presented. The dissipation of the heat away from the converter target and radiation protection measures are also discussed.« less

Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

PubMed

Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

2015-08-01

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

PubMed Central

Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

2015-01-01

Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

Discovery of the leinamycin family of natural products by mining actinobacterial genomes

PubMed Central

Xu, Zhengren; Guo, Zhikai; Hindra; Ma, Ming; Zhou, Hao; Gansemans, Yannick; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Cheng, Jinhua; Van Nieuwerburgh, Filip; Suh, Joo-Won; Duan, Yanwen

2017-01-01

Nature’s ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF–SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF–SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature’s rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature’s biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity. PMID:29229819

Discovery of the leinamycin family of natural products by mining actinobacterial genomes.

PubMed

Pan, Guohui; Xu, Zhengren; Guo, Zhikai; Hindra; Ma, Ming; Yang, Dong; Zhou, Hao; Gansemans, Yannick; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Cheng, Jinhua; Van Nieuwerburgh, Filip; Suh, Joo-Won; Duan, Yanwen; Shen, Ben

2017-12-26

Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm -type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.

Routine {sup 18}F{sup -} production with 180 {mu}A to 200 {mu}A target beam current on a GE PETtrace 800 cyclotron

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

Eberl, S.; Eriksson, T.; Svedberg, O.

2012-12-19

Through upgrades and enhancements, which are now standard on current PETtrace 800 cyclotrons, a GE PETtrace cyclotron installed in 2002 has demonstrated reliable routine [{sup 18}F]FDG production at total target beam currents of 180 {mu}A without detriment to saturation and [{sup 18}F]FDG yields. Routine production at 200 {mu}A has been achieved and its evaluation is continuing. Self-shielded target using W/Cu alloy for the target body afforded a reduction in dose rate from the Havar foils by a factor of {approx} 8-10, reducing dose from the targets and need for removing targets during maintenance. The main activation product in the shieldmore » is {sup 187}W (T1/2 24 h). The {sup 60}Co ((T1/2 5.3 y) activation is about 250 times less at 24 h post EOB and is not considered a major issue despite its long half-life.« less

Routine 18F- production with 180 μA to 200 μA target beam current on a GE PETtrace 800 cyclotron

NASA Astrophysics Data System (ADS)

Eberl, S.; Eriksson, T.; Svedberg, O.; Norling, J.; Henderson, D.; Lam, P.; Bourdier, T.; Fulham, M.

2012-12-01

Through upgrades and enhancements, which are now standard on current PETtrace 800 cyclotrons, a GE PETtrace cyclotron installed in 2002 has demonstrated reliable routine [18F]FDG production at total target beam currents of 180 μA without detriment to saturation and [18F]FDG yields. Routine production at 200 μA has been achieved and its evaluation is continuing. Self-shielded target using W/Cu alloy for the target body afforded a reduction in dose rate from the Havar foils by a factor of ˜ 8-10, reducing dose from the targets and need for removing targets during maintenance. The main activation product in the shield is 187W (T1/2 24 h). The 60Co ((T1/2 5.3 y) activation is about 250 times less at 24 h post EOB and is not considered a major issue despite its long half-life.

Effect of TLR ligands co-encapsulated with multiepitopic antigen in nanoliposomes targeted to human DCs via Fc receptor for cancer vaccines.

PubMed

Rueda, Felix; Eich, Christina; Cordobilla, Begoña; Domingo, Pere; Acosta, Gerardo; Albericio, Fernando; Cruz, Luis J; Domingo, Joan C

2017-11-01

Nanoliposomes (NLs) hold promise as new highly specific nanomedicine for anti-tumor vaccines, since they could be targeted to specific receptors on dendritic cell (DC) to induce maturation and activation and increase the anti-tumor immune response. Here we studied a NLs formulation targeted or not to FcR (the receptor for the IgG Fc fragment) for the treatment of androgen-responsive prostate cancer. Luteinizing-hormone-releasing hormone (LHRH) peptide (B- and T-cell epitopes), in tandem with a tetanus toxoid T-helper epitope (830-844 region) and several TLR (Toll-Like Receptor) ligands as adjuvants were co-encapsulated. Specific uptake in vitro of LHRH-TT liposomes targeted to the FcRs of human DCs was enhanced. DC maturation/activation, cytokine production and lymphocyte activation were consistently higher in targeted than non-targeted liposomes. Similar increase was observed as more adjuvants were administrated. Targeting to specific receptor and co-encapsulation of several TLR adjuvants are essential factors for the immune response in peptide based liposome vaccine. Copyright © 2017 Elsevier GmbH. All rights reserved.

Micro-tube mass production device for microbial culture.

PubMed

Fujimoto, K; Ogawa, M; Higashi, K; Miki, N

2016-08-01

This paper describes mass production system of micro-tubes for microbial culture in an open environment. Microbes are used in many fields, such as food, medicine, environmental and energy. We proposed a microbe culture system using hydrogel micro-tubes, which can protect the target microbes inside from competitive microbes outside of the tubes while allow oxygen and nutrition to diffuse through. The hydrogel micro-tubes can be produced by a microfluidic device, which can precisely control the flow and therefore, the tube geometry. For practical applications of the micro-tube-based microbial culture, one of the biggest challenges is the scale-up of the micro-tube-based culture system, or mass production of the tubes. We developed a fluidic system that can produce multiple micro-tubes in parallel. We characterized the mass-produced micro channels and verified the effectiveness of the system.

Effects of plants and plant products on the testis

PubMed Central

D'Cruz, Shereen Cynthia; Vaithinathan, Selvaraju; Jubendradass, Rajamanickam; Mathur, Premendu Prakash

2010-01-01

For centuries, plants and plant-based products have been used as a valuable and safe natural source of medicines for treating various ailments. The therapeutic potential of most of these plants could be ascribed to their anticancer, antidiabetic, hepatoprotective, cardioprotective, antispasmodic, analgesic and various other pharmacological properties. However, several commonly used plants have been reported to adversely affect male reproductive functions in wildlife and humans. The effects observed with most of the plant and plant-based products have been attributed to the antispermatogenic and/or antisteroidogenic properties of one or more active ingredients. This review discusses the detrimental effects of some of the commonly used plants on various target cells in the testis. A deeper insight into the molecular mechanisms of action of these natural compounds could pave the way for developing therapeutic strategies against their toxicity. PMID:20562897

Model of areas for identifying risks influencing the compliance of technological processes and products

NASA Astrophysics Data System (ADS)

Misztal, A.; Belu, N.

2016-08-01

Operation of every company is associated with the risk of interfering with proper performance of its fundamental processes. This risk is associated with various internal areas of the company, as well as the environment in which it operates. From the point of view of ensuring compliance of the course of specific technological processes and, consequently, product conformity with requirements, it is important to identify these threats and eliminate or reduce the risk of their occurrence. The purpose of this article is to present a model of areas of identifying risk affecting the compliance of processes and products, which is based on multiregional targeted monitoring of typical places of interference and risk management methods. The model is based on the verification of risk analyses carried out in small and medium-sized manufacturing companies in various industries..

Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against Staphylococcus aureus.

PubMed

Gao, Peng; Davies, Julian; Kao, Richard Yi Tsun

2017-09-05

Staphylococcus aureus , especially methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen in hospital- and community-acquired infections. The golden-colored carotenoid pigment of S. aureus , staphyloxanthin, contributes to the resistance to reactive oxygen species (ROS) and host neutrophil-based killing. Here, we describe a novel inhibitor (NP16) of S. aureus pigment production that reduces the survival of S. aureus under oxidative stress conditions. Carotenoid components analysis, enzyme inhibition, and crtN mutational studies indicated that the molecular target of NP16 is dehydrosqualene desaturase (CrtN). S. aureus treated with NP16 showed increased susceptibility to human neutrophil killing and to innate immune clearance in a mouse infection model. Our study validates CrtN as a novel druggable target in S. aureus and presents a potent and effective lead compound for the development of virulence factor-based therapy against S. aureus IMPORTANCE S. aureus staphyloxanthin contributes substantially to pathogenesis by interfering with host immune clearance mechanisms, but it has little impact on ex vivo survival of the bacterium. Agents blocking staphyloxanthin production may discourage the establishment and maintenance of bacterial infection without exerting selective pressure for antimicrobial resistance. Our newly discovered CrtN inhibitor, NP16, may offer an effective strategy for combating S. aureus infections. Copyright © 2017 Gao et al.

N-acetylcysteine Amide Augments the Therapeutic Effect of Neural Stem Cell-Based Antiglioma Oncolytic Virotherapy

PubMed Central

Kim, Chung Kwon; Ahmed, Atique U; Auffinger, Brenda; Ulasov, Ilya V; Tobias, Alex L; Moon, Kyung-Sub; Lesniak, Maciej S

2013-01-01

Current research has evaluated the intrinsic tumor-tropic properties of stem cell carriers for targeted anticancer therapy. Our laboratory has been extensively studying in the preclinical setting, the role of neural stem cells (NSCs) as delivery vehicles of CRAd-S-pk7, a gliomatropic oncolytic adenovirus (OV). However, the mediated toxicity of therapeutic payloads, such as oncolytic adenoviruses, toward cell carriers has significantly limited this targeted delivery approach. Following this rationale, in this study, we assessed the role of a novel antioxidant thiol, N-acetylcysteine amide (NACA), to prevent OV-mediated toxicity toward NSC carriers in an orthotropic glioma xenograft mouse model. Our results show that the combination of NACA and CRAd-S-pk7 not only increases the viability of these cell carriers by preventing reactive oxygen species (ROS)-induced apoptosis of NSCs, but also improves the production of viral progeny in HB1.F3.CD NSCs. In an intracranial xenograft mouse model, the combination treatment of NACA and NSCs loaded with CRAd-S-pk7 showed enhanced CRAd-S-pk7 production and distribution in malignant tissues, which improves the therapeutic efficacy of NSC-based targeted antiglioma oncolytic virotherapy. These data demonstrate that the combination of NACA and NSCs loaded with CRAd-S-pk7 may be a desirable strategy to improve the therapeutic efficacy of antiglioma oncolytic virotherapy. PMID:23883863

Skin surface removal on breast microwave imagery using wavelet multiscale products

NASA Astrophysics Data System (ADS)

Flores-Tapia, Daniel; Thomas, Gabriel; Pistorius, Stephen

2006-03-01

In many parts of the world, breast cancer is the leading cause mortality among women and it is the major cause of cancer death, next only to lung cancer. In recent years, microwave imaging has shown its potential as an alternative approach for breast cancer detection. Although advances have improved the likelihood of developing an early detection system based on this technology, there are still limitations. One of these limitations is that target responses are often obscured by surface reflections. Contrary to ground penetrating radar applications, a simple reference subtraction cannot be easily applied to alleviate this problem due to differences in the breast skin composition between patients. A novel surface removal technique for the removal of these high intensity reflections is proposed in this paper. This paper presents an algorithm based on the multiplication of adjacent wavelet subbands in order to enhance target echoes while reducing skin reflections. In these multiscale products, target signatures can be effectively distinguished from surface reflections. A simple threshold is applied to the signal in the wavelet domain in order to eliminate the skin responses. This final signal is reconstructed to the spatial domain in order to obtain a focused image. The proposed algorithm yielded promising results when applied to real data obtained from a phantom which mimics the dielectric properties of breast, cancer and skin tissues.

The use of targeted selective treatments against gastrointestinal nematodes in milking sheep and goats in Greece based on parasitological and performance criteria.

PubMed

Gallidis, E; Papadopoulos, E; Ptochos, S; Arsenos, G

2009-09-16

This study compared the use of targeted selective treatment (TST) with systematic whole-flock treatments in 38 dairy sheep and goat farms in Greece. Criteria for individual treatments were either parasitological (nematode faecal egg count) or performance-based (body condition score or milk yield). The possible effect of treatment on resistance to benzimidazole anthelmintics was assessed using the Egg Hatch Test. Mean faecal egg counts decreased during the 12-month experimental period in all groups, and were lowest in the TST group treated according to faecal egg count (P<0.05). The number of sheep and goats treated by TST was reduced compared with systematic treatments. Mean thiabendazole-egg death dose(50) (TBZ-ED(50)) values from all groups were similar at the beginning and end of the study (P>0.05), but significant variation in TBZ-ED(50) was noted over the study period in systematically treated goats (P=0.045). Third stage larvae belonging to the genera Teladorsagia, Trichostrongylus and Haemonchus were dominant throughout the experimental period in all flocks. It was concluded that the use of targeted selective treatment reduced the number of anthelmintic treatments to achieve a similar level of parasite control or animal production and may offer a viable option to combine animal production with effective parasite control in Greece.

Mitochondrial targeting increases specific activity of a heterologous valine assimilation pathway in Saccharomyces cerevisiae.

PubMed

Solomon, Kevin V; Ovadia, Elisa; Yu, Fujio; Mizunashi, Wataru; O'Malley, Michelle A

2016-12-01

Bio-based isobutantol is a sustainable 'drop in' substitute for petroleum-based fuels. However, well-studied production routes, such as the Ehrlich pathway, have yet to be commercialized despite more than a century of research. The more versatile bacterial valine catabolism may be a competitive alternate route producing not only an isobutanol precursor but several carboxylic acids with applications as biomonomers, and building blocks for other advanced biofuels. Here, we transfer the first two committed steps of the pathway from pathogenic Pseudomonas aeruginosa PAO1 to yeast to evaluate their activity in a safer model organism. Genes encoding the heteroligomeric branched chain keto-acid dehydrogenase (BCKAD; bkdA1, bkdA2, bkdB, lpdV ), and the homooligomeric acyl-CoA dehydrogenase (ACD; acd1 ) were tagged with fluorescence epitopes and targeted for expression in either the mitochondria or cytoplasm of S. cerevisiae . We verified the localization of our constructs with confocal fluorescence microscopy before measuring the activity of tag-free constructs. Despite reduced heterologous expression of mitochondria-targeted enzymes, their specific activities were significantly improved with total enzyme activities up to 138% greater than those of enzymes expressed in the cytoplasm. In total, our results demonstrate that the choice of protein localization in yeast has significant impact on heterologous activity, and suggests a new path forward for isobutanol production.

Two-Plasmon Decay Mitigation in Direct-Drive Inertial-Confinement-Fusion Experiments Using Multilayer Targets.

PubMed

Follett, R K; Delettrez, J A; Edgell, D H; Goncharov, V N; Henchen, R J; Katz, J; Michel, D T; Myatt, J F; Shaw, J; Solodov, A A; Stoeckl, C; Yaakobi, B; Froula, D H

2016-04-15

Multilayer direct-drive inertial-confinement-fusion targets are shown to significantly reduce two-plasmon decay (TPD) driven hot-electron production while maintaining high hydrodynamic efficiency. Implosion experiments on the OMEGA laser used targets with silicon layered between an inner beryllium and outer silicon-doped plastic ablator. A factor-of-5 reduction in hot-electron generation (>50  keV) was observed in the multilayer targets relative to pure CH targets. Three-dimensional simulations of the TPD-driven hot-electron production using a laser-plasma interaction code (lpse) that includes nonlinear and kinetic effects show good agreement with the measurements. The simulations suggest that the reduction in hot-electron production observed in the multilayer targets is primarily caused by increased electron-ion collisional damping.

Recovery Processes of Organic Acids from Fermentation Broths in the Biomass-Based Industry.

PubMed

Li, Qian-Zhu; Jiang, Xing-Lin; Feng, Xin-Jun; Wang, Ji-Ming; Sun, Chao; Zhang, Hai-Bo; Xian, Mo; Liu, Hui-Zhou

2016-01-01

The new movement towards green chemistry and renewable feedstocks makes microbial production of chemicals more competitive. Among the numerous chemicals, organic acids are more attractive targets for process development efforts in the renewable-based biorefinery industry. However, most of the production costs in microbial processes are higher than that in chemical processes, among which over 60% are generated by separation processes. Therefore, the research of separation and purification processes is important for a promising biorefinery industry. This review highlights the progress of recovery processes in the separation and purification of organic acids, including their advantages and disadvantages, current situation, and future prospects in terms of recovery yields and industrial application.

Development of a rapid SNP-typing assay to differentiate Bifidobacterium animalis ssp. lactis strains used in probiotic-supplemented dairy products.

PubMed

Lomonaco, Sara; Furumoto, Emily J; Loquasto, Joseph R; Morra, Patrizia; Grassi, Ausilia; Roberts, Robert F

2015-02-01

Identification at the genus, species, and strain levels is desirable when a probiotic microorganism is added to foods. Strains of Bifidobacterium animalis ssp. lactis (BAL) are commonly used worldwide in dairy products supplemented with probiotic strains. However, strain discrimination is difficult because of the high degree of genome identity (99.975%) between different genomes of this subspecies. Typing of monomorphic species can be carried out efficiently by targeting informative single nucleotide polymorphisms (SNP). Findings from a previous study analyzing both reference and commercial strains of BAL identified SNP that could be used to discriminate common strains into 8 groups. This paper describes development of a minisequencing assay based on the primer extension reaction (PER) targeting multiple SNP that can allow strain differentiation of BAL. Based on previous data, 6 informative SNP were selected for further testing, and a multiplex preliminary PCR was optimized to amplify the DNA regions containing the selected SNP. Extension primers (EP) annealing immediately adjacent to the selected SNP were developed and tested in simplex and multiplex PER to evaluate their performance. Twenty-five strains belonging to 9 distinct genomic clusters of B. animalis ssp. lactis were selected and analyzed using the developed minisequencing assay, simultaneously targeting the 6 selected SNP. Fragment analysis was subsequently carried out in duplicate and demonstrated that the assay yielded 8 specific profiles separating the most commonly used commercial strains. This novel multiplex PER approach provides a simple, rapid, flexible SNP-based subtyping method for proper characterization and identification of commercial probiotic strains of BAL from fermented dairy products. To assess the usefulness of this method, DNA was extracted from yogurt manufactured with and without the addition of B. animalis ssp. lactis BB-12. Extracted DNA was then subjected to the minisequencing protocol, resulting in a SNP profile matching the profile for the strain BB-12. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Locating Sensors for Detecting Source-to-Target Patterns of Special Nuclear Material Smuggling: A Spatial Information Theoretic Approach

PubMed Central

Przybyla, Jay; Taylor, Jeffrey; Zhou, Xuesong

2010-01-01

In this paper, a spatial information-theoretic model is proposed to locate sensors for detecting source-to-target patterns of special nuclear material (SNM) smuggling. In order to ship the nuclear materials from a source location with SNM production to a target city, the smugglers must employ global and domestic logistics systems. This paper focuses on locating a limited set of fixed and mobile radiation sensors in a transportation network, with the intent to maximize the expected information gain and minimize the estimation error for the subsequent nuclear material detection stage. A Kalman filtering-based framework is adapted to assist the decision-maker in quantifying the network-wide information gain and SNM flow estimation accuracy. PMID:22163641

Locating sensors for detecting source-to-target patterns of special nuclear material smuggling: a spatial information theoretic approach.

PubMed

Przybyla, Jay; Taylor, Jeffrey; Zhou, Xuesong

2010-01-01

In this paper, a spatial information-theoretic model is proposed to locate sensors for detecting source-to-target patterns of special nuclear material (SNM) smuggling. In order to ship the nuclear materials from a source location with SNM production to a target city, the smugglers must employ global and domestic logistics systems. This paper focuses on locating a limited set of fixed and mobile radiation sensors in a transportation network, with the intent to maximize the expected information gain and minimize the estimation error for the subsequent nuclear material detection stage. A Kalman filtering-based framework is adapted to assist the decision-maker in quantifying the network-wide information gain and SNM flow estimation accuracy.

[Quantitative PCR in the diagnosis of Leishmania].

PubMed

Mortarino, M; Franceschi, A; Mancianti, F; Bazzocchi, C; Genchi, C; Bandi, C

2004-06-01

Polymerase chain reaction (PCR) is a sensitive and rapid method for the diagnosis of canine Leishmania infection and can be performed on a variety of biological samples, including peripheral blood, lymph node, bone marrow and skin. Standard PCR requires electrophoretic analysis of the amplification products and is usually not suitable for quantification of the template DNA (unless competitor-based or other methods are developed), being of reduced usefulness when accurate monitoring of target DNA is required. Quantitative real-time PCR allows the continuous monitoring of the accumulation of PCR products during the amplification reaction. This allows the identification of the cycle of near-logarithmic PCR product generation (threshold cycle) and, by inference, the relative quantification of the template DNA present at the start of the reaction. Since the amplification product are monitored in "real-time" as they form cycle-by-cycle, no post-amplification handling is required. The absolute quantification is performed according either to an internal standard co-amplified with the sample DNA, or to an external standard curve obtained by parallel amplification of serial known concentrations of a reference DNA sequence. From the quantification of the template DNA, an estimation of the relative load of parasites in the different samples can be obtained. The advantages compared to standard and semi-quantitative PCR techniques are reduction of the assay's time and contamination risks, and improved sensitivity. As for standard PCR, the minimal components of the quantitative PCR reaction mixture are the DNA target of the amplification, an oligonucleotide primer pair flanking the target sequence, a suitable DNA polymerase, deoxynucleotides, buffer and salts. Different technologies have been set up for the monitoring of amplification products, generally based on the use of fluorescent probes. For instance, SYBR Green technology is a non-specific detection system based on a fluorescent dsDNA intercalator and it is applicable to all potential targets. TaqMan technology is more specific since performs the direct assessment of the amount of amplified DNA using a fluorescent probe specific for the target sequence flanked by the primer pair. This probe is an oligonucleotide labelled with a reporter dye (fluorescent) and a quencher (which absorbs the fluorescent signal generated by the reporter). The thermic protocol of amplification allows the binding of the fluorescent probe to the target sequence before the binding of the primers and the starting of the polymerization by Taq polymerase. During polymerization, 5'-3' exonuclease activity of Taq polymerase digests the probe and in this way the reporter dye is released from the probe and a fluorescent signal is detected. The intensity of the signal accumulates at the end of each cycle and is related to the amount of the amplification product. In recent years, quantitative PCR methods based either on SYBR Green or TaqMan technology have been set up for the quantification of Leishmania in mouse liver, mouse skin and human peripheral blood, targeting either single-copy chromosomal or multi-copy minicircle sequences with high sensitivity and reproducibility. In particular, real-time PCR seems to be a reliable, rapid and noninvasive method for the diagnosis and follow up of visceral leishmaniasis in humans. At present, the application of real-time PCR for research and clinical diagnosis of Leishmania infection in dogs is still foreseable. As for standard PCR, the high sensitivity of real-time PCR could allow the use of blood sampling that is less invasive and easily performed for monitoring the status of the dogs. The development of a real-time PCR assay for Leishmania infantum infection in dogs could support the standard and optimized serological and PCR methods currenly in use for the diagnosis and follow-up of canine leishmaniasis, and perhaps prediction of recurrences associated with tissue loads of residual pathogens after treatment. At this regard, a TaqMan Real Time PCR method developed for the quantification of Leishmania infantum minicircle DNA in peripheral blood of naturally infected dogs sampled before and at different time points after the beginning of a standard antileishmanial therapy will be illustrated.

Generation of TALE-Based Designer Epigenome Modifiers.

PubMed

Nitsch, Sandra; Mussolino, Claudio

2018-01-01

Manipulation of gene expression can be facilitated by editing the genome or the epigenome. Precise genome editing is traditionally achieved by using designer nucleases which are generally exploited to eliminate a specific gene product. Upon the introduction of a site-specific DNA double-strand break (DSB) by the nuclease, endogenous DSB repair mechanisms are in turn harnessed to induce DNA sequence changes that can result in target gene inactivation. Minimal off-target effects can be obtained by endowing designer nucleases with the highly specific DNA-binding domain (DBD) derived from transcription activator-like effectors (TALEs). In contrast, epigenome editing allows gene expression control without inducing changes in the DNA sequence by specifically altering epigenetic marks, as histone tails modifications or DNA methylation patterns within promoter or enhancer regions. Importantly, this approach allows both up- and downregulation of the target gene expression, and the effect is generally reversible. TALE-based designer epigenome modifiers combine the high specificity of TALE-derived DBDs with the power of epigenetic modifier domains to induce fast and long-lasting changes in the epigenetic landscape of a target gene and control its expression. Here we provide a detailed description for the generation of TALE-based designer epigenome modifiers and of a suitable reporter cell line to easily monitor their activity.

Quantitative analysis of pork and chicken products by droplet digital PCR.

PubMed

Cai, Yicun; Li, Xiang; Lv, Rong; Yang, Jielin; Li, Jian; He, Yuping; Pan, Liangwen

2014-01-01

In this project, a highly precise quantitative method based on the digital polymerase chain reaction (dPCR) technique was developed to determine the weight of pork and chicken in meat products. Real-time quantitative polymerase chain reaction (qPCR) is currently used for quantitative molecular analysis of the presence of species-specific DNAs in meat products. However, it is limited in amplification efficiency and relies on standard curves based Ct values, detecting and quantifying low copy number target DNA, as in some complex mixture meat products. By using the dPCR method, we find the relationships between the raw meat weight and DNA weight and between the DNA weight and DNA copy number were both close to linear. This enabled us to establish formulae to calculate the raw meat weight based on the DNA copy number. The accuracy and applicability of this method were tested and verified using samples of pork and chicken powder mixed in known proportions. Quantitative analysis indicated that dPCR is highly precise in quantifying pork and chicken in meat products and therefore has the potential to be used in routine analysis by government regulators and quality control departments of commercial food and feed enterprises.

The distributed agent-based approach in the e-manufacturing environment

NASA Astrophysics Data System (ADS)

Sękala, A.; Kost, G.; Dobrzańska-Danikiewicz, A.; Banaś, W.; Foit, K.

2015-11-01

The deficiency of a coherent flow of information from a production department causes unplanned downtime and failures of machines and their equipment, which in turn results in production planning process based on incorrect and out-of-date information. All of these factors entail, as the consequence, the additional difficulties associated with the process of decision-making. They concern, among other, the coordination of components of a distributed system and providing the access to the required information, thereby generating unnecessary costs. The use of agent technology significantly speeds up the flow of information within the virtual enterprise. This paper includes the proposal of a multi-agent approach for the integration of processes within the virtual enterprise concept. The presented concept was elaborated to investigate the possible solutions of the ways of transmission of information in the production system taking into account the self-organization of constituent components. Thus it implicated the linking of the concept of multi-agent system with the system of managing the production information, based on the idea of e-manufacturing. The paper presents resulting scheme that should be the base for elaborating an informatics model of the target virtual system. The computer system itself is intended to be developed next.

Bulk production and evaluation of high specific activity 186g Re for cancer therapy using enriched 186 WO 3 targets in a proton beam

DOE PAGES

Mastren, Tara; Radchenko, Valery; Bach, Hong T.; ...

2017-06-01

Rhenium-186 g (t 1/2 = 3.72 d) is a β– emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction 185Re(n,γ) 186gRe, which results in low specific activities limiting its use for cancer therapy. Production via charged particle activation of enriched 186W results in a 186gRe product with a much specific activity, allowing it to be used more broadly for targeted radiotherapy applications. Furthermore, this targets the unmet clinical need for more efficient radiotherapeutics.

Bulk production and evaluation of high specific activity 186g Re for cancer therapy using enriched 186 WO 3 targets in a proton beam

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

Mastren, Tara; Radchenko, Valery; Bach, Hong T.

Rhenium-186 g (t 1/2 = 3.72 d) is a β– emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction 185Re(n,γ) 186gRe, which results in low specific activities limiting its use for cancer therapy. Production via charged particle activation of enriched 186W results in a 186gRe product with a much specific activity, allowing it to be used more broadly for targeted radiotherapy applications. Furthermore, this targets the unmet clinical need for more efficient radiotherapeutics.

Morphological and functional effects of graphene on the synthesis of uranium carbide for isotopes production targets.

PubMed

Biasetto, L; Corradetti, S; Carturan, S; Eloirdi, R; Amador-Celdran, P; Staicu, D; Blanco, O Dieste; Andrighetto, A

2018-05-29

The development of tailored targets for the production of radioactive isotopes represents an active field in nuclear research. Radioactive beams find applications in nuclear medicine, in astrophysics, matter physics and materials science. In this work, we study the use of graphene both as carbon source for UO 2 carbothermal reduction to produce UC x targets, and also as functional properties booster. At fixed composition, the UC x target grain size, porosity and thermal conductivity represent the three main points that affect the target production efficiency. UC x was synthesized using both graphite and graphene as the source of carbon and the target properties in terms of composition, grain size, porosity, thermal diffusivity and thermal conductivity were studied. The main output of this work is related to the remarkable enhancement achieved in thermal conductivity, which can profitably improve thermal dissipation during operational stages of UC x targets.

Evidence for Personal Protective Measures to Reduce Human Contact With Blacklegged Ticks and for Environmentally Based Control Methods to Suppress Host-Seeking Blacklegged Ticks and Reduce Infection with Lyme Disease Spirochetes in Tick Vectors and Rodent Reservoirs.

PubMed

Eisen, Lars; Dolan, Marc C

2016-07-20

In the 1980s, the blacklegged tick, Ixodes scapularis Say, and rodents were recognized as the principal vector and reservoir hosts of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, and deer were incriminated as principal hosts for I. scapularis adults. These realizations led to pioneering studies aiming to reduce the risk for transmission of B. burgdorferi to humans by attacking host-seeking ticks with acaricides, interrupting the enzootic transmission cycle by killing immatures infesting rodent reservoirs by means of acaricide-treated nesting material, or reducing deer abundance to suppress tick numbers. We review the progress over the past three decades in the fields of: 1) prevention of human-tick contact with repellents and permethrin-treated clothing, and 2) suppression of I. scapularis and disruption of enzootic B. burgdorferi transmission with environmentally based control methods. Personal protective measures include synthetic and natural product-based repellents that can be applied to skin and clothing, permethrin sprays for clothing and gear, and permethrin-treated clothing. A wide variety of approaches and products to suppress I. scapularis or disrupt enzootic B. burgdorferi transmission have emerged and been evaluated in field trials. Application of synthetic chemical acaricides is a robust method to suppress host-seeking I. scapularis ticks within a treated area for at least 6-8 wk. Natural product-based acaricides or entomopathogenic fungi have emerged as alternatives to kill host-seeking ticks for homeowners who are unwilling to use synthetic chemical acaricides. However, as compared with synthetic chemical acaricides, these approaches appear less robust in terms of both their killing efficacy and persistence. Use of rodent-targeted topical acaricides represents an alternative for homeowners opposed to open distribution of acaricides to the ground and vegetation on their properties. This host-targeted approach also provides the benefit of the intervention impacting the entire rodent home range. Rodent-targeted oral vaccines against B. burgdorferi and a rodent-targeted antibiotic bait have been evaluated in laboratory and field trials but are not yet commercially available. Targeting of deer-via deer reduction or treatment of deer with topical acaricides-can provide area-wide suppression of host-seeking I. scapularis These two deer-targeted approaches combine great potential for protection that impacts the entire landscape with severe problems relating to public acceptance or implementation logistics. Integrated use of two or more methods has unfortunately been evaluated in very few published studies, but additional field evaluations of integrated tick and pathogen strategies are underway. Published by Oxford University Press on behalf of Journal of Medical Entomology 2016. This work is written by US Government employees and is in the public domain in the US.

Evaluation of Australian soup manufacturer compliance with national sodium reduction targets.

PubMed

Levi, Rebecca; Probst, Yasmine; Crino, Michelle; Dunford, Elizabeth

2018-04-01

Packaged foods dominate Australia's food supply and are important contributors to nutrition-related disease. To help address this problem, the Food and Health Dialogue (FHD) was launched in 2009, setting voluntary sodium reduction targets for various categories of packaged foods. The aim of this study was to examine the food industry's progress and compliance with the FHD sodium reduction targets for soup products. Nutritional information was collected from product labels of all soup products available from four major Australian supermarkets annually between 2011 and 2014. Products were assigned to categories in line with those in the FHD. The proportion of soup products meeting sodium reduction targets was examined by (i) soup category; (ii) FHD participant status; and (iii) manufacturer. A 6% reduction in sodium levels in soups overall was found from 2011 to 2014 (P = 0.002). Significant reductions were observed for FHD participants (P < 0.05 for all) but not for non-participants. In 2014, 67% dry soups and 76% of wet soups met national sodium reduction targets. Despite the majority of soup products meeting the sodium reduction targets specified by the FHD, re-evaluation of the targets may be required to further reduce sodium levels in soups. Manufacturers participating in the FHD are likely to be driving sodium reductions in the Australian soup market, further highlighting the need for continued government leadership in this area to ensure all manufacturers are actively involved in the process. © 2017 Dietitians Association of Australia.

Innovative Product Design Based on Comprehensive Customer Requirements of Different Cognitive Levels

PubMed Central

Zhao, Wu; Zheng, Yake; Wang, Rui; Wang, Chen

2014-01-01

To improve customer satisfaction in innovative product design, a topology structure of customer requirements is established and an innovative product approach is proposed. The topology structure provides designers with reasonable guidance to capture the customer requirements comprehensively. With the aid of analytic hierarchy process (AHP), the importance of the customer requirements is evaluated. Quality function deployment (QFD) is used to translate customer requirements into product and process design demands and pick out the technical requirements which need urgent improvement. In this way, the product is developed in a more targeted way to satisfy the customers. the theory of innovative problems solving (TRIZ) is used to help designers to produce innovative solutions. Finally, a case study of automobile steering system is used to illustrate the application of the proposed approach. PMID:25013862