Two Sets of Piwi Proteins Are Involved in Distinct sRNA Pathways Leading to Elimination of Germline-Specific DNA

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Dominique I. Furrer

2017-07-01

Full Text Available Piwi proteins and piRNAs protect eukaryotic germlines against the spread of transposons. During development in the ciliate Paramecium, two Piwi-dependent sRNA classes are involved in the elimination of transposons and transposon-derived DNA: scan RNAs (scnRNAs, associated with Ptiwi01 and Ptiwi09, and iesRNAs, whose binding partners we now identify as Ptiwi10 and Ptiwi11. scnRNAs derive from the maternal genome and initiate DNA elimination during development, whereas iesRNAs continue DNA targeting until the removal process is complete. Here, we show that scnRNAs and iesRNAs are processed by distinct Dicer-like proteins and bind Piwi proteins in a mutually exclusive manner, suggesting separate biogenesis pathways. We also demonstrate that the PTIWI10 gene is transcribed from the developing nucleus and that its transcription depends on prior DNA excision, suggesting a mechanism of gene expression control triggered by the removal of short DNA segments interrupting the gene.

Incorporating Financial Stability in Inflation Targeting Frameworks

OpenAIRE

Burcu Aydin; Engin Volkan

2011-01-01

The global financial crisis has exposed the limitations of a conventional inflation targeting (IT) framework in insulating an economy from shocks, and demonstrated that its rigid application may aggravate the effect of shocks on output and inflation. Accordingly, we investigate possible refinements to the IT framework by incorporating financial stability considerations. We propose a small open economy DSGE model, calibrated for Korea during the period of 2003 - 07, with real and financial fri...

Determination of sRNA expressions by RNA-seq in Yersinia pestis grown in vitro and during infection.

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Yanfeng Yan

Full Text Available BACKGROUND: Small non-coding RNAs (sRNAs facilitate host-microbe interactions. They have a central function in the post-transcriptional regulation during pathogenic lifestyles. Hfq, an RNA-binding protein that many sRNAs act in conjunction with, is required for Y. pestis pathogenesis. However, information on how Yersinia pestis modulates the expression of sRNAs during infection is largely unknown. METHODOLOGY AND PRINCIPAL FINDINGS: We used RNA-seq technology to identify the sRNA candidates expressed from Y. pestis grown in vitro and in the infected lungs of mice. A total of 104 sRNAs were found, including 26 previously annotated sRNAs, by searching against the Rfam database with 78 novel sRNA candidates. Approximately 89% (93/104 of these sRNAs from Y. pestis are shared with its ancestor Y. pseudotuberculosis. Ninety-seven percent of these sRNAs (101/104 are shared among more than 80 sequenced genomes of 135 Y. pestis strains. These 78 novel sRNAs include 62 intergenic and 16 antisense sRNAs. Fourteen sRNAs were selected for verification by independent Northern blot analysis. Results showed that nine selected sRNA transcripts were Hfq-dependent. Interestingly, three novel sRNAs were identified as new members of the transcription factor CRP regulon. Semi-quantitative analysis revealed that Y. pestis from the infected lungs induced the expressions of six sRNAs including RyhB1, RyhB2, CyaR/RyeE, 6S RNA, RybB and sR039 and repressed the expressions of four sRNAs, including CsrB, CsrC, 4.5S RNA and sR027. CONCLUSIONS AND SIGNIFICANCE: This study is the first attempt to subject RNA from Y. pestis-infected samples to direct high-throughput sequencing. Many novel sRNAs were identified and the expression patterns of relevant sRNAs in Y. pestis during in vitro growth and in vivo infection were revealed. The annotated sRNAs accounted for the most abundant sRNAs either expressed in bacteria grown in vitro or differentially expressed in the infected lungs

SRNA-2K5, Proton Transport Using 3-D by Monte Carlo Techniques

International Nuclear Information System (INIS)

Ilic, Radovan D.

2005-01-01

1 - Description of program or function: SRNA-2K5 performs Monte Carlo transport simulation of proton in 3D source and 3D geometry of arbitrary materials. The proton transport based on condensed history model, and on model of compound nuclei decays that creates in nonelastic nuclear interaction by proton absorption. 2 - Methods: The SRNA-2K5 package is developed for time independent simulation of proton transport by Monte Carlo techniques for numerical experiments in complex geometry, using PENGEOM from PENELOPE with different material compositions, and arbitrary spectrum of proton generated from the 3D source. This package developed for 3D proton dose distribution in proton therapy and dosimetry, and it was based on the theory of multiple scattering. The compound nuclei decay was simulated by our and Russian MSDM models using ICRU 49 and ICRU 63 data. If protons trajectory is divided on great number of steps, protons passage can be simulated according to Berger's Condensed Random Walk model. Conditions of angular distribution and fluctuation of energy loss determinate step length. Physical picture of these processes is described by stopping power, Moliere's angular distribution, Vavilov's distribution with Sulek's correction per all electron orbits, and Chadwick's cross sections for nonelastic nuclear interactions, obtained by his GNASH code. According to physical picture of protons passage and with probabilities of protons transition from previous to next stage, which is prepared by SRNADAT program, simulation of protons transport in all SRNA codes runs according to usual Monte Carlo scheme: (i) proton from the spectrum prepared for random choice of energy, position and space angle is emitted from the source; (ii) proton is loosing average energy on the step; (iii) on that step, proton experience a great number of collisions, and it changes direction of movement randomly chosen from angular distribution; (iv) random fluctuation is added to average energy loss; (v

psRNATarget: a plant small RNA target analysis server (2017 release).

Science.gov (United States)

Dai, Xinbin; Zhuang, Zhaohong; Zhao, Patrick Xuechun

2018-04-30

Plant regulatory small RNAs (sRNAs), which include most microRNAs (miRNAs) and a subset of small interfering RNAs (siRNAs), such as the phased siRNAs (phasiRNAs), play important roles in regulating gene expression. Although generated from genetically distinct biogenesis pathways, these regulatory sRNAs share the same mechanisms for post-translational gene silencing and translational inhibition. psRNATarget was developed to identify plant sRNA targets by (i) analyzing complementary matching between the sRNA sequence and target mRNA sequence using a predefined scoring schema and (ii) by evaluating target site accessibility. This update enhances its analytical performance by developing a new scoring schema that is capable of discovering miRNA-mRNA interactions at higher 'recall rates' without significantly increasing total prediction output. The scoring procedure is customizable for the users to search both canonical and non-canonical targets. This update also enables transmitting and analyzing 'big' data empowered by (a) the implementation of multi-threading chunked file uploading, which can be paused and resumed, using HTML5 APIs and (b) the allocation of significantly more computing nodes to its back-end Linux cluster. The updated psRNATarget server has clear, compelling and user-friendly interfaces that enhance user experiences and present data clearly and concisely. The psRNATarget is freely available at http://plantgrn.noble.org/psRNATarget/.

Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.

Science.gov (United States)

Sonnleitner, Elisabeth; Valentini, Martina; Wenner, Nicolas; Haichar, Feth el Zahar; Haas, Dieter; Lapouge, Karine

2012-01-01

The opportunistic human pathogen Pseudomonas aeruginosa is able to utilize a wide range of carbon and nitrogen compounds, allowing it to grow in vastly different environments. The uptake and catabolism of growth substrates are organized hierarchically by a mechanism termed catabolite repression control (Crc) whereby the Crc protein establishes translational repression of target mRNAs at CA (catabolite activity) motifs present in target mRNAs near ribosome binding sites. Poor carbon sources lead to activation of the CbrAB two-component system, which induces transcription of the small RNA (sRNA) CrcZ. This sRNA relieves Crc-mediated repression of target mRNAs. In this study, we have identified novel targets of the CbrAB/Crc system in P. aeruginosa using transcriptome analysis in combination with a search for CA motifs. We characterized four target genes involved in the uptake and utilization of less preferred carbon sources: estA (secreted esterase), acsA (acetyl-CoA synthetase), bkdR (regulator of branched-chain amino acid catabolism) and aroP2 (aromatic amino acid uptake protein). Evidence for regulation by CbrAB, CrcZ and Crc was obtained in vivo using appropriate reporter fusions, in which mutation of the CA motif resulted in loss of catabolite repression. CbrB and CrcZ were important for growth of P. aeruginosa in cystic fibrosis (CF) sputum medium, suggesting that the CbrAB/Crc system may act as an important regulator during chronic infection of the CF lung.

Identification and expression profiles of sRNAs and their biogenesis and action-related genes in male and female cones of Pinus tabuliformis.

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Niu, Shi-Hui; Liu, Chang; Yuan, Hu-Wei; Li, Pei; Li, Yue; Li, Wei

2015-09-15

Small RNA (sRNA) play pivotal roles in reproductive development, and their biogenesis and action mechanisms are well characterised in angiosperm plants; however, corresponding studies in conifers are very limited. To improve our understanding of the roles of sRNA pathways in the reproductive development of conifers, the genes associated with sRNA biogenesis and action pathways were identified and analysed, and sRNA sequencing and parallel analysis of RNA ends (PARE) were performed in male and female cones of the Chinese pine (Pinus tabuliformis). Based on high-quality reference transcriptomic sequences, 21 high-confidence homologues involved in sRNA biogenesis and action in P. tabuliformis were identified, including two different DCL3 genes and one AGO4 gene. More than 75 % of genes involved in sRNA biogenesis and action have higher expression levels in female than in male cones. Twenty-six microRNA (miRNA) families and 74 targets, including 46 24-nt sRNAs with a 5' A, which are specifically expressed in male cones or female cones and probably bind to AGO4, were identified. The sRNA pathways have higher activity in female than in male cones, and the miRNA pathways are the main sRNA pathways in P. tabuliformis. The low level of 24-nt short-interfering RNAs in conifers is not caused by the absence of biogenesis-related genes or AGO-binding proteins, but most likely caused by the low accumulation of these key components. The identification of sRNAs and their targets, as well as genes associated with sRNA biogenesis and action, will provide a good starting point for investigations into the roles of sRNA pathways in cone development in conifers.

Synthesis and biological incorporation of icons into macromolecules for NMR study. Final report, June 1, 1977--May 31, 1978

International Nuclear Information System (INIS)

Grant, D.M.; Horton, W.J.

1978-01-01

Carbon-13 enrichment synthesis and incorporation into three important biological systems have been carried out to provide materials for carbon-13 magnetic resonance studies. These systems include antibody-labeled haptens, labeled t-RNA and 5S-RNA molecules, and pyridoxal-5'-phosphate-labeled substrate mixtures. The synthesis phase of the work has been completed in all three cases, and the NMR studies completed on all but the antibody-hapten system which is still in process having been absorbed into other supported projects. Publications are now in preparation for the RNA and pyridoxal work. Preliminary results on the antibody-haptens work are encouraging as signals of antibody absorbed haptens have been observed but the results are still not yet conclusive

The miRNAome of globe artichoke: conserved and novel micro RNAs and target analysis

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De Paola Domenico

2012-01-01

Full Text Available Abstract Background Plant microRNAs (miRNAs are involved in post-transcriptional regulatory mechanisms of several processes, including the response to biotic and abiotic stress, often contributing to the adaptive response of the plant to adverse conditions. In addition to conserved miRNAs, found in a wide range of plant species a number of novel species-specific miRNAs, displaying lower levels of expression can be found. Due to low abundance, non conserved miRNAs are difficult to identify and isolate using conventional approaches. Conversely, deep-sequencing of small RNA (sRNA libraries can detect even poorly expressed miRNAs. No miRNAs from globe artichoke have been described to date. We analyzed the miRNAome from artichoke by deep sequencing four sRNA libraries obtained from NaCl stressed and control leaves and roots. Results Conserved and novel miRNAs were discovered using accepted criteria. The expression level of selected miRNAs was monitored by quantitative real-time PCR. Targets were predicted and validated for their cleavage site. A total of 122 artichoke miRNAs were identified, 98 (25 families of which were conserved with other plant species, and 24 were novel. Some miRNAs were differentially expressed according to tissue or condition, magnitude of variation after salt stress being more pronounced in roots. Target function was predicted by comparison to Arabidopsis proteins; the 43 targets (23 for novel miRNAs identified included transcription factors and other genes, most of which involved in the response to various stresses. An unusual cleaved transcript was detected for miR393 target, transport inhibitor response 1. Conclusions The miRNAome from artichoke, including novel miRNAs, was unveiled, providing useful information on the expression in different organs and conditions. New target genes were identified. We suggest that the generation of secondary short-interfering RNAs from miR393 target can be a general rule in the plant

Systemic delivery of siRNA in pumpkin by a plant PHLOEM SMALL RNA-BINDING PROTEIN 1-ribonucleoprotein complex.

Science.gov (United States)

Ham, Byung-Kook; Li, Gang; Jia, Weitao; Leary, Julie A; Lucas, William J

2014-11-01

In plants, the vascular system, specifically the phloem, functions in delivery of small RNA (sRNA) to exert epigenetic control over developmental and defense-related processes. Although the importance of systemic sRNA delivery has been established, information is currently lacking concerning the nature of the protein machinery involved in this process. Here, we show that a PHLOEM SMALL-RNA BINDING PROTEIN 1 (PSRP1) serves as the basis for formation of an sRNA ribonucleoprotein complex (sRNPC) that delivers sRNA (primarily 24 nt) to sink organs. Assembly of this complex is facilitated through PSRP1 phosphorylation by a phloem-localized protein kinase, PSRPK1. During long-distance transport, PSRP1-sRNPC is stable against phloem phosphatase activity. Within target tissues, phosphatase activity results in disassembly of PSRP1-sRNPC, a process that is probably required for unloading cargo sRNA into surrounding cells. These findings provide an insight into the mechanism involved in delivery of sRNA associated with systemic gene silencing in plants. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Construction of new synthetic biology tools for the control of gene expression in the cyanobacterium Synechococcus sp. strain PCC 7002.

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Zess, Erin K; Begemann, Matthew B; Pfleger, Brian F

2016-02-01

Predictive control of gene expression is an essential tool for developing synthetic biological systems. The current toolbox for controlling gene expression in cyanobacteria is a barrier to more in-depth genetic analysis and manipulation. Towards relieving this bottleneck, this work describes the use of synthetic biology to construct an anhydrotetracycline-based induction system and adapt a trans-acting small RNA (sRNA) system for use in the cyanobacterium Synechococcus sp. strain PCC 7002. An anhydrotetracycline-inducible promoter was developed to maximize intrinsic strength and dynamic range. The resulting construct, PEZtet , exhibited tight repression and a maximum 32-fold induction upon addition of anhydrotetracycline. Additionally, a sRNA system based on the Escherichia coli IS10 RNA-IN/OUT regulator was adapted for use in Synechococcus sp. strain PCC 7002. This system exhibited 70% attenuation of target gene expression, providing a demonstration of the use of sRNAs for differential gene expression in cyanobacteria. These systems were combined to produce an inducible sRNA system, which demonstrated 59% attenuation of target gene expression. Lastly, the role of Hfq, a critical component of sRNA systems in E. coli, was investigated. Genetic studies showed that the Hfq homolog in Synechococcus sp. strain PCC 7002 did not impact repression by the engineered sRNA system. In summary, this work describes new synthetic biology tools that can be applied to physiological studies, metabolic engineering, or sRNA platforms in Synechococcus sp. strain PCC 7002. © 2015 Wiley Periodicals, Inc.

Rational Modular RNA Engineering Based on In Vivo Profiling of Structural Accessibility.

Science.gov (United States)

Leistra, Abigail N; Amador, Paul; Buvanendiran, Aishwarya; Moon-Walker, Alex; Contreras, Lydia M

2017-12-15

Bacterial small RNAs (sRNAs) have been established as powerful parts for controlling gene expression. However, development and application of engineered sRNAs has primarily focused on regulating novel synthetic targets. In this work, we demonstrate a rational modular RNA engineering approach that uses in vivo structural accessibility measurements to tune the regulatory activity of a multisubstrate sRNA for differential control of its native target network. Employing the CsrB global sRNA regulator as a model system, we use published in vivo structural accessibility data to infer the contribution of its local structures (substructures) to function and select a subset for engineering. We then modularly recombine the selected substructures, differentially representing those of presumed high or low functional contribution, to build a library of 21 CsrB variants. Using fluorescent translational reporter assays, we demonstrate that the CsrB variants achieve a 5-fold gradient of control of well-characterized Csr network targets. Interestingly, results suggest that less conserved local structures within long, multisubstrate sRNAs may represent better targets for rational engineering than their well-conserved counterparts. Lastly, mapping the impact of sRNA variants on a signature Csr network phenotype indicates the potential of this approach for tuning the activity of global sRNA regulators in the context of metabolic engineering applications.

Theoretical studies on sRNA-mediated regulation in bacteria

Science.gov (United States)

Chang, Xiao-Xue; Xu, Liu-Fang; Shi, Hua-Lin

2015-12-01

Small RNA(sRNA)-mediated post-transcriptional regulation differs from protein-mediated regulation. Through base-pairing, sRNA can regulate the target mRNA in a catalytic or stoichiometric manner. Some theoretical models were built for comparison of the protein-mediated and sRNA-mediated modes in the steady-state behaviors and noise properties. Many experiments demonstrated that a single sRNA can regulate several mRNAs, which causes crosstalk between the targets. Here, we focus on some models in which two target mRNAs are silenced by the same sRNA to discuss their crosstalk features. Additionally, the sequence-function relationship of sRNA and its role in the kinetic process of base-pairing have been highlighted in model building. Project supported by the National Basic Research Program of China (Grant No. 2013CB834100), the National Natural Science Foundation of China (Grant Nos. 11121403 and 11274320), the Open Project Program of State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, China (Grant No. Y4KF171CJ1), the National Natural Science Foundation for Young Scholar of China (Grant No. 11304115), and the China Postdoctoral Science Foundation (Grant No. 2013M541282).

Deep sequencing of Salmonella RNA associated with heterologous Hfq proteins in vivo reveals small RNAs as a major target class and identifies RNA processing phenotypes.

Science.gov (United States)

Sittka, Alexandra; Sharma, Cynthia M; Rolle, Katarzyna; Vogel, Jörg

2009-01-01

The bacterial Sm-like protein, Hfq, is a key factor for the stability and function of small non-coding RNAs (sRNAs) in Escherichia coli. Homologues of this protein have been predicted in many distantly related organisms yet their functional conservation as sRNA-binding proteins has not entirely been clear. To address this, we expressed in Salmonella the Hfq proteins of two eubacteria (Neisseria meningitides, Aquifex aeolicus) and an archaeon (Methanocaldococcus jannaschii), and analyzed the associated RNA by deep sequencing. This in vivo approach identified endogenous Salmonella sRNAs as a major target of the foreign Hfq proteins. New Salmonella sRNA species were also identified, and some of these accumulated specifically in the presence of a foreign Hfq protein. In addition, we observed specific RNA processing defects, e.g., suppression of precursor processing of SraH sRNA by Methanocaldococcus Hfq, or aberrant accumulation of extracytoplasmic target mRNAs of the Salmonella GcvB, MicA or RybB sRNAs. Taken together, our study provides evidence of a conserved inherent sRNA-binding property of Hfq, which may facilitate the lateral transmission of regulatory sRNAs among distantly related species. It also suggests that the expression of heterologous RNA-binding proteins combined with deep sequencing analysis of RNA ligands can be used as a molecular tool to dissect individual steps of RNA metabolism in vivo.

Ambient temperature regulates the expression of a small set of sRNAs influencing plant development through NF-YA2 and YUC2.

Science.gov (United States)

Gyula, Péter; Baksa, Ivett; Tóth, Tamás; Mohorianu, Irina; Dalmay, Tamás; Szittya, György

2018-06-01

Plants substantially alter their developmental program upon changes in the ambient temperature. The 21-24 nt small RNAs (sRNAs) are important gene expression regulators, which play a major role in development and adaptation. However, little is known about how the different sRNA classes respond to changes in the ambient temperature. We profiled the sRNA populations in four different tissues of Arabidopsis thaliana plants grown at 15, 21 and 27 °C. We found that only a small fraction (0.6%) of the sRNA loci are ambient temperature-controlled. We identified thermoresponsive miRNAs and identified their target genes using degradome libraries. We verified that the target of the thermoregulated miR169, NF-YA2, is also ambient temperature-regulated. NF-YA2, as the component of the conserved transcriptional regulator NF-Y complex, binds the promoter of the flowering time regulator FT and the auxin biosynthesis gene YUC2. Other differentially expressed loci include thermoresponsive phased siRNA loci that target various auxin pathway genes and tRNA fragments. Furthermore, a temperature dependent 24-nt heterochromatic siRNA locus in the promoter of YUC2 may contribute to the epigenetic regulation of auxin homeostasis. This holistic approach facilitated a better understanding of the role of different sRNA classes in ambient temperature adaptation of plants. This article is protected by copyright. All rights reserved.

Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL): Review from an International Consensus Conference

NARCIS (Netherlands)

T.M. Horton (Terzah); R. Sposto (Richard); P. Brown (Patrick); C.P. Reynolds (Patrick); S.P. Hunger (Stephen); N.J. Winick (Naomi); E.A. Raetz (Elizabeth); W.L. Carroll (William); R.J. Arceci (Robert); M.J. Borowitz (Michael); P.S. Gaynon (Paul); L. Gore (Lia); S. Jeha (Sima); B.J. Maurer (Barry); S.E. Siegel (Stuart); A. Biondi (Andrea); P. Kearns (Pamela); A. Narendran (Aru); L.B. Silverman (Lewis); M.A. Smith (Malcolm); C.M. Zwaan (Christian Michel); J.A. Whitlock (James)

2010-01-01

textabstractOne of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute

Sub-cellular mRNA localization modulates the regulation of gene expression by small RNAs in bacteria

Science.gov (United States)

Teimouri, Hamid; Korkmazhan, Elgin; Stavans, Joel; Levine, Erel

2017-10-01

Small non-coding RNAs can exert significant regulatory activity on gene expression in bacteria. In recent years, substantial progress has been made in understanding bacterial gene expression by sRNAs. However, recent findings that demonstrate that families of mRNAs show non-trivial sub-cellular distributions raise the question of how localization may affect the regulatory activity of sRNAs. Here we address this question within a simple mathematical model. We show that the non-uniform spatial distributions of mRNA can alter the threshold-linear response that characterizes sRNAs that act stoichiometrically, and modulate the hierarchy among targets co-regulated by the same sRNA. We also identify conditions where the sub-cellular organization of cofactors in the sRNA pathway can induce spatial heterogeneity on sRNA targets. Our results suggest that under certain conditions, interpretation and modeling of natural and synthetic gene regulatory circuits need to take into account the spatial organization of the transcripts of participating genes.

Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): review from an international consensus conference.

Science.gov (United States)

Horton, Terzah M; Sposto, Richard; Brown, Patrick; Reynolds, C Patrick; Hunger, Stephen P; Winick, Naomi J; Raetz, Elizabeth A; Carroll, William L; Arceci, Robert J; Borowitz, Michael J; Gaynon, Paul S; Gore, Lia; Jeha, Sima; Maurer, Barry J; Siegel, Stuart E; Biondi, Andrea; Kearns, Pamela R; Narendran, Aru; Silverman, Lewis B; Smith, Malcolm A; Zwaan, C Michel; Whitlock, James A

2010-07-01

One of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute lymphocytic leukemia (ALL) experts addressed this issue (www.ALLNA.org). Two major questions surrounding DLT assessment were explored: (1) how toxicities can be best defined, assessed, and attributed; and (2) how effective dosing of new agents incorporated into multi-agent ALL clinical trials can be safely established in the face of disease- and therapy-related systemic toxicities. The consensus DLT definition incorporates tolerance of resolving Grade 3 and some resolving Grade 4 toxicities with stringent safety monitoring. This functional DLT definition is being tested in two Children's Oncology Group (COG) ALL clinical trials. Copyright 2010 Wiley-Liss, Inc.

Identifying MicroRNAs and Transcript Targets in Jatropha Seeds

Science.gov (United States)

Galli, Vanessa; Guzman, Frank; de Oliveira, Luiz F. V.; Loss-Morais, Guilherme; Körbes, Ana P.; Silva, Sérgio D. A.; Margis-Pinheiro, Márcia M. A. N.; Margis, Rogério

2014-01-01

MicroRNAs, or miRNAs, are endogenously encoded small RNAs that play a key role in diverse plant biological processes. Jatropha curcas L. has received significant attention as a potential oilseed crop for the production of renewable oil. Here, a sRNA library of mature seeds and three mRNA libraries from three different seed development stages were generated by deep sequencing to identify and characterize the miRNAs and pre-miRNAs of J. curcas. Computational analysis was used for the identification of 180 conserved miRNAs and 41 precursors (pre-miRNAs) as well as 16 novel pre-miRNAs. The predicted miRNA target genes are involved in a broad range of physiological functions, including cellular structure, nuclear function, translation, transport, hormone synthesis, defense, and lipid metabolism. Some pre-miRNA and miRNA targets vary in abundance between the three stages of seed development. A search for sequences that produce siRNA was performed, and the results indicated that J. curcas siRNAs play a role in nuclear functions, transport, catalytic processes and disease resistance. This study presents the first large scale identification of J. curcas miRNAs and their targets in mature seeds based on deep sequencing, and it contributes to a functional understanding of these miRNAs. PMID:24551031

Effect of titanium incorporation on the structural, mechanical and biocompatible properties of DLC thin films prepared by reactive-biased target ion beam deposition method

International Nuclear Information System (INIS)

Bharathy, P. Vijai; Nataraj, D.; Chu, Paul K.; Wang, Huaiyu; Yang, Q.; Kiran, M.S.R.N.; Silvestre-Albero, J.; Mangalaraj, D.

2010-01-01

Amorphous diamond like carbon (DLC) and titanium incorporated diamond like carbon (Ti-DLC) thin films were deposited by using reactive-biased target ion beam deposition method. The effects of Ti incorporation and target bias voltage on the microstructure and mechanical properties of the as-deposited films were investigated by means of X-ray photoelectron spectroscopy, Raman spectroscopy, transmission electron microscopy and nano-indentation. It was found that the Ti content in Ti-DLC films gets increased with increasing target bias voltage. At about 4.2 at.% of Ti, uniform sized well dispersed nanocrystals were seen in the DLC matrix. Using FFT analysis, a facility available in the TEM, it was found that the nanocrystals are in cubic TiC phase. Though at the core, the incorporated Ti atoms react with carbon to form cubic TiC; most of the surface exposed Ti atoms were found to react with the atmospheric oxygen to form weakly bonded Ti-O. The presence of TiC nanocrystals greatly modified the sp 3 /sp 2 hybridized bonding ratio and is reflected in mechanical hardness of Ti-DLC films. These films were then tested for their biocompatibility by an invitro cell culturing test. Morphological observation and the cell proliferation test have demonstrated that the human osteoblast cells well attach and proliferate on the surface of Ti incorporated DLC films, suggesting possible applications in bone related implant coatings.

Effect of titanium incorporation on the structural, mechanical and biocompatible properties of DLC thin films prepared by reactive-biased target ion beam deposition method

Energy Technology Data Exchange (ETDEWEB)

Bharathy, P. Vijai [Thin Films and Nanomaterials Lab, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Department of Mechanical Engineering, University of Saskatchewan, Saskatoon (Canada); Nataraj, D., E-mail: de.natraj@gmail.com [Thin Films and Nanomaterials Lab, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Chu, Paul K.; Wang, Huaiyu [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon (Hong Kong); Yang, Q. [Department of Mechanical Engineering, University of Saskatchewan, Saskatoon (Canada); Kiran, M.S.R.N. [School of Physics, University of Hyderabad, Hyderabad, Andra Pradesh (India); Silvestre-Albero, J. [Laboratorio de Materiales Avanzados, Departmento de Quimica Inorganica, Universidad de Alicante, Ap 99, E-03080 Alicante (Spain); Mangalaraj, D. [Thin Films and Nanomaterials Lab, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India)

2010-10-15

Amorphous diamond like carbon (DLC) and titanium incorporated diamond like carbon (Ti-DLC) thin films were deposited by using reactive-biased target ion beam deposition method. The effects of Ti incorporation and target bias voltage on the microstructure and mechanical properties of the as-deposited films were investigated by means of X-ray photoelectron spectroscopy, Raman spectroscopy, transmission electron microscopy and nano-indentation. It was found that the Ti content in Ti-DLC films gets increased with increasing target bias voltage. At about 4.2 at.% of Ti, uniform sized well dispersed nanocrystals were seen in the DLC matrix. Using FFT analysis, a facility available in the TEM, it was found that the nanocrystals are in cubic TiC phase. Though at the core, the incorporated Ti atoms react with carbon to form cubic TiC; most of the surface exposed Ti atoms were found to react with the atmospheric oxygen to form weakly bonded Ti-O. The presence of TiC nanocrystals greatly modified the sp{sup 3}/sp{sup 2} hybridized bonding ratio and is reflected in mechanical hardness of Ti-DLC films. These films were then tested for their biocompatibility by an invitro cell culturing test. Morphological observation and the cell proliferation test have demonstrated that the human osteoblast cells well attach and proliferate on the surface of Ti incorporated DLC films, suggesting possible applications in bone related implant coatings.

A genome-wide analysis of the RNA-guided silencing pathway in coffee reveals insights into its regulatory mechanisms.

Directory of Open Access Journals (Sweden)

Christiane Noronha Fernandes-Brum

Full Text Available microRNAs (miRNAs are derived from self-complementary hairpin structures, while small-interfering RNAs (siRNAs are derived from double-stranded RNA (dsRNA or hairpin precursors. The core mechanism of sRNA production involves DICER-like (DCL in processing the smallRNAs (sRNAs and ARGONAUTE (AGO as effectors of silencing, and siRNA biogenesis also involves action of RNA-Dependent RNA Polymerase (RDR, Pol IV and Pol V in biogenesis. Several other proteins interact with the core proteins to guide sRNA biogenesis, action, and turnover. We aimed to unravel the components and functions of the RNA-guided silencing pathway in a non-model plant species of worldwide economic relevance. The sRNA-guided silencing complex members have been identified in the Coffea canephora genome, and they have been characterized at the structural, functional, and evolutionary levels by computational analyses. Eleven AGO proteins, nine DCL proteins (which include a DCL1-like protein that was not previously annotated, and eight RDR proteins were identified. Another 48 proteins implicated in smallRNA (sRNA pathways were also identified. Furthermore, we identified 235 miRNA precursors and 317 mature miRNAs from 113 MIR families, and we characterized ccp-MIR156, ccp-MIR172, and ccp-MIR390. Target prediction and gene ontology analyses of 2239 putative targets showed that significant pathways in coffee are targeted by miRNAs. We provide evidence of the expansion of the loci related to sRNA pathways, insights into the activities of these proteins by domain and catalytic site analyses, and gene expression analysis. The number of MIR loci and their targeted pathways highlight the importance of miRNAs in coffee. We identified several roles of sRNAs in C. canephora, which offers substantial insight into better understanding the transcriptional and post-transcriptional regulation of this major crop.

RNA-Seq analysis uncovers non-coding small RNA system of Mycobacterium neoaurum in the metabolism of sterols to accumulate steroid intermediates.

Science.gov (United States)

Liu, Min; Zhu, Zhan-Tao; Tao, Xin-Yi; Wang, Feng-Qing; Wei, Dong-Zhi

2016-04-25

Understanding the metabolic mechanism of sterols to produce valuable steroid intermediates in mycobacterium by a noncoding small RNA (sRNA) view is still limited. In the work, RNA-seq was implemented to investigate the noncoding transcriptome of Mycobacterium neoaurum (Mn) in the transformation process of sterols to valuable steroid intermediates, including 9α-hydroxy-4-androstene-3,17-dione (9OHAD), 1,4-androstadiene-3,17-dione (ADD), and 22-hydroxy-23, 24-bisnorchola-1,4-dien-3-one (1,4-BNA). A total of 263 sRNA candidates were predicted from the intergenic regions in Mn. Differential expression of sRNA candidates was explored in the wide type Mn with vs without sterol addition, and the steroid intermediate producing Mn strains vs wide type Mn with sterol addition, respectively. Generally, sRNA candidates were differentially expressed in various strains, but there were still some shared candidates with outstandingly upregulated or downregulated expression in these steroid producing strains. Accordingly, four regulatory networks were constructed to reveal the direct and/or indirect interactions between sRNA candidates and their target genes in four groups, including wide type Mn with vs without sterol addition, 9OHAD, ADD, and BNA producing strains vs wide type Mn with sterol addition, respectively. Based on these constructed networks, several highly focused sRNA candidates were discovered to be prevalent in the networks, which showed comprehensive regulatory roles in various cellular processes, including lipid transport and metabolism, amino acid transport and metabolism, signal transduction, cell envelope biosynthesis and ATP synthesis. To explore the functional role of sRNA candidates in Mn cells, we manipulated the overexpression of candidates 131 and 138 in strain Mn-9OHAD, which led to enhanced production of 9OHAD from 1.5- to 2.3-fold during 6 d' fermentation and a slight effect on growth rate. This study revealed the complex and important regulatory

Extended Fitts' model of pointing time in eye-gaze input system - Incorporating effects of target shape and movement direction into modeling.

Science.gov (United States)

Murata, Atsuo; Fukunaga, Daichi

2018-04-01

This study attempted to investigate the effects of the target shape and the movement direction on the pointing time using an eye-gaze input system and extend Fitts' model so that these factors are incorporated into the model and the predictive power of Fitts' model is enhanced. The target shape, the target size, the movement distance, and the direction of target presentation were set as within-subject experimental variables. The target shape included: a circle, and rectangles with an aspect ratio of 1:1, 1:2, 1:3, and 1:4. The movement direction included eight directions: upper, lower, left, right, upper left, upper right, lower left, and lower right. On the basis of the data for identifying the effects of the target shape and the movement direction on the pointing time, an attempt was made to develop a generalized and extended Fitts' model that took into account the movement direction and the target shape. As a result, the generalized and extended model was found to fit better to the experimental data, and be more effective for predicting the pointing time for a variety of human-computer interaction (HCI) task using an eye-gaze input system. Copyright © 2017. Published by Elsevier Ltd.

Identification and validation of sRNAs in Edwardsiella tarda S08.

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Yuying Sun

Full Text Available Bacterial small non-coding RNAs (sRNAs are known as novel regulators involved in virulence, stress responsibility, and so on. Recently, a lot of new researches have highlighted the critical roles of sRNAs in fine-tune gene regulation in both prokaryotes and eukaryotes. Edwardsiella tarda (E. tarda is a gram-negative, intracellular pathogen that causes edwardsiellosis in fish. Thus far, no sRNA has been reported in E. tarda. The present study represents the first attempt to identify sRNAs in E. tarda S08. Ten sRNAs were validated by RNA sequencing and quantitative PCR (qPCR. ET_sRNA_1 and ET_sRNA_2 were homolous to tmRNA and GcvB, respectively. However, the other candidate sRNAs have not been reported till now. The cellular abundance of 10 validated sRNA was detected by qPCR at different growth phases to monitor their biosynthesis. Nine candidate sRNAs were expressed in the late-stage of exponential growth and stationary stages of growth (36~60 h. And the expression of the nine sRNAs was growth phase-dependent. But ET_sRNA_10 was almost expressed all the time and reached the highest peak at 48 h. Their targets were predicted by TargetRNA2 and each sRNA target contains some genes that directly or indirectly relate to virulence. These results preliminary showed that sRNAs probably play a regulatory role of virulence in E. tarda.

Design of a novel integration-deficient lentivector technology that incorporates genetic and posttranslational elements to target human dendritic cells.

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Tareen, Semih U; Kelley-Clarke, Brenna; Nicolai, Christopher J; Cassiano, Linda A; Nelson, Lisa T; Slough, Megan M; Vin, Chintan D; Odegard, Jared M; Sloan, Derek D; Van Hoeven, Neal; Allen, James M; Dubensky, Thomas W; Robbins, Scott H

2014-03-01

As sentinels of the immune system, dendritic cells (DCs) play an essential role in regulating cellular immune responses. One of the main challenges of developing DC-targeted therapies includes the delivery of antigen to DCs in order to promote the activation of antigen-specific effector CD8 T cells. With the goal of creating antigen-directed immunotherapeutics that can be safely administered directly to patients, Immune Design has developed a platform of novel integration-deficient lentiviral vectors that target and deliver antigen-encoding nucleic acids to human DCs. This platform, termed ID-VP02, utilizes a novel genetic variant of a Sindbis virus envelope glycoprotein with posttranslational carbohydrate modifications in combination with Vpx, a SIVmac viral accessory protein, to achieve efficient targeting and transduction of human DCs. In addition, ID-VP02 incorporates safety features in its design that include two redundant mechanisms to render ID-VP02 integration-deficient. Here, we describe the characteristics that allow ID-VP02 to specifically transduce human DCs, and the advances that ID-VP02 brings to conventional third-generation lentiviral vector design as well as demonstrate upstream production yields that will enable manufacturing feasibility studies to be conducted.

SoMART, a web server for miRNA, tasiRNA and target gene analysis in Solanaceae plants

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Plant micro(mi)RNAs and trans-acting small interfering (tasi)RNAs mediate posttranscriptional silencing of genes and play important roles in a variety of biological processes. Although bioinformatics prediction and small (s)RNA cloning are the key approaches used for identification of miRNAs, tasiRN...

Staphylococcus aureus Sortase A-Mediated Incorporation of Peptides: Effect of Peptide Modification on Incorporation.

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Silvie Hansenová Maňásková

Full Text Available The endogenous Staphylococcus aureus sortase A (SrtA transpeptidase covalently anchors cell wall-anchored (CWA proteins equipped with a specific recognition motif (LPXTG into the peptidoglycan layer of the staphylococcal cell wall. Previous in situ experiments have shown that SrtA is also able to incorporate exogenous, fluorescently labelled, synthetic substrates equipped with the LPXTG motif (K(FITCLPETG-amide into the bacterial cell wall, albeit at high concentrations of 500 μM to 1 mM. In the present study, we have evaluated the effect of substrate modification on the incorporation efficiency. This revealed that (i by elongation of LPETG-amide with a sequence of positively charged amino acids, derived from the C-terminal domain of physiological SrtA substrates, the incorporation efficiency was increased by 20-fold at 10 μM, 100 μM and 250 μM; (ii Substituting aspartic acid (E for methionine increased the incorporation of the resulting K(FITCLPMTG-amide approximately three times at all concentrations tested; (iii conjugation of the lipid II binding antibiotic vancomycin to K(FITCLPMTG-amide resulted in the same incorporation levels as K(FITCLPETG-amide, but much more efficient at an impressive 500-fold lower substrate concentration. These newly developed synthetic substrates can potentially find broad applications in for example the in situ imaging of bacteria; the incorporation of antibody recruiting moieties; the targeted delivery and covalent incorporation of antimicrobial compounds into the bacterial cell wall.

A 3' UTR-Derived Small RNA Provides the Regulatory Noncoding Arm of the Inner Membrane Stress Response.

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Chao, Yanjie; Vogel, Jörg

2016-02-04

Small RNAs (sRNAs) from conserved noncoding genes are crucial regulators in bacterial signaling pathways but have remained elusive in the Cpx response to inner membrane stress. Here we report that an alternative biogenesis pathway releasing the conserved mRNA 3' UTR of stress chaperone CpxP as an ∼60-nt sRNA provides the noncoding arm of the Cpx response. This so-called CpxQ sRNA, generated by general mRNA decay through RNase E, acts as an Hfq-dependent repressor of multiple mRNAs encoding extracytoplasmic proteins. Both CpxQ and the Cpx pathway are required for cell survival under conditions of dissipation of membrane potential. Our discovery of CpxQ illustrates how the conversion of a transcribed 3' UTR into an sRNA doubles the output of a single mRNA to produce two factors with spatially segregated functions during inner membrane stress: a chaperone that targets problematic proteins in the periplasm and a regulatory RNA that dampens their synthesis in the cytosol. Copyright © 2016 Elsevier Inc. All rights reserved.

Incorporation of aptamers in the terminal loop of shRNAs yields an effective and novel combinatorial targeting strategy.

Science.gov (United States)

Pang, Ka Ming; Castanotto, Daniela; Li, Haitang; Scherer, Lisa; Rossi, John J

2018-01-09

Gene therapy by engineering patient's own blood cells to confer HIV resistance can potentially lead to a functional cure for AIDS. Toward this goal, we have previously developed an anti-HIV lentivirus vector that deploys a combination of shRNA, ribozyme and RNA decoy. To further improve this therapeutic vector against viral escape, we sought an additional reagent to target HIV integrase. Here, we report the development of a new strategy for selection and expression of aptamer for gene therapy. We developed a SELEX protocol (multi-tag SELEX) for selecting RNA aptamers against proteins with low solubility or stability, such as integrase. More importantly, we expressed these aptamers in vivo by incorporating them in the terminal loop of shRNAs. This novel strategy allowed efficient expression of the shRNA-aptamer fusions that targeted RNAs and proteins simultaneously. Expressed shRNA-aptamer fusions targeting HIV integrase or reverse transcriptase inhibited HIV replication in cell cultures. Viral inhibition was further enhanced by combining an anti-integrase aptamer with an anti-HIV Tat-Rev shRNA. This construct exhibited efficacy comparable to that of integrase inhibitor Raltegravir. Our strategy for the selection and expression of RNA aptamers can potentially extend to other gene therapy applications. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Spot 42 Small RNA Regulates Arabinose-Inducible araBAD Promoter Activity by Repressing Synthesis of the High-Affinity Low-Capacity Arabinose Transporter

Science.gov (United States)

Chen, Jiandong

2016-01-01

ABSTRACT The l-arabinose-inducible araBAD promoter (PBAD) enables tightly controlled and tunable expression of genes of interest in a broad range of bacterial species. It has been used successfully to study bacterial sRNA regulation, where PBAD drives expression of target mRNA translational fusions. Here we report that in Escherichia coli, Spot 42 sRNA regulates PBAD promoter activity by affecting arabinose uptake. We demonstrate that Spot 42 sRNA represses araF, a gene encoding the AraF subunit of the high-affinity low-capacity arabinose transporter AraFGH, through direct base-pairing interactions. We further show that endogenous Spot 42 sRNA is sufficient to repress araF expression under various growth conditions. Finally, we demonstrate this posttranscriptional repression has a biological consequence, decreasing the induction of PBAD at low levels of arabinose. This problem can be circumvented using strategies reported previously for avoiding all-or-none induction behavior, such as through constitutive expression of the low-affinity high-capacity arabinose transporter AraE or induction with a higher concentration of inducers. This work adds araF to the set of Spot 42-regulated genes, in agreement with previous studies suggesting that Spot 42, itself negatively regulated by the cyclic AMP (cAMP) receptor protein-cAMP complex, reinforces the catabolite repression network. IMPORTANCE The bacterial arabinose-inducible system is widely used for titratable control of gene expression. We demonstrate here that a posttranscriptional mechanism mediated by Spot 42 sRNA contributes to the functionality of the PBAD system at subsaturating inducer concentrations by affecting inducer uptake. Our finding extends the inputs into the known transcriptional control for the PBAD system and has implications for improving its usage for tunable gene expression. PMID:27849174

A qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics.

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Feng, Lihui; Rutherford, Steven T; Papenfort, Kai; Bagert, John D; van Kessel, Julia C; Tirrell, David A; Wingreen, Ned S; Bassler, Bonnie L

2015-01-15

Quorum sensing is a cell-cell communication process that bacteria use to transition between individual and social lifestyles. In vibrios, homologous small RNAs called the Qrr sRNAs function at the center of quorum-sensing pathways. The Qrr sRNAs regulate multiple mRNA targets including those encoding the quorum-sensing regulatory components luxR, luxO, luxM, and aphA. We show that a representative Qrr, Qrr3, uses four distinct mechanisms to control its particular targets: the Qrr3 sRNA represses luxR through catalytic degradation, represses luxM through coupled degradation, represses luxO through sequestration, and activates aphA by revealing the ribosome binding site while the sRNA itself is degraded. Qrr3 forms different base-pairing interactions with each mRNA target, and the particular pairing strategy determines which regulatory mechanism occurs. Combined mathematical modeling and experiments show that the specific Qrr regulatory mechanism employed governs the potency, dynamics, and competition of target mRNA regulation, which in turn, defines the overall quorum-sensing response. Copyright © 2015 Elsevier Inc. All rights reserved.

Trans-kingdom cross-talk

DEFF Research Database (Denmark)

Knip, Marijn; Constantin, Maria-Ermioni; Thordal-Christensen, Hans

2014-01-01

This review focuses on the mobility of small RNA (sRNA) molecules from the perspective of trans-kingdom gene silencing. Mobility of sRNA molecules within organisms is a well-known phenomenon, facilitating gene silencing between cells and tissues. sRNA signals are also transmitted between organism...

Identification of novel growth phase- and media-dependent small non-coding RNAs in Streptococcus pyogenes M49 using intergenic tiling arrays

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Patenge Nadja

2012-10-01

Full Text Available Abstract Background Small non-coding RNAs (sRNAs have attracted attention as a new class of gene regulators in both eukaryotes and bacteria. Genome-wide screening methods have been successfully applied in Gram-negative bacteria to identify sRNA regulators. Many sRNAs are well characterized, including their target mRNAs and mode of action. In comparison, little is known about sRNAs in Gram-positive pathogens. In this study, we identified novel sRNAs in the exclusively human pathogen Streptococcus pyogenes M49 (Group A Streptococcus, GAS M49, employing a whole genome intergenic tiling array approach. GAS is an important pathogen that causes diseases ranging from mild superficial infections of the skin and mucous membranes of the naso-pharynx, to severe toxic and invasive diseases. Results We identified 55 putative sRNAs in GAS M49 that were expressed during growth. Of these, 42 were novel. Some of the newly-identified sRNAs belonged to one of the common non-coding RNA families described in the Rfam database. Comparison of the results of our screen with the outcome of two recently published bioinformatics tools showed a low level of overlap between putative sRNA genes. Previously, 40 potential sRNAs have been reported to be expressed in a GAS M1T1 serotype, as detected by a whole genome intergenic tiling array approach. Our screen detected 12 putative sRNA genes that were expressed in both strains. Twenty sRNA candidates appeared to be regulated in a medium-dependent fashion, while eight sRNA genes were regulated throughout growth in chemically defined medium. Expression of candidate genes was verified by reverse transcriptase-qPCR. For a subset of sRNAs, the transcriptional start was determined by 5′ rapid amplification of cDNA ends-PCR (RACE-PCR analysis. Conclusions In accord with the results of previous studies, we found little overlap between different screening methods, which underlines the fact that a comprehensive analysis of s

Incorporating functionalized polyethylene glycol lipids into reprecipitated conjugated polymer nanoparticles for bioconjugation and targeted labeling of cells

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Kandel, Prakash K.; Fernando, Lawrence P.; Ackroyd, P. Christine; Christensen, Kenneth A.

2011-03-01

We report a simple and rapid method to prepare extremely bright, functionalized, stable, and biocompatible conjugated polymer nanoparticles incorporating functionalized polyethylene glycol (PEG) lipids by reprecipitation. These nanoparticles retain the fundamental spectroscopic properties of conjugated polymer nanoparticles prepared without PEG lipid, but demonstrate greater hydrophilicity and quantum yield compared to unmodified conjugated polymer nanoparticles. The sizes of these nanoparticles, as determined by TEM, were 21-26 nm. Notably, these nanoparticles were prepared with several PEG lipid functional end groups, including biotin and carboxy moieties that can be easily conjugated to biomolecules. We have demonstrated the availability of these end groups for functionalization using the interaction of biotin PEG lipid conjugated polymer nanoparticles with streptavidin. Biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-linked magnetic beads, while carboxy and methoxy PEG lipid modified nanoparticles did not. Similarly, biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-coated glass slides and could be visualized as diffraction-limited spots, while nanoparticles without PEG lipid or with non-biotin PEG lipid end groups were not bound. To demonstrate that nanoparticle functionalization could be used for targeted labelling of specific cellular proteins, biotinylated PEG lipid conjugated polymer nanoparticles were bound to biotinylated anti-CD16/32 antibodies on J774A.1 cell surface receptors, using streptavidin as a linker. This work represents the first demonstration of targeted delivery of conjugated polymer nanoparticles and demonstrates the utility of these new nanoparticles for fluorescence based imaging and sensing.We report a simple and rapid method to prepare extremely bright, functionalized, stable, and biocompatible conjugated polymer nanoparticles incorporating functionalized polyethylene glycol (PEG

Novel meiotic miRNAs and indications for a role of phasiRNAs in meiosis

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Small RNAs (sRNA) add additional layers to the regulation of gene expression, with siRNAs directing gene silencing at the DNA level by RdDM (RNA-directed DNA methylation), and miRNAs directing post-transcriptional regulation of specific target genes, mostly by mRNA cleavage. We used manually isolate...

Plodnost i veličina legla kod europske srne (capreolus capreolus, L.) u šumi Haljevo

OpenAIRE

Nikolandić, Đuro; Degmečić, Dražen

2007-01-01

U razdoblju od 1968. do 1972. godine vršena su ekološka istraživanja srna u šumama Baranje. Iz toga doba jednim projektom istraživanja postavljen je cilj ustanoviti plodnost populacije srna u šumi Haljevo. Redovito parenje srna počinjalo je u drugoj polovici srpnja a završavalo oko sredine kolovoza. Zametak (embrij) oplođenih srna je zbog postojanja embriotenije u fazi mirovanja, odnosno zbog neprimjetne diobe stanica zametka, sve do kraja prosinca, prostim okom čovjeka nije primjetan. Iz tog...

Synthesis and characterization of boron incorporated diamond-like carbon thin films

International Nuclear Information System (INIS)

Zhang, L.L.; Yang, Q.; Tang, Y.; Yang, L.; Zhang, C.; Hu, Y.; Cui, X.

2015-01-01

Boron incorporated diamond-like carbon (B-DLC) (up to 8 wt.% boron) thin films were synthesized on silicon wafers using biased target ion beam deposition technique, where diamond-like carbon (DLC) was deposited by ion beam deposition and boron (B) was simultaneously incorporated by biased target sputtering of a boron carbide (B 4 C) target under different conditions. Pure DLC films and B–C films were also synthesized by ion beam deposition and biased target sputtering of B 4 C under similar conditions, respectively, as reference samples. The microstructure and mechanical properties of the synthesized films have been characterized by various technologies. It has been found that B exists in different states in B-DLC, including carbon-rich and B-rich boron carbides, boron suboxide and boron oxide, and the oxidation of B probably occurs during the film deposition. The incorporation of B into DLC leads to the increase of sp 3 bonded carbon in the films, the increase of both film hardness and elastic modulus, and the decrease of both surface roughness and friction coefficient. Furthermore, the content of sp 3 bonded carbon, film hardness and elastic modulus increase, and the film surface roughness and friction coefficient decrease with the increase of B-rich carbide in the B-DLC films. - Highlights: • Biased target ion beam deposition technique is promising to produce high quality DLC based thin films; • Boron exists in different states in B-DLC thin films; • The incorporation of B to DLC with different levels leads to improved film properties; • The fraction of sp 3 bonded C in B-DLC thin films increase with the increase of B-rich carbide content in the films

Linear energy transfer incorporated intensity modulated proton therapy optimization

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Cao, Wenhua; Khabazian, Azin; Yepes, Pablo P.; Lim, Gino; Poenisch, Falk; Grosshans, David R.; Mohan, Radhe

2018-01-01

The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the

Regulation of bacterial photosynthesis genes by the small noncoding RNA PcrZ.

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Mank, Nils N; Berghoff, Bork A; Hermanns, Yannick N; Klug, Gabriele

2012-10-02

The small RNA PcrZ (photosynthesis control RNA Z) of the facultative phototrophic bacterium Rhodobacter sphaeroides is induced upon a drop of oxygen tension with similar kinetics to those of genes for components of photosynthetic complexes. High expression of PcrZ depends on PrrA, the response regulator of the PrrB/PrrA two-component system with a central role in redox regulation in R. sphaeroides. In addition the FnrL protein, an activator of some photosynthesis genes at low oxygen tension, is involved in redox-dependent expression of this small (s)RNA. Overexpression of full-length PcrZ in R. sphaeroides affects expression of a small subset of genes, most of them with a function in photosynthesis. Some mRNAs from the photosynthetic gene cluster were predicted to be putative PcrZ targets and results from an in vivo reporter system support these predictions. Our data reveal a negative effect of PcrZ on expression of its target mRNAs. Thus, PcrZ counteracts the redox-dependent induction of photosynthesis genes, which is mediated by protein regulators. Because PrrA directly activates photosynthesis genes and at the same time PcrZ, which negatively affects photosynthesis gene expression, this is one of the rare cases of an incoherent feed-forward loop including an sRNA. Our data identified PcrZ as a trans acting sRNA with a direct regulatory function in formation of photosynthetic complexes and provide a model for the control of photosynthesis gene expression by a regulatory network consisting of proteins and a small noncoding RNA.

Translational regulation of gene expression by an anaerobically induced small non-coding RNA in Escherichia coli

DEFF Research Database (Denmark)

Boysen, Anders; Møller-Jensen, Jakob; Kallipolitis, Birgitte H.

2010-01-01

Small non-coding RNAs (sRNA) have emerged as important elements of gene regulatory circuits. In enterobacteria such as Escherichia coli and Salmonella many of these sRNAs interact with the Hfq protein, an RNA chaperone similar to mammalian Sm-like proteins and act in the post...... that adaptation to anaerobic growth involves the action of a small regulatory RNA....... of at least one sRNA regulator. Here, we extend this view by the identification and characterization of a highly conserved, anaerobically induced small sRNA in E. coli, whose expression is strictly dependent on the anaerobic transcriptional fumarate and nitrate reductase regulator (FNR). The sRNA, named Fnr...

Genome-wide identification of microRNA and siRNA responsive to endophytic beneficial diazotrophic bacteria in maize.

Science.gov (United States)

Thiebaut, Flávia; Rojas, Cristian A; Grativol, Clícia; Motta, Mariana Romeiro; Vieira, Tauan; Regulski, Michael; Martienssen, Robert A; Farinelli, Laurent; Hemerly, Adriana S; Ferreira, Paulo C G

2014-09-06

Small RNA (sRNA) has been described as a regulator of gene expression. In order to understand the role of maize sRNA (Zea mays-hybrid UENF 506-8) during association with endophytic nitrogen-fixing bacteria, we analyzed the sRNA regulated by its association with two diazotrophic bacteria, Herbaspirillum seropedicae and Azospirillum brasilense. Deep sequencing analysis was done with RNA extracted from plants inoculated with H. seropedicae, allowing the identification of miRNA and siRNA. A total of 25 conserved miRNA families and 15 novel miRNAs were identified. A dynamic regulation in response to inoculation was also observed. A hypothetical model involving copper-miRNA is proposed, emphasizing the fact that the up-regulation of miR397, miR398, miR408 and miR528, which is followed by inhibition of their targets, can facilitate association with diazotrophic bacteria. Similar expression patterns were observed in samples inoculated with A. brasilense. Moreover, novel miRNA and siRNA were classified in the Transposable Elements (TE) database, and an enrichment of siRNA aligned with TE was observed in the inoculated samples. In addition, an increase in 24-nt siRNA mapping to genes was observed, which was correlated with an increase in methylation of the coding regions and a subsequent reduction in transcription. Our results show that maize has RNA-based silencing mechanisms that can trigger specific responses when plants interact with beneficial endophytic diazotrophic bacteria. Our findings suggest important roles for sRNA regulation in maize, and probably in other plants, during association with diazotrophic bacteria, emphasizing the up-regulation of Cu-miRNA.

Biotechnological uses of RNAi in plants: risk assessment considerations.

Science.gov (United States)

Casacuberta, Josep M; Devos, Yann; du Jardin, Patrick; Ramon, Matthew; Vaucheret, Hervé; Nogué, Fabien

2015-03-01

RNAi offers opportunities to generate new traits in genetically modified (GM) plants. Instead of expressing novel proteins, RNAi-based GM plants reduce target gene expression. Silencing of off-target genes may trigger unintended effects, and identifying these genes would facilitate risk assessment. However, using bioinformatics alone is not reliable, due to the lack of genomic data and insufficient knowledge of mechanisms governing mRNA-small (s)RNA interactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential impact of the HEN1 homolog HENN-1 on 21U and 26G RNAs in the germline of Caenorhabditis elegans.

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Leonie M Kamminga

Full Text Available RNA interference (RNAi-related pathways affect gene activity by sequence-specific recruitment of Ago proteins to mRNA target molecules. The sequence specificity of this process stems from small RNA (sRNA co-factors bound by the Ago protein. Stability of sRNA molecules in some pathways is in part regulated by Hen1-mediated methylation of their 3' ends. Here we describe the effects of the Caenorhabditis elegans HEN1 RNA-methyl-transferase homolog, HENN-1, on the different RNAi pathways in this nematode. We reveal differential effects of HENN-1 on the two pathways that are known to employ methylated sRNA molecules: the 26G and 21U pathways. Surprisingly, in the germline, stability of 21U RNAs, the C. elegans piRNAs, is only mildly affected by loss of methylation; and introduction of artificial 21U target RNA does not further destabilize non-methylated 21U RNAs. In contrast, most 26G RNAs display reduced stability and respond to loss of HENN-1 by displaying increased 3'-uridylation frequencies. Within the 26G RNA class, we find that specifically ERGO-1-bound 26G RNAs are modified by HENN-1, while ALG-3/ALG-4-bound 26G RNAs are not. Global gene expression analysis of henn-1 mutants reveals mild effects, including down-regulation of many germline-expressed genes. Our data suggest that, apart from direct effects of reduced 26G RNA levels of henn-1 on gene expression, most effects on global gene expression are indirect. These studies further refine our understanding of endogenous RNAi in C. elegans and the roles for Hen1 like enzymes in these pathways.

SRD: a Staphylococcus regulatory RNA database.

Science.gov (United States)

Sassi, Mohamed; Augagneur, Yoann; Mauro, Tony; Ivain, Lorraine; Chabelskaya, Svetlana; Hallier, Marc; Sallou, Olivier; Felden, Brice

2015-05-01

An overflow of regulatory RNAs (sRNAs) was identified in a wide range of bacteria. We designed and implemented a new resource for the hundreds of sRNAs identified in Staphylococci, with primary focus on the human pathogen Staphylococcus aureus. The "Staphylococcal Regulatory RNA Database" (SRD, http://srd.genouest.org/) compiled all published data in a single interface including genetic locations, sequences and other features. SRD proposes novel and simplified identifiers for Staphylococcal regulatory RNAs (srn) based on the sRNA's genetic location in S. aureus strain N315 which served as a reference. From a set of 894 sequences and after an in-depth cleaning, SRD provides a list of 575 srn exempt of redundant sequences. For each sRNA, their experimental support(s) is provided, allowing the user to individually assess their validity and significance. RNA-seq analysis performed on strains N315, NCTC8325, and Newman allowed us to provide further details, upgrade the initial annotation, and identified 159 RNA-seq independent transcribed sRNAs. The lists of 575 and 159 sRNAs sequences were used to predict the number and location of srns in 18 S. aureus strains and 10 other Staphylococci. A comparison of the srn contents within 32 Staphylococcal genomes revealed a poor conservation between species. In addition, sRNA structure predictions obtained with MFold are accessible. A BLAST server and the intaRNA program, which is dedicated to target prediction, were implemented. SRD is the first sRNA database centered on a genus; it is a user-friendly and scalable device with the possibility to submit new sequences that should spread in the literature. © 2015 Sassi et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Gene dosage compensation calibrates four regulatory RNAs to control Vibrio cholerae quorum sensing

DEFF Research Database (Denmark)

Svenningsen, Sine L; Tu, Kimberly C; Bassler, Bonnie L

2009-01-01

the quorum regulatory RNAs 1-4 (Qrr1-4). The four Qrr sRNAs are functionally redundant. That is, expression of any one of them is sufficient for wild-type quorum-sensing behaviour. Here, we show that the combined action of two feedback loops, one involving the sRNA-activator LuxO and one involving the sRNA......Quorum sensing is a mechanism of cell-to-cell communication that allows bacteria to coordinately regulate gene expression in response to changes in cell-population density. At the core of the Vibrio cholerae quorum-sensing signal transduction pathway reside four homologous small RNAs (sRNAs), named......-target HapR, promotes gene dosage compensation between the four qrr genes. Gene dosage compensation adjusts the total Qrr1-4 sRNA pool and provides the molecular mechanism underlying sRNA redundancy. The dosage compensation mechanism is exquisitely sensitive to small perturbations in Qrr levels. Precisely...

DeAnnIso: a tool for online detection and annotation of isomiRs from small RNA sequencing data.

Science.gov (United States)

Zhang, Yuanwei; Zang, Qiguang; Zhang, Huan; Ban, Rongjun; Yang, Yifan; Iqbal, Furhan; Li, Ao; Shi, Qinghua

2016-07-08

Small RNA (sRNA) Sequencing technology has revealed that microRNAs (miRNAs) are capable of exhibiting frequent variations from their canonical sequences, generating multiple variants: the isoforms of miRNAs (isomiRs). However, integrated tool to precisely detect and systematically annotate isomiRs from sRNA sequencing data is still in great demand. Here, we present an online tool, DeAnnIso (Detection and Annotation of IsomiRs from sRNA sequencing data). DeAnnIso can detect all the isomiRs in an uploaded sample, and can extract the differentially expressing isomiRs from paired or multiple samples. Once the isomiRs detection is accomplished, detailed annotation information, including isomiRs expression, isomiRs classification, SNPs in miRNAs and tissue specific isomiR expression are provided to users. Furthermore, DeAnnIso provides a comprehensive module of target analysis and enrichment analysis for the selected isomiRs. Taken together, DeAnnIso is convenient for users to screen for isomiRs of their interest and useful for further functional studies. The server is implemented in PHP + Perl + R and available to all users for free at: http://mcg.ustc.edu.cn/bsc/deanniso/ and http://mcg2.ustc.edu.cn/bsc/deanniso/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

The UEA Small RNA Workbench: A Suite of Computational Tools for Small RNA Analysis.

Science.gov (United States)

Mohorianu, Irina; Stocks, Matthew Benedict; Applegate, Christopher Steven; Folkes, Leighton; Moulton, Vincent

2017-01-01

RNA silencing (RNA interference, RNAi) is a complex, highly conserved mechanism mediated by short, typically 20-24 nt in length, noncoding RNAs known as small RNAs (sRNAs). They act as guides for the sequence-specific transcriptional and posttranscriptional regulation of target mRNAs and play a key role in the fine-tuning of biological processes such as growth, response to stresses, or defense mechanism.High-throughput sequencing (HTS) technologies are employed to capture the expression levels of sRNA populations. The processing of the resulting big data sets facilitated the computational analysis of the sRNA patterns of variation within biological samples such as time point experiments, tissue series or various treatments. Rapid technological advances enable larger experiments, often with biological replicates leading to a vast amount of raw data. As a result, in this fast-evolving field, the existing methods for sequence characterization and prediction of interaction (regulatory) networks periodically require adapting or in extreme cases, a complete redesign to cope with the data deluge. In addition, the presence of numerous tools focused only on particular steps of HTS analysis hinders the systematic parsing of the results and their interpretation.The UEA small RNA Workbench (v1-4), described in this chapter, provides a user-friendly, modular, interactive analysis in the form of a suite of computational tools designed to process and mine sRNA datasets for interesting characteristics that can be linked back to the observed phenotypes. First, we show how to preprocess the raw sequencing output and prepare it for downstream analysis. Then we review some quality checks that can be used as a first indication of sources of variability between samples. Next we show how the Workbench can provide a comparison of the effects of different normalization approaches on the distributions of expression, enhanced methods for the identification of differentially expressed

A high-power target experiment

CERN Document Server

Kirk, H G; Ludewig, H; Palmer, Robert; Samulyak, V; Simos, N; Tsang, Thomas; Bradshaw, T W; Drumm, Paul V; Edgecock, T R; Ivanyushenkov, Yury; Bennett, Roger; Efthymiopoulos, Ilias; Fabich, Adrian; Haseroth, H; Haug, F; Lettry, Jacques; Hayato, Y; Yoshimura, Koji; Gabriel, Tony A; Graves, Van; Spampinato, P; Haines, John; McDonald, Kirk T

2005-01-01

We describe an experiment designed as a proof-of-principle test for a target system capable of converting a 4 MW proton beam into a high-intensity muon beam suitable for incorporation into either a neutrino factory complex or a muon collider. The target system is based on exposing a free mercury jet to an intense proton beam in the presence of a high strength solenoidal field.

smRNAome profiling to identify conserved and novel microRNAs in Stevia rebaudiana Bertoni

Science.gov (United States)

2012-01-01

Background MicroRNAs (miRNAs) constitute a family of small RNA (sRNA) population that regulates the gene expression and plays an important role in plant development, metabolism, signal transduction and stress response. Extensive studies on miRNAs have been performed in different plants such as Arabidopsis thaliana, Oryza sativa etc. and volume of the miRNA database, mirBASE, has been increasing on day to day basis. Stevia rebaudiana Bertoni is an important perennial herb which accumulates high concentrations of diterpene steviol glycosides which contributes to its high indexed sweetening property with no calorific value. Several studies have been carried out for understanding molecular mechanism involved in biosynthesis of these glycosides, however, information about miRNAs has been lacking in S. rebaudiana. Deep sequencing of small RNAs combined with transcriptomic data is a powerful tool for identifying conserved and novel miRNAs irrespective of availability of genome sequence data. Results To identify miRNAs in S. rebaudiana, sRNA library was constructed and sequenced using Illumina genome analyzer II. A total of 30,472,534 reads representing 2,509,190 distinct sequences were obtained from sRNA library. Based on sequence similarity, we identified 100 miRNAs belonging to 34 highly conserved families. Also, we identified 12 novel miRNAs whose precursors were potentially generated from stevia EST and nucleotide sequences. All novel sequences have not been earlier described in other plant species. Putative target genes were predicted for most conserved and novel miRNAs. The predicted targets are mainly mRNA encoding enzymes regulating essential plant metabolic and signaling pathways. Conclusions This study led to the identification of 34 highly conserved miRNA families and 12 novel potential miRNAs indicating that specific miRNAs exist in stevia species. Our results provided information on stevia miRNAs and their targets building a foundation for future studies to

Global Systems-Level Analysis of Hfq and SmpB Deletion Mutants in Salmonella: Implications for Virulence and Global Protein Translation

Energy Technology Data Exchange (ETDEWEB)

Ansong, Charles; Yoon, Hyunjin; Porwollik, Steffen; Mottaz-Brewer, Heather; Petritis, Brianne O.; Jaitly, Navdeep; Adkins, Joshua N.; Mcclelland, Michael; Heffron, Fred; Smith, Richard D.

2009-03-11

In recent years the profound importance of sRNA-mediated translational/post-transcriptional regulation has been increasingly appreciated. However, the global role played by translational regulation in control of gene expression has never been elucidated in any organism for the simple reason that global proteomics methods required to accurately characterize post-transcriptional processes and the knowledge of translational control mechanisms have only become available within the last few years. The proteins Hfq and SmpB are essential for the biological activity of a range of regulatory sRNAs and thus provide a means to identify potential targets of sRNA regulation. We performed a sample-matched global proteomics and transcriptional analysis to examine the role of Hfq and SmpB in global protein translation and virulence using the Salmonella typhimurium model system. Samples were analyzed from bacteria grown under four different conditions; two laboratory conditions and two that are thought to mimic the intracellular environment. We show that mutants of hfq and smpB directly or indirectly modulate at least 20% and 4% of all Salmonella proteins, respectively, with limited correlation between transcription and protein expression. This is the first report suggesting that SmpB could be a general translational regulator. The broad spectrum of proteins modulated by Hfq was also surprising including central metabolism, LPS biosynthesis, two-component regulatory systems, quorum sensing, SP1-TTSS, oxidative stress, fatty acid metabolism, nucleoside and nucleotide metabolism, envelope stress, aminoacyl-tRNA synthetases, amino acid biosynthesis, peptide transport, and motility.. The extent of global regulation of translation by Hfq is unexpected, with profound effects in all stages of Salmonella’s life cycle. Our results represent the first global systems-level analysis of translational regulation; the elucidated potential targets of sRNA regulation from our analysis will

Precision Modeling Of Targets Using The VALUE Computer Program

Science.gov (United States)

Hoffman, George A.; Patton, Ronald; Akerman, Alexander

1989-08-01

The 1976-vintage LASERX computer code has been augmented to produce realistic electro-optical images of targets. Capabilities lacking in LASERX but recently incorporated into its VALUE successor include: •Shadows cast onto the ground •Shadows cast onto parts of the target •See-through transparencies (e.g.,canopies) •Apparent images due both to atmospheric scattering and turbulence •Surfaces characterized by multiple bi-directional reflectance functions VALUE provides not only realistic target modeling by its precise and comprehensive representation of all target attributes, but additionally VALUE is very user friendly. Specifically, setup of runs is accomplished by screen prompting menus in a sequence of queries that is logical to the user. VALUE also incorporates the Optical Encounter (OPEC) software developed by Tricor Systems,Inc., Elgin, IL.

Identification of novel non-coding RNAs as potential antisense regulators in the archaeon Sulfolobus solfataricus

DEFF Research Database (Denmark)

tang, T. H.; Polacek, N.; Zywicki, M.

2005-01-01

By generating a specialized cDNA library from the archaeon Sulfolobus solfataricus, we have identified 57 novel small non-coding RNA (ncRNA) candidates and confirmed their expression by Northern blot analysis. The majority was found to belong to one of two classes, either antisense or antisense...... elements by inhibiting expression of the transposase mRNA. Surprisingly, the class of antisense RNAs also contained RNAs complementary to tRNAs or sRNAs (small-nucleolar-like RNAs). For the antisense-box ncRNAs, the majority could be assigned to the class of C/D sRNAs, which specify 2'-O-methylation sites...... on rRNAs or tRNAs. Five C/D sRNAs of this group are predicted to target methylation at six sites in 13 different tRNAs, thus pointing to the widespread role of these sRNA species in tRNA modification in Archaea. Another group of antisense-box RNAs, lacking typical C/D sRNA motifs, was predicted...

Transcriptome and Degradome of microRNAs and Their Targets in Response to Drought Stress in the Plants of a Diploid and Its Autotetraploid Paulownia australis.

Directory of Open Access Journals (Sweden)

Suyan Niu

Full Text Available MicroRNAs (miRNAs are small, non-coding RNAs that play vital roles in plant growth, development, and stress response. Increasing numbers of studies aimed at discovering miRNAs and analyzing their functions in plants are being reported. In this study, we investigated the effect of drought stress on the expression of miRNAs and their targets in plants of a diploid and derived autotetraploid Paulownia australis. Four small RNA (sRNA libraries and four degradome libraries were constructed from diploid and autotetraploid P. australis plants treated with either 75% or 25% relative soil water content. A total of 33 conserved and 104 novel miRNAs (processing precision value > 0.1 were identified, and 125 target genes were identified for 36 of the miRNAs by using the degradome sequencing. Among the identified miRNAs, 54 and 68 were differentially expressed in diploid and autotetraploid plants under drought stress (25% relative soil water content, respectively. The expressions of miRNAs and target genes were also validated by quantitative real-time PCR. The results showed that the relative expression trends of the randomly selected miRNAs were similar to the trends predicted by Illumina sequencing. And the correlations between miRNAs and their target genes were also analyzed. Furthermore, the functional analysis showed that most of these miRNAs and target genes were associated with plant development and environmental stress response. This study provided molecular evidence for the possible involvement of certain miRNAs in the drought response and/or tolerance in P. australis, and certain level of differential expression between diploid and autotetraploid plants.

High-throughput sequencing of RNA silencing-associated small RNAs in olive (Olea europaea L..

Directory of Open Access Journals (Sweden)

Livia Donaire

Full Text Available Small RNAs (sRNAs of 20 to 25 nucleotides (nt in length maintain genome integrity and control gene expression in a multitude of developmental and physiological processes. Despite RNA silencing has been primarily studied in model plants, the advent of high-throughput sequencing technologies has enabled profiling of the sRNA component of more than 40 plant species. Here, we used deep sequencing and molecular methods to report the first inventory of sRNAs in olive (Olea europaea L.. sRNA libraries prepared from juvenile and adult shoots revealed that the 24-nt class dominates the sRNA transcriptome and atypically accumulates to levels never seen in other plant species, suggesting an active role of heterochromatin silencing in the maintenance and integrity of its large genome. A total of 18 known miRNA families were identified in the libraries. Also, 5 other sRNAs derived from potential hairpin-like precursors remain as plausible miRNA candidates. RNA blots confirmed miRNA expression and suggested tissue- and/or developmental-specific expression patterns. Target mRNAs of conserved miRNAs were computationally predicted among the olive cDNA collection and experimentally validated through endonucleolytic cleavage assays. Finally, we use expression data to uncover genetic components of the miR156, miR172 and miR390/TAS3-derived trans-acting small interfering RNA (tasiRNA regulatory nodes, suggesting that these interactive networks controlling developmental transitions are fully operational in olive.

Syntheses and characterization of liposome-incorporated adamantyl aminoguanidines.

Science.gov (United States)

Šekutor, Marina; Štimac, Adela; Mlinarić-Majerski, Kata; Frkanec, Ruža

2014-08-21

A series of mono and bis-aminoguanidinium adamantane derivatives has been synthesized and incorporated into liposomes. They combine two biomedically significant molecules, the adamantane moiety and the guanidinium group. The adamantane moiety possesses the membrane compatible features while the cationic guanidinium subunit was recognized as a favourable structural feature for binding to complementary molecules comprising phosphate groups. The liposome formulations of adamantyl aminoguanidines were characterized and it was shown that the entrapment efficiency of the examined compounds is significant. In addition, it was demonstrated that liposomes with incorporated adamantyl aminoguanidines effectively recognized the complementary liposomes via the phosphate group. These results indicate that adamantane derivatives bearing guanidinium groups might be versatile tools for biomedical application, from studies of molecular recognition processes to usage in drug formulation and cell targeting.

NON-TARGET AND ECOSYSTEM IMPACTS FROM GENETICALLY MODIFIED CROPS CONTAINING PLANT INCORPORATED PROTECTANTS (PIPS)

Science.gov (United States)

The risk of unintended and unexpected adverse impacts on non-target organisms and ecosystems is a key issue in environmental risk assessment of PIP crop plants. While there has been considerable examination of the effects of insect resistant crops on certain non-target organisms...

Sensory Feedback for Lower Extremity Prostheses Incorporating Targeted Muscle Reinnervation (TMR)

Science.gov (United States)

2017-10-01

hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...map and characterize the sensory capabilities of lower extremity Targeted Reinnervation (TR) sites under tactile stimulation , and (2) Measure the...descent machine; developed new tactile stimulators that we expect to use in later stages of this project; and completed baseline studies to calibrate

A moving target--incorporating knowledge of the spatial ecology of fish into the assessment and management of freshwater fish populations.

Science.gov (United States)

Cooke, Steven J; Martins, Eduardo G; Struthers, Daniel P; Gutowsky, Lee F G; Power, Michael; Doka, Susan E; Dettmers, John M; Crook, David A; Lucas, Martyn C; Holbrook, Christopher M; Krueger, Charles C

2016-04-01

Freshwater fish move vertically and horizontally through the aquatic landscape for a variety of reasons, such as to find and exploit patchy resources or to locate essential habitats (e.g., for spawning). Inherent challenges exist with the assessment of fish populations because they are moving targets. We submit that quantifying and describing the spatial ecology of fish and their habitat is an important component of freshwater fishery assessment and management. With a growing number of tools available for studying the spatial ecology of fishes (e.g., telemetry, population genetics, hydroacoustics, otolith microchemistry, stable isotope analysis), new knowledge can now be generated and incorporated into biological assessment and fishery management. For example, knowing when, where, and how to deploy assessment gears is essential to inform, refine, or calibrate assessment protocols. Such information is also useful for quantifying or avoiding bycatch of imperiled species. Knowledge of habitat connectivity and usage can identify critically important migration corridors and habitats and can be used to improve our understanding of variables that influence spatial structuring of fish populations. Similarly, demographic processes are partly driven by the behavior of fish and mediated by environmental drivers. Information on these processes is critical to the development and application of realistic population dynamics models. Collectively, biological assessment, when informed by knowledge of spatial ecology, can provide managers with the ability to understand how and when fish and their habitats may be exposed to different threats. Naturally, this knowledge helps to better evaluate or develop strategies to protect the long-term viability of fishery production. Failure to understand the spatial ecology of fishes and to incorporate spatiotemporal data can bias population assessments and forecasts and potentially lead to ineffective or counterproductive management actions.

Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus.

Science.gov (United States)

Carroll, Ronan K; Weiss, Andy; Broach, William H; Wiemels, Richard E; Mogen, Austin B; Rice, Kelly C; Shaw, Lindsey N

2016-02-09

In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in S. aureus, we generated updated GenBank files for three commonly used S. aureus strains (MRSA252, NCTC 8325, and USA300), in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome-wide annotation of sRNAs in S. aureus, were then used as a foundation to identify novel sRNAs in the community-associated methicillin-resistant strain USA300. This analysis led to the discovery of 39 previously unidentified sRNAs. Investigating the genomic loci of the newly identified sRNAs revealed a surprising degree of inconsistency in genome annotation in S. aureus, which may be hindering the analysis and functional exploration of these elements. Finally, using our newly created annotation files as a reference, we perform a global analysis of sRNA gene expression in S. aureus and demonstrate that the newly identified tsr25 is the most highly upregulated sRNA in human serum. This study provides an invaluable resource to the S. aureus research community in the form of our newly generated annotation files, while at the same time presenting the first examination of differential sRNA expression in pathophysiologically relevant conditions. Despite a large number of studies identifying regulatory or small RNA (sRNA) genes in Staphylococcus aureus, their annotation is notably lacking in available genome files. In addition to this, there has been a considerable lack of cross-referencing in the wealth of studies identifying these elements, often leading to the same sRNA being identified multiple times and bearing multiple names. In this work

Comparative analysis among the small RNA populations of source, sink and conductive tissues in two different plant-virus pathosystems.

Science.gov (United States)

Herranz, Mari Carmen; Navarro, Jose Antonio; Sommen, Evelien; Pallas, Vicente

2015-02-22

In plants, RNA silencing plays a fundamental role as defence mechanism against viruses. During last years deep-sequencing technology has allowed to analyze the sRNA profile of a large variety of virus-infected tissues. Nevertheless, the majority of these studies have been restricted to a unique tissue and no comparative analysis between phloem and source/sink tissues has been conducted. In the present work, we compared the sRNA populations of source, sink and conductive (phloem) tissues in two different plant virus pathosystems. We chose two cucurbit species infected with two viruses very different in genome organization and replication strategy; Melon necrotic spot virus (MNSV) and Prunus necrotic ringspot virus (PNRSV). Our findings showed, in both systems, an increase of the 21-nt total sRNAs together with a decrease of those with a size of 24-nt in all the infected tissues, except for the phloem where the ratio of 21/24-nt sRNA species remained constant. Comparing the vsRNAs, both PNRSV- and MNSV-infected plants share the same vsRNA size distribution in all the analyzed tissues. Similar accumulation levels of sense and antisense vsRNAs were observed in both systems except for roots that showed a prevalence of (+) vsRNAs in both pathosystems. Additionally, the presence of overrepresented discrete sites along the viral genome, hot spots, were identified and validated by stem-loop RT-PCR. Despite that in PNRSV-infected plants the presence of vsRNAs was scarce both viruses modulated the host sRNA profile. We compare for the first time the sRNA profile of four different tissues, including source, sink and conductive (phloem) tissues, in two plant-virus pathosystems. Our results indicate that antiviral silencing machinery in melon and cucumber acts mainly through DCL4. Upon infection, the total sRNA pattern in phloem remains unchanged in contrast to the rest of the analyzed tissues indicating a certain tissue-tropism to this polulation. Independently of the

Method Development for Efficient Incorporation of Unnatural Amino Acids

KAUST Repository

Harris, Paul D.

2014-04-01

The synthesis of proteins bearing unnatural amino acids has the potential to enhance and elucidate many processes in biochemistry and molecular biology. There are two primary methods for site specific unnatural amino acid incorporation, both of which use the cell’s native protein translating machinery: in vitro chemical acylation of suppressor tRNAs and the use of orthogonal amino acyl tRNA synthetases. Total chemical synthesis is theoretically possible, but current methods severely limit the maximum size of the product protein. In vivo orthogonal synthetase methods suffer from the high cost of the unnatural amino acid. In this thesis I sought to address this limitation by increasing cell density, first in shake flasks and then in a bioreactor in order to increase the yield of protein per amount of unnatural amino acid used. In a parallel project, I used the in vitro chemical acylation system to incorporate several unnatural amino acids, key among them the fluorophore BODIPYFL, with the aim of producing site specifically fluorescently labeled protein for single molecule FRET studies. I demonstrated successful incorporation of these amino acids into the trial protein GFP, although incorporation was not demonstrated in the final target, FEN1. This also served to confirm the effectiveness of a new procedure developed for chemical acylation.

Method Development for Efficient Incorporation of Unnatural Amino Acids

KAUST Repository

Harris, Paul D.

2014-01-01

The synthesis of proteins bearing unnatural amino acids has the potential to enhance and elucidate many processes in biochemistry and molecular biology. There are two primary methods for site specific unnatural amino acid incorporation, both of which use the cell’s native protein translating machinery: in vitro chemical acylation of suppressor tRNAs and the use of orthogonal amino acyl tRNA synthetases. Total chemical synthesis is theoretically possible, but current methods severely limit the maximum size of the product protein. In vivo orthogonal synthetase methods suffer from the high cost of the unnatural amino acid. In this thesis I sought to address this limitation by increasing cell density, first in shake flasks and then in a bioreactor in order to increase the yield of protein per amount of unnatural amino acid used. In a parallel project, I used the in vitro chemical acylation system to incorporate several unnatural amino acids, key among them the fluorophore BODIPYFL, with the aim of producing site specifically fluorescently labeled protein for single molecule FRET studies. I demonstrated successful incorporation of these amino acids into the trial protein GFP, although incorporation was not demonstrated in the final target, FEN1. This also served to confirm the effectiveness of a new procedure developed for chemical acylation.

Topics in LIFE Target Survival: 11-SI-004 Final Report

Energy Technology Data Exchange (ETDEWEB)

Miles, Robin [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Benett, Bill [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bond, Tiziana [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Chang, Allan [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Dawson, David [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Fornasiero, Francesco [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hamilton, Julie [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Havstad, Mark [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Kucheyev, Sergei [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); LeBlanc, Mary [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Rosso, Paul [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Schebler, Greg [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Van Cleve, Eli [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Worsley, Marcus [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2014-10-20

The LIFE target design incorporates many considerations to generate the desired fusion gain including the physics design, the cost of manufacturing of the target, the injectability of the target, the aerodynamic flight characteristics of the target, the ability to track and engage the target and to maintain the structural and thermal integrity of the target. This document describes the effort that was made in support of issues of survivability of the target during injection which included issues massmanufactural materials and processes which could be used in the target.

CoLIde

Science.gov (United States)

Mohorianu, Irina; Stocks, Matthew Benedict; Wood, John; Dalmay, Tamas; Moulton, Vincent

2013-01-01

Small RNAs (sRNAs) are 20–25 nt non-coding RNAs that act as guides for the highly sequence-specific regulatory mechanism known as RNA silencing. Due to the recent increase in sequencing depth, a highly complex and diverse population of sRNAs in both plants and animals has been revealed. However, the exponential increase in sequencing data has also made the identification of individual sRNA transcripts corresponding to biological units (sRNA loci) more challenging when based exclusively on the genomic location of the constituent sRNAs, hindering existing approaches to identify sRNA loci.   To infer the location of significant biological units, we propose an approach for sRNA loci detection called CoLIde (Co-expression based sRNA Loci Identification) that combines genomic location with the analysis of other information such as variation in expression levels (expression pattern) and size class distribution. For CoLIde, we define a locus as a union of regions sharing the same pattern and located in close proximity on the genome. Biological relevance, detected through the analysis of size class distribution, is also calculated for each locus. CoLIde can be applied on ordered (e.g., time-dependent) or un-ordered (e.g., organ, mutant) series of samples both with or without biological/technical replicates. The method reliably identifies known types of loci and shows improved performance on sequencing data from both plants (e.g., A. thaliana, S. lycopersicum) and animals (e.g., D. melanogaster) when compared with existing locus detection techniques. CoLIde is available for use within the UEA Small RNA Workbench which can be downloaded from: http://srna-workbench.cmp.uea.ac.uk. PMID:23851377

CoLIde: a bioinformatics tool for CO-expression-based small RNA Loci Identification using high-throughput sequencing data.

Science.gov (United States)

Mohorianu, Irina; Stocks, Matthew Benedict; Wood, John; Dalmay, Tamas; Moulton, Vincent

2013-07-01

Small RNAs (sRNAs) are 20-25 nt non-coding RNAs that act as guides for the highly sequence-specific regulatory mechanism known as RNA silencing. Due to the recent increase in sequencing depth, a highly complex and diverse population of sRNAs in both plants and animals has been revealed. However, the exponential increase in sequencing data has also made the identification of individual sRNA transcripts corresponding to biological units (sRNA loci) more challenging when based exclusively on the genomic location of the constituent sRNAs, hindering existing approaches to identify sRNA loci. To infer the location of significant biological units, we propose an approach for sRNA loci detection called CoLIde (Co-expression based sRNA Loci Identification) that combines genomic location with the analysis of other information such as variation in expression levels (expression pattern) and size class distribution. For CoLIde, we define a locus as a union of regions sharing the same pattern and located in close proximity on the genome. Biological relevance, detected through the analysis of size class distribution, is also calculated for each locus. CoLIde can be applied on ordered (e.g., time-dependent) or un-ordered (e.g., organ, mutant) series of samples both with or without biological/technical replicates. The method reliably identifies known types of loci and shows improved performance on sequencing data from both plants (e.g., A. thaliana, S. lycopersicum) and animals (e.g., D. melanogaster) when compared with existing locus detection techniques. CoLIde is available for use within the UEA Small RNA Workbench which can be downloaded from: http://srna-workbench.cmp.uea.ac.uk.

HomoTarget: a new algorithm for prediction of microRNA targets in Homo sapiens.

Science.gov (United States)

Ahmadi, Hamed; Ahmadi, Ali; Azimzadeh-Jamalkandi, Sadegh; Shoorehdeli, Mahdi Aliyari; Salehzadeh-Yazdi, Ali; Bidkhori, Gholamreza; Masoudi-Nejad, Ali

2013-02-01

MiRNAs play an essential role in the networks of gene regulation by inhibiting the translation of target mRNAs. Several computational approaches have been proposed for the prediction of miRNA target-genes. Reports reveal a large fraction of under-predicted or falsely predicted target genes. Thus, there is an imperative need to develop a computational method by which the target mRNAs of existing miRNAs can be correctly identified. In this study, combined pattern recognition neural network (PRNN) and principle component analysis (PCA) architecture has been proposed in order to model the complicated relationship between miRNAs and their target mRNAs in humans. The results of several types of intelligent classifiers and our proposed model were compared, showing that our algorithm outperformed them with higher sensitivity and specificity. Using the recent release of the mirBase database to find potential targets of miRNAs, this model incorporated twelve structural, thermodynamic and positional features of miRNA:mRNA binding sites to select target candidates. Copyright © 2012 Elsevier Inc. All rights reserved.

New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0.

Science.gov (United States)

Clark, Alex M; Sarker, Malabika; Ekins, Sean

2014-01-01

We recently developed a freely available mobile app (TB Mobile) for both iOS and Android platforms that displays Mycobacterium tuberculosis (Mtb) active molecule structures and their targets with links to associated data. The app was developed to make target information available to as large an audience as possible. We now report a major update of the iOS version of the app. This includes enhancements that use an implementation of ECFP_6 fingerprints that we have made open source. Using these fingerprints, the user can propose compounds with possible anti-TB activity, and view the compounds within a cluster landscape. Proposed compounds can also be compared to existing target data, using a näive Bayesian scoring system to rank probable targets. We have curated an additional 60 new compounds and their targets for Mtb and added these to the original set of 745 compounds. We have also curated 20 further compounds (many without targets in TB Mobile) to evaluate this version of the app with 805 compounds and associated targets. TB Mobile can now manage a small collection of compounds that can be imported from external sources, or exported by various means such as email or app-to-app inter-process communication. This means that TB Mobile can be used as a node within a growing ecosystem of mobile apps for cheminformatics. It can also cluster compounds and use internal algorithms to help identify potential targets based on molecular similarity. TB Mobile represents a valuable dataset, data-visualization aid and target prediction tool.

Common features of microRNA target prediction tools

Directory of Open Access Journals (Sweden)

Sarah M. Peterson

2014-02-01

Full Text Available The human genome encodes for over 1800 microRNAs, which are short noncoding RNA molecules that function to regulate gene expression post-transcriptionally. Due to the potential for one microRNA to target multiple gene transcripts, microRNAs are recognized as a major mechanism to regulate gene expression and mRNA translation. Computational prediction of microRNA targets is a critical initial step in identifying microRNA:mRNA target interactions for experimental validation. The available tools for microRNA target prediction encompass a range of different computational approaches, from the modeling of physical interactions to the incorporation of machine learning. This review provides an overview of the major computational approaches to microRNA target prediction. Our discussion highlights three tools for their ease of use, reliance on relatively updated versions of miRBase, and range of capabilities, and these are DIANA-microT-CDS, miRanda-mirSVR, and TargetScan. In comparison across all microRNA target prediction tools, four main aspects of the microRNA:mRNA target interaction emerge as common features on which most target prediction is based: seed match, conservation, free energy, and site accessibility. This review explains these features and identifies how they are incorporated into currently available target prediction tools. MicroRNA target prediction is a dynamic field with increasing attention on development of new analysis tools. This review attempts to provide a comprehensive assessment of these tools in a manner that is accessible across disciplines. Understanding the basis of these prediction methodologies will aid in user selection of the appropriate tools and interpretation of the tool output.

NCI-MATCH Trial Links Targeted Drugs to Mutations

Science.gov (United States)

Investigators for the nationwide trial, NCI-MATCH: Molecular Analysis for Therapy Choice, announced that the trial will seek to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type. NCI-MATCH will incorporate more than 20 different study drugs or drug combinations, each targeting a specific gene mutation, in order to match each patient in the trial with a therapy that targets a molecular abnormality in their tumor.

Genome-Wide Identification, Characterization, and Expression Analysis of Small RNA Biogenesis Purveyors Reveal Their Role in Regulation of Biotic Stress Responses in Three Legume Crops

Directory of Open Access Journals (Sweden)

Rajeev K. Varshney

2017-04-01

Full Text Available Biotic stress in legume crops is one of the major threats to crop yield and productivity. Being sessile organisms, plants have evolved a myriad of mechanisms to combat different stresses imposed on them. One such mechanism, deciphered in the last decade, is small RNA (sRNA mediated defense in plants. Small RNAs (sRNAs have emerged as one of the major players in gene expression regulation in plants during developmental stages and under stress conditions. They are known to act both at transcriptional and post-transcriptional levels. Dicer-like (DCL, Argonaute (AGO, and RNA dependent RNA polymerase (RDR constitute the major components of sRNA biogenesis machinery and are known to play a significant role in combating biotic and abiotic stresses. This study is, therefore, focused on identification and characterization of sRNA biogenesis proteins in three important legume crops, namely chickpea, pigeonpea, and groundnut. Phylogenetic analysis of these proteins between legume species classified them into distinct clades and suggests the evolutionary conservation of these genes across the members of Papillionidoids subfamily. Variable expression of sRNA biogenesis genes in response to the biotic stresses among the three legumes indicate the possible existence of specialized regulatory mechanisms in different legumes. This is the first ever study to understand the role of sRNA biogenesis genes in response to pathogen attacks in the studied legumes.

Evolutionary patterns of Escherichia coli small RNAs and their regulatory interactions.

Science.gov (United States)

Peer, Asaf; Margalit, Hanah

2014-07-01

Most bacterial small RNAs (sRNAs) are post-transcriptional regulators of gene expression, exerting their regulatory function by base-pairing with their target mRNAs. While it has become evident that sRNAs play central regulatory roles in the cell, little is known about their evolution and the evolution of their regulatory interactions. Here we used the prokaryotic phylogenetic tree to reconstruct the evolutionary history of Escherichia coli sRNAs and their binding sites on target mRNAs. We discovered that sRNAs currently present in E. coli mainly accumulated inside the Enterobacteriales order, succeeding the appearance of other types of noncoding RNAs and concurrently with the evolution of a variant of the Hfq protein exhibiting a longer C-terminal region. Our analysis of the evolutionary ages of sRNA-mRNA interactions revealed that while all sRNAs were evolutionarily older than most of their known binding sites on mRNA targets, for quite a few sRNAs there was at least one binding site that coappeared with or preceded them. It is conceivable that the establishment of these first interactions forced selective pressure on the sRNAs, after which additional targets were acquired by fitting a binding site to the active region of the sRNA. This conjecture is supported by the appearance of many binding sites on target mRNAs only after the sRNA gain, despite the prior presence of the target gene in ancestral genomes. Our results suggest a selective mechanism that maintained the sRNAs across the phylogenetic tree, and shed light on the evolution of E. coli post-transcriptional regulatory network. © 2014 Peer and Margalit; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Identification of miRNAs and their targets through high-throughput sequencing and degradome analysis in male and female Asparagus officinalis.

Science.gov (United States)

Chen, Jingli; Zheng, Yi; Qin, Li; Wang, Yan; Chen, Lifei; He, Yanjun; Fei, Zhangjun; Lu, Gang

2016-04-12

MicroRNAs (miRNAs), a class of non-coding small RNAs (sRNAs), regulate various biological processes. Although miRNAs have been identified and characterized in several plant species, miRNAs in Asparagus officinalis have not been reported. As a dioecious plant with homomorphic sex chromosomes, asparagus is regarded as an important model system for studying mechanisms of plant sex determination. Two independent sRNA libraries from male and female asparagus plants were sequenced with Illumina sequencing, thereby generating 4.13 and 5.88 million final clean reads, respectively. Both libraries predominantly contained 24-nt sRNAs, followed by 21-nt sRNAs. Further analysis identified 154 conserved miRNAs, which belong to 26 families, and 39 novel miRNA candidates seemed to be specific to asparagus. Comparative profiling revealed that 63 miRNAs exhibited significant differential expression between male and female plants, which was confirmed by real-time quantitative PCR analysis. Among them, 37 miRNAs were significantly up-regulated in the female library, whereas the others were preferentially expressed in the male library. Furthermore, 40 target mRNAs representing 44 conserved and seven novel miRNAs were identified in asparagus through high-throughput degradome sequencing. Functional annotation showed that these target mRNAs were involved in a wide range of developmental and metabolic processes. We identified a large set of conserved and specific miRNAs and compared their expression levels between male and female asparagus plants. Several asparagus miRNAs, which belong to the miR159, miR167, and miR172 families involved in reproductive organ development, were differentially expressed between male and female plants, as well as during flower development. Consistently, several predicted targets of asparagus miRNAs were associated with floral organ development. These findings suggest the potential roles of miRNAs in sex determination and reproductive developmental processes in

Two small RNAs, CrcY and CrcZ, act in concert to sequester the Crc global regulator in Pseudomonas putida, modulating catabolite repression.

Science.gov (United States)

Moreno, Renata; Fonseca, Pilar; Rojo, Fernando

2012-01-01

The Crc protein is a translational repressor that recognizes a specific target at some mRNAs, controlling catabolite repression and co-ordinating carbon metabolism in pseudomonads. In Pseudomonas aeruginosa, the levels of free Crc protein are controlled by CrcZ, a sRNA that sequesters Crc, acting as an antagonist. We show that, in Pseudomonas putida, the levels of free Crc are controlled by CrcZ and by a novel 368 nt sRNA named CrcY. CrcZ and CrcY, which contain six potential targets for Crc, were able to bind Crc specifically in vitro. The levels of CrcZ and CrcY were low under conditions generating a strong catabolite repression, and increased strongly when catabolite repression was absent. Deletion of either crcZ or crcY had no effect on catabolite repression, but the simultaneous absence of both sRNAs led to constitutive catabolite repression that compromised growth on some carbon sources. Overproduction of CrcZ or CrcY significantly reduced repression. We propose that CrcZ and CrcY act in concert, sequestering and modulating the levels of free Crc according to metabolic conditions. The CbrA/CbrB two-component system activated crcZ transcription, but had little effect on crcY. CrcY was detected in P. putida, Pseudomonas fluorescens and Pseudomonas syringae, but not in P. aeruginosa. © 2011 Blackwell Publishing Ltd.

A transcriptome-wide, organ-specific regulatory map of Dendrobium officinale, an important traditional Chinese orchid herb

Science.gov (United States)

Meng, Yijun; Yu, Dongliang; Xue, Jie; Lu, Jiangjie; Feng, Shangguo; Shen, Chenjia; Wang, Huizhong

2016-01-01

Dendrobium officinale is an important traditional Chinese herb. Here, we did a transcriptome-wide, organ-specific study on this valuable plant by combining RNA, small RNA (sRNA) and degradome sequencing. RNA sequencing of four organs (flower, root, leaf and stem) of Dendrobium officinale enabled us to obtain 536,558 assembled transcripts, from which 2,645, 256, 42 and 54 were identified to be highly expressed in the four organs respectively. Based on sRNA sequencing, 2,038, 2, 21 and 24 sRNAs were identified to be specifically accumulated in the four organs respectively. A total of 1,047 mature microRNA (miRNA) candidates were detected. Based on secondary structure predictions and sequencing, tens of potential miRNA precursors were identified from the assembled transcripts. Interestingly, phase-distributed sRNAs with degradome-based processing evidences were discovered on the long-stem structures of two precursors. Target identification was performed for the 1,047 miRNA candidates, resulting in the discovery of 1,257 miRNA--target pairs. Finally, some biological meaningful subnetworks involving hormone signaling, development, secondary metabolism and Argonaute 1-related regulation were established. All of the sequencing data sets are available at NCBI Sequence Read Archive (http://www.ncbi.nlm.nih.gov/sra/). Summarily, our study provides a valuable resource for the in-depth molecular and functional studies on this important Chinese orchid herb. PMID:26732614

Incorporating AIDS prevention activities into a family planning organization in Colombia.

Science.gov (United States)

Vernon, R; Ojeda, G; Murad, R

1990-01-01

Three AIDS prevention activities were incorporated into the services offered by PROFAMILIA in two operations research projects. The activities included: (1) informative talks given both to the general public and to members of target groups by PROFAMILIA's community marketing (CM) program field workers (or instructors); (2) the establishment of condom distribution posts in meeting places of target groups; and (3) mass-media information campaigns on AIDS prevention. Community-based distributors were able to successfully provide information on AIDS to their regular audiences as well as to deliver information and condoms to special target groups without negatively affecting family planning information/education/communication activities and contraceptive sales. A radio campaign that promoted condom use for AIDS prevention did not affect public perceptions about the condom and did not jeopardize PROFAMILIA's image.

Incorporation study of 18FDG through its uptake into tumour-derived cell lines

International Nuclear Information System (INIS)

Costa, Flavia M.; Nascimento, Leonardo T.C.; Santos, Raquel G.

2013-01-01

In vitro tests of radiopharmaceuticals are an important instrument to study their mechanisms of action, binding and incorporation. 18 FDG is the most used radiopharmaceutical for diagnostics positron emission tomography (PET) on oncology, on the basis of accelerated rates of absorption of glucose in cell malignancies. This radiotracer has been routinely produced at CDTN; and therefore, it was selected for preliminary assays due to its availability. Nowadays, UPPR at CDTN produces routinely 18 FDG for the local PET Centers but others PET radiopharmaceuticals are in development such as 18 F-Fluorocholine and 18 F-Fluorothymidine. According to the Brazilian Health Regulatory Agency (ANVISA) it is necessary to validate and register these new radiopharmaceuticals in order to get the approval for their commercialization. Targeting efficacy is one of the important issues to be evaluated during radiopharmaceutical validation. The aim of this study was to develop a standard protocol to determine tumor targeting efficacy of PET radiopharmaceuticals in vitro. Therefore it was developed a protocol based on the incorporation og 18 FDG through the uptake in different tumor-derived cell lines. Three variables were investigated for the standardization of the test: the number of cells to be seeded in 96-well plates, the time of incubation with the radiopharmaceutical and the radiotracer concentration. The standardized protocol was considered suitable for 18 FDG incorporation assay and showed reproductive results. The protocol developed in this work will pave the way for the in vitro studies of incorporation of the new PET radiopharmaceuticals to be produced at UPPR-CDTN, such as: 18 F-Fluorocholine and 18 F-Fluorothymidine. (author)

Targeting poverty : lessons from monitoring Ireland's National Anti-Poverty Strategy

OpenAIRE

Layte, Richard; Nolan, Brian; Whelan, Christopher T.

2000-01-01

In 1997 the Irish government adopted the National Anti-Poverty Strategy (NAPS), a global target for the reduction of poverty which illuminates a range of issues relating to official poverty targets. The Irish target is framed in terms of a relative poverty measure incorporating both relative income and direct measures of deprivation based on data on the extent of poverty from 1994. Since 1994 Ireland has experienced an unprecedented period of economic growth that makes it particularly importa...

New Equilibrium Models of Drug-Receptor Interactions Derived from Target-Mediated Drug Disposition.

Science.gov (United States)

Peletier, Lambertus A; Gabrielsson, Johan

2018-05-14

In vivo analyses of pharmacological data are traditionally based on a closed system approach not incorporating turnover of target and ligand-target kinetics, but mainly focussing on ligand-target binding properties. This study incorporates information about target and ligand-target kinetics parallel to binding. In a previous paper, steady-state relationships between target- and ligand-target complex versus ligand exposure were derived and a new expression of in vivo potency was derived for a circulating target. This communication is extending the equilibrium relationships and in vivo potency expression for (i) two separate targets competing for one ligand, (ii) two different ligands competing for a single target and (iii) a single ligand-target interaction located in tissue. The derived expressions of the in vivo potencies will be useful both in drug-related discovery projects and mechanistic studies. The equilibrium states of two targets and one ligand may have implications in safety assessment, whilst the equilibrium states of two competing ligands for one target may cast light on when pharmacodynamic drug-drug interactions are important. The proposed equilibrium expressions for a peripherally located target may also be useful for small molecule interactions with extravascularly located targets. Including target turnover, ligand-target complex kinetics and binding properties in expressions of potency and efficacy will improve our understanding of within and between-individual (and across species) variability. The new expressions of potencies highlight the fact that the level of drug-induced target suppression is very much governed by target turnover properties rather than by the target expression level as such.

Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids.

Science.gov (United States)

Fan, Chenguang; Xiong, Hai; Reynolds, Noah M; Söll, Dieter

2015-12-15

Genetic encoding of noncanonical amino acids (ncAAs) into proteins is a powerful approach to study protein functions. Pyrrolysyl-tRNA synthetase (PylRS), a polyspecific aminoacyl-tRNA synthetase in wide use, has facilitated incorporation of a large number of different ncAAs into proteins to date. To make this process more efficient, we rationally evolved tRNA(Pyl) to create tRNA(Pyl-opt) with six nucleotide changes. This improved tRNA was tested as substrate for wild-type PylRS as well as three characterized PylRS variants (N(ϵ)-acetyllysyl-tRNA synthetase [AcKRS], 3-iodo-phenylalanyl-tRNA synthetase [IFRS], a broad specific PylRS variant [PylRS-AA]) to incorporate ncAAs at UAG codons in super-folder green fluorescence protein (sfGFP). tRNA(Pyl-opt) facilitated a 5-fold increase in AcK incorporation into two positions of sfGFP simultaneously. In addition, AcK incorporation into two target proteins (Escherichia coli malate dehydrogenase and human histone H3) caused homogenous acetylation at multiple lysine residues in high yield. Using tRNA(Pyl-opt) with PylRS and various PylRS variants facilitated efficient incorporation of six other ncAAs into sfGFP. Kinetic analyses revealed that the mutations in tRNA(Pyl-opt) had no significant effect on the catalytic efficiency and substrate binding of PylRS enzymes. Thus tRNA(Pyl-opt) should be an excellent replacement of wild-type tRNA(Pyl) for future ncAA incorporation by PylRS enzymes. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Relationship between Attitude toward Target Language Culture Instruction and Pragmatic Comprehension Development

Science.gov (United States)

Rafieyan, Vahid; Majid, Norazman Bin Abdul; Eng, Lin Siew

2013-01-01

Familiarity with the cultural features of the target language society and interest in learning those cultural features are the key factors to determine language learners' level of pragmatic comprehension. To investigate this issue, this study attempted to assess the relationship between attitude toward incorporating target language culture into…

Increasing the fidelity of noncanonical amino acid incorporation in cell-free protein synthesis.

Science.gov (United States)

Gan, Qinglei; Fan, Chenguang

2017-11-01

Cell-free protein synthesis provides a robust platform for co-translational incorporation of noncanonical amino acid (ncAA) into proteins to facilitate biological studies and biotechnological applications. Recently, eliminating the activity of release factor 1 has been shown to increase ncAA incorporation in response to amber codons. However, this approach could promote mis-incorporation of canonical amino acids by near cognate suppression. We performed a facile protocol to remove near cognate tRNA isoacceptors of the amber codon from total tRNAs, and used the phosphoserine (Sep) incorporation system as validation. By manipulating codon usage of target genes and tRNA species introduced into the cell-free protein synthesis system, we increased the fidelity of Sep incorporation at a specific position. By removing three near cognate tRNA isoacceptors of the amber stop codon [tRNA Lys , tRNA Tyr , and tRNA Gln (CUG)] from the total tRNA, the near cognate suppression decreased by 5-fold without impairing normal protein synthesis in the cell-free protein synthesis system. Mass spectrometry analyses indicated that the fidelity of ncAA incorporation was improved. Removal of near cognate tRNA isoacceptors of the amber codon could increase ncAA incorporation fidelity towards the amber stop codon in release factor deficiency systems. We provide a general strategy to improve fidelity of ncAA incorporation towards stop, quadruplet and sense codons in cell-free protein synthesis systems. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2016 Elsevier B.V. All rights reserved.

The phenotypic and molecular assessment of the non-conserved Arabidopsis MICRORNA163/S-ADENOSYL-METHYLTRANSFERASE regulatory module during biotic stress.

Science.gov (United States)

Litholdo, Celso Gaspar; Eamens, Andrew Leigh; Waterhouse, Peter Michael

2018-04-01

In plants, microRNAs (miRNAs) have evolved in parallel to the protein-coding genes that they target for expression regulation, and miRNA-directed gene expression regulation is central to almost every cellular process. MicroRNA, miR163, is unique to the Arabidopsis genus and is processed into a 24-nucleotide (nt) mature small regulatory RNA (sRNA) from a single precursor transcript transcribed from a single locus, the MIR163 gene. The MIR163 locus is a result of a recent inverted duplication event of one of the five closely related S-ADENOSYL-METHYLTRANSFERASE genes that the mature miR163 sRNA targets for expression regulation. Currently, however, little is known about the role of the miR163/S-ADENOSYL-METHYLTRANSFERASE regulatory module in response to biotic stress. Here, we document the expression domains of MIR163 and the S-ADENOSYL-METHYLTRANSFERASE target genes following fusion of their putative promoter sequences to the β-glucuronidase (GUS) reporter gene and subsequent in planta expression. Further, we report on our phenotypic and molecular assessment of Arabidopsis thaliana plants with altered miR163 accumulation, namely the mir163-1 and mir163-2 insertion knockout mutants and the miR163 overexpression line, the MIR163-OE plant. Finally, we reveal miR163 accumulation and S-ADENOSYL-METHYLTRANSFERASE target gene expression post treatment with the defence elicitors, salicylic acid and jasmonic acid, and following Fusarium oxysporum infection, wounding, and herbivory attack. Together, the work presented here provides a comprehensive new biological insight into the role played by the Arabidopsis genus-specific miR163/S-ADENOSYL-METHYLTRANSFERASE regulatory module in normal A. thaliana development and during the exposure of A. thaliana plants to biotic stress.

Targeting Killing of Breast Tumor Stem Cells

National Research Council Canada - National Science Library

Chen, Si-Yi

2005-01-01

.... Toward the goal, we have prepared HA molecules from human umbilical cord hyaluronic acid by hydrolysed by Bee venom. However, we have encountered the technical difficulty to produce CD44-targeted liposomes that are incorporated with HA molecules. Due to the technical problems, this proposed study has been extended for additional one year.

Real-Time Implementation of an Asynchronous Vision-Based Target Tracking System for an Unmanned Aerial Vehicle

Science.gov (United States)

2007-06-01

Chin Khoon Quek. “Vision Based Control and Target Range Estimation for Small Unmanned Aerial Vehicle.” Master’s Thesis, Naval Postgraduate School...December 2005. [6] Kwee Chye Yap. “Incorporating Target Mensuration System for Target Motion Estimation Along a Road Using Asynchronous Filter

LIFE Target Fabrication Research Plan Sept 2008

Energy Technology Data Exchange (ETDEWEB)

Miles, R; Biener, J; Kucheyev, S; Montesanti, R; Satcher, J; Spadaccini, C; Rose, K; Wang, M; Hamza, A; Alexander, N; Brown, L; Hund, J; Petzoldt, R; Sweet, W; Goodin, D

2008-11-10

The target-system for the baseline LIFE fast-ignition target was analyzed to establish a preliminary estimate for the costs and complexities involved in demonstrating the technologies needed to build a prototype LIFE plant. The baseline fast-ignition target upon which this analysis was developed is shown in Figure 1.0-1 below. The LIFE target-system incorporates requirements for low-cost, high throughput manufacture, high-speed, high accuracy injection of the target into the chamber, production of sufficient energy from implosion and recovery and recycle of the imploded target material residue. None of these functions has been demonstrated to date. Existing target fabrication techniques which lead to current 'hot spot' target costs of {approx}$100,000 per target and at a production rate of 2/day are unacceptable for the LIFE program. Fabrication techniques normally used for low-cost, low accuracy consumer products such as toys must be adapted to the high-accuracy LIFE target. This will be challenge. A research program resulting is the demonstration of the target-cycle technologies needed for a prototype LIFE reactor is expected to cost {approx}$51M over the course of 5 years. The effort will result in targets which will cost an estimated $0.23/target at a rep-rate of 20 Hz or about 1.73M targets/day.

Genome wide identification of chilling responsive microRNAs in Prunus persica

Directory of Open Access Journals (Sweden)

Barakat Abdelali

2012-09-01

Full Text Available Abstract Background MicroRNAs (miRNAs are small RNAs (sRNAs approximately 21 nucleotides in length that negatively control gene expression by cleaving or inhibiting the translation of target gene transcripts. Within this context, miRNAs and siRNAs are coming to the forefront as molecular mediators of gene regulation in plant responses to annual temperature cycling and cold stress. For this reason, we chose to identify and characterize the conserved and non-conserved miRNA component of peach (Prunus persica (L. Batsch focusing our efforts on both the recently released whole genome sequence of peach and sRNA transcriptome sequences from two tissues representing non-dormant leaves and dormant leaf buds. Conserved and non-conserved miRNAs, and their targets were identified. These sRNA resources were used to identify cold-responsive miRNAs whose gene targets co-localize with previously described QTLs for chilling requirement (CR. Results Analysis of 21 million peach sRNA reads allowed us to identify 157 and 230 conserved and non-conserved miRNA sequences. Among the non-conserved miRNAs, we identified 205 that seem to be specific to peach. Comparative genome analysis between peach and Arabidopsis showed that conserved miRNA families, with the exception of miR5021, are similar in size. Sixteen of these conserved miRNA families are deeply rooted in land plant phylogeny as they are present in mosses and/or lycophytes. Within the other conserved miRNA families, five families (miR1446, miR473, miR479, miR3629, and miR3627 were reported only in tree species (Populustrichocarpa, Citrus trifolia, and Prunus persica. Expression analysis identified several up-regulated or down-regulated miRNAs in winter buds versus young leaves. A search of the peach proteome allowed the prediction of target genes for most of the conserved miRNAs and a large fraction of non-conserved miRNAs. A fraction of predicted targets in peach have not been previously reported in other

Genomic Targets and Features of BarA-UvrY (-SirA Signal Transduction Systems.

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Tesfalem R Zere

Full Text Available The two-component signal transduction system BarA-UvrY of Escherichia coli and its orthologs globally regulate metabolism, motility, biofilm formation, stress resistance, virulence of pathogens and quorum sensing by activating the transcription of genes for regulatory sRNAs, e.g. CsrB and CsrC in E. coli. These sRNAs act by sequestering the RNA binding protein CsrA (RsmA away from lower affinity mRNA targets. In this study, we used ChIP-exo to identify, at single nucleotide resolution, genomic sites for UvrY (SirA binding in E. coli and Salmonella enterica. The csrB and csrC genes were the strongest targets of crosslinking, which required UvrY phosphorylation by the BarA sensor kinase. Crosslinking occurred at two sites, an inverted repeat sequence far upstream of the promoter and a site near the -35 sequence. DNAse I footprinting revealed specific binding of UvrY in vitro only to the upstream site, indicative of additional binding requirements and/or indirect binding to the downstream site. Additional genes, including cspA, encoding the cold-shock RNA-binding protein CspA, showed weaker crosslinking and modest or negligible regulation by UvrY. We conclude that the global effects of UvrY/SirA on gene expression are primarily mediated by activating csrB and csrC transcription. We also used in vivo crosslinking and other experimental approaches to reveal new features of csrB/csrC regulation by the DeaD and SrmB RNA helicases, IHF, ppGpp and DksA. Finally, the phylogenetic distribution of BarA-UvrY was analyzed and found to be uniquely characteristic of γ-Proteobacteria and strongly anti-correlated with fliW, which encodes a protein that binds to CsrA and antagonizes its activity in Bacillus subtilis. We propose that BarA-UvrY and orthologous TCS transcribe sRNA antagonists of CsrA throughout the γ-Proteobacteria, but rarely or never perform this function in other species.

HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages

NARCIS (Netherlands)

Sanchez-Gaytan, Brenda L.; Fay, Francois; Lobatto, Mark E.; Tang, Jun; Ouimet, Mireille; Kim, Yongtae; van der Staay, Susanne E. M.; van Rijs, Sarian M.; Priem, Bram; Zhang, Liangfang; Fisher, Edward A.; Moore, Kathryn J.; Langer, Robert; Fayad, Zahi A.; Mulder, Willem J. M.

2015-01-01

High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and

Dual targeting strategy of magnetic nanoparticle-loaded and RGD peptide-activated stimuli-sensitive polymeric micelles for delivery of paclitaxel

Energy Technology Data Exchange (ETDEWEB)

Lin, Meng Meng [Tsinghua University, Department of Chemical Engineering (China); Kang, Yoon Joong [Jungwon University, Department of Biomedical Science (Korea, Republic of); Sohn, Youngjoo [Kyung Hee University, Department of Anatomy, College of Korean Medicine (Korea, Republic of); Kim, Do Kyung, E-mail: eurokorean@gmail.com, E-mail: dokyung@konyang.ac.kr [Konyang University, Industry Cooperation Foundation (Korea, Republic of)

2015-06-15

A double targeting strategy of anti-neoplastic agent paclitaxel (PTX) was developed by incorporating magnetic nanoparticles and RGD peptide for enhanced cell cytotoxicity effect at lower dosage. A dual targeting mechanism including magnetic targeting and RGD ligand-specific targeting enhanced the overall cytotoxicity and reduced the effective dosage of PTX to achieve enhanced and sustained release of PTX in vitro. We addressed the issues of water-insolubility of oleic acid (OA)-stabilized SPIONs and low incorporation efficiency of hydrophobic PTX with SPION nanocarriers by using an amphiphilic polymer poly[(N-isopropylacrylamide-r-acrylamide)-b-l-lactic acid] (PNAL) as micelle-forming materials. A targeting moiety, GGGGRGD peptide, a RGD sequence-containing peptide with a short linker, is attached to the surface of PNAL-SPIONs via a homo-crosslinker. Confocal microscopy image analysis revealed that the cellular uptake was increased from (1.5 ± 0.5 % (PNAL) to 11.7 ± 0.8 % (RGD-PNAL-SPIONs) at 6 h incubation, once both RGD peptide and magnetic force attraction were incorporated into the carriers. Such multi-targeting nanocarriers showed promising potential in cancer-oriented diagnosis and therapy.

Utilize target motion to cover clinical target volume (ctv) - a novel and practical treatment planning approach to manage respiratory motion

International Nuclear Information System (INIS)

Jin Jianyue; Ajlouni, Munther; Kong Fengming; Ryu, Samuel; Chetty, Indrin J.; Movsas, Benjamin

2008-01-01

Purpose: To use probability density function (PDF) to model motion effects and incorporate this information into treatment planning for lung cancers. Material and methods: PDFs were calculated from the respiratory motion traces of 10 patients. Motion effects were evaluated by convolving static dose distributions with various PDFs. Based on a differential dose prescription with relatively lower dose to the clinical target volume (CTV) than to the gross tumor volume (GTV), two approaches were proposed to incorporate PDFs into treatment planning. The first approach uses the GTV-based internal target volume (ITV) as the planning target volume (PTV) to ensure full dose to the GTV, and utilizes the motion-induced dose gradient to cover the CTV. The second approach employs an inhomogeneous static dose distribution within a minimized PTV to best match the prescription dose gradient. Results: Motion effects on dose distributions were minimal in the anterior-posterior (AP) and lateral directions: a 10-mm motion only induced about 3% of dose reduction in the peripheral target region. The motion effect was remarkable in the cranial-caudal direction. It varied with the motion amplitude, but tended to be similar for various respiratory patterns. For the first approach, a 10-15 mm motion would adequately cover the CTV (presumed to be 60-70% of the GTV dose) without employing the CTV in planning. For motions 15-mm. An example of inhomogeneous static dose distribution in a reduced PTV was given, and it showed significant dose reduction in the normal tissue without compromising target coverage. Conclusions: Respiratory motion-induced dose gradient can be utilized to cover the CTV and minimize the lung dose without the need for more sophisticated technologies

Domestication of transposable elements into MicroRNA genes in plants.

Directory of Open Access Journals (Sweden)

Yang Li

Full Text Available Transposable elements (TE usually take up a substantial portion of eukaryotic genome. Activities of TEs can cause genome instability or gene mutations that are harmful or even disastrous to the host. TEs also contribute to gene and genome evolution at many aspects. Part of miRNA genes in mammals have been found to derive from transposons while convincing evidences are absent for plants. We found that a considerable number of previously annotated plant miRNAs are identical or homologous to transposons (TE-MIR, which include a small number of bona fide miRNA genes that conform to generally accepted plant miRNA annotation rules, and hairpin derived siRNAs likely to be pre-evolved miRNAs. Analysis of these TE-MIRs indicate that transitions from the medium to high copy TEs into miRNA genes may undergo steps such as inverted repeat formation, sequence speciation and adaptation to miRNA biogenesis. We also identified initial target genes of the TE-MIRs, which contain homologous sequences in their CDS as consequence of cognate TE insertions. About one-third of the initial target mRNAs are supported by publicly available degradome sequencing data for TE-MIR sRNA induced cleavages. Targets of the TE-MIRs are biased to non-TE related genes indicating their penchant to acquire cellular functions during evolution. Interestingly, most of these TE insertions span boundaries between coding and non-coding sequences indicating their incorporation into CDS through alteration of splicing or translation start or stop signals. Taken together, our findings suggest that TEs in gene rich regions can form foldbacks in non-coding part of transcripts that may eventually evolve into miRNA genes or be integrated into protein coding sequences to form potential targets in a "temperate" manner. Thus, transposons may supply as resources for the evolution of miRNA-target interactions in plants.

[Incorporation monitoring of employees of a radioiodine therapy ward. Is incorporation monitoring required for routine?].

Science.gov (United States)

Happel, C; Kratzel, U; Selkinski, I; Bockisch, B; Etzel, M; Korkusuz, H; Sauter, B; Staudt, J; von Müller, F; Grünwald, F; Kranert, W T

2013-01-01

Aim of the study was to determine the annual incorporation of staff on a radioiodine therapy ward and the resulting annual effective dose (aed). Following the German incorporation guideline (gig), incorporation monitoring is not necessary for potential aed below 0.5 mSv/a. For aed > 0.5 mSv/a adherence to the 1 mSv dose limit must be verified. For doses > 1 mSv/a incorporation has to be monitored by the authority. Furthermore, the (131)I incorporation factor from the gig should be verified. To determine the actual work related incorporation, the (131)I activity concentration in urine samples (collection over 24 h) of 14 employees of different professions were examined over a period of 27 months. Measured activity concentrations were related to the individual time of exposure. A constant activity supply for at least three days was assumed. The mean annual effective doses were 2.4 · 10⁻¹ mSv/a (nursing staff; n = 3), 5.6 · 10⁻² mSv/a (cleaning staff; n = 2), 2.8 · 10⁻³ mSv/a (technical staff; n = 2) and 5.2 · 10⁻³ mSv/a (physicians; n = 7). All aed were below the dose limits of the gig. The calculated mean incorporation factors ranged from 3.0 · 10⁻⁸ for the nursing staff to 3.6 · 10⁻¹⁰ for the technical staff (cleaning staff: 7 · 10⁻⁹; physicians: 6.5 · 10⁻¹⁰) and were therefore well below the (131)I incorporation factor defined by the gig. To estimate the aed caused by incorporation of (131)I it has to be subdivided for the different requirements in the diverse fields of activity of the employees. Regarding those who spend most of their time nearby the patient an incorporation monitoring by the authority might be required. The (131)I incorporation factor from the guideline (10⁻⁶) can be reduced by a factor of 10. For (99m)Tc and (18)F an incorporation factor of 10⁻⁷ is accepted.

Analysis of small RNA production patterns among the two potato spindle tuber viroid variants in tomato plants

Directory of Open Access Journals (Sweden)

Charith Raj Adkar-Purushothama

2015-12-01

Full Text Available In order to analyze the production of small RNA (sRNA by viroids upon infecting the plants, the tomato plants (Solanum lycopersicum cultivar Rutgers were inoculated with the variants of Potato spindle tuber viroid (PSTVd. After 21-days of postinoculation, total RNA was extracted and subjected for deep-sequencing using Illumina HiSeq platform. The primers were trimmed and only 21- to 24-nt long sRNAs were filtered after quality check of the raw data. The filtered sRNA population was then mapped against both the genomic (+ and antigenomic (− strands of the respective PSTVd variants using standard pattern-matching algorithm. The profiling of viroid derived sRNA (vd-sRNA revealed that the viroids are susceptible to host RNA silencing mechanism. High-throughput sequence data linked to this project have been deposited in the Gene Expression Omnibus (GEO database under accession number GSE69225.

The feasibility of incorporating Vpx into lentiviral gene therapy vectors

Directory of Open Access Journals (Sweden)

Samantha A McAllery

2016-01-01

Full Text Available While current antiretroviral therapy has significantly improved, challenges still remain in life-long targeting of HIV-1 reservoirs. Lentiviral gene therapy has the potential to deliver protective genes into the HIV-1 reservoir. However, inefficient reverse transcription (RT occurs in HIV-1 reservoirs during lentiviral gene delivery. The viral protein Vpx is capable of increasing lentiviral RT by antagonizing the restriction factor SAMHD1. Incorporating Vpx into lentiviral vectors could substantially increase gene delivery into the HIV-1 reservoir. The feasibility of this Vpx approach was tested in resting cell models utilizing macrophages and dendritic cells. Our results showed Vpx exposure led to increased permissiveness of cells over a period that exceeded 2 weeks. Consequently, significant lower potency of HIV-1 antiretrovirals inhibiting RT and integration was observed. When Vpx was incorporated with anti-HIV-1 genes inhibiting either pre-RT or post-RT stages of the viral life-cycle, transduction levels significantly increased. However, a stronger antiviral effect was only observed with constructs that inhibit pre-RT stages of the viral life cycle. In conclusion this study demonstrates a way to overcome the major delivery obstacle of gene delivery into HIV-1 reservoir cell types. Importantly, incorporating Vpx with pre-RT anti-HIV-1 genes, demonstrated the greatest protection against HIV-1 infection.

Conceptual design considerations and neutronics of lithium fall laser target chambers

International Nuclear Information System (INIS)

Meier, W.R.; Thomson, W.B.

1978-01-01

Atomics International and Lawrence Livermore Laboratory are involved in the conceptual design of a laser fusion power plant incorporating the lithium fall target chamber. In this paper we discuss some of the more important design considerations for the target chamber and evaluate its nuclear performance. Sizing and configuration of the fall, hydraulic effects, and mechanical design considerations are addressed. The nuclear aspects examined include tritium breeding, energy deposition, and radiation damage

LHRH incorporation in normal and denervated pineal gland, and in pineal gland of rats with constant estrous-anovulatory syndrome: a preliminary study

International Nuclear Information System (INIS)

Trentini, G.P.; DeGaetani, C.F.; DiGregorio, C.; Botticelli, C.S.

1980-01-01

Pineal gland and superior sympathetic cervical ganglia accumulated intravenously injected 3 H-LHRH in an amount significantly higher than anterior and posterior hypothalamus, cerebral cortex and pituitary gland, the latter a specific target for LHRH. The prior administration of unlabelled LHRH significantly decreased the 3 H-LHRH incorporation only in pineal and pituitary gland. Autoradiography showed that the radiolabel was localized at the level of the pinealocytes, with a seemingly, prevalent distribution of grains on the cellular contours. Pineal incorporation of LHRH was not significantly modified by either acute or chronic bilateral cervical ganglionectomy, although acute ganglioectomy resulted in a slight decrease in LHRH accumulation by pineal gland. Constant estrous anovulatory syndromes induced by either frontal hypothalamic deafferentation, or continuous illumination or neonatal androgenization did not appear to modify the LHRH incorporation in either pineal gland or cervical ganglia. Basing on these results, the pineal gland is supposed to be a target organ for LHRH. (author)

A hybrid twin screw extrusion/electrospinning method to process nanoparticle-incorporated electrospun nanofibres

International Nuclear Information System (INIS)

Erisken, Cevat; Kalyon, Dilhan M; Wang Hongjun

2008-01-01

A new hybrid methodology that fully integrates the processing capabilities of the twin screw extrusion process (conveying solids, melting, dispersive and distributive mixing, pressurization, temperature profiling, devolatilization) with electrospinning is described. The hybrid process is especially suited to the dispersion of nanoparticles into polymeric binders and the generation of nanoparticle-incorporated fibres and nanofibres. The new technology base is demonstrated with the dispersion of β-tricalcium phosphate (β-TCP) nanoparticles into poly(ε-caprolactone) (PCL) to generate biodegradable non-woven meshes that can be targeted as scaffolds for tissue engineering applications. The new hybrid method yielded fibre diameters in the range of 200-2000 nm for both PCL and β-TCP/PCL (35% by weight) composite scaffolds. The degree of crystallinity of polycaprolactone meshes could be manipulated in the 35.1-41% range, using the voltage strength as a parameter. The electrospinning process, integrated with dispersive kneading disc elements, facilitated the decrease of the cluster sizes and allowed the continuous compounding of the nanoparticles into the biodegradable polymer prior to electrospinning. Thermogravimetric analysis (TGA) of the non-woven meshes validated the continuous incorporation of 35 ± 1.5% (by weight) β-TCP nanoparticles for a targeted concentration of 35%. Uniaxial tensile testing of the meshes with and without the nanoparticles indicated that the ultimate tensile strength at break of the meshes increased from 0.47 ± 0.04 to 0.79 ± 0.08 MPa upon the incorporation of the β-TCP nanoparticles. This demonstration study suggests that the new technology base is particularly suitable for the concomitant dispersion and electrospinning of nanoparticles in the generation of myriad types of functional nanofibres

Identifying and characterizing Hfq-RNA interactions.

Science.gov (United States)

Faner, M A; Feig, A L

2013-09-15

To regulate stress responses and virulence, bacteria use small regulatory RNAs (sRNAs). These RNAs can up or down regulate target mRNAs through base pairing by influencing ribosomal access and RNA decay. A large class of these sRNAs, called trans-encoded sRNAs, requires the RNA binding protein Hfq to facilitate base pairing between the regulatory RNA and its target mRNA. The resulting network of regulation is best characterized in Escherichia coli and Salmonella typhimurium, but the importance of Hfq dependent sRNA regulation is recognized in a diverse population of bacteria. In this review we present the approaches and methods used to discover Hfq binding RNAs, characterize their interactions and elucidate their functions. Copyright © 2013 Elsevier Inc. All rights reserved.

A new target concept for proton accelerator driven boron neutron capture therapy applications

International Nuclear Information System (INIS)

Powell, J.R.; Ludewig, H.; Todosow, M.; Reich, M.

1998-01-01

A new target concept termed Discs Incorporating Sector Configured Orbiting Sources (DISCOS), is proposed for spallation applications, including BNCT (Boron Neutron Capture Therapy). In the BNCT application a proton beam impacts a sequence of ultra thin lithium DISCOS targets to generate neutrons by the 7 Li(p,n) 7 Be reaction. The proton beam loses only a few keV of its ∼MeV energy as it passes through a given target, and is re-accelerated to its initial energy, by a DC electric field between the targets

CoLIde: A bioinformatics tool for CO-expression based small RNA Loci Identification using high-throughput sequencing data

OpenAIRE

Mohorianu, Irina; Stocks, Matthew Benedict; Wood, John; Dalmay, Tamas; Moulton, Vincent

2013-01-01

Small RNAs (sRNAs) are 20–25 nt non-coding RNAs that act as guides for the highly sequence-specific regulatory mechanism known as RNA silencing. Due to the recent increase in sequencing depth, a highly complex and diverse population of sRNAs in both plants and animals has been revealed. However, the exponential increase in sequencing data has also made the identification of individual sRNA transcripts corresponding to biological units (sRNA loci) more challenging when based exclusively on the...

SU-E-T-147: Beam Specific Planning Target Volumes Incorporating 4DCT for Pencil Beam Scanning Proton Therapy of Thoracic Tumors

Energy Technology Data Exchange (ETDEWEB)

Lin, L; Kang, M; Huang, S; McDonough, J; Solberg, T; Simone, C [University of Pennsylvania, Philadelphia, PA (United States); Mayer, R [Henry Jackson Foundation, Bethesda, MD (United States); Thomas, A [ATC healthcare, Bethesda, MD (United States)

2015-06-15

Purpose: The purpose of this study is to determine whether organ sparing and target coverage can be simultaneously maintained for pencil beam scanning (PBS) proton therapy treatment of thoracic tumors in the presence of motion, stopping power uncertainties and patient setup variations. Methods: Ten consecutive patients that were previously treated with proton therapy to 66.6/1.8 Gy (RBE) using double scattering (DS) were replanned with PBS. Minimum and maximum intensity images from 4DCT were used to introduce flexible smearing in the determination of the beam specific PTV (BSPTV). Datasets from eight 4DCT phases, using ±3% uncertainty in stopping power, and ±3 mm uncertainty in patient setup in each direction were used to create 8*12*10=960 PBS plans for the evaluation of ten patients. Plans were normalized to provide identical coverage between DS and PBS. Results: The average lung V20, V5, and mean doses were reduced from 29.0%, 35.0%, and 16.4 Gy with DS to 24.6%, 30.6%, and 14.1 Gy with PBS, respectively. The average heart V30 and V45 were reduced from 10.4% and 7.5% in DS to 8.1% and 5.4% for PBS, respectively. Furthermore, the maximum spinal cord, esophagus and heart dose were decreased from 37.1 Gy, 71.7 Gy and 69.2 Gy with DS to 31.3 Gy, 67.9 Gy and 64.6 Gy with PBS. The conformity index (CI), homogeneity index (HI), and global maximal dose were improved from 3.2, 0.08, 77.4 Gy with DS to 2.8, 0.04 and 72.1 Gy with PBS. All differences are statistically significant, with p values <0.05, with the exception of the heart V45 (p= 0.146). Conclusion: PBS with BSPTV achieves better organ sparing and improves target coverage using a repainting method for the treatment of thoracic tumors. Incorporating motion-related uncertainties is essential This work was supported by the US Army Medical Research and Materiel Command under Contract Agreement No. DAMD17-W81XWH-07-2-0121 and W81XWH-09-2-0174.

Platelets as Contractile Nanomachines for Targeting Drug Delivery in Hemostasis and Thrombosis

Science.gov (United States)

2015-12-01

capsules were suspended in platelet - rich plasma, which was subsequently exposed to 1 U/mL of thrombin, the capsules successfully targeted target...thrombotic sites via integration into the forming fibrin networks and binding to activated platelets . The delivery vehicles successfully adhere to platelet ...rupture has successfully been achieved in static fibrin gels comprised of a high concentration of platelets (Figure 3). Only capsules incorporated into

Geolocating thermal binoculars based on a software defined camera core incorporating HOT MCT grown by MOVPE

Science.gov (United States)

Pillans, Luke; Harmer, Jack; Edwards, Tim; Richardson, Lee

2016-05-01

Geolocation is the process of calculating a target position based on bearing and range relative to the known location of the observer. A high performance thermal imager with integrated geolocation functions is a powerful long range targeting device. Firefly is a software defined camera core incorporating a system-on-a-chip processor running the AndroidTM operating system. The processor has a range of industry standard serial interfaces which were used to interface to peripheral devices including a laser rangefinder and a digital magnetic compass. The core has built in Global Positioning System (GPS) which provides the third variable required for geolocation. The graphical capability of Firefly allowed flexibility in the design of the man-machine interface (MMI), so the finished system can give access to extensive functionality without appearing cumbersome or over-complicated to the user. This paper covers both the hardware and software design of the system, including how the camera core influenced the selection of peripheral hardware, and the MMI design process which incorporated user feedback at various stages.

Tunable translational control using site-specific unnatural amino acid incorporation in Escherichia coli

Directory of Open Access Journals (Sweden)

Yusuke Kato

2015-04-01

Full Text Available Translation of target gene transcripts in Escherichia coli harboring UAG amber stop codons can be switched on by the amber-codon-specific incorporation of an exogenously supplied unnatural amino acid, 3-iodo-L-tyrosine. Here, we report that this translational switch can control the translational efficiency at any intermediate magnitude by adjustment of the 3-iodo-L-tyrosine concentration in the medium, as a tunable translational controller. The translational efficiency of a target gene reached maximum levels with 10−5 M 3-iodo-L-tyrosine, and intermediate levels were observed with suboptimal concentrations (approximately spanning a 2-log10 concentration range, 10−7–10−5 M. Such intermediate-level expression was also confirmed in individual bacteria.

Conceptual design considerations and neutronics of lithium fall laser fusion target chambers

International Nuclear Information System (INIS)

Meier, W.R.; Thomson, W.B.

1978-01-01

Atomics International and Lawrence Livermore Laboratory are involved in the conceptual design of a laser fusion power plant incorporating the lithium fall target chamber. In this paper we discuss some of the more important design considerations for the target chamber and evaluate its nuclear performance. Sizing and configuration of the fall, hydraulic effects, and mechanical design considerations are addressed. The nuclear aspects examined include tritium breeding, energy deposition, and radiation damage

Steric and thermodynamic limits of design for the incorporation of large unnatural amino acids in aminoacyl-tRNA synthetase enzymes.

Science.gov (United States)

Armen, Roger S; Schiller, Stefan M; Brooks, Charles L

2010-06-01

Orthogonal aminoacyl-tRNA synthetase/tRNA pairs from archaea have been evolved to facilitate site specific in vivo incorporation of unnatural amino acids into proteins in Escherichia coli. Using this approach, unnatural amino acids have been successfully incorporated with high translational efficiency and fidelity. In this study, CHARMM-based molecular docking and free energy calculations were used to evaluate rational design of specific protein-ligand interactions for aminoacyl-tRNA synthetases. A series of novel unnatural amino acid ligands were docked into the p-benzoyl-L-phenylalanine tRNA synthetase, which revealed that the binding pocket of the enzyme does not provide sufficient space for significantly larger ligands. Specific binding site residues were mutated to alanine to create additional space to accommodate larger target ligands, and then mutations were introduced to improve binding free energy. This approach was used to redesign binding sites for several different target ligands, which were then tested against the standard 20 amino acids to verify target specificity. Only the synthetase designed to bind Man-alpha-O-Tyr was predicted to be sufficiently selective for the target ligand and also thermodynamically stable. Our study suggests that extensive redesign of the tRNA synthatase binding pocket for large bulky ligands may be quite thermodynamically unfavorable.

Mining predicted essential genes of Brugia malayi for nematode drug targets.

Directory of Open Access Journals (Sweden)

Sanjay Kumar

Full Text Available We report results from the first genome-wide application of a rational drug target selection methodology to a metazoan pathogen genome, the completed draft sequence of Brugia malayi, a parasitic nematode responsible for human lymphatic filariasis. More than 1.5 billion people worldwide are at risk of contracting lymphatic filariasis and onchocerciasis, a related filarial disease. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. The recent publication of the draft genomic sequence for B. malayi enables a genome-wide search for new drug targets. However, there is no functional genomics data in B. malayi to guide the selection of potential drug targets. To circumvent this problem, we have utilized the free-living model nematode Caenorhabditis elegans as a surrogate for B. malayi. Sequence comparisons between the two genomes allow us to map C. elegans orthologs to B. malayi genes. Using these orthology mappings and by incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens, that already exist for C. elegans, we identify potentially essential genes in B. malayi. Further incorporation of human host genome sequence data and a custom algorithm for prioritization enables us to collect and rank nearly 600 drug target candidates. Previously identified potential drug targets cluster near the top of our prioritized list, lending credibility to our methodology. Over-represented Gene Ontology terms, predicted InterPro domains, and RNAi phenotypes of C. elegans orthologs associated with the potential target pool are identified. By virtue of the selection procedure, the potential B. malayi drug targets highlight components of key processes in nematode biology such as central metabolism, molting and regulation of gene expression.

High Altitude Supersonic Target (HAST), Phase 2

Science.gov (United States)

1974-08-01

consists of a padded cradle assembly and a tubular steel stand with lockable swivel casters on the front wheels . c Tne recovery module lifting handle is...eds no modification of the ordnance fired at it in order to function. With the HAST system a target will be provided to evaluate the most advanced...Components were tested under environmental extremes. With the completion of the preflight readiness tests and with modification incorporated during the

Synthetic LDL as targeted drug delivery vehicle

Science.gov (United States)

Forte, Trudy M [Berkeley, CA; Nikanjam, Mina [Richmond, CA

2012-08-28

The present invention provides a synthetic LDL nanoparticle comprising a lipid moiety and a synthetic chimeric peptide so as to be capable of binding the LDL receptor. The synthetic LDL nanoparticle of the present invention is capable of incorporating and targeting therapeutics to cells expressing the LDL receptor for diseases associated with the expression of the LDL receptor such as central nervous system diseases. The invention further provides methods of using such synthetic LDL nanoparticles.

Design, construction, and characterization of high-performance membrane fusion devices with target-selectivity.

Science.gov (United States)

Kashiwada, Ayumi; Yamane, Iori; Tsuboi, Mana; Ando, Shun; Matsuda, Kiyomi

2012-01-31

Membrane fusion proteins such as the hemagglutinin glycoprotein have target recognition and fusion accelerative domains, where some synergistically working elements are essential for target-selective and highly effective native membrane fusion systems. In this work, novel membrane fusion devices bearing such domains were designed and constructed. We selected a phenylboronic acid derivative as a recognition domain for a sugar-like target and a transmembrane-peptide (Leu-Ala sequence) domain interacting with the target membrane, forming a stable hydrophobic α-helix and accelerating the fusion process. Artificial membrane fusion behavior between the synthetic devices in which pilot and target liposomes were incorporated was characterized by lipid-mixing and inner-leaflet lipid-mixing assays. Consequently, the devices bearing both the recognition and transmembrane domains brought about a remarkable increase in the initial rate for the membrane fusion compared with the devices containing the recognition domain alone. In addition, a weakly acidic pH-responsive device was also constructed by replacing three Leu residues in the transmembrane-peptide domain by Glu residues. The presence of Glu residues made the acidic pH-dependent hydrophobic α-helix formation possible as expected. The target-selective liposome-liposome fusion was accelerated in a weakly acidic pH range when the Glu-substituted device was incorporated in pilot liposomes. The use of this pH-responsive device seems to be a potential strategy for novel applications in a liposome-based delivery system. © 2011 American Chemical Society

Numeral Incorporation in Japanese Sign Language

Science.gov (United States)

Ktejik, Mish

2013-01-01

This article explores the morphological process of numeral incorporation in Japanese Sign Language. Numeral incorporation is defined and the available research on numeral incorporation in signed language is discussed. The numeral signs in Japanese Sign Language are then introduced and followed by an explanation of the numeral morphemes which are…

Detection of Moving Targets Using Soliton Resonance Effect

Science.gov (United States)

Kulikov, Igor K.; Zak, Michail

2013-01-01

The objective of this research was to develop a fundamentally new method for detecting hidden moving targets within noisy and cluttered data-streams using a novel "soliton resonance" effect in nonlinear dynamical systems. The technique uses an inhomogeneous Korteweg de Vries (KdV) equation containing moving-target information. Solution of the KdV equation will describe a soliton propagating with the same kinematic characteristics as the target. The approach uses the time-dependent data stream obtained with a sensor in form of the "forcing function," which is incorporated in an inhomogeneous KdV equation. When a hidden moving target (which in many ways resembles a soliton) encounters the natural "probe" soliton solution of the KdV equation, a strong resonance phenomenon results that makes the location and motion of the target apparent. Soliton resonance method will amplify the moving target signal, suppressing the noise. The method will be a very effective tool for locating and identifying diverse, highly dynamic targets with ill-defined characteristics in a noisy environment. The soliton resonance method for the detection of moving targets was developed in one and two dimensions. Computer simulations proved that the method could be used for detection of singe point-like targets moving with constant velocities and accelerations in 1D and along straight lines or curved trajectories in 2D. The method also allows estimation of the kinematic characteristics of moving targets, and reconstruction of target trajectories in 2D. The method could be very effective for target detection in the presence of clutter and for the case of target obscurations.

Incorporating threat in hotspots and coldspots of biodiversity and ecosystem services.

Science.gov (United States)

Schröter, Matthias; Kraemer, Roland; Ceauşu, Silvia; Rusch, Graciela M

2017-11-01

Spatial prioritization could help target conservation actions directed to maintain both biodiversity and ecosystem services. We delineate hotspots and coldspots of two biodiversity conservation features and five regulating and cultural services by incorporating an indicator of 'threat', i.e. timber harvest profitability for forest areas in Telemark (Norway). We found hotspots, where high values of biodiversity, ecosystem services and threat coincide, ranging from 0.1 to 7.1% of the area, depending on varying threshold levels. Targeting of these areas for conservation follows reactive conservation approaches. In coldspots, high biodiversity and ecosystem service values coincide with low levels of threat, and cover 0.1-3.4% of the forest area. These areas might serve proactive conservation approaches at lower opportunity cost (foregone timber harvest profits). We conclude that a combination of indicators of biodiversity, ecosystem services and potential threat is an appropriate approach for spatial prioritization of proactive and reactive conservation strategies.

Is DNA Alive? a Study of Conceptual Change through Targeted Instruction

Science.gov (United States)

Witzig, Stephen B.; Freyermuth, Sharyn K.; Siegel, Marcelle A.; Izci, Kemal; Pires, J. Chris

2013-01-01

We are involved in a project to incorporate innovative assessments within a reform-based large-lecture biochemistry course for nonmajors. We not only assessed misconceptions but purposefully changed instruction throughout the semester to confront student ideas. Our research questions targeted student conceptions of deoxyribonucleic acid (DNA)…

Integration of Bacterial Small RNAs in Regulatory Networks.

Science.gov (United States)

Nitzan, Mor; Rehani, Rotem; Margalit, Hanah

2017-05-22

Small RNAs (sRNAs) are central regulators of gene expression in bacteria, controlling target genes posttranscriptionally by base pairing with their mRNAs. sRNAs are involved in many cellular processes and have unique regulatory characteristics. In this review, we discuss the properties of regulation by sRNAs and how it differs from and combines with transcriptional regulation. We describe the global characteristics of the sRNA-target networks in bacteria using graph-theoretic approaches and review the local integration of sRNAs in mixed regulatory circuits, including feed-forward loops and their combinations, feedback loops, and circuits made of an sRNA and another regulator, both derived from the same transcript. Finally, we discuss the competition effects in posttranscriptional regulatory networks that may arise over shared targets, shared regulators, and shared resources and how they may lead to signal propagation across the network.

Robust Small Target Co-Detection from Airborne Infrared Image Sequences.

Science.gov (United States)

Gao, Jingli; Wen, Chenglin; Liu, Meiqin

2017-09-29

In this paper, a novel infrared target co-detection model combining the self-correlation features of backgrounds and the commonality features of targets in the spatio-temporal domain is proposed to detect small targets in a sequence of infrared images with complex backgrounds. Firstly, a dense target extraction model based on nonlinear weights is proposed, which can better suppress background of images and enhance small targets than weights of singular values. Secondly, a sparse target extraction model based on entry-wise weighted robust principal component analysis is proposed. The entry-wise weight adaptively incorporates structural prior in terms of local weighted entropy, thus, it can extract real targets accurately and suppress background clutters efficiently. Finally, the commonality of targets in the spatio-temporal domain are used to construct target refinement model for false alarms suppression and target confirmation. Since real targets could appear in both of the dense and sparse reconstruction maps of a single frame, and form trajectories after tracklet association of consecutive frames, the location correlation of the dense and sparse reconstruction maps for a single frame and tracklet association of the location correlation maps for successive frames have strong ability to discriminate between small targets and background clutters. Experimental results demonstrate that the proposed small target co-detection method can not only suppress background clutters effectively, but also detect targets accurately even if with target-like interference.

LHC Report: LHC hit the target!

CERN Multimedia

Enrico Bravin for the LHC team

2016-01-01

Last week, the accumulated integrated luminosity reached the target value for 2016 of 25 fb-1 in both ATLAS and CMS.   The integrated luminosity delivered to ATLAS and CMS reached (and already passed!) 25 fb-1– the target for the whole year! Tuesday, 30 August was just a regular day for the 2016 LHC run. However,  on that day, the integrated luminosity delivered to ATLAS and CMS reached 25 fb-1 – the target for the whole year! How did we get here? A large group of committed scientists and technical experts work behind the scenes at the LHC, ready to adapt to the quirks of this truly impressive machine. After the push to produce as many proton-proton collisions as possible before the summer conferences, several new ideas and production techniques (such as Bunch Compression Multiple Splitting, BCMS) have been incorporated in the operation of LHC in order to boost its performance even further. Thanks to these improvements, the LHC was routinely operated with peak luminos...

Conceptual design studies for the liquid metal target META:LIC

International Nuclear Information System (INIS)

Class, A.G.; Fazio, C.; Fetzer, J.R.; Gordeev, S.

2014-01-01

When the construction of ESS (European Spallation Source) in Sweden was initiated, the target station concept selection group decided to reevaluate a variety of target designs to respect new developments in their selection process. The META:LIC (MEgawatt TArget:Lead bIsmuth Cooled) target concept was developed following an extensive analysis of existing and new proposed designs and reached the level of proof of principle within only 2 years. ESS selected META:LIC as comparative target option for licensing purposes during the design update phase of ESS. The present work describes the design motivation of META:LIC referring to properties and design features of other targets. Therefore, META:LIC design is an evolutionary target which incorporates the extensive experience of liquid metal targets. The modular LBE (Lead Bismuth Eutectic) target concept with focus on the target module is introduced. Both, a window target option for the start of operation and a windowless option with extended lifetime are foreseen. Thermohydraulic simulations show that adequate window cooling can be realized. The stability of the free surface in the windowless option has been shown. Robust target module instrumentation based on free surface levels and the MEGAPIE experience is proposed for target control. Since the META:LIC concept foresees a horizontal extraction for both moderators and target from the monolith a safety concept based on the SNS and JSNS experience is proposed

An efficient protocol for incorporation of an unnatural amino acid in perdeuterated recombinant proteins using glucose-based media

Energy Technology Data Exchange (ETDEWEB)

Venditti, Vincenzo; Fawzi, Nicolas L.; Clore, G. Marius, E-mail: mariusc@mail.nih.gov [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)

2012-03-15

The in vivo incorporation of unnatural amino acids into proteins is a well-established technique requiring an orthogonal tRNA/aminoacyl-tRNA synthetase pair specific for the unnatural amino acid that is incorporated at a position encoded by a TAG amber codon. Although this technology provides unique opportunities to engineer protein structures, poor protein yields are usually obtained in deuterated media, hampering its application in the protein NMR field. Here, we describe a novel protocol for incorporating unnatural amino acids into fully deuterated proteins using glucose-based media (which are relevant to the production, for example, of amino acid-specific methyl-labeled proteins used in the study of large molecular weight systems). The method consists of pre-induction of the pEVOL plasmid encoding the tRNA/aminoacyl-tRNA synthetase pair in a rich, H{sub 2}O-based medium prior to exchanging the culture into a D{sub 2}O-based medium. Our protocol results in high level of isotopic incorporation ({approx}95%) and retains the high expression level of the target protein observed in Luria-Bertani medium.

Methodology of radionuclides dis incorporation in people related to nuclear and radiological accidents

International Nuclear Information System (INIS)

Jimenez F, E. A.

2014-01-01

In this paper a classification of the radiological and nuclear accidents is presented, describing which the activities are, where they have occurred, their incidence and the learned lessons in these successes. The radiological accidents in which radioactive materials intervene can occur anywhere, and they are related to no controlled dangerous sources (abandoned, lost, stolen, or found sources), improper use of dangerous industrial and medical sources, exposition and contamination of people in general by an unknown origin, serious over expositions, menaces and willful misconduct, emergencies during transportation of radioactive material. A person can receive a dose of radiation from an external source, because of radioactive material placed on skin or on equipment, or because of ingestion or inhalation of radiological particles. The ingestion or the inhalation of radioactive material can cause an internal dose to the whole body or to a specific organ during a period of time. That is why a description of the processes of incorporation, the stages of incorporation and a description of the biokinetic models are also realized to understand the ingestion, transference and the excretion of the radioactive elements. In order to offer help to a victim of internal contamination, the dosimetric and medical diagnosis is very important. The most important techniques of dosimetric diagnosis are the dosimetry in vivo (cytogenetics and the counting in vivo of the whole body) and the bioassays. These techniques allow obtain data such as the radionuclide, the target organ, the absorbed dose, etc. At the same time, the doctor in charge must be attentive to the patients symptoms and their manifestation time, since they are an indicator, first, the patient suffered an irradiation, and second, of the range esteem of the received radiation dose. These are the parameters that are useful as criterion to decide if a person has to receive some treatment and select the methodologies that

Targeted two-photon PDT photo-sensitizers for the treatment of subcutaneous tumors

Science.gov (United States)

Spangler, C. W.; Rebane, A.; Starkey, J.; Drobizhev, M.

2009-06-01

New porphyrin-based photo-sensitizers have been designed, synthesized and characterized that exhibit greatly enhanced intrinsic two-photon absorption. These new photo-sensitizers have been incorporated into triad formulations that also incorporate Near-infrared (NIR) imaging agents, and small-molecule targeting agents that direct the triads to cancerous tumors' over-expressed receptor sites. PDT can be initiated deep into the tissue transparency window at 780-800 nm utilizing a regeneratively amplified Ti:sapphire laser using 100-150 fs pulses of 600-800 mW. Human tumor xenografts of human breast cancer (MDA-MB-231) and both small SCLC (NCI-H69) and NSCLC (A-459) have been successfully treated using octreotate targeting of over-expressed SST2 receptors. In particular, the lung cancer xenografts can be successfully treated by irradiating from the side of the mouse opposite the implanted tumor, thereby passing through ca. 2 cm of mouse skin, tissue and organs with no discernible damage to healthy tissue while causing regression in the tumors. These results suggest a new PDT paradigm for the noninvasive treatment of subcutaneous tumors, including the possibility that the targeting moiety could be matched to individual patient genetic profiles (patient-specific therapeutics).

Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients.

NARCIS (Netherlands)

Witte, W.E.; Wong, Y.C.; Nederpelt, I.; Heitman, L.H.; Danhof, M.; Graaf, van der P.H.; Gilissen, R.A.; de, Lange E.C.

2016-01-01

INTRODUCTION Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target

Oasis 2: improved online analysis of small RNA-seq data.

Science.gov (United States)

Rahman, Raza-Ur; Gautam, Abhivyakti; Bethune, Jörn; Sattar, Abdul; Fiosins, Maksims; Magruder, Daniel Sumner; Capece, Vincenzo; Shomroni, Orr; Bonn, Stefan

2018-02-14

Small RNA molecules play important roles in many biological processes and their dysregulation or dysfunction can cause disease. The current method of choice for genome-wide sRNA expression profiling is deep sequencing. Here we present Oasis 2, which is a new main release of the Oasis web application for the detection, differential expression, and classification of small RNAs in deep sequencing data. Compared to its predecessor Oasis, Oasis 2 features a novel and speed-optimized sRNA detection module that supports the identification of small RNAs in any organism with higher accuracy. Next to the improved detection of small RNAs in a target organism, the software now also recognizes potential cross-species miRNAs and viral and bacterial sRNAs in infected samples. In addition, novel miRNAs can now be queried and visualized interactively, providing essential information for over 700 high-quality miRNA predictions across 14 organisms. Robust biomarker signatures can now be obtained using the novel enhanced classification module. Oasis 2 enables biologists and medical researchers to rapidly analyze and query small RNA deep sequencing data with improved precision, recall, and speed, in an interactive and user-friendly environment. Oasis 2 is implemented in Java, J2EE, mysql, Python, R, PHP and JavaScript. It is freely available at https://oasis.dzne.de.

Mal de Río Cuarto Virus Infection Triggers the Production of Distinctive Viral-Derived siRNA Profiles in Wheat and Its Planthopper Vector.

Science.gov (United States)

de Haro, Luis A; Dumón, Analía D; Mattio, María F; Argüello Caro, Evangelina Beatriz; Llauger, Gabriela; Zavallo, Diego; Blanc, Hervé; Mongelli, Vanesa C; Truol, Graciela; Saleh, María-Carla; Asurmendi, Sebastián; Del Vas, Mariana

2017-01-01

Plant reoviruses are able to multiply in gramineae plants and delphacid vectors encountering different defense strategies with unique features. This study aims to comparatively assess alterations of small RNA (sRNA) populations in both hosts upon virus infection. For this purpose, we characterized the sRNA profiles of wheat and planthopper vectors infected by Mal de Río Cuarto virus (MRCV, Fijivirus, Reoviridae ) and quantified virus genome segments by quantitative reverse transcription PCR We provide evidence that plant and insect silencing machineries differentially recognize the viral genome, thus giving rise to distinct profiles of virus-derived small interfering RNAs (vsiRNAs). In plants, most of the virus genome segments were targeted preferentially within their upstream sequences and vsiRNAs mapped with higher density to the smaller genome segments than to the medium or larger ones. This tendency, however, was not observed in insects. In both hosts, vsiRNAs were equally derived from sense and antisense RNA strands and the differences in vsiRNAs accumulation did not correlate with mRNAs accumulation. We also established that the piwi-interacting RNA (piRNA) pathway was active in the delphacid vector but, contrary to what is observed in virus-infected mosquitoes, virus-specific piRNAs were not detected. This work contributes to the understanding of the silencing response in insect and plant hosts.

Double-shell target designs for the Los Alamos Scientific Laboratory eight-beam laser system

International Nuclear Information System (INIS)

Kindel, J.M.; Stroscio, M.A.

1978-03-01

We investigate two double-pusher laser fusion targets, one that incorporates an outer exploding pusher shell and another that uses velocity multiplication. Specific designs are presented for the Los Alamos Scientific Laboratory Eight-Beam Laser System

Polarized photoproduction from nuclear targets with arbitrary spin and relation to deep inelastic scattering

International Nuclear Information System (INIS)

Hoodbhoy, P.; Massachusetts Inst. of Tech., Cambridge; Quaid-i-Azam Univ., Islamabad

1990-01-01

Inclusive photo-production from polarized targets of arbitrary spin is analyzed by using multipoles. The Drell-Hearn-Gerasimov sum rule, which was originally fromulated for spin-1/2 targets, is generalized to all spins and multipoles, and shown to have some interesting consequences. Measurements to test the new rules, or to derive nuclear structure information from them, could be incorporated into existing plans at electron accelerator facilities. Finally, the possible relevance of these generalized sum rules to sum rules measurable in polarized lepton-polarized target deep inelastic inclusive scattering is discussed. (orig.)

Computational design of high efficiency release targets for use at ISOL facilities

CERN Document Server

Liu, Y

1999-01-01

This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat-removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated-vitreous-carbon fiber (RVCF) or carbon-bonded-carbon fiber (CBCF) to form highly permeable composite target matrices. Computational studies that simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived from diffusion release-rate simulation studies for selected t...

A mixed incoherent feed-forward loop contributes to the regulation of bacterial photosynthesis genes.

Science.gov (United States)

Mank, Nils N; Berghoff, Bork A; Klug, Gabriele

2013-03-01

Living cells use a variety of regulatory network motifs for accurate gene expression in response to changes in their environment or during differentiation processes. In Rhodobacter sphaeroides, a complex regulatory network controls expression of photosynthesis genes to guarantee optimal energy supply on one hand and to avoid photooxidative stress on the other hand. Recently, we identified a mixed incoherent feed-forward loop comprising the transcription factor PrrA, the sRNA PcrZ and photosynthesis target genes as part of this regulatory network. This point-of-view provides a comparison to other described feed-forward loops and discusses the physiological relevance of PcrZ in more detail.

New "Risk-Targeted" Seismic Maps Introduced into Building Codes

Science.gov (United States)

Luco, Nicholas; Garrett, B.; Hayes, J.

2012-01-01

Throughout most municipalities of the United States, structural engineers design new buildings using the U.S.-focused International Building Code (IBC). Updated editions of the IBC are published every 3 years. The latest edition (2012) contains new "risk-targeted maximum considered earthquake" (MCER) ground motion maps, which are enabling engineers to incorporate a more consistent and better defined level of seismic safety into their building designs.

Incorporating modern neuroscience findings to improve brain-computer interfaces: tracking auditory attention.

Science.gov (United States)

Wronkiewicz, Mark; Larson, Eric; Lee, Adrian Kc

2016-10-01

Brain-computer interface (BCI) technology allows users to generate actions based solely on their brain signals. However, current non-invasive BCIs generally classify brain activity recorded from surface electroencephalography (EEG) electrodes, which can hinder the application of findings from modern neuroscience research. In this study, we use source imaging-a neuroimaging technique that projects EEG signals onto the surface of the brain-in a BCI classification framework. This allowed us to incorporate prior research from functional neuroimaging to target activity from a cortical region involved in auditory attention. Classifiers trained to detect attention switches performed better with source imaging projections than with EEG sensor signals. Within source imaging, including subject-specific anatomical MRI information (instead of using a generic head model) further improved classification performance. This source-based strategy also reduced accuracy variability across three dimensionality reduction techniques-a major design choice in most BCIs. Our work shows that source imaging provides clear quantitative and qualitative advantages to BCIs and highlights the value of incorporating modern neuroscience knowledge and methods into BCI systems.

Patient-Specific Dosimetry and Radiobiological Modeling of Targeted Radionuclide Therapy Grant - final report

Energy Technology Data Exchange (ETDEWEB)

George Sgouros, Ph.D.

2007-03-20

The broad, long-term objectives of this application are to 1. develop easily implementable tools for radionuclide dosimetry that can be used to predict normal organ toxicity and tumor response in targeted radionuclide therapy; and 2. to apply these tools to the analysis of clinical trial data in order to demonstrate dose-response relationships for radionuclide therapy treatment planning. The work is founded on the hypothesis that robust dose-response relationships have not been observed in targeted radionuclide therapy studies because currently available internal dosimetry methodologies are inadequate, failing to adequately account for individual variations in patient anatomy, radionuclide activity distribution/kinetics, absorbed dose-distribution, and absorbed dose-rate. To reduce development time the previously available software package, 3D-ID, one of the first dosimetry software packages to incorporate 3-D radionuclide distribution with individual patient anatomy; and the first to be applied for the comprehensive analysis of patient data, will be used as a platform to build the functionality listed above. The following specific aims are proposed to satisfy the long-term objectives stated above: 1. develop a comprehensive and validated methodology for converting one or more SPECT images of the radionuclide distribution to a 3-D representation of the cumulated activity distribution; 2. account for differences in tissue density and atomic number by incorporating an easily implementable Monte Carlo methodology for the 3-D dosimetry calculations; 3. incorporate the biologically equivalent dose (BED) and equivalent uniform dose (EUD) models to convert the spatial distribution of absorbed dose and dose-rate into equivalent single values that account for differences in dose uniformity and rate and that may be correlated with tumor response and normal organ toxicity; 4. test the hypothesis stated above by applying the resulting package to patient trials of targeted

Facile Synthesis of Novel Vanillin Derivatives Incorporating a Bis(2-hydroxyethyl)dithhioacetal Moiety as Antiviral Agents.

Science.gov (United States)

Zhang, Jian; Zhao, Lei; Zhu, Chun; Wu, Zengxue; Zhang, Guoping; Gan, Xiuhai; Liu, Dengyue; Pan, Jianke; Hu, Deyu; Song, Baoan

2017-06-14

A series of vanillin derivatives incorporating a bis(2-hydroxyethyl)dithioacetal moiety was designed and synthesized via a facile method. A plausible reaction pathway was proposed and verified by computational studies. Bioassay results demonstrated that target compounds possessed good to excellent activities against potato virus Y (PVY) and cucumber mosaic virus (CMV), of which, compound 6f incorporating a bis(2-hydroxyethyl)dithioacetal moiety, exhibited the best curative and protection activities against PVY and CMV in vivo, with 50% effective concentration values of 217.6, 205.7 μg/mL and 206.3, 186.2 μg/mL, respectively, better than those of ribavirin (848.0, 808.1 μg/mL and 858.2, 766.5 μg/mL, respectively), dufulin (462.6, 454.8 μg/mL and 471.2, 465.4 μg/mL, respectively), and ningnanmycin (440.5, 425.3 μg/mL and 426.1, 405.3 μg/mL, respectively). Current studies provide support for the application of vanillin derivatives incorporating bis(2-hydroxyethyl)dithioacetal as new antiviral agents.

Host thin films incorporating nanoparticles

Science.gov (United States)

Qureshi, Uzma

The focus of this research project was the investigation of the functional properties of thin films that incorporate a secondary nanoparticulate phase. In particular to assess if the secondary nanoparticulate material enhanced a functional property of the coating on glass. In order to achieve this, new thin film deposition methods were developed, namely use of nanopowder precursors, an aerosol assisted transport technique and an aerosol into atmospheric pressure chemical vapour deposition system. Aerosol assisted chemical vapour deposition (AACVD) was used to deposit 8 series of thin films on glass. Five different nanoparticles silver, gold, ceria, tungsten oxide and zinc oxide were tested and shown to successfully deposit thin films incorporating nanoparticles within a host matrix. Silver nanoparticles were synthesised and doped within a titania film by AACVD. This improved solar control properties. A unique aerosol assisted chemical vapour deposition (AACVD) into atmospheric pressure chemical vapour deposition (APCVD) system was used to deposit films of Au nanoparticles and thin films of gold nanoparticles incorporated within a host titania matrix. Incorporation of high refractive index contrast metal oxide particles within a host film altered the film colour. The key goal was to test the potential of nanopowder forms and transfer the suspended nanopowder via an aerosol to a substrate in order to deposit a thin film. Discrete tungsten oxide nanoparticles or ceria nanoparticles within a titanium dioxide thin film enhanced the self-cleaning and photo-induced super-hydrophilicity. The nanopowder precursor study was extended by deposition of zinc oxide thin films incorporating Au nanoparticles and also ZnO films deposited from a ZnO nanopowder precursor. Incorporation of Au nanoparticles within a VO: host matrix improved the thermochromic response, optical and colour properties. Composite VC/TiC and Au nanoparticle/V02/Ti02 thin films displayed three useful

Locked nucleoside analogues expand the potential of DNAzymes to cleave structured RNA targets

Directory of Open Access Journals (Sweden)

Wengel Jesper

2006-06-01

Full Text Available Abstract Background DNAzymes cleave at predetermined sequences within RNA. A prerequisite for cleavage is that the DNAzyme can gain access to its target, and thus the DNAzyme must be capable of unfolding higher-order structures that are present in the RNA substrate. However, in many cases the RNA target sequence is hidden in a region that is too tightly structured to be accessed under physiological conditions by DNAzymes. Results We investigated how incorporation of LNA (locked nucleic acid monomers into DNAzymes improves their ability to gain access and cleave at highly-structured RNA targets. The binding arms of DNAzymes were varied in length and were substituted with up to three LNA and α-L-LNA monomers (forming LNAzymes. For one DNAzyme, the overall cleavage reaction proceeded fifty times faster after incorporation of two α-L-LNA monomers per binding arm (kobs increased from 0.014 min-1 to 0.78 min-1. Conclusion The data demonstrate how hydrolytic performance can be enhanced by design of LNAzymes, and indicate that there are optimal lengths for the binding arms and for the number of modified LNA monomers.

17 CFR 230.411 - Incorporation by reference.

Science.gov (United States)

2010-04-01

... following provisions: (1) Non-financial information may be incorporated by reference to any document; (2) Financial information may be incorporated by reference to any document, provided any financial statement so incorporated meets the requirements of the forms on which the statement is filed. Financial statements or other...

Possible approaches to fast quality control of IFE targets

International Nuclear Information System (INIS)

Koresheva, E.R.; Nikitenko, A.I.; Aleksandrova, I.V.; Bazdenkov, S.V.; Belolipetskiy, A.A.; Chtcherbakov, V.I.; Osipov, I.E.

2006-01-01

In recent years, research into the development of reliable methods and techniques for characterization and quality control of ICF/IFE targets has been carried out very actively. This is motivated by the need to provide the means for precise and accurate knowledge of cryogenic target parameters. On the other hand, particular emphasis should be paid to the fact that fuelling of a commercial power plant requires ∼6 targets each second. This indicates that the development of fast quality control techniques is of critical importance as well. Therefore, in this report we discuss the issues underlying the construction of different algorithms for characterization and quality control of ICF/IFE targets. Among them are: (a) algorithm banks and their structure, (b) algorithm testing, (c) target reconstruction experiments. The algorithm bank incorporates the algorithms for two stages of target production: the stage of fuel layering technique development (motionless target) and the stage of cryogenic target delivery (injected target). In the first case an inverse algorithm for individual target characterization (3D target reconstruction) and two threshold algorithms for fast control of target quality are presented. They are based on tomographic information processing methods. Experimentally, tomographic data acquisition is carried out by a hundred projections microtomograph. The spatial resolution of the optical system of the microtomograph is 1 μm for 490 nm wavelength, the accuracy of target angular positioning is ±1.5-2.5 min. In the second case we describe the algorithm based on Fourier transform holography for ultra fast target characterization during its injection. The performed computer experiments have demonstrated much promise of this approach in the following directions: recognition of the target imperfections in both low- and high- harmonics; quality control of both a single target and a target batch; simultaneous control of both an injected target quality and

Leading by example: a local health department-community collaboration to incorporate physical activity into organizational practice.

Science.gov (United States)

Yancey, Antronette K; Lewis, Lavonna B; Sloane, David C; Guinyard, Joyce Jones; Diamant, Allison L; Nascimento, Lori M; McCarthy, William J

2004-01-01

A multisectoral model promoting sociocultural environmental change to increase physical activity levels among African Americans in Los Angeles County, California, was developed and implemented. This model represents a true collaboration between a local health department and a community lead agency. Community organizations serving targeted areas of the county participated in one or more interventions incorporating physical activity into routine organizational practice, which centered around modeling the behaviors promoted ("walking the talk"). In the current study, level of organizational support for physical activity integration was assessed, as reflected in the extent of organizational commitment associated with each intervention. Individual-level data, characterizing the sociodemography, health status, and health behaviors of organization staff, members, and clients, are presented to document the average risk burden in the targeted population. Nearly half of the more than 200 participating organizations actively embraced incorporating physical activity into their regular work routines, with more than 25 percent committed at the highest level of involvement. Broad capacity and support for organizational integration of physical activity was demonstrated, with the observed level of commitment varying by organization type. Similar to the successful evolution of tobacco control, some of the responsibility ("cost") for physical activity adoption and maintenance can and should be shifted from the individual to organizational entities, such as workplaces.

A Catalog of Cool Dwarf Targets for the Transiting Exoplanet Survey Satellite

Science.gov (United States)

Muirhead, Philip S.; Dressing, Courtney D.; Mann, Andrew W.; Rojas-Ayala, Bárbara; Lépine, Sébastien; Paegert, Martin; De Lee, Nathan; Oelkers, Ryan

2018-04-01

We present a catalog of cool dwarf targets (V-J> 2.7, T eff ≲ 4000 K) and their stellar properties for the upcoming Transiting Exoplanet Survey Satellite (TESS), for the purpose of determining which cool dwarfs should be observed using two minute observations. TESS has the opportunity to search tens of thousands of nearby, cool, late K- and M-type dwarfs for transiting exoplanets, an order of magnitude more than current or previous transiting exoplanet surveys, such as Kepler, K2, and ground-based programs. This necessitates a new approach to choosing cool dwarf targets. Cool dwarfs are chosen by collating parallax and proper motion catalogs from the literature and subjecting them to a variety of selection criteria. We calculate stellar parameters and TESS magnitudes using the best possible relations from the literature while maintaining uniformity of methods for the sake of reproducibility. We estimate the expected planet yield from TESS observations using statistical results from the Kepler mission, and use these results to choose the best targets for two minute observations, optimizing for small planets for which masses can conceivably be measured using follow-up Doppler spectroscopy by current and future Doppler spectrometers. The catalog is available in machine readable format and is incorporated into the TESS Input Catalog and TESS Candidate Target List until a more complete and accurate cool dwarf catalog identified by ESA’s Gaia mission can be incorporated.

Coping with Atmospheric Turbulence in the Selection of Laser Hardening Technology for FCS Targeting Systems

National Research Council Canada - National Science Library

Pritchett, Timothy M

2004-01-01

... by frequency-agile battlefield lasers at both long and short range. Evidently, the selection of sensor protection technologies for incorporation into the final targeting system will be based on their optical limiting performance under field conditions...

The effects of music therapy incorporated with applied behavior analysis verbal behavior approach for children with autism spectrum disorders.

Science.gov (United States)

Lim, Hayoung A; Draper, Ellary

2011-01-01

This study compared a common form of Applied Behavior Analysis Verbal Behavior (ABA VB) approach and music incorporated with ABA VB method as part of developmental speech-language training in the speech production of children with Autism Spectrum Disorders (ASD). This study explored how the perception of musical patterns incorporated in ABA VB operants impacted the production of speech in children with ASD. Participants were 22 children with ASD, age range 3 to 5 years, who were verbal or pre verbal with presence of immediate echolalia. They were randomly assigned a set of target words for each of the 3 training conditions: (a) music incorporated ABA VB, (b) speech (ABA VB) and (c) no-training. Results showed both music and speech trainings were effective for production of the four ABA verbal operants; however, the difference between music and speech training was not statistically different. Results also indicated that music incorporated ABA VB training was most effective in echoic production, and speech training was most effective in tact production. Music can be incorporated into the ABA VB training method, and musical stimuli can be used as successfully as ABA VB speech training to enhance the functional verbal production in children with ASD.

Design of a sensitive aptasensor based on magnetic microbeads-assisted strand displacement amplification and target recycling.

Science.gov (United States)

Li, Ying; Ji, Xiaoting; Song, Weiling; Guo, Yingshu

2013-04-03

A cross-circular amplification system for sensitive detection of adenosine triphosphate (ATP) in cancer cells was developed based on aptamer-target interaction, magnetic microbeads (MBs)-assisted strand displacement amplification and target recycling. Here we described a new recognition probe possessing two parts, the ATP aptamer and the extension part. The recognition probe was firstly immobilized on the surface of MBs and hybridized with its complementary sequence to form a duplex. When combined with ATP, the probe changed its conformation, revealing the extension part in single-strand form, which further served as a toehold for subsequent target recycling. The released complementary sequence of the probe acted as the catalyst of the MB-assisted strand displacement reaction. Incorporated with target recycling, a large amount of biotin-tagged MB complexes were formed to stimulate the generation of chemiluminescence (CL) signal in the presence of luminol and H2O2 by incorporating with streptavidin-HRP, reaching a detection limit of ATP as low as 6.1×10(-10)M. Moreover, sample assays of ATP in Ramos Burkitt's lymphoma B cells were performed, which confirmed the reliability and practicality of the protocol. Copyright © 2013 Elsevier B.V. All rights reserved.

Filling and Recycling Apparatus of a Cyclotron Target with Enriched Krypton for Production of Radiopharmaceuticals

Directory of Open Access Journals (Sweden)

M. Vognar

2001-01-01

Full Text Available An apparatus for multiple filling of a cyclotron target with enriched Kr gas is described. The system is based on recycling pressurized gas by cryogenic pumping between the target tube and storage containers. The design and construction makes use of previous experience in the construction and operation of two analogue apparatuses for Xe124 high pressure gas targets, but major modifications have been incorporated, evoked by the different physical properties of Kr, by the character of the nuclear reaction, and by the demand for automation from the side of the end user.

Isotopic characterization of targets for nuclear measurements at CBNM

International Nuclear Information System (INIS)

Bievre, P. de

1985-01-01

Nuclear measurements for which ''nuclear'' targets are prepared are almost always isotope-specific i.e. they are normally related to a particular nuclide in the target. The amount of this nuclide must be accurately assessed. There are essentially two ways to determine the number of atoms of this particular nuclide. (1) By determination of the amount of element, to which the nuclide belongs, on the target via classsical means; weighing substraction of impurities, calculation of element amount using known of the chemical compound in which the element is incorporated and, finally, measurement of the isotopic composition in order to determine the fraction of the nuclide concerned in the element. An alternative way may be to perform an elemental assay on the target followed by determination of the isotopic composition. (2) Another approach is isotope dilution mass spectrometry where a change in the isotopic composition of the ''target'' is induced by adding a known number of atoms (called ''spike'') of the element with a quite different composition. Measurement of the resulting change in isotopic composition yields directly the number of atoms of the nuclide under investigation. The method is highly selective, accurate and isotope-specific. (orig.)

Can Social Functioning in Schizophrenia Be Improved through Targeted Social Cognitive Intervention?

Directory of Open Access Journals (Sweden)

David L. Roberts

2012-01-01

Full Text Available Efforts to use cognitive remediation in psychosocial intervention for schizophrenia have increasingly incorporated social cognition as a treatment target. A distinction can be made in this work between “broad-based” interventions, which integrate social cognitive training within a multicomponent suite of intervention techniques and “targeted” interventions; which aim to enhance social cognition alone. Targeted interventions have the potential advantage of being more efficient than broad-based interventions; however, they also face difficult challenges. In particular, targeted interventions may be less likely to achieve maintenance and generalization of gains made in treatment. A novel potential solution to this problem is described which draws on the social psychological literature on social cognition.

SU-E-J-76: Incorporation of Ultrasound Elastography in Target Volume Delineation for Partial Breast Radiotherapy Planning: A Comparative Study

Energy Technology Data Exchange (ETDEWEB)

Juneja, P; Harris, E; Bamber, J [The Institute of Cancer Research, London (United Kingdom); Royal Marsden NHS Foundation Trust, London (United Kingdom)

2014-06-01

Purpose: There is substantial observer variability in the delineation of target volumes for post-surgical partial breast radiotherapy because the tumour bed has poor x-ray contrast. This variability may result in substantial variations in planned dose distribution. Ultrasound elastography (USE) has an ability to detect mechanical discontinuities and therefore, the potential to image the scar and distortion in breast tissue architecture. The goal of this study was to compare USE techniques: strain elastography (SE), shear wave elastography (SWE) and acoustic radiation force impulse (ARFI) imaging using phantoms that simulate features of the tumour bed, for the purpose of incorporating USE in breast radiotherapy planning. Methods: Three gelatine-based phantoms (10% w/v) containing: a stiff inclusion (gelatine 16% w/v) with adhered boundaries, a stiff inclusion (gelatine 16% w/v) with mobile boundaries and fluid cavity inclusion (to mimic seroma), were constructed and used to investigate the USE techniques. The accuracy of the elastography techniques was quantified by comparing the imaged inclusion with the modelled ground-truth using the Dice similarity coefficient (DSC). For two regions of interest (ROI), the DSC measures their spatial overlap. Ground-truth ROIs were modelled using geometrical measurements from B-mode images. Results: The phantoms simulating stiff scar tissue with adhered and mobile boundaries and seroma were successfully developed and imaged using SE and SWE. The edges of the stiff inclusions were more clearly visible in SE than in SWE. Subsequently, for all these phantoms the measured DSCs were found to be higher for SE (DSCs: 0.91–0.97) than SWE (DSCs: 0.68–0.79) with an average relative difference of 23%. In the case of seroma phantom, DSC values for SE and SWE were similar. Conclusion: This study presents a first attempt to identify the most suitable elastography technique for use in breast radiotherapy planning. Further analysis will

SU-E-J-76: Incorporation of Ultrasound Elastography in Target Volume Delineation for Partial Breast Radiotherapy Planning: A Comparative Study

International Nuclear Information System (INIS)

Juneja, P; Harris, E; Bamber, J

2014-01-01

Purpose: There is substantial observer variability in the delineation of target volumes for post-surgical partial breast radiotherapy because the tumour bed has poor x-ray contrast. This variability may result in substantial variations in planned dose distribution. Ultrasound elastography (USE) has an ability to detect mechanical discontinuities and therefore, the potential to image the scar and distortion in breast tissue architecture. The goal of this study was to compare USE techniques: strain elastography (SE), shear wave elastography (SWE) and acoustic radiation force impulse (ARFI) imaging using phantoms that simulate features of the tumour bed, for the purpose of incorporating USE in breast radiotherapy planning. Methods: Three gelatine-based phantoms (10% w/v) containing: a stiff inclusion (gelatine 16% w/v) with adhered boundaries, a stiff inclusion (gelatine 16% w/v) with mobile boundaries and fluid cavity inclusion (to mimic seroma), were constructed and used to investigate the USE techniques. The accuracy of the elastography techniques was quantified by comparing the imaged inclusion with the modelled ground-truth using the Dice similarity coefficient (DSC). For two regions of interest (ROI), the DSC measures their spatial overlap. Ground-truth ROIs were modelled using geometrical measurements from B-mode images. Results: The phantoms simulating stiff scar tissue with adhered and mobile boundaries and seroma were successfully developed and imaged using SE and SWE. The edges of the stiff inclusions were more clearly visible in SE than in SWE. Subsequently, for all these phantoms the measured DSCs were found to be higher for SE (DSCs: 0.91–0.97) than SWE (DSCs: 0.68–0.79) with an average relative difference of 23%. In the case of seroma phantom, DSC values for SE and SWE were similar. Conclusion: This study presents a first attempt to identify the most suitable elastography technique for use in breast radiotherapy planning. Further analysis will

Model-based drug administration : current status of target-controlled infusion and closed-loop control

NARCIS (Netherlands)

Kuizenga, Merel H.; Vereecke, Hugo E. M.; Struys, Michel M. R. F.

Purpose of review Drug administration might be optimized by incorporating pharmacokinetic-dynamic (PK/PD) principles and control engineering theories. This review gives an update of the actual status of target-controlled infusion (TCI) and closed-loop computer-controlled drug administration and the

Small regulatory RNA-induced growth rate heterogeneity of Bacillus subtilis.

Science.gov (United States)

Mars, Ruben A T; Nicolas, Pierre; Ciccolini, Mariano; Reilman, Ewoud; Reder, Alexander; Schaffer, Marc; Mäder, Ulrike; Völker, Uwe; van Dijl, Jan Maarten; Denham, Emma L

2015-03-01

Isogenic bacterial populations can consist of cells displaying heterogeneous physiological traits. Small regulatory RNAs (sRNAs) could affect this heterogeneity since they act by fine-tuning mRNA or protein levels to coordinate the appropriate cellular behavior. Here we show that the sRNA RnaC/S1022 from the Gram-positive bacterium Bacillus subtilis can suppress exponential growth by modulation of the transcriptional regulator AbrB. Specifically, the post-transcriptional abrB-RnaC/S1022 interaction allows B. subtilis to increase the cell-to-cell variation in AbrB protein levels, despite strong negative autoregulation of the abrB promoter. This behavior is consistent with existing mathematical models of sRNA action, thus suggesting that induction of protein expression noise could be a new general aspect of sRNA regulation. Importantly, we show that the sRNA-induced diversity in AbrB levels generates heterogeneity in growth rates during the exponential growth phase. Based on these findings, we hypothesize that the resulting subpopulations of fast- and slow-growing B. subtilis cells reflect a bet-hedging strategy for enhanced survival of unfavorable conditions.

The Regulatory Small RNA MarS Supports Virulence of Streptococcus pyogenes.

Science.gov (United States)

Pappesch, Roberto; Warnke, Philipp; Mikkat, Stefan; Normann, Jana; Wisniewska-Kucper, Aleksandra; Huschka, Franziska; Wittmann, Maja; Khani, Afsaneh; Schwengers, Oliver; Oehmcke-Hecht, Sonja; Hain, Torsten; Kreikemeyer, Bernd; Patenge, Nadja

2017-09-25

Small regulatory RNAs (sRNAs) play a role in the control of bacterial virulence gene expression. In this study, we investigated an sRNA that was identified in Streptococcus pyogenes (group A Streptococcus, GAS) but is conserved throughout various streptococci. In a deletion strain, expression of mga, the gene encoding the multiple virulence gene regulator, was reduced. Accordingly, transcript and proteome analyses revealed decreased expression of several Mga-activated genes. Therefore, and because the sRNA was shown to interact with the 5' UTR of the mga transcript in a gel-shift assay, we designated it MarS for m ga-activating regulatory sRNA. Down-regulation of important virulence factors, including the antiphagocytic M-protein, led to increased susceptibility of the deletion strain to phagocytosis and reduced adherence to human keratinocytes. In a mouse infection model, the marS deletion mutant showed reduced dissemination to the liver, kidney, and spleen. Additionally, deletion of marS led to increased tolerance towards oxidative stress. Our in vitro and in vivo results indicate a modulating effect of MarS on virulence gene expression and on the pathogenic potential of GAS.

The Use of Backscattered Electron Imaging and Transmission Electron Microscopy to Assess Bone Architecture and Mineral Loci: Effect of Intermittent Slow-Release Sodium Fluoride Therapy

Science.gov (United States)

Zerwekh, Joseph E.; Bellotto, Dennis; Prostak, Kenneth S.; Hagler, Herbert K.; Pak, Charles Y. C.

1996-04-01

Backscattered electron imaging (BEI) and transmission electron microscopy (TEM) were used to examine the effects of treatment with intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate on bone architecture and crystallinity. Examination was performed in nondecalcified biopsies obtained from patients following up to four years of therapy (placebo or SRNaF) and compared to pretreatment biopsies from each patient, as well as to bone from young, normal subjects. BEI images disclosed increased areas of recent bone formation following fluoride administration. There was no evidence of a mineralization defect in any biopsy and both cortical and trabecular architecture remained normal. TEM analysis demonstrated intrafibrillar platelike crystals and extrafibrillar needlelike crystals for both the pre- and post-treatment biopsies as well as for the bone from young normal subjects. There was no evidence of increased crystal size or of an increase in extrafibrillar mineral deposition. These observations suggest that intermittent SRNaF and continuous calcium therapy exerts an anabolic action on the skeleton not accompanied by a mineralization defect or an alteration of bone mineral deposition. The use of BEI and TEM holds promise for the study of the pathophysiology and treatment of metabolic bone diseases.

Cesium-incorporated indium-tin-oxide films for use as a cathode with low work function for a transparent organic light-emitting device

International Nuclear Information System (INIS)

Uchida, Takayuki; Mimura, Toshifumi; Ohtsuka, Masao; Otomo, Toshio; Ide, Mieko; Shida, Azusa; Sawada, Yutaka

2006-01-01

Transparent organic light-emitting devices (TOLEDs) were successfully fabricated utilizing a novel transparent conducting cathode with low work function. Cesium-incorporated indium-tin-oxide film was deposited on the organic layers with negligible damage by simultaneous operation of RF magnetron sputtering using an ITO target and vacuum evaporation of metallic cesium. Incorporation of cesium in the ITO film was confirmed by XPS analysis. The work function (4.3 eV) determined by photoelectron spectroscopy in air (PESA) was lower than that of 0.3-0.4-eV without cesium-incorporation and stable under the atmospheric environment. The electron injection efficiency of cesium-incorporated ITO cathode in the present transparent OLED fabricated was comparable to that of the previous double-layered structure comprising of ITO cathode and an organic buffer layer (BCP) doped by evaporation of cesium [T. Uchida, S. Kaneta, M. Ichihara, M. Ohtsuka, T. Otomo, D.R. Marx, Jpn. J. Appl. Phys., 44, No. 9 (2005) L282

The saturation phenomenon in Kr85 ion implantation in metallic targets

International Nuclear Information System (INIS)

Baptista Junior, V. de P.

1978-01-01

Noble gases, as Krypton containing the radioative isotope Kr 85 , can be stably incorporated into a wide variety of solids and used as tracers or a kind of sensitive probe to measure chemical and physical phenomena. A general review is presented about the methods of incorporation with emphasis on ion bombardment and saturation. The problem of saturation of metal targets was correlated to certain properties in order to get a mathematical approach. Six properties were chosen as more significative to produce a simple model of saturation on experiments of ion implantation with Kr 85 at 45 KeV. The accuracy of the model is limited by the experimental error, the available data and its own simplicity. (Author) [pt

Cluster-Randomized Trial of a Behavioral Intervention to Incorporate a Treat-to-Target Approach to Care of US Patients With Rheumatoid Arthritis.

Science.gov (United States)

Harrold, Leslie R; Reed, George W; John, Ani; Barr, Christine J; Soe, Kevin; Magner, Robert; Saunders, Katherine C; Ruderman, Eric M; Haselkorn, Tmirah; Greenberg, Jeffrey D; Gibofsky, Allan; Harrington, J Timothy; Kremer, Joel M

2018-03-01

To assess the feasibility and efficacy of implementing a treat-to-target approach versus usual care in a US-based cohort of rheumatoid arthritis patients. In this behavioral intervention trial, rheumatology practices were cluster-randomized to provide treat-to-target care or usual care. Eligible patients with moderate/high disease activity (Clinical Disease Activity Index [CDAI] score >10) were followed for 12 months. Both treat-to-target and usual care patients were seen every 3 months. Treat-to-target providers were to have monthly visits with treatment acceleration at a minimum of every 3 months in patients with CDAI score >10; additional visits and treatment acceleration were at the discretion of usual care providers and patients. Coprimary end points were feasibility, assessed by rate of treatment acceleration conditional on CDAI score >10, and achievement of low disease activity (LDA; CDAI score ≤10) by an intent-to-treat analysis. A total of 14 practice sites per study arm were included (246 patients receiving treat-to-target and 286 receiving usual care). The groups had similar baseline demographic and clinical characteristics. Rates of treatment acceleration (treat-to-target 47% versus usual care 50%; odds ratio [OR] 0.92 [95% confidence interval (95% CI) 0.64, 1.34]) and achievement of LDA (treat-to-target 57% versus usual care 55%; OR 1.05 [95% CI 0.60, 1.84]) were similar between groups. Treat-to-target providers reported patient reluctance and medication lag time as common barriers to treatment acceleration. This study is the first to examine the feasibility and efficacy of a treat-to-target approach in typical US rheumatology practice. Treat-to-target care was not associated with increased likelihood of treatment acceleration or achievement of LDA, and barriers to treatment acceleration were identified. © 2017, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Genome‐wide identification of novel small RNAs in Pseudomonas aeruginosa

DEFF Research Database (Denmark)

Gómez Lozano, María; Marvig, Rasmus Lykke; Molin, Søren

2012-01-01

Bacterial small regulatory RNAs (sRNAs) function in post‐transcriptional control of gene expression and control a variety of processes including metabolic reactions, stress responses and pathogenesis in response to environmental signals. A variety of approaches have been used previously to identify...... with this approach. Although the use of three libraries increased the number of novel transcripts identified, there were significant differences in the subset of transcripts detected in each library, underscoring the importance of library preparation strategy and relative sRNA abundance for successful sRNA detection...... and that the approach described here may be applied to identify sRNAs in any bacterium under different growth and stress conditions....

Temporal succession in carbon incorporation from macromolecules by particle-attached bacteria in marine microcosms: Particle-attached bacteria incorporating organic carbon

Energy Technology Data Exchange (ETDEWEB)

Mayali, Xavier [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Stewart, Benjamin [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Mabery, Shalini [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Weber, Peter K. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2015-12-21

Here, we investigated bacterial carbon assimilation from stable isotope-labelled macromolecular substrates (proteins; lipids; and two types of polysaccharides, starch and cellobiose) while attached to killed diatom detrital particles during laboratory microcosms incubated for 17 days. Using Chip-SIP (secondary ion mass spectrometry analysis of RNA microarrays), we identified generalist operational taxonomic units (OTUs) from the Gammaproteobacteria, belonging to the genera Colwellia, Glaciecola, Pseudoalteromonas and Rheinheimera, and from the Bacteroidetes, genera Owenweeksia and Maribacter, that incorporated the four tested substrates throughout the incubation period. Many of these OTUs exhibited the highest isotope incorporation relative to the others, indicating that they were likely the most active. Additional OTUs from the Gammaproteobacteria, Bacteroidetes and Alphaproteobacteria exhibited generally (but not always) lower activity and did not incorporate all tested substrates at all times, showing species succession in organic carbon incorporation. We also found evidence to suggest that both generalist and specialist OTUs changed their relative substrate incorporation over time, presumably in response to changing substrate availability as the particles aged. This pattern was demonstrated by temporal succession from relatively higher starch incorporation early in the incubations, eventually switching to higher cellobiose incorporation after 2 weeks.

Discrimination between landmine and mine-like targets using wavelets and spectral analysis

Directory of Open Access Journals (Sweden)

Mahmoud A. Mohana

2013-06-01

Ground penetrating radar (GPR is a powerful and non-destructive geophysical approach with a wide range of advantages in the field of landmine inspection. In the present paper, we apply different simulation models with Vivaldi antenna and mine-like targets by using the CST Microwave studio program. The field work is carried out by using a GPR device of model SIR 2000 from GSSI (Geophysical Survey Systems Incorporation connected to 900 MHz antenna where the targets were buried in sand soil. Depending on the fact that the receiving powers (reflected, refracted and scattered from the different materials are different, we study the spectral power densities for the received power from the different targets. The techniques used in this study are: direct fast Fourier transform, short time Fourier transform (spectrogram, wavelets transform and denoising techniques. Our results ought to be considered as finger prints for different scanned targets during this work. So we can discriminate between landmines and mine-like targets.

Selection of targets and ion sources for RIB generation at the Holifield Radioactive Ion Beam Facility

International Nuclear Information System (INIS)

Alton, G.D.

1995-01-01

In this report, the authors describe the performance characteristics for a selected number of target ion sources that will be employed for initial use at the Holifield Radioactive Ion Beam Facility (HRIBF) as well as prototype ion sources that show promise for future use for RIB applications. A brief review of present efforts to select target materials and to design composite target matrix/heat-sink systems that simultaneously incorporate the short diffusion lengths, high permeabilities, and controllable temperatures required to effect fast and efficient diffusion release of the short-lived species is also given

A modular platform for targeted RNAi therapeutics.

Science.gov (United States)

Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

2018-03-01

Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs 1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting 4-8 , their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

A modular platform for targeted RNAi therapeutics

Science.gov (United States)

Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

2018-01-01

Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting4-8, their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

Drug-Target Interaction Prediction through Label Propagation with Linear Neighborhood Information.

Science.gov (United States)

Zhang, Wen; Chen, Yanlin; Li, Dingfang

2017-11-25

Interactions between drugs and target proteins provide important information for the drug discovery. Currently, experiments identified only a small number of drug-target interactions. Therefore, the development of computational methods for drug-target interaction prediction is an urgent task of theoretical interest and practical significance. In this paper, we propose a label propagation method with linear neighborhood information (LPLNI) for predicting unobserved drug-target interactions. Firstly, we calculate drug-drug linear neighborhood similarity in the feature spaces, by considering how to reconstruct data points from neighbors. Then, we take similarities as the manifold of drugs, and assume the manifold unchanged in the interaction space. At last, we predict unobserved interactions between known drugs and targets by using drug-drug linear neighborhood similarity and known drug-target interactions. The experiments show that LPLNI can utilize only known drug-target interactions to make high-accuracy predictions on four benchmark datasets. Furthermore, we consider incorporating chemical structures into LPLNI models. Experimental results demonstrate that the model with integrated information (LPLNI-II) can produce improved performances, better than other state-of-the-art methods. The known drug-target interactions are an important information source for computational predictions. The usefulness of the proposed method is demonstrated by cross validation and the case study.

Type I-E CRISPR-Cas Systems Discriminate Target from Non-Target DNA through Base Pairing-Independent PAM Recognition

Science.gov (United States)

Datsenko, Kirill A.; Jackson, Ryan N.; Wiedenheft, Blake; Severinov, Konstantin; Brouns, Stan J. J.

2013-01-01

Discriminating self and non-self is a universal requirement of immune systems. Adaptive immune systems in prokaryotes are centered around repetitive loci called CRISPRs (clustered regularly interspaced short palindromic repeat), into which invader DNA fragments are incorporated. CRISPR transcripts are processed into small RNAs that guide CRISPR-associated (Cas) proteins to invading nucleic acids by complementary base pairing. However, to avoid autoimmunity it is essential that these RNA-guides exclusively target invading DNA and not complementary DNA sequences (i.e., self-sequences) located in the host's own CRISPR locus. Previous work on the Type III-A CRISPR system from Staphylococcus epidermidis has demonstrated that a portion of the CRISPR RNA-guide sequence is involved in self versus non-self discrimination. This self-avoidance mechanism relies on sensing base pairing between the RNA-guide and sequences flanking the target DNA. To determine if the RNA-guide participates in self versus non-self discrimination in the Type I-E system from Escherichia coli we altered base pairing potential between the RNA-guide and the flanks of DNA targets. Here we demonstrate that Type I-E systems discriminate self from non-self through a base pairing-independent mechanism that strictly relies on the recognition of four unchangeable PAM sequences. In addition, this work reveals that the first base pair between the guide RNA and the PAM nucleotide immediately flanking the target sequence can be disrupted without affecting the interference phenotype. Remarkably, this indicates that base pairing at this position is not involved in foreign DNA recognition. Results in this paper reveal that the Type I-E mechanism of avoiding self sequences and preventing autoimmunity is fundamentally different from that employed by Type III-A systems. We propose the exclusive targeting of PAM-flanked sequences to be termed a target versus non-target discrimination mechanism. PMID:24039596

3D target array for pulsed multi-sourced radiography

Science.gov (United States)

Le Galloudec, Nathalie Joelle

2016-02-23

The various technologies presented herein relate to the generation of x-rays and other charged particles. A plurality of disparate source materials can be combined on an array to facilitate fabrication of co-located mixed tips (point sources) which can be utilized to form a polychromatic cloud, e.g., a plurality of x-rays having a range of energies and or wavelengths, etc. The tips can be formed such that the x-rays are emitted in a direction different to other charged particles to facilitate clean x-ray sourcing. Particles, such as protons, can be directionally emitted to facilitate generation of neutrons at a secondary target. The various particles can be generated by interaction of a laser irradiating the array of tips. The tips can be incorporated into a plurality of 3D conical targets, the conical target sidewall(s) can be utilized to microfocus a portion of a laser beam onto the tip material.

Mung bean nuclease treatment increases capture specificity of microdroplet-PCR based targeted DNA enrichment.

Directory of Open Access Journals (Sweden)

Zhenming Yu

Full Text Available Targeted DNA enrichment coupled with next generation sequencing has been increasingly used for interrogation of select sub-genomic regions at high depth of coverage in a cost effective manner. Specificity measured by on-target efficiency is a key performance metric for target enrichment. Non-specific capture leads to off-target reads, resulting in waste of sequencing throughput on irrelevant regions. Microdroplet-PCR allows simultaneous amplification of up to thousands of regions in the genome and is among the most commonly used strategies for target enrichment. Here we show that carryover of single-stranded template genomic DNA from microdroplet-PCR constitutes a major contributing factor for off-target reads in the resultant libraries. Moreover, treatment of microdroplet-PCR enrichment products with a nuclease specific to single-stranded DNA alleviates off-target load and improves enrichment specificity. We propose that nuclease treatment of enrichment products should be incorporated in the workflow of targeted sequencing using microdroplet-PCR for target capture. These findings may have a broad impact on other PCR based applications for which removal of template DNA is beneficial.

Design and syntheses of mono and multivalent mannosyl-lipoconjugates for targeted liposomal drug delivery.

Science.gov (United States)

Štimac, Adela; Cvitaš, Jelena TrmĿiĿ; Frkanec, Leo; Vugrek, Oliver; Frkanec, Ruža

2016-09-10

Multivalent mannosyl-lipoconjugates may be of interest for glycosylation of liposomes and targeted drug delivery because the mannose specifically binds to C-type lectin receptors on the particular cells. In this paper syntheses of two types of novel O-mannosides are presented. Conjugates 1 and 2 with a COOH- and NH2-functionalized spacer and the connection to a lysine and FmocNH-PEG-COOH, are described. The coupling reactions of prepared intermediates 6 and 4 with a PEGylated-DSPE or palmitic acid, respectively, are presented. Compounds 5, mono-, 8, di- and 12, tetravalent mannosyl-lipoconjugates, were synthesized. The synthesized compounds were incorporated into liposomes and liposomal preparations featuring exposed mannose units were characterized. Carbohydrate liposomal quartz crystal microbalance based assay has been established for studying carbohydrate-lectin binding. It was demonstrated that liposomes with incorporated mannosyl-lipoconjugates were effectively recognized by Con A and have great potential to be used for targeted liposomal drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

VIBA-LAB2: a virtual ion beam analysis laboratory software package incorporating elemental map simulations

International Nuclear Information System (INIS)

Zhou, S.J.; Orlic, I.; Sanchez, J.L.; Watt, F.

1999-01-01

The software package VIBA-lab1, which incorporates PIXE and RBS energy spectra simulation has now been extended to include the simulation of elemental maps from 3D structures. VIBA-lab1 allows the user to define a wide variety of experimental parameters, e.g. energy and species of incident ions, excitation and detection geometry, etc. When the relevant experimental parameters as well as target composition are defined, the program can then simulate the corresponding PIXE and RBS spectra. VIBA-LAB2 has been written with applications in nuclear microscopy in mind. A set of drag-and-drop tools has been incorporated to allow the user to define a three-dimensional sample object of mixed elemental composition. PIXE energy spectra simulations are then carried out on pixel-by-pixel basis and the corresponding intensity distributions or elemental maps can be computed. Several simulated intensity distributions for some 3D objects are demonstrated, and simulations obtained from a simple IC are compared with experimental results

43 CFR 46.110 - Incorporating consensus-based management.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Incorporating consensus-based management... § 46.110 Incorporating consensus-based management. (a) Consensus-based management incorporates direct... carry out those plans and activities. For the purposes of this Part, consensus-based management involves...

Sindbis Virus-Pseudotyped Lentiviral Vectors Carrying VEGFR2-Specific Nanobody for Potential Transductional Targeting of Tumor Vasculature.

Science.gov (United States)

Ahani, Roshank; Roohvand, Farzin; Cohan, Reza Ahangari; Etemadzadeh, Mohammad Hossein; Mohajel, Nasir; Behdani, Mahdi; Shahosseini, Zahra; Madani, Navid; Azadmanesh, Kayhan

2016-11-01

Introduction of selectivity/specificity into viral-based gene delivery systems, such as lentiviral vectors (LVs), is crucial in their systemic administration for cancer gene therapy. The pivotal role of tumor-associated endothelial cells (TAECs) in tumor angiogenesis and overexpression of vascular endothelial growth factor receptor-2 (VEGFR2 or KDR) in TAECs makes them a potent target in cancer treatment. Herein, we report the development of VEGFR2-targeted LVs pseudotyped with chimeric sindbis virus E2 glycoprotein (cSVE2s). For this purpose, either sequence of a VEGFR2-specific nanobody or its natural ligand (VEGF 121 ) was inserted into the binding site of sindbis virus E2 glycoprotein. In silico modeling data suggested that the inserted targeting motifs were exposed in the context of cSVE2s. Western blot analysis of LVs indicated the incorporation of cSVE2s into viral particles. Capture ELISA demonstrated the specificity/functionality of the incorporated cSVE2s. Transduction of 293/KDR (expressing VEGFR2) or 293T cells (negative control) by constructed LVs followed by fluorescent microscopy and flow cytometric analyses indicated selective transduction of 293/KDR cells (30 %) by both targeting motifs compared to 293T control cells (1-2 %). These results implied similar targeting properties of VEGFR2-specific nanobody compared to the VEGF 121 and indicated the potential for transductional targeting of tumor vasculature by the nanobody displaying LVs.

Incorporating Ecosystem Services into Community-level ...

Science.gov (United States)

EPA’s Office of Research and Development’s Sustainable and Healthy Communities Research Program is developing tools and approaches to incorporate ecosystem goods and services concepts into community-level decision-making. The San Juan Community Study is one of a series of coordinated community studies, which also include Mobile Bay, AL, Great Lakes Areas of Concern, and the Pacific Northwest. Common elements across the community studies include a focus on watershed management and national estuary programs (National Estuary Program, National Estuarine Research Reserve System). San Juan, Puerto Rico, is unique from the other community studies in that it is located in a highly urbanized watershed integrated with a number of freshwater and coastal ecosystems. The San Juan Community Study will explore linkages between watershed management decisions (e.g., dredging canals, restoration of mangrove buffers, sewage discharge interventions, climate adaptive strategies) targeting priority stressors (e.g., nutrients, contaminants, and pathogens; aquatic debris; habitat loss; modified hydrology and water circulation; sea level rise; storm intensity and frequency) effecting the condition of ecosystems (e.g., estuarine habitats and fish, as well as the connected terrestrial and coastal ecosystems), associated ecosystem goods and services (e.g., tourism and recreation, fishing, nutrient & sediment retention, contaminant processing, carbon sequestration, flood protection),

Physico-chemical and mechanical characterization of in-situ forming xyloglucan gels incorporating a growth factor to promote cartilage reconstruction

International Nuclear Information System (INIS)

Dispenza, Clelia; Todaro, Simona; Bulone, Donatella; Sabatino, Maria Antonietta; Ghersi, Giulio; San Biagio, Pier Luigi; Lo Presti, Caterina

2017-01-01

The development of growth factors is very promising in the field of tissue regeneration but specifically designed formulations have to be developed in order to enable such new biological entities (NBEs). In particular, the range of therapeutic concentrations is usually very low compared to other active proteins and the confinement in the target site can be of crucial importance. In-situ forming scaffolds are very promising solutions for minimally invasive intervention in cartilage reconstruction and targeting of NBEs. In this work injectable, in-situ forming gels of a temperature responsive partially degalactosylated xyloglucan (Deg-XG) incorporating the growth factor FGF-18 are formulated and characterized. In particular, injectability and shear viscosity at room temperature, time-to-gel at body temperature, morphology and mechanical properties of gels are investigated. The highly hydrophobic growth factor is favorably incorporated and retained by the gel. Gels undergo a slow erosion process when immersed in PBS at 37 °C that opens up their porous structure. The prolonged hydrothermal treatment leads to structural rearrangements towards tougher networks with increased dynamic shear modulus. Preliminary biological evaluations confirm absence of cytotoxicity and the ability of these scaffolds to host cells and promote their proliferation. - Highlights: • In-situ forming gels incorporating a growth factor are formulated and characterized. • The gel retains the growth factor and is colonized by chondrocytes. • Mechanical properties and porosity of gels are controlled by polymer concentration. • Incubation at 37 °C increases the gel strength and opens up the porous structure.

Incorporating the Impacts of Small Scale Rock Heterogeneity into Models of Flow and Trapping in Target UK CO2 Storage Systems

Science.gov (United States)

Jackson, S. J.; Reynolds, C.; Krevor, S. C.

2017-12-01

Predictions of the flow behaviour and storage capacity of CO2 in subsurface reservoirs are dependent on accurate modelling of multiphase flow and trapping. A number of studies have shown that small scale rock heterogeneities have a significant impact on CO2flow propagating to larger scales. The need to simulate flow in heterogeneous reservoir systems has led to the development of numerical upscaling techniques which are widely used in industry. Less well understood, however, is the best approach for incorporating laboratory characterisations of small scale heterogeneities into models. At small scales, heterogeneity in the capillary pressure characteristic function becomes significant. We present a digital rock workflow that combines core flood experiments with numerical simulations to characterise sub-core scale capillary pressure heterogeneities within rock cores from several target UK storage reservoirs - the Bunter, Captain and Ormskirk sandstone formations. Measured intrinsic properties (permeability, capillary pressure, relative permeability) and 3D saturations maps from steady-state core flood experiments were the primary inputs to construct a 3D digital rock model in CMG IMEX. We used vertical end-point scaling to iteratively update the voxel by voxel capillary pressure curves from the average MICP curve; with each iteration more closely predicting the experimental saturations and pressure drops. Once characterised, the digital rock cores were used to predict equivalent flow functions, such as relative permeability and residual trapping, across the range of flow conditions estimated to prevail in the CO2 storage reservoirs. In the case of the Captain sandstone, rock cores were characterised across an entire 100m vertical transect of the reservoir. This allowed analysis of the upscaled impact of small scale heterogeneity on flow and trapping. Figure 1 shows the varying degree to which heterogeneity impacted flow depending on the capillary number in the

On the efficient bio-incorporation of 5-hydroxy-tryptophan in recombinant proteins expressed in Escherichia coli with T7 RNA polymerase-based vectors.

Science.gov (United States)

Oliveira-Souza, Wellington P; Bronze, Fellipe; Broos, Jaap; Marcondes, Marcelo F M; Oliveira, Vitor

2017-10-21

Biosynthetic incorporation of non-canonic amino acids is an attractive strategy to introduce new properties in recombinant proteins. Trp analogs can be incorporated in recombinant proteins replacing regular Trp during protein translation into a Trp-auxotrophic cell host. This straightforward method however, is limited to few analogs recognized and accepted by the cellular protein production machinery. 5-hydroxy-tryptophan (5OH-Trp) can be bio-incorporated using E. coli as expression host however; we have experienced very low incorporation yields - amount of protein containing regular Trp/amount of protein containing the Trp analog - during expressions of 5OH-Trp labeled proteins. Furthermore, this low incorporation yield were verified especially when the widely-used vectors based on the T7 RNA polymerase were used. Testing different 5OH-Trp incorporation protocols we verified that in these T7-based systems, the production of the T7 RNA polymerase is driven by the same elements - lac promoter/IPTG - as the target protein. Consequently, the bio-incorporation of the 5OH-Trp residues also occurs in this crucial enzyme, but, the produced T7 RNA polymerase labeled with 5OH-Trp is inactive or much less active. In the present work, we describe an efficient method to overcome this mentioned problem and bio-incorporate 5OH-Trp in proteins expressed in E. coli., using vectors based on the T7 RNA polymerase-T7 promoter. The two-step induction protocol here described showed incorporation efficiencies of 5OH-Trp higher than 90%. Copyright © 2017 Elsevier Inc. All rights reserved.

Further studies of Fermi-motion effects in lepton scattering from nuclear targets

International Nuclear Information System (INIS)

Bodek, A.; Ritchie, J.L.

1981-01-01

We have calculated the ratio of deep-inelastic structure functions of nuclear targets to the sum of free-neutron and -proton structure functions. The calculations incorporate structure-function fits which are based on quantum-chromodynamic considerations. This paper is an addendum to an earlier publication in which we calculated the Fermi-motion corrections using other fits to the nucleon structure functions

Novel modeling of combinatorial miRNA targeting identifies SNP with potential role in bone density.

Directory of Open Access Journals (Sweden)

Claudia Coronnello

Full Text Available MicroRNAs (miRNAs are post-transcriptional regulators that bind to their target mRNAs through base complementarity. Predicting miRNA targets is a challenging task and various studies showed that existing algorithms suffer from high number of false predictions and low to moderate overlap in their predictions. Until recently, very few algorithms considered the dynamic nature of the interactions, including the effect of less specific interactions, the miRNA expression level, and the effect of combinatorial miRNA binding. Addressing these issues can result in a more accurate miRNA:mRNA modeling with many applications, including efficient miRNA-related SNP evaluation. We present a novel thermodynamic model based on the Fermi-Dirac equation that incorporates miRNA expression in the prediction of target occupancy and we show that it improves the performance of two popular single miRNA target finders. Modeling combinatorial miRNA targeting is a natural extension of this model. Two other algorithms show improved prediction efficiency when combinatorial binding models were considered. ComiR (Combinatorial miRNA targeting, a novel algorithm we developed, incorporates the improved predictions of the four target finders into a single probabilistic score using ensemble learning. Combining target scores of multiple miRNAs using ComiR improves predictions over the naïve method for target combination. ComiR scoring scheme can be used for identification of SNPs affecting miRNA binding. As proof of principle, ComiR identified rs17737058 as disruptive to the miR-488-5p:NCOA1 interaction, which we confirmed in vitro. We also found rs17737058 to be significantly associated with decreased bone mineral density (BMD in two independent cohorts indicating that the miR-488-5p/NCOA1 regulatory axis is likely critical in maintaining BMD in women. With increasing availability of comprehensive high-throughput datasets from patients ComiR is expected to become an essential

Intercomparison on the usage of computational codes in radiation dosimetry

International Nuclear Information System (INIS)

Ilic, R.; Pesic, M.; Pavlovic, R.

2003-01-01

SRNA-2KG software package was modified for this work to include necessary input and output data and for predicted voxelized geometry and dosimetry. SRNA is a Monte Carlo code developed for applications in proton transport, radiotherapy and dosimetry. Protons within energy range from 100 keV to 250 MeV with predefined spectra are transported in 3D geometry through material zones confined by planes and second order surfaces or in 3D voxelized geometry. The code can treat proton transport in a few hundred different materials including elements from Z=1 to Z=98. Simulation of proton transport is based on the multiple scattering theory of charged particles and on the model for compound nucleus decay

Target discovery focused approaches to overcome bottlenecks in the exploitation of antimycobacterial natural products.

Science.gov (United States)

Baptista, Rafael; Bhowmick, Sumana; Nash, Robert J; Baillie, Les; Mur, Luis Aj

2018-04-01

Tuberculosis is a major global health hazard. The search for new antimycobacterials has focused on such as screening combinational chemistry libraries or designing chemicals to target predefined pockets of essential bacterial proteins. The relative ineffectiveness of these has led to a reappraisal of natural products for new antimycobacterial drug leads. However, progress has been limited, we suggest through a failure in many cases to define the drug target and optimize the hits using this information. We highlight methods of target discovery needed to develop a drug into a candidate for clinical trials. We incorporate these into suggested analysis pipelines which could inform the research strategies to accelerate the development of new drug leads from natural products.

The use of an intermediate wavelength laser for alignment to inertial confinement fusion targets

International Nuclear Information System (INIS)

English, R.E. Jr.; Seppala, L.G.; Vann, C.S.; Bliss, E.S.

1995-01-01

The conceptual design of the National Ignition Facility (NIF) 192 beam laser incorporates a low-power alignment beam injected in the pinhole plane of the final spatial filter with a wave length intermediate between the 1053 mn laser output and the 351 mn frequency-converted beam that illuminates the target Choosing the specific wavelength for which the spatial filter plane is reimaged in the same target chamber plane as the frequency-converted main laser pulse, achieves optimum accuracy without the need for additional means to insure precise overlap between the two beams. Insertion of the alignment beam after the last laser amplifier also allows alignment to the target while the amplifiers are still cooling from a previous shot

Extrapolation of vertical target motion through a brief visual occlusion.

Science.gov (United States)

Zago, Myrka; Iosa, Marco; Maffei, Vincenzo; Lacquaniti, Francesco

2010-03-01

It is known that arbitrary target accelerations along the horizontal generally are extrapolated much less accurately than target speed through a visual occlusion. The extent to which vertical accelerations can be extrapolated through an occlusion is much less understood. Here, we presented a virtual target rapidly descending on a blank screen with different motion laws. The target accelerated under gravity (1g), decelerated under reversed gravity (-1g), or moved at constant speed (0g). Probability of each type of acceleration differed across experiments: one acceleration at a time, or two to three different accelerations randomly intermingled could be presented. After a given viewing period, the target disappeared for a brief, variable period until arrival (occluded trials) or it remained visible throughout (visible trials). Subjects were asked to press a button when the target arrived at destination. We found that, in visible trials, the average performance with 1g targets could be better or worse than that with 0g targets depending on the acceleration probability, and both were always superior to the performance with -1g targets. By contrast, the average performance with 1g targets was always superior to that with 0g and -1g targets in occluded trials. Moreover, the response times of 1g trials tended to approach the ideal value with practice in occluded protocols. To gain insight into the mechanisms of extrapolation, we modeled the response timing based on different types of threshold models. We found that occlusion was accompanied by an adaptation of model parameters (threshold time and central processing time) in a direction that suggests a strategy oriented to the interception of 1g targets at the expense of the interception of the other types of tested targets. We argue that the prediction of occluded vertical motion may incorporate an expectation of gravity effects.

New evaporator station for the center for accelerator target science

Science.gov (United States)

Greene, John P.; Labib, Mina

2018-05-01

As part of an equipment grant provided by DOE-NP for the Center for Accelerator Target Science (CATS) initiative, the procurement of a new, electron beam, high-vacuum deposition system was identified as a priority to insure reliable and continued availability of high-purity targets. The apparatus is designed to contain TWO electron beam guns; a standard 4-pocket 270° geometry source as well as an electron bombardment source. The acquisition of this new system allows for the replacement of TWO outdated and aging vacuum evaporators. Also included is an additional thermal boat source, enhancing our capability within this deposition unit. Recommended specifications for this system included an automated, high-vacuum pumping station, a deposition chamber with a rotating and heated substrate holder for uniform coating capabilities and incorporating computer-controlled state-of-the-art thin film technologies. Design specifications, enhanced capabilities and the necessary mechanical modifications for our target work are discussed.

Aspects of the incorporation of spatial data into radioecological and restoration analysis

International Nuclear Information System (INIS)

Beresford, N.A.; Wright, S.M.; Howard, B.J.; Crout, N.M.J.; Arkhipov, A.; Voigt, G.

2002-01-01

In the last decade geographical information systems have been increasingly used to incorporate spatial data into radioecological analysis. This has allowed the development of models with spatially variable outputs. Two main approaches have been adopted in the development of spatial models. Empirical Tag based models applied across a range of spatial scales utilize underlying soil type maps and readily available radioecological data. Soil processes can also be modelled to allow the dynamic prediction of radionuclide soil to plant transfer. We discuss a dynamic semi-mechanistic radiocaesium soil to plant-transfer model, which utilizes readily available spatially variable soil parameters. Both approaches allow the identification of areas that may be vulnerable to radionuclide deposition, therefore enabling the targeting of intervention measures. Improved estimates of radionuclide fluxes and ingestion doses can be achieved by incorporating spatially varying inputs such as agricultural production and dietary habits in to these models. In this paper, aspects of such models, including data requirements, implementation and outputs are discussed and critically evaluated. The relative merits and disadvantages of the two spatial model approaches adopted within radioecology are discussed. We consider the usefulness of such models to aid decision-makers and access the requirements and potential of further application within radiological protection. (author)

Photosynthetic incorporation of 14C by Stevia rebaudiana

International Nuclear Information System (INIS)

Ferraresi, M. de L.; Ferraresi Filho, O.; Bracht, A.

1985-01-01

The photosynthetic incorporation of 14 by Stevia rebaudiana specimens was investigated. The 14 C incorporation, when the isotope was furnished to the plant in form of 14 CO 2 , was rapid. After 24 hours, the radioactivity has been incorporated into a great number of compounds including pigments, terpenes, glucose, cellulose and also stevioside and its derivatives. (M.A.C.) [pt

A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.

Science.gov (United States)

Guo, Wei-Feng; Zhang, Shao-Wu; Shi, Qian-Qian; Zhang, Cheng-Ming; Zeng, Tao; Chen, Luonan

2018-01-19

practical strategic utility of TCOA to incorporate prior drug information into potential drug-target forecasts. Thus applicably, our method paves a novel and efficient way to identify the drug targets for leading the phenotype transitions of underlying biological networks.

48 CFR 2852.102-270 - Incorporation in full text.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Incorporation in full text... 2852.102-270 Incorporation in full text. JAR provisions or clauses shall be incorporated in solicitations and contracts in full text. ...

Implementation of 5E Inquiry Incorporated with Analogy Learning Approach to Enhance Conceptual Understanding of Chemical Reaction Rate for Grade 11 Students

Science.gov (United States)

Supasorn, Saksri; Promarak, Vinich

2015-01-01

The main purpose of this study was to enhance student understanding of the scientific concepts of chemical reaction rate. Forty-four grade 11 students were the target group. The treatment tools were seven learning plans of 5E inquiry incorporated with an analogy learning approach during 15 hours of class time. In each learning plan, the students…

Nanocomposite scaffold fabrication by incorporating gold nanoparticles into biodegradable polymer matrix: Synthesis, characterization, and photothermal effect

Energy Technology Data Exchange (ETDEWEB)

Abdelrasoul, Gaser N.; Farkas, Balazs; Romano, Ilaria; Diaspro, Alberto; Beke, Szabolcs, E-mail: szabolcs.beke@iit.it

2015-11-01

Nanoparticle incorporation into scaffold materials is a valuable route to deliver various therapeutic agents, such as drug molecules or large biomolecules, proteins (e.g. DNA or RNA) into their targets. In particular, gold nanoparticles (Au NPs) with their low inherent toxicity, tunable stability and high surface area provide unique attributes facilitating new delivery strategies. A biodegradable, photocurable polymer resin, polypropylene fumarate (PPF) along with Au NPs were utilized to synthesize a hybrid nanocomposite resin, directly exploitable in stereolithography (SL) processes. To increase the particles' colloidal stability, the Au NP nanofillers were coated with polyvinyl pyrrolidone (PVP). The resulting resin was used to fabricate a new type of composite scaffold via mask projection excimer laser stereolithography. The thermal properties of the nanocomposite scaffolds were found to be sensitive to the concentration of NPs. The mechanical properties were augmented by the NPs up to 0.16 μM, though further increase in the concentration led to a gradual decrease. Au NP incorporation rendered the biopolymer scaffolds photosensitive, i.e. the presence of Au NPs enhanced the optical absorption of the scaffolds as well, leading to possible localized temperature rise when irradiated with 532 nm laser, known as the photothermal effect. - Highlights: • Gold nanoparticle incorporation into biopolymer resin was realized. • Gold incorporation into biopolymer resin is a big step in tissue engineering. • Composite scaffolds were synthesized and thoroughly characterized. • Gold nanoparticles are remarkable candidates to be utilized as “transport vehicles”. • The photothermal effect was demonstrated using a 532-nm laser.

40 CFR 76.4 - Incorporation by reference.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Incorporation by reference. 76.4 Section 76.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.4 Incorporation by reference. (a) The...

Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma

International Nuclear Information System (INIS)

McNeeley, Kathleen M; Annapragada, Ananth; Bellamkonda, Ravi V

2007-01-01

Liposomal and other nanocarrier based drug delivery vehicles can localize to tumours through passive and/or active targeting. Passively targeted liposomal nanocarriers accumulate in tumours via 'leaky' vasculature through the enhanced permeability and retention (EPR) effect. Passive accumulation depends upon the circulation time and the degree of tumour vessel 'leakiness'. After extravasation, actively targeted liposomal nanocarriers efficiently deliver their payload by receptor-mediated uptake. However, incorporation of targeting moieties can compromise circulation time in the blood due to recognition and clearance by the reticuloendothelial system, decreasing passive accumulation. Here, we compare the efficacy of passively targeted doxorubicin-loaded PEGylated liposomal nanocarriers to that of actively targeted liposomal nanocarriers in a rat 9L brain tumour model. Although folate receptor (FR)-targeted liposomal nanocarriers had significantly reduced blood circulation time compared to PEGylated liposomal nanocarriers; intratumoural drug concentrations both at 20 and 50 h after administration were equal for both treatments. Both treatments significantly increased tumour inoculated animal survival by 60-80% compared to non-treated controls, but no difference in survival was observed between FR-targeted and passively targeted nanocarriers. Therefore, alternate approaches allowing for active targeting without compromising circulation time may be important for fully realizing the benefits of receptor-mediated active targeting of gliomas

Minefield overwatch using moving target indicator radar

Science.gov (United States)

Donadio, Anthony; Ewing, Robert; Kenneally, William J.; Santapietro, John J.

1999-07-01

Traditional antipersonnel land mines are an effective military tool, but they are unable to distinguish friend from foe, or civilian from military personnel. The concept described here uses an advanced moving target indicator (MTI) radar to scan the minefield in order to detect movement towards or within the minefield, coupled with visual identification by a human operator and a communication link for command and control. Selected mines in the minefield can then be activated by means of the command link. In order to demonstrate this concept, a 3D, interactive simulation has been developed. This simulation builds on previous work by integrating a detailed analytical model of an MTI radar. This model has been tailored to the specific application of detection of slowly moving dismounted entities immersed in ground clutter. The model incorporates the effects of internal scatterer motion and antenna scanning modulation in order to provide a realistic representation of the detection problem in this environment. The angle information on the MTI target detection is then passed to a virtual 3D sight which cues a human operator to the target location. In addition, radar propagation effects and an experimental design in which the radar itself is used as a command link are explored.

48 CFR 1952.102-2 - Incorporation in full text.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Incorporation in full text... Clauses 1952.102-2 Incorporation in full text. All IAAR provisions and clauses shall be incorporated in solicitations and/or contracts in full text. ...

22 CFR 212.13 - Incorporation by reference.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Incorporation by reference. 212.13 Section 212.13 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT PUBLIC INFORMATION Publication in the Federal Register § 212.13 Incorporation by reference. For purposes of this subpart B, USAID matters which...

NIF Ignition Target 3D Point Design

Energy Technology Data Exchange (ETDEWEB)

Jones, O; Marinak, M; Milovich, J; Callahan, D

2008-11-05

We have developed an input file for running 3D NIF hohlraums that is optimized such that it can be run in 1-2 days on parallel computers. We have incorporated increasing levels of automation into the 3D input file: (1) Configuration controlled input files; (2) Common file for 2D and 3D, different types of capsules (symcap, etc.); and (3) Can obtain target dimensions, laser pulse, and diagnostics settings automatically from NIF Campaign Management Tool. Using 3D Hydra calculations to investigate different problems: (1) Intrinsic 3D asymmetry; (2) Tolerance to nonideal 3D effects (e.g. laser power balance, pointing errors); and (3) Synthetic diagnostics.

Effect of organoclay incorporation on dental resin morphology

International Nuclear Information System (INIS)

Oliveira, Nadja M.S.; Reis, Romulo P.B.; Leite, Itamara F.; Morais, Crislene R.S.; Silva, Suedina M.L.

2009-01-01

The objective of the present work was to incorporate nanosilicates in commercial dental resins in order to prepare dental nanocomposites competitive as commercial nanoparticulates dental resins. Thus, a silicate, Cloisite 20A (C20A), was incorporated in a microhybrid dental resin (Z100) and morphological properties of the nanocomposites evaluated as a function of the incorporation method and the amount of filler employed. The samples were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The XRD results evidence that nanocomposites have been obtained and according to SEM results, the morphology of microhybrid resin was modified when C20A nanoparticulate was incorporated improve the size distribution and reduce the agglomeration of the particles. (author)

Efficacy and Ecotoxicity of Novel Anti-Fouling Nanomaterials in Target and Non-Target Marine Species.

Science.gov (United States)

Avelelas, Francisco; Martins, Roberto; Oliveira, Tânia; Maia, Frederico; Malheiro, Eliana; Soares, Amadeu M V M; Loureiro, Susana; Tedim, João

2017-04-01

Biofouling is a global problem that affects virtually all the immersed structures. Currently, several novel environmentally friendly approaches are being tested worldwide to decrease the toxicity of biocides in non-fouling species, such as the encapsulation/immobilization of commercially available biocides, in order to achieve control over the leaching rate. The present study addresses the toxicity of two widely used booster biocides, zinc pyrithione (ZnPT) and copper pyrithione (CuPT), in its free and incorporated forms in order to assess their toxicity and anti-fouling efficacy in target and non-target species. To achieve this goal, the following marine organisms were tested; the green microalgae Tetraselmis chuii (non-target species) and both target species, the diatom Phaeodactylum tricornutum and the mussel Mytilus edulis. Organisms were exposed to both biocides, two unloaded nanostructured materials and nanomaterials loaded with biocides, from 10 μg/L to 100 mg/L total weight, following standard protocols. The most eco-friendly and simultaneously efficient anti-fouling solution against the two photosynthetic species (nanoclays loaded with ZnPT) was then tested on mussels to assess its lethal efficacy (LC 50  = 123 μg/L) and compared with free biocide (LC 50  = 211 μg/L) and unloaded material (LC 50  > 1000 μg/L). A second exposure test with sub-lethal concentrations (lower than 100 μg/L), using mussels, was carried out to assess biochemical changes caused by the tested compounds. Oxidative stress, detoxification and neurotransmission markers were not responsive; however, different antioxidant patterns were found with free ZnPT and loaded nanoclay exposures. Thus, the immobilization of the biocide ZnPT into nanoclays proved to be a promising efficient and eco-friendly anti-fouling strategy.

Dead-blow hammer design applied to a calibration target mechanism to dampen excessive rebound

Science.gov (United States)

Lim, Brian Y.

1991-01-01

An existing rotary electromagnetic driver was specified to be used to deploy and restow a blackbody calibration target inside of a spacecraft infrared science instrument. However, this target was much more massive than any other previously inherited design applications. The target experienced unacceptable bounce when reaching its stops. Without any design modification, the momentum generated by the driver caused the target to bounce back to its starting position. Initially, elastomeric dampers were used between the driver and the target. However, this design could not prevent the bounce, and it compromised the positional accuracy of the calibration target. A design that successfully met all the requirements incorporated a sealed pocket 85 percent full of 0.75 mm diameter stainless steel balls in the back of the target to provide the effect of a dead-blow hammer. The energy dissipation resulting from the collision of balls in the pocket successfully dampened the excess momentum generated during the target deployment. The disastrous effects of new requirements on a design with a successful flight history, the modifications that were necessary to make the device work, and the tests performed to verify its functionality are described.

40 CFR 59.412 - Incorporations by reference.

Science.gov (United States)

2010-07-01

... Test Method for Chemical Resistance of Coatings Used in Light-Water Nuclear Power Plants, incorporation by reference approved for § 59.401, Nuclear coating. (5) ASTM Method D 4082-89, Standard Test Method for Effects of Gamma Radiation on Coatings for Use in Light-Water Nuclear Power Plants, incorporation...

Differentiating leucine incorporation of

NARCIS (Netherlands)

Yokokawa, T.; Sintes, E.; de Corte, D.; Olbrich, K.; Herndl, G.J.

2012-01-01

The abundance (based on catalyzed reporter deposition-fluorescence in situ hybrid ization, CARD-FISH) and leucine incorporation rates of Archaea and Bacteria were determined throughout the water column in the eastern Atlantic. Bacteria dominated throughout the water column, although their

Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress.

Science.gov (United States)

Lammers, Twan; Kiessling, Fabian; Hennink, Wim E; Storm, Gert

2012-07-20

Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells, active drug targeting to endothelial cells and triggered drug delivery. Significant progress has been made in this area of research both at the preclinical and at the clinical level, and a number of (primarily passively tumor-targeted) nanomedicine formulations have been approved for clinical use. Significant progress has also been made with regard to better understanding the (patho-) physiological principles of drug targeting to tumors. This has led to the identification of several important pitfalls in tumor-targeted drug delivery, including I) overinterpretation of the EPR effect; II) poor tumor and tissue penetration of nanomedicines; III) misunderstanding of the potential usefulness of active drug targeting; IV) irrational formulation design, based on materials which are too complex and not broadly applicable; V) insufficient incorporation of nanomedicine formulations in clinically relevant combination regimens; VI) negligence of the notion that the highest medical need relates to metastasis, and not to solid tumor treatment; VII) insufficient integration of non-invasive imaging techniques and theranostics, which could be used to personalize nanomedicine-based therapeutic interventions; and VIII) lack of (efficacy analyses in) proper animal models, which are physiologically more relevant and more predictive for the clinical situation. These insights strongly suggest that besides making ever more nanomedicine formulations, future efforts should also address some of the conceptual drawbacks of drug targeting to tumors, and that strategies should be developed to overcome these shortcomings. Copyright © 2011 Elsevier B.V. All rights reserved.

Diversity, expression and mRNA targeting abilities of Argonaute-targeting miRNAs among selected vascular plants.

Science.gov (United States)

Jagtap, Soham; Shivaprasad, Padubidri V

2014-12-02

Micro (mi)RNAs are important regulators of plant development. Across plant lineages, Dicer-like 1 (DCL1) proteins process long ds-like structures to produce micro (mi) RNA duplexes in a stepwise manner. These miRNAs are incorporated into Argonaute (AGO) proteins and influence expression of RNAs that have sequence complementarity with miRNAs. Expression levels of AGOs are greatly regulated by plants in order to minimize unwarranted perturbations using miRNAs to target mRNAs coding for AGOs. AGOs may also have high promoter specificity-sometimes expression of AGO can be limited to just a few cells in a plant. Viral pathogens utilize various means to counter antiviral roles of AGOs including hijacking the host encoded miRNAs to target AGOs. Two host encoded miRNAs namely miR168 and miR403 that target AGOs have been described in the model plant Arabidopsis and such a mechanism is thought to be well conserved across plants because AGO sequences are well conserved. We show that the interaction between AGO mRNAs and miRNAs is species-specific due to the diversity in sequences of two miRNAs that target AGOs, sequence diversity among corresponding target regions in AGO mRNAs and variable expression levels of these miRNAs among vascular plants. We used miRNA sequences from 68 plant species representing 31 plant families for this analysis. Sequences of miR168 and miR403 are not conserved among plant lineages, but surprisingly they differ drastically in their sequence diversity and expression levels even among closely related plants. Variation in miR168 expression among plants correlates well with secondary structures/length of loop sequences of their precursors. Our data indicates a complex AGO targeting interaction among plant lineages due to miRNA sequence diversity and sequences of miRNA targeting regions among AGO mRNAs, thus leading to the assumption that the perturbations by viruses that use host miRNAs to target antiviral AGOs can only be species-specific. We also show

The Spot 42 RNA: A regulatory small RNA with roles in the central metabolism

Science.gov (United States)

Bækkedal, Cecilie; Haugen, Peik

2015-01-01

The Spot 42 RNA is a 109 nucleotide long (in Escherichia coli) noncoding small regulatory RNA (sRNA) encoded by the spf (spot fourty-two) gene. spf is found in gamma-proteobacteria and the majority of experimental work on Spot 42 RNA has been performed using E. coli, and recently Aliivibrio salmonicida. In the cell Spot 42 RNA plays essential roles as a regulator in carbohydrate metabolism and uptake, and its expression is activated by glucose, and inhibited by the cAMP-CRP complex. Here we summarize the current knowledge on Spot 42, and present the natural distribution of spf, show family-specific secondary structural features of Spot 42, and link highly conserved structural regions to mRNA target binding. PMID:26327359

The Spot 42 RNA: A regulatory small RNA with roles in the central metabolism.

Science.gov (United States)

Bækkedal, Cecilie; Haugen, Peik

2015-01-01

The Spot 42 RNA is a 109 nucleotide long (in Escherichia coli) noncoding small regulatory RNA (sRNA) encoded by the spf (spot fourty-two) gene. spf is found in gamma-proteobacteria and the majority of experimental work on Spot 42 RNA has been performed using E. coli, and recently Aliivibrio salmonicida. In the cell Spot 42 RNA plays essential roles as a regulator in carbohydrate metabolism and uptake, and its expression is activated by glucose, and inhibited by the cAMP-CRP complex. Here we summarize the current knowledge on Spot 42, and present the natural distribution of spf, show family-specific secondary structural features of Spot 42, and link highly conserved structural regions to mRNA target binding.

Concentration-Dependent Patterns of Leucine Incorporation by Coastal Picoplankton

Science.gov (United States)

Alonso, Cecilia; Pernthaler, Jakob

2006-01-01

Coastal pelagic environments are believed to feature concentration gradients of dissolved organic carbon at a microscale, and they are characterized by pronounced seasonal differences in substrate availability for the heterotrophic picoplankton. Microbial taxa that coexist in such habitats might thus differ in their ability to incorporate substrates at various concentrations. We investigated the incorporation patterns of leucine in four microbial lineages from the coastal North Sea at concentrations between 0.1 and 100 nM before and during a spring phytoplankton bloom. Community bulk incorporation rates and the fraction of leucine-incorporating cells in the different populations were analyzed. Significantly fewer bacterial cells incorporated the amino acid before (13 to 35%) than during (23 to 47%) the bloom at all but the highest concentration. The incorporation rate per active cell in the prebloom situation was constant above 0.1 nM added leucine, whereas it increased steeply with substrate concentration during the bloom. At both time points, a high proportion of members of the Roseobacter clade incorporated leucine at all concentrations (55 to 80% and 86 to 94%, respectively). In contrast, the fractions of leucine-incorporating cells increased substantially with substrate availability in bacteria from the SAR86 clade (8 to 31%) and from DE cluster 2 of the Flavobacteria-Sphingobacteria (14 to 33%). The incorporation patterns of marine Euryarchaeota were between these extremes (30 to 56% and 48 to 70%, respectively). Our results suggest that the contribution of microbial taxa to the turnover of particular substrates may be concentration dependent. This may help us to understand the specific niches of coexisting populations that appear to compete for the same resources. PMID:16517664

Folate-targeted amphiphilic cyclodextrin nanoparticles incorporating a fusogenic peptide deliver therapeutic siRNA and inhibit the invasive capacity of 3D prostate cancer tumours.

Science.gov (United States)

Evans, James C; Malhotra, Meenakshi; Sweeney, Katrina; Darcy, Raphael; Nelson, Colleen C; Hollier, Brett G; O'Driscoll, Caitriona M

2017-10-30

The main barrier to the development of an effective RNA interference (RNAi) therapy is the lack of a suitable delivery vector. Modified cyclodextrins have emerged in recent years for the delivery of siRNA. In the present study, a folate-targeted amphiphilic cyclodextrin was formulated using DSPE-PEG 5000 -folate to target prostate cancer cells. The fusogenic peptide GALA was included in the formulation to aid in the endosomal release of siRNA. Targeted nanoparticles were less than 200nm in size with a neutral surface charge. The complexes were able to bind siRNA and protect it from serum nucleases. Incubation with excess free folate resulted in a significant decrease in the uptake of targeted nanoparticles in LNCaP and PC3 cells, both of which have been reported to have differing pathways of folate uptake. There was a significant reduction in the therapeutic targets, ZEB1 and NRP1 at mRNA and protein level following treatment with targeted complexes. In preliminary functional assays using 3D spheroids, treatment of PC3 tumours with targeted complexes with ZEB1 and NRP1 siRNA resulted in more compact colonies relative to the untargeted controls and inhibited infiltration into the Matrigel™ layer. Copyright © 2017 Elsevier B.V. All rights reserved.

Combinatorial synthesis and screening of cancer cell-specific nanomedicines targeted via phage fusion proteins

Directory of Open Access Journals (Sweden)

James W. Gillespie

2015-06-01

Full Text Available Active tumor targeting of nanomedicines has recently shown significant improvements in the therapeutic activity of currently existing drug delivery systems, such as liposomal doxorubicin (Doxil/Caelyx/Lipodox. Previously, we have shown that isolated pVIII major coat proteins of the fd tet filamentous phage vector, containing cancer cell-specific peptide fusions at their N terminus, can be used as active targeting ligands in a liposomal doxorubicin delivery system in vitro and in vivo. Here, we show a novel major coat protein isolation procedure in 2-propanol that allows spontaneous incorporation of the hydrophobic protein core into preformed liposomal doxorubicin with minimal damage or drug loss while still retaining the targeting ligand exposed for cell-specific targeting. Using a panel of 12 structurally unique ligands with specificity towards breast, lung, and/or pancreatic cancer, we showed the feasibility of pVIII major coat proteins to significantly increase the throughput of targeting ligand screening in a common nanomedicine core. Phage protein-modified Lipodox samples showed an average doxorubicin recovery of 82.8% across all samples with 100% of protein incorporation in the correct orientation (N-terminus exposed. Following cytotoxicity screening in a doxorubicin-sensitive breast cancer line (MCF-7, three major groups of ligands were identified. Ligands showing the most improved cytotoxicity included: DMPGTVLP, ANGRPSMT, VNGRAEAP, and ANDVYLD showing a 25-fold improvement (p < 0.05 in toxicity. Similarly DGQYLGSQ, ETYNQPYL, and GSSEQLYL ligands with specificity towards a doxorubicin-insensitive pancreatic cancer line (PANC-1 showed significant increases in toxicity (2-fold; p < 0.05. Thus, we demonstrated proof-of-concept that pVIII major coat proteins can be screened in significantly higher throughput to identify novel ligands displaying improved therapeutic activity in a desired cancer phenotype.

Advanced cell therapies: targeting, tracking and actuation of cells with magnetic particles.

Science.gov (United States)

Connell, John J; Patrick, P Stephen; Yu, Yichao; Lythgoe, Mark F; Kalber, Tammy L

2015-01-01

Regenerative medicine would greatly benefit from a new platform technology that enabled measurable, controllable and targeting of stem cells to a site of disease or injury in the body. Superparamagnetic iron-oxide nanoparticles offer attractive possibilities in biomedicine and can be incorporated into cells, affording a safe and reliable means of tagging. This review describes three current and emerging methods to enhance regenerative medicine using magnetic particles to guide therapeutic cells to a target organ; track the cells using MRI and assess their spatial localization with high precision and influence the behavior of the cell using magnetic actuation. This approach is complementary to the systemic injection of cell therapies, thus expanding the horizon of stem cell therapeutics.

Incorporation of fluconazole in copolymer PMMA-g-PEG derivatives

International Nuclear Information System (INIS)

Silveira, B.M.; Santos, V.M.R. dos; Novack, K.M.; Lopes, S.A.

2014-01-01

The graft copolymer PMMA-g-PEG went through chemical transformations in its chain through acetylation, halogenation, methylation and esterification followed by hydrolysis reactions. Subsequently, the copolymer PMMA-g-PEG derivatives passed through the process of emulsification and incorporation of the drug fluconazole. Derivatives copolymers were characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) after incorporation in order to evaluate their effectiveness. The efficiency of incorporation was observed and it was also verified that the complexity of polymer chain influence in the incorporated fluconazole content. (author)

Rates of incorporation of radioactive molecules during the cell cycle

International Nuclear Information System (INIS)

Gray, J.W.; Pallavicini, M.G.; George, Y.S.; Groppi, V.; Look, M.; Dean, P.N.

1981-01-01

We report measurements of the incorporation of radioactive molecules during short labeling periods, as a function of cell-cycle stage, using a cell-sorter-based technique that does not require cell synchronization. We have determined: (1) tritiated thymidine ( 3 H-TdR) incorporation throughout S-phase in Lewis lung tumor cells in vitro both before and after treatment with cytosine arabinoside; (2) 3 H-TdR incorporation throughout S-phase in KHT tumor cells in vitro and in vivo; (3) 3 H-TdR incorporation throughout S-phase in Chinese hamster ovary cells and compared it with DNA synthesis throughout S-phase; (4) a mathematical expression describing 3 H-TdR incorporation throughout S-phase in Chinese hamster M3-1 cells; and (5) the simultaneous incorporation of 3 H-TdR and 35 S-methionine as they are related to cell size and DNA content in S49 mouse lymphoma cells. In asynchronously growing cells in vitro and in vivo, 3 H-TdR incorporation was generally low in early and late S-phase and highest in mid-S-phase. However, in Lewis lung tumor cells treated with cytosine arabinoside 3 H-TdR incorporation was highest in early and late S-phase and lowest in mid-S-phase. Incorporation of 35 S-methionine increased continuously with cell size and DNA content. Incorporation of 3 H-TdR in CHO cells was proportional to DNA synthesis

NIF target fill, transport and insertion cryostat

International Nuclear Information System (INIS)

Warren, R.

1994-01-01

A cryostat to support the fielding of a cryogenic target within the NIF is described. The present design is predicated upon fuel layer symmetry being achieved with the β layering process and modifications needed for other fuel symmetrization processes are discussed. These include the vertically differentially heated capsule with a uniform liquid layer stabilized by a surface tension gradient, foam supported liquid layers and solid D 2 or HD layers symmetrized by bulk irradiation from a laser source. The cold sinks to be incorporated in these techniques could, in principal, be cooled with the high pressure helium envisioned for the heat sink rings of the present design. Supplementary laser access would be provided for differential heating of the capsule for surface tension gradient stabilization of a liquid layer or bulk heating of a solid layer. The cryostat in each of these cases would look substantially the same as in the present case with the only significant differences being in the details of the design in the immediate vicinity of the target

Influences of target geometry on the microdosimetry of alpha particles in water

International Nuclear Information System (INIS)

Huston, T.E.

1992-01-01

Application of microdosimetric concepts to radiation exposure situations requires knowledge of the single-event density function, f 1 (z) , where z denotes specific energy imparted to target matter. Multiple-event density functions are calculated by taking convolutions of f 1 (z) with itself with the overall specific energy density function is then found by employing a compound Poisson process involving single and multiple-event spectra. The f l (z), depends strongly on the geometric details of a the source, target, and all intermediate matter. While most past applications of microdosimetry have been represented targets as spheres, may be better modeled as prolate or oblate spheroids. Using a ray-tracing technique coupled with a continuous-slowing-down approximation, methods are developed and presented for calculating single-event density functions for spheroidal targets irradiated by alpha-emitting point sources. Computational methods are incorporated into a fortran computer code entitled SEROID (single-event density functions for spheroids), which is listed in this paper. This was used to generate several single-event density functions, along with related means and standard deviations in specific energy, for spheroidal targets irradiated by alpha particles. Targets of varying shapes and orientations are examined. Results for non-spherical targets are compared to spherical targets of equal volume in order to assess influences which target geometry has on single-event quantities. From these comparisons it is found that both target shape and orientation are important in adequately characterizing the quantities examined in this study; over-simplifying the target geometry can lead to substantial error

Incorporating Feminist Standpoint Theory

DEFF Research Database (Denmark)

Ahlström, Kristoffer

2005-01-01

As has been noted by Alvin Goldman, there are some very interesting similarities between his Veritistic Social Epistemology (VSE) and Sandra Harding’s Feminist Standpoint Theory (FST). In the present paper, it is argued that these similarities are so significant as to motivate an incorporation...

Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles.

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Nie, Shufang; Zhang, Jia; Martinez-Zaguilan, Raul; Sennoune, Souad; Hossen, Md Nazir; Lichtenstein, Alice H; Cao, Jun; Meyerrose, Gary E; Paone, Ralph; Soontrapa, Suthipong; Fan, Zhaoyang; Wang, Shu

2015-12-28

Current approaches to the diagnosis and therapy of atherosclerosis cannot target lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing inflammatory responses. The presence of these cells is positively associated with lesion progression, severity and destabilization. Hence, they are an important diagnostic and therapeutic target. The objective of this study was to noninvasively assess the distribution and accumulation of intimal macrophages using CD36-targeted nanovesicles. Soy phosphatidylcholine was used to synthesize liposome-like nanovesicles. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine was incorporated on their surface to target the CD36 receptor. All in vitro data demonstrate that these targeted nanovesicles had a high binding affinity for the oxLDL binding site of the CD36 receptor and participated in CD36-mediated recognition and uptake of nanovesicles by macrophages. Intravenous administration into LDL receptor null mice of targeted compared to non-targeted nanovesicles resulted in higher uptake in aortic lesions. The nanovesicles co-localized with macrophages and their CD36 receptors in aortic lesions. This molecular target approach may facilitate the in vivo noninvasive imaging of atherosclerotic lesions in terms of intimal macrophage accumulation and distribution and disclose lesion features related to inflammation and possibly vulnerability thereby facilitate early lesion detection and targeted delivery of therapeutic compounds to intimal macrophages. Copyright © 2015 Elsevier B.V. All rights reserved.

Analysis of CdS/CdTe devices incorporating a ZnTe:Cu/Ti Contact

International Nuclear Information System (INIS)

Gessert, T.A.; Asher, S.; Johnston, S.; Young, M.; Dippo, P.; Corwine, C.

2007-01-01

High-performance CdS/CdTe photovoltaic devices can be produced using a ZnTe:Cu/Ti back contact deposited onto the CdTe layer. We observe that prolonged exposure of the ZnTe:Cu and Ti sputtering targets to an oxygen-containing plasma significantly reduces device open-circuit voltage and fill factor. High-resolution compositional analysis of these devices reveals that Cu concentration in the CdTe and CdS layers is lower for devices with poor performance. Capacitance-voltage analysis and related numerical simulations indicate that the net acceptor concentration in the CdTe is also lower for devices with poor performance. Photoluminescence analyses of the junction region reveal that the intensity of a luminescent peak associated with a defect complex involving interstitial Cu (Cu i ) and oxygen on Te (O Te ) is reduced in devices with poor performance. Combined with thermodynamic considerations, these results suggest that oxygen incorporation into the ZnTe:Cu sputtering target reduces the ability of sputtered ZnTe:Cu film to diffuse Cu into the CdTe

Optimum combination of targeted 131I and total body irradiation for treatment of disseminated cancer

International Nuclear Information System (INIS)

Amin, Amin E.; Wheldon, Tom E.; O'Donoghue, Joseph A.; Gaze, Mark N.; Barrett, Ann

1995-01-01

Purpose: Radiobiological modeling was used to explore optimum combination strategies for treatment of disseminated malignancies of differing radiosensitivity and differing patterns of metastatic spread. The purpose of the study was to derive robust conclusions about the design of combination strategies that incorporate a targeting component. Preliminary clinical experience of a neuroblastoma treatment strategy, which is based upon general principles obtained from modelling, is briefly described. Methods and Materials: The radiobiological analysis was based on an extended (dose-rate dependent) formulation of the linear quadratic model. Radiation dose and dose rate for targeted irradiation of tumors of differing size was in part based on microdosimetric considerations. The analysis was applied to several tumor types with postulated differences in the pattern of metastatic spread, represented by the steepness of the slope of the relationship between numbers of tumors present and tumor diameter. The clinical pilot study entailed the treatment of five children with advanced neuroblastoma using a combination of 131 I metaiodobenzylguanidine (mIBG) and total body irradiation followed by bone marrow rescue. Results: The theoretical analysis shows that both intrinsic radiosensitivity and pattern of metastatic spread can influence the composition of the ideal optimum combination strategy. High intrinsic radiosensitivity generally favors a high proportion of targeting component in the combination treatment, while a strong tendency to micrometastatic spread favors a major contribution by total body irradiation. The neuroblastoma patients were treated using a combination regimen with an initially low targeting component (2 Gy whole body dose from targeting component plus 12 Gy from total body irradiation). The treatment was tolerable and resulted in remissions in excess of 9 months in each of these advanced neuroblastoma patients. Conclusions: Radiobiological analysis, which

An amino acid depleted cell-free protein synthesis system for the incorporation of non-canonical amino acid analogs into proteins.

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Singh-Blom, Amrita; Hughes, Randall A; Ellington, Andrew D

2014-05-20

Residue-specific incorporation of non-canonical amino acids into proteins is usually performed in vivo using amino acid auxotrophic strains and replacing the natural amino acid with an unnatural amino acid analog. Herein, we present an efficient amino acid depleted cell-free protein synthesis system that can be used to study residue-specific replacement of a natural amino acid by an unnatural amino acid analog. This system combines a simple methodology and high protein expression titers with a high-efficiency analog substitution into a target protein. To demonstrate the productivity and efficacy of a cell-free synthesis system for residue-specific incorporation of unnatural amino acids in vitro, we use this system to show that 5-fluorotryptophan and 6-fluorotryptophan substituted streptavidin retain the ability to bind biotin despite protein-wide replacement of a natural amino acid for the amino acid analog. We envisage this amino acid depleted cell-free synthesis system being an economical and convenient format for the high-throughput screening of a myriad of amino acid analogs with a variety of protein targets for the study and functional characterization of proteins substituted with unnatural amino acids when compared to the currently employed in vivo methodologies. Copyright © 2014 Elsevier B.V. All rights reserved.

Preferential lentiviral targeting of astrocytes in the central nervous system.

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Michael Fassler

Full Text Available The ability to visualize and genetically manipulate specific cell populations of the central nervous system (CNS is fundamental to a better understanding of brain functions at the cellular and molecular levels. Tools to selectively target cells of the CNS include molecular genetics, imaging, and use of transgenic animals. However, these approaches are technically challenging, time consuming, and difficult to control. Viral-mediated targeting of cells in the CNS can be highly beneficial for studying and treating neurodegenerative diseases. Yet, despite specific marking of numerous cell types in the CNS, in vivo selective targeting of astrocytes has not been optimized. In this study, preferential targeting of astrocytes in the CNS was demonstrated using engineered lentiviruses that were pseudotyped with a modified Sindbis envelope and displayed anti-GLAST IgG on their surfaces as an attachment moiety. Viral tropism for astrocytes was initially verified in vitro in primary mixed glia cultures. When injected into the brains of mice, lentiviruses that displayed GLAST IgG on their surface, exhibited preferential astrocyte targeting, compared to pseudotyped lentiviruses that did not incorporate any IgG or that expressed a control isotype IgG. Overall, this approach is highly flexible and can be exploited to selectively target astrocytes or other cell types of the CNS. As such, it can open a window to visualize and genetically manipulate astrocytes or other cells of the CNS as means of research and treatment.

Identification of isoforms of microRNAs in wheat (Triticum aestivum L. and their role in leaf rust pathogenesis

Directory of Open Access Journals (Sweden)

Summi Dutta

2017-10-01

Full Text Available Bread wheat, a type of grass under genus Triticum and species aestivum covers the largest land area when production of cereal crops is considered. Being an allohexaploid (2n=6x=42; AABBDD, its genome is contributed by three progenitors and is evolutionarily rich. Rust in leaves, caused by Puccinia triticina, severely affects grain quality. MicroRNAs are considered as major components of gene silencing and so have deep role to play during stress. Post transcriptional modification of miRNAs which generates isomiRNAs significantly affects target specificity especially when the modification occurs in 5′end. A total of four small RNA libraries were prepared through next-generation Illumina sequencing techniques from leaves of two wheat Near Isogenic Lines (NILs, HD2329 (susceptible and HD2329 + LR24 (resistant. Prior to this, one set of the two NILs was mock inoculated and considered as control (with sRNA library code named SM-mi and RM-mi while other was treated with urediniospores of leaf rust fungus (with sRNA library code named SPI-mi and RPI-mi. Clean reads in all four libraries were previously used for prediction of 559 novel miRNAs and in the current study it was used to detect isoforms of these miRNAs. A total of 237 isoforms were detected for 41 miRNAs. These isoforms included both 5′ and 3′ modifications of miRNAs. There were 27 miRNAs with 5′ modifications and five miRNAs with 3′ modifications while nine miRNAs showed both types of modifications.

Report of the consultants' meeting on target and processing technologies for cyclotron production of radionuclides

International Nuclear Information System (INIS)

1999-11-01

Cyclotron produced radionuclides are used routinely for the diagnosis of a wide variety of diseases. Recently a number of radionuclides available from cyclotrons have been proposed for use in radiotherapy. In fact Pd-103 has become routinely available in some parts of the world for incorporation into brachytherapy seeds for treating prostate cancer. The consultants meeting reviewed the status of target and processing technologies associated with cyclotron production of radionuclides. The main topics of discussion included the basic nuclear data that is crucial to the production of the desired radionuclides, gas and solid target systems, the automated chemical processing units, the Good Manufacturing Practices (GMP) required in order to use these radionuclides in human patients in a safe and efficacious manner and a review of possible candidate nuclides that show promise for use in Nuclear Medicine in the near future. Advances in the preparation of solid targets using electroplating technology has created the possibility of preparing targets capable of operating at very high beam currents which would make the production of large quantities of SPECT agents possible at cyclotron facilities throughout the world. Recognising the needs of the developing countries which have established cyclotron facilities, the consultants focussed on how to provide the technology for preparing solid targets that could be used in the existing facilities. While solid target technology can be used for many radionuclides the report concentrated on several key radionuclides, which are of current importance or show potential for use in the near future. Tl-201 is currently used for cardiac profusion studies throughout the world. New target preparation techniques could potentially make many of the member states self sufficient in the production of this nuclide. I-123 has tremendous potential because of the near ideal photon energy for SPECT cameras and its well-understood chemistry. However, it

Pros and cons of the liposome platform in cancer drug targeting.

Science.gov (United States)

Gabizon, Alberto A; Shmeeda, Hilary; Zalipsky, Samuel

2006-01-01

Coating of liposomes with polyethylene-glycol (PEG) by incorporation in the liposome bilayer of PEG-derivatized lipids results in inhibition of liposome uptake by the reticulo-endothelial system and significant prolongation of liposome residence time in the blood stream. Parallel developments in drug loading technology have improved the efficiency and stability of drug entrapment in liposomes, particularly with regard to cationic amphiphiles such as anthracyclines. An example of this new generation of liposomes is a formulation of pegylated liposomal doxorubicin known as Doxil or Caelyx, whose clinical pharmacokinetic profile is characterized by slow plasma clearance and small volume of distribution. A hallmark of these long-circulating liposomal drug carriers is their enhanced accumulation in tumors. The mechanism underlying this passive targeting effect is the phenomenon known as enhanced permeability and retention (EPR) which has been described in a broad variety of experimental tumor types. Further to the passive targeting effect, the liposome drug delivery platform offers the possibility of grafting tumor-specific ligands on the liposome membrane for active targeting to tumor cells, and potentially intracellular drug delivery. The pros and cons of the liposome platform in cancer targeting are discussed vis-à-vis nontargeted drugs, using as an example a liposome drug delivery system targeted to the folate receptor.

Targeting Epidermal Growth Factor Receptor-Related Signaling Pathways in Pancreatic Cancer.

Science.gov (United States)

Philip, Philip A; Lutz, Manfred P

2015-10-01

Pancreatic cancer is aggressive, chemoresistant, and characterized by complex and poorly understood molecular biology. The epidermal growth factor receptor (EGFR) pathway is frequently activated in pancreatic cancer; therefore, it is a rational target for new treatments. However, the EGFR tyrosine kinase inhibitor erlotinib is currently the only targeted therapy to demonstrate a very modest survival benefit when added to gemcitabine in the treatment of patients with advanced pancreatic cancer. There is no molecular biomarker to predict the outcome of erlotinib treatment, although rash may be predictive of improved survival; EGFR expression does not predict the biologic activity of anti-EGFR drugs in pancreatic cancer, and no EGFR mutations are identified as enabling the selection of patients likely to benefit from treatment. Here, we review clinical studies of EGFR-targeted therapies in combination with conventional cytotoxic regimens or multitargeted strategies in advanced pancreatic cancer, as well as research directed at molecules downstream of EGFR as alternatives or adjuncts to receptor targeting. Limitations of preclinical models, patient selection, and trial design, as well as the complex mechanisms underlying resistance to EGFR-targeted agents, are discussed. Future clinical trials must incorporate translational research end points to aid patient selection and circumvent resistance to EGFR inhibitors.

Difference in target definition using three different methods to include respiratory motion in radiotherapy of lung cancer.

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Sloth Møller, Ditte; Knap, Marianne Marquard; Nyeng, Tine Bisballe; Khalil, Azza Ahmed; Holt, Marianne Ingerslev; Kandi, Maria; Hoffmann, Lone

2017-11-01

Minimizing the planning target volume (PTV) while ensuring sufficient target coverage during the entire respiratory cycle is essential for free-breathing radiotherapy of lung cancer. Different methods are used to incorporate the respiratory motion into the PTV. Fifteen patients were analyzed. Respiration can be included in the target delineation process creating a respiratory GTV, denoted iGTV. Alternatively, the respiratory amplitude (A) can be measured based on the 4D-CT and A can be incorporated in the margin expansion. The GTV expanded by A yielded GTV + resp, which was compared to iGTV in terms of overlap. Three methods for PTV generation were compared. PTV del (delineated iGTV expanded to CTV plus PTV margin), PTV σ (GTV expanded to CTV and A was included as a random uncertainty in the CTV to PTV margin) and PTV ∑ (GTV expanded to CTV, succeeded by CTV linear expansion by A to CTV + resp, which was finally expanded to PTV ∑ ). Deformation of tumor and lymph nodes during respiration resulted in volume changes between the respiratory phases. The overlap between iGTV and GTV + resp showed that on average 7% of iGTV was outside the GTV + resp implying that GTV + resp did not capture the tumor during the full deformable respiration cycle. A comparison of the PTV volumes showed that PTV σ was smallest and PTV Σ largest for all patients. PTV σ was in mean 14% (31 cm 3 ) smaller than PTV del , while PTV del was 7% (20 cm 3 ) smaller than PTV Σ . PTV σ yields the smallest volumes but does not ensure coverage of tumor during the full respiratory motion due to tumor deformation. Incorporating the respiratory motion in the delineation (PTV del ) takes into account the entire respiratory cycle including deformation, but at the cost, however, of larger treatment volumes. PTV Σ should not be used, since it incorporates the disadvantages of both PTV del and PTV σ .

A mathematical model and quantitative comparison of the small RNA circuit in the Vibrio harveyi and Vibrio cholerae quorum sensing systems

International Nuclear Information System (INIS)

Hunter, G A M; Vasquez, F Guevara; Keener, J P

2013-01-01

Quorum sensing is the process by which bacteria regulate their gene expression based on the local cell-population density. The quorum sensing systems of Vibrio harveyi and Vibrio cholerae are comprised of a phosphorelay cascade coupled to a small RNA (sRNA) circuit. The sRNA circuit contains multiple quorum regulated small RNA (Qrr) that regulate expression of the homologous master transcriptional regulators LuxR (in V. harveyi) and HapR (in V. cholerae). Their quorum sensing systems are topologically similar and homologous thereby making it difficult to understand why repression of HapR is more robust than LuxR to changes in Qrr. In this work we formulate and parameterize a novel mathematical model of the V. harveyi and V. cholerae sRNA circuit. We parameterize the model by fitting it to a variety of empirical data from both species. We show that we can distinguish all of the parameters and that the parameterizations (one for each species) are robust to errors in the data. We then use our model to propose some experiments to identify and explain kinetic differences between the species. We find that V. cholerae Qrr are more abundant and more sensitive to changes in LuxO than V. harveyi Qrr and argue that this is why expression of HapR is more robust than LuxR to changes in Qrr. (paper)

Assessment of small RNA sorting into different extracellular fractions revealed by high-throughput sequencing of breast cell lines

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Tosar, Juan Pablo; Gámbaro, Fabiana; Sanguinetti, Julia; Bonilla, Braulio; Witwer, Kenneth W.; Cayota, Alfonso

2015-01-01

Intercellular communication can be mediated by extracellular small regulatory RNAs (sRNAs). Circulating sRNAs are being intensively studied for their promising use as minimally invasive disease biomarkers. To date, most attention is centered on exosomes and microRNAs as the vectors and the secreted species, respectively. However, this field would benefit from an increased understanding of the plethora of sRNAs secreted by different cell types in different extracellular fractions. It is still not clear if specific sRNAs are selected for secretion, or if sRNA secretion is mostly passive. We sequenced the intracellular sRNA content (19–60 nt) of breast epithelial cell lines (MCF-7 and MCF-10A) and compared it with extracellular fractions enriched in microvesicles, exosomes and ribonucleoprotein complexes. Our results are consistent with a non-selective secretion model for most microRNAs, although a few showed secretion patterns consistent with preferential secretion. On the contrary, 5′ tRNA halves and 5′ RNA Y4-derived fragments of 31–33 were greatly and significantly enriched in the extracellular space (even in non-mammary cell lines), where tRNA halves were detected as part of ∼45 kDa ribonucleoprotein complexes. Overall, we show that different sRNA families have characteristic secretion patterns and open the question of the role of these sRNAs in the extracellular space. PMID:25940616

Signal integration: a framework for understanding the efficacy of therapeutics targeting the human EGFR family

Science.gov (United States)

Shepard, H. Michael; Brdlik, Cathleen M.; Schreiber, Hans

2008-01-01

The human EGFR (HER) family is essential for communication between many epithelial cancer cell types and the tumor microenvironment. Therapeutics targeting the HER family have demonstrated clinical success in the treatment of diverse epithelial cancers. Here we propose that the success of HER family–targeted monoclonal antibodies in cancer results from their ability to interfere with HER family consolidation of signals initiated by a multitude of other receptor systems. Ligand/receptor systems that initiate these signals include cytokine receptors, chemokine receptors, TLRs, GPCRs, and integrins. We further extrapolate that improvements in cancer therapeutics targeting the HER family are likely to incorporate mechanisms that block or reverse stromal support of malignant progression by isolating the HER family from autocrine and stromal influences. PMID:18982164

Structural and functional characterization of Rpn12 identifies residues required for Rpn10 proteasome incorporation.

Science.gov (United States)

Boehringer, Jonas; Riedinger, Christiane; Paraskevopoulos, Konstantinos; Johnson, Eachan O D; Lowe, Edward D; Khoudian, Christina; Smith, Dominique; Noble, Martin E M; Gordon, Colin; Endicott, Jane A

2012-11-15

The ubiquitin-proteasome system targets selected proteins for degradation by the 26S proteasome. Rpn12 is an essential component of the 19S regulatory particle and plays a role in recruiting the extrinsic ubiquitin receptor Rpn10. In the present paper we report the crystal structure of Rpn12, a proteasomal PCI-domain-containing protein. The structure helps to define a core structural motif for the PCI domain and identifies potential sites through which Rpn12 might form protein-protein interactions. We demonstrate that mutating residues at one of these sites impairs Rpn12 binding to Rpn10 in vitro and reduces Rpn10 incorporation into proteasomes in vivo.

Understanding the value of emergency care: a framework incorporating stakeholder perspectives.

Science.gov (United States)

Sharp, Adam L; Cobb, Enesha M; Dresden, Scott M; Richardson, Derek K; Sabbatini, Amber K; Sauser, Kori; Kocher, Keith E

2014-09-01

In the face of escalating spending, measuring and maximizing the value of health services has become an important focus of health reform. Recent initiatives aim to incentivize high-value care through provider and hospital payment reform, but the role of the emergency department (ED) remains poorly defined. To achieve an improved understanding of the value of emergency care, we have developed a framework that incorporates the perspectives of stakeholders in the delivery of health services. A pragmatic review of the literature informed the design of this framework to standardize the definition of value in emergency care and discuss outcomes and costs from different stakeholder perspectives. The viewpoint of patient, provider, payer, health system, and society is each used to assess value for emergency medical conditions. We found that the value attributed to emergency care differs substantially by stakeholder perspective. Potential targets to improve ED value may be aimed at improving outcomes or controlling costs, depending on the acuity of the clinical condition. The value of emergency care varies by perspective, and a better understanding is achieved when specific outcomes and costs can be identified, quantified, and measured. Using this framework can help stakeholders find common ground to prioritize which costs and outcomes to target for research, quality improvement efforts, and future health policy impacting emergency care. Copyright © 2014 Elsevier Inc. All rights reserved.

HIV-1 Envelope Glycoprotein Trafficking through the Endosomal Recycling Compartment Is Required for Particle Incorporation.

Science.gov (United States)

Kirschman, Junghwa; Qi, Mingli; Ding, Lingmei; Hammonds, Jason; Dienger-Stambaugh, Krista; Wang, Jaang-Jiun; Lapierre, Lynne A; Goldenring, James R; Spearman, Paul

2018-03-01

The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) encodes specific trafficking signals within its long cytoplasmic tail (CT) that regulate incorporation into HIV-1 particles. Rab11-family interacting protein 1C (FIP1C) and Rab14 are host trafficking factors required for Env particle incorporation, suggesting that Env undergoes sorting from the endosomal recycling compartment (ERC) to the site of particle assembly on the plasma membrane. We disrupted outward sorting from the ERC by expressing a C-terminal fragment of FIP1C (FIP1C 560-649 ) and examined the consequences on Env trafficking and incorporation into particles. FIP1C 560-649 reduced cell surface levels of Env and prevented its incorporation into HIV-1 particles. Remarkably, Env was trapped in an exaggerated perinuclear ERC in a CT-dependent manner. Mutation of either the Yxxϕ endocytic motif or the YW 795 motif in the CT prevented Env trapping in the ERC and restored incorporation into particles. In contrast, simian immunodeficiency virus SIVmac239 Env was not retained in the ERC, while substitution of the HIV-1 CT for the SIV CT resulted in SIV Env retention in this compartment. These results provide the first direct evidence that Env traffics through the ERC and support a model whereby HIV-1 Env is specifically targeted to the ERC prior to FIP1C- and CT-dependent outward sorting to the particle assembly site on the plasma membrane. IMPORTANCE The HIV envelope protein is an essential component of the viral particle. While many aspects of envelope protein structure and function have been established, the pathway it follows in the cell prior to reaching the site of particle assembly is not well understood. The envelope protein has a very long cytoplasmic tail that interacts with the host cell trafficking machinery. Here, we utilized a truncated form of the trafficking adaptor FIP1C protein to arrest the intracellular transport of the envelope protein, demonstrating that it becomes

Activity incorporation into zinc doped PWR oxides

International Nuclear Information System (INIS)

Maekelae, Kari

1998-01-01

Activity incorporation into the oxide layers of PWR primary circuit constructional materials has been studied in Halden since 1993. The first zinc injection tests showed that zinc addition resulted in thinner oxide layers on new metal surfaces and reduced further incorporation of activity into already existing oxides. These tests were continued to find out the effects of previous zinc additions on the pickup of activity onto the surface oxides which were subsequently exposed to zinc-free coolant. The results showed that previous zinc addition will continue to reduce the rate of Co-60 build-up on out-of-core surfaces in subsequent exposure to zinc-free coolants. However, the previous Zn free test was performed for a relatively short period of time and the water chemistry programme was continued to find out the long term effects for extended periods without zinc. The activity incorporation into the stainless steel oxides started to increase as soon as zinc dosing to the coolant was stopped. The Co-60 concentration was lowest on all of the coupons which were first oxidised in Zn containing primary coolant. After the zinc injection period the thickness of the oxides increased, but activity in the oxide films did not increase at the same rate. This could indicate that zinc in the oxide blocks the adsorption sites for Co-60 incorporation. The Co-60 incorporation rate into the oxides on Inconel 600 seemed to be linear whether the oxide was pre-oxidised with or without Zn. The results indicate that zinc can either replace or prevent cobalt transport in the oxides. The results show that for zinc injection to be effective it should be carried out continuously. Furthermore the actual mechanism by which Zn inhibits the activity incorporation into the oxides is still not clear. Therefore, additional work has to follow with specified materials to verify the conclusions drawn in this work. (author)

Radiological accidents: methodologies of radio nuclides dis incorporation

International Nuclear Information System (INIS)

Jimenez F, E. A.; Paredes G, L.; Cortes, A.

2014-08-01

Derived of the radioactive or nuclear material management, exists the risk that accidents can happen where people cases are presented with internal radioactive contamination, who will receive specialized medical care to accelerate the radioactive dis incorporation with the purpose of diminishing the absorbed dose and the associate biological effects. In this work treatments of radioactive dis incorporation were identified, in function of the radionuclide, radiation type, radioactive half life, biological half life, critical organ, ingestion duct and patient type. The factor time is decisive for the effectiveness of the selected treatment in the blockade stage (before the accident) or dis incorporation (after the accident); this factor is related with the radioactive and biological half lives. So to achieve dis incorporation efficiencies of more to 70%, the patient clinical treatment will begin before the first third of the biological half life of the radionuclide that generated the internal contamination. (Author)

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent

Energy Technology Data Exchange (ETDEWEB)

Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, Melbourne (Australia); University of Melbourne, Department of Medicine, St Vincent' s Medical School, Melbourne (Australia); Rischin, Danny [University of Melbourne, Department of Medicine, St Vincent' s Medical School, Melbourne (Australia); Peter MacCallum Cancer Centre, Division of Haematology and Medical Oncology, Melbourne (Australia); Fisher, Richard [Peter MacCallum Cancer Centre, Centre for Biostatistics and Clinical Trials, Melbourne (Australia); Binns, David [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, Melbourne (Australia); Scott, Andrew M. [Austin Hospital, Centre for PET, and Ludwig Institute for Cancer Research, Melbourne (Australia); Peters, Lester J. [Peter MacCallum Cancer Centre, Division of Radiation Oncology, Melbourne (Australia)

2005-12-01

The purpose of the study was to evaluate [{sup 18}F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy. Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [{sup 18}F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort. Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%). The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer. (orig.)

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent

International Nuclear Information System (INIS)

Hicks, Rodney J.; Rischin, Danny; Fisher, Richard; Binns, David; Scott, Andrew M.; Peters, Lester J.

2005-01-01

The purpose of the study was to evaluate [ 18 F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy. Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [ 18 F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort. Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%). The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer. (orig.)

Quantum-Mechanical Methods for Quantifying Incorporation of Contaminants in Proximal Minerals

Directory of Open Access Journals (Sweden)

Lindsay C. Shuller-Nickles

2014-07-01

Full Text Available Incorporation reactions play an important role in dictating immobilization and release pathways for chemical species in low-temperature geologic environments. Quantum-mechanical investigations of incorporation seek to characterize the stability and geometry of incorporated structures, as well as the thermodynamics and kinetics of the reactions themselves. For a thermodynamic treatment of incorporation reactions, a source of the incorporated ion and a sink for the released ion is necessary. These sources/sinks in a real geochemical system can be solids, but more commonly, they are charged aqueous species. In this contribution, we review the current methods for ab initio calculations of incorporation reactions, many of which do not consider incorporation from aqueous species. We detail a recently-developed approach for the calculation of incorporation reactions and expand on the part that is modeling the interaction of periodic solids with aqueous source and sink phases and present new research using this approach. To model these interactions, a systematic series of calculations must be done to transform periodic solid source and sink phases to aqueous-phase clusters. Examples of this process are provided for three case studies: (1 neptunyl incorporation into studtite and boltwoodite: for the layered boltwoodite, the incorporation energies are smaller (more favorable for reactions using environmentally relevant source and sink phases (i.e., ΔErxn(oxides > ΔErxn(silicates > ΔErxn(aqueous. Estimates of the solid-solution behavior of Np5+/P5+- and U6+/Si4+-boltwoodite and Np5+/Ca2+- and U6+/K+-boltwoodite solid solutions are used to predict the limit of Np-incorporation into boltwoodite (172 and 768 ppm at 300 °C, respectively; (2 uranyl and neptunyl incorporation into carbonates and sulfates: for both carbonates and sulfates, it was found that actinyl incorporation into a defect site is more favorable than incorporation into defect-free periodic

Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida.

Science.gov (United States)

Bojanovič, Klara; D'Arrigo, Isotta; Long, Katherine S

2017-04-01

Bacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response of Pseudomonas putida KT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification of differentially expressed mRNAs and small RNAs (sRNAs). A total of 440 sRNA transcripts were detected, of which 10% correspond to previously annotated sRNAs, 40% to novel intergenic transcripts, and 50% to novel transcripts antisense to annotated genes. Each stress elicits a unique response as far as the extent and dynamics of the transcriptional changes. Nearly 200 protein-encoding genes exhibited significant changes in all stress types, implicating their participation in a general stress response. Almost half of the sRNA transcripts were differentially expressed under at least one condition, suggesting possible functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through which P. putida responds to different stress conditions and increases understanding of bacterial adaptation in natural and industrial settings. IMPORTANCE This study maps the complete transcriptional response of P. putida KT2440 to osmotic, oxidative, and imipenem stress conditions at short and long exposure times. Over 400 sRNA transcripts, consisting of both intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous knowledge of stress response mechanisms due to the depth of the RNA sequencing data. Almost half of the sRNAs exhibit significant expression changes under at least one

Charge compensation and the incorporation of cerium in zirconolite and perovskite

International Nuclear Information System (INIS)

Begg, B.D.; Vance, E.R.; Lumpkin, G.R.

1998-01-01

Full text: Synroc is a mineral-analogue based titanate ceramic, consisting of a series of extremely stable, mutually compatible phases capable of incorporating HLW elements within their crystal structures. Waste elements are incorporated into the each of the Synroc phases via a substitutional solid solution mechanism. A given waste element is substituted directly for a host matrix element, of a similar ionic size, and where a charge imbalance exists between the waste and the host ions, suitable charge compensation is made to maintain overall charge neutrality. Charge compensation may take the form of an additional ion of appropriate charge substituting on either the same or a separate site, in such a manner so as to offset the original charge imbalance. In this way, waste ions are chemically bonded into the crystal structure of the durable host Synroc phase. The major rare earth/actinide-bearing Synroc phase is zirconolite. Previously we have reported on the incorporation of both cerium, which was used as a non-radioactive simulant for plutonium, and plutonium in zirconolite. We demonstrated how the valence of both ions can be varied by changing the firing atmosphere without significantly altering the composition of the zirconolite. This raised a number of significant questions about the nature of charge compensation at work in these zirconolites. In an effort to further investigate the charge compensation mechanisms at work in these cerium- and plutonium-doped zirconolites, it was decided to examine the incorporation of Ce in the simpler, but closely related, perovskite (CaTiO 3 ) system in addition to making further studies of Ce-doped zirconolites. Of course perovskite is also a component of Synroc which is also capable of incorporating significant amounts of rare earths and actinides. In an analogous way to the zirconolite series, the Ce was incorporated on the Ca site, with specific Ce valence states being targeted via the provision of appropriate amounts of

Phosphate incorporation in organic compounds in roots of maize

Energy Technology Data Exchange (ETDEWEB)

Michalik, I; Ivanko, S [Vysoka Skola Polnohospodarska, Nitra (Czechoslovakia)

1976-01-01

/sup 32/P incorporation and metabolism was investigated for short exposure times of 1 sec, 10 sec and 1, 10, 30 and 120 min. By stepwise extraction with a methanol-chloroform-formic acid-water mixture, various fractions of P compounds were obtained. Low-molecular acid-soluble P compounds were separated by one-dimensional paper chromatography. Of the total amount of /sup 32/P absorbed by the roots of maize in the form of phosphate ions during the short incubation time of 1 sec, more than 33% was incorporated into organic compounds. With increasing incubation time, the proportion of /sup 32/P in low-molecular organic compounds increased with the decreasing proportion of inorganic phosphorus. In the 1 sec, exposure incorporation was found in 3 low-molecular organic compounds only, namely ATP, ADP and diphosphoglyceric acid. The /sup 32/P incorporation into ATP and ADP, in contrast with incorporation into diphosphoglyceric acid, increased markedly with increased exposure time.

Phosphate incorporation in organic compounds in roots of maize

International Nuclear Information System (INIS)

Michalik, I.; Ivanko, S.

1976-01-01

32 P incorporation and metabolism was investigated for short exposure times of 1 sec, 10 sec and 1, 10, 30 and 120 min. By stepwise extraction with a methanol-chloroform-formic acid-water mixture, various fractions of P compounds were obtained. Low-molecular acid-soluble P compounds were separated by one-dimensional paper chromatography. Of the total amount of 32 P absorbed by the roots of maize in the form of phosphate ions during the short incubation time of 1 sec, more than 33% was incorporated into organic compounds. With increasing incubation time, the proportion of 32 P in low-molecular organic compounds increased with the decreasing proportion of inorganic phosphorus. In the 1 sec, exposure incorporation was found in 3 low-molecular organic compounds only, namely ATP, ADP and diphosphoglyceric acid. The 32 P incorporation into ATP and ADP, in contrast with incorporation into diphosphoglyceric acid, increased markedly with increased exposure time. (author)

Targets for ion sources for RIB generation at the Holifield Radioactive Ion Beam Facility

International Nuclear Information System (INIS)

Alton, G.D.

1995-01-01

The Holifield Radioactive Ion Beam Facility (HRIBF), now under construction at the Oak Ridge National Laboratory, is based on the use of the well-known on-line isotope separator (ISOL) technique in which radioactive nuclei are produced by fusion type reactions in selectively chosen target materials by high-energy proton, deuteron, or He ion beams from the Oak Ridge Isochronous Cyclotron (ORIC). Among several major challenges posed by generating and accelerating adequate intensities of radioactive ion beams (RIBs), selection of the most appropriate target material for production of the species of interest is, perhaps, the most difficult. In this report, we briefly review present efforts to select target materials and to design composite target matrix/heat-sink systems that simultaneously incorporate the short diffusion lengths, high permeabilities, and controllable temperatures required to effect maximum diffusion release rates of the short-lived species that can be realized at the temperature limits of specific target materials. We also describe the performance characteristics for a selected number of target ion sources that will be employed for initial use at the HRIBF as well as prototype ion sources that show promise for future use for RIB applications

Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

International Nuclear Information System (INIS)

Park, Ji-Ae; Lee, Yong Jin; Ko, In Ok; Kim, Tae-Jeong; Chang, Yongmin; Lim, Sang Moo; Kim, Kyeong Min; Kim, Jung Young

2014-01-01

Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images

Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

Energy Technology Data Exchange (ETDEWEB)

Park, Ji-Ae, E-mail: jpark@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yong Jin; Ko, In Ok [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Tae-Jeong; Chang, Yongmin [Institute of Biomedical Engineering, Kyungpook National University, Daegu (Korea, Republic of); Lim, Sang Moo [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kyeong Min [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jung Young, E-mail: jykim@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2014-12-12

Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

36 CFR 13.320 - Preference to Cook Inlet Region, Incorporated.

Science.gov (United States)

2010-07-01

... Region, Incorporated. 13.320 Section 13.320 Parks, Forests, and Public Property NATIONAL PARK SERVICE... to Cook Inlet Region, Incorporated. (a) The Cook Inlet Region, Incorporated (CIRI), in cooperation with village corporations within the Cook Inlet region when appropriate, will have a right of first...

Final report for ER65039, The Role of Small RNA in Biomass Deposition

Energy Technology Data Exchange (ETDEWEB)

Hudson, Matthew E. [Univ. of Illinois, Urbana, IL (United States)

2015-03-12

Our objective in this project was to discover the role of sRNA in regulating both biomass biosynthesis and perenniality in the Andropogoneae feedstock grasses. Our central hypothesis was that there is a time-and space specific sRNA network playing a crucial role in regulating processes associated with cell wall biosynthesis, flowering time control, overwintering/juvenility, and nutrient sequestration in the feedstock grasses. To address this, we performed a large scale biological project consisting of the growth of material, generation of Illumina libraries, sequencing and analysis for small RNA, mRNA and Degradome / cmRNA. Our subsidiary objectives included analysis of the biology of small RNAs and the cell wall composition of Miscanthus. These objectives have all been completed, one publication is in print, one is submitted and several more are in progress.

Dopant Adsorption and Incorporation at Irradiated GaN Surfaces

Science.gov (United States)

Sun, Qiang; Selloni, Annabella; Myers, Thomas; Doolittle, W. Alan

2006-03-01

Mg and O are two of the common dopants in GaN, but, in spite of extensive investigation, the atomic scale understanding of their adsorption and incorporation is still incomplete. In particular, high-energy electron irradiation, such as occurring during RHEED, has been reported to have an important effect on the incorporation of these impurities, but no study has addressed the detailed mechanisms of this effect yet. Here we use DFT calculations to study the adsorption and incorporation of Mg and O at the Ga- and N-polar GaN surfaces under various Ga, Mg and O coverage conditions as well as in presence of light or electron beam-induced electronic excitation. We find that the adsorption and incorporation of the two impurities have opposite surface polarity dependence: substitutional Mg prefers to incorporate at the GaN(0001) surface, while O prefers to adsorb and incorporate at the N-polar surface. In addition, our results indicate that in presence of light irradiation the tendency of Mg to surface-segregate is reduced. The O adsorption energy on the N-polar surface is also significantly reduced, consistent with the experimental observation of a much smaller concentration of oxygen in the irradiated samples.

HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

Science.gov (United States)

Sanchez-Gaytan, Brenda L; Fay, Francois; Lobatto, Mark E; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E M; van Rijs, Sarian M; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J; Langer, Robert; Fayad, Zahi A; Mulder, Willem J M

2015-03-18

High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers.

Incorporating Duration Information in Activity Recognition

Science.gov (United States)

Chaurasia, Priyanka; Scotney, Bryan; McClean, Sally; Zhang, Shuai; Nugent, Chris

Activity recognition has become a key issue in smart home environments. The problem involves learning high level activities from low level sensor data. Activity recognition can depend on several variables; one such variable is duration of engagement with sensorised items or duration of intervals between sensor activations that can provide useful information about personal behaviour. In this paper a probabilistic learning algorithm is proposed that incorporates episode, time and duration information to determine inhabitant identity and the activity being undertaken from low level sensor data. Our results verify that incorporating duration information consistently improves the accuracy.

Novel Mitochondria-Targeted Furocoumarin Derivatives as Possible Anti-Cancer Agents

Directory of Open Access Journals (Sweden)

Andrea Mattarei

2018-04-01

Full Text Available Targeting small molecules to appropriate subcellular compartments is a way to increase their selectivity and effectiveness while minimizing side effects. This can be accomplished either by stably incorporating specific “homing” properties into the structure of the active principle, or by attaching to it a targeting moiety via a labile linker, i.e., by producing a “targeting pro-drug.” Mitochondria are a recognized therapeutic target in oncology, and blocking the population of the potassium channel Kv1.3 residing in the inner mitochondrial membrane (mtKv1.3 has been shown to cause apoptosis of cancerous cells expressing it. These concepts have led us to devise novel, mitochondria-targeted, membrane-permeant drug candidates containing the furocoumarin (psoralenic ring system and the triphenylphosphonium (TPP lipophilic cation. The strategy has proven effective in various cancer models, including pancreatic ductal adenocarcinoma, melanoma, and glioblastoma, stimulating us to devise further novel molecules to extend and diversify the range of available drugs of this type. New compounds were synthesized and tested in vitro; one of them—a prodrug in which the coumarinic moiety and the TPP group are linked by a bridge comprising a labile carbonate bond system—proved quite effective in in vitro cytotoxicity assays. Selective death induction is attributed to inhibition of mtKv1.3. This results in oxidative stress, which is fatal for the already-stressed malignant cells. This compound may thus be a candidate drug for the mtKv1.3-targeting therapeutic approach.

Improvement of Meloxicam Solubility Using a β-Cyclodextrin Complex Prepared via the Kneading Method and Incorporated into an Orally Disintegrating Tablet

Directory of Open Access Journals (Sweden)

Ahmad Ainurofiq

2016-09-01

Conclusion: Incorporation of the MEL/β-CD complex during ODT formulation using the QbD approach serves as a model for ODT product development, with optimal product performance based on the specification of quality target product profiles. To understand more specific phenomena, one point in the middle of the design for each factor should be added to more powerfully estimate this effect and avoid the lack of estimate due to an inadequate equation.

An open workflow to generate “MS Ready” structures and improve non-targeted mass spectrometry (ACS Fall 1 of 3)

Science.gov (United States)

High-throughput non-targeted analyses (NTA) rely on chemical reference databases for tentative identification of observed chemical features. Many of these databases and online resources incorporate chemical structure data not in a form that is readily observed by mass spectromet...

Premature drug release of polymeric micelles and its effects on tumor targeting.

Science.gov (United States)

Miller, Tobias; Breyer, Sandra; van Colen, Gwenaelle; Mier, Walter; Haberkorn, Uwe; Geissler, Simon; Voss, Senta; Weigandt, Markus; Goepferich, Achim

2013-03-10

Based on the enhanced permeability and retention (EPR) effect, nanoparticles are believed to accumulate in tumors. In this conjunction, the stability of drug encapsulation is assumed to be sufficient. For clarification purposes, PEGylated poly-(D,L-lactic acid) (PEG-PDLLA) micelles which incorporated the hydrophobic model drug dechloro-4-iodo-fenofibrate (IFF) were investigated. H2N-PEG-PDLLA was synthesized, coupled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and labeled with 111-indium. From this polymeric species, mixed micelles with H3CO-PEG-PDLLA were prepared which encapsulated the 125-iodine or 131-iodine labeled drug IFF. Bioimaging and biodistribution experiments in healthy and AR42J-tumor bearing mice were carried out to quantify the uptake of the drug and its carrier in single organs. As a result, upon injection of this system, a rapid dissociation of the polymeric carrier and the incorporated drug (system allowed for successful solubilization of the hydrophobic drug by physical incorporation into micelles whereas the tumor targeting properties of the drug delivery system could not be sufficiently shown. Copyright © 2013 Elsevier B.V. All rights reserved.

Context incorporation using context-aware language features

OpenAIRE

Vlachostergiou, Aggeliki; Marandianos, George; Kollias, Stefanos

2017-01-01

This paper investigates the problem of context incorporation into human language systems and particular in Sentiment Analysis (SA) systems. So far, the analysis of how different features, when incorporated into such systems, improve their performance, has been discussed in a number of studies. However, a complete picture of their effectiveness remains unexplored. With this work, we attempt to extend the pool of the context - aware language features at the sentence level and to provide the ...

Multi-Stage System for Automatic Target Recognition

Science.gov (United States)

Chao, Tien-Hsin; Lu, Thomas T.; Ye, David; Edens, Weston; Johnson, Oliver

2010-01-01

A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feedforward back-propagation neural network (NN) is then trained to classify each feature vector and to remove false positives. The system parameter optimizations process has been developed to adapt to various targets and datasets. The objective was to design an efficient computer vision system that can learn to detect multiple targets in large images with unknown backgrounds. Because the target size is small relative to the image size in this problem, there are many regions of the image that could potentially contain the target. A cursory analysis of every region can be computationally efficient, but may yield too many false positives. On the other hand, a detailed analysis of every region can yield better results, but may be computationally inefficient. The multi-stage ATR system was designed to achieve an optimal balance between accuracy and computational efficiency by incorporating both models. The detection stage first identifies potential ROIs where the target may be present by performing a fast Fourier domain OT-MACH filter-based correlation. Because threshold for this stage is chosen with the goal of detecting all true positives, a number of false positives are also detected as ROIs. The verification stage then transforms the regions of interest into feature space, and eliminates false positives using an

Targeting nanoparticles to M cells with non-peptidic ligands for oral vaccination.

Science.gov (United States)

Fievez, Virginie; Plapied, Laurence; des Rieux, Anne; Pourcelle, Vincent; Freichels, Hélène; Wascotte, Valentine; Vanderhaeghen, Marie-Lyse; Jerôme, Christine; Vanderplasschen, Alain; Marchand-Brynaert, Jacqueline; Schneider, Yves-Jacques; Préat, Véronique

2009-09-01

The presence of RGD on nanoparticles allows the targeting of beta1 integrins at the apical surface of human M cells and the enhancement of an immune response after oral immunization. To check the hypothesis that non-peptidic ligands targeting intestinal M cells or APCs would be more efficient for oral immunization than RGD, novel non-peptidic and peptidic analogs (RGD peptidomimitic (RGDp), LDV derivative (LDVd) and LDV peptidomimetic (LDVp)) as well as mannose were grafted on the PEG chain of PCL-PEG and incorporated in PLGA-based nanoparticles. RGD and RGDp significantly increased the transport of nanoparticles across an in vitro model of human M cells as compared to enterocytes. RGD, LDVp, LDVd and mannose enhanced nanoparticle uptake by macrophages in vitro. The intraduodenal immunization with RGDp-, LDVd- or mannose-labeled nanoparticles elicited a higher production of IgG antibodies than the intramuscular injection of free ovalbumin or intraduodenal administration of either non-targeted or RGD-nanoparticles. Targeted formulations were also able to induce a cellular immune response. In conclusion, the in vitro transport of nanoparticles, uptake by macrophages and the immune response were positively influenced by the presence of ligands at the surface of nanoparticles. These targeted-nanoparticles could thus represent a promising delivery system for oral immunization.

Glucan Particles for Macrophage Targeted Delivery of Nanoparticles

Directory of Open Access Journals (Sweden)

Ernesto R. Soto

2012-01-01

Full Text Available Glucan particles (GPs are hollow, porous 2–4 μm microspheres derived from the cell walls of Baker's yeast (Saccharomyces cerevisiae. The 1,3-β-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for macrophage-targeted delivery of soluble payloads (DNA, siRNA, protein, and small molecules encapsulated inside the hollow GPs via core polyplex and layer-by-layer (LbL synthetic strategies. In this communication, we report the incorporation of nanoparticles as cores inside GPs (GP-NP or electrostatically bound to the surface of chemically derivatized GPs (NP-GP. GP nanoparticle formulations benefit from the drug encapsulation properties of NPs and the macrophage-targeting properties of GPs. GP nanoparticle formulations were synthesized using fluorescent anionic polystyrene nanoparticles allowing visualization and quantitation of NP binding and encapsulation. Mesoporous silica nanoparticles (MSNs containing the chemotherapeutic doxorubicin (Dox were bound to cationic GPs. Dox-MSN-GPs efficiently delivered Dox into GP phagocytic cells resulting in enhanced Dox-mediated growth arrest.

A review on target drug delivery: magnetic microspheres

Directory of Open Access Journals (Sweden)

Amit Chandna

2013-01-01

Magnetic microsphere is newer approach in pharmaceutical field. Magnetic microspheres as an alternative to traditional radiation methods which use highly penetrating radiation that is absorbed throughout the body. Its use is limited by toxicity and side effects. The aim of the specific targeting is to enhance the efficiency of drug delivery & at the same time to reduce the toxicity & side effects. This kind of delivery system is very much important which localises the drug to the disease site. In this larger amount of freely circulating drug can be replaced by smaller amount of magnetically targeted drug. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials that are used for magnetic microspheres are chitosan, dextran etc. magnetic microspheres can be prepared from a variety of carrier material. One of the most utilized is serum albumin from human or other appropriate species. Drug release from albumin microspheres can be sustained or controlled by various stabilization procedures generally involving heat or chemical cross-linking of the protein carrier matrix.

Alzheimer’s Disease, Brain Injury, and C.N.S. Nanotherapy in Humans: Sonoporation Augmenting Drug Targeting

Directory of Open Access Journals (Sweden)

Joseph S. D’Arrigo

2017-11-01

Full Text Available Owing to the complexity of neurodegenerative diseases, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted nanoemulsion are available. Versatile small-molecule drug(s targeting multiple pathways of Alzheimer’s disease pathogenesis are known. By incorporating such drug(s into the targeted lipid-coated microbubble/nanoparticle-derived (LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly scavenger receptor class B type I (SR-BI, making it possible for various Alzheimer’s-related cell types to be simultaneously sought for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s include a characteristic lipid-coated microbubble (LCM subpopulation (i.e., a stable LCM suspension; such LCM substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer’s patient.

Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging

Science.gov (United States)

Kuijten, Maayke M. P.; Hannah Degeling, M.; Chen, John W.; Wojtkiewicz, Gregory; Waterman, Peter; Weissleder, Ralph; Azzi, Jamil; Nicolay, Klaas; Tannous, Bakhos A.

2015-11-01

Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging.

Dual peptide conjugation strategy for improved cellular uptake and mitochondria targeting.

Science.gov (United States)

Lin, Ran; Zhang, Pengcheng; Cheetham, Andrew G; Walston, Jeremy; Abadir, Peter; Cui, Honggang

2015-01-21

Mitochondria are critical regulators of cellular function and survival. Delivery of therapeutic and diagnostic agents into mitochondria is a challenging task in modern pharmacology because the molecule to be delivered needs to first overcome the cell membrane barrier and then be able to actively target the intracellular organelle. Current strategy of conjugating either a cell penetrating peptide (CPP) or a subcellular targeting sequence to the molecule of interest only has limited success. We report here a dual peptide conjugation strategy to achieve effective delivery of a non-membrane-penetrating dye 5-carboxyfluorescein (5-FAM) into mitochondria through the incorporation of both a mitochondrial targeting sequence (MTS) and a CPP into one conjugated molecule. Notably, circular dichroism studies reveal that the combined use of α-helix and PPII-like secondary structures has an unexpected, synergistic contribution to the internalization of the conjugate. Our results suggest that although the use of positively charged MTS peptide allows for improved targeting of mitochondria, with MTS alone it showed poor cellular uptake. With further covalent linkage of the MTS-5-FAM conjugate to a CPP sequence (R8), the dually conjugated molecule was found to show both improved cellular uptake and effective mitochondria targeting. We believe these results offer important insight into the rational design of peptide conjugates for intracellular delivery.

Incorporation of Uranium into Hematite during Crystallization from Ferrihydrite

Science.gov (United States)

2014-01-01

Ferrihydrite was exposed to U(VI)-containing cement leachate (pH 10.5) and aged to induce crystallization of hematite. A combination of chemical extractions, TEM, and XAS techniques provided the first evidence that adsorbed U(VI) (≈3000 ppm) was incorporated into hematite during ferrihydrite aggregation and the early stages of crystallization, with continued uptake occurring during hematite ripening. Analysis of EXAFS and XANES data indicated that the U(VI) was incorporated into a distorted, octahedrally coordinated site replacing Fe(III). Fitting of the EXAFS showed the uranyl bonds lengthened from 1.81 to 1.87 Å, in contrast to previous studies that have suggested that the uranyl bond is lost altogether upon incorporation into hematite. The results of this study both provide a new mechanistic understanding of uranium incorporation into hematite and define the nature of the bonding environment of uranium within the mineral structure. Immobilization of U(VI) by incorporation into hematite has clear and important implications for limiting uranium migration in natural and engineered environments. PMID:24580024

Genetic incorporation of the protein transduction domain of Tat into Ad5 fiber enhances gene transfer efficacy

Directory of Open Access Journals (Sweden)

Siegal Gene P

2007-10-01

Full Text Available Abstract Background Human adenovirus serotype 5 (Ad5 has been widely explored as a gene delivery vector for a variety of diseases. Many target cells, however, express low levels of Ad5 native receptor, the Coxsackie-Adenovirus Receptor (CAR, and thus are resistant to Ad5 infection. The Protein Transduction Domain of the HIV Tat protein, namely PTDtat, has been shown to mediate protein transduction in a wide range of cells. We hypothesize that re-targeting Ad5 vector via the PTDtat motif would improve the efficacy of Ad5-mediated gene delivery. Results In this study, we genetically incorporated the PTDtat motif into the knob domain of Ad5 fiber, and rescued the resultant viral vector, Ad5.PTDtat. Our data showed the modification did not interfere with Ad5 binding to its native receptor CAR, suggesting Ad5 infection via the CAR pathway is retained. In addition, we found that Ad5.PTDtat exhibited enhanced gene transfer efficacy in all of the cell lines that we have tested, which included both low-CAR and high-CAR decorated cells. Competitive inhibition assays suggested the enhanced infectivity of Ad5.PTDtat was mediated by binding of the positively charged PTDtat peptide to the negatively charged epitopes on the cells' surface. Furthermore, we investigated in vivo gene delivery efficacy of Ad5.PTDtat using subcutaneous tumor models established with U118MG glioma cells, and found that Ad5.PTDtat exhibited enhanced gene transfer efficacy compared to unmodified Ad5 vector as analyzed by a non-invasive fluorescence imaging technique. Conclusion Genetic incorporation of the PTDtat motif into Ad5 fiber allowed Ad5 vectors to infect cells via an alternative PTDtat targeting motif while retaining the native CAR-mediated infection pathway. The enhanced infectivity was demonstrated in both cultured cells and in in vivo tumor models. Taken together, our study identifies a novel tropism expanded Ad5 vector that may be useful for clinical gene therapy

Investigating membrane-bound Argonaute functions in Arabidopsis

DEFF Research Database (Denmark)

Barghetti, Andrea

and how AGO1 membrane recruitment is mediated as well as its functional importance remain poorly characterized. Isoprenoid biogenesis was previously found to be required for both AGO1 activity and membrane association, but the mechanistic connection between the two pathways was not discovered. Since....... The key effectors of sRNA-guided gene regulation are ARGONAUTE (AGO) proteins. A group of Heat Shock Proteins of the HSP70/HSP90 chaperone machinery mediates the process, termed loading, that allow the functional association of sRNA with AGOs. Upon loading, Argonautes regulate complementary mRNA targets...... with the rough endoplasmic reticulum (rER). Membranelocalized argonaute functions include translational repression, production of secondary phased small interfering RNA (siRNA) and autophagy-mediated turnover. However proteins interacting with AGO1 specifically on membrane fractions have not been identified...

Genetic incorporation of recycled unnatural amino acids.

Science.gov (United States)

Ko, Wooseok; Kim, Sanggil; Jo, Kyubong; Lee, Hyun Soo

2016-02-01

The genetic incorporation of unnatural amino acids (UAAs) into proteins has been a useful tool for protein engineering. However, most UAAs are expensive, and the method requires a high concentration of UAAs, which has been a drawback of the technology, especially for large-scale applications. To address this problem, a method to recycle cultured UAAs was developed. The method is based on recycling a culture medium containing the UAA, in which some of essential nutrients were resupplemented after each culture cycle, and induction of protein expression was controlled with glucose. Under optimal conditions, five UAAs were recycled for up to seven rounds of expression without a decrease in expression level, cell density, or incorporation fidelity. This method can generally be applied to other UAAs; therefore, it is useful for reducing the cost of UAAs for genetic incorporation and helpful for expanding the use of the technology to industrial applications.

Incorporation of photosenzitizer hypericin into synthetic lipid-based nano-particles for drug delivery and large unilamellar vesicles with different content of cholesterol

Science.gov (United States)

Joniova, Jaroslava; Blascakova, Ludmila; Jancura, Daniel; Nadova, Zuzana; Sureau, Franck; Miskovsky, Pavol

2014-08-01

Low-density lipoproteins (LDL) and high-density lipoproteins (HDL) are attractive natural occurring vehicles for drug delivery and targeting to cancer tissues. The capacity of both types of the lipoproteins to bind hydrophobic drugs and their functionality as drug carriers have been examined in several studies and it has been also shown that mixing of anticancer drugs with LDL or HDL before administration led to an increase of cytotoxic effects of the drugs in the comparison when the drugs were administered alone. However, a difficult isolation of the lipoproteins in large quantity from a biological organism as well as a variability of the composition and size of these molecules makes practical application of LDL and HDL as drug delivery systems quite complicated. Synthetic LDL and HDL and large unilamellar vesicles (LUV) are potentially suitable candidates to substitute the native lipoproteins for targeted and effective drug delivery. In this work, we have studied process of an association of potent photosensitizer hypericin (Hyp) with synthetic lipid-based nano-particles (sLNP) and large unilamellar vesicles (LUV) containing various amount of cholesterol. Cholesterol is one of the main components of both LDL and HDL particles and its presence in biological membranes is known to be a determining factor for membrane properties. It was found that the behavior of Hyp incorporation into sLNP particles with diameter ca ~ 90 nm is qualitatively very similar to that of Hyp incorporation into LDL (diameter ca. 22 nm) and these particles are able to enter U-87 MG cells by endocytosis. The presence of cholesterol in LUV influences the capacity of these vesicles to incorporate Hyp into their structure.

Incorporating Twitter, Instagram, and Facebook in Economics Classrooms

Science.gov (United States)

Al-Bahrani, Abdullah; Patel, Darshak

2015-01-01

Social media is one of the most current and dynamic developments in education. In general, the field of economics has lagged behind other disciplines in incorporating technologies in the classroom. In this article, the authors provide a guide for economics educators on how to incorporate Twitter, Instagram, and Facebook inside and outside of the…

Neutronics and radiation field studies for the RIA fragmentation target area

Energy Technology Data Exchange (ETDEWEB)

Reyes, Susana [Lawrence Livermore National Laboratory, P.O. Box 808, L-446, Livermore, CA 94550 (United States)]. E-mail: reyes20@llnl.gov; Boles, Jason L. [Lawrence Livermore National Laboratory, P.O. Box 808, L-446, Livermore, CA 94550 (United States); Ahle, Larry E. [Lawrence Livermore National Laboratory, P.O. Box 808, L-446, Livermore, CA 94550 (United States); Stein, Werner [Lawrence Livermore National Laboratory, P.O. Box 808, L-446, Livermore, CA 94550 (United States)

2006-06-23

Neutronics simulations and activation evaluations are currently in progress as part of the pre-conceptual research and development effort for the Rare Isotope Accelerator (RIA). The RIA project involves generating heavy element ion beams with powers up to 400 kw for use in a fragmentation target line to produce selected ion beams for physics research experiments. Designing a fragmentation beam dump for RIA is one of the most critical challenges for such a facility. Here, we present the results from neutronics and radiation field assessments for various beam dump concepts that can meet requirements for the RIA fragmentation line. Preliminary results from heavy ion transport including radiation damage evaluations for the RIA fragmentation beam dump are also presented. Initial neutronics and activation studies will be incorporated with other target area considerations to identify important challenges and explore possible solutions.

Neutronics and radiation field studies for the RIA fragmentation target area

Science.gov (United States)

Reyes, Susana; Boles, Jason L.; Ahle, Larry E.; Stein, Werner

2006-06-01

Neutronics simulations and activation evaluations are currently in progress as part of the pre-conceptual research and development effort for the Rare Isotope Accelerator (RIA). The RIA project involves generating heavy element ion beams with powers up to 400 kW for use in a fragmentation target line to produce selected ion beams for physics research experiments. Designing a fragmentation beam dump for RIA is one of the most critical challenges for such a facility. Here, we present the results from neutronics and radiation field assessments for various beam dump concepts that can meet requirements for the RIA fragmentation line. Preliminary results from heavy ion transport including radiation damage evaluations for the RIA fragmentation beam dump are also presented. Initial neutronics and activation studies will be incorporated with other target area considerations to identify important challenges and explore possible solutions.

Metal doped fluorocarbon polymer films prepared by plasma polymerization using an RF planar magnetron target

International Nuclear Information System (INIS)

Biederman, H.; Holland, L.

1983-01-01

Fluorocarbon films have been prepared by plasma polymerization of CF 4 using an RF planar magnetron with an aluminium target. More than one order of magnitude higher deposition rate has been achieved in comparison with an r.f. diode system operated under similar conditions of monomer pressure and flow rate and power input. A glow discharge in a CF 4 [25%]-argon[75%] mixture was used to incorporate aluminium from a target electrode into the polymer films. The foregoing mixture and another based on CF 4 [87%]-argon[13%] were used in the RF discharge with a copper target. Some experiments with a gold target and pure CF 4 as the inlet gas were also made. The film structure was examined by SEM and TEM and characteristic micrographs are presented here. The composition of the films was estimated from an EAS study. The sheet resistivity of the metal/polymer film complexes was determined. (orig.)

Metal doped fluorocarbon polymer films prepared by plasma polymerization using an RF planar magnetron target

Energy Technology Data Exchange (ETDEWEB)

Biederman, H.; Holland, L. (Sussex Univ., Brighton (UK). Lab. for Plasma Materials Processing)

1983-07-01

Fluorocarbon films have been prepared by plasma polymerization of CF/sub 4/ using an RF planar magnetron with an aluminium target. More than one order of magnitude higher deposition rate has been achieved in comparison with an R.F. diode system operated under similar conditions of monomer pressure and flow rate and power input. A glow discharge in a CF/sub 4/(25%)-argon(75%) mixture was used to incorporate aluminium from a target electrode into the polymer films. The foregoing mixture and another based on CF/sub 4/(87%)-argon(13%) were used in the RF discharge with a copper target. Some experiments with a gold target and pure CF/sub 4/ as the inlet gas were also made. The film structure was examined by SEM and TEM and characteristic micrographs are presented here. The composition of the films was estimated from an EAS study. The sheet resistivity of the metal/polymer film complexes was determined.

Identification and Expression Analyses of miRNAs from Two Contrasting Flower Color Cultivars of Canna by Deep Sequencing.

Science.gov (United States)

Roy, Sribash; Tripathi, Abhinandan Mani; Yadav, Amrita; Mishra, Parneeta; Nautiyal, Chandra Shekhar

2016-01-01

miRNAs are endogenous small RNA (sRNA) that play critical roles in plant development processes. Canna is an ornamental plant belonging to family Cannaceae. Here, we report for the first time the identification and differential expression of miRNAs in two contrasting flower color cultivars of Canna, Tropical sunrise and Red president. A total of 313 known miRNAs belonging to 78 miRNA families were identified from both the cultivars. Thirty one miRNAs (17 miRNA families) were specific to Tropical sunrise and 43 miRNAs (10 miRNA families) were specific to Red president. Thirty two and 18 putative new miRNAs were identified from Tropical sunrise and Red president, respectively. One hundred and nine miRNAs were differentially expressed in the two cultivars targeting 1343 genes. Among these, 16 miRNAs families targeting 60 genes were involved in flower development related traits and five miRNA families targeting five genes were involved in phenyl propanoid and pigment metabolic processes. We further validated the expression analysis of a few miRNA and their target genes by qRT-PCR. Transcription factors were the major miRNA targets identified. Target validation of a few randomly selected miRNAs by RLM-RACE was performed but was successful with only miR162. These findings will help in understanding flower development processes, particularly the color development in Canna.

Emergence of target waves in paced populations of cyclically competing species

Energy Technology Data Exchange (ETDEWEB)

Jiang Luoluo; Zhou Tao; Wang Binghong [Department of Modern Physics, University of Science and Technology of China, Hefei 230026 (China); Perc, Matjaz [Department of Physics, Faculty of Natural Sciences and Mathematics, University of Maribor, Koroska cesta 160, SI-2000 Maribor (Slovenia); Huang Xin [Department of Physics, University of Science and Technology of China, Hefei 230026 (China)], E-mail: jiangluo@mail.ustc.edu.cn, E-mail: zhutou@ustc.edu, E-mail: matjaz.perc@uni-mb.si, E-mail: bhwang@ustc.edu.cn

2009-10-15

We investigate the emergence of target waves in a cyclic predator-prey model incorporating a periodic current of the three competing species in a small area situated at the center of a square lattice. The periodic current acts as a pacemaker, trying to impose its rhythm on the overall spatiotemporal evolution of the three species. We show that the pacemaker is able to nucleate target waves that eventually spread across the whole population, whereby three routes leading to this phenomenon can be distinguished depending on the mobility of the three species and the oscillation period of the localized current. First, target waves can emerge due to the synchronization between the periodic current and oscillations of the density of the three species on the spatial grid. The second route is similar to the first, the difference being that the synchronization sets in only intermittently. Finally, the third route toward target waves is realized when the frequency of the pacemaker is much higher than that characterizing the oscillations of the overall density of the three species. By considering the mobility and frequency of the current as variable parameters, we thus provide insights into the mechanisms of pattern formation resulting from the interplay between local and global dynamics in systems governed by cyclically competing species.

A moving target for accelerated charged particle induced X-ray measurement

International Nuclear Information System (INIS)

Chuang, L.S.; Shima, K.; Ebihara, H.; Seki, R.; Mikumo, T.

1980-01-01

To attain good reproducibility as well as to enable an absolute determination in the measurement of X-ray fluorescences, resulting from bombardment of a heterogeneous sample by accelerated charged particles, a moving-target mechanism incorporating an electronic remote control system has been devised. The system is designed to scan the whole sample area with a chosen constant linear speed, by a fixed particle beam with a cross-sectional area a small fraction of that of the sample. Using 16 MeV protons and 40 MeV oxygen-ion beams, test runs of this system showed that the attempted objectives are attainable with good accuracies: reproducibility of the data for a given target is better than 3%, the linearity of the calibration curve is in good agreement, within the weighing errors of the standard elements and the uncertainty due to beam current fluctuation, with the expected values, and the results of absolute determinations using both metal foils and heterogeneous powder samples are in good agreement with accepted results using different methods. Detailed accounts of the moving-target system, and the test for reproducibility and linearity are presented. An absolute determination of the quantities related to accelerated charged-particle induced X-ray fluorescence (PIXE) using the moving target is presented for samples in different forms. (orig./HP)

Transtuzumab-conjugated liposome-coated fluorscent magnetic namoparticles to target breast cancer

Energy Technology Data Exchange (ETDEWEB)

Jang, Mi Jung; Lee, Hak Jong; Hwang, Sung Il; Yun, Bo La; Kim, Sun Mi [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Yoon, Young Il; Kwon, Yong Soo [Nanoimaging and Therapy Research Center, Institute of Nanoconvergence, Advanced Institutes of Convergence Technology, Seoul National University, Suwon (Korea, Republic of); Yoon, Tae Jong [NanoBio Materials Chemistry Lab., Dept. of Applied Bioscience, CHA University, Pocheon (Korea, Republic of)

2014-08-15

To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNPm-SiO{sub 2}]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNPm-SiO{sub 2}]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer. The physiochemical characteristics of Lipo[MNPm-SiO{sub 2}] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNPm-SiO{sub 2}] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin)-conjugated Lipo[MNPm-SiO{sub 2}] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging. We obtained uniformly-sized and evenly distributed Lipo[MNPm-SiO{sub 2}] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNPm-SiO{sub 2}] was observed by in vitro fluorescence and MR imaging. Trastuzumab-conjugated Lipo[MNPm-SiO{sub 2}] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.

Predicting drug-target interactions using restricted Boltzmann machines.

Science.gov (United States)

Wang, Yuhao; Zeng, Jianyang

2013-07-01

In silico prediction of drug-target interactions plays an important role toward identifying and developing new uses of existing or abandoned drugs. Network-based approaches have recently become a popular tool for discovering new drug-target interactions (DTIs). Unfortunately, most of these network-based approaches can only predict binary interactions between drugs and targets, and information about different types of interactions has not been well exploited for DTI prediction in previous studies. On the other hand, incorporating additional information about drug-target relationships or drug modes of action can improve prediction of DTIs. Furthermore, the predicted types of DTIs can broaden our understanding about the molecular basis of drug action. We propose a first machine learning approach to integrate multiple types of DTIs and predict unknown drug-target relationships or drug modes of action. We cast the new DTI prediction problem into a two-layer graphical model, called restricted Boltzmann machine, and apply a practical learning algorithm to train our model and make predictions. Tests on two public databases show that our restricted Boltzmann machine model can effectively capture the latent features of a DTI network and achieve excellent performance on predicting different types of DTIs, with the area under precision-recall curve up to 89.6. In addition, we demonstrate that integrating multiple types of DTIs can significantly outperform other predictions either by simply mixing multiple types of interactions without distinction or using only a single interaction type. Further tests show that our approach can infer a high fraction of novel DTIs that has been validated by known experiments in the literature or other databases. These results indicate that our approach can have highly practical relevance to DTI prediction and drug repositioning, and hence advance the drug discovery process. Software and datasets are available on request. Supplementary data are

Incorporating travel time reliability into the Highway Capacity Manual.

Science.gov (United States)

2014-01-01

This final report documents the activities performed during SHRP 2 Reliability Project L08: Incorporating Travel Time Reliability into the Highway Capacity Manual. It serves as a supplement to the proposed chapters for incorporating travel time relia...

Effect of an insecticide on growth and metabolism of some non-target soil micro-organisms

International Nuclear Information System (INIS)

Balasubramanian, A.; Nilakantan, Gita

1975-01-01

Aldicarb, a systemic insecticide, enhanced the growth of Rhizobium japonicum in vitro at 1 ppm concentration but inhibited it at 5 ppm level. The cell yields of Azotobacter chroococcum and Pseudomonas solanacearum were reduced by both the concentrations of the chemical. 1 and 5 ppm levels of the insecticide the incorporation of 14 C-glucose by R. japonicum, but it was stimulated in the case of R. chroococcum. In the case of P. solanacearum, however, 1 ppm level of the insecticide enhanced the incorporation of the label. Uptake of 32 P-di-potassium hydrogen phosphate by the cells was also significantly reduced indicating that the metabolic activities of these non-target soil micro-organisms are altered by the insecticide treatment. (author)

Incorporating ecosystem services into environmental management of deep-seabed mining

Science.gov (United States)

Le, Jennifer T.; Levin, Lisa A.; Carson, Richard T.

2017-03-01

Accelerated exploration of minerals in the deep sea over the past decade has raised the likelihood that commercial mining of the deep seabed will commence in the near future. Environmental concerns create a growing urgency for development of environmental regulations under commercial exploitation. Here, we consider an ecosystem services approach to the environmental policy and management of deep-sea mineral resources. Ecosystem services link the environment and human well-being, and can help improve sustainability and stewardship of the deep sea by providing a quantitative basis for decision-making. This paper briefly reviews ecosystem services provided by habitats targeted for deep-seabed mining (hydrothermal vents, seamounts, nodule provinces, and phosphate-rich margins), and presents practical steps to incorporate ecosystem services into deep-seabed mining regulation. The linkages and translation between ecosystem structure, ecological function (including supporting services), and ecosystem services are highlighted as generating human benefits. We consider criteria for identifying which ecosystem services are vulnerable to potential mining impacts, the role of ecological functions in providing ecosystem services, development of ecosystem service indicators, valuation of ecosystem services, and implementation of ecosystem services concepts. The first three steps put ecosystem services into a deep-seabed mining context; the last two steps help to incorporate ecosystem services into a management and decision-making framework. Phases of environmental planning discussed in the context of ecosystem services include conducting strategic environmental assessments, collecting baseline data, monitoring, establishing marine protected areas, assessing cumulative impacts, identifying thresholds and triggers, and creating an environmental damage compensation regime. We also identify knowledge gaps that need to be addressed in order to operationalize ecosystem services

[Target volume margins for lung cancer: internal target volume/clinical target volume].

Science.gov (United States)

Jouin, A; Pourel, N

2013-10-01

The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. Copyright © 2013. Published by Elsevier SAS.

Improving small RNA-seq by using a synthetic spike-in set for size-range quality control together with a set for data normalization.

Science.gov (United States)

Locati, Mauro D; Terpstra, Inez; de Leeuw, Wim C; Kuzak, Mateusz; Rauwerda, Han; Ensink, Wim A; van Leeuwen, Selina; Nehrdich, Ulrike; Spaink, Herman P; Jonker, Martijs J; Breit, Timo M; Dekker, Rob J

2015-08-18

There is an increasing interest in complementing RNA-seq experiments with small-RNA (sRNA) expression data to obtain a comprehensive view of a transcriptome. Currently, two main experimental challenges concerning sRNA-seq exist: how to check the size distribution of isolated sRNAs, given the sensitive size-selection steps in the protocol; and how to normalize data between samples, given the low complexity of sRNA types. We here present two separate sets of synthetic RNA spike-ins for monitoring size-selection and for performing data normalization in sRNA-seq. The size-range quality control (SRQC) spike-in set, consisting of 11 oligoribonucleotides (10-70 nucleotides), was tested by intentionally altering the size-selection protocol and verified via several comparative experiments. We demonstrate that the SRQC set is useful to reproducibly track down biases in the size-selection in sRNA-seq. The external reference for data-normalization (ERDN) spike-in set, consisting of 19 oligoribonucleotides, was developed for sample-to-sample normalization in differential-expression analysis of sRNA-seq data. Testing and applying the ERDN set showed that it can reproducibly detect differential expression over a dynamic range of 2(18). Hence, biological variation in sRNA composition and content between samples is preserved while technical variation is effectively minimized. Together, both spike-in sets can significantly improve the technical reproducibility of sRNA-seq. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Synthesis and in vitro evaluation of novel isatin- incorporated ...

African Journals Online (AJOL)

incorporated thiadiazole hybrids as potential anti-breast ... Abstract. Purpose: To synthesis and characterize some novel isatin-incorporated ... Results: Compounds 3a, 3c, 3d, 3g and 3j showed anticancer activity in both MTT and SRB assay.

Np Incorporation into Uranyl Alteration Phases: A Quantum Mechanical Approach

International Nuclear Information System (INIS)

L.C. Huller; R.C. Win; U.Ecker

2006-01-01

Neptunium is a major contributor to the long-term radioactivity in a geologic repository for spent nuclear fuel (SNF) due to its long half-life (2.1 million years). The mobility of Np may be decreased by incorporation into the U 6+ phases that form during the corrosion of SNF. The ionic radii of Np (0.089nm) and U (0.087nm) are similar, as is their chemistry. Experimental studies have shown Np can be incorporated into uranyl phases at concentrations of ∼ 100 ppm. The low concentration of Np in the uranyl phases complicates experimental detection and presents a significant challenge for determining the incorporation mechanism. Therefore, we have used quantum mechanical calculations to investigate incorporation mechanisms and evaluate the energetics of Np substituting for U. CASTEP, a density functional theory based code that uses plane waves and pseudo-potentials, was used to calculate optimal H positions, relaxed geometry, and energy of different uranyl phases. The incorporation energy for Np in uranyl alteration phases was calculated for studtite, [(UO 2 )O 2 (H 2 O) 2 ](H 2 ) 2 , and boltwoodite, HK(UO 2 )(SiO 4 )* 1.5(H 2 O). Studtite is the rare case of a stable uranyl hydroxyl-peroxide mineral that forms in the presence of H 2 O 2 from the radiolysis of H 2 O. For studtite, two incorporation mechanisms were evaluated: (1) charge-balanced substitution of Np 5+ and H + for one U 6+ , and (2) direct substitution of Np 6+ for U 6+ . For boltwoodite, the H atomic positions prior to Np incorporation were determined, as well as the Np incorporation mechanisms and the corresponding substitution energies. The preferential incorporation of Np into different structure types of U 6+ minerals was also investigated. Quantum mechanical substitution energies have to be derived at Np concentrations higher than the ones found in experiments or expected in a repository. However, the quantum mechanical results are crucial for subsequent empirical force-field and Monte

Dual-Functional Nanoparticles Targeting CXCR4 and Delivering Antiangiogenic siRNA Ameliorate Liver Fibrosis.

Science.gov (United States)

Liu, Chun-Hung; Chan, Kun-Ming; Chiang, Tsaiyu; Liu, Jia-Yu; Chern, Guann-Gen; Hsu, Fu-Fei; Wu, Yu-Hsuan; Liu, Ya-Chi; Chen, Yunching

2016-07-05

The progression of liver fibrosis, an intrinsic response to chronic liver injury, is associated with hepatic hypoxia, angiogenesis, abnormal inflammation, and significant matrix deposition, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Due to the complex pathogenesis of liver fibrosis, antifibrotic drug development has faced the challenge of efficiently and specifically targeting multiple pathogenic mechanisms. Therefore, CXCR4-targeted nanoparticles (NPs) were formulated to deliver siRNAs against vascular endothelial growth factor (VEGF) into fibrotic livers to block angiogenesis during the progression of liver fibrosis. AMD3100, a CXCR4 antagonist that was incorporated into the NPs, served dual functions: it acted as a targeting moiety and suppressed the progression of fibrosis by inhibiting the proliferation and activation of hepatic stellate cells (HSCs). We demonstrated that CXCR4-targeted NPs could deliver VEGF siRNAs to fibrotic livers, decrease VEGF expression, suppress angiogenesis and normalize the distorted vessels in the fibrotic livers in the carbon tetrachloride (CCl4) induced mouse model. Moreover, blocking SDF-1α/CXCR4 by CXCR4-targeted NPs in combination with VEGF siRNA significantly prevented the progression of liver fibrosis in CCl4-treated mice. In conclusion, the multifunctional CXCR4-targeted NPs delivering VEGF siRNAs provide an effective antifibrotic therapeutic strategy.

SAR Target Recognition via Local Sparse Representation of Multi-Manifold Regularized Low-Rank Approximation

Directory of Open Access Journals (Sweden)

Meiting Yu

2018-02-01

Full Text Available The extraction of a valuable set of features and the design of a discriminative classifier are crucial for target recognition in SAR image. Although various features and classifiers have been proposed over the years, target recognition under extended operating conditions (EOCs is still a challenging problem, e.g., target with configuration variation, different capture orientations, and articulation. To address these problems, this paper presents a new strategy for target recognition. We first propose a low-dimensional representation model via incorporating multi-manifold regularization term into the low-rank matrix factorization framework. Two rules, pairwise similarity and local linearity, are employed for constructing multiple manifold regularization. By alternately optimizing the matrix factorization and manifold selection, the feature representation model can not only acquire the optimal low-rank approximation of original samples, but also capture the intrinsic manifold structure information. Then, to take full advantage of the local structure property of features and further improve the discriminative ability, local sparse representation is proposed for classification. Finally, extensive experiments on moving and stationary target acquisition and recognition (MSTAR database demonstrate the effectiveness of the proposed strategy, including target recognition under EOCs, as well as the capability of small training size.

Proteasomal targeting and minigene repetition improve cell-surface presentation of a transfected, modified melanoma tumour antigen

DEFF Research Database (Denmark)

Rasmussen, A B; Zocca, M-B; Bonefeld, C M

2004-01-01

Melanoma antigen recognized by T cell 1 (MART-1) is regarded as a candidate peptide for vaccination against malignant melanoma, and it is of importance to develop strategies to improve the vaccine-elicited T-cell activation towards MART-1. T-cell activation is, among other determinants, dependent...... on the density of specific major histocompatibility complex-peptide complexes on the surface of the antigen-presenting cell. In this study, we explored the cell-surface presentation of a substituted MART-1 peptide encoded by transfected minigenes. We investigated the potential of proteasomal targeting compared...... to non-proteasomal targeting of the epitope to increase its cell-surface presentation. Furthermore, we explored the potential of incorporating multiple minigenes instead of one to increase cell-surface presentation. We show that both proteasomal targeting and repetition of the minigene increase cell...

Scale invariant SURF detector and automatic clustering segmentation for infrared small targets detection

Science.gov (United States)

Zhang, Haiying; Bai, Jiaojiao; Li, Zhengjie; Liu, Yan; Liu, Kunhong

2017-06-01

The detection and discrimination of infrared small dim targets is a challenge in automatic target recognition (ATR), because there is no salient information of size, shape and texture. Many researchers focus on mining more discriminative information of targets in temporal-spatial. However, such information may not be available with the change of imaging environments, and the targets size and intensity keep changing in different imaging distance. So in this paper, we propose a novel research scheme using density-based clustering and backtracking strategy. In this scheme, the speeded up robust feature (SURF) detector is applied to capture candidate targets in single frame at first. And then, these points are mapped into one frame, so that target traces form a local aggregation pattern. In order to isolate the targets from noises, a newly proposed density-based clustering algorithm, fast search and find of density peak (FSFDP for short), is employed to cluster targets by the spatial intensive distribution. Two important factors of the algorithm, percent and γ , are exploited fully to determine the clustering scale automatically, so as to extract the trace with highest clutter suppression ratio. And at the final step, a backtracking algorithm is designed to detect and discriminate target trace as well as to eliminate clutter. The consistence and continuity of the short-time target trajectory in temporal-spatial is incorporated into the bounding function to speed up the pruning. Compared with several state-of-arts methods, our algorithm is more effective for the dim targets with lower signal-to clutter ratio (SCR). Furthermore, it avoids constructing the candidate target trajectory searching space, so its time complexity is limited to a polynomial level. The extensive experimental results show that it has superior performance in probability of detection (Pd) and false alarm suppressing rate aiming at variety of complex backgrounds.

Small RNA-Sequencing Links Physiological Changes and RdDM Process to Vegetative-to-Floral Transition in Apple

Directory of Open Access Journals (Sweden)

Xinwei Guo

2017-05-01

Full Text Available Transition from vegetative to floral buds is a critical physiological change during flower induction that determines fruit productivity. Small non-coding RNAs (sRNAs including microRNAs (miRNAs and small interfering RNAs (siRNAs are pivotal regulators of plant growth and development. Although the key role of sRNAs in flowering regulation has been well-described in Arabidopsis and some other annual plants, their relevance to vegetative-to-floral transition (hereafter, referred to floral transition in perennial woody trees remains under defined. Here, we performed Illumina sequencing of sRNA libraries prepared from vegetative and floral bud during flower induction of the apple trees. A large number of sRNAs exemplified by 33 previously annotated miRNAs and six novel members display significant differential expression (DE patterns. Notably, most of these DE-miRNAs in floral transition displayed opposite expression changes in reported phase transition in apple trees. Bioinformatics analysis suggests most of the DE-miRNAs targeted transcripts involved in SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL gene regulation, stress responses, and auxin and gibberellin (GA pathways, with further suggestion that there is an inherent link between physiological stress response and metabolism reprogramming during floral transition. We also observed significant changes in 24 nucleotide (nt sRNAs that are hallmarks for RNA-dependent DNA methylation (RdDM pathway, suggestive of the correlation between epigenetic modifications and the floral transition. The study not only provides new insight into our understanding of fundamental mechanism of poorly studied floral transition in apple and other woody plants, but also presents important sRNA resource for future in-depth research in the apple flowering physiology.

A Regulatory Circuit Composed of a Transcription Factor, IscR, and a Regulatory RNA, RyhB, Controls Fe-S Cluster Delivery

Directory of Open Access Journals (Sweden)

Pierre Mandin

2016-09-01

Full Text Available Fe-S clusters are cofactors conserved through all domains of life. Once assembled by dedicated ISC and/or SUF scaffolds, Fe-S clusters are conveyed to their apo-targets via A-type carrier proteins (ATCs. Escherichia coli possesses four such ATCs. ErpA is the only ATC essential under aerobiosis. Recent studies reported a possible regulation of the erpA mRNA by the small RNA (sRNA RyhB, which controls the expression of many genes under iron starvation. Surprisingly, erpA has not been identified in recent transcriptomic analysis of the iron starvation response, thus bringing into question the actual physiological significance of the putative regulation of erpA by RyhB. Using an sRNA library, we show that among 26 sRNAs, only RyhB represses the expression of an erpA-lacZ translational fusion. We further demonstrate that this repression occurs during iron starvation. Using mutational analysis, we show that RyhB base pairs to the erpA mRNA, inducing its disappearance. In addition, IscR, the master regulator of Fe-S homeostasis, represses expression of erpA at the transcriptional level when iron is abundant, but depleting iron from the medium alleviates this repression. The conjunction of transcriptional derepression by IscR and posttranscriptional repression by RyhB under Fe-limiting conditions is best described as an incoherent regulatory circuit. This double regulation allows full expression of erpA at iron concentrations for which Fe-S biogenesis switches from the ISC to the SUF system. We further provide evidence that this regulatory circuit coordinates ATC usage to iron availability.

Transcriptome landscape of Lactococcus lactis reveals many novel RNAs including a small regulatory RNA involved in carbon uptake and metabolism.

Science.gov (United States)

van der Meulen, Sjoerd B; de Jong, Anne; Kok, Jan

2016-01-01

RNA sequencing has revolutionized genome-wide transcriptome analyses, and the identification of non-coding regulatory RNAs in bacteria has thus increased concurrently. Here we reveal the transcriptome map of the lactic acid bacterial paradigm Lactococcus lactis MG1363 by employing differential RNA sequencing (dRNA-seq) and a combination of manual and automated transcriptome mining. This resulted in a high-resolution genome annotation of L. lactis and the identification of 60 cis-encoded antisense RNAs (asRNAs), 186 trans-encoded putative regulatory RNAs (sRNAs) and 134 novel small ORFs. Based on the putative targets of asRNAs, a novel classification is proposed. Several transcription factor DNA binding motifs were identified in the promoter sequences of (a)sRNAs, providing insight in the interplay between lactococcal regulatory RNAs and transcription factors. The presence and lengths of 14 putative sRNAs were experimentally confirmed by differential Northern hybridization, including the abundant RNA 6S that is differentially expressed depending on the available carbon source. For another sRNA, LLMGnc_147, functional analysis revealed that it is involved in carbon uptake and metabolism. L. lactis contains 13% leaderless mRNAs (lmRNAs) that, from an analysis of overrepresentation in GO classes, seem predominantly involved in nucleotide metabolism and DNA/RNA binding. Moreover, an A-rich sequence motif immediately following the start codon was uncovered, which could provide novel insight in the translation of lmRNAs. Altogether, this first experimental genome-wide assessment of the transcriptome landscape of L. lactis and subsequent sRNA studies provide an extensive basis for the investigation of regulatory RNAs in L. lactis and related lactococcal species.

Incorporating parametric uncertainty into population viability analysis models

Science.gov (United States)

McGowan, Conor P.; Runge, Michael C.; Larson, Michael A.

2011-01-01

Uncertainty in parameter estimates from sampling variation or expert judgment can introduce substantial uncertainty into ecological predictions based on those estimates. However, in standard population viability analyses, one of the most widely used tools for managing plant, fish and wildlife populations, parametric uncertainty is often ignored in or discarded from model projections. We present a method for explicitly incorporating this source of uncertainty into population models to fully account for risk in management and decision contexts. Our method involves a two-step simulation process where parametric uncertainty is incorporated into the replication loop of the model and temporal variance is incorporated into the loop for time steps in the model. Using the piping plover, a federally threatened shorebird in the USA and Canada, as an example, we compare abundance projections and extinction probabilities from simulations that exclude and include parametric uncertainty. Although final abundance was very low for all sets of simulations, estimated extinction risk was much greater for the simulation that incorporated parametric uncertainty in the replication loop. Decisions about species conservation (e.g., listing, delisting, and jeopardy) might differ greatly depending on the treatment of parametric uncertainty in population models.

7 CFR 801.12 - Design requirements incorporated by reference.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Design requirements incorporated by reference. 801.12 Section 801.12 Agriculture Regulations of the Department of Agriculture (Continued) GRAIN INSPECTION... OFFICIAL PERFORMANCE REQUIREMENTS FOR GRAIN INSPECTION EQUIPMENT § 801.12 Design requirements incorporated...

The Development of Target-Specific Pose Filter Ensembles To Boost Ligand Enrichment for Structure-Based Virtual Screening.

Science.gov (United States)

Xia, Jie; Hsieh, Jui-Hua; Hu, Huabin; Wu, Song; Wang, Xiang Simon

2017-06-26

Structure-based virtual screening (SBVS) has become an indispensable technique for hit identification at the early stage of drug discovery. However, the accuracy of current scoring functions is not high enough to confer success to every target and thus remains to be improved. Previously, we had developed binary pose filters (PFs) using knowledge derived from the protein-ligand interface of a single X-ray structure of a specific target. This novel approach had been validated as an effective way to improve ligand enrichment. Continuing from it, in the present work we attempted to incorporate knowledge collected from diverse protein-ligand interfaces of multiple crystal structures of the same target to build PF ensembles (PFEs). Toward this end, we first constructed a comprehensive data set to meet the requirements of ensemble modeling and validation. This set contains 10 diverse targets, 118 well-prepared X-ray structures of protein-ligand complexes, and large benchmarking actives/decoys sets. Notably, we designed a unique workflow of two-layer classifiers based on the concept of ensemble learning and applied it to the construction of PFEs for all of the targets. Through extensive benchmarking studies, we demonstrated that (1) coupling PFE with Chemgauss4 significantly improves the early enrichment of Chemgauss4 itself and (2) PFEs show greater consistency in boosting early enrichment and larger overall enrichment than our prior PFs. In addition, we analyzed the pairwise topological similarities among cognate ligands used to construct PFEs and found that it is the higher chemical diversity of the cognate ligands that leads to the improved performance of PFEs. Taken together, the results so far prove that the incorporation of knowledge from diverse protein-ligand interfaces by ensemble modeling is able to enhance the screening competence of SBVS scoring functions.

Target Control in Logical Models Using the Domain of Influence of Nodes.

Science.gov (United States)

Yang, Gang; Gómez Tejeda Zañudo, Jorge; Albert, Réka

2018-01-01

Dynamical models of biomolecular networks are successfully used to understand the mechanisms underlying complex diseases and to design therapeutic strategies. Network control and its special case of target control, is a promising avenue toward developing disease therapies. In target control it is assumed that a small subset of nodes is most relevant to the system's state and the goal is to drive the target nodes into their desired states. An example of target control would be driving a cell to commit to apoptosis (programmed cell death). From the experimental perspective, gene knockout, pharmacological inhibition of proteins, and providing sustained external signals are among practical intervention techniques. We identify methodologies to use the stabilizing effect of sustained interventions for target control in Boolean network models of biomolecular networks. Specifically, we define the domain of influence (DOI) of a node (in a certain state) to be the nodes (and their corresponding states) that will be ultimately stabilized by the sustained state of this node regardless of the initial state of the system. We also define the related concept of the logical domain of influence (LDOI) of a node, and develop an algorithm for its identification using an auxiliary network that incorporates the regulatory logic. This way a solution to the target control problem is a set of nodes whose DOI can cover the desired target node states. We perform greedy randomized adaptive search in node state space to find such solutions. We apply our strategy to in silico biological network models of real systems to demonstrate its effectiveness.

Targeted Sterically Stabilized Phospholipid siRNA Nanomedicine for Hepatic and Renal Fibrosis

Directory of Open Access Journals (Sweden)

Fatima Khaja

2016-01-01

Full Text Available Since its discovery, small interfering RNA (siRNA has been considered a potent tool for modulating gene expression. It has the ability to specifically target proteins via selective degradation of messenger RNA (mRNA not easily accessed by conventional drugs. Hence, RNA interference (RNAi therapeutics have great potential in the treatment of many diseases caused by faulty protein expression such as fibrosis and cancer. However, for clinical application siRNA faces a number of obstacles, such as poor in vivo stability, and off-target effects. Here we developed a unique targeted nanomedicine to tackle current siRNA delivery issues by formulating a biocompatible, biodegradable and relatively inexpensive nanocarrier of sterically stabilized phospholipid nanoparticles (SSLNPs. This nanocarrier is capable of incorporating siRNA in its core through self-association with a novel cationic lipid composed of naturally occuring phospholipids and amino acids. This overall assembly protects and delivers sufficient amounts of siRNA to knockdown over-expressed protein in target cells. The siRNA used in this study, targets connective tissue growth factor (CTGF, an important regulator of fibrosis in both hepatic and renal cells. Furthermore, asialoglycoprotein receptors are targeted by attaching the galactosamine ligand to the nanocarries which enhances the uptake of nanoparticles by hepatocytes and renal tubular epithelial cells, the major producers of CTGF in fibrosis. On animals this innovative nanoconstruct, small interfering RNA in sterically stabilized phospholipid nanoparticles (siRNA-SSLNP, showed favorable pharmacokinetic properties and accumulated mostly in hepatic and renal tissues making siRNA-SSLNP a suitable system for targeting liver and kidney fibrotic diseases.

Therapy for incorporated radionuclides: scope and need

International Nuclear Information System (INIS)

Smith, V.H.

1981-03-01

In the United States the recent termination of funding for research on therapy for incorporated radionuclides has virtually halted progress on improved or new agents and procedures for removing radioactivity from the body. Research was eliminated, but is still needed on new removal agents, improved delivery system, in vitro test systems, and the toxicology of treatments. For many radionuclides, no adequate therapy exists. The relationship between radionuclide removal and reduction in cancer risk is still unanswered. Without proper research support, needed improvements in the treatment for incorporated radionuclides in the US are uncertain

Hepatitis C Virus NS3/4A Protease Inhibitors Incorporating Flexible P2 Quinoxalines Target Drug Resistant Viral Variants.

Science.gov (United States)

Matthew, Ashley N; Zephyr, Jacqueto; Hill, Caitlin J; Jahangir, Muhammad; Newton, Alicia; Petropoulos, Christos J; Huang, Wei; Kurt-Yilmaz, Nese; Schiffer, Celia A; Ali, Akbar

2017-07-13

A substrate envelope-guided design strategy is reported for improving the resistance profile of HCV NS3/4A protease inhibitors. Analogues of 5172-mcP1P3 were designed by incorporating diverse quinoxalines at the P2 position that predominantly interact with the invariant catalytic triad of the protease. Exploration of structure-activity relationships showed that inhibitors with small hydrophobic substituents at the 3-position of P2 quinoxaline maintain better potency against drug resistant variants, likely due to reduced interactions with residues in the S2 subsite. In contrast, inhibitors with larger groups at this position were highly susceptible to mutations at Arg155, Ala156, and Asp168. Excitingly, several inhibitors exhibited exceptional potency profiles with EC 50 values ≤5 nM against major drug resistant HCV variants. These findings support that inhibitors designed to interact with evolutionarily constrained regions of the protease, while avoiding interactions with residues not essential for substrate recognition, are less likely to be susceptible to drug resistance.

EFFECT OF INCORPORATING EXPANDED POLYSTYRENE ...

African Journals Online (AJOL)

2012-11-03

Nov 3, 2012 ... Incorporating expanded polystyrene granules in concrete matrix can produce lightweight polystyrene aggregate concrete of ... structure. [1] reported that the standard workability tests are not suitable for the polystyrene aggregate concrete since they are sensitive to the unit weight of concrete. [2] made ...

75 FR 17737 - Industrial Economics, Incorporated; Transfer of Data

Science.gov (United States)

2010-04-07

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2010-0194; FRL-8820-2] Industrial Economics... (CBI) by the submitter, will be transferred to Industrial Economics, Incorporated in accordance with 40 CFR 2.307(h)(3) and 2.308(i)(2). Industrial Economics, Incorporated has been awarded multiple...

Role of Glycol Chitosan-incorporated Ursolic Acid Nanoparticles in ...

African Journals Online (AJOL)

Purpose: To investigate the effect of ursolic acid (UA)-incorporated glycol chitosan (GC) nanoparticles on inhibition of human osteosarcoma. Methods: U2OS and Saos-2 osteosarcoma cells were transfected with ursolic acid (UA) incorporated glycol chitosan (GC) nanoparticles. Ultraviolet (UV) spectrophotometry was used ...

Aluminum-doped Zn O polycrystalline films prepared by co-sputtering of a Zn O-Al target

Energy Technology Data Exchange (ETDEWEB)

Becerril, M.; Silva L, H.; Guillen C, A.; Zelaya A, O. [Instituto Politecnico Nacional, Centro de Investigacion y de Estudios Avanzados, Departamento de Fisica, Apdo. Postal 14-740, 07000 Mexico D. F. (Mexico)

2014-07-01

Aluminum-doped Zinc oxide polycrystalline thin films (Azo) were grown on 7059 Corning glass substrates at room temperature by co-sputtering from a Zn O-Al target. The target was designed as follows, high purity elemental Aluminum was evaporated onto a Zn O target covering small areas. The structural, optical and electrical properties were analyzed as a function of Al content. The Al doped Zn O polycrystalline films showed an n-type conductivity. It was found that the electrical resistivity drops and the carrier concentration increases as a consequence of Al incorporation within the Zn O lattice. In both cases, the changes are of several orders of magnitude. From the results, we conclude that, using these Zn O-Al targets, n-type Al doped Zn O polycrystalline films with high transmittance and low resistivity can be obtained. The crystalline structure of the films was determined by X-ray diffraction. Atomic Force Microscopy images were obtained with an Auto probe C P (Veeco Metrology Group) Microscope. (Author)

Formation of two ripple modes on Si by ion erosion with simultaneous Fe incorporation

International Nuclear Information System (INIS)

Cornejo, Marina; Ziberi, Bashkim; Meinecke, Christoph; Frost, Frank

2011-01-01

This report focuses on the self organized nanostructure formation on Si (0 0 1) by erosion with low energy Kr + ions with simultaneous incorporation of metallic atoms, in particular Fe. The incorporation of Fe is thought to play an important role in the formation of some features. In the experimental set-up used here the Fe atoms come from the sputtering of a cylindrical stainless steel target situated between the source and the sample holder. It is demonstrated how the Fe flux can be regulated by operational parameters of the ion source. It is shown that two different ripple modes, one perpendicular to the ion beam projection on the surface and the other parallel, were formed at near normal incidence (α = 20 o ) with ion energy between 300 eV and 2000 eV and a fluence of 6.7 x 10 18 cm -2 . The perpendicular mode ripples dominated the topography when E ion = 2000 eV, while the parallel mode ripples were the main features observed when E ion = 300 eV. The correlation of Fe concentration with ion sources parameters and resulting topography is analyzed. It is demonstrated that a certain Fe concentration is necessary for the formation of ripples that are oriented perpendicular to the ion beam and that the Fe concentration alone does not determine the evolving topography.

The Tax oncogene enhances ELL incorporation into p300 and P-TEFb containing protein complexes to activate transcription.

Science.gov (United States)

Fufa, Temesgen D; Byun, Jung S; Wakano, Clay; Fernandez, Alfonso G; Pise-Masison, Cynthia A; Gardner, Kevin

2015-09-11

The eleven-nineteen lysine-rich leukemia protein (ELL) is a key regulator of RNA polymerase II mediated transcription. ELL facilitates RNA polymerase II transcription pause site entry and release by dynamically interacting with p300 and the positive transcription elongation factor b (P-TEFb). In this study, we investigated the role of ELL during the HTLV-1 Tax oncogene induced transactivation. We show that ectopic expression of Tax enhances ELL incorporation into p300 and P-TEFb containing transcriptional complexes and the subsequent recruitment of these complexes to target genes in vivo. Depletion of ELL abrogates Tax induced transactivation of the immediate early genes Fos, Egr2 and NF-kB, suggesting that ELL is an essential cellular cofactor of the Tax oncogene. Thus, our study identifies a novel mechanism of ELL-dependent transactivation of immediate early genes by Tax and provides the rational for further defining the genome-wide targets of Tax and ELL. Published by Elsevier Inc.

Exogenous Gene Integration for Microalgal Cell Transformation Using a Nanowire-Incorporated Microdevice.

Science.gov (United States)

Bae, Sunwoong; Park, Seunghye; Kim, Jung; Choi, Jong Seob; Kim, Kyung Hoon; Kwon, Donguk; Jin, EonSeon; Park, Inkyu; Kim, Do Hyun; Seo, Tae Seok

2015-12-16

Superior green algal cells showing high lipid production and rapid growth rate are considered as an alternative for the next generation green energy resources. To achieve the biomass based energy generation, transformed microalgae with superlative properties should be developed through genetic engineering. Contrary to the normal cells, microalgae have rigid cell walls, so that target gene delivery into cells is challengeable. In this study, we report a ZnO nanowire-incorporated microdevice for a high throughput microalgal transformation. The proposed microdevice was equipped with not only a ZnO nanowire in the microchannel for gene delivery into cells but also a pneumatic polydimethylsiloxane (PDMS) microvalve to modulate the cellular attachment and detachment from the nanowire. As a model, hygromycin B resistance gene cassette (Hyg3) was functionalized on the hydrothermally grown ZnO nanowires through a disulfide bond and released into green algal cells, Chlamydomonas reinhardtii, by reductive cleavage. During Hyg3 gene delivery, a monolithic PDMS membrane was bent down, so that algal cells were pushed down toward ZnO nanowires. The supply of vacuum in the pneumatic line made the PDMS membrane bend up, enabling the gene delivered algal cells to be recovered from the outlet of the microchannel. We successfully confirmed Hyg3 gene integrated in microalgae by amplifying the inserted gene through polymerase chain reaction (PCR) and DNA sequencing. The efficiency of the gene delivery to algal cells using the ZnO nanowire-incorporated microdevice was 6.52 × 10(4)- and 9.66 × 10(4)-fold higher than that of a traditional glass bead beating and electroporation.

Ba incorporation in benthic foraminifera

NARCIS (Netherlands)

de Nooijer, L.J.; Brombacher, Anieke; Mewes, A.; Langer, Gerald; Nehrke, G.; Bijma, Jelle; Reichart, G.J.

2017-01-01

Barium (Ba) incorporated in the calcite of many foraminiferal species is proportional to the concentration of Ba in seawater. Since the open ocean concentration of Ba closely follows seawater alkalinity, foraminiferal Ba ∕ Ca can be used to reconstruct the latter. Alternatively, Ba ∕ Ca from

Heterogeneous Information about the Term Structure of Interest rates, Least-Squares Learning and Optimal Interest Rate Rules for Inflation Forecast Targeting

NARCIS (Netherlands)

Schaling, E.; Eijffinger, S.C.W.; Tesfaselassie, M.F.

2004-01-01

In this paper we incorporate the term structure of interest rates in a standard inflation forecast targeting framework.Learning about the transmission process of monetary policy is introduced by having heterogeneous agents - i.e. the central bank and private agents - who have different information

Drug-target interaction prediction: A Bayesian ranking approach.

Science.gov (United States)

Peska, Ladislav; Buza, Krisztian; Koller, Júlia

2017-12-01

In silico prediction of drug-target interactions (DTI) could provide valuable information and speed-up the process of drug repositioning - finding novel usage for existing drugs. In our work, we focus on machine learning algorithms supporting drug-centric repositioning approach, which aims to find novel usage for existing or abandoned drugs. We aim at proposing a per-drug ranking-based method, which reflects the needs of drug-centric repositioning research better than conventional drug-target prediction approaches. We propose Bayesian Ranking Prediction of Drug-Target Interactions (BRDTI). The method is based on Bayesian Personalized Ranking matrix factorization (BPR) which has been shown to be an excellent approach for various preference learning tasks, however, it has not been used for DTI prediction previously. In order to successfully deal with DTI challenges, we extended BPR by proposing: (i) the incorporation of target bias, (ii) a technique to handle new drugs and (iii) content alignment to take structural similarities of drugs and targets into account. Evaluation on five benchmark datasets shows that BRDTI outperforms several state-of-the-art approaches in terms of per-drug nDCG and AUC. BRDTI results w.r.t. nDCG are 0.929, 0.953, 0.948, 0.897 and 0.690 for G-Protein Coupled Receptors (GPCR), Ion Channels (IC), Nuclear Receptors (NR), Enzymes (E) and Kinase (K) datasets respectively. Additionally, BRDTI significantly outperformed other methods (BLM-NII, WNN-GIP, NetLapRLS and CMF) w.r.t. nDCG in 17 out of 20 cases. Furthermore, BRDTI was also shown to be able to predict novel drug-target interactions not contained in the original datasets. The average recall at top-10 predicted targets for each drug was 0.762, 0.560, 1.000 and 0.404 for GPCR, IC, NR, and E datasets respectively. Based on the evaluation, we can conclude that BRDTI is an appropriate choice for researchers looking for an in silico DTI prediction technique to be used in drug

Statistical inference on censored data for targeted clinical trials under enrichment design.

Science.gov (United States)

Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

2013-01-01

For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

Targeting global protected area expansion for imperiled biodiversity.

Science.gov (United States)

Venter, Oscar; Fuller, Richard A; Segan, Daniel B; Carwardine, Josie; Brooks, Thomas; Butchart, Stuart H M; Di Marco, Moreno; Iwamura, Takuya; Joseph, Liana; O'Grady, Damien; Possingham, Hugh P; Rondinini, Carlo; Smith, Robert J; Venter, Michelle; Watson, James E M

2014-06-01

Governments have agreed to expand the global protected area network from 13% to 17% of the world's land surface by 2020 (Aichi target 11) and to prevent the further loss of known threatened species (Aichi target 12). These targets are interdependent, as protected areas can stem biodiversity loss when strategically located and effectively managed. However, the global protected area estate is currently biased toward locations that are cheap to protect and away from important areas for biodiversity. Here we use data on the distribution of protected areas and threatened terrestrial birds, mammals, and amphibians to assess current and possible future coverage of these species under the convention. We discover that 17% of the 4,118 threatened vertebrates are not found in a single protected area and that fully 85% are not adequately covered (i.e., to a level consistent with their likely persistence). Using systematic conservation planning, we show that expanding protected areas to reach 17% coverage by protecting the cheapest land, even if ecoregionally representative, would increase the number of threatened vertebrates covered by only 6%. However, the nonlinear relationship between the cost of acquiring land and species coverage means that fivefold more threatened vertebrates could be adequately covered for only 1.5 times the cost of the cheapest solution, if cost efficiency and threatened vertebrates are both incorporated into protected area decision making. These results are robust to known errors in the vertebrate range maps. The Convention on Biological Diversity targets may stimulate major expansion of the global protected area estate. If this expansion is to secure a future for imperiled species, new protected areas must be sited more strategically than is presently the case.

Liposomes as potential carrier system for targeted delivery of polyene antibiotics.

Science.gov (United States)

Naik, Suresh R; Desai, Sandhya K; Shah, Priyank D; Wala, Santosh M

2013-09-01

The development of new therapeutic modalities involves the use of drug carrier, such as liposomes, which can modify pharmacokinetic and bio-distribution of drug profile. Polyene antibiotics incorporation into liposomes improves its availability at the site, bio-distribution and therapeutic index mainly through the engulfment of liposomes by circulating monocytes/macrophages and transportation to the site of infection. Polyene antibiotics (AmB, SJA-95, HA-1-92) and other antibiotics (streptomycin, tobramycin, quinolones, anti-tubercular and anti-cancer drugs), liposomal preparations are described with possible advantages from therapeutic efficacy and toxicity point of view. The polyene macrolide antibiotics liposomal preparations proved to be more effective in the treatment of systemic mycosis. The AmB-cyclodextrin derivatives inclusion complex is a major breakthrough in liposomal preparation which can be converted into aqueous phase of liposome. Liposomal drug incorporated preparation has been one of the important areas of research for developing the existing polyene antibiotics into useful chemotherapeutic agents in clinical medicine. In recent past other antibiotics have also been incorporated into liposomes using wide variety of materials, phosphatidylethanolamine derivatives (pegylated liposomes, enzyme sensitive conjugates, fluidosomes of anti-cancer drugs and poly lactic/glycolic acid microspheres for anti-tuberculosis drugs). In addition, attempts were also made to extend the receptor mediated drug targeting and to review some relevant patents.

Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application.

Science.gov (United States)

Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia

2009-06-16

microRNAs (miRNAs) are single-stranded RNA molecules of about 20-23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA.

Drug-target interaction prediction via class imbalance-aware ensemble learning.

Science.gov (United States)

Ezzat, Ali; Wu, Min; Li, Xiao-Li; Kwoh, Chee-Keong

2016-12-22

Multiple computational methods for predicting drug-target interactions have been developed to facilitate the drug discovery process. These methods use available data on known drug-target interactions to train classifiers with the purpose of predicting new undiscovered interactions. However, a key challenge regarding this data that has not yet been addressed by these methods, namely class imbalance, is potentially degrading the prediction performance. Class imbalance can be divided into two sub-problems. Firstly, the number of known interacting drug-target pairs is much smaller than that of non-interacting drug-target pairs. This imbalance ratio between interacting and non-interacting drug-target pairs is referred to as the between-class imbalance. Between-class imbalance degrades prediction performance due to the bias in prediction results towards the majority class (i.e. the non-interacting pairs), leading to more prediction errors in the minority class (i.e. the interacting pairs). Secondly, there are multiple types of drug-target interactions in the data with some types having relatively fewer members (or are less represented) than others. This variation in representation of the different interaction types leads to another kind of imbalance referred to as the within-class imbalance. In within-class imbalance, prediction results are biased towards the better represented interaction types, leading to more prediction errors in the less represented interaction types. We propose an ensemble learning method that incorporates techniques to address the issues of between-class imbalance and within-class imbalance. Experiments show that the proposed method improves results over 4 state-of-the-art methods. In addition, we simulated cases for new drugs and targets to see how our method would perform in predicting their interactions. New drugs and targets are those for which no prior interactions are known. Our method displayed satisfactory prediction performance and was

28 CFR 10.5 - Incorporation of papers previously filed.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Incorporation of papers previously filed... CARRYING ON ACTIVITIES WITHIN THE UNITED STATES Registration Statement § 10.5 Incorporation of papers previously filed. Papers and documents already filed with the Attorney General pursuant to the said act and...

Zero emission targets as long-term global goals for climate protection

International Nuclear Information System (INIS)

Rogelj, Joeri; Riahi, Keywan; Schaeffer, Michiel; Hare, William; Meinshausen, Malte; Knutti, Reto; Alcamo, Joseph

2015-01-01

Recently, assessments have robustly linked stabilization of global-mean temperature rise to the necessity of limiting the total amount of emitted carbon-dioxide (CO 2 ). Halting global warming thus requires virtually zero annual CO 2 emissions at some point. Policymakers have now incorporated this concept in the negotiating text for a new global climate agreement, but confusion remains about concepts like carbon neutrality, climate neutrality, full decarbonization, and net zero carbon or net zero greenhouse gas (GHG) emissions. Here we clarify these concepts, discuss their appropriateness to serve as a long-term global benchmark for achieving temperature targets, and provide a detailed quantification. We find that with current pledges and for a likely (>66%) chance of staying below 2 °C, the scenario literature suggests net zero CO 2 emissions between 2060 and 2070, with net negative CO 2 emissions thereafter. Because of residual non-CO 2 emissions, net zero is always reached later for total GHG emissions than for CO 2 . Net zero emissions targets are a useful focal point for policy, linking a global temperature target and socio-economic pathways to a necessary long-term limit on cumulative CO 2 emissions. (letter)

Radionuclides incorporation in activated natural nanotubes

International Nuclear Information System (INIS)

Silva, Jose Parra

2016-01-01

Natural palygorskite nanotubes show suitable physical and chemical properties and characteristics to be use as potential nanosorbent and immobilization matrix for the concentration and solidification of radionuclides present in nuclear wastes. In the development process of materials with sorption properties for the incorporation and subsequent immobilization of radionuclides, the most important steps are related with the generation of active sites simultaneously to the increase of the specific surface area and suitable heat treatment to producing the structural folding. This study evaluated the determining parameters and conditions for the activation process of the natural palygorskite nanotubes aiming at the sorption of radionuclides in the nanotubes structure and subsequent evaluation of the parameters involve in the structural folding by heat treatments. The optimized results about the maximum sorption capacity of nickel in activated natural nanotubes show that these structures are apt and suitable for incorporation of radionuclides similar to nickel. By this study is verified that the optimization of the acid activation process is fundamental to improve the sorption capacities for specifics radionuclides by activated natural nanotubes. Acid activation condition optimized maintaining structural integrity was able to remove around 33.3 wt.% of magnesium cations, equivalent to 6.30·10 -4 g·mol -1 , increasing in 42.8% the specific surface area and incorporating the same molar concentration of nickel present in the liquid radioactive waste at 80 min. (author)

Sparse regularization for EIT reconstruction incorporating structural information derived from medical imaging.

Science.gov (United States)

Gong, Bo; Schullcke, Benjamin; Krueger-Ziolek, Sabine; Mueller-Lisse, Ullrich; Moeller, Knut

2016-06-01

Electrical impedance tomography (EIT) reconstructs the conductivity distribution of a domain using electrical data on its boundary. This is an ill-posed inverse problem usually solved on a finite element mesh. For this article, a special regularization method incorporating structural information of the targeted domain is proposed and evaluated. Structural information was obtained either from computed tomography images or from preliminary EIT reconstructions by a modified k-means clustering. The proposed regularization method integrates this structural information into the reconstruction as a soft constraint preferring sparsity in group level. A first evaluation with Monte Carlo simulations indicated that the proposed solver is more robust to noise and the resulting images show fewer artifacts. This finding is supported by real data analysis. The structure based regularization has the potential to balance structural a priori information with data driven reconstruction. It is robust to noise, reduces artifacts and produces images that reflect anatomy and are thus easier to interpret for physicians.

Electron and ion beam transport to fusion targets

International Nuclear Information System (INIS)

Freeman, J.R.; Baker, L.; Miller, P.A.; Mix, L.P.; Olsen, J.N.; Poukey, J.W.; Wright, T.P.

1979-01-01

ICF reactors have been proposed which incorporate a gas-filled chamber to reduce x-ray and debris loading of the first wall. Focused beams of either electrons or ions must be transported efficiently for 2-4 m to a centrally located fusion target. Laser-initiated current-carrying plasma discharge channels provide the guiding magnetic field and the charge- and current-neutralizing medium required for beam propagation. Computational studies of plasma channel formation in air using a 1-D MHD model with multigroup radiation diffusion have provided a good comparison with the expansions velocity and time dependent refractivity profile determined by holographic interferometry. Trajectory calculations have identified a beam expansion mechanism which combines with the usual ohmic dissipation to reduce somewhat the transported beam fluence for electrons. Additional trajectory calculations have been performed for both electrons and light ions to predict the limits on the particle current density which can be delivered to a central target by overlapping the many independently-generated beams. Critical features of the use of plasma channels for transport and overlap of charged particle beams are being tested experimentally with up to twelve electron beams from the Proto II accelerator

Effect of a viscoelastic target on the impact response of a flat-nosed projectile

Science.gov (United States)

Liu, Hu; Yang, Jialing; Liu, Hua

2018-02-01

Taylor impact is a widely used strategy in which a flat-nosed projectile is fired onto a rigid anvil directly to determine the dynamic strength of rod specimens. Nowadays, the rigid anvil is often replaced by an output target bar to ensure the accuracy of measurement via recording strain signals in the output bar. For testing the dynamic strength of low-density materials, a low-impedance target bar, which exhibits viscoelastic characteristics is often employed. In this paper, an extended Taylor model is proposed to improve the idealization of treating the target bar as perfectly rigid material in the classic Taylor model, and the viscoelastic effect of the target bar is incorporated. The viscoelastic target bar is depicted by two elastic springs and one dashpot. Based on the plastic shock wave theory in the flat-nosed projectile associated with the viscoelastic wave analysis in the target bar, the viscoelastic effect of the target bar on the impact response of the flat-nosed projectile is investigated. The finite element simulation is also carried out to verify the theoretical model, and good agreement is found. The present theoretical model is also called the Taylor-cylinder Hopkinson impact, which provides a more accurate way to identify the dynamic material parameters. The dynamic responses of the present model are further compared with previous elastic and rigid target bar models. It is found that the viscoelastic effect of the target bar should be taken into consideration in the Taylor-cylinder Hopkinson impact test for low-impedance materials.

Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image-Guided Approaches.

Science.gov (United States)

Huang, Jing; Li, Yuancheng; Orza, Anamaria; Lu, Qiong; Guo, Peng; Wang, Liya; Yang, Lily; Mao, Hui

2016-06-14

With rapid advances in nanomedicine, magnetic nanoparticles (MNPs) have emerged as a promising theranostic tool in biomedical applications, including diagnostic imaging, drug delivery and novel therapeutics. Significant preclinical and clinical research has explored their functionalization, targeted delivery, controllable drug release and image-guided capabilities. To further develop MNPs for theranostic applications and clinical translation in the future, we attempt to provide an overview of the recent advances in the development and application of MNPs for drug delivery, specifically focusing on the topics concerning the importance of biomarker targeting for personalized therapy and the unique magnetic and contrast-enhancing properties of theranostic MNPs that enable image-guided delivery. The common strategies and considerations to produce theranostic MNPs and incorporate payload drugs into MNP carriers are described. The notable examples are presented to demonstrate the advantages of MNPs in specific targeting and delivering under image guidance. Furthermore, current understanding of delivery mechanisms and challenges to achieve efficient therapeutic efficacy or diagnostic capability using MNP-based nanomedicine are discussed.

Functionalized mesoporous silicon for targeted-drug-delivery.

Science.gov (United States)

Tabasi, Ozra; Falamaki, Cavus; Khalaj, Zahra

2012-10-01

The present work concerns a preliminary step in the production of anticancer drug loaded porous silicon (PSi) for targeted-drug-delivery applications. A successful procedure for the covalent attachment of folic acid, polyethylene glycol (PEG) and doxorubicin to hydrophilic mesoporous silicon layers is presented. A systematic approach has been followed to obtain the optimal composition of the N,N'-dicyclohexylcarbodiimide (DCC)/N-hydroxysuccimide (NHS) in dimethylsulfoxide (DMSO) solution for the surface activation process of the undecylenic acid (UD) grafted molecules to take place with minimal undesired byproduct formation. The effect of reactant concentration and kind of solvent (aqueous or DMSO) on the attachment of folic acid to the activated PSi layer has been investigated. The covalent attachment of the doxorubicin molecules to the PSi layer functionalized with folic acid and PEG is discussed. The drug release kinetics as a function of pH has been studied. The functionalized PSi particles show a high cytotoxicity compared to the equivalent amount of free drug. Cell toxicity tests show clearly that the incorporation of folate molecules increases substantially the toxicity of the loaded PSi particles. Accordingly this new functionalized PSi may be considered a proper candidate for targeted drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

Autonomous target tracking of UAVs based on low-power neural network hardware

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Yang, Wei; Jin, Zhanpeng; Thiem, Clare; Wysocki, Bryant; Shen, Dan; Chen, Genshe

2014-05-01

Detecting and identifying targets in unmanned aerial vehicle (UAV) images and videos have been challenging problems due to various types of image distortion. Moreover, the significantly high processing overhead of existing image/video processing techniques and the limited computing resources available on UAVs force most of the processing tasks to be performed by the ground control station (GCS) in an off-line manner. In order to achieve fast and autonomous target identification on UAVs, it is thus imperative to investigate novel processing paradigms that can fulfill the real-time processing requirements, while fitting the size, weight, and power (SWaP) constrained environment. In this paper, we present a new autonomous target identification approach on UAVs, leveraging the emerging neuromorphic hardware which is capable of massively parallel pattern recognition processing and demands only a limited level of power consumption. A proof-of-concept prototype was developed based on a micro-UAV platform (Parrot AR Drone) and the CogniMemTMneural network chip, for processing the video data acquired from a UAV camera on the y. The aim of this study was to demonstrate the feasibility and potential of incorporating emerging neuromorphic hardware into next-generation UAVs and their superior performance and power advantages towards the real-time, autonomous target tracking.

Photophysical studies of zinc phthalocyanine and chloroaluminum phthalocyanine incorporated into liposomes in the presence of additives

Directory of Open Access Journals (Sweden)

S.M.T. Nunes

2004-02-01

Full Text Available The photophysical properties of zinc phthalocyanine (ZnPC and chloroaluminum phthalocyanine (AlPHCl incorporated into liposomes of dimyristoyl phosphatidylcholine in the presence and absence of additives such as cholesterol or cardiolipin were studied by time-resolved fluorescence, laser flash photolysis and steady-state techniques. The absorbance of the drugs changed linearly with drug concentration, at least up to 5.0 µM in homogeneous and heterogeneous media, indicating that aggregation did not occur in these media within this concentration range. The incorporation of the drugs into liposomes increases the dimerization constant by one order of magnitude (for ZnPC, 3.6 x 10(4 to 1.0 x 10(5 M-1 and for AlPHCl, 3.7 x 10(4 to 1.5 x 10(5 M-1, but this feature dose does not rule out the use of this carrier, since the incorporation of these hydrophobic drugs into liposomes permits their systemic administration. Probe location in biological membranes and predominant positions of the phthalocyanines in liposomes were inferred on the basis of their fluorescence and triplet state properties. Both phthalocyanines are preferentially distributed in the internal regions of the liposome bilayer. The additives affect the distribution of these drugs within the liposomes, a fact that controls their delivery when both are used in a biological medium, retarding their release. The addition of the additives to the liposomes increases the internalization of phthalocyanines. The interaction of the drugs with a plasma protein, bovine serum albumin, was examined quantitatively by the fluorescence technique. The results show that when the drugs were incorporated into small unilamellar liposomes, the association with albumin was enhanced when compared with organic media, a fact that should increase the selectivity of tumor targeting by these phthalocyanines (for ZnPC, 0.71 x 10(6 to 1.30 x 10(7 M-1 and for AlPHCl, 4.86 x 10(7 to 3.10 x 10(8 M-1.

Targeted Screening With Combined Age- and Morphology-Based Criteria Enriches Detection of Lynch Syndrome in Endometrial Cancer.

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Lin, Douglas I; Hecht, Jonathan L

2016-06-01

Endometrial cancer is associated with Lynch syndrome in 2% to 6% of cases. Adequate screening may prevent of a second cancer and incident cancers in family members via risk-reducing strategies. The goal of the study was to evaluate the detection rate of Lynch syndrome via a targeted screening approach. In 2009, we incorporated targeted Lynch syndrome screening via immunohistochemistry for MLH1, PMS2, MSH2, and MSH6, followed by MLH1 promoter hypermethylation, in select cases of endometrial carcinoma. Criteria for patient selection included (1) all patients Lynch syndrome. Therefore, targeted screening with combined age and morphology based criteria enriches detection of Lynch syndrome in endometrial cancer. However, the detection rate is lower than the rates from published series that offer universal screening. © The Author(s) 2016.

Dosimetric effects of rotational output variation and x-ray target degradation on helical tomotherapy plans

International Nuclear Information System (INIS)

Staton, Robert J.; Langen, Katja M.; Kupelian, Patrick A.; Meeks, Sanford L.

2009-01-01

In this study, two potential sources of IMRT delivery error have been identified for helical tomotherapy delivery using the HiART system (TomoTherapy, Inc., Madison, WI): Rotational output variation and target degradation. The HiArt system is known to have output variation, typically about ±2%, due to the absence of a dose servo system. On the HiArt system, x-ray target replacement is required approximately every 10-12 months due to target degradation. Near the end of target life, the target thins and causes a decrease in the beam energy and a softening of the beam profile at the lateral edges of the beam. The purpose of this study is to evaluate the dosimetric effects of rotational output variation and target degradation by modeling their effects and incorporating them into recalculated treatment plans for three clinical scenarios: Head and neck, partial breast, and prostate. Models were created to emulate both potential sources of error. For output variation, a model was created using a sine function to match the amplitude (±2%), frequency, and phase of the measured rotational output variation data. A second model with a hypothetical variation of ±7% was also created to represent the largest variation that could exist without violating the allowable dose window in the delivery system. A measured beam profile near the end of target life was used to create a modified beam profile model for the target degradation. These models were then incorporated into the treatment plan by modifying the leaf opening times in the delivery sinogram. A new beam model was also created to mimic the change in beam energy seen near the end of target life. The plans were then calculated using a research version of the PLANNED ADAPTIVE treatment planning software from TomoTherapy, Inc. Three plans were evaluated in this study: Head and neck, partial breast, and prostate. The D 50 of organs at risk, the D 95 for planning target volumes (PTVs), and the local dose difference were used to

Buoyancy-activated cell sorting using targeted biotinylated albumin microbubbles.

Directory of Open Access Journals (Sweden)

Yu-Ren Liou

Full Text Available Cell analysis often requires the isolation of certain cell types. Various isolation methods have been applied to cell sorting, including fluorescence-activated cell sorting and magnetic-activated cell sorting. However, these conventional approaches involve exerting mechanical forces on the cells, thus risking cell damage. In this study we applied a novel isolation method called buoyancy-activated cell sorting, which involves using biotinylated albumin microbubbles (biotin-MBs conjugated with antibodies (i.e., targeted biotin-MBs. Albumin MBs are widely used as contrast agents in ultrasound imaging due to their good biocompatibility and stability. For conjugating antibodies, biotin is conjugated onto the albumin MB shell via covalent bonds and the biotinylated antibodies are conjugated using an avidin-biotin system. The albumin microbubbles had a mean diameter of 2 μm with a polydispersity index of 0.16. For cell separation, the MDA-MB-231 cells are incubated with the targeted biotin-MBs conjugated with anti-CD44 for 10 min, centrifuged at 10 g for 1 min, and then allowed 1 hour at 4 °C for separation. The results indicate that targeted biotin-MBs conjugated with anti-CD44 antibodies can be used to separate MDA-MB-231 breast cancer cells; more than 90% of the cells were collected in the MB layer when the ratio of the MBs to cells was higher than 70:1. Furthermore, we found that the separating efficiency was higher for targeted biotin-MBs than for targeted avidin-incorporated albumin MBs (avidin-MBs, which is the most common way to make targeted albumin MBs. We also demonstrated that the recovery rate of targeted biotin-MBs was up to 88% and the sorting purity was higher than 84% for a a heterogenous cell population containing MDA-MB-231 cells (CD44(+ and MDA-MB-453 cells (CD44-, which are classified as basal-like breast cancer cells and luminal breast cancer cells, respectively. Knowing that the CD44(+ is a commonly used cancer

TH-A-9A-04: Incorporating Liver Functionality in Radiation Therapy Treatment Planning

International Nuclear Information System (INIS)

Wu, V; Epelman, M; Feng, M; Cao, Y; Wang, H; Romeijn, E; Matuszak, M

2014-01-01

Purpose: Liver SBRT patients have both variable pretreatment liver function (e.g., due to degree of cirrhosis and/or prior treatments) and sensitivity to radiation, leading to high variability in potential liver toxicity with similar doses. This work aims to explicitly incorporate liver perfusion into treatment planning to redistribute dose to preserve well-functioning areas without compromising target coverage. Methods: Voxel-based liver perfusion, a measure of functionality, was computed from dynamic contrast-enhanced MRI. Two optimization models with different cost functions subject to the same dose constraints (e.g., minimum target EUD and maximum critical structure EUDs) were compared. The cost functions minimized were EUD (standard model) and functionality-weighted EUD (functional model) to the liver. The resulting treatment plans delivering the same target EUD were compared with respect to their DVHs, their dose wash difference, the average dose delivered to voxels of a particular perfusion level, and change in number of high-/low-functioning voxels receiving a particular dose. Two-dimensional synthetic and three-dimensional clinical examples were studied. Results: The DVHs of all structures of plans from each model were comparable. In contrast, in plans obtained with the functional model, the average dose delivered to high-/low-functioning voxels was lower/higher than in plans obtained with its standard counterpart. The number of high-/low-functioning voxels receiving high/low dose was lower in the plans that considered perfusion in the cost function than in the plans that did not. Redistribution of dose can be observed in the dose wash differences. Conclusion: Liver perfusion can be used during treatment planning potentially to minimize the risk of toxicity during liver SBRT, resulting in better global liver function. The functional model redistributes dose in the standard model from higher to lower functioning voxels, while achieving the same target EUD

Incorporation of Mobile Application (App) Measures Into the Diagnosis of Smartphone Addiction.

Science.gov (United States)

Lin, Yu-Hsuan; Lin, Po-Hsien; Chiang, Chih-Lin; Lee, Yang-Han; Yang, Cheryl C H; Kuo, Terry B J; Lin, Sheng-Hsuan

2017-07-01

Global smartphone expansion has brought about unprecedented addictive behaviors. The current diagnosis of smartphone addiction is based solely on information from clinical interview. This study aimed to incorporate application (app)-recorded data into psychiatric criteria for the diagnosis of smartphone addiction and to examine the predictive ability of the app-recorded data for the diagnosis of smartphone addiction. Smartphone use data of 79 college students were recorded by a newly developed app for 1 month between December 1, 2013, and May 31, 2014. For each participant, psychiatrists made a diagnosis for smartphone addiction based on 2 approaches: (1) only diagnostic interview (standard diagnosis) and (2) both diagnostic interview and app-recorded data (app-incorporated diagnosis). The app-incorporated diagnosis was further used to build app-incorporated diagnostic criteria. In addition, the app-recorded data were pooled as a score to predict smartphone addiction diagnosis. When app-incorporated diagnosis was used as a gold standard for 12 candidate criteria, 7 criteria showed significant accuracy (area under receiver operating characteristic curve [AUC] > 0.7) and were constructed as app-incorporated diagnostic criteria, which demonstrated remarkable accuracy (92.4%) for app-incorporated diagnosis. In addition, both frequency and duration of daily smartphone use significantly predicted app-incorporated diagnosis (AUC = 0.70 for frequency; AUC = 0.72 for duration). The combination of duration, frequency, and frequency trend for 1 month can accurately predict smartphone addiction diagnosis (AUC = 0.79 for app-incorporated diagnosis; AUC = 0.71 for standard diagnosis). The app-incorporated diagnosis, combining both psychiatric interview and app-recorded data, demonstrated substantial accuracy for smartphone addiction diagnosis. In addition, the app-recorded data performed as an accurate screening tool for app-incorporated diagnosis. © Copyright 2017 Physicians

Molecular Targets for Targeted Radionuclide Therapy

International Nuclear Information System (INIS)

Mather, S.J.

2009-01-01

Molecular targeted radionuclide cancer therapy is becoming of increasing importance, especially for disseminated diseases. Systemic chemotherapies often lack selectivity while targeted radionuclide therapy has important advantages as the radioactive cytotoxic unit of the targeting vector is specifically directed to the cancer, sparing normal tissues. The principle strategy to improve cancer selectivity is to couple therapeutic agents to tumour-targeting vectors. In targeted radionuclide therapy (TRT), the cytotoxic portion of the conjugates normally contains a therapeutic radiometal immobilised by a bifunctional chelator. The aim is therefore to use as ligand-targeted therapeutics vectors coupled to Auger-, alpha- and/or beta-emitting radionuclides. An advantage of using radiation instead of chemotherapeutics as the cytotoxic agent is the so called 'crossfire effect'. This allows sterilisation of tumour cells that are not directly targeted due to heterogeneity in target molecule expression or inhomogeneous vector delivery. However, before the targeting ligands can be selected, the target molecule on the tumour has to be selected. It should be uniquely expressed, or at least highly overexpressed, on or in the target cells relative to normal tissues. The target should be easily accessible for ligand delivery and should not be shed or down- regulated after ligand binding. An important property of a receptor (or antigen) is its potential to be internalized upon binding of the ligand. This provides an active uptake mechanism and allows the therapeutic agent to be trapped within the tumour cells. Molecular targets of current interest include: Receptors: G-protein coupled receptors are overexpressed on many major human tumours. The prototype of these receptors are somatostatin receptors which show very high density in neuroendocrine tumours, but there are many other most interesting receptors to be applied for TRT. The targeting ligands for these receptors are

High neutronic efficiency, low current targets for accelerator-based BNCT applications

International Nuclear Information System (INIS)

Powell, J.R.; Ludewig, H.; Todosow, M.

1998-01-01

The neutronic efficiency of target/filters for accelerator-based BNCT applications is measured by the proton current required to achieve a desirable neutron current at the treatment port (10 9 n/cm 2 /s). In this paper the authors describe two possible targeyt/filter concepts wihch minimize the required current. Both concepts are based on the Li-7 (p,n)Be-7 reaction. Targets that operate near the threshold energy generate neutrons that are close tothe desired energy for BNCT treatment. Thus, the filter can be extremely thin (∼ 5 cm iron). However, this approach has an extremely low neutron yield (n/p ∼ 1.0(-6)), thus requiring a high proton current. The proposed solutino is to design a target consisting of multiple extremely thin targets (proton energy loss per target ∼ 10 keV), and re-accelerate the protons between each target. Targets operating at ihgher proton energies (∼ 2.5 MeV) have a much higher yield (n/p ∼ 1.0(-4)). However, at these energies the maximum neutron energy is approximately 800 keV, and thus a neutron filter is required to degrade the average neutron energy to the range of interest for BNCT (10--20 keV). A neutron filter consisting of fluorine compounds and iron has been investigated for this case. Typically a proton current of approximately 5 mA is required to generate the desired neutron current at the treatment port. The efficiency of these filter designs can be further increased by incorporating neutron reflectors that are co-axial with the neutron source. These reflectors are made of materials which have high scattering cross sections in the range 0.1--1.0 MeV

A Microdosimetric-Kinetic Model of Cell Killing by Irradiation from Permanently Incorporated Radionuclides.

Science.gov (United States)

Hawkins, Roland B

2018-01-01

An expression for the surviving fraction of a replicating population of cells exposed to permanently incorporated radionuclide is derived from the microdosimetric-kinetic model. It includes dependency on total implant dose, linear energy transfer (LET), decay rate of the radionuclide, the repair rate of potentially lethal lesions in DNA and the volume doubling time of the target population. This is used to obtain an expression for the biologically effective dose ( BED α / β ) based on the minimum survival achieved by the implant that is equivalent to, and can be compared and combined with, the BED α / β calculated for a fractionated course of radiation treatment. Approximate relationships are presented that are useful in the calculation of BED α / β for alpha- or beta-emitting radionuclides with half-life significantly greater than, or nearly equal to, the approximately 1-h repair half-life of radiation-induced potentially lethal lesions.

Incorporating Argumentation through Forensic Science

Science.gov (United States)

Wheeler, Lindsay B.; Maeng, Jennifer L.; Smetana, Lara K.

2014-01-01

This article outlines how to incorporate argumentation into a forensic science unit using a mock trial. Practical details of the mock trial include: (1) a method of scaffolding students' development of their argument for the trial, (2) a clearly outlined set of expectations for students during the planning and implementation of the mock…

Incorporating Psychological Predictors of Treatment Response into Health Economic Simulation Models: A Case Study in Type 1 Diabetes.

Science.gov (United States)

Kruger, Jen; Pollard, Daniel; Basarir, Hasan; Thokala, Praveen; Cooke, Debbie; Clark, Marie; Bond, Rod; Heller, Simon; Brennan, Alan

2015-10-01

. Health economic modeling has paid limited attention to the effects that patients' psychological characteristics have on the effectiveness of treatments. This case study tests 1) the feasibility of incorporating psychological prediction models of treatment response within an economic model of type 1 diabetes, 2) the potential value of providing treatment to a subgroup of patients, and 3) the cost-effectiveness of providing treatment to a subgroup of responders defined using 5 different algorithms. . Multiple linear regressions were used to investigate relationships between patients' psychological characteristics and treatment effectiveness. Two psychological prediction models were integrated with a patient-level simulation model of type 1 diabetes. Expected value of individualized care analysis was undertaken. Five different algorithms were used to provide treatment to a subgroup of predicted responders. A cost-effectiveness analysis compared using the algorithms to providing treatment to all patients. . The psychological prediction models had low predictive power for treatment effectiveness. Expected value of individualized care results suggested that targeting education at responders could be of value. The cost-effectiveness analysis suggested, for all 5 algorithms, that providing structured education to a subgroup of predicted responders would not be cost-effective. . The psychological prediction models tested did not have sufficient predictive power to make targeting treatment cost-effective. The psychological prediction models are simple linear models of psychological behavior. Collection of data on additional covariates could potentially increase statistical power. . By collecting data on psychological variables before an intervention, we can construct predictive models of treatment response to interventions. These predictive models can be incorporated into health economic models to investigate more complex service delivery and reimbursement strategies. �

[BMIM][PF6] Incorporation Doubles CO2 Selectivity of ZIF-8: Elucidation of Interactions and Their Consequences on Performance.

Science.gov (United States)

Kinik, F Pelin; Altintas, Cigdem; Balci, Volkan; Koyuturk, Burak; Uzun, Alper; Keskin, Seda

2016-11-16

Experiments were combined with atomically detailed simulations and density functional theory (DFT) calculations to understand the effect of incorporation of an ionic liquid (IL), 1-n-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF 6 ]), into a metal organic framework (MOF with a zeolitic imidazolate framework), ZIF-8, on the CO 2 separation performance. The interactions between [BMIM][PF 6 ] and ZIF-8 were examined in deep detail, and their consequences on CO 2 /CH 4 , CO 2 /N 2 , and CH 4 /N 2 separation have been elucidated by using experimental measurements complemented by DFT calculations and atomically detailed simulations. Results suggest that IL-MOF interactions strongly affect the gas affinity of materials at low pressure, whereas available pore volume plays a key role for gas adsorption at high pressures. Direct interactions between IL and MOF lead to at least a doubling of CO 2 /CH 4 and CO 2 /N 2 selectivities of ZIF-8. These results provide opportunities for rational design and development of IL-incorporated MOFs with exceptional selectivity for target gas separation applications.

Lung cancer risk and exposure from incorporated plutonium

International Nuclear Information System (INIS)

Koshurnikova, N.A.; Bolotnikova, M.G.; Il'in, L.A.

1996-01-01

Coefficients of risk of death from lung cancer caused by incorporated plutonium for the personnel of the Mayak plant, working there since its foundation are obtained. Values of mortality from lung cancer are analysed as well as individual incorporated dose per lung assessed from regular measurement of plutonium in the urine and radiometry of autopsy material and from the results of individual photocontrol of external exposure. It was shown that the risk of death from lung cancer caused by external gamma-irradiation is statistically unreliable, whereas that from disease caused by incorporated plutonium is dose-dependent. The risk of death from lung cancer is two times higher for the personnel with increased level of plutonium carriership as against the level stated in ICRP Publication 60. The conclusion is made that hygienic standards for lung exposure should be specified. 11 refs.; 3 figs.; 5 tabs

Fluorometric detection of adenine in target DNA by exciplex formation with fluorescent 8-arylethynylated deoxyguanosine.

Science.gov (United States)

Saito, Yoshio; Kugenuma, Kenji; Tanaka, Makiko; Suzuki, Azusa; Saito, Isao

2012-06-01

We demonstrated an intriguing method to discriminate adenine by incident appearance of an intense new emission via exciplex formation in hybridization of target DNA with newly designed fluorescent 8-arylethynylated deoxyguanosine derivatives. We described the synthesis of such highly electron donating fluorescent guanosine derivatives and their incorporation into DNA oligomers which may be used for the structural study and the fluorometric analysis of nucleic acids. Copyright © 2012 Elsevier Ltd. All rights reserved.

Engineering a Functional Small RNA Negative Autoregulation Network with Model-Guided Design.

Science.gov (United States)

Hu, Chelsea Y; Takahashi, Melissa K; Zhang, Yan; Lucks, Julius B

2018-05-22

RNA regulators are powerful components of the synthetic biology toolbox. Here, we expand the repertoire of synthetic gene networks built from these regulators by constructing a transcriptional negative autoregulation (NAR) network out of small RNAs (sRNAs). NAR network motifs are core motifs of natural genetic networks, and are known for reducing network response time and steady state signal. Here we use cell-free transcription-translation (TX-TL) reactions and a computational model to design and prototype sRNA NAR constructs. Using parameter sensitivity analysis, we design a simple set of experiments that allow us to accurately predict NAR function in TX-TL. We transfer successful network designs into Escherichia coli and show that our sRNA transcriptional network reduces both network response time and steady-state gene expression. This work broadens our ability to construct increasingly sophisticated RNA genetic networks with predictable function.

Incorporation of squalene into rod outer segments

International Nuclear Information System (INIS)

Keller, R.K.; Fliesler, S.J.

1990-01-01

We have reported previously that squalene is the major radiolabeled nonsaponifiable lipid product derived from [ 3 H]acetate in short term incubations of frog retinas. In the present study, we demonstrate that newly synthesized squalene is incorporated into rod outer segments under similar in vitro conditions. We show further that squalene is an endogenous constituent of frog rod outer segment membranes; its concentration is approximately 9.5 nmol/mumol of phospholipid or about 9% of the level of cholesterol. Pulse-chase experiments with radiolabeled precursors revealed no metabolism of outer segment squalene to sterols in up to 20 h of chase. Taken together with our previous absolute rate studies, these results suggest that most, if not all, of the squalene synthesized by the frog retina is transported to rod outer segments. Synthesis of protein is not required for squalene transport since puromycin had no effect on squalene incorporation into outer segments. Conversely, inhibition of isoprenoid synthesis with mevinolin had no effect on the incorporation of opsin into the outer segment. These latter results support the conclusion that the de novo synthesis and subsequent intracellular trafficking of opsin and isoprenoid lipids destined for the outer segment occur via independent mechanisms

Incorporation feasibility of leather residues in bricks

Energy Technology Data Exchange (ETDEWEB)

Aguiar, J.B. [Minho Univ. (Portugal). Civil Engineering Dept.; Valente, A.; Pires, M.J. [Inst. of Development and Innovation Technology of Minho, Braga (Portugal); Tavares, T. [Biological Engineering Dept., Univ. of Minho, Braga (Portugal)

2002-07-01

The footwear industry has strips of leather as one of its by-products. These leather residues, due to their high chromium content, can be regarded as a threat to the environment, particularly if no care is taken with their disposal. With the incorporation of the residues in ceramic products, after trituration, is possible to neutralise the eventual toxicity of chromium. In a laboratory study we produced prismatic bricks using clay from the region and incorporating 1, 3 and 5% (by mass) of leather residues. This corresponds at about 20, 60 and 100% (by apparent volume). The moulds were filled up with paste and, in order to have some compactness, the ceramic paste was compressed with a spatula. After that, it began the process of drying and burning the bricks. They were tested to flexure, compression and leaching. The results showed that the toxicity of chromium disappeared in the bricks. The mechanical tests showed a decrease in strength for the specimens with leather residue. The compressive strength decreases about 22% for 1% of incorporation of leather residue. However, as bricks were lighter and more porous, we can expect that they are better for thermal isolation. (orig.)

Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients.

Science.gov (United States)

de Witte, Wilhelmus E A; Wong, Yin Cheong; Nederpelt, Indira; Heitman, Laura H; Danhof, Meindert; van der Graaf, Piet H; Gilissen, Ron A H J; de Lange, Elizabeth C M

2016-01-01

Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target binding kinetics in drug discovery. A meaningful application of in vitro drug-target binding kinetics in drug discovery requires insight into the relation between in vivo drug effect and in vitro measured drug-target binding kinetics. In this review, the authors discuss both the relation between in vitro and in vivo measured binding kinetics and the relation between in vivo binding kinetics, target occupancy and effect profiles. More scientific evidence is required for the rational selection and development of drug-candidates on the basis of in vitro estimates of drug-target binding kinetics. To elucidate the value of in vitro binding kinetics measurements, it is necessary to obtain information on system-specific properties which influence the kinetics of target occupancy and drug effect. Mathematical integration of this information enables the identification of drug-specific properties which lead to optimal target occupancy and drug effect in patients.

Numerical Simulation of Doped Targets for ICF

Science.gov (United States)

Phillips, Lee; Gardner, John H.; Bodner, Stephen E.; Colombant, Denis; Klapisch, Marcel; Bar-Shalom, Avraham

1997-11-01

The ablative Rayleigh-Taylor (RT) instability can be reduced by preheating the ablator, thereby reducing the peak density and increasing the mass ablation velocity. The ablator can be preheated with radiation from higher Z dopants.(Gardner, J.H., Bodner, S.E., Dahlburg, J.P., Phys. Fluids 3), 1070 (1991) Dopants also reduce the density gradient at the ablator, which provides a second mechanism to reduce the RT growth rate. We have recently developed a more sophisticated and detailed radiation package that uses opacities generated by an STA code, with non-LTE radiation transport based on the Busquet method. This radiation package has been incorporated into NRL's FAST2D radiation hydrodynamics code, which has been used to evaluate and optimize the use of various dopants that can provide interesting levels of preheat for an ICF target.

RISC-Target Interaction: Cleavage and Translational Suppression

Science.gov (United States)

van den Berg, Arjen; Mols, Johann; Han, Jiahuai

2008-01-01

Summary Small RNA molecules have been known and utilized to suppress gene expression for more than a decade. The discovery that these small RNA molecules are endogenously expressed in many organisms and have a critical role in controlling gene expression have led to the arising of a whole new field of research. Termed small interfering RNA (siRNA) or microRNA (miRNA) these ~22 nt RNA molecules have the capability to suppress gene expression through various mechanisms once they are incorporated in the multi-protein RNA-Induced Silencing Complex (RISC) and interact with their target mRNA. This review introduces siRNAs and microRNAs in a historical perspective and focuses on the key molecules in RISC, structural properties and mechanisms underlying the process of small RNA regulated post-transcriptional suppression of gene expression. PMID:18692607

Incorporating other texts: Intertextuality in Malaysian CSR reports

Directory of Open Access Journals (Sweden)

Kumaran Rajandran

2016-11-01

Full Text Available In Malaysia, corporate social responsibility (CSR is relatively new but corporations have been required to engage in and disclose their CSR. A typical genre for disclosure is CSR reports and these reports often refer to other texts. The article investigates the act of referencing to other texts or intertextuality in Malaysian CSR reports. It creates an archive of CEO Statements and Environment Sections in CSR reports and studies the archive for keywords, which can identify the incorporated texts. The function of these texts is examined in relation to Malaysia’s corporate context. CSR reports contain explicit references to documents (policies, regulations, reports, research, standards and to individuals/groups (CEOs, stakeholders, expert organizations. The incorporated texts display variation in corporate control, which organizes these texts along an intertextual cline. The cline helps to identify corporate and non-corporate sources among the texts. The selection of incorporated texts may reflect government and stock exchange demands. The texts are not standardized and are relevant for the CSR domain and corporations, where these texts monitor and justify CSR performance. Yet, the incorporated texts may perpetuate inexact reporting because corporations select the texts and the parts of texts to refer to. Since these texts have been employed to scrutinize initiatives and results, CSR reports can claim to represent the “truth” about a corporation’s CSR. Hence, intertextuality serves corporate interests.

Incorporation of Ba in Al and Fe pollucite

Energy Technology Data Exchange (ETDEWEB)

Vance, Eric R., E-mail: erv@ansto.gov.au [Institute of Materials Engineering, Australian Nuclear Science and Technology Organisation, Locked Bag 2001 Kirrawee DC, NSW 2232 (Australia); Gregg, Daniel J.; Griffiths, Grant J. [Institute of Materials Engineering, Australian Nuclear Science and Technology Organisation, Locked Bag 2001 Kirrawee DC, NSW 2232 (Australia); Gaugliardo, Paul R. [Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Crawley, WA 6009 (Australia); Grant, Charmaine [Institute of Materials Engineering, Australian Nuclear Science and Technology Organisation, Locked Bag 2001 Kirrawee DC, NSW 2232 (Australia)

2016-09-15

Ba, the transmutation product of radioactive Cs, can be incorporated at levels of up to ∼0.07 formula units in Cs{sub (1−2x)}Ba{sub x}AlSi{sub 2}O{sub 6} aluminium pollucite formed by sol-gel methods and sintering at 1400 °C, with more Ba forming BaAl{sub 2}Si{sub 2}O{sub 8} phases. The effect of Ba substitution in pollucite-structured CsFeSi{sub 2}O{sub 6} was also studied and no evidence of Ba substitution in the pollucite structure via cation vacancies or Fe{sup 2+} formation was obtained. The Ba entered a Fe-silicate glass structure. Charge compensation was also attempted with a Cs{sup +} + Fe{sup 3+} ↔ Ba{sup 2+} + Ni{sup 2+} scheme but again the Ba formed a glass and NiO was evident. PCT leaching data showed CsFeSi{sub 2}O{sub 6} to be very leach resistant. - Highlights: • Barium can be incorporated into aluminium pollucite. • Positron annihilation lifetime spectroscopy supports a charge vacancy mechanism of incorporation. • Iron pollucite does not appear to incorporate any barium with either vacancy or charge compensation mechanisms. • Leaching data suggest iron pollucite is very leach resistant.

Quantitative isotope incorporation reveals substrate partitioning in a coastal microbial community.

Science.gov (United States)

Mayali, Xavier; Weber, Peter K

2018-05-01

To quantitatively link microbial identity with biogeochemical function, we carried out 14 simultaneous stable isotope probing experiments with organic and inorganic C and N substrates to measure the isotope incorporation by over one hundred co-occurring eukaryotic and prokaryotic populations in a coastal community. We found that nitrate was the most commonly incorporated substrate, and that light-driven carbon fixation was carried out by some bacterial taxa from the Flavobacteriales and OM60 (NOR5) clade, in addition to photoautotrophic phytoplankton. We found that organisms that incorporated starch, maltose, glucose, lactose and bicarbonate were phylogenetically clustered, suggesting that specific bacterial lineages specialized in the incorporation of these substrates. The data further revealed that coastal microorganisms spanned a range of resource utilization strategies from generalists to specialists and demonstrated a high level of substrate partitioning, with two thirds of taxa exhibiting unique substrate incorporation patterns and the remaining third shared by no more than three OTUs each. Specialists exhibited more extreme incorporation levels (high or low), whereas generalists displayed more intermediate activity levels. These results shed valuable insights into the bottom-up ecological strategies enabling the persistence of high microbial diversity in aquatic ecosystems.

The Advanced Linked Extended Reconnaissance & Targeting Technology Demonstration project

Science.gov (United States)

Edwards, Mark

2008-04-01

The Advanced Linked Extended Reconnaissance & Targeting (ALERT) Technology Demonstration (TD) project is addressing many operational needs of the future Canadian Army's Surveillance and Reconnaissance forces. Using the surveillance system of the Coyote reconnaissance vehicle as an experimental platform, the ALERT TD project aims to significantly enhance situational awareness by fusing multi-sensor and tactical data, developing automated processes, and integrating beyond line-of-sight sensing. The project is exploiting important advances made in computer processing capability, displays technology, digital communications, and sensor technology since the design of the original surveillance system. As the major research area within the project, concepts are discussed for displaying and fusing multi-sensor and tactical data within an Enhanced Operator Control Station (EOCS). The sensor data can originate from the Coyote's own visible-band and IR cameras, laser rangefinder, and ground-surveillance radar, as well as from beyond line-of-sight systems such as mini-UAVs and unattended ground sensors. Video-rate image processing has been developed to assist the operator to detect poorly visible targets. As a second major area of research, automatic target cueing capabilities have been added to the system. These include scene change detection, automatic target detection and aided target recognition algorithms processing both IR and visible-band images to draw the operator's attention to possible targets. The merits of incorporating scene change detection algorithms are also discussed. In the area of multi-sensor data fusion, up to Joint Defence Labs level 2 has been demonstrated. The human factors engineering aspects of the user interface in this complex environment are presented, drawing upon multiple user group sessions with military surveillance system operators. The paper concludes with Lessons Learned from the project. The ALERT system has been used in a number of C4ISR

/sup 3/H-UTP incorporation in polytene chromosomes of Chironomus permeabilized cells

Energy Technology Data Exchange (ETDEWEB)

Diez, J L; de la Torre, C [Consejo Superior de Investigacionis Cientificas, Madrid (Spain). Inst. Biologia Celular

1979-01-01

A method is described that allows the cytologic detection of the transcriptional activity of endogenous RNA polymerase in fixed Chironomus polytene chromosomes. /sup 3/H-UTP is preferentially incorporated onto nucleoli and Balbiani rings where transcription is specially high. The former incorporation was sensitive to actinomycin D while incorporation on Balbiani rings was sensitive to ..cap alpha..-amanitin. The label pattern and frequency resemble those detected by /sup 3/H-uridine incorporation in the living state.

MoO3 incorporation in magnesium aluminosilicate glasses

International Nuclear Information System (INIS)

Tan, Shengheng; Ojovan, Michael I.; Hyatt, Neil C.; Hand, Russell J.

2015-01-01

Molybdate has a very low solubility in silicate and borosilicate glass systems and its excess presence in nuclear waste glass can cause the formation of a readily soluble “yellow phase”. In this study, the incorporation of molybdenum oxide (MoO 3 ) in a magnesium aluminosilicate glass system has been investigated. The prepared glasses show a higher than 90% molybdenum retention rate and up to 5.34 mol% (12.28 wt%) MoO 3 can be incorporated into these glasses without causing visible phase separation. The incorporation of MoO 3 increases glass density, decreases glass transition and crystallisation temperatures and intensifies Raman bands assigned to vibrations of MoO 4 2− units. When excess molybdate is added liquid–liquid phase separation and crystallisation occurs. The separated phase is spherical, 200–400 nm in diameter and randomly dispersed. Based on powder X-ray diffraction, Raman spectroscopy and transmission electron microscopy, the separated phase is identified as MgMoO 4

Thymidine uptake, thymidine incorporation, and thymidine kinase activity in marine bacterium isolates

International Nuclear Information System (INIS)

Jeffrey, W.H.; Paul, J.H.

1990-01-01

One assumption made in bacterial production estimates from [ 3 H]thymidine incorporation is that all heterotrophic bacteria can incorporate exogenous thymidine into DNA. Heterotrophic marine bacterium isolates from Tampa Bay, Fla., Chesapeake Bay, Md., and a coral surface microlayer were examined for thymidine uptake (transport), thymidine incorporation, the presence of thymidine kinase genes, and thymidine kinase enzyme activity. Of the 41 isolates tested, 37 were capable of thymidine incorporation into DNA. The four organisms that could not incorporate thymidine also transported the thymidine poorly and lacked thymidine kinase activity. Attempts to detect thymidine kinase genes in the marine isolates by molecular probing with gene probes made from Escherichia coli and herpes simplex virus thymidine kinase genes proved unsuccessful. To determine if the inability to incorporate thymidine was due to the lack of thymidine kinase, one organism, Vibro sp. strain DI9, was transformed with a plasmid (pGQ3) that contained an E. coli thymidine kinase gene. Although enzyme assays indicated high levels of thymidine kinase activity in transformants, these cells still failed to incorporate exogenous thymidine into DNA or to transport thymidine into cells. These results indicate that the inability of certain marine bacteria to incorporate thymidine may not be solely due to the lack of thymidine kinase activity but may also be due to the absence of thymidine transport systems

Calculated activity incorporated in the therapy with I131

International Nuclear Information System (INIS)

Chica, L.G.; Puerta, J.A.

1998-01-01

By means of the product S(T→ S).A s (T e ), the absorbed dose to thyroid delivered by I 131 incorporated is calculated. Where S(T→ S) is the absorbed dose in the thyroid per nuclear transformation (tn.) of I 131 localized in the thyroid and as a potential function of the mass is expressed. A s (T e ) is the number of tn. of I 131 in the thyroid since the moment of the incorporation until the time T e (the effective middle time); to find A s (T e ) to normal as different pathological conditions, the metabolic model of the iodo proposed by the ICRP is used. Of the expressions of the doses, the incorporated activity, l o , is obtained

Genome-wide identification of novel small RNAs in Pseudomonas aeruginosa

DEFF Research Database (Denmark)

Gómez Lozano, María

and RNA sequencing (RNAseq) technologies. The latter approach, in particular, has revolutionized sRNA discovery by enabling interrogation of the transcriptome at unprecedented depths. The size and complexity of the P. aeruginosa genome suggests that it encodes many hitherto undetected sRNAs. In this study...

6S RNA modulates growth and antibiotic production in Streptomyces coelicolor

Czech Academy of Sciences Publication Activity Database

Mikulík, Karel; Bobek, Jan; Zídková, J.; Felsberg, Jürgen

2014-01-01

Roč. 98, č. 16 (2014), s. 7185-7197 ISSN 0175-7598 R&D Projects: GA ČR GAP302/10/0468 Institutional support: RVO:61388971 Keywords : 6SRNA * Secondary structure * pRNAs Subject RIV: EE - Microbiology, Virology Impact factor: 3.337, year: 2014

Targets of balancing selection in the human genome

DEFF Research Database (Denmark)

Andrés, Aida M; Hubisz, Melissa J; Indap, Amit

2009-01-01

Balancing selection is potentially an important biological force for maintaining advantageous genetic diversity in populations, including variation that is responsible for long-term adaptation to the environment. By serving as a means to maintain genetic variation, it may be particularly relevant...... to maintaining phenotypic variation in natural populations. Nevertheless, its prevalence and specific targets in the human genome remain largely unknown. We have analyzed the patterns of diversity and divergence of 13,400 genes in two human populations using an unbiased single-nucleotide polymorphism data set......, a genome-wide approach, and a method that incorporates demography in neutrality tests. We identified an unbiased catalog of genes with signatures of long-term balancing selection, which includes immunity genes as well as genes encoding keratins and membrane channels; the catalog also shows enrichment...

GDP-tubulin incorporation into growing microtubules modulates polymer stability.

Science.gov (United States)

Valiron, Odile; Arnal, Isabelle; Caudron, Nicolas; Job, Didier

2010-06-04

Microtubule growth proceeds through the endwise addition of nucleotide-bound tubulin dimers. The microtubule wall is composed of GDP-tubulin subunits, which are thought to come exclusively from the incorporation of GTP-tubulin complexes at microtubule ends followed by GTP hydrolysis within the polymer. The possibility of a direct GDP-tubulin incorporation into growing polymers is regarded as hardly compatible with recent structural data. Here, we have examined GTP-tubulin and GDP-tubulin incorporation into polymerizing microtubules using a minimal assembly system comprised of nucleotide-bound tubulin dimers, in the absence of free nucleotide. We find that GDP-tubulin complexes can efficiently co-polymerize with GTP-tubulin complexes during microtubule assembly. GDP-tubulin incorporation into microtubules occurs with similar efficiency during bulk microtubule assembly as during microtubule growth from seeds or centrosomes. Microtubules formed from GTP-tubulin/GDP-tubulin mixtures display altered microtubule dynamics, in particular a decreased shrinkage rate, apparently due to intrinsic modifications of the polymer disassembly properties. Thus, although microtubules polymerized from GTP-tubulin/GDP-tubulin mixtures or from homogeneous GTP-tubulin solutions are both composed of GDP-tubulin subunits, they have different dynamic properties, and this may reveal a novel form of microtubule "structural plasticity."

The multilayer nanoparticles formed by layer by layer approach for cancer-targeting therapy.

Science.gov (United States)

Oh, Keun Sang; Lee, Hwanbum; Kim, Jae Yeon; Koo, Eun Jin; Lee, Eun Hee; Park, Jae Hyung; Kim, Sang Yoon; Kim, Kwangmeyung; Kwon, Ick Chan; Yuk, Soon Hong

2013-01-10

The multilayer nanoparticles (NPs) were prepared for cancer-targeting therapy using the layer by layer approach. When drug-loaded Pluronic NPs were mixed with vesicles (liposomes) in the aqueous medium, Pluronic NPs were incorporated into the vesicles to form the vesicle NPs. Then, the multilayer NPs were formed by freeze-drying the vesicle NPs in a Pluronic aqueous solution. The morphology and size distribution of the multilayer NPs were observed using a TEM and a particle size analyzer. In order to apply the multilayer NPs as a delivery system for docetaxel (DTX), which is a model anticancer drug, the release pattern of the DTX was observed and the tumor growth was monitored by injecting the multilayer NPs into the tail veins of tumor (squamous cell carcinoma)-bearing mice. The cytotoxicity of free DTX (commercial DTX formulation (Taxotere®)) and the multilayer NPs was evaluated using MTT assay. We also evaluated the tumor targeting ability of the multilayer NPs using magnetic resonance imaging. The multilayer NPs showed excellent tumor targetability and antitumor efficacy in tumor-bearing mice, caused by the enhanced permeation and retention (EPR) effect. These results suggest that the multilayer NPs could be a potential drug delivery system for cancer-targeting therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Active Microwave Metamaterials Incorporating Ideal Gain Devices

Directory of Open Access Journals (Sweden)

Hao Xin

2010-12-01

Full Text Available Incorporation of active devices/media such as transistors for microwave and gain media for optics may be very attractive for enabling desired low loss and broadband metamaterials. Such metamaterials can even have gain which may very well lead to new and exciting physical phenomena. We investigate microwave composite right/left-handed transmission lines (CRLH-TL incorporating ideal gain devices such as constant negative resistance. With realistic lumped element values, we have shown that the negative phase constant of this kind of transmission lines is maintained (i.e., left-handedness kept while gain can be obtained (negative attenuation constant of transmission line simultaneously. Possible implementation and challenging issues of the proposed active CRLH-TL are also discussed.

Incorporation of mammalian actin into microfilaments in plant cell nucleus

Directory of Open Access Journals (Sweden)

Paves Heiti

2004-04-01

Full Text Available Abstract Background Actin is an ancient molecule that shows more than 90% amino acid homology between mammalian and plant actins. The regions of the actin molecule that are involved in F-actin assembly are largely conserved, and it is likely that mammalian actin is able to incorporate into microfilaments in plant cells but there is no experimental evidence until now. Results Visualization of microfilaments in onion bulb scale epidermis cells by different techniques revealed that rhodamine-phalloidin stained F-actin besides cytoplasm also in the nuclei whereas GFP-mouse talin hybrid protein did not enter the nuclei. Microinjection of fluorescently labeled actin was applied to study the presence of nuclear microfilaments in plant cells. Ratio imaging of injected fluorescent rabbit skeletal muscle actin and phalloidin staining of the microinjected cells showed that mammalian actin was able to incorporate into plant F-actin. The incorporation occurred preferentially in the nucleus and in the perinuclear region of plant cells whereas part of plant microfilaments, mostly in the periphery of cytoplasm, did not incorporate mammalian actin. Conclusions Microinjected mammalian actin is able to enter plant cell's nucleus, whereas incorporation of mammalian actin into plant F-actin occurs preferentially in the nucleus and perinuclear area.

Incorporation and Effects of Nanoparticles in a Supramolecular Polymer

Science.gov (United States)

2016-05-01

polymerizations and main-chain supramolecular polymers . Macromolecules. 2009;42:6823–6835. 17. Wojtecki RJ, Meador MA, Rowan SJ. Using the dynamic bond...ARL-TR-7687 ● MAY 2016 US Army Research Laboratory Incorporation and Effects of Nanoparticles in a Supramolecular Polymer by...Laboratory Incorporation and Effects of Nanoparticles in a Supramolecular Polymer by Alice M Savage Oak Ridge Institute of Science and Education

Comparison of adenovirus fiber, protein IX, and hexon capsomeres as scaffolds for vector purification and cell targeting

International Nuclear Information System (INIS)

Campos, Samuel K.; Barry, Michael A.

2006-01-01

The direct genetic modification of adenoviral capsid proteins with new ligands is an attractive means to confer targeted tropism to adenoviral vectors. Although several capsid proteins have been reported to tolerate the genetic fusion of foreign peptides and proteins, direct comparison of cell targeting efficiencies through the different capsomeres has been lacking. Likewise, direct comparison of with one or multiple ligands has not been performed due to a lack of capsid-compatible ligands available for retargeting. Here we utilize a panel of metabolically biotinylated Ad vectors to directly compare targeted transduction through the fiber, protein IX, and hexon capsomeres using a variety of biotinylated ligands including antibodies, transferrin, EGF, and cholera toxin B. These results clearly demonstrate that cell targeting with a variety of high affinity receptor-binding ligands is only effective when transduction is redirected through the fiber protein. In contrast, protein IX and hexon-mediated targeting by the same set of ligands failed to mediate robust vector targeting, perhaps due to aberrant trafficking at the cell surface or inside targeted cells. These data suggest that vector targeting by genetic incorporation of high affinity ligands will likely be most efficient through modification of the adenovirus fiber rather than the protein IX and hexon capsomeres. In contrast, single-step monomeric avidin affinity purification of Ad vectors using the metabolic biotinylation system is most effective through capsomeres like protein IX and hexon

Incorporating political socialization theory into baccalaureate nursing education.

Science.gov (United States)

Brown, S G

1996-01-01

Political socialization theory explains how an individual develops a political belief system. As the health care system undergoes dramatic changes, nursing faculty should use political socialization theory to enhance the education of student nurses. A political thread can be woven through the nursing curricula, and students can be socialized to the political role. The new generation of nurses must incorporate a political component into their professional role identity. Political socialization theory can guide nursing faculty as knowledge of the political system and political skills are incorporated into nursing curricula.

Selective incorporation of 5-hydroxytryptophan into proteins in mammalian cells

Science.gov (United States)

Zhang, Zhiwen; Alfonta, Lital; Schultz, Peter G

2014-02-25

This invention provides methods and compositions for incorporation of an unnatural amino acid into a peptide using an orthogonal aminoacyl tRNA synthetase/tRNA pair. In particular, an orthogonal pair is provided to incorporate 5-hydroxy-L-tryptophan in a position encoded by an opal mutation.

Assessing Multiple Pathways for Achieving China’s National Emissions Reduction Target

Directory of Open Access Journals (Sweden)

Mingyue Wang

2018-06-01

Full Text Available In order to achieve China’s target of carbon intensity emissions reduction in 2030, there is a need to identify a scientific pathway and feasible strategies. In this study, we used stochastic frontier analysis method of energy efficiency, incorporating energy structure, economic structure, human capital, capital stock and potential energy efficiency to identify an efficient pathway for achieving emissions reduction target. We set up 96 scenarios including single factor scenarios and multi-factors combination scenarios for the simulation. The effects of each scenario on achieving the carbon intensity reduction target are then evaluated. It is found that: (1 Potential energy efficiency has the greatest contribution to the carbon intensity emissions reduction target; (2 they are unlikely to reach the 2030 carbon intensity reduction target of 60% by only optimizing a single factor; (3 in order to achieve the 2030 target, several aspects have to be adjusted: the fossil fuel ratio must be lower than 80%, and its average growth rate must be decreased by 2.2%; the service sector ratio in GDP must be higher than 58.3%, while the growth rate of non-service sectors must be lowered by 2.4%; and both human capital and capital stock must achieve and maintain a stable growth rate and a 1% increase annually in energy efficiency. Finally, the specific recommendations of this research were discussed, including constantly improved energy efficiency; the upgrading of China’s industrial structure must be accelerated; emissions reduction must be done at the root of energy sources; multi-level input mechanisms in overall levels of education and training to cultivate the human capital stock must be established; investment in emerging equipment and accelerate the closure of backward production capacity to accumulate capital stock.

A computational framework for modeling targets as complex adaptive systems

Science.gov (United States)

Santos, Eugene; Santos, Eunice E.; Korah, John; Murugappan, Vairavan; Subramanian, Suresh

2017-05-01

Modeling large military targets is a challenge as they can be complex systems encompassing myriad combinations of human, technological, and social elements that interact, leading to complex behaviors. Moreover, such targets have multiple components and structures, extending across multiple spatial and temporal scales, and are in a state of change, either in response to events in the environment or changes within the system. Complex adaptive system (CAS) theory can help in capturing the dynamism, interactions, and more importantly various emergent behaviors, displayed by the targets. However, a key stumbling block is incorporating information from various intelligence, surveillance and reconnaissance (ISR) sources, while dealing with the inherent uncertainty, incompleteness and time criticality of real world information. To overcome these challenges, we present a probabilistic reasoning network based framework called complex adaptive Bayesian Knowledge Base (caBKB). caBKB is a rigorous, overarching and axiomatic framework that models two key processes, namely information aggregation and information composition. While information aggregation deals with the union, merger and concatenation of information and takes into account issues such as source reliability and information inconsistencies, information composition focuses on combining information components where such components may have well defined operations. Since caBKBs can explicitly model the relationships between information pieces at various scales, it provides unique capabilities such as the ability to de-aggregate and de-compose information for detailed analysis. Using a scenario from the Network Centric Operations (NCO) domain, we will describe how our framework can be used for modeling targets with a focus on methodologies for quantifying NCO performance metrics.

Enhancement of antibacterial activity in nanofillers incorporated PSF/PVP membranes

Science.gov (United States)

Pramila, P.; Gopalakrishnan, N.

2018-04-01

An attempt has been made to investigate the nanofillers incorporated polysulfone (PSF) and polyvinylpyrrolidone (PVP) polymer membranes prepared by phase inversion method. Initially, the nanofillers, viz, Zinc Oxide (ZnO) nanoparticle, Graphene Oxide-Zinc Oxide (GO-ZnO) nanocomposite were synthesized and then directly incorporated into PSF/PVP blend during the preparation of membranes. The prepared membranes have been subjected to FE-SEM, AFM, BET, contact angle, tensile test and anti-bacterial studies. Significant membrane morphologies and nanoporous properties have been observed by FE-SEM and BET, respectively. It has been observed that hydrophilicity, mechanical strength and water permeability of the ZnO and GO-ZnO incorporated membranes were enhanced than bare membrane. Antibacterial activity was assessed by measuring the inhibition zones formed around the membrane by disc-diffusion method using Escherichia coli (gram-negative) as a model bacterium. Again, it has been observed that nanofillers incorporated membrane exhibits high antibacterial performance compared to bare membrane.

Incorporating Feminism into Rehabilitation Counselor Education

Science.gov (United States)

Jeon, Mookyong

2015-01-01

Purpose: The author describes how rehabilitation counselor educators can incorporate the feminist perspective in teaching rehabilitation counselors-in-training by exploring history, core values, and training methods of feminism. Method: Based on a literature review, the author compares philosophy and concepts of rehabilitation counseling and…

Onondaga Noun Incorporation: Some Notes on the Interdependence of Syntax and Semantics

Science.gov (United States)

Woodbury, Hanni

1975-01-01

In Onondaga and all northern Iroquoian languages, nouns can be incorporated into verbs. The function of this is semantic as well as syntactic. It is semantic in that the sense of an incorporated noun will be narrower than its unincorporated counterpart regardless of modifiers. Incorporation changes the transformational structure of the sentence.…

[3H] Thymidine incorporation to estimate growth rates of anaerobic bacterial strains

International Nuclear Information System (INIS)

Winding, A.

1992-01-01

The incorporation of [ 3 H] thymidine by axenic cultures of anaerobic bacteria was investigated as a means to measure growth. The three fermentative strains and one of the methanogenic strains tested incorporated [ 3 H] thymidine during growth. It is concluded that the [ 3 H] thymidine incorporation method underestimates bacterial growth in anaerobic environments

Chitosan-based multifunctional nanomedicines and theranostics for targeted therapy of cancer.

Science.gov (United States)

Fathi, Marziyeh; Majidi, Sima; Zangabad, Parham Sahandi; Barar, Jaleh; Erfan-Niya, Hamid; Omidi, Yadollah

2018-05-30

Nanotechnology as an emerging field has established inevitable impacts on nano-biomedicine and treatment of formidable diseases, inflammations, and malignancies. In this regard, substantial advances in the design of systems for delivery of therapeutic agents have emerged magnificent and innovative pathways in biomedical applications. Chitosan (CS) is derived via deacetylation of chitin as the second most abundant polysaccharide. Owing to the unique properties of CS (e.g., biocompatibility, biodegradability, bioactivity, mucoadhesion, cationic nature and functional groups), it is an excellent candidate for diverse biomedical and pharmaceutical applications such as drug/gene delivery, transplantation of encapsulated cells, tissue engineering, wound healing, antimicrobial purposes, etc. In this review, we will document, discuss, and provide some key insights toward design and application of miscellaneous nanoplatforms based on CS. The CS-based nanosystems (NSs) can be employed as advanced drug delivery systems (DDSs) in large part due to their remarkable physicochemical and biological characteristics. The abundant functional groups of CS allow the facile functionalization in order to engineer multifunctional NSs, which can simultaneously incorporate therapeutic agents, molecular targeting, and diagnostic/imaging capabilities in particular against malignancies. These multimodal NSs can be literally translated into clinical applications such as targeted diagnosis and therapy of cancer because they offer minimal systemic toxicity and maximal cytotoxicity against cancer cells and tumors. The recent developments in the CS-based NSs functionalized with targeting and imaging agents prove CS as a versatile polymer in targeted imaging and therapy. © 2018 Wiley Periodicals, Inc.

Targeted transgene insertion into the CHO cell genome using Cre recombinase-incorporating integrase-defective retroviral vectors.

Science.gov (United States)

Kawabe, Yoshinori; Shimomura, Takuya; Huang, Shuohao; Imanishi, Suguru; Ito, Akira; Kamihira, Masamichi

2016-07-01

Retroviral vectors have served as efficient gene delivery tools in various biotechnology fields. However, viral DNA is randomly inserted into the genome, which can cause problems, such as insertional mutagenesis and gene silencing. Previously, we reported a site-specific gene integration system, in which a transgene is integrated into a predetermined chromosomal locus of Chinese hamster ovary (CHO) cells using integrase-defective retroviral vectors (IDRVs) and Cre recombinase. In this system, a Cre expression plasmid is transfected into founder cells before retroviral transduction. In practical applications of site-specific gene modification such as for hard-to-transfect cells or for in vivo gene delivery, both the transgene and the Cre protein into retroviral virions should be encapsulate. Here, we generated novel hybrid IDRVs in which viral genome and enzymatically active Cre can be delivered (Cre-IDRVs). Cre-IDRVs encoding marker genes, neomycin resistance and enhanced green fluorescent protein (EGFP), flanked by wild-type and mutated loxP sites were produced using an expression plasmid for a chimeric protein of Cre and retroviral gag-pol. After analyzing the incorporation of the Cre protein into retroviral virions by Western blotting, the Cre-IDRV was infected into founder CHO cells, in which marker genes (hygromycin resistance and red fluorescent protein) flanked with corresponding loxP sites are introduced into the genome. G418-resistant colonies expressing GFP appeared and the site-specific integration of the transgene into the expected chromosomal site was confirmed by PCR and sequencing of amplicons. Moreover, when Cre-IDRV carried a gene expression unit for a recombinant antibody, the recombinant cells in which the antibody expression cassette was integrated in a site-specific manner were generated and the cells produced the recombinant antibody. This method may provide a promising tool to perform site-specific gene modification according to Cre

A Genome-Wide Identification of the miRNAome in Response to Salinity Stress in Date palm (Phoenix dactylifera L.

Directory of Open Access Journals (Sweden)

Mahmoud W Yaish

2015-11-01

Full Text Available Although date palm is relatively salt-tolerant, little is known about the underlying molecular mechanisms that contribute to its salt tolerance. Only recently, investigators have uncovered microRNA-mediated post-transcriptional gene regulation, which is critical for typical plant development and adaptation to stress conditions such as salinity. To identify conserved and novel miRNAs in date palm and to characterise miRNAs that could play a role in salt tolerance, we have generated sRNA libraries from the leaves and roots of NaCl-treated and untreated seedlings of date palm. Deep sequencing of these four sRNA libraries yielded approximately 251 million reads. The bioinformatics analysis has identified 153 homologs of conserved miRNAs, 89 miRNA variants, and 180 putative novel miRNAs in date palm. Expression profiles under salinity revealed differential regulation of some miRNAs in date palm. In leaves, 54 of the identified miRNAs were significantly affected and the majority (70% of them were upregulated, whereas in roots, 25 of the identified miRNAs were significantly affected and 76% of them were upregulated by the salinity stress. The salt-responsiveness of some of these miRNAs was further validated using semi-quantitative PCR (qPCR. Some of the predicted targets for the identified miRNA include genes with known functions in plant salt tolerance, such as potassium channel AKT2-like proteins, vacuolar protein sorting-associated protein, calcium-dependent and mitogen-activated proteins. As one of the first cultivated trees in the world that can tolerate a wide range of abiotic stresses, date palm contains a large population of conserved and nonconserved miRNAs that function at the post-transcriptional level. This study provided insights into miRNA-mediated gene expression that are important for adaptation to salinity in date palms.

A Collaborative Approach to Incorporating Statistics in the Physiology Classroom

Science.gov (United States)

Potterfield, April; Majerus, Mary

2008-01-01

Both the National Science Education Standards (NSES) and the National Council of Teachers of Mathematics (NCTM) recommend appropriately incorporating mathematics into other disciplines (NRC 1996; NRC 2003; NCTM 2000). With this in mind, an interdisciplinary, inquiry-based project was undertaken to incorporate mathematical analysis of data into a…

Vector-transmitted disease vaccines: targeting salivary proteins in transmission (SPIT).

Science.gov (United States)

McDowell, Mary Ann

2015-08-01

More than half the population of the world is at risk for morbidity and mortality from vector-transmitted diseases, and emerging vector-transmitted infections are threatening new populations. Rising insecticide resistance and lack of efficacious vaccines highlight the need for novel control measures. One such approach is targeting the vector-host interface by incorporating vector salivary proteins in anti-pathogen vaccines. Debate remains about whether vector saliva exposure exacerbates or protects against more severe clinical manifestations, induces immunity through natural exposure or extends to all vector species and associated pathogens. Nevertheless, exploiting this unique biology holds promise as a viable strategy for the development of vaccines against vector-transmitted diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis and characterization of Au incorporated Alq3 nanowires

Science.gov (United States)

Khan, Mohammad Bilal; Ahmad, Sultan; Parwaz, M.; Rahul, Khan, Zishan H.

2018-05-01

We report the synthesis and characterization of pure and Au incorporated Alq3 nanowires. These nanowires are synthesized using thermal vapor transport method. The luminescence intensity of Au incorporated Alq3 nanowires are recorded to be higher than that of pure Alq3 nanowires, which is found to increase with the increase in Au concentration. Fluorescence quenching is also observed when Au concentration is increased beyond the certain limit.

Conceptualising how SMEs incorporate green content in their websites

OpenAIRE

Craig M. Parker; Emilia Bellucci; Luba Torlina; Ambika Zutshi; Bardo Fraunholz

2014-01-01

This paper presents a framework on how Small and Medium Enterprises (SMEs) can proactively incorporate content relating to their ecological responsibility (or green) activities in their websites. SME studies offer limited guidance on, and conceptualisation of, how organisations can incorporate different types of content into their website designs. This paper addresses this problem by presenting the results of an exploratory, qualitative content analysis of Australian SME websites where emerge...

Parameterization of Fuel-Optimal Synchronous Approach Trajectories to Tumbling Targets

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David Charles Sternberg

2018-04-01

Full Text Available Docking with potentially tumbling Targets is a common element of many mission architectures, including on-orbit servicing and active debris removal. This paper studies synchronized docking trajectories as a way to ensure the Chaser satellite remains on the docking axis of the tumbling Target, thereby reducing collision risks and enabling persistent onboard sensing of the docking location. Chaser satellites have limited computational power available to them and the time allowed for the determination of a fuel optimal trajectory may be limited. Consequently, parameterized trajectories that approximate the fuel optimal trajectory while following synchronous approaches may be used to provide a computationally efficient means of determining near optimal trajectories to a tumbling Target. This paper presents a method of balancing the computation cost with the added fuel expenditure required for parameterization, including the selection of a parameterization scheme, the number of parameters in the parameterization, and a means of incorporating the dynamics of a tumbling satellite into the parameterization process. Comparisons of the parameterized trajectories are made with the fuel optimal trajectory, which is computed through the numerical propagation of Euler’s equations. Additionally, various tumble types are considered to demonstrate the efficacy of the presented computation scheme. With this parameterized trajectory determination method, Chaser satellites may perform terminal approach and docking maneuvers with both fuel and computational efficiency.

Predicting success of oligomerized pool engineering (OPEN for zinc finger target site sequences

Directory of Open Access Journals (Sweden)

Goodwin Mathew J

2010-11-01

successfully in vivo, substantially reducing the experimental effort required. ZiFOpT is freely available and incorporated in the Zinc Finger Targeter web server (http://bindr.gdcb.iastate.edu/ZiFiT.

Physicochemical and Antioxidant Properties of Chitosan Films Incorporated with Cinnamon Oil

Directory of Open Access Journals (Sweden)

Marco A. López-Mata

2015-01-01

Full Text Available Chitosan films (CF with cinnamon bark oil (CO incorporated at 0% (control, 0.25%, 0.5%, and 1.0% v/v were prepared by an emulsion method. The films were characterized based on their physical properties (solubility, water vapor permeability, optical property, and microstructure and antioxidant properties (DPPH, ABTS, and its protective effects on human erythrocytes. The results showed that the incorporation of 0.5 and 1.0% of CO into the CF significantly decreased its solubility to 22% of the control (p<0.05. The water vapor permeability of the CF-CO was significantly reduced to 40% with low concentrations of CO (0.25% incorporated into the CF. In general, the films presented a yellow coloration and an increase in transparency with the incorporation of CO into the CF. It was also observed that the incorporation of CO increased the antioxidant activity between 6.0-fold and 14.5-fold compared to the control, and the protective capacity against erythrocyte hemolysis increased by as much as 80%.

An efficient and high fidelity method for amplification, cloning and sequencing of complete tospovirus genomic RNA segments

Science.gov (United States)

Amplification and sequencing of the complete M- and S-RNA segments of Tomato spotted wilt virus and Impatiens necrotic spot virus as a single fragment is useful for whole genome sequencing of tospoviruses co-infecting a single host plant. It avoids issues associated with overlapping amplicon-based ...

Semiconducting compounds and devices incorporating same

Science.gov (United States)

Marks, Tobin J.; Facchetti, Antonio; Boudreault, Pierre-Luc; Miyauchi, Hiroyuki

2016-01-19

Disclosed are molecular and polymeric compounds having desirable properties as semiconducting materials. Such compounds can exhibit desirable electronic properties and possess processing advantages including solution-processability and/or good stability. Organic transistor and photovoltaic devices incorporating the present compounds as the active layer exhibit good device performance.

Microstructural analysis of clayey ceramic incorporated with fluorescent lamp glass

International Nuclear Information System (INIS)

Morais, A.S.C.; Caldas, T.C.C.; Pereira, P.S.; Monteiro, S.N.; Vieira, C.M.F.

2011-01-01

This study aims to evaluate the effect of the incorporation of glass powder fluorescent lamp, from a decontamination process, in the microstructure of clayey ceramic. Formulations were prepared with incorporation of the waste in amounts of up to 10 wt.% into the clayey body. Specimens were prepared by uniaxial mold-press at 20 MPa and then fired at 850 and 1050°C. After firing, the microstructure of the ceramics was evaluated by optical microscopy (OM), scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results showed that the incorporation of glass powder into the clayey body changes the microstructure of the ceramics. (author)

A Regulatory Circuit Composed of a Transcription Factor, IscR, and a Regulatory RNA, RyhB, Controls Fe-S Cluster Delivery.

Science.gov (United States)

Mandin, Pierre; Chareyre, Sylvia; Barras, Frédéric

2016-09-20

Fe-S clusters are cofactors conserved through all domains of life. Once assembled by dedicated ISC and/or SUF scaffolds, Fe-S clusters are conveyed to their apo-targets via A-type carrier proteins (ATCs). Escherichia coli possesses four such ATCs. ErpA is the only ATC essential under aerobiosis. Recent studies reported a possible regulation of the erpA mRNA by the small RNA (sRNA) RyhB, which controls the expression of many genes under iron starvation. Surprisingly, erpA has not been identified in recent transcriptomic analysis of the iron starvation response, thus bringing into question the actual physiological significance of the putative regulation of erpA by RyhB. Using an sRNA library, we show that among 26 sRNAs, only RyhB represses the expression of an erpA-lacZ translational fusion. We further demonstrate that this repression occurs during iron starvation. Using mutational analysis, we show that RyhB base pairs to the erpA mRNA, inducing its disappearance. In addition, IscR, the master regulator of Fe-S homeostasis, represses expression of erpA at the transcriptional level when iron is abundant, but depleting iron from the medium alleviates this repression. The conjunction of transcriptional derepression by IscR and posttranscriptional repression by RyhB under Fe-limiting conditions is best described as an incoherent regulatory circuit. This double regulation allows full expression of erpA at iron concentrations for which Fe-S biogenesis switches from the ISC to the SUF system. We further provide evidence that this regulatory circuit coordinates ATC usage to iron availability. Regulatory small RNAs (sRNAs) have emerged as major actors in the control of gene expression in the last few decades. Relatively little is known about how these regulators interact with classical transcription factors to coordinate genetic responses. We show here how an sRNA, RyhB, and a transcription factor, IscR, regulate expression of an essential gene, erpA, in the bacterium E

Radiation dose to trabecular bone marrow stem cells from 3H, 14C and selected α-emitters incorporated in a bone remodeling compartment

International Nuclear Information System (INIS)

Nie Huiling; Richardson, Richard B

2009-01-01

A Monte Carlo simulation of repeated cubic units representing trabecular bone cavities in adult bone was employed to determine absorbed dose fractions evaluated for 3 H, 14 C and a set of α-emitters incorporated within a bone remodeling compartment (BRC). The BRC consists of a well-oxygenated vascular microenvironment located within a canopy of bone-lining cells. The International Commission on Radiological Protection (ICRP) considers that an important target for radiation-induced bone cancer is the endosteum marrow layer adjacent to bone surface where quiescent bone stem cells reside. It is proposed that the active stem cells and progenitor cells located above the BRC canopy, the 'BRC stem cell niche', is a more important radiation-induced cancer target volume. Simulation results from a static model, where no remodeling occurs, indicate that the mean dose from bone and bone surface to the 50 μm quiescent bone stem cell niche, the current ICRP target, was substantially lower (two to three times lower) than that to the narrower and hypoxic 10 μm endosteum for 3 H, 14 C and α-particles with energy range 0.5-10 MeV. The results from a dynamic model indicate that the temporal α-radiation dose to active stem/progenitor cells located in the BRC stem cell niche from the material incorporated in and buried by forming bone was 9- to 111-fold greater than the dose to the quiescent bone stem cell niche. This work indicates that the remodeling portion of the bone surface, rather than the quiescent (endosteal) surface, has the greatest risk of radiation-induced bone cancer, particularly from short-range radiation, due to the elevated dose and the radiosensitizing oxygen effect.

THE INCORPORATION OF RADIOACTIVITY FROM GLYCINE-C$sup 14$ BY MAMMALIAN SPERMATOZOA

Energy Technology Data Exchange (ETDEWEB)

Graves, C. N.

1962-05-15

The metabolic pathways of glycine incorporation were investigated by biochemical and radibautographic methods. Results show that glycine is utilized hy bovine spermatoza and is incorporated into all fractions of the sperm cell. Incorporation into the nucleic acid fraction and especially into thymine indicates that there is a turnover in the desoxyribenucleic acid during storage of bovine spermatoza. (C.H.)

iTAR: a web server for identifying target genes of transcription factors using ChIP-seq or ChIP-chip data.

Science.gov (United States)

Yang, Chia-Chun; Andrews, Erik H; Chen, Min-Hsuan; Wang, Wan-Yu; Chen, Jeremy J W; Gerstein, Mark; Liu, Chun-Chi; Cheng, Chao

2016-08-12

Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) or microarray hybridization (ChIP-chip) has been widely used to determine the genomic occupation of transcription factors (TFs). We have previously developed a probabilistic method, called TIP (Target Identification from Profiles), to identify TF target genes using ChIP-seq/ChIP-chip data. To achieve high specificity, TIP applies a conservative method to estimate significance of target genes, with the trade-off being a relatively low sensitivity of target gene identification compared to other methods. Additionally, TIP's output does not render binding-peak locations or intensity, information highly useful for visualization and general experimental biological use, while the variability of ChIP-seq/ChIP-chip file formats has made input into TIP more difficult than desired. To improve upon these facets, here we present are fined TIP with key extensions. First, it implements a Gaussian mixture model for p-value estimation, increasing target gene identification sensitivity and more accurately capturing the shape of TF binding profile distributions. Second, it enables the incorporation of TF binding-peak data by identifying their locations in significant target gene promoter regions and quantifies their strengths. Finally, for full ease of implementation we have incorporated it into a web server ( http://syslab3.nchu.edu.tw/iTAR/ ) that enables flexibility of input file format, can be used across multiple species and genome assembly versions, and is freely available for public use. The web server additionally performs GO enrichment analysis for the identified target genes to reveal the potential function of the corresponding TF. The iTAR web server provides a user-friendly interface and supports target gene identification in seven species, ranging from yeast to human. To facilitate investigating the quality of ChIP-seq/ChIP-chip data, the web server generates the chart of the

Controlled nitrogen incorporation in GaNSb alloys

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M. J. Ashwin

2011-09-01

Full Text Available The incorporation of N in molecular-beam epitaxy of GaNxSb1−x alloys with x ⩽ 0.022 has been investigated as a function of temperature (325–400°C and growth rate 0.25–1.6 μmh−1. At fixed growth rate, the incorporated N fraction increases as the temperature is reduced until a maximum N content for the particular growth rate reached. At each temperature, there is a range of growth rates over which the N content is inversely proportional to the growth rate; the results are understood in terms of a kinetic model. The systematic growth rate- and temperature-dependence enables the N content and resulting band gap to be controlled.

Fluorine incorporation during Si solid phase epitaxy

International Nuclear Information System (INIS)

Impellizzeri, G.; Mirabella, S.; Romano, L.; Napolitani, E.; Carnera, A.; Grimaldi, M.G.; Priolo, F.

2006-01-01

We have investigated the F incorporation and segregation in preamorphized Si during solid phase epitaxy (SPE) at different temperatures and for several implanted-F energies and fluences. The Si samples were amorphized to a depth of 550 nm by implanting Si at liquid nitrogen temperature and then enriched with F at different energies (65-150 keV) and fluences (0.07-5 x 10 14 F/cm 2 ). Subsequently, the samples were regrown by SPE at different temperatures: 580, 700 and 800 deg. C. We have found that the amount of F incorporated after SPE strongly depends on the SPE temperature and on the energy and fluence of the implanted-F, opening the possibility to tailor the F profile during SPE

Organelle targeting: third level of drug targeting

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Sakhrani NM

2013-07-01

Full Text Available Niraj M Sakhrani, Harish PadhDepartment of Cell and Molecular Biology, BV Patel Pharmaceutical Education and Research Development (PERD Centre, Gujarat, IndiaAbstract: Drug discovery and drug delivery are two main aspects for treatment of a variety of disorders. However, the real bottleneck associated with systemic drug administration is the lack of target-specific affinity toward a pathological site, resulting in systemic toxicity and innumerable other side effects as well as higher dosage requirement for efficacy. An attractive strategy to increase the therapeutic index of a drug is to specifically deliver the therapeutic molecule in its active form, not only into target tissue, nor even to target cells, but more importantly, into the targeted organelle, ie, to its intracellular therapeutic active site. This would ensure improved efficacy and minimize toxicity. Cancer chemotherapy today faces the major challenge of delivering chemotherapeutic drugs exclusively to tumor cells, while sparing normal proliferating cells. Nanoparticles play a crucial role by acting as a vehicle for delivery of drugs to target sites inside tumor cells. In this review, we spotlight active and passive targeting, followed by discussion of the importance of targeting to specific cell organelles and the potential role of cell-penetrating peptides. Finally, the discussion will address the strategies for drug/DNA targeting to lysosomes, mitochondria, nuclei and Golgi/endoplasmic reticulum.Keywords: intracellular drug delivery, cancer chemotherapy, therapeutic index, cell penetrating peptides

Sample sequencing of vascular plants demonstrates widespread conservation and divergence of microRNAs.

Science.gov (United States)

Chávez Montes, Ricardo A; de Fátima Rosas-Cárdenas, Flor; De Paoli, Emanuele; Accerbi, Monica; Rymarquis, Linda A; Mahalingam, Gayathri; Marsch-Martínez, Nayelli; Meyers, Blake C; Green, Pamela J; de Folter, Stefan

2014-04-23

Small RNAs are pivotal regulators of gene expression that guide transcriptional and post-transcriptional silencing mechanisms in eukaryotes, including plants. Here we report a comprehensive atlas of sRNA and miRNA from 3 species of algae and 31 representative species across vascular plants, including non-model plants. We sequence and quantify sRNAs from 99 different tissues or treatments across species, resulting in a data set of over 132 million distinct sequences. Using miRBase mature sequences as a reference, we identify the miRNA sequences present in these libraries. We apply diverse profiling methods to examine critical sRNA and miRNA features, such as size distribution, tissue-specific regulation and sequence conservation between species, as well as to predict putative new miRNA sequences. We also develop database resources, computational analysis tools and a dedicated website, http://smallrna.udel.edu/. This study provides new insights on plant sRNAs and miRNAs, and a foundation for future studies.

The strontium-90 equilibrium parameters in Saclay soil; Les parametres d'equilibre du strontium 90 dans le sol de Saclay

Energy Technology Data Exchange (ETDEWEB)

Cohen, P; Gailledreau, C [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1960-07-01

The equilibrium parameters of {sup 90}Sr in the presence of the following elements: Ca, Na, K, NH{sub 4} are measured in the soil at Saclay for each of the pairs Sr-Ca, Sr-Na, Sr-K, Sr-NH{sub 4}. The adsorption mechanism for Sr is studied in comparison with a synthetic resin which is a pure ion-exchanger. A preliminary study of a three component system; one being a tracer, is outlined. (author) [French] Les parametres d'equilibre du {sup 90}Sr en presence des elements suivants: Ca, Na, K, NH{sub 4} sont mesures sur le sol de Saclay pour chacun des couples Sr-Ca, Sr-Na, Sr-K, Sr-NH{sub 4}. Le mecanisme d'adsorption du Sr est etudie par comparaison avec une resine synthetique qui est un echangeur d'ions pur. Une etude preliminaire d'un systeme a trois composants, dont l'un est un traceur, est exposee. (auteur)

Fluorescent molecule incorporated metal-organic framework for fluoride sensing in aqueous solution

Energy Technology Data Exchange (ETDEWEB)

Zhao, Xudong, E-mail: zhaoxd_tykj@163.com; Wang, Yuanyang; Hao, Xiuli; Liu, Wen, E-mail: 13700509372@163.com

2017-04-30

Highlights: • Fluorescein sodium was successfully encapsulated in UiO-66 via in-situ synthesis. • FS@UiO-66 is one of the few Zr-MOF-based probes for fluoride so far. • FS@UiO-66 is a highly effective, fast-response and naked-eye sensor for fluoride. - Abstract: In this work, the fluorescent molecule (fluorescein sodium, FS) was successfully incorporated in the zirconium-based MOF (UiO-66) via in-situ synthesis method, which can be confirmed by FTIR spectra and fluorescence microscopic images. Based on this in-situ synthesis strategy, FS molecule can be immobilized tightly in the framework. Furthermore, the resulting FS@UiO-66 demonstrates to be a highly selective, real-time and naked-eye chemical sensor for fluoride in aqueous solution, which is mainly due to the release of FS molecule from FS@UiO-66 into the aqueous solution. Meanwhile, to the best of our knowledge, such Zr-MOF-based fluoride sensor is very rare so far. These results provide a promising approach to rationally design novel MOF-based fluorescent sensor for the target molecules.

Incorporation of metal nanoparticles into wood substrate and methods

Science.gov (United States)

Rector, Kirk D; Lucas, Marcel

2015-11-04

Metal nanoparticles were incorporated into wood. Ionic liquids were used to expand the wood cell wall structure for nanoparticle incorporation into the cell wall structure. Nanoparticles of elemental gold or silver were found to be effective surface enhanced Raman spectroscopy (SERS) imaging contrast or sensing agents. Nanoparticles of elemental iron were found to be efficient microwave absorbers and caused localized heating for disrupting the integrity of the lignocellulosic matrix. Controls suggest that the localized heating around the iron nanoparticles reduces losses of cellulose in the form of water, volatiles and CO.sub.2. The ionic liquid is needed during the incorporation process at room temperature. The use of small amounts of ionic liquid combined with the absence of an ionic liquid purification step and a lower energy and water use are expected to reduce costs in an up-scaled pretreatment process.

External tandem target system for efficient production of short-lived positron emitting radionuclides

International Nuclear Information System (INIS)

Koh, K.; Dwyer, J.; Finn, R.; Sheh, Y.; Sinnreich, J.; Wooten, T.

1983-01-01

Recent developments in radiopharmaceutical chemistry allow the incorporation of short-lived, positron-emitting radionuclides into a variety of compounds which when used with a positron emission tomograph provide a means of monitoring physiological disorders by a standard technique. To effectively meet the increased ''in-house'' clinical demands while maintaining a production schedule, a tandem target was designed and has been installed for the simultaneous ''on-line'' preparation of oxygen-15 labelled compounds such as CO 2 15 , H 2 O 15 ; and nitrogen-13 labelled compounds such as 13 NH 3 , 13 N 2 O, and 13 N 2 . The processing time required for the synthesis of the nitrogen-13 products as compared to the essentially instantaneous formation of oxygen-15 labelled compounds has provided the necessary time delay for clinical utilization. The characterisitcs of this external tandem target system as well as the automation for the dual processing are presented

Between economic and legal analysis of incorporeal things: A critical

African Journals Online (AJOL)

The author uses practical economic examples to argue for the development of common law. The author identifies relevant Roman law principles which justify the legal nature of incorporeal things. It is demonstrated that the value of incorporeal things depends greatly on future circumstances. It is argued in this article that the ...

The biokinetic of incorporates radionuclides; Die Biokinetik von inkorporierten Radionukliden

Energy Technology Data Exchange (ETDEWEB)

Breustedt, Bastian [Karlsruher Institut fuer Technologie (KIT), Eggenstein-Leopoldshafen (Germany). Inst. fuer Strahlenforschung; Giussani, Augusto [Bundesamt fuer Strahlenschutz, Oberschleissheim (Germany). Arbeitsgruppe ' ' Externe und interne Dosimetrie, Biokinetik' '

2017-08-01

Incorporated radionuclides from nuclear accidents, fission product releases or nuclear medical administration are distributed in the human body in organs and tissue, absorbed 9or excreted. The interpretation of incorporation monitoring results and the estimation of the internal doses that cannot be measured directly need mathematical methods and the formulation of biokinetic models.

A terminal-labelling microcytotoxity assay with 125I-iododeoxyuridine as a label for target cells

International Nuclear Information System (INIS)

Stirrat, G.M.

1976-01-01

The development of a terminal-labelling microcytotoxicity assay is described in which target cells (fetal fibroblasts) were labelled with 125 I-iododeoxyuridine after effector (lymphoid) cells had been incubated with them for 24 h. The time-course for the development of cell-mediated cytotoxicity was assessed following allogeneic skin grafting. 'Non-specific' cytotoxicity detracts from the sensitivity of all microcytotoxicity assays and the terminal-labelling assay using 125 I is no exception. The non-specific effects can be reduced but not eliminated by the removal of adherent cells. The optimum target cell/effector cell ratio would seem to be between 1:100 and 1:250. Residual lymph node cells did not appear to incorporate enough label to affect the test results. In vivo correlates of in vitro findings are still not easy to determine

Incorporating single detector failure into the ROP detector layout optimization for CANDU reactors

Energy Technology Data Exchange (ETDEWEB)

Kastanya, Doddy, E-mail: Doddy.Kastanya@snclavalin.com

2015-12-15

Highlights: • ROP TSP value needs to be adjusted when any detector in the system fails. • Single detector failure criterion has been incorporated into the detector layout optimization as a constraint. • Results show that the optimized detector layout is more robust with respect to its vulnerability to a single detector failure. • An early rejection scheme has been introduced to speed-up the optimization process. - Abstract: In CANDU{sup ®} reactors, the regional overpower protection (ROP) systems are designed to protect the reactor against overpower in the fuel which could reduce the safety margin-to-dryout. In the CANDU{sup ®} 600 MW (CANDU 6) design, there are two ROP systems in the core, each of which is connected to a fast-acting shutdown system. Each ROP system consists of a number of fast-responding, self-powered flux detectors suitably distributed throughout the core within vertical and horizontal flux detector assemblies. The placement of these ROP detectors is a challenging discrete optimization problem. In the past few years, two algorithms, DETPLASA and ADORE, have been developed to optimize the detector layout for the ROP systems in CANDU reactors. These algorithms utilize the simulated annealing (SA) technique to optimize the placement of the detectors in the core. The objective of the optimization process is typically either to maximize the TSP value for a given number of detectors in the system or to minimize the number of detectors in the system to obtain a target TSP value. One measure to determine the robustness of the optimized detector layout is to evaluate the maximum decrease (penalty) in TSP value when any single detector in the system fails. The smaller the penalty, the more robust the design is. Therefore, in order to ensure that the optimized detector layout is robust, the single detector failure (SDF) criterion has been incorporated as an additional constraint into the ADORE algorithm. Results from this study indicate that there

Analysis of pools of targeted Salmonella deletion mutants identifies novel genes affecting fitness during competitive infection in mice.

Directory of Open Access Journals (Sweden)

Carlos A Santiviago

2009-07-01

Full Text Available Pools of mutants of minimal complexity but maximal coverage of genes of interest facilitate screening for genes under selection in a particular environment. We constructed individual deletion mutants in 1,023 Salmonella enterica serovar Typhimurium genes, including almost all genes found in Salmonella but not in related genera. All mutations were confirmed simultaneously using a novel amplification strategy to produce labeled RNA from a T7 RNA polymerase promoter, introduced during the construction of each mutant, followed by hybridization of this labeled RNA to a Typhimurium genome tiling array. To demonstrate the ability to identify fitness phenotypes using our pool of mutants, the pool was subjected to selection by intraperitoneal injection into BALB/c mice and subsequent recovery from spleens. Changes in the representation of each mutant were monitored using T7 transcripts hybridized to a novel inexpensive minimal microarray. Among the top 120 statistically significant spleen colonization phenotypes, more than 40 were mutations in genes with no previously known role in this model. Fifteen phenotypes were tested using individual mutants in competitive assays of intraperitoneal infection in mice and eleven were confirmed, including the first two examples of attenuation for sRNA mutants in Salmonella. We refer to the method as Array-based analysis of cistrons under selection (ABACUS.

Catalytic properties of RNA polymerases IV and V: accuracy, nucleotide incorporation and rNTP/dNTP discrimination.

Science.gov (United States)

Marasco, Michelle; Li, Weiyi; Lynch, Michael; Pikaard, Craig S

2017-11-02

All eukaryotes have three essential nuclear multisubunit RNA polymerases, abbreviated as Pol I, Pol II and Pol III. Plants are remarkable in having two additional multisubunit RNA polymerases, Pol IV and Pol V, which synthesize noncoding RNAs that coordinate RNA-directed DNA methylation for silencing of transposons and a subset of genes. Based on their subunit compositions, Pols IV and V clearly evolved as specialized forms of Pol II, but their catalytic properties remain undefined. Here, we show that Pols IV and V differ from one another, and Pol II, in nucleotide incorporation rate, transcriptional accuracy and the ability to discriminate between ribonucleotides and deoxyribonucleotides. Pol IV transcription is considerably more error-prone than Pols II or V, which may be tolerable in its synthesis of short RNAs that serve as precursors for siRNAs targeting non-identical members of transposon families. By contrast, Pol V exhibits high fidelity transcription, similar to Pol II, suggesting a need for Pol V transcripts to faithfully reflect the DNA sequence of target loci to which siRNA-Argonaute silencing complexes are recruited. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Isotopic incorporation rates and discrimination factors in mantis shrimp crustaceans.

Directory of Open Access Journals (Sweden)

Maya S deVries

Full Text Available Stable isotope analysis has provided insights into the trophic ecology of a wide diversity of animals. Knowledge about isotopic incorporation rates and isotopic discrimination between the consumer and its diet for different tissue types is essential for interpreting stable isotope data, but these parameters remain understudied in many animal taxa and particularly in aquatic invertebrates. We performed a 292-day diet shift experiment on 92 individuals of the predatory mantis shrimp, Neogonodactylus bredini, to quantify carbon and nitrogen incorporation rates and isotope discrimination factors in muscle and hemolymph tissues. Average isotopic discrimination factors between mantis shrimp muscle and the new diet were 3.0 ± 0.6 ‰ and 0.9 ± 0.3 ‰ for carbon and nitrogen, respectively, which is contrary to what is seen in many other animals (e.g. C and N discrimination is generally 0-1 ‰ and 3-4 ‰, respectively. Surprisingly, the average residence time of nitrogen in hemolymph (28.9 ± 8.3 days was over 8 times longer than that of carbon (3.4 ± 1.4 days. In muscle, the average residence times of carbon and nitrogen were of the same magnitude (89.3 ± 44.4 and 72.8 ± 18.8 days, respectively. We compared the mantis shrimps' incorporation rates, along with rates from four other invertebrate taxa from the literature, to those predicted by an allometric equation relating carbon incorporation rate to body mass that was developed for teleost fishes and sharks. The rate of carbon incorporation into muscle was consistent with rates predicted by this equation. Our findings provide new insight into isotopic discrimination factors and incorporation rates in invertebrates with the former showing a different trend than what is commonly observed in other animals.

[3H]uridine uptake by target monolayers as a terminal label in an in vitro cell-mediated cytotoxicity assay

International Nuclear Information System (INIS)

Smith, G.; Nicklin, S.

1979-01-01

A terminal labelling method is described for measuring cell-mediated cytotoxicity based on the ability of surviving target cells to incorporate [ 3 H]uridine into their RNA precursor pools. Parameters of the system were examined using whole and damaged embryonic mouse fibroblast monolayers. This assay is less laborious than direct cell counting and gives increased sensitivity at low target to effector cell ratios. The labelling time is short and, unlike similar techniques, it allows target cell monolayers to remain intact after completion of the radioassay and available for histological examination. This is important where heterogeneous target populations are employed since it allows assessment of differential cell killing and eliminates the need for duplicate cultures. The assay was used in conjunction with a well defined mouse popliteal lymph node assay to investigate the appearance of cytotoxic cells during a localised graft versus host response. Results showed a direct correlation between proliferative index and the development of highly specific cell-mediated cytotoxicity. (Auth.)

Mechanical properties of Self-Consolidating Concrete incorporating Cement Kiln Dust

Directory of Open Access Journals (Sweden)

Mostafa Abd El-Mohsen

2015-04-01

Full Text Available Self-Consolidating Concrete (SCC has been widely used in both practical and laboratory applications. Selection of its components and their ratios depends, mainly, on the target mechanical and physical properties recommended by the project consultant. Partial replacement of cement in SCC with cheap available industrial by-product could produce environmentally durable concrete with similar properties of normal concrete. In the current research, SCC was produced by blending Cement Kiln Dust (CKD with cement in different ratios. Four mixes incorporating cement kiln dust with partial cement replacement of 10%, 20%, 30%, and 40% were produced and compared with a control mix of Normally Vibrated Concrete (NVC. Superplasticizer was used to increase the flow-ability of SCC mixes. The fresh and hardened mechanical properties of all mixes were determined and evaluated. Moreover, time-dependent behavior was investigated for all mixes in terms of drying shrinkage test. The shrinkage strain was measured for all specimens for a period of 120 days. Based on the experimental results, it was found that SCC mixture containing 20% cement replacement of CKD exhibited the highest mechanical strength compared to other SCC mixes and NVC mix as well. It was observed that the volumetric changes of specimens were directly proportional to the increase of the cement replacement ratio.

Formulation of Bioadhesive Carbomer Gel Incorporating Drug ...

African Journals Online (AJOL)

incorporated into carbomer gel and evaluated for drug release. Results: ... localized delivery system for the treatment inflammation and infection in periodontal pockets. ..... loaded with diclofenac sodium for intra- articular administration. J Drug ...

Incorporation of a lambda phage recombination system and EGFP detection to simplify mutagenesis of Herpes simplex virus bacterial artificial chromosomes

Directory of Open Access Journals (Sweden)

Weir Jerry P

2007-05-01

Full Text Available Abstract Background Targeted mutagenesis of the herpesvirus genomes has been facilitated by the use of bacterial artificial chromosome (BAC technology. Such modified genomes have potential uses in understanding viral pathogenesis, gene identification and characterization, and the development of new viral vectors and vaccines. We have previously described the construction of a herpes simplex virus 2 (HSV-2 BAC and the use of an allele replacement strategy to construct HSV-2 recombinants. While the BAC mutagenesis procedure is a powerful method to generate HSV-2 recombinants, particularly in the absence of selective marker in eukaryotic culture, the mutagenesis procedure is still difficult and cumbersome. Results Here we describe the incorporation of a phage lambda recombination system into an allele replacement vector. This strategy enables any DNA fragment containing the phage attL recombination sites to be efficiently inserted into the attR sites of the allele replacement vector using phage lambda clonase. We also describe how the incorporation of EGFP into the allele replacement vector can facilitate the selection of the desired cross-over recombinant BACs when the allele replacement reaction is a viral gene deletion. Finally, we incorporate the lambda phage recombination sites directly into an HSV-2 BAC vector for direct recombination of gene cassettes using the phage lambda clonase-driven recombination reaction. Conclusion Together, these improvements to the techniques of HSV BAC mutagenesis will facilitate the construction of recombinant herpes simplex viruses and viral vectors.

In vitro incorporation of the phage Phi29 connector complex

International Nuclear Information System (INIS)

Fu Chiyu; Prevelige, Peter E.

2009-01-01

The incorporation of the DNA packaging connector complex during lambdoid phage assembly in vivo is strictly controlled-one and only one of the twelve identical icosahedral vertices is differentiated by the inclusion of a portal or connector dodecamer. Proposed control mechanisms include obligate nucleation from a connector containing complex, addition of the connector as the final step during assembly, and a connector-mediated increase in the growth rate. The inability to recapitulate connector incorporation in vitro has made it difficult to obtain direct biochemical evidence in support of one model over another. Here we report the development an in vitro assembly system for the well characterized dsDNA phage Phi29 which results in the co-assembly of connector with capsid and scaffolding proteins to form procapsid-like particles (PLPs). Immuno-electron microscopy demonstrates the specific incorporation of connector vertex in PLPs. The connector protein increases both the yield and the rate of capsid assembly suggesting that the incorporation of the connector in Phi29 likely promotes nucleation of assembly.

Leachability of fired clay brick incorporating with sewage sludge waste

Science.gov (United States)

Kadir, Aeslina Abdul; Salim, Nurul Salhana Abdul; Sarani, Noor Amira; Rahmat, Nur Aqma Izurin; Abdullah, Mohd Mustafa Al Bakri

2017-09-01

Sewage sludge is sewerage from wastewater treatment plants that generates millions tons of sludge ever year. Regarding this activity, it causes lack management of waste which is harmful to the surrounding conditions. Therefore, this study is focuses on the incorporation of sewage sludge waste into fired clay brick to provide an option of disposal method, producing adequate quality of brick as well as limiting the heavy metal leachability to the environment. Sewage sludge brick (SSB) mixtures were incorporated with 0%, 1%, 5%, 10%, 20% and 30% of sewage sludge waste (SSW). Heavy metals of crushed SSB were determined by using Toxicity Characteristic Leaching Procedure (TCLP) according to Method 1311 of United State Environment Protection Agency (USEPA) standard. From the results obtained, up to 20% of SSW could be incorporated into fired clay brick and comply with the USEPA standard. Therefore, this study revealed that by incorporating SSW into fired clay brick it could be an alternative method to dispose the SSW and also could act as a replacement material for brick manufacturing with appropriate mix and design.

Target dependence of K+-nucleus total cross sections

International Nuclear Information System (INIS)

Jiang, M.F.; Ernst, D.J.; Chen, C.M.

1995-01-01

We investigate the total cross section and its target dependence for K + -nucleus scattering using a relativistic momentum-space optical potential model which incorporates relativistically normalized wave functions, invariant two-body amplitudes, covariant kinematics, and an exact full-Fermi averaging integral. The definition of the total cross section in the presence of a Coulomb interaction is reviewed and the total cross section is calculated in a way that is consistent with what is extracted from experiment. In addition, the total cross sections for a nucleus and for the deuteron are calculated utilizing the same theory. This minimizes the dependence of the ratio of these cross sections on the details of the theory. The model dependence of the first-order optical potential calculations is investigated. The theoretical results are found to be systematically below all existing data

Head-and-Neck Target Delineation Among Radiation Oncology Residents After a Teaching Intervention: A Prospective, Blinded Pilot Study

International Nuclear Information System (INIS)

Bekelman, Justin E.; Wolden, Suzanne; Lee, Nancy

2009-01-01

Purpose: We conducted this study to determine the feasibility of incorporating a teaching intervention on target delineation into the educational curriculum of a radiation oncology residency program and to assess the short-term effects on resident skills. Methods and Materials: The study schema consisted of a baseline evaluation, the teaching intervention, and a follow-up evaluation. At the baseline evaluation, the participants contoured three clinical tumor volumes (CTVs) (70 Gy, 59.4 Gy, and 54 Gy) on six contrast-enhanced axial computed tomography images of a de-identified patient with Stage T2N2bM0 squamous cell carcinoma of the right base of the tongue. The participants attended a series of head-and-neck oncology and anatomy seminars. The teaching intervention consisted of a didactic lecture and an interactive hands-on practical session designed to improve the knowledge and skills for target delineation in the head and neck. At the follow-up evaluation, the residents again contoured the CTVs. Results: Of the 14 eligible residents, 11 (79%) actually participated in the study. For all participants, but especially for those who had not had previous experience with head-and-neck target delineation, the teaching intervention was associated with improvement in the delineation of the node-negative neck (CTV 54 Gy contour). Regardless of clinical experience, participants had difficulty determining what should be included in the CTV 59.4 Gy contour to ensure adequate coverage of potential microscopic disease. Conclusion: Incorporating a teaching intervention into the education curriculum of a radiation oncology residency program is feasible and was associated with short-term improvements in target delineation skills. Subsequent interventions will require content refinement, additional validation, longer term follow-up, and multi-institutional collaboration

Incorporating the life course model into MCH nutrition leadership education and training programs.

Science.gov (United States)

Haughton, Betsy; Eppig, Kristen; Looney, Shannon M; Cunningham-Sabo, Leslie; Spear, Bonnie A; Spence, Marsha; Stang, Jamie S

2013-01-01

Life course perspective, social determinants of health, and health equity have been combined into one comprehensive model, the life course model (LCM), for strategic planning by US Health Resources and Services Administration's Maternal and Child Health Bureau. The purpose of this project was to describe a faculty development process; identify strategies for incorporation of the LCM into nutrition leadership education and training at the graduate and professional levels; and suggest broader implications for training, research, and practice. Nineteen representatives from 6 MCHB-funded nutrition leadership education and training programs and 10 federal partners participated in a one-day session that began with an overview of the models and concluded with guided small group discussions on how to incorporate them into maternal and child health (MCH) leadership training using obesity as an example. Written notes from group discussions were compiled and coded emergently. Content analysis determined the most salient themes about incorporating the models into training. Four major LCM-related themes emerged, three of which were about training: (1) incorporation by training grants through LCM-framed coursework and experiences for trainees, and similarly framed continuing education and skills development for professionals; (2) incorporation through collaboration with other training programs and state and community partners, and through advocacy; and (3) incorporation by others at the federal and local levels through policy, political, and prevention efforts. The fourth theme focused on anticipated challenges of incorporating the model in training. Multiple methods for incorporating the LCM into MCH training and practice are warranted. Challenges to incorporating include the need for research and related policy development.

Analysis of Myc-induced histone modifications on target chromatin.

Directory of Open Access Journals (Sweden)

Francesca Martinato

Full Text Available The c-myc proto-oncogene is induced by mitogens and is a central regulator of cell growth and differentiation. The c-myc product, Myc, is a transcription factor that binds a multitude of genomic sites, estimated to be over 10-15% of all promoter regions. Target promoters generally pre-exist in an active or poised chromatin state that is further modified by Myc, contributing to fine transcriptional regulation (activation or repression of the afferent gene. Among other mechanisms, Myc recruits histone acetyl-transferases to target chromatin and locally promotes hyper-acetylation of multiple lysines on histones H3 and H4, although the identity and combination of the modified lysines is unknown. Whether Myc dynamically regulates other histone modifications (or marks at its binding sites also remains to be addressed. Here, we used quantitative chromatin immunoprecipitation (qChIP to profile a total of 24 lysine-acetylation and -methylation marks modulated by Myc at target promoters in a human B-cell line with a regulatable c-myc transgene. Myc binding promoted acetylation of multiple lysines, primarily of H3K9, H3K14, H3K18, H4K5 and H4K12, but significantly also of H4K8, H4K91 and H2AK5. Dimethylation of H3K79 was also selectively induced at target promoters. A majority of target promoters showed co-induction of multiple marks - in various combinations - correlating with recruitment of the two HATs tested (Tip60 and HBO1, incorporation of the histone variant H2A.Z and transcriptional activation. Based on this and previous findings, we surmise that Myc recruits the Tip60/p400 complex to achieve a coordinated histone acetylation/exchange reaction at activated promoters. Our data are also consistent with the additive and redundant role of multiple acetylation events in transcriptional activation.

International network on incorporation of ageing effects into PSA

International Nuclear Information System (INIS)

Kirchsteiger, C.; Patrik, M.

2006-01-01

This paper describes the background and status of a new International Network on ''Incorporating Ageing Effects into Probabilistic Safety Assessment''. The Joint Research Centre (JRC) of the European Commission organized in September 2004 the kickoff meeting of this Network at JRC's Institute for Energy in Petten, Netherlands, with the aims to open the APSA Network, to start discussion of ageing issues in relation to incorporating ageing effects into PSA tools and to come to consensus on objectives and work packages of the Network, taking into account the specific expectations of potential Network partners. The presentations and discussions at the meeting confirmed the main conclusion from the previously organized PSAM 7 pre-conference workshop on ''Incorporating PSA into Ageing Management'', Budapest, June 2004, namely that incorporating ageing effects into PSA seems to be more and more a hot topic particularly for risk assessment and ageing management of nuclear power plants operating at advanced age (more than 25-30 years) and for the purpose of plant life extension. However, it also appeared that, especially regarding the situation in Europe, at present there are several on-going feasibility or full studies in this area, but not yet a completed Ageing PSA leading to applications. The project's working method is a NETWORK of operators, industry, research, academia and consultants with an active interest in the area (physical networking via a series of workshops and virtual networking via the Internet). The resulting knowledge should help PSA developers and users to incorporate the effects of equipment ageing into current PSA tools and models, to identify and/or develop most effective corresponding methods, to focus on dominant ageing contributors and components and to promote the use of PSA for ageing management of Nuclear Power Plants. (orig.)

Down the slippery slop: Utility incorporation of environmental externalities

International Nuclear Information System (INIS)

Vandenberg, A.J.; Tempchin, R.S.; Mitnick, S.A.; Harron, A.L.

1993-01-01

Advocates of incorporating environmental externalities in electric utility decision-making have concentrated on new electric generating resources, with some success. Such public utility commission actions compel utilities to consider, explicitly, the cost of sulfur dioxide, carbon dioxide, nitrogen oxides and other emission of power-plants when comparing the economics of new generating resources with those of other resource options (e.g., demand-side management and gas-fired non-utility generator projects). This paper summarizes a study which estimated costs of incorporating externalities in utility system operations. We also present an analysis of the Tellus work in this area, and contrast Tellus' methodology, assumptions and results with our own. Estimates of the cost of incorporating externalities in system operations is rather large, in terms of the increased fuel and purchased power cost that ratepayers would have to bear. For the eight cases we examined, the incorporation of externalities caused fuel and purchased power cost to be 9.3 to 69.5 percent higher, relative to what it would have been under traditional generating unit commitment and dispatch. Furthermore, we believe that these estimates of fuel and purchased power cost increases are conservative. In particular, because our analyses focused on utility system operations in 1995, the key assumption about the fuel cost differential (i.e., coal versus natural gas) probably underestimates the differential in later years, significantly, when virtually all forecasters foresee faster cost escalation rates for gas. In general, the higher the fuel cost differential, the faster cost escalation rates for gas. In general, the higher the fuel cost differential, the greater the cost of an externality policy. Unless the record is set straight soon, the idea that incorporating externalities is virtually costless will further spread in the regulatory community and among government policy-makers

Incorporation of [h]leucine and [h]valine into protein of freshwater bacteria: field applications.

Science.gov (United States)

Jørgensen, N O

1992-11-01

Incorporation of leucine and valine into proteins of freshwater bacteria as a measure of bacterial production was tested in two eutrophic Danish lakes and was related to bacterial production measured by thymidine incorporation. In a depth profile (0 to 8 m) in Frederiksborg Castle Lake, incorporation of 100 nM leucine and valine gave similar rates of protein production. In terms of carbon, this production was about 50% lower than incorporation of 10 nM thymidine. In another depth profile in the same lake, incorporations of 10 nM valine and 100 nM leucine were identical, but differed from incorporations of 10 nM leucine and 100 nM valine. Bacterial carbon production calculated from incorporations of 10 nM thymidine and 10 nM leucine was similar, whereas 10 nM valine and 100 nM leucine and valine indicated an up to 2.4-fold-higher rate of carbon production. In a diel study in Lake Bagsvaerd, incorporation of 100 nM leucine and valine indicated a similar protein production, but the calculated carbon production was about 1.9-fold higher than the production based on uptake of 10 nM thymidine. Different diel changes in incorporation of the two amino acids and in incorporation of thymidine were observed. In both lakes, concentrations of naturally occurring leucine and valine were activity of a H isotope added at a concentration of 100 nM usually was diluted a maximum of 5%. Net assimilation of natural free amino acids in the lakes sustained 8 to 69% of the net bacterial carbon requirement, estimated from incorporation of leucine, valine, or thymidine. The present results indicate that incorporation of leucine and valine permits realistic measurements of bacterial production in freshwater environments.

Effect of boron incorporation on the structure and electrical properties of diamond-like carbon films deposited by femtosecond and nanosecond pulsed laser ablation

Energy Technology Data Exchange (ETDEWEB)

Sikora, A. [Laboratoire Hubert Curien, UMR 5516 CNRS, Universite Jean Monnet, 18 Rue Pr. Benoit Lauras, 42000 Saint-Etienne (France); Bourgeois, O. [Institut Neel, UPR 2940 CNRS, 25 Avenue des Martyrs, 38042 Grenoble Cedex 9 (France); Sanchez-Lopez, J.C. [Instituto de Ciencia de Materiales de Sevilla, Avda. Americo Vespucio, 49 41092 Sevilla (Spain); Rouzaud, J.-N. [Laboratoire de Geologie, UMR 8538 CNRS, Ecole Normale Superieure, 45 Rue d' Ulm, 75230 Paris Cedex 05 (France); Rojas, T.C. [Instituto de Ciencia de Materiales de Sevilla, Avda. Americo Vespucio, 49 41092 Sevilla (Spain); Loir, A.-S. [Laboratoire Hubert Curien, UMR 5516 CNRS, Universite Jean Monnet, 18 Rue Pr. Benoit Lauras, 42000 Saint-Etienne (France); Garden, J.-L. [Institut Neel, UPR 2940 CNRS, 25 Avenue des Martyrs, 38042 Grenoble Cedex 9 (France); Garrelie, F. [Laboratoire Hubert Curien, UMR 5516 CNRS, Universite Jean Monnet, 18 Rue Pr. Benoit Lauras, 42000 Saint-Etienne (France); Donnet, C., E-mail: christophe.donnet@univ-st-etienne.f [Laboratoire Hubert Curien, UMR 5516 CNRS, Universite Jean Monnet, 18 Rue Pr. Benoit Lauras, 42000 Saint-Etienne (France)

2009-12-31

The influence of the incorporation of boron in diamond-like carbon (DLC) films on the microstructure of the coatings has been investigated. The boron-containing DLC films (a-C:B) have been deposited by pulsed laser deposition (PLD) at room temperature in high vacuum conditions, by ablating graphite and boron targets either with a femtosecond pulsed laser (800 nm, 150 fs, fs-DLC) or with a nanosecond pulsed laser (248 nm, 20 ns, ns-DLC). Alternative ablation of the graphite and boron targets has been carried out to deposit the a-C:B films. The film structure and composition have been highlighted by coupling Field Emission Scanning Electron Microscopy, Electron Energy Loss Spectroscopy and High Resolution Transmission Electron Microscopy. Using the B K-edge, EELS characterization reveals the boron effect on the carbon bonding. Moreover, the plasmon energy reveals a tendency of graphitization associated to the boron doping. Pure boron particles have been characterized by HRTEM and reveal that those particles are amorphous or crystallized. The nanostructures of the boron-doped ns-DLC and the boron-doped fs-DLC are thus compared. In particular, the incorporation of boron in the DLC matrix is highlighted, depending on the laser used for deposition. Electrical measurements show that some of these films have potentialities to be used in low temperature thermometry, considering their conductivity and temperature coefficient of resistance (TCR) estimated within the temperature range 160-300 K.

77 FR 12284 - Access to Confidential Business Information; Protection Strategies Incorporated

Science.gov (United States)

2012-02-29

... Business Information; Protection Strategies Incorporated AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: EPA has authorized its contractor, Protection Strategies Incorporated (PSI) of... Business Information (CBI). DATES: Access to the confidential data occurred on or about February 16, 2012...

Self-assembled Multifunctional DNA Nanoflowers for the Circumvention of Multidrug Resistance in Targeted Anticancer Drug Delivery.

Science.gov (United States)

Mei, Lei; Zhu, Guizhi; Qiu, Liping; Wu, Cuichen; Chen, Huapei; Liang, Hao; Cansiz, Sena; Lv, Yifan; Zhang, Xiaobing; Tan, Weihong

2015-11-01

Cancer chemotherapy has been impeded by side effects and multidrug resistance (MDR) partially caused by drug efflux from cancer cells, which call for targeted drug delivery systems additionally able to circumvent MDR. Here we report multifunctional DNA nanoflowers (NFs) for targeted drug delivery to both chemosensitive and MDR cancer cells and circumvent MDR in both leukemia and breast cancer cell models. NFs are self-assembled via liquid crystallization of DNA generated by Rolling Circle Replication, during which NFs are incorporated with aptamers for specific cancer cell recognition, fluorophores for bioimaging, and Doxorubicin (Dox)-binding DNA for drug delivery. NF sizes are tunable (down to ~200 nm in diameter), and the densely packed drug-binding motifs and porous intrastructures endow NFs with high drug loading capacity (71.4%, wt/wt). The Dox-loaded NFs (NF-Dox) are stable at physiological pH, yet drug release is facilitated in acidic or basic conditions. NFs deliver Dox into target chemosensitive and MDR cancer cells, preventing drug efflux and enhancing drug retention in MDR cells. Consequently, NF-Dox induces potent cytotoxicity in both target chemosensitive cells and MDR cells, but not nontarget cells, thus concurrently circumventing MDR and reducing side effects. Overall, these NFs are promising to circumvent MDR in targeted cancer therapy.

Predictive Treatment Management: Incorporating a Predictive Tumor Response Model Into Robust Prospective Treatment Planning for Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Zhang, Pengpeng, E-mail: zhangp@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yorke, Ellen; Hu, Yu-Chi; Mageras, Gig [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

2014-02-01

Purpose: We hypothesized that a treatment planning technique that incorporates predicted lung tumor regression into optimization, predictive treatment planning (PTP), could allow dose escalation to the residual tumor while maintaining coverage of the initial target without increasing dose to surrounding organs at risk (OARs). Methods and Materials: We created a model to estimate the geometric presence of residual tumors after radiation therapy using planning computed tomography (CT) and weekly cone beam CT scans of 5 lung cancer patients. For planning purposes, we modeled the dynamic process of tumor shrinkage by morphing the original planning target volume (PTV{sub orig}) in 3 equispaced steps to the predicted residue (PTV{sub pred}). Patients were treated with a uniform prescription dose to PTV{sub orig}. By contrast, PTP optimization started with the same prescription dose to PTV{sub orig} but linearly increased the dose at each step, until reaching the highest dose achievable to PTV{sub pred} consistent with OAR limits. This method is compared with midcourse adaptive replanning. Results: Initial parenchymal gross tumor volume (GTV) ranged from 3.6 to 186.5 cm{sup 3}. On average, the primary GTV and PTV decreased by 39% and 27%, respectively, at the end of treatment. The PTP approach gave PTV{sub orig} at least the prescription dose, and it increased the mean dose of the true residual tumor by an average of 6.0 Gy above the adaptive approach. Conclusions: PTP, incorporating a tumor regression model from the start, represents a new approach to increase tumor dose without increasing toxicities, and reduce clinical workload compared with the adaptive approach, although model verification using per-patient midcourse imaging would be prudent.

Determination of rumen microbial growth in vitro form 32P-labelled phosphate incorporation

International Nuclear Information System (INIS)

Nevel, C.J. Van; Demeyer, D.I.

1977-01-01

The extracellular phosphate pool in incubations of rumen fluid or washed cell suspensions of mixed rumen bacteria (WCS) was labelled with 32 P. From the constant extracellular phosphate pool specific activity and the amount of radioactivity incorporated during incubation, the amount of P incorporated in the microbial fraction was calculated. From the value for nitrogen: P determined in microbial matter, the amount of N incorporated was calculated as a measure of microbial growth. Incorporation of soluble non-protein-N in incubations devoid of substrate protein was 50 and 80% of the values obtained using isotope method for rumen fluid and WCS respectively. Incorporation of 32 P in P-containing microbial components (mainly nucleic acids) was compared with net synthesis of these components in incubations of WCS. When N incorporation, calculated from results obtained using isotope method in incubations with rumen fluid, was compared with the amount of carbohydrate substrate fermented and the type of fermentation, values between 18.3 and 44.6 g N incorporated kg of organic matter fermented were obtained. The use of isotopes for determination of rumen microbial growth in vitro is critically discussed. (author)

sRNA-Mediated Regulation of P-Fimbriae Phase Variation in Uropathogenic Escherichia coli

DEFF Research Database (Denmark)

Khandige, Surabhi; Kronborg, Tina; Uhlin, Bernt Eric

2015-01-01

Uropathogenic Escherichia coli (UPEC) are capable of occupying physiologically distinct intracellular and extracellular niches within the urinary tract. This feat requires the timely regulation of gene expression and small RNAs (sRNAs) are known to mediate such rapid adjustments in response to ch...... to changing environmental cues. This study aimed to uncover sRNA-mediated gene regulation in the UPEC strain UTI89, during infection of bladder epithelial cells. Hfq is an RNA chaperone known to facilitate and stabilize sRNA and target mRNA interactions with bacterial cells. The co...... to the discovery of a novel virulence-associated trans-acting sRNA-PapR. Deletion of papR was found to enhance adhesion of UTI89 to both bladder and kidney cell lines in a manner independent of type-1 fimbriae. We demonstrate PapR mediated posttranscriptional repression of the P-fimbriae phase regulator gene pap...

KRYPTON INCORPORATION IN SPUTTERED SILICON FILMS

NARCIS (Netherlands)

GREUTER, MJW; NIESEN, L; HAKVOORT, RA; DEROODE, J; VANVEEN, A; BERNTSEN, AJM; SLOOF, WG

1993-01-01

The incorporation of Kr in sputtered a-Si films has been investigated in a systematic way by varying the Kr to Si flux, yielding Kr concentrations up to 5 at %. Compositions were determined with X-ray microanalysis. A model has been applied to describe the composition of the growing film. The layers

A Bayesian approach for incorporating economic factors in sample size design for clinical trials of individual drugs and portfolios of drugs.

Science.gov (United States)

Patel, Nitin R; Ankolekar, Suresh

2007-11-30

Classical approaches to clinical trial design ignore economic factors that determine economic viability of a new drug. We address the choice of sample size in Phase III trials as a decision theory problem using a hybrid approach that takes a Bayesian view from the perspective of a drug company and a classical Neyman-Pearson view from the perspective of regulatory authorities. We incorporate relevant economic factors in the analysis to determine the optimal sample size to maximize the expected profit for the company. We extend the analysis to account for risk by using a 'satisficing' objective function that maximizes the chance of meeting a management-specified target level of profit. We extend the models for single drugs to a portfolio of clinical trials and optimize the sample sizes to maximize the expected profit subject to budget constraints. Further, we address the portfolio risk and optimize the sample sizes to maximize the probability of achieving a given target of expected profit.

Influence of incorporated radionuclides on the life span of Drosophila melanogaster

International Nuclear Information System (INIS)

Koshel', N.M.; Vajserman, O.M.; Vojtenko, V.P.; Kutlakhmedov, Yu.O.; Mikhjejev, O.M.

2004-01-01

Influence of incorporated radionuclides ( 137 Cs and 90 Sr) on the life span of Drosophila melanogaster was studied. External irradiation modified the formation of cumulative dose of incorporated radionuclides. All influences leaded to significant (p 90 Sr was higher comparing to 137 Cs

Empirical Analysis of the Impact of Inflation Targeting on the Risk Premium

Directory of Open Access Journals (Sweden)

Krušković Borivoje D.

2014-09-01

Full Text Available The basis for the conduct of monetary policy is monetary policy strategy. Monetary strategy is necessary for monetary policy makers to analyse all relevant information in order to undertake effective policy actions. Inflation targeting has enabled countries to achieve low inflation in the very short term. Due to this, the financial markets have adjusted their long-term inflation expectations and incorporated them into the interest rate. Risk premiums that compensate for the uncertainty of inflation have fallen. The aim of this paper is to examine how the adoption of inflation targeting affects the movement of the risk premium. The hypothesis we want to test is that the adoption of inflation targeting affects the reduction of the country risk premium by affecting the formation of a more stable macroeconomic environment through a more stable and predictable inflation rate in the medium and long term. The method used for evaluating the regression coefficients is the dynamic panel generalized method of moments (GMM. This method involves the use of conditional moments in endogenous and exogenous variables with a lag as instruments for the assessment of differential equations, while the difference lagged endogenous variables are used as instruments in the levels equation.

Multiplex target enrichment using DNA indexing for ultra-high throughput SNP detection.

LENUS (Irish Health Repository)

Kenny, Elaine M

2011-02-01

Screening large numbers of target regions in multiple DNA samples for sequence variation is an important application of next-generation sequencing but an efficient method to enrich the samples in parallel has yet to be reported. We describe an advanced method that combines DNA samples using indexes or barcodes prior to target enrichment to facilitate this type of experiment. Sequencing libraries for multiple individual DNA samples, each incorporating a unique 6-bp index, are combined in equal quantities, enriched using a single in-solution target enrichment assay and sequenced in a single reaction. Sequence reads are parsed based on the index, allowing sequence analysis of individual samples. We show that the use of indexed samples does not impact on the efficiency of the enrichment reaction. For three- and nine-indexed HapMap DNA samples, the method was found to be highly accurate for SNP identification. Even with sequence coverage as low as 8x, 99% of sequence SNP calls were concordant with known genotypes. Within a single experiment, this method can sequence the exonic regions of hundreds of genes in tens of samples for sequence and structural variation using as little as 1 μg of input DNA per sample.

29 CFR 1917.3 - Incorporation by reference.

Science.gov (United States)

2010-07-01

... incorporated by reference in this part, have the same force and effect as other standards in this part. Only... Administration (OSHA), or at the OSHA Docket Office, U.S. Department of Labor, 200 Constitution Avenue, NW., Room...

A free Hg jet system for use in a high-power target experiment

CERN Document Server

Spampinato, Philip; Gabriel, Tony A; Graves, Van; Haseroth, H; Kirk, Harold G; Lettry, Jacques; McDonald, Kirk T; Rennich, Mark; Simos, Nikolaos; Titus, P; Tsang, Thomas

2005-01-01

We describe a mercury jet system that is suitable for insertion into the 15cm diameter bore of a high-field solenoid magnet. The device features a hermetically sealed primary containment volume which is enclosed in a secondary containment system to insure isolation of mercury vapors from the remaining experimental environment. The jet diameter is 1-cm while the jet velocity will be up to 20 m/s. Optical diagnostics is incorporated into the target design to allow observation of the dispersal of the mercury as a result of interaction with a 24 GeV proton beam with up to 20 x 10

TargetVue: Visual Analysis of Anomalous User Behaviors in Online Communication Systems.

Science.gov (United States)

Cao, Nan; Shi, Conglei; Lin, Sabrina; Lu, Jie; Lin, Yu-Ru; Lin, Ching-Yung

2016-01-01

Users with anomalous behaviors in online communication systems (e.g. email and social medial platforms) are potential threats to society. Automated anomaly detection based on advanced machine learning techniques has been developed to combat this issue; challenges remain, though, due to the difficulty of obtaining proper ground truth for model training and evaluation. Therefore, substantial human judgment on the automated analysis results is often required to better adjust the performance of anomaly detection. Unfortunately, techniques that allow users to understand the analysis results more efficiently, to make a confident judgment about anomalies, and to explore data in their context, are still lacking. In this paper, we propose a novel visual analysis system, TargetVue, which detects anomalous users via an unsupervised learning model and visualizes the behaviors of suspicious users in behavior-rich context through novel visualization designs and multiple coordinated contextual views. Particularly, TargetVue incorporates three new ego-centric glyphs to visually summarize a user's behaviors which effectively present the user's communication activities, features, and social interactions. An efficient layout method is proposed to place these glyphs on a triangle grid, which captures similarities among users and facilitates comparisons of behaviors of different users. We demonstrate the power of TargetVue through its application in a social bot detection challenge using Twitter data, a case study based on email records, and an interview with expert users. Our evaluation shows that TargetVue is beneficial to the detection of users with anomalous communication behaviors.

Measurement of the incorporation rates of four amino acids into proteins for estimating bacterial production.

Science.gov (United States)

Servais, P

1995-03-01

In aquatic ecosystems, [(3)H]thymidine incorporation into bacterial DNA and [(3)H]leucine incorporation into proteins are usually used to estimate bacterial production. The incorporation rates of four amino acids (leucine, tyrosine, lysine, alanine) into proteins of bacteria were measured in parallel on natural freshwater samples from the basin of the river Meuse (Belgium). Comparison of the incorporation into proteins and into the total macromolecular fraction showed that these different amino acids were incorporated at more than 90% into proteins. From incorporation measurements at four subsaturated concentrations (range, 2-77 nm), the maximum incorporation rates were determined. Strong correlations (r > 0.91 for all the calculated correlations) were found between the maximum incorporation rates of the different tested amino acids over a range of two orders of magnitude of bacterial activity. Bacterial production estimates were calculated using theoretical and experimental conversion factors. The productions calculated from the incorporation rates of the four amino acids were in good concordance, especially when the experimental conversion factors were used (slope range, 0.91-1.11, and r > 0.91). This study suggests that the incorporation of various amino acids into proteins can be used to estimate bacterial production.

Cytotoxic chromosomal targeting by CRISPR/Cas systems can reshape bacterial genomes and expel or remodel pathogenicity islands.

Science.gov (United States)

Vercoe, Reuben B; Chang, James T; Dy, Ron L; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R; Fineran, Peter C

2013-04-01

In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas-mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA-targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity.

Incorporating A Structured Writing Process into Existing CLS Curricula.

Science.gov (United States)

Honeycutt, Karen; Latshaw, Sandra

2014-01-01

Good communication and critical thinking are essential skills for all successful professionals, including Clinical Laboratory Science/Medical Laboratory Science (CLS/MLS) practitioners. Professional programs can incorporate writing assignments into their curricula to improve student written communication and critical thinking skills. Clearly defined, scenario-focused writing assignments provide student practice in clearly articulating responses to proposed problems or situations, researching and utilizing informational resources, and applying and synthesizing relevant information. Assessment rubrics, structured feedback, and revision writing methodologies help guide students through the writing process. This article describes how a CLS Program in a public academic medical center, located in the central United States (US) serving five centrally-located US states has incorporated writing intensive assignments into an existing 11-month academic year using formal, informal and reflective writing to improve student written communication and critical thinking skills. Faculty members and employers of graduates assert that incorporating writing intensive requirements have better prepared students for their professional role to effectively communicate and think critically.

Utilization of Glycosaminoglycans/Proteoglycans as Carriers for Targeted Therapy Delivery

Science.gov (United States)

Misra, Suniti; Hascall, Vincent C.; Atanelishvili, Ilia; Moreno Rodriguez, Ricardo; Markwald, Roger R.; Ghatak, Shibnath

2015-01-01

The outcome of patients with cancer has improved significantly in the past decade with the incorporation of drugs targeting cell surface adhesive receptors, receptor tyrosine kinases, and modulation of several molecules of extracellular matrices (ECMs), the complex composite of collagens, glycoproteins, proteoglycans, and glycosaminoglycans that dictates tissue architecture. Cancer tissue invasive processes progress by various oncogenic strategies, including interfering with ECM molecules and their interactions with invasive cells. In this review, we describe how the ECM components, proteoglycans and glycosaminoglycans, influence tumor cell signaling. In particular this review describes how the glycosaminoglycan hyaluronan (HA) and its major receptor CD44 impact invasive behavior of tumor cells, and provides useful insight when designing new therapeutic strategies in the treatment of cancer. PMID:26448753

FDTD analysis of 3-D conducting target coated by anisotropic magnetized plasma

International Nuclear Information System (INIS)

Xu Lijun; Liu Shaobin; Mo Jinjun; Yuan Naichang

2006-01-01

The JEC finite-difference time-domain (JEC-FDTD) method is extended to three dimensional anisotropic dispersive media- the magnetized plasma. The problem which incorporates both anisotropy and frequency dispersion at the same time is solved for the electromagnetic wave propagation. The three dimensional JEC-FDTD formulations for anisotropic magnetized plasma are derived. The method is applied to the electromagnetic scattering of dihedral corner reflector and sphere-cone coated with anisotropic magnetized plasma. By simulating the interaction of electromagnetic wave with magnetized plasma, some numerical results are obtained, which indicate that an appropriate plasma coating may efficiently reduce the RCS of a metallic target. (authors)

Direct incorporation of guanosine 5'-diphosphate into microtubules without guanosine 5'-triphosphate hydrolysis

International Nuclear Information System (INIS)

Hamel, E.; Batra, J.K.; Lin, C.M.

1986-01-01

Using highly purified calf brain tubulin bearing [8- 14 C]guanosine 5'-diphosphate (GDP) in the exchangeable nucleotide site and heat-treated microtubule-associated proteins, the authors have found that a significant proportion of exchangeable-site GDP in microtubules can be incorporated directly during guanosine 5'-triphosphate (GTP) dependent polymerization of tubulin, without an initial exchange of GDP for GTP and subsequent GTP hydrolysis during assembly. The precise amount of GDP incorporated directly into microtubules is highly dependent on specific reaction conditions, being favored by high tubulin concentrations, low GTP and Mg 2+ concentrations, and exogenous GDP in the reaction mixture. Minimum effects were observed with changes in reaction pH or temperature, changes in concentration of microtubule-associated proteins, alteration of the sulfonate buffer, or the presence of a calcium chelator in the reaction mixture. Under conditions most favorable for direct GDP incorporation, about one-third of the GDP in microtubules is incorporated directly (without GTP hydrolysis) and two-thirds is incorporated hydrolytically (as a consequence of GTP hydrolysis). Direct incorporation of GDP occurs in a constant proportion throughout elongation, and the amount of direct incorporation probably reflects the rapid equilibration of GDP and GTP at the exchangeable site that occurs before the onset of assembly

Heavy-ion targets

International Nuclear Information System (INIS)

Adair, H.L.; Kobisk, E.H.

1985-01-01

This chapter examines the characteristics of targets required in heavy-ion accelerator physics experiments. The effects of target parameters on heavy-ion experimental results are reviewed. The target fabrication and characterization techniques used to minimize experimental problems during heavy-ion bombardment are described. Topics considered include target thickness and uniformity, target lifetime, target purity, substrate materials, Doppler shift effects, metal preparations, and target preparation methods

Radwaste disposal by incorporation in matrix

International Nuclear Information System (INIS)

Curtiss, D.H.; Heacock, H.W.

1976-01-01

A process of safe disposal, handling, or storae of radwaste associated with nuclear power productin is described. A feature of the invention is to incorporate the radwaste in a hardenable, matrix-forming mass employing a cement-type binding agent to which alkali or alkaline-earth silicate is added, among other things, to increase liquid absorption. 9 claims

Dual function of the McaS small RNA in controlling biofilm formation

DEFF Research Database (Denmark)

Jørgensen, Mikkel Girke; Thomason, Maureen K.; Havelund, Johannes

2013-01-01

, and biofilm formation. Moreover, ectopic McaS expression leads to induction of two additional CsrA-repressed genes encoding diguanylate cyclases. Collectively, our study shows that McaS is a dual-function sRNA with roles in the two major post-transcriptional regulons controlled by the RNA-binding proteins Hfq...

Estimating the fraction of progeny virions that must incorporate APOBEC3G for suppression of productive HIV-1 infection

International Nuclear Information System (INIS)

Thangavelu, Pulari U.; Gupta, Vipul; Dixit, Narendra M.

2014-01-01

The contest between the host factor APOBEC3G (A3G) and the HIV-1 protein Vif presents an attractive target of intervention. The extent to which the A3G–Vif interaction must be suppressed to tilt the balance in favor of A3G remains unknown. We employed stochastic simulations and mathematical modeling of the within-host dynamics and evolution of HIV-1 to estimate the fraction of progeny virions that must incorporate A3G to render productive infection unsustainable. Using three different approaches, we found consistently that a transition from sustained infection to suppression of productive infection occurred when the latter fraction exceeded ∼0.8. The transition was triggered by A3G-induced hypermutations that led to premature stop codons compromising viral production and was consistent with driving the basic reproductive number, R 0 , below unity. The fraction identified may serve as a quantitative guideline for strategies targeting the A3G–Vif axis. - Highlights: • We perform simulations and mathematical modeling of the role of APOBEC3G in suppressing HIV-1 infection. • In three distinct ways, we estimate that when over 80% of progeny virions carry APOBEC3G, productive HIV-1 infection would be suppressed. • Our estimate of this critical fraction presents quantitative guidelines for strategies targeting the APOBEC3G–Vif axis

Intrinsic stress modulation in diamond like carbon films with incorporation of gold nanoparticles by PLA

Science.gov (United States)

Panda, Madhusmita; Krishnan, R.; Krishna, Nanda Gopala; Madapu, Kishore K.; Kamruddin, M.

2018-04-01

Intrinsic stress modulation in the diamond-like carbon (DLC) coatings with incorporation of gold nanoparticles was studied qualitatively from Raman shift. The films were deposited on Si (1 0 0) substrates by using Pulsed laser ablation (PLA) of pure pyrolytic graphite target and with a gold foil on it. Films compositional and chemical behavior was studied by X-ray photoelectron spectroscopy (XPS) and Visible Raman spectroscopy, respectively. The sp3 content obtained from XPS shows dramatic variation in DLC, DLC-Au(100), DLC-Au(200) and DLC-Au(300) as 39%, 41%, 47% and 66% with various gold contentsas 0%, 12%, 7.3% and 4.7%, respectively. The Raman spectra of DLC/Au films showed G-peak shift towards lower wavenumber indicating the reduction of intrinsic stress (internal compressive stress). The sp2, sp3 fraction in the films are also determined from FWHM (G-Peak).

Heterovalent Dopant Incorporation for Bandgap and Type Engineering of Perovskite Crystals

KAUST Repository

Abdelhady, Ahmed L.

2016-01-02

Controllable doping of semiconductors is a fundamental technological requirement for electronic and optoelectronic devices. As intrinsic semiconductors, hybrid perovskites have so far been a phenomenal success in photovoltaics. The inability to dope these materials heterovalently (or aliovalently) has greatly limited their wider utilizations in electronics. Here we show an efficient in situ chemical route that achieves the controlled incorporation of trivalent cations (Bi3+, Au3+, or In3+) by exploiting the retrograde solubility behavior of perovskites. We term the new method dopant incorporation in the retrograde regime. We achieve Bi3+ incorporation that leads to bandgap tuning (∼300 meV), 104 fold enhancement in electrical conductivity, and a change in the sign of majority charge carriers from positive to negative. This work demonstrates the successful incorporation of dopants into perovskite crystals while preserving the host lattice structure, opening new avenues to tailor the electronic and optoelectronic properties of this rapidly emerging class of solution-processed semiconductors. © 2016 American Chemical Society.

Heterovalent Dopant Incorporation for Bandgap and Type Engineering of Perovskite Crystals

KAUST Repository

Abdelhady, Ahmed L.; Saidaminov, Makhsud I.; Banavoth, Murali; Adinolfi, Valerio; Voznyy, Oleksandr; Katsiev, Khabiboulakh; Alarousu, Erkki; Comin, Riccardo; Dursun, Ibrahim; Sinatra, Lutfan; Sargent, Edward H.; Mohammed, Omar F.; Bakr, Osman

2016-01-01

Controllable doping of semiconductors is a fundamental technological requirement for electronic and optoelectronic devices. As intrinsic semiconductors, hybrid perovskites have so far been a phenomenal success in photovoltaics. The inability to dope these materials heterovalently (or aliovalently) has greatly limited their wider utilizations in electronics. Here we show an efficient in situ chemical route that achieves the controlled incorporation of trivalent cations (Bi3+, Au3+, or In3+) by exploiting the retrograde solubility behavior of perovskites. We term the new method dopant incorporation in the retrograde regime. We achieve Bi3+ incorporation that leads to bandgap tuning (∼300 meV), 104 fold enhancement in electrical conductivity, and a change in the sign of majority charge carriers from positive to negative. This work demonstrates the successful incorporation of dopants into perovskite crystals while preserving the host lattice structure, opening new avenues to tailor the electronic and optoelectronic properties of this rapidly emerging class of solution-processed semiconductors. © 2016 American Chemical Society.

49 CFR 193.2013 - Incorporation by reference.

Science.gov (United States)

2010-10-01

... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL... incorporated materials are available for inspection in the Pipeline and Hazardous Materials Safety... referenced material 49 CFR Reference A. American Gas Association (AGA): (1) “Purging Principles and Practices...

7 CFR 1755.901 - Incorporation by Reference.

Science.gov (United States)

2010-01-01

...”), incorporation by reference approved for § 1755.902(h). (e) The following Telecommunications Industry Association... AGRICULTURE TELECOMMUNICATIONS POLICIES ON SPECIFICATIONS, ACCEPTABLE MATERIALS, AND STANDARD CONTRACT FORMS... Performance Properties of Insulations and Jackets for Telecommunications Wire and Cable, approved March 10...

Quality Assurance of Ultrasound Imaging Systems for Target Localization and Online Setup Corrections

International Nuclear Information System (INIS)

Tome, Wolfgang A.; Orton, Nigel P.

2008-01-01

We describe quality assurance paradigms for ultrasound imaging systems for target localization (UISTL). To determine the absolute localization accuracy of a UISTL, an absolute coordinate system can be established in the treatment room and spherical targets at various depths can be localized. To test the ability of such a system to determine the magnitude of internal organ motion, a phantom that mimics the human male pelvic anatomy can be used to simulate different organ motion ranges. To assess the interuser variability of ultrasound (US) guidance, different experienced users can independently determine the daily organ shifts for the same patients for a number of consecutive fractions. The average accuracy for a UISTL for the localization of spherical targets at various depths has been found to be 0.57 ± 0.47 mm in each spatial dimension for various focal depths. For the phantom organ motion test it was found that the true organ motion could be determined to within 1.0 mm along each axis. The variability between different experienced users who localized the same 5 patients for five consecutive fractions was small in comparison to the indicated shifts. In addition to the quality assurance tests that address the ability of a UISTL to accurately localize a target, a thorough quality assurance program should also incorporate the following two aspects to ensure consistent and accurate localization in daily clinical use: (1) adequate training and performance monitoring of users of the US target localization system, and (2) prescreening of patients who may not be good candidates for US localization

Interacting with target tracking algorithms in a gaze-enhanced motion video analysis system

Science.gov (United States)

Hild, Jutta; Krüger, Wolfgang; Heinze, Norbert; Peinsipp-Byma, Elisabeth; Beyerer, Jürgen

2016-05-01

Motion video analysis is a challenging task, particularly if real-time analysis is required. It is therefore an important issue how to provide suitable assistance for the human operator. Given that the use of customized video analysis systems is more and more established, one supporting measure is to provide system functions which perform subtasks of the analysis. Recent progress in the development of automated image exploitation algorithms allow, e.g., real-time moving target tracking. Another supporting measure is to provide a user interface which strives to reduce the perceptual, cognitive and motor load of the human operator for example by incorporating the operator's visual focus of attention. A gaze-enhanced user interface is able to help here. This work extends prior work on automated target recognition, segmentation, and tracking algorithms as well as about the benefits of a gaze-enhanced user interface for interaction with moving targets. We also propose a prototypical system design aiming to combine both the qualities of the human observer's perception and the automated algorithms in order to improve the overall performance of a real-time video analysis system. In this contribution, we address two novel issues analyzing gaze-based interaction with target tracking algorithms. The first issue extends the gaze-based triggering of a target tracking process, e.g., investigating how to best relaunch in the case of track loss. The second issue addresses the initialization of tracking algorithms without motion segmentation where the operator has to provide the system with the object's image region in order to start the tracking algorithm.

Benchmarking spliced alignment programs including Spaln2, an extended version of Spaln that incorporates additional species-specific features.

Science.gov (United States)

Iwata, Hiroaki; Gotoh, Osamu

2012-11-01

Spliced alignment plays a central role in the precise identification of eukaryotic gene structures. Even though many spliced alignment programs have been developed, recent rapid progress in DNA sequencing technologies demands further improvements in software tools. Benchmarking algorithms under various conditions is an indispensable task for the development of better software; however, there is a dire lack of appropriate datasets usable for benchmarking spliced alignment programs. In this study, we have constructed two types of datasets: simulated sequence datasets and actual cross-species datasets. The datasets are designed to correspond to various real situations, i.e. divergent eukaryotic species, different types of reference sequences, and the wide divergence between query and target sequences. In addition, we have developed an extended version of our program Spaln, which incorporates two additional features to the scoring scheme of the original version, and examined this extended version, Spaln2, together with the original Spaln and other representative aligners based on our benchmark datasets. Although the effects of the modifications are not individually striking, Spaln2 is consistently most accurate and reasonably fast in most practical cases, especially for plants and fungi and for increasingly divergent pairs of target and query sequences.

Incorporation monitoring during handling of medically used radionuclides; Inkorporationsueberwachung beim Umgang mit medizinisch genutzten Radionukliden

Energy Technology Data Exchange (ETDEWEB)

Buchholz, Werner; Gerstmann, Udo [Bundesamt fuer Strahlenschutz, Oberschleissheim (Germany). FB Strahlenschutz und Gesundheit; Scholl, Clemens [Landesinstitut fuer Arbeitsgestaltung NRW, Duesseldorf (Germany). Inkorporationsmessstelle; Wanke, Carsten [Medizinische Hochschule Hannover (Germany). Strahlenschutz und Medizinische Physik

2017-08-01

The necessity of incorporation monitoring in nuclear medicine is dependent of the incorporation factor. For important applications, such as Tc-99m diagnostics and the radioiodine therapy specific measuring programs allow the determination of the incorporation factor. These factors are usually marginal so that a periodic monitoring is either not necessary or replaced by simple threshold measurements. Experiences of incorporation measuring stations show that incorporation might occur but does not induce significant doses.

Mg Incorporation Efficiency in Pulsed MOCVD of N-Polar GaN:Mg

Science.gov (United States)

Marini, Jonathan; Mahaboob, Isra; Hogan, Kasey; Novak, Steve; Bell, L. D.; Shahedipour-Sandvik, F.

2017-10-01

We report on the effect of growth polarity and pulsed or δ -doped growth mode on impurity incorporation in metalorganic chemical vapor deposition-grown GaN. In Ga-polar orientation, up to 12× enhancement in Mg concentration for given Mg flow rate is observed, resulting in enhanced p-type conductivity for these samples. In contrast, this enhancement effect is greatly diminished for N-polar samples, falling off with increasing Mg flow and showing maximum enhancement of 2.7× at 30 nmol/min Mg flow. At higher Mg flow rates, Mg incorporation at normal levels did not correspond to p-type conductivity, which may be due to Mg incorporation at nonacceptor sites. Concentrations of C, O, and Si were also investigated, revealing dependence on Mg flow in N-polar pulsed samples. Carbon incorporation was found to decrease with increasing Mg flow, and oxygen incorporation was found to remain high across varied Mg flow. These effects combine to result in N-polar samples that are not p-type when using the pulsed growth mode.

27 CFR 31.102 - Addition of partners or incorporation of partnership.

Science.gov (United States)

2010-04-01

... incorporation of partnership. 31.102 Section 31.102 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS ALCOHOL BEVERAGE DEALERS Partnerships § 31.102 Addition of partners or incorporation of partnership. Where a number of persons who have filed a...

Emerging investigator series: As( v ) in magnetite: incorporation and redistribution

Energy Technology Data Exchange (ETDEWEB)

Huhmann, Brittany L. [Department of Civil and Environmental Engineering; University of Iowa; Iowa City; USA; Neumann, Anke [School of Engineering; Newcastle University; Newcastle upon Tyne; UK; Boyanov, Maxim I. [Biosciences Division; Argonne National Laboratory; Argonne; USA; Institute of Chemical Engineering; Kemner, Kenneth M. [Biosciences Division; Argonne National Laboratory; Argonne; USA; Scherer, Michelle M. [Department of Civil and Environmental Engineering; University of Iowa; Iowa City; USA

2017-01-01

As coprecipitated with magnetite remained incorporated over time whereas sorbed As was redistributed and became increasingly incorporated into magnetite, both the absence and presence of aqueous Fe(ii).

The Mechanisms of Virulence Regulation by Small Noncoding RNAs in Low GC Gram-Positive Pathogens

Directory of Open Access Journals (Sweden)

Stephanie Pitman

2015-12-01

Full Text Available The discovery of small noncoding regulatory RNAs (sRNAs in bacteria has grown tremendously recently, giving new insights into gene regulation. The implementation of computational analysis and RNA sequencing has provided new tools to discover and analyze potential sRNAs. Small regulatory RNAs that act by base-pairing to target mRNAs have been found to be ubiquitous and are the most abundant class of post-transcriptional regulators in bacteria. The majority of sRNA studies has been limited to E. coli and other gram-negative bacteria. However, examples of sRNAs in gram-positive bacteria are still plentiful although the detailed gene regulation mechanisms behind them are not as well understood. Strict virulence control is critical for a pathogen’s survival and many sRNAs have been found to be involved in that process. This review outlines the targets and currently known mechanisms of trans-acting sRNAs involved in virulence regulation in various gram-positive pathogens. In addition, their shared characteristics such as CU interaction motifs, the role of Hfq, and involvement in two-component regulators, riboswitches, quorum sensing, or toxin/antitoxin systems are described.

Sorting nexin 6 enhances lamin a synthesis and incorporation into the nuclear envelope.

Directory of Open Access Journals (Sweden)

Jose M González-Granado

Full Text Available Nuclear lamins are important structural and functional proteins in mammalian cells, but little is known about the mechanisms and cofactors that regulate their traffic into the nucleus. Here, we demonstrate that trafficking of lamin A, but not lamin B1, and its assembly into the nuclear envelope are regulated by sorting nexin 6 (SNX6, a major component of the retromer that targets proteins and other molecules to specific subcellular locations. SNX6 interacts with lamin A in vitro and in vivo and links it to the outer surface of the endoplasmic reticulum in human and mouse cells. SNX6 transports its lamin A cargo to the nuclear envelope in a process that takes several hours. Lamin A protein levels in the nucleus augment or decrease, respectively, upon gain or loss of SNX6 function. We further show that SNX6-dependent lamin A nuclear import occurs across the nuclear pore complex via a RAN-GTP-dependent mechanism. These results identify SNX6 as a key regulator of lamin A synthesis and incorporation into the nuclear envelope.

Sorting Nexin 6 Enhances Lamin A Synthesis and Incorporation into the Nuclear Envelope

Science.gov (United States)

González-Granado, Jose M.; Navarro-Puche, Ana; Molina-Sanchez, Pedro; Blanco-Berrocal, Marta; Viana, Rosa; de Mora, Jaime Font; Andrés, Vicente

2014-01-01

Nuclear lamins are important structural and functional proteins in mammalian cells, but little is known about the mechanisms and cofactors that regulate their traffic into the nucleus. Here, we demonstrate that trafficking of lamin A, but not lamin B1, and its assembly into the nuclear envelope are regulated by sorting nexin 6 (SNX6), a major component of the retromer that targets proteins and other molecules to specific subcellular locations. SNX6 interacts with lamin A in vitro and in vivo and links it to the outer surface of the endoplasmic reticulum in human and mouse cells. SNX6 transports its lamin A cargo to the nuclear envelope in a process that takes several hours. Lamin A protein levels in the nucleus augment or decrease, respectively, upon gain or loss of SNX6 function. We further show that SNX6-dependent lamin A nuclear import occurs across the nuclear pore complex via a RAN-GTP-dependent mechanism. These results identify SNX6 as a key regulator of lamin A synthesis and incorporation into the nuclear envelope. PMID:25535984

In vivo incorporation of labeled fatty acids in rat liver lipids after oral administration

International Nuclear Information System (INIS)

Leyton, J.; Drury, P.J.; Crawford, M.A.

1987-01-01

Striking differences were found in the compartmentalization of fatty acids into liver lipid fractions. The saturated fatty acids--lauric, myristic, palmitic and stearic--were incorporated into phosphoglycerides at faster rates with increasing chain lengths, while triglyceride incorporation was almost uniform. The degree of incorporation of the unsaturated fatty acids into phosphoglycerides (structural) compared to triglyceride (storage and energy) was the converse of their oxidation rates. The incorporation of oleic, linoleic and alpha-linolenic acids was mainly into triglyceride, whereas dihomo-gamma-linolenic acid and arachidonic acid were preferentially incorporated into phosphoglycerides. The data suggest that distribution of each fatty acid is different depending on its destination for structural or energy function

Incorporation of T4 bacteriophage in electrospun fibres.

Science.gov (United States)

Korehei, R; Kadla, J

2013-05-01

Antibacterial food packaging materials, such as bacteriophage-activated electrospun fibrous mats, may address concerns triggered by waves of bacterial food contamination. To address this, we investigated several efficient methods for incorporating T4 bacteriophage into electrospun fibrous mats. The incorporation of T4 bacteriophage using simple suspension electrospinning led to more than five orders of magnitude decrease in bacteriophage activity. To better maintain bacteriophage viability, emulsion electrospinning was developed where the T4 bacteriophage was pre-encapsulated in an alginate reservoir via an emulsification process and subsequently electrospun into fibres. This resulted in an increase in bacteriophage viability, but there was still two orders of magnitude drop in activity. Using a coaxial electrospinning process, full bacteriophage activity could be maintained. In this process, a core/shell fibre structure was formed with the T4 bacteriophage being directly incorporated into the fibre core. The core/shell fibre encapsulated bacteriophage exhibited full bacteriophage viability after storing for several weeks at +4°C. Coaxial electrospinning was shown to be capable of encapsulating bacteriophages with high loading capacity, high viability and long storage time. These results are significant in the context of controlling and preventing bacterial infections in perishable foods during storage. © 2013 The Society for Applied Microbiology.

Antiproton Target

CERN Multimedia

1980-01-01

Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

Incorporating biological control into IPM decision making

Science.gov (United States)

Of the many ways biological control can be incorporated into Integrated Pest Management (IPM) programs, natural enemy thresholds are arguably most easily adopted by stakeholders. Integration of natural enemy thresholds into IPM programs requires ecological and cost/benefit crop production data, thr...

High-Strain Rate Failure Modeling Incorporating Shear Banding and Fracture

Science.gov (United States)

2017-11-22

High Strain Rate Failure Modeling Incorporating Shear Banding and Fracture The views, opinions and/or findings contained in this report are those of...SECURITY CLASSIFICATION OF: 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND SUBTITLE 13. SUPPLEMENTARY NOTES 12. DISTRIBUTION AVAILIBILITY STATEMENT 6. AUTHORS...Report as of 05-Dec-2017 Agreement Number: W911NF-13-1-0238 Organization: Columbia University Title: High Strain Rate Failure Modeling Incorporating

Biocompatibility of poly(lactic acid) with incorporated graphene-based materials

OpenAIRE

Pinto, Artur Moreira; Moreira, Susana Margarida Gomes; Gonçalves, Inês; Gama, F. M.; Mendes, Adélio; Magalhães, Fernão D.

2013-01-01

The incorporation of graphene-based materials has been shown to improve mechanical properties of poly(lactic acid) (PLA). In this work, PLA films and composite PLA films incorporating two graphene-based materials – graphene oxide (GO) and graphene nanoplatelets (GNP) – were prepared and characterized regarding not only biocompatibility, but also surface topography, chemistry and wettability. The presence of both fillers changed the films surface topography, increasing the roughness, and modif...

Pyrazolopyrimidines establish MurC as a vulnerable target in Pseudomonas aeruginosa and Escherichia coli.

Science.gov (United States)

Hameed P, Shahul; Manjrekar, Praveena; Chinnapattu, Murugan; Humnabadkar, Vaishali; Shanbhag, Gajanan; Kedari, Chaitanyakumar; Mudugal, Naina Vinay; Ambady, Anisha; de Jonge, Boudewijn L M; Sadler, Claire; Paul, Beena; Sriram, Shubha; Kaur, Parvinder; Guptha, Supreeth; Raichurkar, Anandkumar; Fleming, Paul; Eyermann, Charles J; McKinney, David C; Sambandamurthy, Vasan K; Panda, Manoranjan; Ravishankar, Sudha

2014-10-17

The bacterial peptidoglycan biosynthesis pathway provides multiple targets for antibacterials, as proven by the clinical success of β-lactam and glycopeptide classes of antibiotics. The Mur ligases play an essential role in the biosynthesis of the peptidoglycan building block, N-acetyl-muramic acid-pentapeptide. MurC, the first of four Mur ligases, ligates l-alanine to UDP-N-acetylmuramic acid, initiating the synthesis of pentapeptide precursor. Therefore, inhibiting the MurC enzyme should result in bacterial cell death. Herein, we report a novel class of pyrazolopyrimidines with subnanomolar potency against both Escherichia coli and Pseudomonas aeruginosa MurC enzymes, which demonstrates a concomitant bactericidal activity against efflux-deficient strains. Radio-labeled precursor incorporation showed these compounds selectively inhibited peptidoglycan biosynthesis, and genetic studies confirmed the target of pyrazolopyrimidines to be MurC. In the presence of permeability enhancers such as colistin, pyrazolopyrimidines exhibited low micromolar MIC against the wild-type bacteria, thereby, indicating permeability and efflux as major challenges for this chemical series. Our studies provide biochemical and genetic evidence to support the essentiality of MurC and serve to validate the attractiveness of target for antibacterial discovery.

Tritiated thymidine incorporation and the growth of heterotrophic bacteria in warm core rings

International Nuclear Information System (INIS)

Ducklow, H.W.; Hill, S.M.

1985-01-01

The time-course of the incorporation rate of [methyl- 3 H]thymidine ([ 3 H]TdR) was established during 6-12 h incubations of natural bacterial populations sampled from the surface layers of warm core Gulf Stream rings. Parallel estimates of changes in cell numbers were made in order to examine the relationships between TdR incorporation and population growth for oceanic bacterial populations. Their results indicate that a conversion factor of 4 x 10 18 cells produced per mole of [ 3 H]TdR incorporated yielded estimates of bacterial production which were within a factor of 2 or 3 of production estimates derived from changes in cell numbers in seawater cultures. The authors observed a significant, direct relationship between the initial rates of TdR incorporation per cell and specific growth rates and conclude that initial short term (15-45 min) assays of TdR incorporation are a valuable tool for studying bacterial production in oceanic waters. In most incubations, the rate of TdR incorporation increased more rapidly than did cell numbers. Very large conversion factor values were derived from these data. The discrepancy between growth determined from TdR incorporation rates and total bacterial numbers in seawater cultures has not been observed in previous studies of coastal, estuarine, or lacustrine bacteria, but was a consistent feature of our studies on oceanic populations

Development and electrochemical characterization of Ni‐P coated tungsten incorporated electroless nickel coatings

Energy Technology Data Exchange (ETDEWEB)

Shibli, S.M.A., E-mail: smashibli@yahoo.com; Chinchu, K.S.

2016-08-01

Ni‐P-W alloy and composite coatings were prepared by incorporation of sodium tungstate/tungsten and Ni‐P coated tungsten into electroless nickel bath respectively. Good inter-particle interactions among the depositing elements i.e. Ni and P with the incorporating tungsten particles were achieved by means of pre-coated tungsten particle by electroless nickel covering prior to its addition into the electroless bath. The pre-coated tungsten particles got incorporated uniformly into the Ni-P matrix of the coating. The particles and the coatings were characterized at different stages by different techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS). The electroless Ni-P coating incorporated with pre-coated tungsten exhibited considerably high hardness, thickness and deposition rate. The performance and corrosion resistance characteristics of the composite coating incorporated with the nickel coated tungsten were found to be superior over other conventional Ni-P-W ternary alloy coatings currently reported. - Highlights: • An amorphous Ni-P coating was effectively formed on tungsten particles. • Electroless ternary Ni-P-W composite coatings were successfully prepared. • Enhancement in the inter-particle interaction in the Ni-P composite matrix was achieved. • Efficient and uniform incorporation of the composite in the internal layer was evident. • The tungsten incorporated coating possessed effective barrier protection.

Minority Political Incorporation and Policy Outcomes in U.S. School Districts

Science.gov (United States)

Leon, Ana L.

2017-01-01

This study examines if gains in ethnic political representation and incorporation on local school boards result in policy responsiveness, as well as improved student achievement in a way that benefits minorities. By applying the political incorporation framework developed by Browning, Marshall, and Tabb (1984) to the education policy arena, gains…

Target laboratory

International Nuclear Information System (INIS)

Ephraim, D.C.; Pednekar, A.R.

1993-01-01

A target laboratory to make stripper foils for the accelerator and various targets for use in the experiments is set up in the pelletron accelerator facility. The facilities available in the laboratory are: (1) D.C. glow discharge setup, (2) carbon arc set up, and (3) vacuum evaporation set up (resistance heating), electron beam source, rolling mill - all for target preparation. They are described. Centrifugal deposition technique is used for target preparation. (author). 3 figs

Emissive sensors and devices incorporating these sensors

Science.gov (United States)

Swager, Timothy M; Zhang, Shi-Wei

2013-02-05

The present invention generally relates to luminescent and/or optically absorbing compositions and/or precursors to those compositions, including solid films incorporating these compositions/precursors, exhibiting increased luminescent lifetimes, quantum yields, enhanced stabilities and/or amplified emissions. The present invention also relates to sensors and methods for sensing analytes through luminescent and/or optically absorbing properties of these compositions and/or precursors. Examples of analytes detectable by the invention include electrophiles, alkylating agents, thionyl halides, and phosphate ester groups including phosphoryl halides, cyanides and thioates such as those found in certain chemical warfare agents. The present invention additionally relates to devices and methods for amplifying emissions, such as those produced using the above-described compositions and/or precursors, by incorporating the composition and/or precursor within a polymer having an energy migration pathway. In some cases, the compositions and/or precursors thereof include a compound capable of undergoing a cyclization reaction.

A Framework Incorporating Community Preferences in Use ...

Science.gov (United States)

The report is intended to assist water quality officials, watershed managers, members of stakeholder groups, and other interested individuals in fully evaluating ecological and socioeconomic objectives and the gains and losses that often are involved in use attainment decisions. In addition, this report enables local, state, and tribal managers to better understand the benefits, as well as the costs, of attaining high water quality, and to incorporate community preferences in decision-making. Specific objectives are (1) to provide an introduction to the CWA and WQS regulation and analyses related to setting or changing designated uses; (2) create a basis for understanding the relationship between use-attainment decisions and the effects on ecosystems, ecosystem services, and ecological benefits; (3) serve as reference for methods that elicit or infer preferences for benefits and costs related to attaining uses and (4) present process for incorporating new approaches in water quality decisions.

Hypericum perforatum incorporated chitosan films as potential bioactive wound dressing material.

Science.gov (United States)

Güneş, Seda; Tıhmınlıoğlu, Funda

2017-09-01

Recent studies in wound dressing applications offer new therapies and promote wound healing process. The aim of this study was to develop Hypericum perforatum (St John's Wort) oil incorporated chitosan films for wound dressing applications. H. perforatum oil as a potential therapeutic agent was encapsulated in chitosan film to achieve a better wound dressing material. Oil incorporated chitosan films were successfully prepared by solvent casting method in different oil concentrations (0.25-1.5%v/v). Water vapor permeability (WVP), mechanical test, swelling behavior and surface hydrophobicity were performed in order to characterize the prepared films. Antimicrobial test was performed by disc diffusion method and the growth inhibition effects of the films including different amount of H. perforatum oil were investigated on Escherichia coli and Staphylococcus aureus. WVP increased with oil incorporation and the highest value was obtained for 0.25% oil concentration.The highest strain value was obtained in 0.25% oil content films although tensile stress decreased with increasing oil content. H. perforatum oil incorporated films had antimicrobial effect on both microorganisms. Chitosan based films had no cytotoxic effects on NIH3T3fibroblast cells and provided a good surface for cell attachment and proliferation. The results showed that the H. perforatum incorporated chitosan films seems to be a potential and novel biomaterial for wound healing applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidic platform for efficient Nanodisc assembly, membrane protein incorporation, and purification.

Science.gov (United States)

Wade, James H; Jones, Joshua D; Lenov, Ivan L; Riordan, Colleen M; Sligar, Stephen G; Bailey, Ryan C

2017-08-22

The characterization of integral membrane proteins presents numerous analytical challenges on account of their poor activity under non-native conditions, limited solubility in aqueous solutions, and low expression in most cell culture systems. Nanodiscs are synthetic model membrane constructs that offer many advantages for studying membrane protein function by offering a native-like phospholipid bilayer environment. The successful incorporation of membrane proteins within Nanodiscs requires experimental optimization of conditions. Standard protocols for Nanodisc formation can require large amounts of time and input material, limiting the facile screening of formation conditions. Capitalizing on the miniaturization and efficient mass transport inherent to microfluidics, we have developed a microfluidic platform for efficient Nanodisc assembly and purification, and demonstrated the ability to incorporate functional membrane proteins into the resulting Nanodiscs. In addition to working with reduced sample volumes, this platform simplifies membrane protein incorporation from a multi-stage protocol requiring several hours or days into a single platform that outputs purified Nanodiscs in less than one hour. To demonstrate the utility of this platform, we incorporated Cytochrome P450 into Nanodiscs of variable size and lipid composition, and present spectroscopic evidence for the functional active site of the membrane protein. This platform is a promising new tool for membrane protein biology and biochemistry that enables tremendous versatility for optimizing the incorporation of membrane proteins using microfluidic gradients to screen across diverse formation conditions.

Tailoring the vortex pinning strength of YBCO thin films by systematic incorporation of hybrid artificial pinning centers

International Nuclear Information System (INIS)

Jha, Alok K; Matsumoto, Kaname; Horide, Tomoya; Saini, Shrikant; Mele, Paolo; Ichinose, Ataru; Yoshida, Yutaka; Awaji, Satoshi

2015-01-01

The effect of hybrid (columnar and spherical together) artificial pinning centers (APCs) on the vortex pinning properties of YBa 2 Cu 3 O 7−δ (YBCO) thin films is investigated in detail on the basis of variation of critical current density (J C ) with applied magnetic field and also with the orientation of the applied magnetic field at 65 K and 77 K. Premixed YBCO + BaSnO 3 composite targets are used for the deposition of the YBCO films which consist of self-assembled BaSnO 3 nanocolumns (1D APCs); on the other hand, for the deposition of the YBCO films with hybrid APCs (BaSnO 3 nanocolumns together with Y 2 O 3 nanoparticles), the surface of the premixed YBCO + BaSnO 3 composite targets are modified by putting a thin Y 2 O 3 sectored piece on the premixed YBCO + BaSnO 3 composite targets by means of silver paste. F pmax value increases systematically with incorporation of 1D and 1D and 3D APCs and it also shifts towards higher applied magnetic fields. Films with 1D APCs exhibit a strong J C peak at Θ = 0° (H//c-axis) whereas films consisting of hybrid APCs exhibit enhanced J C at all the investigated angular regimes. A possible mechanism of vortex pinning in samples with hybrid APCs is also discussed suggesting the role of 1D and 3D APCs. (paper)

Incorporating Lean Construction agent into the Building Standards Act: the Spanish case study

Directory of Open Access Journals (Sweden)

Brioso Xavier

2016-12-01

Full Text Available There is a demand for lean construction in Europe; even though lean construction is still an emerging field and there is growing interest, there are no regulations on this topic. The main objective of this research is to regulate this role when in a project and to define and develop a building agent structure, according to the Building Standards Act (LOE by its acronym in Spanish, to be able to incorporate it into the Spanish law, protecting it from civil liabilities. In Spain, there is jurisprudence in civil jurisdiction based on the LOE to acquit or convict building agents, who are defined in the courts as “constructive managers” or similar. For this reason, courts could establish in the future several liabilities for the lean construction specialist and other agents of the project, depending on their actions and based on the implementation of the lean project delivery system, the target value design and the integrated project delivery. Conversely, it is possible that the level of action of the lean construction specialist may comprise design management, construction management and contract management. Accordingly, one or more building agents should be appropriately incorporated into the LOE according to their functions and responsibilities and based on the levels of action of the lean construction specialist. The creation of the following agents is proposed: design manager, construction manager and contract manager, definitions that are developed in this study. These agents are loosely defined, because any project manager, building information modeling manager or similar may act as one or as more-than-one of them. Finally, the creation of the lean construction manager is also proposed, as the agent who takes on the role of the design manager, construction manager and contract manager, but focused on the lean production principles.

Art. 70-71: Incorporation and making available of standard contract terms

NARCIS (Netherlands)

Loos, M.; Colombi Ciacchi, A.

2016-01-01

Incorporation of standard terms is a much-debated issue in almost all legal systems. Any legal instrument on contract law therefore must provide an answer as to when terms are incorporated – but answers may vary considerably from one legal system to the next. In this chapter the provisions of the –

An integrated expression atlas of miRNAs and their promoters in human and mouse

DEFF Research Database (Denmark)

de Rie, Derek; Abugessaisa, Imad; Alam, Tanvir

2017-01-01

MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libr...

Incorporation of iodine into calcium phosphates with apatitic structure

International Nuclear Information System (INIS)

Coulon, Antoine

2014-01-01

In order to avoid the release of 129 I (long-lived intermediate-level waste) in the environment, we describe a novel material incorporating iodine under the form of iodate in a calcium phosphate based hydroxyapatite. This material is prepared by two synthetic processes: a wet precipitation route followed by a spark plasma sintering and a cementitious route. A high iodine content (with a maximum incorporation rate of 10 wt.%) is reached for both processes, by incorporation of the iodate in the apatitic structure. A monolith with relative density of 88.6% was obtained after shaping of the precipitated powders by spark plasma sintering. This material reveals satisfactory leaching properties, with an initial leaching rate in pure water at 50 C of 10 -2 g.m -2 .j -1 , and a residual leaching rate at 50 C of 10 -5 g.m -2 .j -1 in underground water of potential geological repositories. All in all, this material is a potential candidate for the conditioning of radioactive iodine. (author) [fr

Optimum sizing of wind-battery systems incorporating resource uncertainty

International Nuclear Information System (INIS)