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Sample records for specific molecular beacon

  1. Molecular Beacons in Diagnostics

    OpenAIRE

    Tyagi, Sanjay; Kramer, Fred Russell

    2012-01-01

    Recent technical advances have begun to realize the potential of molecular beacons to test for diverse infections in clinical diagnostic laboratories. These include the ability to test for, and quantify, multiple pathogens in the same clinical sample, and to detect antibiotic resistant strains within hours. The design principles of molecular beacons have also spawned a variety of allied technologies.

  2. Molecular beacon based biosensor for the sequence-specific detection of DNA using DNA-capped gold nanoparticles-streptavidin conjugates for signal amplification

    International Nuclear Information System (INIS)

    Fang, Xian; Jiang, Wei; Han, Xiaowei; Zhang, Yuzhong

    2013-01-01

    We describe a highly sensitive and selective molecular beacon-based electrochemical impedance biosensor for the sequence-specific detection of DNA. DNA-capped conjugates between gold nanoparticles (Au-NPs) and streptavidin are used for signal amplification. The molecular beacon was labeled with a thiol at its 5′ end and with biotin at its 3′ end, and then immobilized on the surface of a bare gold electrode through the formation of Au-S bonds. Initially, the molecular beacon is present in the “closed” state, and this shields the biotin from being approached by streptavidin due to steric hindrance. In the presence of the target DNA, the target DNA molecules hybridize with the loop and cause a conformational change that moves the biotin away from the surface of the electrode. The biotin thereby becomes accessible for the reporter (the DNA-streptavidin capped Au-NPs), and this results in a distinct increase in electron transfer resistance. Under optimal conditions, the increase in resistance is linearly related to the logarithm of the concentration of complementary target DNA in the range from 1.0 fM to 0.1 μM, with a detection limit of 0.35 fM (at an S/N of 3). This biosensor exhibits good selectivity, and acceptable stability and reproducibility. (author)

  3. Diagnosis of Neisseria gonorrhoeae Using Molecular Beacon

    Science.gov (United States)

    Patel, Achchhe Lal; Sonkar, Subash Chandra; Kumari, Indu; Saluja, Daman

    2015-01-01

    Neisseria gonorrhoeae is an important sexually transmitted diseases (STD) causing pathogen worldwide. Due to absence of an affordable diagnostic assay, routine screening of gonococcal infection becomes impossible in developing countries where infection rates are maximum. Treatment is given on the basis of symptoms alone which leads to spread of infection. Thus, development of a rapid, sensitive, specific, and PCR based visual diagnostic assay suitable for developing countries, required for better disease management, is aimed at in present study. Endocervical swabs were collected from patients visiting gynecology department of various hospitals in Delhi. In-house PCR based assay was developed and modified to visual assay using molecular beacon for end-point detection. It was evaluated against Roche AMPLICOR NG kit and rmp gene. Specificity of beacon was confirmed by competition experiments. Diagnostic test was 98.21% specific and 99.59% sensitive whereas negative and positive predicted value were 99.40% and 98.78%, respectively. We also observed that twice the concentration (2X) of premix was stable at 4°C for 4 months and dry swab samples gave concordant results with that of wet swabs. These features make the test best suitable for routine diagnosis of genital infections in developing countries. PMID:25802857

  4. Synthesis and Characterization of a Magnetically Active 19F Molecular Beacon.

    Science.gov (United States)

    Dempsey, Megan E; Marble, Hetal D; Shen, Tun-Li; Fawzi, Nicolas L; Darling, Eric M

    2018-02-21

    Gene expression is used extensively to describe cellular characteristics and behaviors; however, most methods of assessing gene expression are unsuitable for living samples, requiring destructive processes such as fixation or lysis. Recently, molecular beacons have become a viable tool for live-cell imaging of mRNA molecules in situ. Historically, beacon-mediated imaging has been limited to fluorescence-based approaches. We propose the design and synthesis of a novel molecular beacon for magnetic resonance detection of any desired target nucleotide sequence. The biologically compatible synthesis incorporates commonly used bioconjugation reactions in aqueous conditions and is accessible for laboratories without extensive synthesis capabilities. The resulting beacon uses fluorine ( 19 F) as a reporter, which is broadened, or turned "off", via paramagnetic relaxation enhancement from a stabilized nitroxide radical spin label when the beacon is not bound to its nucleic acid target. Therefore, the 19 F NMR signal of the beacon is quenched in its hairpin conformation when the spin label and the 19 F substituent are held in proximity, but the signal is recovered upon beacon hybridization to its specific complementary nucleotide sequence by physical separation of the radical from the 19 F reporter. This study establishes a path for magnetic resonance-based assessment of specific mRNA expression, providing new possibilities for applying molecular beacon technology in living systems.

  5. Highly sensitive and rapid bacteria detection using molecular beacon-Au nanoparticles hybrid nanoprobes.

    Science.gov (United States)

    Cao, Jing; Feng, Chao; Liu, Yan; Wang, Shouyu; Liu, Fei

    2014-07-15

    Since many diseases are caused by pathogenic bacterial infections, accurate and rapid detection of pathogenic bacteria is in urgent need to timely apply appropriate treatments and to reduce economic costs. To end this, we designed molecular beacon-Au nanoparticle hybrid nanoprobes to improve the bacterial detection efficiency and sensitivity. Here, we show that the designed molecular beacon modified Au nanoparticles could specifically recognize synthetic DNAs targets and can readily detect targets in clinical samples. Moreover, the hybrid nanoprobes can recognize Escherichia coli within an hour at a concentration of 10(2) cfu/ml, which is 1000-folds sensitive than using molecular beacon directly. Our results show that the molecular beacon-Au nanoparticle hybrid nanoprobes have great potential in medical and biological applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Early Detection of Breast Cancer Using Molecular Beacons

    National Research Council Canada - National Science Library

    Yang, Lily

    2008-01-01

    .... We proposed to use molecular beacon technology to detect the level of expression of several biomarker genes that are highly expressed in breast cancer cells but not in normal breast epithelial cells...

  7. Molecular Beacon-Based MicroRNA Imaging During Neurogenesis.

    Science.gov (United States)

    Lee, Jonghwan; Kim, Soonhag

    2016-01-01

    The fluorescence monitoring system for examining endogenous microRNA (miRNA) activity in cellular level provides crucial information on not only understanding a critical role of miRNA involving a variety of biological processes, but also evaluating miRNA expression patterns in a noninvasive manner. In this protocol, we report the details of a new procedure for a molecular beacon-based miRNA monitoring system, which includes the illustration scheme for miRNA detection strategy, exogenous miRNA detection, and measurement of endogenous miRNA expression level during neurogenesis. The fluorescence signal of miR-124a beacon quenched by BHQ2 was gradually recovered as increasing concentration of the miR-124a in tube. The functional work of miR-124a beacon was examined in intracellular environment, allowing for the internalization of the miR-124a beacon by lipofectamine, which resulted in activated fluorescent signals of the miR-124a beacon in the HeLa cells after the addition of synthetic miR-124a. The endogenous miR-124a expression level was detected by miR-124a beacon system during neurogenesis, showing brighter fluorescence intensity in cytoplasmic area of P19 cells after induction of neuronal differentiation by retinoic acid. The molecular beacon based-miRNA detection technique could be applicable to the simultaneous visualization of a variety of miRNA expression patterns using different fluorescence dyes. For the study of examining endogenous miRNA expression level using miRNA-beacon system, if cellular differentiation step is already prepared, transfection step of miR-124a beacon into P19 cells, and acquisition of activated fluorescence signal measured by confocal microscope can be conducted approximately within 6 h.

  8. Molecular beacon – tool for real time studying gene activity in stem cells

    DEFF Research Database (Denmark)

    Ilieva, Mirolyuba; Dufva, Martin

    Cells respond to their internal genetic programs and external stimuli by modulating the synthesis of specific mRNAs. Direct observation of mRNA expression in living cells can provide valuable information with regards to understanding fundamental processes such cell differentiation, regeneration...... and cancerogenesis. Molecular beacon technology is based on fluorescence resonance energy transfer (FRET) and the complementary pairing principles. These fluorescent molecular probes are highly specific and sensitive and are one important tool in in vitro diagnostics. Here molecular beacons are used to follow...

  9. Analyte-Triggered DNA-Probe Release from a Triplex Molecular Beacon for Nanopore Sensing.

    Science.gov (United States)

    Guo, Bingyuan; Sheng, Yingying; Zhou, Ke; Liu, Quansheng; Liu, Lei; Wu, Hai-Chen

    2018-03-26

    A new nanopore sensing strategy based on triplex molecular beacon was developed for the detection of specific DNA or multivalent proteins. The sensor is composed of a triplex-forming molecular beacon and a stem-forming DNA component that is modified with a host-guest complex. Upon target DNA hybridizing with the molecular beacon loop or multivalent proteins binding to the recognition elements on the stem, the DNA probe is released and produces highly characteristic current signals when translocated through α-hemolysin. The frequency of current signatures can be used to quantify the concentrations of the target molecules. This sensing approach provides a simple, quick, and modular tool for the detection of specific macromolecules with high sensitivity and excellent selectivity. It may find useful applications in point-of-care diagnostics with a portable nanopore kit in the future. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Caged molecular beacons: controlling nucleic acid hybridization with light.

    Science.gov (United States)

    Wang, Chunming; Zhu, Zhi; Song, Yanling; Lin, Hui; Yang, Chaoyong James; Tan, Weihong

    2011-05-28

    We have constructed a novel class of light-activatable caged molecular beacons (cMBs) that are caged by locking two stems with a photo-labile biomolecular interaction or covalent bond. With the cMBs, the nucleic acid hybridization process can be easily controlled with light, which offers the possibility for a high spatiotemporal resolution study of intracellular mRNAs. © The Royal Society of Chemistry 2011

  11. Molecular beacon probes-base multiplex NASBA Real-time for detection of HIV-1 and HCV.

    Science.gov (United States)

    Mohammadi-Yeganeh, S; Paryan, M; Mirab Samiee, S; Kia, V; Rezvan, H

    2012-06-01

    Developed in 1991, nucleic acid sequence-based amplification (NASBA) has been introduced as a rapid molecular diagnostic technique, where it has been shown to give quicker results than PCR, and it can also be more sensitive. This paper describes the development of a molecular beacon-based multiplex NASBA assay for simultaneous detection of HIV-1 and HCV in plasma samples. A well-conserved region in the HIV-1 pol gene and 5'-NCR of HCV genome were used for primers and molecular beacon design. The performance features of HCV/HIV-1 multiplex NASBA assay including analytical sensitivity and specificity, clinical sensitivity and clinical specificity were evaluated. The analysis of scalar concentrations of the samples indicated that the limit of quantification of the assay was beacon probes detected all HCV genotypes and all major variants of HIV-1. This method may represent a relatively inexpensive isothermal method for detection of HIV-1/HCV co-infection in monitoring of patients.

  12. Molecular beacon anchored onto a graphene oxide substrate

    Science.gov (United States)

    Darbandi, Arash; Datta, Debopam; Patel, Krunal; Lin, Gary; Stroscio, Michael A.; Dutta, Mitra

    2017-09-01

    In this article, we report a graphene oxide-based nanosensor incorporating semiconductor quantum dots linked to DNA-aptamers that functions as a ‘turn-off’ fluorescent nanosensor for detection of low concentrations of analytes. A specific demonstration of this turn-off aptasensor is presented for the case of the detection of mercury (II) ions. In this system, ensembles of aptamer-based quantum-dot sensors are anchored onto graphene oxide (GO) flakes which provide a platform for analyte detection in the vicinity of GO. Herein, the operation of this ensemble-based nanosensor is demonstrated for mercury ions, which upon addition of mercury, quenching of the emission intensity from the quantum dots is observed due to resonance energy transfer between quantum dots and the gold nanoparticle connected via a mercury target aptamer. A key result is that the usually dominant effect of quenching of the quantum dot due to close proximity to the GO can be reduced to negligible levels by using a linker molecule in conjunctions with the aptamer-based nanosensor. The effect of ionic concentration of the background matrix on the emission intensity was also investigated. The sensor system is found to be highly selective towards mercury and exhibits a linear behavior (r 2 > 0.99) in the nanomolar concentration range. The detection limit of the sensor towards mercury with no GO present was found to be 16.5 nM. With GO attached to molecular beacon via 14 base, 35 base, and 51 base long linker DNA, the detection limit was found to be 38.4 nM, 9.45 nM, and 11.38 nM; respectively.

  13. Detection of DNA damage by using hairpin molecular beacon probes and graphene oxide.

    Science.gov (United States)

    Zhou, Jie; Lu, Qian; Tong, Ying; Wei, Wei; Liu, Songqin

    2012-09-15

    A hairpin molecular beacon tagged with carboxyfluorescein in combination with graphene oxide as a quencher reagent was used to detect the DNA damage by chemical reagents. The fluorescence of molecular beacon was quenched sharply by graphene oxide; while in the presence of its complementary DNA the quenching efficiency decreased because their hybridization prevented the strong adsorbability of molecular beacon on graphene oxide. If the complementary DNA was damaged by a chemical reagent and could not form intact duplex structure with molecular beacon, more molecular beacon would adsorb on graphene oxide increasing the quenching efficiency. Thus, damaged DNA could be detected based on different quenching efficiencies afforded by damaged and intact complementary DNA. The damage effects of chlorpyrifos-methyl and three metabolites of styrene such as mandelieaeids, phenylglyoxylieaeids and epoxystyrene on DNA were studied as models. The method for detection of DNA damage was reliable, rapid and simple compared to the biological methods. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Chimeric peptide beacons: a direct polypeptide analog of DNA molecular beacons†

    OpenAIRE

    Oh, Kenneth J.; Cash, Kevin J.; Lubin, Arica A.; Plaxco, Kevin W.

    2007-01-01

    We have developed a new biosensor architecture, which is comprised of a polypeptide–peptide nucleic acid tri-block copolymer and which we have termed chimeric peptide beacons (CPB), that generates an optical output via a mechanism analogous to that employed in DNA-based molecular beacons.

  15. High-throughput SNP genotyping: combining tag SNPs and molecular beacons

    CSIR Research Space (South Africa)

    Barreiro, LB

    2009-10-01

    Full Text Available In the last decade, molecular beacons have emerged to become a widely used tool in the multiplex typing of single nucleotide polymorphisms (SNPs). Improvements in detection technologies in instrumentation and chemistries to label these probes have...

  16. A molecular-beacon-based asymmetric PCR assay for easy visualization of amplicons in the diagnosis of trichomoniasis.

    Science.gov (United States)

    Sonkar, Subash C; Sachdev, Divya; Mishra, Prashant K; Kumar, Anita; Mittal, Pratima; Saluja, Daman

    2016-12-15

    The currently available nucleic acid amplification tests (NAATs) for trichomoniasis are accurate, quick and confirmative with superior sensitivity than traditional culture-based microbiology assays. However, these assays are associated with problems of carry over contamination, false positive results, requirement of technical expertise for performance and detection of end product. Hence, a diagnostic assay with easy visualization of the amplified product will be profitable. An in-house, rapid, sensitive, specific molecular-beacon-based PCR assay, using primers against pfoB gene of Trichomonas vaginalis, was developed and evaluated using dry ectocervical swabs (n=392) from symptomatic females with vaginal discharge. Total DNA was isolated and used as template for the PCR assays. The performance and reproducibility of PCR assay was evaluated by composite reference standard (CRS). For easy visualization of the amplified product, molecular-beacon was designed and amplicons were visualized directly using fluorescent handheld dark reader or by Micro-Plate Reader. Molecular-beacons are single-stranded hairpin shaped nucleic acid probes composed of a stem, with fluorophore/quencher pair and a loop region complementary to the desired DNA. The beacon-based PCR assay designed in the present study is highly specific as confirmed by competition experiments and extremely sensitive with detection limit of 20fg of genomic DNA (3-4 pathogens). The minimum infrastructure requirement and ease to perform the assay makes this method highly useful for resource poor countries for better disease management. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Optical Fiber Nanotips Coated with Molecular Beacons for DNA Detection

    Directory of Open Access Journals (Sweden)

    Ambra Giannetti

    2015-04-01

    Full Text Available Optical fiber sensors, thanks to their compactness, fast response and real-time measurements, have a large impact in the fields of life science research, drug discovery and medical diagnostics. In recent years, advances in nanotechnology have resulted in the development of nanotools, capable of entering the single cell, resulting in new nanobiosensors useful for the detection of biomolecules inside living cells. In this paper, we provide an application of a nanotip coupled with molecular beacons (MBs for the detection of DNA. The MBs were characterized by hybridization studies with a complementary target to prove their functionality both free in solution and immobilized onto a solid support. The solid support chosen as substrate for the immobilization of the MBs was a 30 nm tapered tip of an optical fiber, fabricated by chemical etching. With this set-up promising results were obtained and a limit of detection (LOD of 0.57 nM was reached, opening up the possibility of using the proposed nanotip to detect mRNAs inside the cytoplasm of living cells.

  18. [Molecular beacon based PNA-FISH method combined with fluorescence scanning for rapid detection of Listeria monocytogenes].

    Science.gov (United States)

    Wu, Shan; Zhang, Xiaofeng; Shuai, Jiangbing; Li, Ke; Yu, Huizhen; Jin, Chenchen

    2016-07-04

    To simplify the PNA-FISH (Peptide nucleic acid-fluorescence in situ hybridization) test, molecular beacon based PNA probe combined with fluorescence scanning detection technology was applied to replace the original microscope observation to detect Listeria monocytogenes The 5′ end and 3′ end of the L. monocytogenes specific PNA probes were labeled with the fluorescent group and the quenching group respectively, to form a molecular beacon based PNA probe. When PNA probe used for fluorescence scanning and N1 treatment as the control, the false positive rate was 11.4%, and the false negative rate was 0; when N2 treatment as the control, the false positive rate decreased to 4.3%, but the false negative rate rose to 18.6%. When beacon based PNA probe used for fluorescence scanning, taken N1 treatment as blank control, the false positive rate was 8.6%, and the false negative rate was 1.4%; taken N2 treatment as blank control, the false positive rate was 5.7%, and the false negative rate was 1.4%. Compared with PNA probe, molecular beacon based PNA probe can effectively reduce false positives and false negatives. The success rates of hybridization of the two PNA probes were 83.3% and 95.2% respectively; and the rates of the two beacon based PNA probes were 91.7% and 90.5% respectively, which indicated that labeling the both ends of the PNA probe dose not decrease the hybridization rate with the target bacteria. The combination of liquid phase PNA-FISH and fluorescence scanning method, can significantly improve the detection efficiency.

  19. Detection of Candida species in pregnant Chinese women with a molecular beacon method.

    Science.gov (United States)

    Zhai, Yanhong; Liu, Jing; Zhou, Li; Ji, Tongzhen; Meng, Lingxin; Gao, Yang; Liu, Ran; Wang, Xiao; Li, Lin; Lu, Binghuai; Cao, Zheng

    2018-04-20

    Candida pathogens are commonly found in women and can cause vulvovaginal candidiasis (VVC), whose infection rate is further increased during pregnancy. We aimed to study the Candida prevalence and strain distribution in pregnant Chinese women with a molecular beacon assay. From March 2016 to February 2017, a total of 993 pregnant women attending routine antenatal visits at the Beijing Obstetrics and Gynecology Hospital were enrolled. For Candida detection and identification, a unique molecular beacon assay was presented and compared with a traditional phenotypic method. Antifungal susceptibility was tested with the following agents: 5-flucytosine, amphotericin B, fluconazole, itraconazole and voriconazole. The prevalence of Candida was found to be 21.8 % when using the molecular method and 15.0 % when using the phenotypic method. The distribution of the Candida spp. was listed in order of decreasing prevalence: Candida albicans (79.8 %), Candida glabrata (13.5 %), Candida parapsilosis (3.7 %), Candida krusei (2.2 %) and Candida tropicalis (1.1 %). We found that 90.7 % of the Candida detection results were consistent between the molecular and the phenotypic methods. In the cases where the sequencing analyses for the Candida isolates resulted in inconsistent identification, the molecular method showed higher sensitivity than the phenotypic method (96.0 vs 64.6 %). C. albicans, C. glabrata and C. parapsilosis were essentially susceptible to all five antifungal agents tested, whereas C. tropicalis and C. krusei were susceptible to voriconazole and amphotericin B. By exhibiting good sensitivity and specificity, the molecular assay may offer a fast and accurate Candida screening platform for pregnant women.

  20. Quencher-free molecular beacon tethering 7-hydroxycoumarin detects targets through protonation/deprotonation.

    Science.gov (United States)

    Kashida, Hiromu; Yamaguchi, Kyohei; Hara, Yuichi; Asanuma, Hiroyuki

    2012-07-15

    In this study, we synthesized a simple but efficient quencher-free molecular beacon tethering 7-hydroxycoumarin on D-threoninol based on its pK(a) change. The pK(a) of 7-hydroxycoumarin in a single strand was determined as 8.8, whereas that intercalated in the duplex was over 10. This large pK(a) shift (more than 1.2) upon hybridization could be attributed to the anionic and hydrophobic microenvironment inside the DNA duplex. Because 7-hydroxycoumarin quenches its fluorescence upon protonation, the emission intensity of the duplex at pH 8.5 was 1/15 that of the single strand. We applied this quenching mechanism to the preparation of a quencher-free molecular beacon by introducing the dye into the middle of the stem part. In the absence of the target, the stem region formed a duplex and fluorescence was quenched. However, when the target was added, the molecular beacon opened and the dye was deprotonated. As a result, the emission intensity of the molecular beacon with the target was 10 times higher than that without the target. Accordingly, a quencher-free molecular beacon utilizing the pK(a) change was successfully developed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Detection of DNA damage based on metal-mediated molecular beacon and DNA strands displacement reaction

    Science.gov (United States)

    Xiong, Yanxiang; Wei, Min; Wei, Wei; Yin, Lihong; Pu, Yuepu; Liu, Songqin

    2014-01-01

    DNA hairpin structure probes are usually designed by forming intra-molecular duplex based on Watson-Crick hydrogen bonds. In this paper, a molecular beacon based on silver ions-mediated cytosine-Ag+-cytosine base pairs was used to detect DNA. The inherent characteristic of the metal ligation facilitated the design of functional probe and the adjustment of its binding strength compared to traditional DNA hairpin structure probes, which make it be used to detect DNA in a simple, rapid and easy way with the help of DNA strands displacement reaction. The method was sensitive and also possesses the good specificity to differentiate the single base mismatched DNA from the complementary DNA. It was also successfully applied to study the damage effect of classic genotoxicity chemicals such as styrene oxide and sodium arsenite on DNA, which was significant in food science, environmental science and pharmaceutical science.

  2. Application of a molecular beacon based real-time isothermal amplification (MBRTIA) technology for simultaneous detection of Bacillus cereus and Staphylococcus aureus.

    Science.gov (United States)

    Mandappa, I M; Joglekar, Prasanna; Manonmani, H K

    2015-07-01

    A multiplex real-time isothermal amplification assay was developed using molecular beacons for the detection of Bacillus cereus and Staphylococcus aureus by targeting four important virulence genes. A correlation between targeting highly accessible DNA sequences and isothermal amplification based molecular beacon efficiency and sensitivity was demonstrated using phi(Φ)29 DNA polymerase at a constant isothermal temperature of 30 °C. It was very selective and consistently detected down to 10(1) copies of DNA. The specificity and sensitivity of this assay, when tested with pure culture were high, surpassing those of currently used PCR assays for the detection of these organisms. The molecular beacon based real-time isothermal amplification (MBRTIA) assay could be carried out entirely in 96 well plates or well strips, enabling a rapid and high-throughput detection of food borne pathogens.

  3. Quantum dot-based molecular beacon to monitor intracellular microRNAs.

    Science.gov (United States)

    Lee, Jonghwan; Moon, Sung Ung; Lee, Yong Seung; Ali, Bahy A; Al-Khedhairy, Abdulaziz A; Ali, Daoud; Ahmed, Javed; Al Salem, Abdullah M; Kim, Soonhag

    2015-06-02

    Fluorescence monitoring of endogenous microRNA (miRNA or miR) activity related to neuronal development using nano-sized materials provides crucial information on miRNA expression patterns in a noninvasive manner. In this study, we report a new method to monitor intracellular miRNA124a using quantum dot-based molecular beacon (R9-QD-miR124a beacon). The R9-QD-miR124a beacon was constructed using QDs and two probes, miR124a-targeting oligomer and arginine rich cell-penetrating peptide (R9 peptide). The miR124a-targeting oligomer contains a miR124a binging sequence and a black hole quencher 1 (BHQ1). In the absence of target miR124a, the R9-QD-miR124a beacon forms a partial duplex beacon and remained in quenched state because the BHQ1 quenches the fluorescence signal of the R9-QD-miR124a beacon. The binding of miR124a to the miR124a binding sequence of the miR124a-targeting oligomer triggered the separation of the BHQ1 quencher and subsequent signal-on of a red fluorescence signal. Moreover, enhanced cellular uptake was achieved by conjugation with the R9 peptide, which resulted in increased fluorescent signal of the R9-QD-miR124a beacons in P19 cells during neurogenesis due to the endogenous expression of miR124a.

  4. Quantum Dot-Based Molecular Beacon to Monitor Intracellular MicroRNAs

    Directory of Open Access Journals (Sweden)

    Jonghwan Lee

    2015-06-01

    Full Text Available Fluorescence monitoring of endogenous microRNA (miRNA or miR activity related to neuronal development using nano-sized materials provides crucial information on miRNA expression patterns in a noninvasive manner. In this study, we report a new method to monitor intracellular miRNA124a using quantum dot-based molecular beacon (R9-QD-miR124a beacon. The R9-QD-miR124a beacon was constructed using QDs and two probes, miR124a-targeting oligomer and arginine rich cell-penetrating peptide (R9 peptide. The miR124a-targeting oligomer contains a miR124a binging sequence and a black hole quencher 1 (BHQ1. In the absence of target miR124a, the R9-QD-miR124a beacon forms a partial duplex beacon and remained in quenched state because the BHQ1 quenches the fluorescence signal of the R9-QD-miR124a beacon. The binding of miR124a to the miR124a binding sequence of the miR124a-targeting oligomer triggered the separation of the BHQ1 quencher and subsequent signal-on of a red fluorescence signal. Moreover, enhanced cellular uptake was achieved by conjugation with the R9 peptide, which resulted in increased fluorescent signal of the R9-QD-miR124a beacons in P19 cells during neurogenesis due to the endogenous expression of miR124a.

  5. Cleavable DNA-protein hybrid molecular beacon: A novel efficient signal translator for sensitive fluorescence anisotropy bioassay.

    Science.gov (United States)

    Hu, Pan; Yang, Bin

    2016-01-15

    Due to its unique features such as high sensitivity, homogeneous format, and independence on fluorescent intensity, fluorescence anisotropy (FA) assay has become a hotspot of study in oligonucleotide-based bioassays. However, until now most FA probes require carefully customized structure designs, and thus are neither generalizable for different sensing systems nor effective to obtain sufficient signal response. To address this issue, a cleavable DNA-protein hybrid molecular beacon was successfully engineered for signal amplified FA bioassay, via combining the unique stable structure of molecular beacon and the large molecular mass of streptavidin. Compared with single DNA strand probe or conventional molecular beacon, the DNA-protein hybrid molecular beacon exhibited a much higher FA value, which was potential to obtain high signal-background ratio in sensing process. As proof-of-principle, this novel DNA-protein hybrid molecular beacon was further applied for FA bioassay using DNAzyme-Pb(2+) as a model sensing system. This FA assay approach could selectively detect as low as 0.5nM Pb(2+) in buffer solution, and also be successful for real samples analysis with good recovery values. Compatible with most of oligonucleotide probes' designs and enzyme-based signal amplification strategies, the molecular beacon can serve as a novel signal translator to expand the application prospect of FA technology in various bioassays. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Surface-attached molecular beacons light the way for DNA sequencing

    Czech Academy of Sciences Publication Activity Database

    Paleček, Emil

    2004-01-01

    Roč. 22, č. 2 (2004), s. 55-58 ISSN 0167-7799 R&D Projects: GA AV ČR IBS5004355; GA ČR GA204/03/0566 Institutional research plan: CEZ:AV0Z5004920 Keywords : molecular beacon * DNA stem-loop structure * DNA sensors Subject RIV: BO - Biophysics Impact factor: 8.606, year: 2004

  7. A molecular beacon microarray based on a quantum dot label for detecting single nucleotide polymorphisms.

    Science.gov (United States)

    Guo, Qingsheng; Bai, Zhixiong; Liu, Yuqian; Sun, Qingjiang

    2016-03-15

    In this work, we report the application of streptavidin-coated quantum dot (strAV-QD) in molecular beacon (MB) microarray assays by using the strAV-QD to label the immobilized MB, avoiding target labeling and meanwhile obviating the use of amplification. The MBs are stem-loop structured oligodeoxynucleotides, modified with a thiol and a biotin at two terminals of the stem. With the strAV-QD labeling an "opened" MB rather than a "closed" MB via streptavidin-biotin reaction, a sensitive and specific detection of label-free target DNA sequence is demonstrated by the MB microarray, with a signal-to-background ratio of 8. The immobilized MBs can be perfectly regenerated, allowing the reuse of the microarray. The MB microarray also is able to detect single nucleotide polymorphisms, exhibiting genotype-dependent fluorescence signals. It is demonstrated that the MB microarray can perform as a 4-to-2 encoder, compressing the genotype information into two outputs. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Studying the influence of stem composition in pH-sensitive molecular beacons onto their sensing properties.

    Science.gov (United States)

    Dembska, Anna; Kierzek, Elzbieta; Juskowiak, Bernard

    2017-10-16

    Intracellular sensing using fluorescent molecular beacons is a potentially useful strategy for real-time, in vivo monitoring of important cellular events. This work is focused on evaluation of pyrene excimer signaling molecular beacons (MBs) for the monitoring of pH changes in vitro as well as inside living cells. The recognition element in our MB called pHSO (pH-sensitive oligonucleotide) is the loop enclosing cytosine-rich fragment that is able to form i-motif structure in a specific pH range. However, alteration of a sequence of the 6 base pairs containing stem of MB allowed the design of pHSO probes that exhibited different dynamic pH range and possessed slightly different transition midpoint between i-motif and open loop configuration. Moreover, this conformational transition was accompanied by spectral changes showing developed probes different pyrene excimer-monomer emission ratio triggered by pH changes. The potential of these MBs for intracellular pH sensing is demonstrated on the example of HeLa cells line. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. A distance-dependent metal-enhanced fluorescence sensing platform based on molecular beacon design.

    Science.gov (United States)

    Zhou, Zhenpeng; Huang, Hongduan; Chen, Yang; Liu, Feng; Huang, Cheng Zhi; Li, Na

    2014-02-15

    A new metal-enhanced fluorescence (MEF) based platform was developed on the basis of distance-dependent fluorescence quenching-enhancement effect, which combined the easiness of Ag-thiol chemistry with the MEF property of noble-metal structures as well as the molecular beacon design. For the given sized AgNPs, the fluorescence enhancement factor was found to increase with a d(6) dependency in agreement with fluorescence resonance energy transfer mechanism at shorter distance and decrease with a d(-3) dependency in agreement with plasmonic enhancement mechanism at longer distance between the fluorophore and the AgNP surface. As a proof of concept, the platform was demonstrated by a sensitive detection of mercuric ions, using thymine-containing molecular beacon to tune silver nanoparticle (AgNP)-enhanced fluorescence. Mercuric ions were detected via formation of a thymine-mercuric-thymine structure to open the hairpin, facilitating fluorescence recovery and AgNP enhancement to yield a limit of detection of 1 nM, which is well below the U.S. Environmental Protection Agency regulation of the Maximum Contaminant Level Goal (10nM) in drinking water. Since the AgNP functioned as not only a quencher to reduce the reagent blank signal but also an enhancement substrate to increase fluorescence of the open hairpin when target mercuric ions were present, the quenching-enhancement strategy can greatly improve the detection sensitivity and can in principle be a universal approach for various targets when combined with molecular beacon design. © 2013 Elsevier B.V. All rights reserved.

  11. Enzymatic Amplification of DNA/RNA Hybrid Molecular Beacon Signaling in Nucleic Acid Detection

    OpenAIRE

    Jacroux, Thomas; Rieck, Daniel C.; Cui, Rong; Ouyang, Yexin; Dong, Wen-Ji

    2012-01-01

    A rapid assay operable under isothermal or non-isothermal conditions is described wherein the sensitivity of a typical molecular beacon (MB) system is improved by utilizing thermostable RNase H to enzymatically cleave an MB comprised of a DNA stem and RNA loop (R/D-MB). Upon hybridization of the R/D-MB to target DNA, there was a modest increase in fluorescence intensity (~5.7x above background) due to an opening of the probe and concomitant reduction in the Förster resonance energy transfer e...

  12. A molecular beacon based on DNA-templated silver nanoclusters for the highly sensitive and selective multiplexed detection of virulence genes.

    Science.gov (United States)

    Han, Dan; Wei, Chunying

    2018-05-01

    In this work, we develop a fluorescent molecular beacon based on the DNA-templated silver nanoclusters (DNA-Ag NCs). The skillfully designed molecular beacon can be conveniently used for detection of diverse virulence genes as long as the corresponding recognition sequences are embedded. Importantly, the constructed detection system allows simultaneous detection of multiple nucleic acids, which is attributed to non-overlapping emission spectra of the as-synthesized silver nanoclusters. Based on the target-induced fluorescence enhancement, three infectious disease-related genes HIV, H1N1, and H5N1 are detected, and the corresponding detection limits are 3.53, 0.12 and 3.95nM, respectively. This design allows specific, versatile and simultaneous detection of diverse targets with easy operation and low cost. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. In-cell protease assay systems based on trans-localizing molecular beacon proteins using HCV protease as a model system.

    Directory of Open Access Journals (Sweden)

    Jeong Hee Kim

    Full Text Available This study describes a sensitive in-cell protease detection system that enables direct fluorescence detection of a target protease and its inhibition inside living cells. This live-cell imaging system provides a fluorescent molecular beacon protein comprised of an intracellular translocation signal sequence, a protease-specific cleavage sequence, and a fluorescent tag sequence(s. The molecular beacon protein is designed to change its intracellular localization upon cleavage by a target protease, i.e., from the cytosol to a subcellular organelle or from a subcellular organelle to the cytosol. Protease activity can be monitored at the single cell level, and accordingly the entire cell population expressing the protease can be accurately enumerated. The clear cellular change in fluorescence pattern makes this system an ideal tool for various life science and drug discovery research, including high throughput and high content screening applications.

  14. A Biofunctional Molecular Beacon for Detecting Single Base Mutations in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Haiyan Dong

    2016-01-01

    Full Text Available The development of a convenient and sensitive biosensing system to detect specific DNA sequences is an important issue in the field of genetic disease therapy. As a classic DNA detection technique, molecular beacon (MB is often used in the biosensing system. However, it has intrinsic drawbacks, including high assay cost, complicated chemical modification, and operational complexity. In this study, we developed a simple and cost-effective label-free multifunctional MB (LMMB by integrating elements of polymerization primer, template, target recognition, and G-quadruplex into one entity to detect target DNA. The core technique was accomplished by introducing a G-hairpin that features fragments of both G-quadruplex and target DNA recognition in the G-hairpin stem. Hybridization between LMMB and target DNA triggered conformational change between the G-hairpin and the common C-hairpin, resulting in significant SYBR-green signal amplification. The hybridization continues to the isothermal circular strand-displacement polymerization and accumulation of the double-stranded fragments, causing the uninterrupted extension of the LMMB without a need of chemical modification and other assistant DNA sequences. The novel and programmable LMMB could detect target DNA with sensitivity at 250 pmol/l with a linear range from 2 to 100 nmol/l and the relative standard deviation of 7.98%. The LMMB could sense a single base mutation from the normal DNA, and polymerase chain reaction (PCR amplicons of the mutant-type cell line from the wild-type one. The total time required for preparation and assaying was only 25 minutes. Apparently, the LMMB shows great potential for detecting DNA and its mutations in biosamples, and therefore it opens up a new prospect for genetic disease therapy.

  15. A NASBA on microgel-tethered molecular-beacon microarray for real-time microbial molecular diagnostics.

    Science.gov (United States)

    Ma, Y; Dai, X; Hong, T; Munk, G B; Libera, M

    2016-12-19

    Despite their many advantages and successes, molecular beacon (MB) hybridization probes have not been extensively used in microarray formats because of the complicating probe-substrate interactions that increase the background intensity. We have previously shown that tethering to surface-patterned microgels is an effective means for localizing MB probes to specific surface locations in a microarray format while simultaneously maintaining them in as water-like an environment as possible and minimizing probe-surface interactions. Here we extend this approach to include both real-time detection together with integrated NASBA amplification. We fabricate small (∼250 μm × 250 μm) simplex, duplex, and five-plex assays with microarray spots of controllable size (∼20 μm diameter), position, and shape to detect bacteria and fungi in a bloodstream-infection model. The targets, primers, and microgel-tethered probes can be combined in a single isothermal reaction chamber with no post-amplification labelling. We extract total RNA from clinical blood samples and differentiate between Gram-positive and Gram-negative bloodstream infection in a duplex assay to detect RNA- amplicons. The sensitivity based on our current protocols in a simplex assay to detect specific ribosomal RNA sequences within total RNA extracted from S. aureus and E. coli cultures corresponds to tens of bacteria per ml. We furthermore show that the platform can detect RNA- amplicons from synthetic target DNA with 1 fM sensitivity in sample volumes that contain about 12 000 DNA molecules. These experiments demonstrate an alternative approach that can enable rapid and real-time microarray-based molecular diagnostics.

  16. Real-time monitoring of disintegration activity of catalytic core domain of HIV-1 integrase using molecular beacon.

    Science.gov (United States)

    Zhang, Da-wei; Zhao, Ming-ming; He, Hong-qiu; Guo, Shun-xing

    2013-09-15

    HIV-1 integrase, an essential enzyme for retroviral replication, is a validated target for anti-HIV therapy development. The catalytic core domain of integrase (IN-CCD) is capable of catalyzing disintegration reaction. In this work, a hairpin-shaped disintegration substrate was designed and validated by enzyme-linked immunosorbent assay; a molecular beacon-based assay was developed for disintegration reaction of IN-CCD. Results showed that the disintegration substrate could be recognized and catalyzed by IN-CCD, and the disintegration reaction can be monitored according to the increase of fluorescent signal. The assay can be applied to real-time detection of disintegration with advantages of simplicity, high sensitivity, and excellent specificity. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. A quencher-free molecular beacon design based on pyrene excimer fluorescence using pyrene-labeled UNA (unlocked nucleic acid)

    DEFF Research Database (Denmark)

    Karlsen, Kasper Kannegård; Okholm, Anders Hauge; Kjems, Jørgen

    2013-01-01

    A quencher-free molecular beacon capable of generating pyrene excimer fluorescence has been constructed using strategically positioned pyrene-UNA monomers. Hybridization of a fully complementary RNA target was accompanied by a pyrene excimer emission increase of more than 900%, and detection of RNA...

  18. Surveillance technology for HIV-1 subtype C in Ethiopia: an env-based NASBA molecular beacon assay to discriminate between subcluster C and C'

    NARCIS (Netherlands)

    Ayele, Workenesh; Baar, Michel P. de; Goudsmit, Jaap; Kliphuis, Aletta; Tilahun, Tesfaye; Dorigo-Zetsma, Wendelien; Wolday, Dawit; Abebe, Almaz; Mengistu, Yohannes; Pollakis, Georgios

    2005-01-01

    Forty-nine samples with known C2V3 sequences were used for the evaluation of an env-based molecular beacon assay to distinguish between the two genetic subclusters C and C' which characterize the HIV-1 epidemic in Ethiopia. Two subcluster C and two subcluster C' beacons targeting two different loci

  19. Simple fluorescence-based detection of protein kinase A activity using a molecular beacon probe.

    Science.gov (United States)

    Ma, Changbei; Lv, Xiaoyuan; Wang, Kemin; Jin, Shunxin; Liu, Haisheng; Wu, Kefeng; Zeng, Weimin

    2017-11-02

    Protein kinase A was detected by quantifying the amount of ATP used after a protein kinase reaction. The ATP assay was performed using the T4 DNA ligase and a molecular beacon (MB). In the presence of ATP, DNA ligase catalyzed the ligation of short DNA. The ligation product then hybridized to MB, resulting in a fluorescence enhancement of the MB. This assay was capable of determining protein kinase A in the range of 12.5∼150 nM, with a detection limit of 1.25 nM. Furthermore, this assay could also be used to investigate the effect of genistein on protein kinase A. It was a universal, non-radioisotopic, and homogeneous method for assaying protein kinase A.

  20. Facile conversion of ATP-binding RNA aptamer to quencher-free molecular aptamer beacon.

    Science.gov (United States)

    Park, Yoojin; Nim-Anussornkul, Duangrat; Vilaivan, Tirayut; Morii, Takashi; Kim, Byeang Hyean

    2018-01-15

    We have developed RNA-based quencher-free molecular aptamer beacons (RNA-based QF-MABs) for the detection of ATP, taking advantage of the conformational changes associated with ATP binding to the ATP-binding RNA aptamer. The RNA aptamer, with its well-defined structure, was readily converted to the fluorescence sensors by incorporating a fluorophore into the loop region of the hairpin structure. These RNA-based QF-MABs exhibited fluorescence signals in the presence of ATP relative to their low background signals in the absence of ATP. The fluorescence emission intensity increased upon formation of a RNA-based QF-MAB·ATP complex. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Pyrene functionalized molecular beacon with pH-sensitive i-motif in a loop.

    Science.gov (United States)

    Dembska, Anna; Juskowiak, Bernard

    2015-01-01

    In this work, we present a spectral characterization of pH-sensitive system, which combines the i-motif properties with the spatially sensitive fluorescence signal of pyrene molecules attached to hairpin ends. The excimer production (fluorescence max. ∼480 nm) by pyrene labels at the ends of the molecular beacon is driven by pH-dependent i-motif formation in the loop. To illustrate the performance and reversible work of our systems, we performed the experiments with repeatedly pH cycling between pH values of 7.5±0.3 and 6.5±0.3. The sensor gives analytical response in excimer-monomer switching mode in narrow pH range (1.5 pH units) and exhibits high pH resolution (0.1 pH unit). Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Novel Molecular Beacon Probe-Based Real-Time RT-PCR Assay for Diagnosis of Crimean-Congo Hemorrhagic Fever Encountered in India

    Directory of Open Access Journals (Sweden)

    Aman Kamboj

    2014-01-01

    Full Text Available Crimean-Congo hemorrhagic fever (CCHF is an emerging zoonotic disease in India and requires immediate detection of infection both for preventing further transmission and for controlling the infection. The present study describes development, optimization, and evaluation of a novel molecular beacon-based real-time RT-PCR assay for rapid, sensitive, and specific diagnosis of Crimean-Congo hemorrhagic fever virus (CCHFV. The developed assay was found to be a better alternative to the reported TaqMan assay for routine diagnosis of CCHF.

  3. Quantum Dot-Fullerene Based Molecular Beacon Nanosensors for Rapid, Highly Sensitive Nucleic Acid Detection.

    Science.gov (United States)

    Liu, Ye; Kannegulla, Akash; Wu, Bo; Cheng, Li-Jing

    2018-05-15

    Spherical fullerene (C 60 ) can quench the fluorescence of a quantum dot (QD) through energy transfer and charge transfer processes, with the quenching efficiency regulated by the number of proximate C 60 on each QD. With the quenching property and its small size compared with other nanoparticle-based quenchers, it is advantageous to group a QD reporter and multiple C 60 -labeled oligonucleotide probes to construct a molecular beacon (MB) probe for sensitive, robust nucleic acid detection. We demonstrated a rapid, high-sensitivity DNA detection method using the nanosensors composed of QD-C 60 based MBs carried by magnetic nanoparticles (MNPs). The assay was accelerated by first dispersing the nanosensors in analytes for highly efficient DNA capture resulting from short-distance 3-dimensional diffusion of targets to the sensor surface and then concentrating the nanosensors to a substrate by magnetic force to amplify the fluorescence signal for target quantification. The enhanced mass transport enabled a rapid detection (< 10 min) with a small sample volume (1-10 µl). The high signal-to-noise ratio produced by the QD-C 60 pairs and magnetic concentration yielded a detection limit of 100 fM (~106 target DNA copies for a 10 µl analyte). The rapid, sensitive, label-free detection method will benefit the applications in point-of-care molecular diagnostic technologies.

  4. Theranostic properties of a survivin-directed molecular beacon in human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Sara Carpi

    Full Text Available Survivin is an inhibitor of apoptosis overexpressed in different types of tumors and undetectable in most terminally differentiated normal tissues. In the current study, we sought to evaluate the in vitro theranostic properties of a molecular beacon-oligodeoxynucleotide (MB that targets survivin mRNA. We used laser scanning confocal microscopy to study MB delivery in living cells and real-time PCR and western blot to assess selective survivin-targeting in human malignant melanoma cells. We further assess the pro-apoptotic effect of MB by measuring internucleosomal DNA fragmentation, dissipation of mitochondrial membrane potential (MMP and changes in nuclear morphology. Transfection of MB into A375 and 501 Mel cells generated high signal intensity from the cytoplasm, while no signal was detected in the extracellular environment and in survivin-negative cells (i.e., human melanocytes and monocytes. MB time dependently decreased survivin mRNA and protein expression in melanoma cells with the maximum effect reached at 72 h. Treatment of melanoma cells with MB induced apoptosis by significant changes in MMP, accumulation of histone-complexed DNA fragments in the cytoplasm and nuclear condensation. MB also enhanced the pro-apoptotic effect of standard chemotherapeutic drugs tested at clinically relevant concentrations. The MB tested in the current study conjugates the ability of imaging with the pharmacological silencing activity against survivin mRNA in human melanoma cells and may represent an innovative approach for cancer diagnosis and treatment.

  5. Recognition of dual targets by a molecular beacon-based sensor: subtyping of influenza A virus.

    Science.gov (United States)

    Lee, Chun-Ching; Liao, Yu-Chieh; Lai, Yu-Hsuan; Lee, Chang-Chun David; Chuang, Min-Chieh

    2015-01-01

    A molecular beacon (MB)-based sensor to offer a decisive answer in combination with information originated from dual-target inputs is designed. The system harnesses an assistant strand and thermodynamically favored designation of unpaired nucleotides (UNs) to process the binary targets in "AND-gate" format and report fluorescence in "off-on" mechanism via a formation of a DNA four-way junction (4WJ). By manipulating composition of the UNs, the dynamic fluorescence difference between the binary targets-coexisting circumstance and any other scenario was maximized. Characteristic equilibrium constant (K), change of entropy (ΔS), and association rate constant (k) between the association ("on") and dissociation ("off") states of the 4WJ were evaluated to understand unfolding behavior of MB in connection to its sensing capability. Favorable MB and UNs were furthermore designed toward analysis of genuine genetic sequences of hemagglutinin (HA) and neuraminidase (NA) in an influenza A H5N2 isolate. The MB-based sensor was demonstrated to yield a linear calibration range from 1.2 to 240 nM and detection limit of 120 pM. Furthermore, high-fidelity subtyping of influenza virus was implemented in a sample of unpurified amplicons. The strategy opens an alternative avenue of MB-based sensors for dual targets toward applications in clinical diagnosis.

  6. Design of two and three input molecular logic gates using non-Watson-Crick base pairing-based molecular beacons.

    Science.gov (United States)

    Lin, Jia-Hui; Tseng, Wei-Lung

    2014-03-21

    This study presents a single, resettable, and sensitive molecular beacon (MB) used to operate molecular-scale logic gates. The MB consists of a random DNA sequence, a fluorophore at the 5'-end, and a quencher at the 3'-end. The presence of Hg(2+), Ag(+), and coralyne promoted the formation of stable T-Hg(2+)-T, C-Ag(+)-C, and A2-coralyne-A2 coordination in the MB probe, respectively, thereby driving its conformational change. The metal ion or small molecule-mediated coordination of mismatched DNA brought the fluorophore and the quencher into close proximity, resulting in collisional quenching of fluorescence between the two organic dyes. Because thiol can bind Hg(2+) and remove it from the T-Hg(2+)-T-based MB, adding thiol to a solution of the T-Hg(2+)-T-based MB allowed the fluorophore and the quencher to be widely separated. A similar phenomenon was observed when replacing Hg(2+) with Ag(+). Because Ag(+) strongly binds to iodide, cyanide, and cysteine, they were capable of removing Ag(+) from the C-Ag(+)-C-based MB, restoring the fluorescence of the MB. Moreover, the fluorescence of the A2-coralyne-A2-based MB could be switched on by adding polyadenosine. Using these analytes as inputs and the MB as a signal transducer, we successfully developed a series of two-input, three-input, and set-reset logic gates at the molecular level.

  7. Long-stem shaped multifunctional molecular beacon for highly sensitive nucleic acids determination via intramolecular and intermolecular interactions based strand displacement amplification.

    Science.gov (United States)

    Xu, Jianguo; Zheng, Tingting; Le, Jingqing; Jia, Lee

    2017-11-20

    Occurrence and application of oligonucleotide probes have promoted great progress in the biochemical analysis field due to their unique biological and chemical properties. In this work, a long-stem shaped multifunctional molecular beacon (LS-MMB) that is responsive to a cancer-related gene, p53, is well-prepared. By designing the probe with long-paired bases at its two ends and short-paired bases between the middle region and the 3' end, the LS-MMB is intelligently endowed with the ability to recognize the target analyte, serve as the polymerization primer/template, and signal the hybridization event synchronously, which is distinctly advantageous over the traditional molecular beacons (MBs). Moreover, it is excitingly found that the LS-MMB can be employed to exert intramolecular and intermolecular interactions for strand displacement amplification (SDA) without the involvement of any assistant probes; this therapy results in a really easy and rapid sensing system that provides an extremely low background noise and high target output signal. In this case, an excellent sensitivity and specificity to detect target gene down to picomolar level and resolution to even one nucleotide variation are achieved, respectively. In addition, the application potential for real genomic DNA analysis is realized. We envision that the probe of LS-MMB can act as a universal platform for biosensing and biomedical research.

  8. Detection of Naja atra Cardiotoxin Using Adenosine-Based Molecular Beacon.

    Science.gov (United States)

    Shi, Yi-Jun; Chen, Ying-Jung; Hu, Wan-Ping; Chang, Long-Sen

    2017-01-07

    This study presents an adenosine (A)-based molecular beacon (MB) for selective detection of Naja atra cardiotoxin (CTX) that functions by utilizing the competitive binding between CTX and the poly(A) stem of MB to coralyne. The 5'- and 3'-end of MB were labeled with a reporter fluorophore and a non-fluorescent quencher, respectively. Coralyne induced formation of the stem-loop MB structure through A₂-coralyne-A₂ coordination, causing fluorescence signal turn-off due to fluorescence resonance energy transfer between the fluorophore and quencher. CTX3 could bind to coralyne. Moreover, CTX3 alone induced the folding of MB structure and quenching of MB fluorescence. Unlike that of snake venom α-neurotoxins, the fluorescence signal of coralyne-MB complexes produced a bell-shaped concentration-dependent curve in the presence of CTX3 and CTX isotoxins; a turn-on fluorescence signal was noted when CTX concentration was ≤80 nM, while a turn-off fluorescence signal was noted with a further increase in toxin concentrations. The fluorescence signal of coralyne-MB complexes yielded a bell-shaped curve in response to varying concentrations of N. atra crude venom but not those of Bungarus multicinctus and Protobothrops mucrosquamatus venoms. Moreover, N. nigricollis venom also functioned as N. atra venom to yield a bell-shaped concentration-dependent curve of MB fluorescence signal, again supporting that the hairpin-shaped MB could detect crude venoms containing CTXs. Taken together, our data validate that a platform composed of coralyne-induced stem-loop MB structure selectively detects CTXs.

  9. G-Quadruplex DNAzyme Molecular Beacon for Amplified Colorimetric Biosensing of Pseudostellaria heterophylla

    Directory of Open Access Journals (Sweden)

    Juan Hu

    2013-01-01

    Full Text Available With an internal transcribed spacer of 18 S, 5.8 S and 26 S nuclear ribosomal DNA (nrDNA ITS as DNA marker, we report a colorimetric approach for authentication of Pseudostellaria heterophylla (PH and its counterfeit species based on the differentiation of the nrDNA ITS sequence. The assay possesses an unlabelled G-quadruplex DNAzyme molecular beacon (MB probe, employing complementary sequence as biorecognition element and 1:1:1:1 split G-quadruplex halves as reporter. In the absence of target DNA (T-DNA, the probe can shape intermolecular G-quadruplex structures capable of binding hemin to form G-quadruplex-hemin DNAzyme and catalyze the oxidation of ABTS2− to blue-green ABTS•− by H2O2. In the presence of T-DNA, T-DNA can hybridize with the complementary sequence to form a duplex structure, hindering the formation of the G-quadruplex structure and resulting in the loss of the catalytic activity. Consequently, a UV-Vis absorption signal decrease is observed in the ABTS2−-H2O2 system. The “turn-off” assay allows the detection of T-DNA from 1.0 × 10−9 to 3.0 × 10−7 mol·L−1 (R2 = 0.9906, with a low detection limit of 3.1 × 10−10 mol·L−1. The present study provides a sensitive and selective method and may serve as a foundation of utilizing the DNAzyme MB sensor for identifying traditional Chinese medicines.

  10. Molecular beacon-based real-time PCR method for detection of porcine DNA in gelatin and gelatin capsules.

    Science.gov (United States)

    Mohamad, Nurhidayatul Asma; Mustafa, Shuhaimi; Khairil Mokhtar, Nur Fadhilah; El Sheikha, Aly Farag

    2018-03-05

    The pharmaceutical industry has boosted gelatin consumption worldwide. This is supported by the availability of cost-effective gelatin production from porcine by-products. However, cross-contamination of gelatin materials, where porcine gelatin was unintentionally included in the other animal sources of gelatin, has caused significant concerns about halal authenticity. The real-time polymerase chain reaction (PCR) has enabled a highly specific and sensitive animal species detection method in various food products. Hence, such a technique was employed in the present study to detect and quantify porcine DNA in gelatin using a molecular beacon probe, with differences in performance between mitochondrial (cytochrome b gene) and chromosomal DNA-(MPRE42 repetitive element) based porcine-specific PCR assays being compared. A higher sensitivity was observed in chromosomal DNA (MPRE-PCR assay), where this assay allows the detection of gelatin DNA at amounts as as low as 1 pg, whereas mitochondrial DNA (CBH-PCR assay) can only detect at levels down to 10 pg of gelatin DNA. When an analysis with commercial gelatin and gelatin capsule samples was conducted, the same result was observed, with a significantly more sensitive detection being provided by the repetitive element of chromosomal DNA. The present study has established highly sensitive DNA-based porcine detection systems derived from chromosomal DNA that are feasible for highly processed products such as gelatin and gelatin capsules containing a minute amount of DNA. This sensitive detection method can also be implemented to assist the halal authentication process of various food products available on the market. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  11. SOX2 and OCT4 mRNA-Expressing Cells, Detected by Molecular Beacons, Localize to the Center of Neurospheres during Differentiation

    DEFF Research Database (Denmark)

    Ilieva, Mirolyuba; Dufva, Martin

    2013-01-01

    Neurospheres are used as in vitro assay to measure the properties of neural stem cells. To investigate the molecular and phenotypic heterogeneity of neurospheres, molecular beacons (MBs) targeted against the stem cell markers OCT4 and SOX2 were designed, and synthesized with a 2'-O-methyl RNA...

  12. Molecular Beacon Enables Combination of Highly Processive and Highly Sensitive Rolling Circle Amplification Readouts for Detection of DNA-Modifying Enzymes

    DEFF Research Database (Denmark)

    Kristoffersen, Emil Laust; Gonzales, Maria; Stougaard, Magnus

    2015-01-01

    is separated, giving rise to a fluorescent signal, measurable in pseudo real-time using a qPCR machine or in a fluorimeter. The RCA products in complex with the molecular beacon can subsequently be moved to microscopic slides and analyzed in a fluorescence microscope. We describe the proof of the principle...

  13. Experimental study of the evanescent-wave photonic sensors response in presence of molecular beacon conformational changes.

    Science.gov (United States)

    Ruiz-Tórtola, Ángela; Prats-Quílez, Francisco; Gónzalez-Lucas, Daniel; Bañuls, María-José; Maquieira, Ángel; Wheeler, Guy; Dalmay, Tamas; Griol, Amadeu; Hurtado, Juan; Bohlmann, Helge; Götzen, Reiner; García-Rupérez, Jaime

    2018-04-17

    An experimental study of the influence of the conformational change suffered by molecular beacon (MB) probes -upon the biorecognition of nucleic acid target oligonucleotides over evanescent wave photonic sensors- is reported. To this end, high sensitivity photonic sensors based on silicon photonic bandgap (PBG) structures were used, where the MB probes were immobilized via their 5' termination. Those MBs incorporate a biotin moiety close to their 3' termination in order to selectively bind a streptavidin molecule to them. The different photonic sensing responses obtained towards the target oligonucleotide detection, when the streptavidin molecule was bound to the MB probes or not, demonstrate the conformational change suffered by the MB upon hybridization, which promotes the displacement of the streptavidin molecule away from the surface of the photonic sensing structure. Schematic diagram of the PBG sensing structure on which the streptavidin-labeled MB probes were immobilized. This article is protected by copyright. All rights reserved.

  14. "Molecular beacon"-hosted thioflavin T: Applications for label-free fluorescent detection of iodide and logic operations.

    Science.gov (United States)

    Li, Yan-Yun; Jiang, Xiao-Qin; Lu, Ling-Fei; Zhang, Min; Shi, Guoyue

    2016-04-01

    In this work, we presented a simple, label-free and rapid-responsive fluorescence assay for iodide (I(-)) detection based on "molecular beacon (MB)"-hosted thioflavin T (ThT), achieving a limit of detection as low as 158 nM. The proposed method exhibited very good selectivity to I(-) ions over other anions interference due to the strong binding force between I(-) ions with Hg(2+). Upon the addition of I(-) ions, it would capture Hg(2+) from a T-Hg(2+)-T complex belonging to the MB-like DNA hairpin structure, which eventually quenched the initial fluorescence as output. In addition, it was successfully applied for operation of an integrated DNA logic gate system and to the determination of I(-) in real samples such as human urine. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. SOX2 and OCT4 mRNA-expressing cells, detected by molecular beacons, localize to the center of neurospheres during differentiation.

    Directory of Open Access Journals (Sweden)

    Mirolyuba Ilieva

    Full Text Available Neurospheres are used as in vitro assay to measure the properties of neural stem cells. To investigate the molecular and phenotypic heterogeneity of neurospheres, molecular beacons (MBs targeted against the stem cell markers OCT4 and SOX2 were designed, and synthesized with a 2'-O-methyl RNA backbone. OCT4 and SOX2 MBs were transfected into human embryonic mesencephalon derived cells, which spontaneously form neurospheres when grown on poly-L-ornitine/fibronectin matrix and medium complemented with bFGF. OCT4 and SOX2 gene expression were tracked in individual cell using the MBs. Quantitative image analysis every day for seven days showed that the OCT4 and SOX2 mRNA-expressing cells clustered in the centre of the neurospheres cultured in differentiation medium. By contrast, cells at the periphery of the differentiating spheres developed neurite outgrowths and expressed the tyrosine hydroxylase protein, indicating terminal differentiation. Neurospheres cultured in growth medium contained OCT4 and SOX2-positive cells distributed throughout the entire sphere, and no differentiating neurones. Gene expression of SOX2 and OCT4 mRNA detected by MBs correlated well with gene and protein expression measured by qRT-PCR and immunostaining, respectively. These experimental data support the theoretical model that stem cells cluster in the centre of neurospheres, and demonstrate the use of MBs for the spatial localization of specific gene-expressing cells within heterogeneous cell populations.

  16. Personal Beacon

    Science.gov (United States)

    2000-01-01

    The MicroPLB (personal locator beacon) is a search and rescue satellite-aided tracking (SARSAT) transmitter. When activated it emits a distress signal to a constellation of internationally operated satellites. The endangered person's identity and location anywhere on Earth is automatically forwarded to central monitoring stations around the world. It is accurate to within just a few meters. The user uses the device to download navigation data from a global positioning satellite receiver. After the download is complete, the MicroPLB functions as a self-locating beacon. Also, it is the only PLB to use a safe battery. In the past, other PLB devices have used batteries that have enough volatility to explode with extreme force. It was developed by Microwave Monolithic, Inc. through SBIR funding from Glenn Research Center and Goddard Space Flight Center.

  17. Selective amyloid β oligomer assay based on abasic site-containing molecular beacon and enzyme-free amplification.

    Science.gov (United States)

    Zhu, Linling; Zhang, Junying; Wang, Fengyang; Wang, Ya; Lu, Linlin; Feng, Chongchong; Xu, Zhiai; Zhang, Wen

    2016-04-15

    Amyloid-beta (Aβ) oligomers are highly toxic species in the process of Aβ aggregation and are regarded as potent therapeutic targets and diagnostic markers for Alzheimer's disease (AD). Herein, a label-free molecular beacon (MB) system integrated with enzyme-free amplification strategy was developed for simple and highly selective assay of Aβ oligomers. The MB system was constructed with abasic site (AP site)-containing stem-loop DNA and a fluorescent ligand 2-amino-5,6,7-trimethyl-1,8-naphyridine (ATMND), of which the fluorescence was quenched upon binding to the AP site in DNA stem. Enzyme-free amplification was realized by target-triggered continuous opening of two delicately designed MBs (MB1 and MB2). Target DNA hybridization with MB1 and then MB2 resulted in the release of two ATMND molecules in one binding event. Subsequent target recycling could greatly amplify the detection sensitivity due to the greatly enhanced turn-on emission of ATMND fluorescence. Combining with Aβ oligomers aptamers, the strategy was applied to analyze Aβ oligomers and the results showed that it could quantify Aβ oligomers with high selectivity and monitor the Aβ aggregation process. This novel method may be conducive to improve the diagnosis and pathogenic study of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Rapid, High-Throughput, and Direct Molecular Beacon Delivery to Human Cancer Cells Using a Nanowire-Incorporated and Pneumatic Pressure-Driven Microdevice.

    Science.gov (United States)

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

    2015-12-01

    Tracking and monitoring the intracellular behavior of mRNA is of paramount importance for understanding real-time gene expression in cell biology. To detect specific mRNA sequences, molecular beacons (MBs) have been widely employed as sensing probes. Although numerous strategies for MB delivery into the target cells have been reported, many issues such as the cytotoxicity of the carriers, dependence on the random probability of MB transfer, and critical cellular damage still need to be overcome. Herein, we have developed a nanowire-incorporated and pneumatic pressure-driven microdevice for rapid, high-throughput, and direct MB delivery to human breast cancer MCF-7 cells to monitor survivin mRNA expression. The proposed microdevice is composed of three layers: a pump-associated glass manifold layer, a monolithic polydimethylsiloxane (PDMS) membrane, and a ZnO nanowire-patterned microchannel layer. The MB is immobilized on the ZnO nanowires by disulfide bonding, and the glass manifold and PDMS membrane serve as a microvalve, so that the cellular attachment and detachment on the MB-coated nanowire array can be manipulated. The combination of the nanowire-mediated MB delivery and the microvalve function enable the transfer of MB into the cells in a controllable way with high cell viability and to detect survivin mRNA expression quantitatively after docetaxel treatment. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Nicking endonuclease-assisted signal amplification of a split molecular aptamer beacon for biomolecule detection using graphene oxide as a sensing platform.

    Science.gov (United States)

    Li, Xiang; Ding, Xuelian; Fan, Jing

    2015-12-07

    Sensitive and selective detection of ultralow concentrations of specific biomolecules is important in early clinical diagnoses and biomedical applications. Many types of aptasensors have been developed for the detection of various biomolecules, but usually suffer from false positive signals and high background signals. In this work, we have developed an amplified fluorescence aptasensor platform for ultrasensitive biomolecule detection based on enzyme-assisted target-recycling signal amplification and graphene oxide. By using a split molecular aptamer beacon and a nicking enzyme, the typical problem of false positive signals can be effectively resolved. Only in the presence of a target biomolecule, the sensor system is able to generate a positive signal, which significantly improves the selectivity of the aptasensor. Moreover, using graphene oxide as a super-quencher can effectively reduce the high background signal of a sensing platform. We select vascular endothelial growth factor (VEGF) and adenosine triphosphate (ATP) as model analytes in the current proof-of-concept experiments. It is shown that under optimized conditions, our strategy exhibits high sensitivity and selectivity for the quantification of VEGF and ATP with a low detection limit (1 pM and 4 nM, respectively). In addition, this biosensor has been successfully utilized in the analysis of real biological samples.

  20. Super-resolution imaging of a 2.5 kb non-repetitive DNA in situ in the nuclear genome using molecular beacon probes

    Science.gov (United States)

    Ni, Yanxiang; Cao, Bo; Ma, Tszshan; Niu, Gang; Huo, Yingdong; Huang, Jiandong; Chen, Danni; Liu, Yi; Yu, Bin; Zhang, Michael Q; Niu, Hanben

    2017-01-01

    High-resolution visualization of short non-repetitive DNA in situ in the nuclear genome is essential for studying looping interactions and chromatin organization in single cells. Recent advances in fluorescence in situ hybridization (FISH) using Oligopaint probes have enabled super-resolution imaging of genomic domains with a resolution limit of 4.9 kb. To target shorter elements, we developed a simple FISH method that uses molecular beacon (MB) probes to facilitate the probe-target binding, while minimizing non-specific fluorescence. We used three-dimensional stochastic optical reconstruction microscopy (3D-STORM) with optimized imaging conditions to efficiently distinguish sparsely distributed Alexa-647 from background cellular autofluorescence. Utilizing 3D-STORM and only 29–34 individual MB probes, we observed 3D fine-scale nanostructures of 2.5 kb integrated or endogenous unique DNA in situ in human or mouse genome, respectively. We demonstrated our MB-based FISH method was capable of visualizing the so far shortest non-repetitive genomic sequence in 3D at super-resolution. DOI: http://dx.doi.org/10.7554/eLife.21660.001 PMID:28485713

  1. Molecular beacon-decorated polymethylmethacrylate core-shell fluorescent nanoparticles for the detection of survivin mRNA in human cancer cells.

    Science.gov (United States)

    Adinolfi, Barbara; Pellegrino, Mario; Giannetti, Ambra; Tombelli, Sara; Trono, Cosimo; Sotgiu, Giovanna; Varchi, Greta; Ballestri, Marco; Posati, Tamara; Carpi, Sara; Nieri, Paola; Baldini, Francesco

    2017-02-15

    One of the main goals of nanomedicine in cancer is the development of effective drug delivery systems, primarily nanoparticles. Survivin, an overexpressed anti-apoptotic protein in cancer, represents a pharmacological target for therapy and a Molecular Beacon (MB) specific for survivin mRNA is available. In this study, the ability of polymethylmethacrylate nanoparticles (PMMA-NPs) to promote survivin MB uptake in human A549 cells was investigated. Fluorescent and positively charged core PMMA-NPs of nearly 60nm, obtained through an emulsion co-polymerization reaction, and the MB alone were evaluated in solution, for their analytical characterization; then, the MB specificity and functionality were verified after adsorption onto the PMMA-NPs. The carrier ability of PMMA-NPs in A549 was examined by confocal microscopy. With the optimized protocol, a hardly detectable fluorescent signal was obtained after incubation of the cells with the MB alone (fluorescent spots per cell of 1.90±0.40 with a mean area of 1.04±0.20µm 2 ), while bright fluorescent spots inside the cells were evident by using the MB loaded onto the PMMA-NPs. (27.50±2.30 fluorescent spots per cell with a mean area of 2.35±0.16µm 2 ). These results demonstrate the ability of the PMMA-NPs to promote the survivin-MB internalization, suggesting that this complex might represent a promising strategy for intracellular sensing and for the reduction of cancer cell proliferation. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Hairpin-Hairpin Molecular Beacon Interactions for Detection of Survivin mRNA in Malignant SW480 Cells.

    Science.gov (United States)

    Ratajczak, Katarzyna; Krazinski, Bartlomiej E; Kowalczyk, Anna E; Dworakowska, Beata; Jakiela, Slawomir; Stobiecka, Magdalena

    2018-05-07

    Cancer biomarkers offer unique prospects for the development of cancer diagnostics and therapy. One of such biomarkers, protein survivin (Sur), exhibits strong antiapoptotic and proliferation-enhancing properties and is heavily expressed in multiple cancers. Thus, it can be utilized to provide new modalities for modulating the cell-growth rate, essential for effective cancer treatment. Herein, we have focused on the development of a new survivin-based cancer detection platform for colorectal cancer cells SW480 using a turn-on fluorescence oligonucleotide molecular beacon (MB) probe, encoded to recognize Sur messenger RNA (mRNA). Contrary to the expectations, we have found that both the complementary target oligonucleotide strands as well as the single- and double-mismatch targets, instead of exhibiting the anticipated simple random conformations, preferentially formed secondary structure motifs by folding into small-loop hairpin structures. Such a conformation may interfere with, or even undermine, the biorecognition process. To gain better understanding of the interactions involved, we have replaced the classical Tyagi-Kramer model of interactions between a straight target oligonucleotide strand and a hairpin MB with a new model to account for the hairpin-hairpin interactions as the biorecognition principle. A detailed mechanism of these interactions has been proposed. Furthermore, in experimental work, we have demonstrated an efficient transfection of malignant SW480 cells with SurMB probes containing a fluorophore Joe (SurMB-Joe) using liposomal nanocarriers. The green emission from SurMB-Joe in transfected cancer cells, due to the hybridization of the SurMB-Joe loop with Sur mRNA hairpin target, corroborates Sur overexpression. On the other hand, healthy human-colon epithelial cells CCD 841 CoN show only negligible expression of survivin mRNA. These experiments provide the proof-of-concept for distinguishing between the cancer and normal cells by the proposed

  3. Voltammetric determination of attomolar levels of a sequence derived from the genom of hepatitis B virus by using molecular beacon mediated circular strand displacement and rolling circle amplification.

    Science.gov (United States)

    Huang, Shan; Feng, Mengmeng; Li, Jiawen; Liu, Yi; Xiao, Qi

    2018-03-03

    The authors describe an electrochemical method for the determination of the single-stranded DNA (ssDNA) oligonucleotide with a sequence derived from the genom of hepatitis B virus (HBV). It is making use of circular strand displacement (CSD) and rolling circle amplification (RCA) strategies mediated by a molecular beacon (MB). This ssDNA hybridizes with the loop portion of the MB immobilized on the surface of a gold electrode, while primer DNA also hybridizes with the rest of partial DNA sequences of MB. This triggers the MB-mediated CSD. The RCA is then initiated to produce a long DNA strand with multiple tandem-repeat sequences, and this results in a significant increase of the differential pulse voltammetric response of the electrochemical probe Methylene Blue at a rather low working potential of -0.24 V (vs. Ag/AgCl). Under optimal experimental conditions, the assay displays an ultrahigh sensitivity (with a 2.6 aM detection limit) and excellent selectivity. Response is linear in the 10 to 700 aM DNA concentration range. Graphical abstract Schematic of a voltammetric method for the determination of attomolar levels of target DNA. It is based on molecular beacon mediated circular strand displacement and rolling circle amplification strategies. Under optimal experimental conditions, the assay displays an ultrahigh sensitivity with a 2.6 aM detection limit and excellent selectivity.

  4. Molecular detection of Phytophthora ramorum by real-time PCR using Taqman, SYBR Green and molecular beacons with three genes

    Science.gov (United States)

    G.J. Bilodeau; C.A. Lévesque; A.W.A.M. De Cock; C. Duchaine; G. Kristjansson; R.C. Hamelin

    2006-01-01

    Sudden oak death, caused by Phytophthora ramorum, is a severe disease that can affect numerous species of trees and shrubs. This pathogen has been spread via nursery stock, and quarantine measures are currently in place to prevent further spread. Molecular assays have been developed to rapidly detect and identify P. ramorum, but...

  5. Nucleic acid detection using BRET-beacons based on bioluminescent protein-DNA hybrids

    NARCIS (Netherlands)

    Engelen, W.; van de Wiel, K.M.; Meijer, L.H.H.; Saha, B.; Merkx, M.

    2017-01-01

    Bioluminescent molecular beacons have been developed using a modular design approach that relies on BRET between the bright luciferase NanoLuc and a Cy3 acceptor. While classical molecular beacons are hampered by background fluorescence and scattering, these BRET-beacons allow detection of low pM

  6. Auditory evacuation beacons

    NARCIS (Netherlands)

    Wijngaarden, S.J. van; Bronkhorst, A.W.; Boer, L.C.

    2005-01-01

    Auditory evacuation beacons can be used to guide people to safe exits, even when vision is totally obscured by smoke. Conventional beacons make use of modulated noise signals. Controlled evacuation experiments show that such signals require explicit instructions and are often misunderstood. A new

  7. RAPID DETECTION OF MICROORGANISMS USING 5S RRNA SPECIFIC MOLECULAR BEACONS. (R825354)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  8. Development of a universal RNA beacon for exogenous gene detection.

    Science.gov (United States)

    Guo, Yuanjian; Lu, Zhongju; Cohen, Ira Stephen; Scarlata, Suzanne

    2015-05-01

    Stem cell therapy requires a nontoxic and high-throughput method to achieve a pure cell population to prevent teratomas that can occur if even one cell in the implant has not been transformed. A promising method to detect and separate cells expressing a particular gene is RNA beacon technology. However, developing a successful, specific beacon to a particular transfected gene can take months to develop and in some cases is impossible. Here, we report on an off-the-shelf universal beacon that decreases the time and cost of applying beacon technology to select any living cell population transfected with an exogenous gene. ©AlphaMed Press.

  9. The G-BHQ synergistic effect: Improved double quenching molecular beacons based on guanine and Black Hole Quencher for sensitive simultaneous detection of two DNAs.

    Science.gov (United States)

    Xiang, Dongshan; Li, Fengquan; Wu, Chenyi; Shi, Boan; Zhai, Kun

    2017-11-01

    We designed two double quenching molecular beacons (MBs) with simple structure based on guanine (G base) and Black Hole Quencher (BHQ), and developed a new analytical method for sensitive simultaneous detection of two DNAs by synchronous fluorescence analysis. In this analytical method, carboxyl fluorescein (FAM) and tetramethyl-6-carboxyrhodamine (TAMRA) were respectively selected as fluorophore of two MBs, Black Hole Quencher 1 (BHQ-1) and Black Hole Quencher 2 (BHQ-2) were respectively selected as organic quencher, and three continuous nucleotides with G base were connected to organic quencher (BHQ-1 and BHQ-2). In the presence of target DNAs, the two MBs hybridize with the corresponding target DNAs, the fluorophores are separated from organic quenchers and G bases, leading to recovery of fluorescence of FAM and TAMRA. Under a certain conditions, the fluorescence intensities of FAM and TAMRA all exhibited good linear dependence on their concentration of target DNAs (T1 and T2) in the range from 4 × 10 -10 to 4 × 10 -8 molL -1 (M). The detection limit (3σ, n = 13) of T1 was 3 × 10 -10 M and that of T2 was 2×10 -10 M, respectively. Compared with the existing analysis methods for multiplex DNA with MBs, this proposed method based on double quenching MBs is not only low fluorescence background, short analytical time and low detection cost, but also easy synthesis and good stability of MB probes. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A Turn-on Fluorescence Sensor for Heparin Detection Based on a Release of Taiwan Cobra Cardiotoxin from a DNA Aptamer or Adenosine-Based Molecular Beacon.

    Science.gov (United States)

    Shi, Yi-Jun; Wang, Liang-Jun; Lee, Yuan-Chin; Huang, Chia-Hui; Hu, Wan-Ping; Chang, Long-Sen

    2018-02-19

    This study presents two sensitive fluorescent assays for sensing heparin on the basis of the electrostatic interaction between heparin and Naja naja atra cardiotoxin 3 (CTX3). Owing to CTX3-induced folded structure of an adenosine-based molecular beacon (MB) or a DNA aptamer against CTX3, a reduction in the fluorescent signal of the aptamer or MB 5'-end labeled with carboxyfluorescein (FAM) and 3'-end labeled with 4-([4-(dimethylamino)phenyl]azo)-benzoic acid (DABCYL) was observed upon the addition of CTX3. The presence of heparin and formation of the CTX3-heparin complex caused CTX3 detachment from the MB or aptamer, and restoration of FAM fluorescence of the 5'-FAM-and-3'-DABCYL-labeled MB and aptamer was subsequently noted. Moreover, the detection of heparin with these CTX3-aptamer and CTX3-MB sensors showed high sensitivity and selectivity toward heparin over chondroitin sulfate and hyaluronic acid regardless of the presence of plasma. The limit of detection for heparin in plasma was determined to be 16 ng/mL and 15 ng/mL, respectively, at a signal-to-noise ratio of 3. This study validates the practical utility of the CTX3-aptamer and CTX3-MB systems for determining the concentration of heparin in a biological matrix.

  11. Beacon-based tourist information system to identify visiting trends of tourists

    Directory of Open Access Journals (Sweden)

    Akihiro Yamaguchi

    2017-11-01

    Full Text Available In this study, we propose a system that provides tourist information and obtains trends of visiting tourists using beacons and cloud service. As part of our research, we are working on the promotion of local area tourism in cooperation with a local community. A low energy Bluetooth device is used as a beacon to transmit a universally unique identifier. In addition, beacons are placed at sightseeing spots and tourist facilities. Our proposed system comprises two application programs; one is a client-side application program that provides area-specific tourist information corresponding to the detected beacon. The other is a server-side application to record time and location information of the detected beacons. In this paper, we describe the scheme of our system, and present the results of experiments conducted using the prototype system in the local tourist area. In addition, we discuss an open platform for information collection services using beacons.

  12. Specific Electrostatic Molecular Recognition in Water

    DEFF Research Database (Denmark)

    Li, Ming; Hoeck, Casper; Schoffelen, Sanne

    2016-01-01

    The identification of pairs of small peptides that recognize each other in water exclusively through electrostatic interactions is reported. The target peptide and a structure-biased combinatorial ligand library consisting of ≈78 125 compounds were synthesized on different sized beads. Peptide......-bead binding assay and by 2D NMR spectroscopy. Molecular dynamics (MD) studies revealed a putative mode of interaction for this unusual electrostatic binding event. High binding specificity occurred through a combination of topological matching and electrostatic and hydrogen-bond complementarities. From MD...

  13. Development of Aptamer Beacons for Antemortem Diagnosis of Chronic Wasting Disease

    National Research Council Canada - National Science Library

    Clinkenbeard, Kenneth D

    2005-01-01

    .... Once selected, the CWD aptamers will be configured as aptamer beacons that can act as molecular switches to turn "on" a novel and highly sensitive diagnostic technology termed amplifying fluorescing polymer...

  14. Development of Aptamer Beacons for Antemortem Diagnosis of Chronic Wasting Disease

    National Research Council Canada - National Science Library

    Clinkenbeard, Kenneth

    2004-01-01

    .... Once selected, the CWD aptamers will be configured as aptamer beacons that can act as molecular switches to turn on a novel and highly sensitive diagnostic technology termed amplifying fluorescing polymer. Objective...

  15. The use of BEACON monitoring in plant power uprates

    International Nuclear Information System (INIS)

    Miller, Wade

    2003-01-01

    BEACON is the core support software technology that provides Utilities with continuous 3-D core power distribution monitoring, operational analysis capability, and operations support capability. BEACON monitoring delivers quantifiable plant margins for both reload design and plant operations improvement. When linked to Plant Power Upratings, BEACON permits an improvement in fuel cycle economics through higher peaking factors, higher power levels and higher discharge burnups. Operational flexibility of Uprated Plants is enhanced through elimination of axial power shape and core power tilt specifications. Also, the number of flux maps for these plants is reduced and local power is monitored continuously, permitting faster power escalation. Integrated 3-D power distribution analysis capabilities provide core designers with historical margin data that permits a reduction in core follow requirements as well as reduced curve book data related scope. Examples of specific Uprated Plant applications will be discussed. In anticipation of future needs of Uprated Plants, plans to integrate the technology of BEACON with COLSS are being executed. Finally, the capability to monitor Crud Induced Power Shift (axial offset) is also planned for incorporation into BEACON in the near future and will be discussed

  16. COSPAS-SARSAT Beacon Certification Facility

    Data.gov (United States)

    Federal Laboratory Consortium — EPG's COSPAS-SARSAT Beacon Certification Facility is one of five certification facilities in the world. Formal certifications are available for all beacon types and...

  17. 47 CFR 97.203 - Beacon station.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Beacon station. 97.203 Section 97.203... SERVICE Special Operations § 97.203 Beacon station. (a) Any amateur station licensed to a holder of a Technician, Technician Plus, General, Advanced or Amateur Extra Class operator license may be a beacon. A...

  18. An Interactive Real-Time Locating System Based on Bluetooth Low-Energy Beacon Network †.

    Science.gov (United States)

    Lin, You-Wei; Lin, Chi-Yi

    2018-05-21

    The ubiquity of Bluetooth-enabled smartphones and peripherals has brought tremendous convenience to our daily life. In recent years, Bluetooth beacons have also been gaining popularity in implementing a variety of innovative location-based services such as self-guided systems in exhibition centers. However, the broadcast-based beacon technology can only provide unidirectional communication. In case smartphone users would like to respond to the beacon messages, they have to rely on their own mobile Internet connections to send the information back to the backend system. Nevertheless, mobile Internet services may not be always available or too costly. In this work, we develop a real-time locating system based only on the Bluetooth low energy (BLE) technology to support interactive communications by combining the broadcast and mesh topology options to extend the applicability of beacon solutions. Specifically, we turn the smartphone into a beacon device and augment the beacon devices with the capability of forming a mesh network. The implementation result shows that our beacon devices can detect the presence of specific users at specific locations, and then the presence state can be sent to the application server via the relay of beacon devices. Moreover, the application server can send personalized location-based messages to the users, again via the relay of beacon devices. With the capability of relaying messages between the beacon devices, it would be convenient for developers to implement a variety of interactive applications such as tracking VIP customers at the airport, or tracking an elder with Alzheimer’s disease in the neighborhood.

  19. An Interactive Real-Time Locating System Based on Bluetooth Low-Energy Beacon Network †

    Directory of Open Access Journals (Sweden)

    You-Wei Lin

    2018-05-01

    Full Text Available The ubiquity of Bluetooth-enabled smartphones and peripherals has brought tremendous convenience to our daily life. In recent years, Bluetooth beacons have also been gaining popularity in implementing a variety of innovative location-based services such as self-guided systems in exhibition centers. However, the broadcast-based beacon technology can only provide unidirectional communication. In case smartphone users would like to respond to the beacon messages, they have to rely on their own mobile Internet connections to send the information back to the backend system. Nevertheless, mobile Internet services may not be always available or too costly. In this work, we develop a real-time locating system based only on the Bluetooth low energy (BLE technology to support interactive communications by combining the broadcast and mesh topology options to extend the applicability of beacon solutions. Specifically, we turn the smartphone into a beacon device and augment the beacon devices with the capability of forming a mesh network. The implementation result shows that our beacon devices can detect the presence of specific users at specific locations, and then the presence state can be sent to the application server via the relay of beacon devices. Moreover, the application server can send personalized location-based messages to the users, again via the relay of beacon devices. With the capability of relaying messages between the beacon devices, it would be convenient for developers to implement a variety of interactive applications such as tracking VIP customers at the airport, or tracking an elder with Alzheimer’s disease in the neighborhood.

  20. Crowdsourcing for Context: Regarding Privacy in Beacon Encounters via Contextual Integrity

    Directory of Open Access Journals (Sweden)

    Bello-Ogunu Emmanuel

    2016-07-01

    Full Text Available Research shows that context is important to the privacy perceptions associated with technology. With Bluetooth Low Energy beacons, one of the latest technologies for providing proximity and indoor tracking, the current identifiers that characterize a beacon are not sufficient for ordinary users to make informed privacy decisions about the location information that could be shared. One solution would be to have standardized category and privacy labels, produced by beacon providers or an independent third-party. An alternative solution is to find an approach driven by users, for users. In this paper, we propose a novel crowdsourcing based approach to introduce elements of context in beacon encounters.We demonstrate the effectiveness of this approach through a user study, where participants use a crowd-based mobile app designed to collect beacon category and privacy information as a scavenger hunt game. Results show that our approach was effective in helping users label beacons according to the specific context of a given beacon encounter, as well as the privacy perceptions associated with it. This labeling was done with an accuracy of 92%, and with an acceptance rate of 82% of all recommended crowd labels. Lastly, we conclusively show how crowdsourcing for context can be used towards a user-centric framework for privacy management during beacon encounters.

  1. Addressing Beacon re-identification attacks: quantification and mitigation of privacy risks.

    Science.gov (United States)

    Raisaro, Jean Louis; Tramèr, Florian; Ji, Zhanglong; Bu, Diyue; Zhao, Yongan; Carey, Knox; Lloyd, David; Sofia, Heidi; Baker, Dixie; Flicek, Paul; Shringarpure, Suyash; Bustamante, Carlos; Wang, Shuang; Jiang, Xiaoqian; Ohno-Machado, Lucila; Tang, Haixu; Wang, XiaoFeng; Hubaux, Jean-Pierre

    2017-07-01

    The Global Alliance for Genomics and Health (GA4GH) created the Beacon Project as a means of testing the willingness of data holders to share genetic data in the simplest technical context-a query for the presence of a specified nucleotide at a given position within a chromosome. Each participating site (or "beacon") is responsible for assuring that genomic data are exposed through the Beacon service only with the permission of the individual to whom the data pertains and in accordance with the GA4GH policy and standards.While recognizing the inference risks associated with large-scale data aggregation, and the fact that some beacons contain sensitive phenotypic associations that increase privacy risk, the GA4GH adjudged the risk of re-identification based on the binary yes/no allele-presence query responses as acceptable. However, recent work demonstrated that, given a beacon with specific characteristics (including relatively small sample size and an adversary who possesses an individual's whole genome sequence), the individual's membership in a beacon can be inferred through repeated queries for variants present in the individual's genome.In this paper, we propose three practical strategies for reducing re-identification risks in beacons. The first two strategies manipulate the beacon such that the presence of rare alleles is obscured; the third strategy budgets the number of accesses per user for each individual genome. Using a beacon containing data from the 1000 Genomes Project, we demonstrate that the proposed strategies can effectively reduce re-identification risk in beacon-like datasets. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.

  2. Electroactive crown ester-Cu2+ complex with in-situ modification at molecular beacon probe serving as a facile electrochemical DNA biosensor for the detection of CaMV 35s.

    Science.gov (United States)

    Zhan, Fengping; Liao, Xiaolei; Gao, Feng; Qiu, Weiwei; Wang, Qingxiang

    2017-06-15

    A novel electrochemical DNA biosensor has been facilely constructed by in-situ assembly of electroactive 4'-aminobenzo-18-crown-6-copper(II) complex (AbC-Cu 2+ ) on the free terminal of the hairpin-structured molecule beacon. The 3'-SH modified molecule beacon probe was first immobilized on the gold electrode (AuE) surface through self-assembly chemistry of Au-S bond. Then the crow ester of AbC was covalently coupled with 5'-COOH on the molecule beacon, and served as a platform to attach the Cu 2+ by coordination with ether bond (-O-) of the crown cycle. Thus, an electroactive molecule beacon-based biosensing interface was constructed. In comparison with conventional methods for preparation of electroactive molecule beacon, the approach presented in this work is much simpler, reagent- and labor-saving. Selectivity study shows that the in-situ fabricated electroactive molecule beacon remains excellent recognition ability of pristine molecule beacon probe to well differentiate various DNA fragments. The target DNA can be quantatively determined over the range from 0.10pM to 0.50nM. The detection limit of 0.060pM was estimated based on signal-to-noise ratio of 3. When the biosensor was applied for the detection cauliflower mosaic virus 35s (CaMV 35s) in soybean extraction samples, satisfactory results are achieved. This work opens a new strategy for facilely fabricating electrochemical sensing interface, which also shows great potential in aptasensor and immurosensor fabrication. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. The Westinghouse BEACON on-line core monitoring system

    International Nuclear Information System (INIS)

    Buechel, Robert J.; Boyd, William A.; Casadei, Alberto L.

    1995-01-01

    BEACON (Best Estimate Analysis of Core Operations - Nuclear), a core monitoring and operational support package developed by Westinghouse, has been installed at many operating PWRs worldwide. The BEACON system is a real-time monitoring system which can be used in plants with both fixed and movable incore detector systems and utilizes an on-line nodal model combined with core instrumentation data to provide continuous core power distribution monitoring. In addition, accurate core-predictive capabilities utilizing a full core nodal model updated according to plant operating history can be made to provide operational support. Core history information is kept and displayed to help operators anticipate core behavior and take pro-active control actions. The BEACON system has been licensed by the U.S. Nuclear Regulatory Commission for direct, continuous monitoring of DNBR and peak linear heat rate. This allows BEACON to be integrated into the plant technical specifications to permit significant relaxation of operating limitations defined by conventional technical specifications. (author). 4 refs, 2 figs, 1 tab

  4. Palindromic Molecule Beacon-Based Cascade Amplification for Colorimetric Detection of Cancer Genes.

    Science.gov (United States)

    Shen, Zhi-Fa; Li, Feng; Jiang, Yi-Fan; Chen, Chang; Xu, Huo; Li, Cong-Cong; Yang, Zhe; Wu, Zai-Sheng

    2018-03-06

    A highly sensitive and selective colorimetric assay based on a multifunctional molecular beacon with palindromic tail (PMB) was proposed for the detection of target p53 gene. The PMB probe can serve as recognition element, primer, and polymerization template and contains a nicking site and a C-rich region complementary to a DNAzyme. In the presence of target DNA, the hairpin of PMB is opened, and the released palindromic tails intermolecularly hybridize with each other, triggering the autonomous polymerization/nicking/displacement cycles. Although only one type of probe is involved, the system can execute triple and continuous polymerization strand displacement amplifications, generating large amounts of G-quadruplex fragments. These G-rich fragments can bind to hemin and form the DNAzymes that possess the catalytic activity similar to horseradish peroxidase, catalyzing the oxidation of ABTS by H 2 O 2 and producing the colorimetric signal. Utilizing the newly proposed sensing system, target DNA can be detected down to 10 pM with a linear response range from 10 pM to 200 nM, and mutant target DNAs are able to be distinguished even by the naked eye. The desirable detection sensitivity, high specificity, and operation convenience without any separation step and chemical modification demonstrate that the palindromic molecular beacon holds the potential for detecting and monitoring a variety of nucleic acid-related biomarkers.

  5. Easy-to-Build Satellite Beacon Receiver for Propagation Experimentation at Millimeter Bands

    Directory of Open Access Journals (Sweden)

    F. Machado

    2014-04-01

    Full Text Available This paper describes the design and development of a digital satellite beacon receiver for propagation experimentation. Satellite beacons are frequently available for pointing large antennas, but such signals can be used for measuring rain attenuation and other phenomena as, for example, tropospheric scintillation. A fairly inexpensive beacon receiver has been built using off-the-shelf parts. This instrument is not at all bulky making it suitable for easy transportation. This article analyzes the receiver specifications, describes in detail its structure and presents some operational test results.

  6. Pedestrian and motorists' actions at pedestrian hybrid beacon sites: findings from a pilot study.

    Science.gov (United States)

    Pulugurtha, Srinivas S; Self, Debbie R

    2015-01-01

    This paper focuses on an analysis of pedestrian and motorists' actions at sites with pedestrian hybrid beacons and assesses their effectiveness in improving the safety of pedestrians. Descriptive and statistical analyses (one-tail two-sample T-test and two-proportion Z-test) were conducted using field data collected during morning and evening peak hours at three study sites in the city of Charlotte, NC, before and after the installation of pedestrian hybrid beacons. Further, an analysis was conducted to assess the change in pedestrian and motorists' actions over time (before the installation; 1 month, 3 months, 6 months, and 12 months after the installation). Results showed an increase in average traffic speed at one of the pedestrian hybrid beacon sites while no specific trends were observed at the other two pedestrian hybrid beacon sites. A decrease in the number of motorists not yielding to pedestrians, pedestrians trapped in the middle of the street, and pedestrian-vehicle conflicts were observed at all the three pedestrian hybrid beacon sites. The installation of pedestrian hybrid beacons did not have a negative effect on pedestrian actions at two out of the three sites. Improvements seem to be relatively more consistent 3 months after the installation of the pedestrian hybrid beacon.

  7. Development of real-time NASBA assays with molecular beacon detection to quantify mRNA coding for HHV-8 lytic and latent genes

    NARCIS (Netherlands)

    Polstra, Abeltje M.; Goudsmit, J.; Cornelissen, M.

    2002-01-01

    Background: Human herpesvirus-8 (HHV-8) is linked to the pathogenesis of Kaposi's sarcoma (KS), and the HHV-8 DNA load in peripheral blood mononuclear cells ( PBMC) is associated with the clinical stage of KS. To examine the expression of HHV-8 in PBMC, four HHV-8 mRNA specific NASBA assays were

  8. The ANTARES optical beacon system

    International Nuclear Information System (INIS)

    Ageron, M.; Aguilar, J.A.; Albert, A.

    2007-01-01

    ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three-dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular, when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented

  9. The ANTARES optical beacon system

    Energy Technology Data Exchange (ETDEWEB)

    Ageron, M. [CPPM - Centre de Physique des Particules de Marseille, CNRS/IN2P3 et Universite de la Mediterranee, 163 Avenue de Luminy, Case 902, 13288 Marseille Cedex 9 (France); Aguilar, J.A. [IFIC - Instituto de Fisica Corpuscular, Edificios de Investigacion de Paterna, CSIC - Universitat de Valencia, Apdo. de Correos 22085, 46071 Valencia (Spain)]. E-mail: J.A.Aguilar@ific.uv.es; Albert, A. [GRPHE - Groupe de Recherche en Physique des Hautes Energies, Universite de Haute Alsace, 61 Rue Albert Camus, 68093 Mulhouse Cedex (France)) (and others)

    2007-08-11

    ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three-dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular, when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented.

  10. The ANTARES optical beacon system

    Science.gov (United States)

    Ageron, M.; Aguilar, J. A.; Albert, A.; Ameli, F.; Anghinolfi, M.; Anton, G.; Anvar, S.; Ardellier-Desages, F.; Aslanides, E.; Aubert, J.-J.; Auer, R.; Barbarito, E.; Basa, S.; Battaglieri, M.; Becherini, Y.; Beltramelli, J.; Bertin, V.; Bigi, A.; Billault, M.; Blaes, R.; de Botton, N.; Bouwhuis, M. C.; Bradbury, S. M.; Bruijn, R.; Brunner, J.; Burgio, G. F.; Busto, J.; Cafagna, F.; Caillat, L.; Calzas, A.; Capone, A.; Caponetto, L.; Carmona, E.; Carr, J.; Cartwright, S. L.; Castel, D.; Castorina, E.; Cavasinni, V.; Cecchini, S.; Ceres, A.; Charvis, P.; Chauchot, P.; Chiarusi, T.; Circella, M.; Colnard, C.; Compère, C.; Coniglione, R.; Cottini, N.; Coyle, P.; Cuneo, S.; Cussatlegras, A.-S.; Damy, G.; van Dantzig, R.; de Bonis, G.; de Marzo, C.; de Vita, R.; Dekeyser, I.; Delagnes, E.; Denans, D.; Deschamps, A.; Destelle, J.-J.; Dinkespieler, B.; Distefano, C.; Donzaud, C.; Drogou, J.-F.; Druillole, F.; Durand, D.; Ernenwein, J.-P.; Escoffier, S.; Falchini, E.; Favard, S.; Fehr, F.; Feinstein, F.; Ferry, S.; Fiorello, C.; Flaminio, V.; Fratini, K.; Fuda, J.-L.; Galeotti, S.; Gallone, J.-M.; Giacomelli, G.; Girard, N.; Gojak, C.; Goret, Ph.; Graf, K.; Hallewell, G.; Harakeh, M. N.; Hartmann, B.; Heijboer, A.; Heine, E.; Hello, Y.; Hernández-Rey, J. J.; Hößl, J.; Hoffman, C.; Hogenbirk, J.; Hubbard, J. R.; Jaquet, M.; Jaspers, M.; de Jong, M.; Jouvenot, F.; Kalantar-Nayestanaki, N.; Kappes, A.; Karg, T.; Katz, U.; Keller, P.; Kok, E.; Kok, H.; Kooijman, P.; Kopper, C.; Korolkova, E. V.; Kouchner, A.; Kretschmer, W.; Kruijer, A.; Kuch, S.; Kudryavstev, V. A.; Lagier, P.; Lahmann, R.; Lamanna, G.; Lamare, P.; Lambard, G.; Languillat, J.-C.; Laschinsky, H.; Lavalle, J.; Le Guen, Y.; Le Provost, H.; Le van Suu, A.; Lefèvre, D.; Legou, T.; Lelaizant, G.; Lim, G.; Lo Presti, D.; Loehner, H.; Loucatos, S.; Louis, F.; Lucarelli, F.; Lyashuk, V.; Marcelin, M.; Margiotta, A.; Masullo, R.; Mazéas, F.; Mazure, A.; McMillan, J. E.; Megna, R.; Melissas, M.; Migneco, E.; Milovanovic, A.; Mongelli, M.; Montaruli, T.; Morganti, M.; Moscoso, L.; Musumeci, M.; Naumann-Godo, M.; Naumann, C.; Niess, V.; Noble, T.; Olivetto, C.; Ostasch, R.; Palanque-Delabrouille, N.; Payre, P.; Peek, H.; Perez, A.; Petta, C.; Piattelli, P.; Pillet, R.; Pineau, J.-P.; Poinsignon, J.; Popa, V.; Pradier, T.; Racca, C.; Randazzo, N.; van Randwijk, J.; Real, D.; van Rens, B.; Réthoré, F.; Rewiersma, P.; Riccobene, G.; Rigaud, V.; Ripani, M.; Roca, V.; Roda, C.; Rolin, J. F.; Rose, H. J.; Rostovtsev, A.; Roux, J.; Ruppi, M.; Russo, G. V.; Rusydi, G.; Salesa, F.; Salomon, K.; Sapienza, P.; Schmitt, F.; Schuller, J.-P.; Shanidze, R.; Sokalski, I.; Spona, T.; Spurio, M.; van der Steenhoven, G.; Stolarczyk, T.; Streeb, K.; Sulak, L.; Taiuti, M.; Tamburini, C.; Tao, C.; Terreni, G.; Thompson, L. F.; Urbano, F.; Valdy, P.; Valente, V.; Vallage, B.; Vaudaine, G.; Venekamp, G.; Verlaat, B.; Vernin, P.; de Vries-Uiterweerd, G.; van Wijk, R.; Wijnker, G.; de Witt Huberts, P.; Wobbe, G.; de Wolf, E.; Yao, A.-F.; Zaborov, D.; Zaccone, H.; Zornoza, J. D.; Zúñiga, J.

    2007-08-01

    ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three-dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular, when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented.

  11. Serum inverts and improves the fluorescence response of an aptamer beacon to various vitamin D analytes.

    Science.gov (United States)

    Bruno, John G; Carrillo, Maria P; Phillips, Taylor; Edge, Allison

    2012-01-01

    A dominant aptamer loop structure from a library of nearly 100 candidate aptamer sequences developed against immobilized 25-hydroxyvitamin D(3) (calcidiol) was converted into a 5'-TYE 665 and 3'-Iowa black-labelled aptamer beacon. The aptamer beacon exhibited a mild 'lights on' reaction in buffer as a function of increasing concentrations of several vitamin D analogues and metabolites, with a limit of detection of approximately 200 ng/mL, and was not specific for any particular congener. In 10% or 50% human serum, the same aptamer beacon inverted its fluorescence behaviour to become a more intense 'lights off' reaction with an improved limit of detection in the range 4-16 ng/mL. We hypothesized that this drastic change in fluorescence behaviour was due to the presence of creatinine and urea in serum, which might destabilize the quenched beacon, causing an increase in fluorescence followed by decreasing fluorescence as a function of vitamin D concentrations that may bind and quench increasingly greater fractions of the denatured beacons. However, the results of several control experiments in the presence of physiological or greater concentrations of creatinine and urea, alone or combined in buffer, failed to produce the beacon fluorescence inversion. Other possible mechanistic hypotheses are also discussed. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Isothermal amplification detection of nucleic acids by a double-nicked beacon.

    Science.gov (United States)

    Shi, Chao; Zhou, Meiling; Pan, Mei; Zhong, Guilin; Ma, Cuiping

    2016-03-01

    Isothermal and rapid amplification detection of nucleic acids is an important technology in environmental monitoring, foodborne pathogen detection, and point-of-care clinical diagnostics. Here we have developed a novel method of isothermal signal amplification for single-stranded DNA (ssDNA) detection. The ssDNA target could be used as an initiator, coupled with a double-nicked molecular beacon, to originate amplification cycles, achieving cascade signal amplification. In addition, the method showed good specificity and strong anti-jamming capability. Overall, it is a one-pot and isothermal strand displacement amplification method without the requirement of a stepwise procedure, which greatly simplifies the experimental procedure and decreases the probability of contamination of samples. With its advantages, the method would be very useful to detect nucleic acids in point-of-care or field use. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Aftermath of bustamante attack on genomic beacon service.

    Science.gov (United States)

    Aziz, Md Momin Al; Ghasemi, Reza; Waliullah, Md; Mohammed, Noman

    2017-07-26

    With the enormous need for federated eco-system for holding global genomic and clinical data, Global Alliance for Genomic and Health (GA4GH) has created an international website called beacon service which allows a researcher to find out whether a specific dataset can be utilized to his or her research beforehand. This simple webservice is quite useful as it allows queries like whether a certain position of a target chromosome has a specific nucleotide. However, the increased integration of individuals genomic data into clinical practice and research raised serious privacy concern. Though the answer of such queries are yes or no in Bacon network, it results in serious privacy implication as demonstrated in a recent work from Shringarpure and Bustamante. In their attack model, the authors demonstrated that with a limited number of queries, presence of an individual in any dataset can be determined. We propose two lightweight algorithms (based on randomized response) which captures the efficacy while preserving the privacy of the participants in a genomic beacon service. We also elaborate the strength and weakness of the attack by explaining some of their statistical and mathematical models using real world genomic database. We extend their experimental simulations for different adversarial assumptions and parameters. We experimentally evaluated the solutions on the original attack model with different parameters for better understanding of the privacy and utility tradeoffs provided by these two methods. Also, the statistical analysis further elaborates the different aspects of the prior attack which leads to a better risk management for the participants in a beacon service. The differentially private and lightweight solutions discussed here will make the attack much difficult to succeed while maintaining the fundamental motivation of beacon database network.

  14. Searching for Cost-Optimized Interstellar Beacons

    Science.gov (United States)

    Benford, Gregory; Benford, James; Benford, Dominic

    2010-06-01

    What would SETI beacon transmitters be like if built by civilizations that had a variety of motives but cared about cost? In a companion paper, we presented how, for fixed power density in the far field, a cost-optimum interstellar beacon system could be built. Here, we consider how we should search for a beacon if it were produced by a civilization similar to ours. High-power transmitters could be built for a wide variety of motives other than the need for two-way communication; this would include beacons built to be seen over thousands of light-years. Extraterrestrial beacon builders would likely have to contend with economic pressures just as their terrestrial counterparts do. Cost, spectral lines near 1 GHz, and interstellar scintillation favor radiating frequencies substantially above the classic "water hole." Therefore, the transmission strategy for a distant, cost-conscious beacon would be a rapid scan of the galactic plane with the intent to cover the angular space. Such pulses would be infrequent events for the receiver. Such beacons built by distant, advanced, wealthy societies would have very different characteristics from what SETI researchers seek. Future searches should pay special attention to areas along the galactic disk where SETI searches have seen coherent signals that have not recurred on the limited listening time intervals we have used. We will need to wait for recurring events that may arriarrive in intermittent bursts. Several new SETI search strategies have emerged from these ideas. We propose a new test for beacons that is based on the Life Plane hypotheses.

  15. Visual detection of STAT5B gene expression in living cell using the hairpin DNA modified gold nanoparticle beacon.

    Science.gov (United States)

    Xue, Jianpeng; Shan, Lingling; Chen, Haiyan; Li, Yang; Zhu, Hongyan; Deng, Dawei; Qian, Zhiyu; Achilefu, Samuel; Gu, Yueqing

    2013-03-15

    Signal transducer and activator of transcription 5B (STAT5B) is an important protein in JAK-STAT signaling pathway that is responsible for the metastasis and proliferation of tumor cells. Determination of the STAT5B messenger Ribonucleic Acid (mRNA) relating to the STAT5B expression provides insight into the mechanism of tumor progression. In this study, we designed and used a special hairpin deoxyribonucleic acid (DNA) for human STAT5B mRNA to functionalize gold nanoparticles, which served as a beacon for detecting human STAT5B expression. Up to 90% quenching efficiency was achieved. Upon hybridizing with the target mRNA, the hairpin DNA modified gold nanoparticle beacons (hDAuNP beacons) release the fluorophores attached at 5' end of the oligonucleotide sequence. The fluorescence properties of the beacon before and after the hybridization with the complementary DNA were confirmed in vitro. The stability of hDAuNP beacons against degradation by DNase I and GSH indicated that the prepared beacon is stable inside cells. The detected fluorescence in MCF-7 cancer cells correlates with the specific STAT5B mRNA expression, which is consistent with the result from PCR measurement. Fluorescence microscopy showed that the hDAuNP beacons internalized in cells without using transfection agents, with intracellular distribution in the cytoplasm rather than the nucleus. The results demonstrated that this beacon could directly provide quantitative measurement of the intracellular STAT5B mRNA in living cells. Compared to the previous approaches, this beacon has advantages of higher target to background ratio of detection and an increased resistance to nuclease degradation. The strategy reported in this study is a promising approach for the intracellular measurement of RNA or protein expression in living cells, and has great potential in the study of drug screening and discovery. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Biotin-specific synthetic receptors prepared using molecular imprinting

    Energy Technology Data Exchange (ETDEWEB)

    Piletska, Elena; Piletsky, Sergey; Karim, Kal; Terpetschnig, Ewald; Turner, Anthony

    2004-02-16

    The composition of new molecularly imprinted polymers (MIPs) specific for biotin was optimised using molecular modelling software. Three functional monomers: methacrylic acid (MAA), 2-(trifluoromethyl)acrylic acid (TFAA) and 2-acrylamido-2-methylpropanesulfonic acid (AMPSA), which demonstrated the highest binding scores with biotin, were tested on their ability to generate specific binding sites. The imprinted polymers were photografted to the surface of polystyrene microspheres in water. The affinity of the synthetic 'receptor' sites was evaluated in binding experiments using horseradish peroxidase-labelled biotin. Good correlation was found between the modelling results and the performance of the materials in the template re-binding study. The dissociation constants for all MIPs were 1.4-16.8 nM, which is sufficient for most analytical applications where biotin is used as a label.

  17. Biotin-specific synthetic receptors prepared using molecular imprinting

    International Nuclear Information System (INIS)

    Piletska, Elena; Piletsky, Sergey; Karim, Kal; Terpetschnig, Ewald; Turner, Anthony

    2004-01-01

    The composition of new molecularly imprinted polymers (MIPs) specific for biotin was optimised using molecular modelling software. Three functional monomers: methacrylic acid (MAA), 2-(trifluoromethyl)acrylic acid (TFAA) and 2-acrylamido-2-methylpropanesulfonic acid (AMPSA), which demonstrated the highest binding scores with biotin, were tested on their ability to generate specific binding sites. The imprinted polymers were photografted to the surface of polystyrene microspheres in water. The affinity of the synthetic 'receptor' sites was evaluated in binding experiments using horseradish peroxidase-labelled biotin. Good correlation was found between the modelling results and the performance of the materials in the template re-binding study. The dissociation constants for all MIPs were 1.4-16.8 nM, which is sufficient for most analytical applications where biotin is used as a label

  18. Beach Advisory and Closing Online Notification (BEACON) system

    Data.gov (United States)

    U.S. Environmental Protection Agency — Beach Advisory and Closing Online Notification system (BEACON) is a colletion of state and local data reported to EPA about beach closings and advisories. BEACON is...

  19. BEACON: automated tool for Bacterial GEnome Annotation ComparisON

    KAUST Repository

    Kalkatawi, Manal M.; Alam, Intikhab; Bajic, Vladimir B.

    2015-01-01

    We developed BEACON, a fast tool for an automated and a systematic comparison of different annotations of single genomes. The extended annotation assigns putative functions to many genes with unknown functions. BEACON is available under GNU General Public License version 3.0 and is accessible at: http://www.cbrc.kaust.edu.sa/BEACON/

  20. 14 CFR 171.269 - Marker beacon performance requirements.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Marker beacon performance requirements. 171.269 Section 171.269 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... Landing System (ISMLS) § 171.269 Marker beacon performance requirements. ISMLS marker beacon equipment...

  1. Doing Forensic on DTUsat-2 Using the Beacon Counter

    DEFF Research Database (Denmark)

    Fléron, René

    2016-01-01

    DTUsat-2 was launched into a Polar LEO on a Dnepr rocket out of Yasny on 19th June 2014. After the first few days of beacon recording and precise orbit determination it became apparent that all was not nominal. One notable thing was the relatively low beacon count number. The beacon count reflects...

  2. Improved margin utilization through the use of beacon power distribution surveillance

    International Nuclear Information System (INIS)

    Miller, R. Wade; Boyd, William A.

    2002-01-01

    Core Operations, including fuel cycle costs, can be significantly improved when state of the art surveillance techniques are employed for core power distribution monitoring. Core power distribution monitoring and Technical Specification surveillance are major operational issues at PWR's, particularly in plants with movable in core detectors. Even plants with fixed in core detectors do not always make use of the continuous data that is available. The BEACON TM system (Best Estimate Analysis of Core Operations - Nuclear) is a core monitoring and operational support package developed by Westinghouse for use in PWR plants with fixed or movable in core detectors. BEACON is a real time core monitoring system, which uses existing core instrumentation data and an on-line neutronics model to provide continuous monitored of the core power distribution information. With this information available the BEACON system can be used to continuously monitor core power margin for the plant Tech Spec surveillance requirements and for plant operational guidance

  3. Cellular and molecular specificity of pituitary gland physiology.

    Science.gov (United States)

    Perez-Castro, Carolina; Renner, Ulrich; Haedo, Mariana R; Stalla, Gunter K; Arzt, Eduardo

    2012-01-01

    The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis.

  4. Molecularly Imprinted Polymers: Thermodynamic and Kinetic Considerations on the Specific Sorption and Molecular Recognition

    Directory of Open Access Journals (Sweden)

    Kejun Tong

    2008-04-01

    Full Text Available This article presents a work aiming at thermodynamically and kinetically interpreting the specific sorption and recognition by a molecularly imprinted polymer. Using Boc-L-Phe-OH as a template, the imprinted material was prepared. The result indicates that the prepared polymer can well discriminate the imprint species from its analogue (Boc-D-Phe-OH, so as to adsorb more for the former but less for the latter. Kinetic analysis indicates that this specific sorption, in nature, can be a result of a preferential promotion. The imprint within the polymer causes a larger adsorption rate for the template than for the analogue. Thermodynamic study also implies that the molecular induction from the specific imprint to the template is larger than to the analogue, which thus makes the polymer capable of preferentially alluring the template to bind.

  5. Greek PDO saffron authentication studies using species specific molecular markers.

    Science.gov (United States)

    Bosmali, I; Ordoudi, S A; Tsimidou, M Z; Madesis, P

    2017-10-01

    Saffron, the spice produced from the red stigmas of the flower of Crocus sativus L. is a frequent target of fraud and mislabeling practices that cannot be fully traced using the ISO 3632 trade standard specifications and test methods. A molecular approach is proposed herein as a promising branding strategy for the authentication of highly esteemed saffron brands such as the Greek Protected Designation of Origin (PDO) "Krokos Kozanis". Specific ISSR (inter-simple sequence repeat) markers were used to assess for the first time, the within species variability of several populations of C. sativus L. from the cultivation area of "Krokos Kozanis" as well as the potential differences with the band pattern produced by other Crocus species. Then, species-specific markers were developed taking advantage of an advanced molecular technique such as the HRM analysis coupled with universal DNA barcoding regions (trnL) (Bar-HRM) and applied to saffron admixtures with some of the most common plant adulterants (Calendula officinalis, Carthamus tinctorius, Gardenia jasminoides, Zea mays and Curcuma longa). The sensitivity of the procedure was tested for turmeric as a case study whereas HPLC-fluorescence determination of secondary metabolites was also employed for comparison. The overall results indicated that the Bar-HRM approach is quite effective in terms of specificity and sensitivity. Its effectiveness regarding the detection of turmeric was comparable to that of a conventional HPLC method (0.5% vs 1.0%, w/w). Yet, the proposed DNA-based method is much faster, cost-effective and can be used even by non-geneticists, in any laboratory having access to an HRM-capable real-time PCR instrumentation. It can be, thus, regarded as a strong analytical tool in saffron authentication studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Beacon satellite studies and modelling of total electron contents of the ionosphere

    International Nuclear Information System (INIS)

    Tyagi, T.R.

    1990-01-01

    An attempt is made to highlight some of the beacon satellite studies, particularly those relating to total electron content (TEC) and scintillations, with special attention to Indian subcontinent observations. The modelling of TEC is described. The scope of new experiments for specific problem is indicated. (author). 78 refs., 12 figs

  7. Sequential strand displacement beacon for detection of DNA coverage on functionalized gold nanoparticles.

    Science.gov (United States)

    Paliwoda, Rebecca E; Li, Feng; Reid, Michael S; Lin, Yanwen; Le, X Chris

    2014-06-17

    Functionalizing nanomaterials for diverse analytical, biomedical, and therapeutic applications requires determination of surface coverage (or density) of DNA on nanomaterials. We describe a sequential strand displacement beacon assay that is able to quantify specific DNA sequences conjugated or coconjugated onto gold nanoparticles (AuNPs). Unlike the conventional fluorescence assay that requires the target DNA to be fluorescently labeled, the sequential strand displacement beacon method is able to quantify multiple unlabeled DNA oligonucleotides using a single (universal) strand displacement beacon. This unique feature is achieved by introducing two short unlabeled DNA probes for each specific DNA sequence and by performing sequential DNA strand displacement reactions. Varying the relative amounts of the specific DNA sequences and spacing DNA sequences during their coconjugation onto AuNPs results in different densities of the specific DNA on AuNP, ranging from 90 to 230 DNA molecules per AuNP. Results obtained from our sequential strand displacement beacon assay are consistent with those obtained from the conventional fluorescence assays. However, labeling of DNA with some fluorescent dyes, e.g., tetramethylrhodamine, alters DNA density on AuNP. The strand displacement strategy overcomes this problem by obviating direct labeling of the target DNA. This method has broad potential to facilitate more efficient design and characterization of novel multifunctional materials for diverse applications.

  8. Solar powered aviation beacon/landing light

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    The objective of the work was to design, develop and test Solar Powered Aviation Landing Lights/Obstruction Beacons. The entire lighting units were to be stand alone devices capable of producing their own individual power supply. The whole process was to be documented to provide insight into the processes and decisions involved. (author)

  9. An analytical model for beaconing in VANETs

    NARCIS (Netherlands)

    van Eenennaam, Martijn; Remke, Anne Katharina Ingrid; Heijenk, Geert

    2012-01-01

    IEEE 802.11 CSMA/CA is generally considered to be well-understood, and many detailed models are available. However, most models focus on Unicast in small-scale W-LAN scenarios. When modelling beaconing in VANETs, the Broadcast nature and the (potentially) large number of nodes cause phenomena

  10. Building and strengthening infrastructure for data exchange: lessons from the beacon communities.

    Science.gov (United States)

    Torres, Gretchen W; Swietek, Karen; Ubri, Petry S; Singer, Rachel F; Lowell, Kristina H; Miller, Wilhelmine

    2014-01-01

    The Beacon Community Cooperative Agreement Program supports interventions, including care-delivery innovations, provider performance measurement and feedback initiatives, and tools for providers and consumers to enhance care. Using a learning health system framework, we examine the Beacon Communities' processes in building and strengthening health IT (HIT) infrastructures, specifically successes and challenges in sharing patient information to improve clinical care. In 2010, the Office of the National Coordinator for Health Information Technology (ONC) launched the three-year program, which provided $250 million to 17 Beacon Communities to invest in HIT and health information exchange (HIE) infrastructure. Beacon Communities used this funding to develop and disseminate HIT-enabled quality improvement practices found effective in particular community and practice environments. NORC conducted 7 site visits, November 2012-March 2013, selecting Communities to represent diverse program features. From August-October 2013, NORC held discussions with the remaining 10 Communities. Following each visit or discussion, NORC summarized the information gathered, including transcripts, team observations, and other documents the Community provided, to facilitate a within-Community analysis of context and stakeholders, intervention strategies, enabling factors, and challenges. Although each Community designed and implemented data-sharing strategies in a unique environment, similar challenges and enabling factors emerged across the Beacons. From a learning health system perspective, their strategies to build and strengthen data-sharing infrastructures address the following crosscutting priorities: promoting technical advances and innovations by helping providers adapt EHRs for data exchange and performance measurement with customizable IT and offering technical support to smaller, independent providers; engaging key stakeholders; and fostering transparent governance and stewardship

  11. Near-Infrared Fluorescence Imaging Guided Therapy: Molecular Beacon-Based Photosensitizers Triggered by Breast Cancer-Specific mRNA

    Science.gov (United States)

    2007-05-01

    experiments was first dissolved in dimethylsulfoxide ( DMSO ) (no more than 0.5% of total volume) and then diluted with 0.1% Tween 80 in DNA-water, filtered...Abbreviations: BSA, bovine serum albumin; DCM, dichlo- romethane; DIPEA, diisopropylethylamine; DMSO , dimethylsulfoxide ; EDTA...example, the standard aqueous solution-based oligonucleotide conjugation protocol, even with the help of organic solvents (ACN), can not be used for

  12. A domain specific language for performance portable molecular dynamics algorithms

    Science.gov (United States)

    Saunders, William Robert; Grant, James; Müller, Eike Hermann

    2018-03-01

    Developers of Molecular Dynamics (MD) codes face significant challenges when adapting existing simulation packages to new hardware. In a continuously diversifying hardware landscape it becomes increasingly difficult for scientists to be experts both in their own domain (physics/chemistry/biology) and specialists in the low level parallelisation and optimisation of their codes. To address this challenge, we describe a "Separation of Concerns" approach for the development of parallel and optimised MD codes: the science specialist writes code at a high abstraction level in a domain specific language (DSL), which is then translated into efficient computer code by a scientific programmer. In a related context, an abstraction for the solution of partial differential equations with grid based methods has recently been implemented in the (Py)OP2 library. Inspired by this approach, we develop a Python code generation system for molecular dynamics simulations on different parallel architectures, including massively parallel distributed memory systems and GPUs. We demonstrate the efficiency of the auto-generated code by studying its performance and scalability on different hardware and compare it to other state-of-the-art simulation packages. With growing data volumes the extraction of physically meaningful information from the simulation becomes increasingly challenging and requires equally efficient implementations. A particular advantage of our approach is the easy expression of such analysis algorithms. We consider two popular methods for deducing the crystalline structure of a material from the local environment of each atom, show how they can be expressed in our abstraction and implement them in the code generation framework.

  13. 76 FR 17625 - Proposed Information Collection; Comment Request; Emergency Beacon Registrations

    Science.gov (United States)

    2011-03-30

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Proposed Information Collection; Comment Request; Emergency Beacon Registrations AGENCY: National Oceanic and Atmospheric... emergency radio beacon. Persons purchasing a digital distress beacon, operating in the frequency range of...

  14. Localization with a mobile beacon in underwater acoustic sensor networks.

    Science.gov (United States)

    Lee, Sangho; Kim, Kiseon

    2012-01-01

    Localization is one of the most important issues associated with underwater acoustic sensor networks, especially when sensor nodes are randomly deployed. Given that it is difficult to deploy beacon nodes at predetermined locations, localization schemes with a mobile beacon on the sea surface or along the planned path are inherently convenient, accurate, and energy-efficient. In this paper, we propose a new range-free Localization with a Mobile Beacon (LoMoB). The mobile beacon periodically broadcasts a beacon message containing its location. Sensor nodes are individually localized by passively receiving the beacon messages without inter-node communications. For location estimation, a set of potential locations are obtained as candidates for a node's location and then the node's location is determined through the weighted mean of all the potential locations with the weights computed based on residuals.

  15. Localization with a Mobile Beacon in Underwater Acoustic Sensor Networks

    Directory of Open Access Journals (Sweden)

    Sangho Lee

    2012-04-01

    Full Text Available Localization is one of the most important issues associated with underwater acoustic sensor networks, especially when sensor nodes are randomly deployed. Given that it is difficult to deploy beacon nodes at predetermined locations, localization schemes with a mobile beacon on the sea surface or along the planned path are inherently convenient, accurate, and energy-efficient. In this paper, we propose a new range-free Localization with a Mobile Beacon (LoMoB. The mobile beacon periodically broadcasts a beacon message containing its location. Sensor nodes are individually localized by passively receiving the beacon messages without inter-node communications. For location estimation, a set of potential locations are obtained as candidates for a node’s location and then the node’s location is determined through the weighted mean of all the potential locations with the weights computed based on residuals.

  16. High-visibility infrared beacons for IFF and combat ID

    Science.gov (United States)

    Pralle, Martin; Puscasu, Irina; Johnson, Edward; Loges, Peter; Melnyk, James

    2005-05-01

    A new kind of Identification Friend or Foe (IFF) infrared beacon has been demonstrated. The omni-directional beacon consists of a pyramidal array of 1W pulsIR thermal light sources. Operating at a total power of 84W, the beacon can be used to track and identify surface vehicles and personnel with a recognition range of up to 6 miles on the battlefield and in urban environments or the marine boundary layer. Advanced photonic technology enables the beacon to be seen only while using a 3-5 μm or 8-12 μm thermal imaging system. There is no visible or near-IR emission to betray the location of the beacon. The beacon is rugged and will operate from -40 to 50°C ambient temperature, 0-100% relative humidity, 0 - 10,000 ft altitude, and meets MIL-STD 810F and MIL-STD 461E.

  17. Aircraft Position Measurement Using Laser Beacon Optics.

    Science.gov (United States)

    1981-01-01

    8217Comparison of Solar Concentrators .’ Solar Energy, Vol. 10, p. 93, 1976. 7. Winston , R., ’Light Collection Within the Framework of Goemetrical Optics ...8217 J. Optical Society of Am., Vol. 60, p. 245, 1970. 8. Welford, W. T., tics of Nonimaging Concentrators . New York, Academic Press, T978. 9. Bracewell...helicopter pilot and the flight engineer on board the YO-3A. This thesis will concentrate on the development of the laser beacon, the detector optics

  18. Design and Practical Evaluation of a Family of Lightweight Protocols for Heterogeneous Sensing through BLE Beacons in IoT Telemetry Applications.

    Science.gov (United States)

    Hernández-Rojas, Dixys L; Fernández-Caramés, Tiago M; Fraga-Lamas, Paula; Escudero, Carlos J

    2017-12-27

    The Internet of Things (IoT) involves a wide variety of heterogeneous technologies and resource-constrained devices that interact with each other. Due to such constraints, IoT devices usually require lightweight protocols that optimize the use of resources and energy consumption. Among the different commercial IoT devices, Bluetooth and Bluetooth Low Energy (BLE)-based beacons, which broadcast periodically certain data packets to notify their presence, have experienced a remarkable growth, specially due to their application in indoor positioning systems. This article proposes a family of protocols named Lightweight Protocol for Sensors (LP4S) that provides fast responses and enables plug-and-play mechanisms that allow IoT telemetry systems to discover new nodes and to describe and auto-register the sensors and actuators connected to a beacon. Thus, three protocols are defined depending on the beacon hardware characteristics: LP4S-6 (for resource-constraint beacons), LP4S-X (for more powerful beacons) and LP4S-J (for beacons able to run complex firmware). In order to demonstrate the capabilities of the designed protocols, the most restrictive (LP4S-6) is tested after implementing it for a telemetry application in a beacon based on Eddystone (Google's open beacon format). Thus, the beacon specification is extended in order to increase its ability to manage unlimited sensors in a telemetry system without interfering in its normal operation with Eddystone frames. The performed experiments show the feasibility of the proposed solution and its superiority, in terms of latency and energy consumption, with respect to approaches based on Generic Attribute Profile (GATT) when multiple users connect to a mote or in scenarios where latency is not a restriction, but where low-energy consumption is essential.

  19. Design and Practical Evaluation of a Family of Lightweight Protocols for Heterogeneous Sensing through BLE Beacons in IoT Telemetry Applications

    Science.gov (United States)

    2017-01-01

    The Internet of Things (IoT) involves a wide variety of heterogeneous technologies and resource-constrained devices that interact with each other. Due to such constraints, IoT devices usually require lightweight protocols that optimize the use of resources and energy consumption. Among the different commercial IoT devices, Bluetooth and Bluetooth Low Energy (BLE)-based beacons, which broadcast periodically certain data packets to notify their presence, have experienced a remarkable growth, specially due to their application in indoor positioning systems. This article proposes a family of protocols named Lightweight Protocol for Sensors (LP4S) that provides fast responses and enables plug-and-play mechanisms that allow IoT telemetry systems to discover new nodes and to describe and auto-register the sensors and actuators connected to a beacon. Thus, three protocols are defined depending on the beacon hardware characteristics: LP4S-6 (for resource-constraint beacons), LP4S-X (for more powerful beacons) and LP4S-J (for beacons able to run complex firmware). In order to demonstrate the capabilities of the designed protocols, the most restrictive (LP4S-6) is tested after implementing it for a telemetry application in a beacon based on Eddystone (Google’s open beacon format). Thus, the beacon specification is extended in order to increase its ability to manage unlimited sensors in a telemetry system without interfering in its normal operation with Eddystone frames. The performed experiments show the feasibility of the proposed solution and its superiority, in terms of latency and energy consumption, with respect to approaches based on Generic Attribute Profile (GATT) when multiple users connect to a mote or in scenarios where latency is not a restriction, but where low-energy consumption is essential. PMID:29280975

  20. Design and Practical Evaluation of a Family of Lightweight Protocols for Heterogeneous Sensing through BLE Beacons in IoT Telemetry Applications

    Directory of Open Access Journals (Sweden)

    Dixys L. Hernández-Rojas

    2017-12-01

    Full Text Available The Internet of Things (IoT involves a wide variety of heterogeneous technologies and resource-constrained devices that interact with each other. Due to such constraints, IoT devices usually require lightweight protocols that optimize the use of resources and energy consumption. Among the different commercial IoT devices, Bluetooth and Bluetooth Low Energy (BLE-based beacons, which broadcast periodically certain data packets to notify their presence, have experienced a remarkable growth, specially due to their application in indoor positioning systems. This article proposes a family of protocols named Lightweight Protocol for Sensors (LP4S that provides fast responses and enables plug-and-play mechanisms that allow IoT telemetry systems to discover new nodes and to describe and auto-register the sensors and actuators connected to a beacon. Thus, three protocols are defined depending on the beacon hardware characteristics: LP4S-6 (for resource-constraint beacons, LP4S-X (for more powerful beacons and LP4S-J (for beacons able to run complex firmware. In order to demonstrate the capabilities of the designed protocols, the most restrictive (LP4S-6 is tested after implementing it for a telemetry application in a beacon based on Eddystone (Google’s open beacon format. Thus, the beacon specification is extended in order to increase its ability to manage unlimited sensors in a telemetry system without interfering in its normal operation with Eddystone frames. The performed experiments show the feasibility of the proposed solution and its superiority, in terms of latency and energy consumption, with respect to approaches based on Generic Attribute Profile (GATT when multiple users connect to a mote or in scenarios where latency is not a restriction, but where low-energy consumption is essential.

  1. Radiolabelled peptides and nanoparticles for specific molecular targeting in oncology

    International Nuclear Information System (INIS)

    Helbok, A.

    2011-01-01

    The aim of this thesis is the development of radiolabelled peptides and nanoparticles (NP) for specific molecular targeting in oncology. Three different types of NP were investigated in this study: lipid - based NP (liposomes and micelles), human serum albumin - based NP (albumin NP) and protamine - oligonucleotide - based NP (proticles). In a first step, radiolabelling protocols were set up for the different NP - formulations. The variety of radioisotopes used, covers the whole spectrum of applications in nuclear medicine: SPECT (111In, 99mTc), (2) PET (68Ga) and therapeutic applications (177Lu, 90Y) opening a manifold administration potential for these NP aiming towards multiple targeting and hybrid imaging strategies (combined SPECT / PET and MRI). Radiolabelling quality was analyzed by instant thin layer chromatography (ITLC). High radiochemical yields (RCY >90 %) and high specific activity (SA) were achieved. NP - formulations were derivatized with the chelating agent Diethylenetriaminepentaacetic acid (DTPA) allowing complexation of trivalent radiometals, and potentially nonradioactive metals, such as Gd3+, for MRI imaging leading to the development of multifunctionalized NP for a unified labelling approach. Furthermore, NP were derivatized with the pharmacokinetic modifier polyethylene glycol (PEG) to maintain NP with long circulating ability. Stability assessments included incubation in different media (serum, 4 mM DTPA - solution and PBS pH 7.4, at 37 o C for a period of 24 h). For the in vivo biodistribution of the NP, static and / or dynamic SPECT / PET imaging studies were performed at different time points with Lewis rats and correlated to results from quantification of tissue - uptake. Results indicate differences in stability and general pharmacokinetic behaviour depended on the NP - formulation. However, a positive influence expressed in a prolonged retention time in circulation was investigated for all different NP - formulations due to PEG

  2. Topical MMP beacon enabled fluorescence-guided resection of oral carcinoma

    Science.gov (United States)

    Burgess, Laura; Chen, Juan; Wolter, Nikolaus E.; Wilson, Brian; Zheng, Gang

    2016-01-01

    Each year almost 300,000 individuals worldwide are diagnosed with oral cancer, more than 90% of these being oral carcinoma [N. Engl. J. Med. 328, 184 19938417385]. Surgical resection is the standard of care, but accurate delineation of the tumor boundaries is challenging, resulting in either under-resection with risk of local recurrence or over-resection with increased functional loss and negative impact on quality of life. This study evaluates, in two pre-clinical in vivo tumor models, the potential of fluorescence-guided resection using molecular beacons activated by metalloproteinases, which are frequently upregulated in human oral cancer. In both models there was rapid (beacon activation upon local application, allowing clear fluoresecence imaging in vivo and confirmed by ex vivo fluorescence microscopy and HPLC, with minimal activation in normal oral tissues. Although the tissue penetration was limited using topical application, these findings support further development of this approach towards translation to first-in-human trials. PMID:27231609

  3. Beach Advisory and Closing Online Notification (BEACON) system

    Science.gov (United States)

    Beach Advisory and Closing Online Notification system (BEACON) is a colletion of state and local data reported to EPA about beach closings and advisories. BEACON is the public-facing query of the Program tracking, Beach Advisories, Water quality standards, and Nutrients database (PRAWN) which tracks beach closing and advisory information.

  4. Recent progress in satellite radio beacon studies with particular emphasis on the ATS-6 radio beacon experiment

    International Nuclear Information System (INIS)

    Davies, K.

    1980-01-01

    In May 1974 a new era in satellite radio beacon studies of the ionosphere opened with the ATS-6 Radio Beacon Experiment. The history of radio beacon studies up to that time is reviewed briefly and the particular features of the ATS-6 beacon are discussed together with the basic theory required to interpret the measurements. The main emphasis is on the ATS-6 beacon experiment but other beacon data are discussed which provide the necessary background. The diurnal and seasonal variations of the total electron content and the plasmaspheric content are presented for the U.S.A. and Europe. In winter the plasmaspheric content over the Western Hemisphere maximizes at night while in Europe and the Pacific it appears to peak near noon. This is thought to be caused by flow of plasma from the local and conjugate ionospheres. Night maxima of total electron content are found showing that they do not arise from depletions of the plasmaspheric content. The plasmaspheric content is highly sensitive to solar-terrestrial disturbance, it reaches a minimum on the third day of a storm and may take between 10 and 20 days of partial filling and emptying to recover. Travelling disturbances in U.S.A., Europe, and India show similarities of speeds but not of direction. Beacon observations of micropulsations in total content, tropospheric fluctuations and Fresnel diffraction by intense ionospheric irregularities are discussed together with radio wave scintillations and some applications of beacon radio data to communications and navigation. (orig.)

  5. Molecular Mechanisms of Ion-Specific Effects on Proteins

    Czech Academy of Sciences Publication Activity Database

    Rembert, K. B.; Paterová, Jana; Heyda, Jan; Hilty, Ch.; Jungwirth, Pavel; Cremer, P. S.

    2012-01-01

    Roč. 134, č. 24 (2012), s. 10039-10046 ISSN 0002-7863 R&D Projects: GA ČR GA203/08/0114 Institutional research plan: CEZ:AV0Z40550506 Keywords : ions * proteins * molecular dynamics * NMR Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 10.677, year: 2012

  6. 76 FR 65216 - Beacon Medical Services, LLC, Aurora, CO; Notice of Negative Determination Regarding Application...

    Science.gov (United States)

    2011-10-20

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-80,219] Beacon Medical Services... workers and former workers of Beacon Medical Services, LLC, Aurora, Colorado (Beacon Medical Services... published in the Federal Register on July 8, 2011 (76 FR 40401). The workers of Beacon Medical Services are...

  7. 78 FR 75392 - American Beacon Funds, et al.; Notice of Application

    Science.gov (United States)

    2013-12-11

    ... Asset Management LLC; (b) American Beacon Balanced Fund--the Manager, Barrow, Hanley, Mewhinney... Beacon Funds, et al.; Notice of Application December 5, 2013. AGENCY: Securities and Exchange Commission...) (order). Applicants: American Beacon Funds and American Beacon Select Funds (collectively, the ``Trusts...

  8. A Microfluidic Love-Wave Biosensing Device for PSA Detection Based on an Aptamer Beacon Probe.

    Science.gov (United States)

    Zhang, Feng; Li, Shuangming; Cao, Kang; Wang, Pengjuan; Su, Yan; Zhu, Xinhua; Wan, Ying

    2015-06-11

    A label-free and selective aptamer beacon-based Love-wave biosensing device was developed for prostate specific antigen (PSA) detection. The device consists of the following parts: LiTaO3 substrate with SiO2 film as wave guide layer, two set of inter-digital transducers (IDT), gold film for immobilization of the biorecongniton layer and a polydimethylsiloxane (PDMS) microfluidic channels. DNA aptamer, or "artificial antibody", was used as the specific biorecognition probe for PSA capture. Some nucleotides were added to the 3'-end of the aptamer to form a duplex with the 3'-end, turning the aptamer into an aptamer-beacon. Taking advantage of the selective target-induced assembly changes arising from the "aptamer beacon", highly selective and specific detection of PSA was achieved. Furthermore, PDMS microfluidic channels were designed and fabricated to realize automated quantitative sample injection. After optimization of the experimental conditions, the established device showed good performance for PSA detection between 10 ng/mL to 1 μg/mL, with a detection limit of 10 ng/mL. The proposed sensor might be a promising alternative for point of care diagnostics.

  9. Do rufous hummingbirds (Selasphorus rufus) use visual beacons?

    Science.gov (United States)

    Hurly, T Andrew; Franz, Simone; Healy, Susan D

    2010-03-01

    Animals are often assumed to use highly conspicuous features of a goal to head directly to that goal ('beaconing'). In the field it is generally assumed that flowers serve as beacons to guide pollinators. Artificial hummingbird feeders are coloured red to serve a similar function. However, anecdotal reports suggest that hummingbirds return to feeder locations in the absence of the feeder (and thus the beacon). Here we test these reports for the first time in the field, using the natural territories of hummingbirds and manipulating flowers on a scale that is ecologically relevant to the birds. We compared the predictions from two distinct hypotheses as to how hummingbirds might use the visual features of rewards: the distant beacon hypothesis and the local cue hypothesis. In two field experiments, we found no evidence that rufous hummingbirds used a distant visual beacon to guide them to a rewarded location. In no case did birds abandon their approach to the goal location from a distance; rather they demonstrated remarkable accuracy of navigation by approaching to within about 70 cm of a rewarded flower's original location. Proximity varied depending on the size of the training flower: birds flew closer to a previously rewarded location if it had been previously signalled with a small beacon. Additionally, when provided with a beacon at a new location, birds did not fly directly to the new beacon. Taken together, we believe these data demonstrate that these hummingbirds depend little on visual characteristics to beacon to rewarded locations, but rather that they encode surrounding landmarks in order to reach the goal and then use the visual features of the goal as confirmation that they have arrived at the correct location.

  10. Molecular design of sequence specific DNA alkylating agents.

    Science.gov (United States)

    Minoshima, Masafumi; Bando, Toshikazu; Shinohara, Ken-ichi; Sugiyama, Hiroshi

    2009-01-01

    Sequence-specific DNA alkylating agents have great interest for novel approach to cancer chemotherapy. We designed the conjugates between pyrrole (Py)-imidazole (Im) polyamides and DNA alkylating chlorambucil moiety possessing at different positions. The sequence-specific DNA alkylation by conjugates was investigated by using high-resolution denaturing polyacrylamide gel electrophoresis (PAGE). The results showed that polyamide chlorambucil conjugates alkylate DNA at flanking adenines in recognition sequences of Py-Im polyamides, however, the reactivities and alkylation sites were influenced by the positions of conjugation. In addition, we synthesized conjugate between Py-Im polyamide and another alkylating agent, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). DNA alkylation reactivies by both alkylating polyamides were almost comparable. In contrast, cytotoxicities against cell lines differed greatly. These comparative studies would promote development of appropriate sequence-specific DNA alkylating polyamides against specific cancer cells.

  11. Snapshot analysis for rhodium fixed incore detector using BEACON methodology

    International Nuclear Information System (INIS)

    Cha, Kyoon Ho; Choi, Yu Sun; Lee, Eun Ki; Park, Moon Ghu; Morita, Toshio; Heibel, Michael D.

    2004-01-01

    The purpose of this report is to process the rhodium detector data of the Yonggwang nuclear unit 4 cycle 5 core for the measured power distribution by using the BEACON methodology. Rhodium snapshots of the YGN 4 cycle 5 have been analyzed by both BEACON/SPINOVA and CECOR to compare the results of both codes. By analyzing a large number of snapshots obtained during normal plant operation. Reviewing the results of this analysis, the BEACON/SPNOVA can be used for the snapshot analysis of Korean Standard Nuclear Power (KSNP) plants

  12. BEACON TSM application system to the operation of PWR reactors

    International Nuclear Information System (INIS)

    Lozano, J. A.; Mildrum, C.; Serrano, J. F.

    2012-01-01

    BEACON-TSM is an advanced core monitoring system for PWR reactor cores, and also offers the possibility to perform a wide range of predictive calculation in support of reactor operation. BEACON-TSM is presently installed and licensed in the 5 Spanish PWR reactors of standard Westinghouse design. the purpose of this paper is to describe the features of this software system and to show the advantages obtainable by a nuclear power plant from its use. To illustrate the capabilities and benefits of BEACON-TSM two real case reactor operating situations are presented. (Author)

  13. Beacon-S TM: Non-uniform attenuation correction for SPECT imaging. The new medium-energy transmission device for AXIS and IRIX

    International Nuclear Information System (INIS)

    Daniel Gagnon, D.

    1999-01-01

    The paper presents new medium-energy transmission device for SPECT imaging. Beacon-S includes a 356-keV medium energy 133 Ba source with a 10.54-year half-life. Beacon-S provide high-resolution and high-contrast transmission scans. The higher energy of the gamma substantially improves the transmission contrast for larger patients by virtue of better penetration through the body

  14. Evaluation of light-emitting diode beacon light fixtures.

    Science.gov (United States)

    2009-12-01

    Rotating beacons containing filament light sources have long been used on highway maintenance trucks : to indicate the presence of the truck to other drivers. Because of advances in light-emitting diode (LED) : technologies, flashing lights containin...

  15. Evaluation of BEACON-COLSS Core Monitoring System Benefits

    International Nuclear Information System (INIS)

    Kim, Joon Sung; Park, Young Ho; Morita, Toshio; Book, Michael A.

    2005-01-01

    In Korean Standard Nuclear Power Plant COLSS (Core Operating Limit Supervisory System) is used to monitor the DNBR Power Operating Limit (DNBRPOL) and Linear Heat Rate POL (KWPFPOL). Westinghouse and KNFC have developed an upgraded core monitoring system by combining the BEACON TM core monitoring system 1 (Best Estimate Analyzer for Core Operation . Nuclear) and COLSS into an integrated product that is called BEACON-COLSS. BEACON-COLSS generates the 3-D power distribution corrected by the in-core detectors measurements. The 3-D core power distribution methodology in BEACON-COLSS is significantly better than the synthesis methodology in COLSS. BEACONCOLSS uses the CETOP-D 2 thermal hydraulic code instead of CETOP-1. CETOP-D is a multi-channel thermal hydraulics code that will provide more accurate DNBR calculations than the DNBR calculators currently used in COLSS

  16. Pedestrian hybrid beacon guide : recommendations and case study.

    Science.gov (United States)

    2014-01-01

    A pedestrian hybrid beacon (PHB) is a traffic control : device similar to a European pedestrian signal : (PELICAN) that was imported to the US and adapted by : engineers in Arizona to increase motorists awareness of : pedestrian crossings at uncon...

  17. A heuristic evaluation of the Facebook's advertising tool beacon

    OpenAIRE

    Jamal, A; Cole, M

    2009-01-01

    Interface usability is critical to the successful adoption of information systems. The aim of this study is to evaluate interface of Facebook's advertising tool Beacon by using privacy heuristics [4]. Beacon represents an interesting case study because of the negative media and user backlash it received. The findings of heuristic evaluation suggest violation of privacy heuristics [4]. Here, analysis identified concerns about user choice and consent, integrity and security of data, and awarene...

  18. Molecular basis of coiled-coil oligomerization-state specificity.

    Science.gov (United States)

    Ciani, Barbara; Bjelic, Saša; Honnappa, Srinivas; Jawhari, Hatim; Jaussi, Rolf; Payapilly, Aishwarya; Jowitt, Thomas; Steinmetz, Michel O; Kammerer, Richard A

    2010-11-16

    Coiled coils are extensively and successfully used nowadays to rationally design multistranded structures for applications, including basic research, biotechnology, nanotechnology, materials science, and medicine. The wide range of applications as well as the important functions these structures play in almost all biological processes highlight the need for a detailed understanding of the factors that control coiled-coil folding and oligomerization. Here, we address the important and unresolved question why the presence of particular oligomerization-state determinants within a coiled coil does frequently not correlate with its topology. We found an unexpected, general link between coiled-coil oligomerization-state specificity and trigger sequences, elements that are indispensable for coiled-coil formation. By using the archetype coiled-coil domain of the yeast transcriptional activator GCN4 as a model system, we show that well-established trimer-specific oligomerization-state determinants switch the peptide's topology from a dimer to a trimer only when inserted into the trigger sequence. We successfully confirmed our results in two other, unrelated coiled-coil dimers, ATF1 and cortexillin-1. We furthermore show that multiple topology determinants can coexist in the same trigger sequence, revealing a delicate balance of the resulting oligomerization state by position-dependent forces. Our experimental results should significantly improve the prediction of the oligomerization state of coiled coils. They therefore should have major implications for the rational design of coiled coils and consequently many applications using these popular oligomerization domains.

  19. Beacon-Colss core monitoring system application and benefits

    International Nuclear Information System (INIS)

    Boyd, W.A.; Yoon, T.Y.

    2005-01-01

    Westinghouse and KNFC are creating an upgraded core monitoring system by merging the BEACON system (best estimate analyzer for core operation-nuclear) and COLSS (core operating limit supervisory system) into an integrated product. Although both BEACON and COLSS are core monitoring systems that have been in operation at many plants for a number of years, they each have some features and capabilities that are not in the other. Therefore it has been decided to incorporate portions of COLSS into the beacon system to create an optional level to support core monitoring applications on selected combustion engineering (C-E) designed plants. This optional level in the beacon system will be called BEACON-COLSS and will allow the beacon system to monitor the LCO's and Tech Spec limits at CE plants that currently use COLSS. This paper will present the structure of the new core monitoring system and the benefits it achieves for current COLSS plants, i.e., CE plants in the US and KSNP (Korean standard nuclear power plant). (authors)

  20. Development of haplotype-specific molecular markers for the low-molecular-weight glutenin subunits

    Science.gov (United States)

    Low-molecular-weight glutenin subunits (LMW-GSs) are one of the major components of gluten and their allelic variation has been widely associated with numerous wheat end-use quality parameters. These proteins are encoded by multigene families located at the orthologous Glu-3 loci (Glu-A3, Glu-B3 and...

  1. Molecular-targeted nanotherapies in cancer: enabling treatment specificity.

    Science.gov (United States)

    Blanco, Elvin; Hsiao, Angela; Ruiz-Esparza, Guillermo U; Landry, Matthew G; Meric-Bernstam, Funda; Ferrari, Mauro

    2011-12-01

    Chemotherapy represents a mainstay and powerful adjuvant therapy in the treatment of cancer. The field has evolved from drugs possessing all-encompassing cell-killing effects to those with highly targeted, specific mechanisms of action; a direct byproduct of enhanced understanding of tumorigenic processes. However, advances regarding development of agents that target key molecules and dysregulated pathways have had only modest impacts on patient survival. Several biological barriers preclude adequate delivery of drugs to tumors, and remain a formidable challenge to overcome in chemotherapy. Currently, the field of nanomedicine is enabling the delivery of chemotherapeutics, including repositioned drugs and siRNAs, by giving rise to carriers that provide for protection from degradation, prolonged circulation times, and increased tumor accumulation, all the while resulting in reduced patient morbidity. This review aims to highlight several innovative, nanoparticle-based platforms with the potential of providing clinical translation of several novel chemotherapeutic agents. We will also summarize work regarding the development of a multistage drug delivery strategy, a robust carrier platform designed to overcome several biological barriers while en route to tumors. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. A quantum dot-aptamer beacon using a DNA intercalating dye as the FRET reporter: application to label-free thrombin detection.

    Science.gov (United States)

    Chi, Chun-Wei; Lao, Yeh-Hsing; Li, Yi-Shan; Chen, Lin-Chi

    2011-03-15

    A new quantum dot (QD)-aptamer (apt) beacon that acts by folding-induced dissociation of a DNA intercalating dye, BOBO-3(B), is demonstrated with label-free thrombin detection. The beacon, denoted as QD-apt:B, is constructed by (1) coupling of a single-stranded thrombin aptamer to Qdot 565 via EDC/Sulfo-NHS chemistry and (2) staining the duplex regions of the aptamer on QD with excess BOBO-3 before thrombin binding. When mixing a thrombin sample with QD-apt:B, BOBO-3 is competed away from the beacon due to target-induced aptamer folding, which then causes a decrease in QD fluorescence resonance energy transfer (FRET)-mediated BOBO-3 emission and achieves thrombin quantitation. In this work, the effects of Mg(2+), coupling time, and aptamer type on the beacon's performances are investigated and discussed thoroughly with various methods, including transmission electron microscopy (TEM), dynamic light scattering (DLS), and two-color differential gel electrophoresis. Using the best aptamer beacon (HTQ37), we attain highly specific and wide-range detection (from nM to μM) of thrombin in buffer, and the beacon can sense nM-range thrombin in 15% diluted serum. Compared to the reported QD aptamer assays, our method is advantageous from the aspect of using a simple sensory unit design without losing the detection sensitivity. Therefore, we consider the QD-apt:B beacon a potential alternative to immuno-reagents and an effective tool to study nucleic acid folding on QD as well. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

    International Nuclear Information System (INIS)

    Matsushita, Y.; Murakawa, T.; Shimamura, K.; Oishi, M.; Ohyama, T.; Kurita, N.

    2015-01-01

    The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA

  4. Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Y., E-mail: kurita@cs.tut.ac.jp; Murakawa, T., E-mail: kurita@cs.tut.ac.jp; Shimamura, K., E-mail: kurita@cs.tut.ac.jp; Oishi, M., E-mail: kurita@cs.tut.ac.jp; Ohyama, T., E-mail: kurita@cs.tut.ac.jp; Kurita, N., E-mail: kurita@cs.tut.ac.jp [Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi, 441-8580 (Japan)

    2015-02-27

    The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA.

  5. Data governance and data sharing agreements for community-wide health information exchange: lessons from the beacon communities.

    Science.gov (United States)

    Allen, Claudia; Des Jardins, Terrisca R; Heider, Arvela; Lyman, Kristin A; McWilliams, Lee; Rein, Alison L; Schachter, Abigail A; Singh, Ranjit; Sorondo, Barbara; Topper, Joan; Turske, Scott A

    2014-01-01

    Unprecedented efforts are underway across the United States to electronically capture and exchange health information to improve health care and population health, and reduce costs. This increased collection and sharing of electronic patient data raises several governance issues, including privacy, security, liability, and market competition. Those engaged in such efforts have had to develop data sharing agreements (DSAs) among entities involved in information exchange, many of whom are "nontraditional" health care entities and/or new partners. This paper shares lessons learned based on the experiences of six federally funded communities participating in the Beacon Community Cooperative Agreement Program, and offers guidance for navigating data governance issues and developing DSAs to facilitate community-wide health information exchange. While all entities involved in electronic data sharing must address governance issues and create DSAs accordingly, until recently little formal guidance existed for doing so - particularly for community-based initiatives. Despite this lack of guidance, together the Beacon Communities' experiences highlight promising strategies for navigating complex governance issues, which may be useful to other entities or communities initiating information exchange efforts to support delivery system transformation. For the past three years, AcademyHealth has provided technical assistance to most of the 17 Beacon Communities, 6 of whom contributed to this collaborative writing effort. Though these communities varied widely in terms of their demographics, resources, and Beacon-driven priorities, common themes emerged as they described their approaches to data governance and DSA development. The 6 Beacon Communities confirmed that DSAs are necessary to satisfy legal and market-based concerns, and they identified several specific issues, many of which have been noted by others involved in network data sharing initiatives. More importantly, these

  6. 14 CFR 171.321 - DME and marker beacon performance requirements.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false DME and marker beacon performance... (MLS) § 171.321 DME and marker beacon performance requirements. (a) The DME equipment must meet the..._regulations/ibr_locations.html. (b) MLS marker beacon equipment must meet the performance requirements...

  7. 33 CFR 149.580 - What are the requirements for a radar beacon?

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false What are the requirements for a radar beacon? 149.580 Section 149.580 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Navigation Miscellaneous § 149.580 What are the requirements for a radar beacon? (a) A radar beacon (RACON...

  8. 77 FR 41271 - Safety Zone; Newburgh to Beacon Swim, Newburgh, Hudson River, NY

    Science.gov (United States)

    2012-07-13

    ... 1625-AA00 Safety Zone; Newburgh to Beacon Swim, Newburgh, Hudson River, NY AGENCY: Coast Guard, DHS... navigable waters of the Hudson River, NY in the vicinity of Newburgh, NY for the annual Newburgh Beacon Swim... Beacon Swim is an annual recurring event that has a permanent safety zone found at 33 CFR 165.160. The...

  9. Information Dissemination in VANETS by Piggybacking on Beacons -- An Analysis of the Impact of Network Parameters

    NARCIS (Netherlands)

    Klein Wolterink, W.; Heijenk, Geert; Karagiannis, Georgios

    2011-01-01

    Piggybacking on beacons is a forwarding technique that is regularly used in vehicular ad-hoc network (VANET) research as a means to disseminate data. With this technique data is attached to and transmitted along with scheduled beacons, without changing the timing of the beacons. In this paper we

  10. All-organic microelectromechanical systems integrating specific molecular recognition--a new generation of chemical sensors.

    Science.gov (United States)

    Ayela, Cédric; Dubourg, Georges; Pellet, Claude; Haupt, Karsten

    2014-09-03

    Cantilever-type all-organic microelectromechanical systems based on molecularly imprinted polymers for specific analyte recognition are used as chemical sensors. They are produced by a simple spray-coating-shadow-masking process. Analyte binding to the cantilever generates a measurable change in its resonance frequency. This allows label-free detection by direct mass sensing of low-molecular-weight analytes at nanomolar concentrations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Gold nanoparticle-based beacon to detect STAT5b mRNA expression in living cells: a case optimized by bioinformatics screen

    Directory of Open Access Journals (Sweden)

    Deng D

    2015-04-01

    Full Text Available Dawei Deng,* Yang Li,* Jianpeng Xue, Jie Wang, Guanhua Ai, Xin Li, Yueqing GuDepartment of Biomedical Engineering, China Pharmaceutical University, Nanjing, People’s Republic of China*These authors contributed equally to this workAbstract: Messenger RNA (mRNA, a single-strand ribonucleic acid with functional gene information is usually abnormally expressed in cancer cells and has become a promising biomarker for the study of tumor progress. Hairpin DNA-coated gold nanoparticle (hDAuNP beacon containing a bare gold nanoparticle (AuNP as fluorescence quencher and thiol-terminated fluorescently labeled stem–loop–stem oligonucleotide sequences attached by Au–S bond is currently a new nanoscale biodiagnostic platform capable of mRNA detection, in which the design of the loop region sequence is crucial for hybridizing with the target mRNA. Hence, in this study, to improve the sensitivity and selectivity of hDAuNP beacon simultaneously, the loop region of hairpin DNA was screened by bioinformatics strategy. Here, signal transducer and activator of transcription 5b (STAT5b mRNA was selected and used as a practical example. The results from the combined characterizations using optical techniques, flow cytometry assay, and cell microscopic imaging showed that after optimization, the as-prepared hDAuNP beacon had higher selectivity and sensitivity for the detection of STAT5b mRNA in living cells, as compared with our previous beacon. Thus, the bioinformatics method may be a promising new strategy for assisting in the designing of the hDAuNP beacon, extending its application in the detection of mRNA expression and the resultant mRNA-based biological processes and disease pathogenesis.Keywords: molecular beacon, bioinformatics, gold nanoparticle, STAT5b mRNA, visual detection

  12. Exploring the transformative potential of Bluetooth beacons in higher education

    Directory of Open Access Journals (Sweden)

    Kieran McDonald

    2016-11-01

    Full Text Available The growing ubiquity of smartphones and tablet devices integrated into personal, social and professional life, facilitated by expansive communication networks globally, has the potential to disrupt higher education. Academics and students are considering the future possibilities of exploiting these tools and utilising networks to consolidate and expand knowledge, enhancing learning gain. Bluetooth beacon technology has been developed by both Apple and Google as a way to situate digital information within physical spaces, and this paper reflects on a beacon intervention in a contemporary art school in higher education conducted by the authors intended to develop a situated community of practice in Art & Design. The paper describes the project, including relevant theoretical foundations and background to the beacon technology, with regards to the potential of using these devices to create a connected learning community by enhancing learning and facilitating knowledge creation in a borderless learning space.

  13. Detection of thermocouple malfunction in the Beacon system

    International Nuclear Information System (INIS)

    Morita, T.; Heibel, M.D.; Congedo, T.V.

    1992-01-01

    The BEACON system uses Core Exit Thermocouples (T/C) extensively for continuous radial power distribution monitoring. The T/C's are used to adjust the reference power distribution generated by the BEACON system to match the current radial power distribution. T/C reliability, repeatability, and relative accuracy have been very satisfactory. However, it is very important to detect any T/C malfunctions during operation, since a T/C signal change caused by an undetected malfunction can lead to serious errors in the radial power distribution developed by BEACON. A simple procedure has been developed which is capable of discriminating between changes in T/C signals caused by actual changes in reactor conditions and signal changes caused by T/C malfunctions

  14. Comparison of BEACON and COMPARE reactor cavity subcompartment analyses

    International Nuclear Information System (INIS)

    Burkett, M.W.; Idar, E.S.; Gido, R.G.; Lime, J.F.; Koestel, A.

    1984-04-01

    In this study, a more advanced best-estimate containment code, BEACON-MOD3A, was ued to calculate force and moment loads resulting from a high-energy blowdown for two reactor cavity geometries previously analyzed with the licensing computer code COMPARE-MOD1A. The BEACON force and moment loads were compared with the COMPARE results to determine the safety margins provided by the COMPARE code. The forces and moments calculated by the codes were found to be different, although not in any consistent manner, for the two reactor cavity geometries studied. Therefore, generic summary statements regarding margins cannot be made because of the effects of the detailed physical configuration. However, differences in the BEACON and COMPARE calculated forces and moments can be attributed to differences in the modeling assumptions used in the codes and the analyses

  15. Some early results from the ATS-6 radio beacon experiment

    International Nuclear Information System (INIS)

    Davies, K.; Fritz, R.B.; Grubb, R.N.; Jones, J.E.

    1975-01-01

    The multifrequency satellite radio beacon enables the measurement of the columnar electron content of the ionosphere and plasmasphere along the ray path and its spatial and temporal structure. Measurements include modulation phase, Faraday rotation, and amplitude. The characteristics of the beacon transmitter and its design are presented together with the design of the Boulder receiver and antennas and the calibration procedures. A shape factor F is defined which depends on the electron density and geomagnetic field distributions. It is found that F varies by about 30 percent from day to night. It is shown that the ratio of the plasmaspheric content to total content varies from about 0.08 during the day to about 0.35 at night. Other examples which are presented to illustrate the uses of the radio beacon include sunrise effects, solar flare enhancements of total content, and the ionospheric storms of early July 1974

  16. BEACON: automated tool for Bacterial GEnome Annotation ComparisON.

    Science.gov (United States)

    Kalkatawi, Manal; Alam, Intikhab; Bajic, Vladimir B

    2015-08-18

    Genome annotation is one way of summarizing the existing knowledge about genomic characteristics of an organism. There has been an increased interest during the last several decades in computer-based structural and functional genome annotation. Many methods for this purpose have been developed for eukaryotes and prokaryotes. Our study focuses on comparison of functional annotations of prokaryotic genomes. To the best of our knowledge there is no fully automated system for detailed comparison of functional genome annotations generated by different annotation methods (AMs). The presence of many AMs and development of new ones introduce needs to: a/ compare different annotations for a single genome, and b/ generate annotation by combining individual ones. To address these issues we developed an Automated Tool for Bacterial GEnome Annotation ComparisON (BEACON) that benefits both AM developers and annotation analysers. BEACON provides detailed comparison of gene function annotations of prokaryotic genomes obtained by different AMs and generates extended annotations through combination of individual ones. For the illustration of BEACON's utility, we provide a comparison analysis of multiple different annotations generated for four genomes and show on these examples that the extended annotation can increase the number of genes annotated by putative functions up to 27%, while the number of genes without any function assignment is reduced. We developed BEACON, a fast tool for an automated and a systematic comparison of different annotations of single genomes. The extended annotation assigns putative functions to many genes with unknown functions. BEACON is available under GNU General Public License version 3.0 and is accessible at: http://www.cbrc.kaust.edu.sa/BEACON/ .

  17. Beacon communities' public health initiatives: a case study analysis.

    Science.gov (United States)

    Massoudi, Barbara L; Marcial, Laura H; Haque, Saira; Bailey, Robert; Chester, Kelley; Cunningham, Shellery; Riley, Amanda; Soper, Paula

    2014-01-01

    The Beacon Communities for Public Health (BCPH) project was launched in 2011 to gain a better understanding of the range of activities currently being conducted in population- and public health by the Beacon Communities. The project highlighted the successes and challenges of these efforts with the aim of sharing this information broadly among the public health community. The Beacon Community Program, designed to showcase technology-enabled, community-based initiatives to improve outcomes, focused on: building and strengthening health information technology (IT) infrastructure and exchange capabilities; translating investments in health IT to measureable improvements in cost, quality, and population health; and, developing innovative approaches to performance measurement, technology, and care delivery. Four multimethod case studies were conducted based on a modified sociotechnical framework to learn more about public health initiative implementation and use in the Beacon Communities. Our methodological approach included using document review and semistructured key informant interviews. NACCHO Model Practice Program criteria were used to select the public health initiatives included in the case studies. Despite differences among the case studies, common barriers and facilitators were found to be present in all areas of the sociotechnical framework application including structure, people, technology, tasks, overarching considerations, and sustainability. Overall, there were many more facilitators (range = 7-14) present for each Beacon compared to barriers (range = 4-6). Four influential promising practices were identified through the work: forging strong and sustainable partnerships; ensuring a good task-technology fit and a flexible and iterative design; fostering technology acceptance; and, providing education and demonstrating value. A common weakness was the lack of a framework or model for the Beacon Communities evaluation work. Sharing a framework or approach

  18. Beacon Communities’ Public Health Initiatives: A Case Study Analysis

    Science.gov (United States)

    Massoudi, Barbara L.; Marcial, Laura H.; Haque, Saira; Bailey, Robert; Chester, Kelley; Cunningham, Shellery; Riley, Amanda; Soper, Paula

    2014-01-01

    Introduction: The Beacon Communities for Public Health (BCPH) project was launched in 2011 to gain a better understanding of the range of activities currently being conducted in population- and public health by the Beacon Communities. The project highlighted the successes and challenges of these efforts with the aim of sharing this information broadly among the public health community. Background: The Beacon Community Program, designed to showcase technology-enabled, community-based initiatives to improve outcomes, focused on: building and strengthening health information technology (IT) infrastructure and exchange capabilities; translating investments in health IT to measureable improvements in cost, quality, and population health; and, developing innovative approaches to performance measurement, technology, and care delivery. Methods: Four multimethod case studies were conducted based on a modified sociotechnical framework to learn more about public health initiative implementation and use in the Beacon Communities. Our methodological approach included using document review and semistructured key informant interviews. NACCHO Model Practice Program criteria were used to select the public health initiatives included in the case studies. Findings: Despite differences among the case studies, common barriers and facilitators were found to be present in all areas of the sociotechnical framework application including structure, people, technology, tasks, overarching considerations, and sustainability. Overall, there were many more facilitators (range = 7–14) present for each Beacon compared to barriers (range = 4–6). Discussion: Four influential promising practices were identified through the work: forging strong and sustainable partnerships; ensuring a good task-technology fit and a flexible and iterative design; fostering technology acceptance; and, providing education and demonstrating value. Conclusions: A common weakness was the lack of a framework or model for

  19. Simultaneous visualization of the subfemtomolar expression of microRNA and microRNA target gene using HILO microscopy† †Electronic supplementary information (ESI) available: The LED device for the sample photobleaching, a schematic presentation of HILO microscopy, fluorescence spectra and hybridization curves of the molecular beacons, the linear correlation between the miRNA fluorescence intensity and the miRNA copy number, a validation of the miRNA adsorption and miRNA target gene expression via RT-qPCR, a validation of RT-qPCR using capillary electrophoresis, the reproducibility of RT-qPCR and Poisson distribution of the miRNA pipetting as well as a complete list of the oligonucleotides used in this study. See DOI: 10.1039/c7sc02701j Click here for additional data file.

    Science.gov (United States)

    Lin, Yi-Zhen; Ou, Da-Liang; Chang, Hsin-Yuan; Lin, Wei-Yu; Hsu, Chiun

    2017-01-01

    The family of microRNAs (miRNAs) not only plays an important role in gene regulation but is also useful for the diagnosis of diseases. A reliable method with high sensitivity may allow researchers to detect slight fluctuations in ultra-trace amounts of miRNA. In this study, we propose a sensitive imaging method for the direct probing of miR-10b (miR-10b-3p, also called miR-10b*) and its target (HOXD10 mRNA) in fixed cells based on the specific recognition of molecular beacons combined with highly inclined and laminated optical sheet (HILO) fluorescence microscopy. The designed dye-quencher-labelled molecular beacons offer excellent efficiencies of fluorescence resonance energy transfer that allow us to detect miRNA and the target mRNA simultaneously in hepatocellular carcinoma cells using HILO fluorescence microscopy. Not only can the basal trace amount of miRNA be observed in each individual cell, but the obtained images also indicate that this method is useful for monitoring the fluctuations in ultra-trace amounts of miRNA when the cells are transfected with a miRNA precursor or a miRNA inhibitor (anti-miR). Furthermore, a reasonable causal relation between the miR-10b and HOXD10 expression levels was observed in miR-10b* precursor-transfected cells and miR-10b* inhibitor-transfected cells. The trends of the miRNA alterations obtained using HILO microscopy completely matched the RT-qPCR data and showed remarkable reproducibility (the coefficient of variation [CV] = 0.86%) and sensitivity (<1.0 fM). This proposed imaging method appears to be useful for the simultaneous visualisation of ultra-trace amounts of miRNA and target mRNA and excludes the procedures for RNA extraction and amplification. Therefore, the visualisation of miRNA and the target mRNA should facilitate the exploration of the functions of ultra-trace amounts of miRNA in fixed cells in biological studies and may serve as a powerful tool for diagnoses based on circulating cancer cells. PMID:28989695

  20. Frequency Estimator Performance for a Software-Based Beacon Receiver

    Science.gov (United States)

    Zemba, Michael J.; Morse, Jacquelynne Rose; Nessel, James A.; Miranda, Felix

    2014-01-01

    As propagation terminals have evolved, their design has trended more toward a software-based approach that facilitates convenient adjustment and customization of the receiver algorithms. One potential improvement is the implementation of a frequency estimation algorithm, through which the primary frequency component of the received signal can be estimated with a much greater resolution than with a simple peak search of the FFT spectrum. To select an estimator for usage in a QV-band beacon receiver, analysis of six frequency estimators was conducted to characterize their effectiveness as they relate to beacon receiver design.

  1. Early Detection of Breast Cancer Using Molecular Beacons

    Science.gov (United States)

    2008-01-01

    therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. We thank Dr. Toncred Styblo and Beth...charges. This article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 To whom...Ambrosini, G., Adida , C., and Altieri, D. C. (1997) Nat. Med. 3, 917–921 17. Tanaka, K., Iwamoto, S., Gon, G., Nohara, T., Iwamoto,M., andTanigawa, N

  2. New frontiers of molecular beacons: signal amplification and nanomachines

    DEFF Research Database (Denmark)

    Della Vedova, Paolo

    2013-01-01

    by two complementary strands (stem), conjugated respectively with a fluorophore and a quencher. Upon hybridization with complementary target, the stem bonds break, parting the fluorophore from the quencher and resulting in a detectable signal. This thesis is divided in two major sections. The first...

  3. Optimalization of Beacon Selection for Localization in Wireless AD-HOC Networks

    Directory of Open Access Journals (Sweden)

    Martin Matula

    2008-01-01

    Full Text Available In this paper we engage in optimalization of convenient beacons for localization position of a node in the ad-hoc network. An algorithm designed by us localizes position of moving or static node by RSS (Received Signal Strength method and trilateration. At first, localization of unknown node runs by combination of all beacons. Than optimalizating algorithmreduces the number of beacons (and repeats localization, while only three left. Its reduction is based on highest levels of received signal strength. It is only when signals are from the nearest beacons. Position localizating exactness is statistically interpreted from all localization by beacons combination and its repeating.

  4. Overshadowing of geometric cues by a beacon in a spatial navigation task.

    Science.gov (United States)

    Redhead, Edward S; Hamilton, Derek A; Parker, Matthew O; Chan, Wai; Allison, Craig

    2013-06-01

    In three experiments, we examined whether overshadowing of geometric cues by a discrete landmark (beacon) is due to the relative saliences of the cues. Using a virtual water maze task, human participants were required to locate a platform marked by a beacon in a distinctively shaped pool. In Experiment 1, the beacon overshadowed geometric cues in a trapezium, but not in an isosceles triangle. The longer escape latencies during acquisition in the trapezium control group with no beacon suggest that the geometric cues in the trapezium were less salient than those in the triangle. In Experiment 2, we evaluated whether generalization decrement, caused by the removal of the beacon at test, could account for overshadowing. An additional beacon was placed in an alternative corner. For the control groups, the beacons were identical; for the overshadow groups, they were visually unique. Overshadowing was again found in the trapezium. In Experiment 3, we tested whether the absence of overshadowing in the triangle was due to the geometric cues being more salient than the beacon. Following training, the beacon was relocated to a different corner. Participants approached the beacon rather than the trained platform corner, suggesting that the beacon was more salient. These results suggest that associative processes do not fully explain cue competition in the spatial domain.

  5. Robot-Beacon Distributed Range-Only SLAM for Resource-Constrained Operation.

    Science.gov (United States)

    Torres-González, Arturo; Martínez-de Dios, Jose Ramiro; Ollero, Anibal

    2017-04-20

    This work deals with robot-sensor network cooperation where sensor nodes (beacons) are used as landmarks for Range-Only (RO) Simultaneous Localization and Mapping (SLAM). Most existing RO-SLAM techniques consider beacons as passive devices disregarding the sensing, computational and communication capabilities with which they are actually endowed. SLAM is a resource-demanding task. Besides the technological constraints of the robot and beacons, many applications impose further resource consumption limitations. This paper presents a scalable distributed RO-SLAM scheme for resource-constrained operation. It is capable of exploiting robot-beacon cooperation in order to improve SLAM accuracy while meeting a given resource consumption bound expressed as the maximum number of measurements that are integrated in SLAM per iteration. The proposed scheme combines a Sparse Extended Information Filter (SEIF) SLAM method, in which each beacon gathers and integrates robot-beacon and inter-beacon measurements, and a distributed information-driven measurement allocation tool that dynamically selects the measurements that are integrated in SLAM, balancing uncertainty improvement and resource consumption. The scheme adopts a robot-beacon distributed approach in which each beacon participates in the selection, gathering and integration in SLAM of robot-beacon and inter-beacon measurements, resulting in significant estimation accuracies, resource-consumption efficiency and scalability. It has been integrated in an octorotor Unmanned Aerial System (UAS) and evaluated in 3D SLAM outdoor experiments. The experimental results obtained show its performance and robustness and evidence its advantages over existing methods.

  6. The BEACON on-line core monitoring system. Functional upgrades and applications

    International Nuclear Information System (INIS)

    Boyd, W.A.; Miller, R.W.

    1997-01-01

    The BEACON TM core monitor system has been in commercial operation since 1989 and was licensed by the USNRC for on-line core power distribution and thermal power limit monitoring in 1994. Since that time BEACON has been installed at 17 plants. Each of these customers has a different perspective on the use of data from BEACON and a different approach on the application of BEACON to support their plant operations. To support these varied needs and approaches the BEACON system has been divided into three operational levels to better match the system functions to the customer needs and approaches to system integration. Based on customer feedback, the BEACON system was upgraded in some areas and streamlined in other areas to better support the needs of each customer. The three operational levels of the BEACON system, the major product upgrades and system evolution that has taken place to support the needs and applications of our customers are discussed. (authors)

  7. A molecular-gap device for specific determination of mercury ions

    Science.gov (United States)

    Guo, Zheng; Liu, Zhong-Gang; Yao, Xian-Zhi; Zhang, Kai-Sheng; Chen, Xing; Liu, Jin-Huai; Huang, Xing-Jiu

    2013-11-01

    Specific determination/monitoring of trace mercury ions (Hg2+) in environmental water is of significant importance for drinking safety. Complementarily to conventional inductively coupled plasma mass spectrometry and atomic emission/absorption spectroscopy, several methods, i.e., electrochemical, fluorescent, colorimetric, and surface enhanced Raman scattering approaches, have been developed recently. Despite great success, many inevitably encounter the interferences from other metal ions besides the complicated procedures and sophisticated equipments. Here we present a molecular-gap device for specific determination of trace Hg2+ in both standardized solutions and environmental samples based on conductivity-modulated glutathione dimer. Through a self-assembling technique, a thin film of glutathione monolayer capped Au nanoparticles is introduced into 2.5 μm-gap-electrodes, forming numerous double molecular layer gaps. Notably, the fabricated molecular-gap device shows a specific response toward Hg2+ with a low detection limit actually measured down to 1 nM. Theoretical calculations demonstrate that the specific sensing mechanism greatly depends on the electron transport ability of glutathione dimer bridged by heavy metal ions, which is determined by its frontier molecular orbital, not the binding energy.

  8. Making it local: Beacon Communities use health information technology to optimize care management.

    Science.gov (United States)

    Allen, Amy; Des Jardins, Terrisca R; Heider, Arvela; Kanger, Chatrian R; Lobach, David F; McWilliams, Lee; Polello, Jennifer M; Rein, Alison L; Schachter, Abigail A; Singh, Ranjit; Sorondo, Barbara; Tulikangas, Megan C; Turske, Scott A

    2014-06-01

    Care management aims to provide cost-effective, coordinated, non-duplicative care to improve care quality, population health, and reduce costs. The 17 communities receiving funding from the Office of the National Coordinator for Health Information Technology through the Beacon Community Cooperative Agreement Program are leaders in building and strengthening their health information technology (health IT) infrastructure to provide more effective and efficient care management. This article profiles 6 Beacon Communities' health IT-enabled care management programs, highlighting the influence of local context on program strategy and design, and describing challenges, lessons learned, and policy implications for care delivery and payment reform. The unique needs (eg, disease burden, demographics), community partnerships, and existing resources and infrastructure all exerted significant influence on the overall priorities and design of each community's care management program. Though each Beacon Community needed to engage in a similar set of care management tasks--including patient identification, stratification, and prioritization; intervention; patient engagement; and evaluation--the contextual factors helped shape the specific strategies and tools used to carry out these tasks and achieve their objectives. Although providers across the country are striving to deliver standardized, high-quality care, the diverse contexts in which this care is delivered significantly influence the priorities, strategies, and design of community-based care management interventions. Gaps and challenges in implementing effective community-based care management programs include: optimizing allocation of care management services; lack of available technology tailored to care management needs; lack of standards and interoperability; integrating care management into care settings; evaluating impact; and funding and sustainability.

  9. Remarks on the observability of single beacon underwater navigation

    DEFF Research Database (Denmark)

    Jouffroy, Jerome; Ross, Andrew

    This paper contributes a simple and intuitive result in the analysis of underwater navigation using a single ranging beacon. This analysis should help with the design of small and lightweight underwater vehicles by reducing the amount of instrumentation required for accurate navigation. The concept...

  10. On the Efficiency of Secure Beaconing in VANETs

    NARCIS (Netherlands)

    Schoch, Elmar; Kargl, Frank

    Direct inter-vehicle communication enables numerous safety applications like intersection collision warning. Beacons - periodic one-hop link-layer broadcast messages containing, e.g., location, heading, and speed - are the basis for many such applications. For security, current work often requires

  11. Smartphone-Based Indoor Localization with Bluetooth Low Energy Beacons

    Directory of Open Access Journals (Sweden)

    Yuan Zhuang

    2016-04-01

    Full Text Available Indoor wireless localization using Bluetooth Low Energy (BLE beacons has attracted considerable attention after the release of the BLE protocol. In this paper, we propose an algorithm that uses the combination of channel-separate polynomial regression model (PRM, channel-separate fingerprinting (FP, outlier detection and extended Kalman filtering (EKF for smartphone-based indoor localization with BLE beacons. The proposed algorithm uses FP and PRM to estimate the target’s location and the distances between the target and BLE beacons respectively. We compare the performance of distance estimation that uses separate PRM for three advertisement channels (i.e., the separate strategy with that use an aggregate PRM generated through the combination of information from all channels (i.e., the aggregate strategy. The performance of FP-based location estimation results of the separate strategy and the aggregate strategy are also compared. It was found that the separate strategy can provide higher accuracy; thus, it is preferred to adopt PRM and FP for each BLE advertisement channel separately. Furthermore, to enhance the robustness of the algorithm, a two-level outlier detection mechanism is designed. Distance and location estimates obtained from PRM and FP are passed to the first outlier detection to generate improved distance estimates for the EKF. After the EKF process, the second outlier detection algorithm based on statistical testing is further performed to remove the outliers. The proposed algorithm was evaluated by various field experiments. Results show that the proposed algorithm achieved the accuracy of <2.56 m at 90% of the time with dense deployment of BLE beacons (1 beacon per 9 m, which performs 35.82% better than <3.99 m from the Propagation Model (PM + EKF algorithm and 15.77% more accurate than <3.04 m from the FP + EKF algorithm. With sparse deployment (1 beacon per 18 m, the proposed algorithm achieves the accuracies of <3.88 m at

  12. BEACON: automated tool for Bacterial GEnome Annotation ComparisON

    KAUST Repository

    Kalkatawi, Manal M.

    2015-08-18

    Background Genome annotation is one way of summarizing the existing knowledge about genomic characteristics of an organism. There has been an increased interest during the last several decades in computer-based structural and functional genome annotation. Many methods for this purpose have been developed for eukaryotes and prokaryotes. Our study focuses on comparison of functional annotations of prokaryotic genomes. To the best of our knowledge there is no fully automated system for detailed comparison of functional genome annotations generated by different annotation methods (AMs). Results The presence of many AMs and development of new ones introduce needs to: a/ compare different annotations for a single genome, and b/ generate annotation by combining individual ones. To address these issues we developed an Automated Tool for Bacterial GEnome Annotation ComparisON (BEACON) that benefits both AM developers and annotation analysers. BEACON provides detailed comparison of gene function annotations of prokaryotic genomes obtained by different AMs and generates extended annotations through combination of individual ones. For the illustration of BEACON’s utility, we provide a comparison analysis of multiple different annotations generated for four genomes and show on these examples that the extended annotation can increase the number of genes annotated by putative functions up to 27 %, while the number of genes without any function assignment is reduced. Conclusions We developed BEACON, a fast tool for an automated and a systematic comparison of different annotations of single genomes. The extended annotation assigns putative functions to many genes with unknown functions. BEACON is available under GNU General Public License version 3.0 and is accessible at: http://www.cbrc.kaust.edu.sa/BEACON/

  13. Smartphone-Based Indoor Localization with Bluetooth Low Energy Beacons.

    Science.gov (United States)

    Zhuang, Yuan; Yang, Jun; Li, You; Qi, Longning; El-Sheimy, Naser

    2016-04-26

    Indoor wireless localization using Bluetooth Low Energy (BLE) beacons has attracted considerable attention after the release of the BLE protocol. In this paper, we propose an algorithm that uses the combination of channel-separate polynomial regression model (PRM), channel-separate fingerprinting (FP), outlier detection and extended Kalman filtering (EKF) for smartphone-based indoor localization with BLE beacons. The proposed algorithm uses FP and PRM to estimate the target's location and the distances between the target and BLE beacons respectively. We compare the performance of distance estimation that uses separate PRM for three advertisement channels (i.e., the separate strategy) with that use an aggregate PRM generated through the combination of information from all channels (i.e., the aggregate strategy). The performance of FP-based location estimation results of the separate strategy and the aggregate strategy are also compared. It was found that the separate strategy can provide higher accuracy; thus, it is preferred to adopt PRM and FP for each BLE advertisement channel separately. Furthermore, to enhance the robustness of the algorithm, a two-level outlier detection mechanism is designed. Distance and location estimates obtained from PRM and FP are passed to the first outlier detection to generate improved distance estimates for the EKF. After the EKF process, the second outlier detection algorithm based on statistical testing is further performed to remove the outliers. The proposed algorithm was evaluated by various field experiments. Results show that the proposed algorithm achieved the accuracy of EKF algorithm and 15.77% more accurate than EKF algorithm. With sparse deployment (1 beacon per 18 m), the proposed algorithm achieves the accuracies of EKF algorithm and 21.41% better than EKF algorithm. Therefore, the proposed algorithm is especially useful to improve the localization accuracy in environments with sparse beacon deployment.

  14. Molecular Mechanisms of Synaptic Specificity: Spotlight on Hippocampal and Cerebellar Synapse Organizers.

    Science.gov (United States)

    Park, Dongseok; Bae, Sungwon; Yoon, Taek Han; Ko, Jaewon

    2018-04-18

    Synapses and neural circuits form with exquisite specificity during brain development to allow the precise and appropriate flow of neural information. Although this property of synapses and neural circuits has been extensively investigated for more than a century, molecular mechanisms underlying this property are only recently being unveiled. Recent studies highlight several classes of cell-surface proteins as organizing hubs in building structural and functional architectures of specific synapses and neural circuits. In the present minireview, we discuss recent findings on various synapse organizers that confer the distinct properties of specific synapse types and neural circuit architectures in mammalian brains, with a particular focus on the hippocampus and cerebellum.

  15. Molecular passportization of clones of karelian birch using PCRwith semi-specific primers

    Directory of Open Access Journals (Sweden)

    Tatyana V Matveeva

    2008-09-01

    Full Text Available Using 4 clones of Karelian birch (Betula pendula Roth var caretica Merckl. from the collection of the karelian birch of the laboratory of genetics of Research Institute of Forest Genetics and Breeding, Voronezh, one normal tree of Betula pendula Roth, and one tree of B. pubescens Ehrh., collected from the nature, we have analyzed the possibility of application of PCR with semi-specific primers for molecular typing. We found primers with high percentage of polymorphic markers. These primers could be recommended for molecular typing of birch.

  16. A Two-Layer Method for Sedentary Behaviors Classification Using Smartphone and Bluetooth Beacons.

    Science.gov (United States)

    Cerón, Jesús D; López, Diego M; Hofmann, Christian

    2017-01-01

    Among the factors that outline the health of populations, person's lifestyle is the more important one. This work focuses on the caracterization and prevention of sedentary lifestyles. A sedentary behavior is defined as "any waking behavior characterized by an energy expenditure of 1.5 METs (Metabolic Equivalent) or less while in a sitting or reclining posture". To propose a method for sedentary behaviors classification using a smartphone and Bluetooth beacons considering different types of classification models: personal, hybrid or impersonal. Following the CRISP-DM methodology, a method based on a two-layer approach for the classification of sedentary behaviors is proposed. Using data collected from a smartphones' accelerometer, gyroscope and barometer; the first layer classifies between performing a sedentary behavior and not. The second layer of the method classifies the specific sedentary activity performed using only the smartphone's accelerometer and barometer data, but adding indoor location data, using Bluetooth Low Energy (BLE) beacons. To improve the precision of the classification, both layers implemented the Random Forest algorithm and the personal model. This study presents the first available method for the automatic classification of specific sedentary behaviors. The layered classification approach has the potential to improve processing, memory and energy consumption of mobile devices and wearables used.

  17. Controlling the signal: Practical privacy protection of genomic data sharing through Beacon services.

    Science.gov (United States)

    Wan, Zhiyu; Vorobeychik, Yevgeniy; Kantarcioglu, Murat; Malin, Bradley

    2017-07-26

    Genomic data is increasingly collected by a wide array of organizations. As such, there is a growing demand to make summary information about such collections available more widely. However, over the past decade, a series of investigations have shown that attacks, rooted in statistical inference methods, can be applied to discern the presence of a known individual's DNA sequence in the pool of subjects. Recently, it was shown that the Beacon Project of the Global Alliance for Genomics and Health, a web service for querying about the presence (or absence) of a specific allele, was vulnerable. The Integrating Data for Analysis, Anonymization, and Sharing (iDASH) Center modeled a track in their third Privacy Protection Challenge on how to mitigate the Beacon vulnerability. We developed the winning solution for this track. This paper describes our computational method to optimize the tradeoff between the utility and the privacy of the Beacon service. We generalize the genomic data sharing problem beyond that which was introduced in the iDASH Challenge to be more representative of real world scenarios to allow for a more comprehensive evaluation. We then conduct a sensitivity analysis of our method with respect to several state-of-the-art methods using a dataset of 400,000 positions in Chromosome 10 for 500 individuals from Phase 3 of the 1000 Genomes Project. All methods are evaluated for utility, privacy and efficiency. Our method achieves better performance than all state-of-the-art methods, irrespective of how key factors (e.g., the allele frequency in the population, the size of the pool and utility weights) change from the original parameters of the problem. We further illustrate that it is possible for our method to exhibit subpar performance under special cases of allele query sequences. However, we show our method can be extended to address this issue when the query sequence is fixed and known a priori to the data custodian, so that they may plan stage their

  18. Quantum state specific reactant preparation in a molecular beam by rapid adiabatic passage

    Science.gov (United States)

    Chadwick, Helen; Hundt, P. Morten; van Reijzen, Maarten E.; Yoder, Bruce L.; Beck, Rainer D.

    2014-01-01

    Highly efficient preparation of molecules in a specific rovibrationally excited state for gas/surface reactivity measurements is achieved in a molecular beam using tunable infrared (IR) radiation from a single mode continuous wave optical parametric oscillator (cw-OPO). We demonstrate that with appropriate focusing of the IR radiation, molecules in the molecular beam crossing the fixed frequency IR field experience a Doppler tuning that can be adjusted to achieve complete population inversion of a two-level system by rapid adiabatic passage (RAP). A room temperature pyroelectric detector is used to monitor the excited fraction in the molecular beam and the population inversion is detected and quantified using IR bleaching by a second IR-OPO. The second OPO is also used for complete population transfer to an overtone or combination vibration via double resonance excitation using two spatially separated RAP processes.

  19. Investigation of arc repressor DNA-binding specificity by comparative molecular dynamics simulations.

    Science.gov (United States)

    Song, Wei; Guo, Jun-Tao

    2015-01-01

    Transcription factors regulate gene expression through binding to specific DNA sequences. How transcription factors achieve high binding specificity is still not well understood. In this paper, we investigated the role of protein flexibility in protein-DNA-binding specificity by comparative molecular dynamics (MD) simulations. Protein flexibility has been considered as a key factor in molecular recognition, which is intrinsically a dynamic process involving fine structural fitting between binding components. In this study, we performed comparative MD simulations on wild-type and F10V mutant P22 Arc repressor in both free and complex conformations. The F10V mutant has lower DNA-binding specificity though both the bound and unbound main-chain structures between the wild-type and F10V mutant Arc are highly similar. We found that the DNA-binding motif of wild-type Arc is structurally more flexible than the F10V mutant in the unbound state, especially for the six DNA base-contacting residues in each dimer. We demonstrated that the flexible side chains of wild-type Arc lead to a higher DNA-binding specificity through forming more hydrogen bonds with DNA bases upon binding. Our simulations also showed a possible conformational selection mechanism for Arc-DNA binding. These results indicate the important roles of protein flexibility and dynamic properties in protein-DNA-binding specificity.

  20. Bio-specific recognition and applications: from molecular to colloidal scales

    International Nuclear Information System (INIS)

    Baudry, Jean; Bertrand, Emanuel; Lequeux, Nicolas; Bibette, Jerome

    2004-01-01

    Biomolecules have the well-known ability to build reversible complexes. Indeed, antigens and antibodies or adhesion molecules are able to recognize one another with a strong affinity and a very high specificity. This paper first reviews the various techniques and related results about binding and unbinding, at the scale of a unique ligand/receptor couple. One important biotechnological application arising from these recognition phenomena concerns immuno-diagnosis, which is essentially based on the formation of these specific complexes. We show how the physics of colloids associated with the growing scientific background concerning molecular recognition helps in rationalizing and inventing new diagnostic strategies. Finally the concept of colloidal self-assembling systems as biosensors is presented as directly impacting the most important questions related to molecular recognition and their biotechnological implications. (topical review)

  1. Communication: High pressure specific heat spectroscopy reveals simple relaxation behavior of glass forming molecular liquid

    DEFF Research Database (Denmark)

    Roed, Lisa Anita; Niss, Kristine; Jakobsen, Bo

    2015-01-01

    The frequency dependent specific heat has been measured under pressure for the molecular glass forming liquid 5-polyphenyl-4-ether in the viscous regime close to the glass transition. The temperature and pressure dependences of the characteristic time scale associated with the specific heat...... is compared to the equivalent time scale from dielectric spectroscopy performed under identical conditions. It is shown that the ratio between the two time scales is independent of both temperature and pressure. This observation is non-trivial and demonstrates the existence of specially simple molecular...... liquids in which different physical relaxation processes are both as function of temperature and pressure/density governed by the same underlying “inner clock.” Furthermore, the results are discussed in terms of the recent conjecture that van der Waals liquids, like the measuredliquid, comply...

  2. Genetic characterization, molecular epidemiology, and phylogenetic relationships of insect-specific viruses in the taxon Negevirus.

    Science.gov (United States)

    Nunes, Marcio R T; Contreras-Gutierrez, María Angélica; Guzman, Hilda; Martins, Livia C; Barbirato, Mayla Feitoza; Savit, Chelsea; Balta, Victoria; Uribe, Sandra; Vivero, Rafael; Suaza, Juan David; Oliveira, Hamilton; Nunes Neto, Joaquin P; Carvalho, Valeria L; da Silva, Sandro Patroca; Cardoso, Jedson F; de Oliveira, Rodrigo Santo; da Silva Lemos, Poliana; Wood, Thomas G; Widen, Steven G; Vasconcelos, Pedro F C; Fish, Durland; Vasilakis, Nikos; Tesh, Robert B

    2017-04-01

    The recently described taxon Negevirus is comprised of a diverse group of insect-specific viruses isolated from mosquitoes and phlebotomine sandflies. In this study, a comprehensive genetic characterization, molecular, epidemiological and evolutionary analyses were conducted on nearly full-length sequences of 91 new negevirus isolates obtained in Brazil, Colombia, Peru, Panama, USA and Nepal. We demonstrated that these arthropod restricted viruses are clustered in two major phylogenetic groups with origins related to three plant virus genera (Cilevirus, Higrevirus and Blunevirus). Molecular analyses demonstrated that specific host correlations are not present with most negeviruses; instead, high genetic variability, wide host-range, and cross-species transmission were noted. The data presented here also revealed the existence of five novel insect-specific viruses falling into two arthropod-restrictive virus taxa, previously proposed as distinct genera, designated Nelorpivirus and Sandewavirus. Our results provide a better understanding of the molecular epidemiology, evolution, taxonomy and stability of this group of insect-restricted viruses. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Molecular Design of Antifouling Polymer Brushes Using Sequence-Specific Peptoids.

    Science.gov (United States)

    Lau, King Hang Aaron; Sileika, Tadas S; Park, Sung Hyun; Sousa, Ana Maria Leal; Burch, Patrick; Szleifer, Igal; Messersmith, Phillip B

    2015-01-07

    Material systems that can be used to flexibly and precisely define the chemical nature and molecular arrangement of a surface would be invaluable for the control of complex biointerfacial interactions. For example, progress in antifouling polymer biointerfaces that prevent non-specific protein adsorption and cell attachment, which can significantly improve the performance of an array of biomedical and industrial applications, is hampered by a lack of chemical models to identify the molecular features conferring their properties. Poly(N-substituted glycine) "peptoids" are peptidomimetic polymers that can be conveniently synthesized with specific monomer sequences and chain lengths, and are presented as a versatile platform for investigating the molecular design of antifouling polymer brushes. Zwitterionic antifouling polymer brushes have captured significant recent attention, and a targeted library of zwitterionic peptoid brushes with a different charge densities, hydration, separations between charged groups, chain lengths, and grafted chain densities, is quantitatively evaluated for their antifouling properties through a range of protein adsorption and cell attachment assays. Specific zwitterionic brush designs were found to give rise to distinct but subtle differences in properties. The results also point to the dominant roles of the grafted chain density and chain length in determining the performance of antifouling polymer brushes.

  4. Fusarium diversity in soil using a specific molecular approach and a cultural approach.

    Science.gov (United States)

    Edel-Hermann, Véronique; Gautheron, Nadine; Mounier, Arnaud; Steinberg, Christian

    2015-04-01

    Fusarium species are ubiquitous in soil. They cause plant and human diseases and can produce mycotoxins. Surveys of Fusarium species diversity in environmental samples usually rely on laborious culture-based methods. In the present study, we have developed a molecular method to analyze Fusarium diversity directly from soil DNA. We designed primers targeting the translation elongation factor 1-alpha (EF-1α) gene and demonstrated their specificity toward Fusarium using a large collection of fungi. We used the specific primers to construct a clone library from three contrasting soils. Sequence analysis confirmed the specificity of the assay, with 750 clones identified as Fusarium and distributed among eight species or species complexes. The Fusarium oxysporum species complex (FOSC) was the most abundant one in the three soils, followed by the Fusarium solani species complex (FSSC). We then compared our molecular approach results with those obtained by isolating Fusarium colonies on two culture media and identifying species by sequencing part of the EF-1α gene. The 750 isolates were distributed into eight species or species complexes, with the same dominant species as with the cloning method. Sequence diversity was much higher in the clone library than in the isolate collection. The molecular approach proved to be a valuable tool to assess Fusarium diversity in environmental samples. Combined with high throughput sequencing, it will allow for in-depth analysis of large numbers of samples. Published by Elsevier B.V.

  5. In Vitro Selection of a Single-Stranded DNA Molecular Recognition Element Specific for Bromacil

    Directory of Open Access Journals (Sweden)

    Ryan M. Williams

    2014-01-01

    Full Text Available Bromacil is a widely used herbicide that is known to contaminate environmental systems. Due to the hazards it presents and inefficient detection methods, it is necessary to create a rapid and efficient sensing device. Towards this end, we have utilized a stringent in vitro selection method to identify single-stranded DNA molecular recognition elements (MRE specific for bromacil. We have identified one MRE with high affinity (Kd=9.6 nM and specificity for bromacil compared to negative targets of selection and other pesticides. The selected ssDNA MRE will be useful as the sensing element in a field-deployable bromacil detection device.

  6. Nanomechanical DNA origami 'single-molecule beacons' directly imaged by atomic force microscopy

    Science.gov (United States)

    Kuzuya, Akinori; Sakai, Yusuke; Yamazaki, Takahiro; Xu, Yan; Komiyama, Makoto

    2011-01-01

    DNA origami involves the folding of long single-stranded DNA into designed structures with the aid of short staple strands; such structures may enable the development of useful nanomechanical DNA devices. Here we develop versatile sensing systems for a variety of chemical and biological targets at molecular resolution. We have designed functional nanomechanical DNA origami devices that can be used as 'single-molecule beacons', and function as pinching devices. Using 'DNA origami pliers' and 'DNA origami forceps', which consist of two levers ~170 nm long connected at a fulcrum, various single-molecule inorganic and organic targets ranging from metal ions to proteins can be visually detected using atomic force microscopy by a shape transition of the origami devices. Any detection mechanism suitable for the target of interest, pinching, zipping or unzipping, can be chosen and used orthogonally with differently shaped origami devices in the same mixture using a single platform. PMID:21863016

  7. Scrambled eggs: A highly sensitive molecular diagnostic workflow for Fasciola species specific detection from faecal samples

    Science.gov (United States)

    Calvani, Nichola Eliza Davies; Windsor, Peter Andrew; Bush, Russell David

    2017-01-01

    Background Fasciolosis, due to Fasciola hepatica and Fasciola gigantica, is a re-emerging zoonotic parasitic disease of worldwide importance. Human and animal infections are commonly diagnosed by the traditional sedimentation and faecal egg-counting technique. However, this technique is time-consuming and prone to sensitivity errors when a large number of samples must be processed or if the operator lacks sufficient experience. Additionally, diagnosis can only be made once the 12-week pre-patent period has passed. Recently, a commercially available coprological antigen ELISA has enabled detection of F. hepatica prior to the completion of the pre-patent period, providing earlier diagnosis and increased throughput, although species differentiation is not possible in areas of parasite sympatry. Real-time PCR offers the combined benefits of highly sensitive species differentiation for medium to large sample sizes. However, no molecular diagnostic workflow currently exists for the identification of Fasciola spp. in faecal samples. Methodology/Principal findings A new molecular diagnostic workflow for the highly-sensitive detection and quantification of Fasciola spp. in faecal samples was developed. The technique involves sedimenting and pelleting the samples prior to DNA isolation in order to concentrate the eggs, followed by disruption by bead-beating in a benchtop homogeniser to ensure access to DNA. Although both the new molecular workflow and the traditional sedimentation technique were sensitive and specific, the new molecular workflow enabled faster sample throughput in medium to large epidemiological studies, and provided the additional benefit of speciation. Further, good correlation (R2 = 0.74–0.76) was observed between the real-time PCR values and the faecal egg count (FEC) using the new molecular workflow for all herds and sampling periods. Finally, no effect of storage in 70% ethanol was detected on sedimentation and DNA isolation outcomes; enabling

  8. Scrambled eggs: A highly sensitive molecular diagnostic workflow for Fasciola species specific detection from faecal samples.

    Directory of Open Access Journals (Sweden)

    Nichola Eliza Davies Calvani

    2017-09-01

    Full Text Available Fasciolosis, due to Fasciola hepatica and Fasciola gigantica, is a re-emerging zoonotic parasitic disease of worldwide importance. Human and animal infections are commonly diagnosed by the traditional sedimentation and faecal egg-counting technique. However, this technique is time-consuming and prone to sensitivity errors when a large number of samples must be processed or if the operator lacks sufficient experience. Additionally, diagnosis can only be made once the 12-week pre-patent period has passed. Recently, a commercially available coprological antigen ELISA has enabled detection of F. hepatica prior to the completion of the pre-patent period, providing earlier diagnosis and increased throughput, although species differentiation is not possible in areas of parasite sympatry. Real-time PCR offers the combined benefits of highly sensitive species differentiation for medium to large sample sizes. However, no molecular diagnostic workflow currently exists for the identification of Fasciola spp. in faecal samples.A new molecular diagnostic workflow for the highly-sensitive detection and quantification of Fasciola spp. in faecal samples was developed. The technique involves sedimenting and pelleting the samples prior to DNA isolation in order to concentrate the eggs, followed by disruption by bead-beating in a benchtop homogeniser to ensure access to DNA. Although both the new molecular workflow and the traditional sedimentation technique were sensitive and specific, the new molecular workflow enabled faster sample throughput in medium to large epidemiological studies, and provided the additional benefit of speciation. Further, good correlation (R2 = 0.74-0.76 was observed between the real-time PCR values and the faecal egg count (FEC using the new molecular workflow for all herds and sampling periods. Finally, no effect of storage in 70% ethanol was detected on sedimentation and DNA isolation outcomes; enabling transport of samples from endemic

  9. Scrambled eggs: A highly sensitive molecular diagnostic workflow for Fasciola species specific detection from faecal samples.

    Science.gov (United States)

    Calvani, Nichola Eliza Davies; Windsor, Peter Andrew; Bush, Russell David; Šlapeta, Jan

    2017-09-01

    Fasciolosis, due to Fasciola hepatica and Fasciola gigantica, is a re-emerging zoonotic parasitic disease of worldwide importance. Human and animal infections are commonly diagnosed by the traditional sedimentation and faecal egg-counting technique. However, this technique is time-consuming and prone to sensitivity errors when a large number of samples must be processed or if the operator lacks sufficient experience. Additionally, diagnosis can only be made once the 12-week pre-patent period has passed. Recently, a commercially available coprological antigen ELISA has enabled detection of F. hepatica prior to the completion of the pre-patent period, providing earlier diagnosis and increased throughput, although species differentiation is not possible in areas of parasite sympatry. Real-time PCR offers the combined benefits of highly sensitive species differentiation for medium to large sample sizes. However, no molecular diagnostic workflow currently exists for the identification of Fasciola spp. in faecal samples. A new molecular diagnostic workflow for the highly-sensitive detection and quantification of Fasciola spp. in faecal samples was developed. The technique involves sedimenting and pelleting the samples prior to DNA isolation in order to concentrate the eggs, followed by disruption by bead-beating in a benchtop homogeniser to ensure access to DNA. Although both the new molecular workflow and the traditional sedimentation technique were sensitive and specific, the new molecular workflow enabled faster sample throughput in medium to large epidemiological studies, and provided the additional benefit of speciation. Further, good correlation (R2 = 0.74-0.76) was observed between the real-time PCR values and the faecal egg count (FEC) using the new molecular workflow for all herds and sampling periods. Finally, no effect of storage in 70% ethanol was detected on sedimentation and DNA isolation outcomes; enabling transport of samples from endemic to non

  10. SU-E-J-257: Image Artifacts Caused by Implanted Calypso Beacons in MRI Studies

    International Nuclear Information System (INIS)

    Amro, H; Chetty, I; Gordon, J; Wen, N

    2014-01-01

    Purpose: The presence of Calypso Beacon-transponders in patients can cause artifacts during MRI imaging studies. This could be a problem for post-treatment follow up of cancer patients using MRI studies to evaluate metastasis and for functional imaging studies.This work assesses (1) the volume immediately surrounding the transponders that will not be visualized by the MRI due to the beacons, and (2) the dependence of the non-visualized volume on beacon orientation, and scanning techniques. Methods: Two phantoms were used in this study (1) water filled box, (2) and a 2300 cc block of pork meat. Calypso beacons were implanted in the phantoms both in parallel and perpendicular orientations with respect to the MR scanner magnetic field. MR image series of the phantom were obtained with on a 1.0T high field open MR-SIM with multiple pulse sequences, for example, T1-weighted fast field echo and T2-weighted turbo spin echo. Results: On average, a no-signal region with 2 cm radius and 3 cm length was measured. Image artifacts are more significant when beacons are placed parallel to scanner magnetic field; the no-signal area around the beacon was about 0.5 cm larger in orthogonal orientation. The no-signal region surrounding the beacons slightly varies in dimension for the different pulse sequences. Conclusion: The use of Calypso beacons can prohibit the use of MRI studies in post-treatment assessments, especially in the immediate region surrounding the implanted beacon. A characterization of the MR scanner by identifying the no-signal regions due to implanted beacons is essential. This may render the use of Calypso beacons useful for some cases and give the treating physician a chance to identify those patients prior to beacon implantation

  11. Q-Band (37-41 GHz) Satellite Beacon Architecture for RF Propagation Experiments

    Science.gov (United States)

    Simmons, Rainee N.; Wintucky, Edwin G.

    2012-01-01

    In this paper, the design of a beacon transmitter that will be flown as a hosted payload on a geostationary satellite to enable propagation experiments at Q-band (37-41 GHz) frequencies is presented. The beacon uses a phased locked loop stabilized dielectric resonator oscillator and a solid-state power amplifier to achieve the desired output power. The satellite beacon antenna is configured as an offset-fed cut-paraboloidal reflector.

  12. Q-Band (37 to 41 GHz) Satellite Beacon Architecture for RF Propagation Experiments

    Science.gov (United States)

    Simons, Rainee N.; Wintucky, Edwin G.

    2014-01-01

    In this paper, the design of a beacon transmitter that will be flown as a hosted payload on a geostationary satellite to enable propagation experiments at Q-band (37 to 41 GHz) frequencies is presented. The beacon uses a phased locked loop stabilized dielectric resonator oscillator and a solid-state power amplifier to achieve the desired output power. The satellite beacon antenna is configured as an offset-fed cutparaboloidal reflector.

  13. An Analysis of the Optimal Placement of Beacon in Bluetooth-INS Indoor Localization

    OpenAIRE

    Zhao, Xinyu; Ruan, Ling; Zhang, Ling; Long, Yi; Cheng, Fei

    2018-01-01

    The placement of Bluetooth beacon has immediate impact on the accuracy and stability of indoor positioning. Affected by the shelter of building and human, Bluetooth shows uncertain spatial transmission characteristics. Therefore, the scientific deployment of the beacon nodes is closely related to the indoor space environment. In the study of positioning technology using Bluetooth, some scholars have discussed the deployment of Bluetooth beacon in different scenarios. In the principle of avoid...

  14. SU-E-J-257: Image Artifacts Caused by Implanted Calypso Beacons in MRI Studies

    Energy Technology Data Exchange (ETDEWEB)

    Amro, H; Chetty, I; Gordon, J; Wen, N [Henry Ford Health System, Detroit, MI (United States)

    2014-06-01

    Purpose: The presence of Calypso Beacon-transponders in patients can cause artifacts during MRI imaging studies. This could be a problem for post-treatment follow up of cancer patients using MRI studies to evaluate metastasis and for functional imaging studies.This work assesses (1) the volume immediately surrounding the transponders that will not be visualized by the MRI due to the beacons, and (2) the dependence of the non-visualized volume on beacon orientation, and scanning techniques. Methods: Two phantoms were used in this study (1) water filled box, (2) and a 2300 cc block of pork meat. Calypso beacons were implanted in the phantoms both in parallel and perpendicular orientations with respect to the MR scanner magnetic field. MR image series of the phantom were obtained with on a 1.0T high field open MR-SIM with multiple pulse sequences, for example, T1-weighted fast field echo and T2-weighted turbo spin echo. Results: On average, a no-signal region with 2 cm radius and 3 cm length was measured. Image artifacts are more significant when beacons are placed parallel to scanner magnetic field; the no-signal area around the beacon was about 0.5 cm larger in orthogonal orientation. The no-signal region surrounding the beacons slightly varies in dimension for the different pulse sequences. Conclusion: The use of Calypso beacons can prohibit the use of MRI studies in post-treatment assessments, especially in the immediate region surrounding the implanted beacon. A characterization of the MR scanner by identifying the no-signal regions due to implanted beacons is essential. This may render the use of Calypso beacons useful for some cases and give the treating physician a chance to identify those patients prior to beacon implantation.

  15. Remote sensing of the ionosphere using satellite radio beacons

    International Nuclear Information System (INIS)

    Davies, Kenneth

    1991-01-01

    Since the launch of Sputnik I in 1957, satellite radio beacons have been used to measure the total electron content of the ionosphere. A review of the role of satellite beacons in studies of the vertical and spatial structure of the total electron content and on the occurrence of plasma irregularities, both of which affect transionospheric radio signals, is presented. Measurements of Faraday rotation and time of flight give information on the topside of the ionosphere and on the protonosphere. Morphological studies show that the slab thickness of the ionosphere depends on the solar index but is approximately independent of geographical location. Scintillation of amplitude, phase, polarization, and angle provide information on plasma irregularity occurrence in space and time. (author). 23 refs., 16 figs ., 4 tabs

  16. Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers.

    Science.gov (United States)

    Lanjakornsiripan, Darin; Pior, Baek-Jun; Kawaguchi, Daichi; Furutachi, Shohei; Tahara, Tomoaki; Katsuyama, Yu; Suzuki, Yutaka; Fukazawa, Yugo; Gotoh, Yukiko

    2018-04-24

    Non-pial neocortical astrocytes have historically been thought to comprise largely a nondiverse population of protoplasmic astrocytes. Here we show that astrocytes of the mouse somatosensory cortex manifest layer-specific morphological and molecular differences. Two- and three-dimensional observations revealed that astrocytes in the different layers possess distinct morphologies as reflected by differences in cell orientation, territorial volume, and arborization. The extent of ensheathment of synaptic clefts by astrocytes in layer II/III was greater than that by those in layer VI. Moreover, differences in gene expression were observed between upper-layer and deep-layer astrocytes. Importantly, layer-specific differences in astrocyte properties were abrogated in reeler and Dab1 conditional knockout mice, in which neuronal layers are disturbed, suggesting that neuronal layers are a prerequisite for the observed morphological and molecular differences of neocortical astrocytes. This study thus demonstrates the existence of layer-specific interactions between neurons and astrocytes, which may underlie their layer-specific functions.

  17. Radio beacon synchronization in coherent receivers for nanosatellite applications

    OpenAIRE

    Camps Llorente, Daniel; Piera González, Joan

    2017-01-01

    This document presents a study about the Radio beacon synchronization in coherent receivers for nanosatellite applications. First of all, it is studied the history of these nanosatellites and their actual role in the Aerospace industry, considering their low cost compared to bigger satellites and also because of their availability for all types of companies and people (as universities). These nanosatellites have a wide range of applications, and lots of them depend on the imagination of the u...

  18. Beta aerosols beacon, a truly portable continuous air monitor

    International Nuclear Information System (INIS)

    Prince, R.P.; Garber, F.W.

    1987-01-01

    The Beta Aerosols Beacon (BAB) is a portable (57 lbs) continuous air monitor designed to detect airborne radiation. Utilizing solid state detectors has eliminated the use of lead shielding usually necessary for achieving accurate readings in high background areas, making the monitor lightweight as well as portable. The size of a small suitcase, it can be carried into confined work areas, eliminating the requirement for workers to wear respirators for many maintenance tasks. This paper describes the operation and applications of the BAB

  19. Performance of MAC protocols in beaconing Mobile Adhoc Multibroadcast Networks

    OpenAIRE

    Rico García, Cristina; Lehner, Andreas; Robertson, Patrick; Strang, Thomas

    2010-01-01

    The investigation of infrastructureless safety applications in dierent transportation systems is a hot research topic. The nodes in thevnetwork are designed to advertise to the rest of the nodes informationabout the current traffic situation by means of short beacon messages containing speed, direction, positions and other relevant safety information. The scheduling should be organized by the MAC layer so that the transmitted messages arrive successfully as soon as possible at the recei...

  20. Temperature specification in atomistic molecular dynamics and its impact on simulation efficacy

    Science.gov (United States)

    Ocaya, R. O.; Terblans, J. J.

    2017-10-01

    Temperature is a vital thermodynamical function for physical systems. Knowledge of system temperature permits assessment of system ergodicity, entropy, system state and stability. Rapid theoretical and computational developments in the fields of condensed matter physics, chemistry, material science, molecular biology, nanotechnology and others necessitate clarity in the temperature specification. Temperature-based materials simulations, both standalone and distributed computing, are projected to grow in prominence over diverse research fields. In this article we discuss the apparent variability of temperature modeling formalisms used currently in atomistic molecular dynamics simulations, with respect to system energetics,dynamics and structural evolution. Commercial simulation programs, which by nature are heuristic, do not openly discuss this fundamental question. We address temperature specification in the context of atomistic molecular dynamics. We define a thermostat at 400K relative to a heat bath at 300K firstly using a modified ab-initio Newtonian method, and secondly using a Monte-Carlo method. The thermostatic vacancy formation and cohesion energies, equilibrium lattice constant for FCC copper is then calculated. Finally we compare and contrast the results.

  1. Distributed Beacon Requirements for Branch Point Tolerant Laser Beam Compensation in Extended Atmospheric Turbulence

    National Research Council Canada - National Science Library

    Zetterlind, Virgil

    2002-01-01

    .... A least squares reconstructor is implemented for comparison. System performance is presented for various scenarios, including correction time-delays, wave-front sensor noise, and extended beacons...

  2. Rayleigh beacon for measuring the surface profile of a radio telescope.

    Science.gov (United States)

    Padin, S

    2014-12-01

    Millimeter-wavelength Rayleigh scattering from water droplets in a cloud is proposed as a means of generating a bright beacon for measuring the surface profile of a radio telescope. A λ=3  mm transmitter, with an output power of a few watts, illuminating a stratiform cloud, can generate a beacon with the same flux as Mars in 10 GHz bandwidth, but the beacon has a narrow line width, so it is extremely bright. The key advantage of the beacon is that it can be used at any time, and positioned anywhere in the sky, as long as there are clouds.

  3. Custom-Designed Molecular Scissors for Site-Specific Manipulation of the Plant and Mammalian Genomes

    Science.gov (United States)

    Kandavelou, Karthikeyan; Chandrasegaran, Srinivasan

    Zinc finger nucleases (ZFNs) are custom-designed molecular scissors, engineered to cut at specific DNA sequences. ZFNs combine the zinc finger proteins (ZFPs) with the nonspecific cleavage domain of the FokI restriction enzyme. The DNA-binding specificity of ZFNs can be easily altered experimentally. This easy manipulation of the ZFN recognition specificity enables one to deliver a targeted double-strand break (DSB) to a genome. The targeted DSB stimulates local gene targeting by several orders of magnitude at that specific cut site via homologous recombination (HR). Thus, ZFNs have become an important experimental tool to make site-specific and permanent alterations to genomes of not only plants and mammals but also of many other organisms. Engineering of custom ZFNs involves many steps. The first step is to identify a ZFN site at or near the chosen chromosomal target within the genome to which ZFNs will bind and cut. The second step is to design and/or select various ZFP combinations that will bind to the chosen target site with high specificity and affinity. The DNA coding sequence for the designed ZFPs are then assembled by polymerase chain reaction (PCR) using oligonucleotides. The third step is to fuse the ZFP constructs to the FokI cleavage domain. The ZFNs are then expressed as proteins by using the rabbit reticulocyte in vitro transcription/translation system and the protein products assayed for their DNA cleavage specificity.

  4. a Search for New Physics with the Beacon Mission

    Science.gov (United States)

    Turyshev, Slava G.; Shao, Michael; Girerd, André; Lane, Benjamin

    The primary objective of the Beyond Einstein Advanced Coherent Optical Network (BEACON) mission is a search for new physics beyond general relativity by measuring the curvature of relativistic space-time around the Earth. This curvature is characterized by the Eddington parameter γ — the most fundamental relativistic gravity parameter and a direct measure for the presence of new physical interactions. BEACON will achieve an accuracy of 1 × 10-9 in measuring the parameter γ, thereby going a factor of 30,000 beyond the present best result involving the Cassini spacecraft. Secondary mission objectives include: (i) a direct measurement of the "frame-dragging" and geodetic precessions in the Earth's rotational gravitomagnetic field, to 0.05% and 0.03% accuracy respectively, (ii) the first measurement of gravity's nonlinear effects on light and the corresponding second order spatial metric's effects to 0.01% accuracy. BEACON will lead to robust advances in tests of fundamental physics — this mission could discover a violation or extension of general relativity and/or reveal the presence of an additional long range interaction in physics. It will provide crucial information to separate modern scalar-tensor theories of gravity from general relativity, probe possible ways for gravity quantization, and test modern theories of cosmological evolution.

  5. Adapting Mobile Beacon-Assisted Localization in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Wei Dong

    2009-04-01

    Full Text Available The ability to automatically locate sensor nodes is essential in many Wireless Sensor Network (WSN applications. To reduce the number of beacons, many mobile-assisted approaches have been proposed. Current mobile-assisted approaches for localization require special hardware or belong to centralized localization algorithms involving some deterministic approaches due to the fact that they explicitly consider the impreciseness of location estimates. In this paper, we first propose a range-free, distributed and probabilistic Mobile Beacon-assisted Localization (MBL approach for static WSNs. Then, we propose another approach based on MBL, called Adapting MBL (A-MBL, to increase the efficiency and accuracy of MBL by adapting the size of sample sets and the parameter of the dynamic model during the estimation process. Evaluation results show that the accuracy of MBL and A-MBL outperform both Mobile and Static sensor network Localization (MSL and Arrival and Departure Overlap (ADO when both of them use only a single mobile beacon for localization in static WSNs.

  6. Adapting mobile beacon-assisted localization in wireless sensor networks.

    Science.gov (United States)

    Teng, Guodong; Zheng, Kougen; Dong, Wei

    2009-01-01

    The ability to automatically locate sensor nodes is essential in many Wireless Sensor Network (WSN) applications. To reduce the number of beacons, many mobile-assisted approaches have been proposed. Current mobile-assisted approaches for localization require special hardware or belong to centralized localization algorithms involving some deterministic approaches due to the fact that they explicitly consider the impreciseness of location estimates. In this paper, we first propose a range-free, distributed and probabilistic Mobile Beacon-assisted Localization (MBL) approach for static WSNs. Then, we propose another approach based on MBL, called Adapting MBL (A-MBL), to increase the efficiency and accuracy of MBL by adapting the size of sample sets and the parameter of the dynamic model during the estimation process. Evaluation results show that the accuracy of MBL and A-MBL outperform both Mobile and Static sensor network Localization (MSL) and Arrival and Departure Overlap (ADO) when both of them use only a single mobile beacon for localization in static WSNs.

  7. Impact of beacon wavelength on phase-compensation performance

    Science.gov (United States)

    Enterline, Allison A.; Spencer, Mark F.; Burrell, Derek J.; Brennan, Terry J.

    2017-09-01

    This study evaluates the effects of beacon-wavelength mismatch on phase-compensation performance. In general, beacon-wavelength mismatch occurs at the system level because the beacon-illuminator laser (BIL) and high-energy laser (HEL) are often at different wavelengths. Such is the case, for example, when using an aperture sharing element to isolate the beam-control sensor suite from the blinding nature of the HEL. With that said, this study uses the WavePlex Toolbox in MATLAB® to model ideal spherical wave propagation through various atmospheric-turbulence conditions. To quantify phase-compensation performance, we also model a nominal adaptive-optics (AO) system. We achieve correction from a Shack-Hartmann wavefront sensor and continuous-face-sheet deformable mirror using a least-squares phase reconstruction algorithm in the Fried geometry and a leaky integrator control law. To this end, we plot the power in the bucket metric as a function of BIL-HEL wavelength difference. Our initial results show that positive BIL-HEL wavelength differences achieve better phase compensation performance compared to negative BIL-HEL wavelength differences (i.e., red BILs outperform blue BILs). This outcome is consistent with past results.

  8. Environmental Molecular Sciences Laboratory Operations System: Version 4.0 - system requirements specification

    Energy Technology Data Exchange (ETDEWEB)

    Kashporenko, D.

    1996-07-01

    This document is intended to provide an operations standard for the Environmental Molecular Sciences Laboratory OPerations System (EMSL OPS). It is directed toward three primary audiences: (1) Environmental Molecular Sciences Laboratory (EMSL) facility and operations personnel; (2) laboratory line managers and staff; and (3) researchers, equipment operators, and laboratory users. It is also a statement of system requirements for software developers of EMSL OPS. The need for a finely tuned, superior research environment as provided by the US Department of Energy`s (DOE) Environmental Molecular Sciences Laboratory has never been greater. The abrupt end of the Cold War and the realignment of national priorities caused major US and competing overseas laboratories to reposition themselves in a highly competitive research marketplace. For a new laboratory such as the EMSL, this means coming into existence in a rapidly changing external environment. For any major laboratory, these changes create funding uncertainties and increasing global competition along with concomitant demands for higher standards of research product quality and innovation. While more laboratories are chasing fewer funding dollars, research ideas and proposals, especially for molecular-level research in the materials and biological sciences, are burgeoning. In such an economically constrained atmosphere, reduced costs, improved productivity, and strategic research project portfolio building become essential to establish and maintain any distinct competitive advantage. For EMSL, this environment and these demands require clear operational objectives, specific goals, and a well-crafted strategy. Specific goals will evolve and change with the evolution of the nature and definition of DOE`s environmental research needs. Hence, EMSL OPS is designed to facilitate migration of these changes with ease into every pertinent job function, creating a facile {open_quotes}learning organization.{close_quotes}

  9. Substrate specificity of low-molecular mass bacterial DD-peptidases.

    Science.gov (United States)

    Nemmara, Venkatesh V; Dzhekieva, Liudmila; Sarkar, Kumar Subarno; Adediran, S A; Duez, Colette; Nicholas, Robert A; Pratt, R F

    2011-11-22

    The bacterial DD-peptidases or penicillin-binding proteins (PBPs) catalyze the formation and regulation of cross-links in peptidoglycan biosynthesis. They are classified into two groups, the high-molecular mass (HMM) and low-molecular mass (LMM) enzymes. The latter group, which is subdivided into classes A-C (LMMA, -B, and -C, respectively), is believed to catalyze DD-carboxypeptidase and endopeptidase reactions in vivo. To date, the specificity of their reactions with particular elements of peptidoglycan structure has not, in general, been defined. This paper describes the steady-state kinetics of hydrolysis of a series of specific peptidoglycan-mimetic peptides, representing various elements of stem peptide structure, catalyzed by a range of LMM PBPs (the LMMA enzymes, Escherichia coli PBP5, Neisseria gonorrhoeae PBP4, and Streptococcus pneumoniae PBP3, and the LMMC enzymes, the Actinomadura R39 dd-peptidase, Bacillus subtilis PBP4a, and N. gonorrhoeae PBP3). The R39 enzyme (LMMC), like the previously studied Streptomyces R61 DD-peptidase (LMMB), specifically and rapidly hydrolyzes stem peptide fragments with a free N-terminus. In accord with this result, the crystal structures of the R61 and R39 enzymes display a binding site specific to the stem peptide N-terminus. These are water-soluble enzymes, however, with no known specific function in vivo. On the other hand, soluble versions of the remaining enzymes of those noted above, all of which are likely to be membrane-bound and/or associated in vivo and have been assigned particular roles in cell wall biosynthesis and maintenance, show little or no specificity for peptides containing elements of peptidoglycan structure. Peptidoglycan-mimetic boronate transition-state analogues do inhibit these enzymes but display notable specificity only for the LMMC enzymes, where, unlike peptide substrates, they may be able to effectively induce a specific active site structure. The manner in which LMMA (and HMM) DD

  10. A primate specific extra domain in the molecular chaperone Hsp90.

    Directory of Open Access Journals (Sweden)

    Vishwadeepak Tripathi

    Full Text Available Hsp90 (heat shock protein 90 is an essential molecular chaperone that mediates folding and quality control of client proteins. Many of them such as protein kinases, steroid receptors and transcription factors are involved in cellular signaling processes. Hsp90 undergoes an ATP hydrolysis dependent conformational cycle to assist folding of the client protein. The canonical Hsp90 shows a typical composition of three distinct domains and interacts with individual cochaperone partners such as Hop, Cdc37 and Aha1 (activator of Hsp90 ATPase that regulate the reaction cycle of the molecular chaperone. A bioinformatic survey identified an additional domain of 122 amino acids in front of the canonical Hsp90 sequence. This extra domain (E domain is specific to the Catarrhini or drooping nose monkeys, a subdivision of the higher primates that includes man, the great apes and the old world monkeys but is absent from all other species. Our biochemical analysis reveals that Hsp103 associates with cochaperone proteins such as Hop, Cdc37 and Aha1 similar to Hsp90. However, the extra domain reduces the ATP hydrolysis rate to about half when compared to Hsp90 thereby acting as a negative regulator of the molecular chaperonés intrinsic ATPase activity.

  11. Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Robert Lesurf

    2016-07-01

    Full Text Available Breast cancer consists of at least five main molecular “intrinsic” subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

  12. Surface functionalization of SPR chip for specific molecular interaction analysis under flow condition

    Directory of Open Access Journals (Sweden)

    Tao Ma

    2017-03-01

    Full Text Available Surface functionalization of sensor chip for probe immobilization is crucial for the biosensing applications of surface plasmon resonance (SPR sensors. In this paper, we report a method circulating the dopamine aqueous solution to coat polydopamine film on sensing surface for surface functionalization of SPR chip. The polydopamine film with available thickness can be easily prepared by controlling the circulation time and the biorecognition elements can be immobilized on the polydopamine film for specific molecular interaction analysis. These operations are all performed under flow condition in the fluidic system, and have the advantages of easy implementation, less time consuming, and low cost, because the reagents and devices used in the operations are routinely applied in most laboratories. In this study, the specific absorption between the protein A probe immobilized on the sensing surface and human immunoglobulin G in the buffer is monitored based on this surface functionalization strategy to demonstrated its feasibility for SPR biosensing applications.

  13. Identification of differentiation-stage specific molecular markers for the osteoblastic phenotype

    DEFF Research Database (Denmark)

    Twine, Natalie; Chen, Li; Wilkins, Marc

    to age-matched control (n=4). Using RNA-seq and cluster analysis, we identified a set of stage-specific molecular markers that define the progression of OB phenotype during ex vivo culture of hMSC, predict in vivo bone formation capacity of hMSC and can be employed to study the mechanisms of impaired......The phenotype of osteoblastic (OB) cells in culture is currently defined using a limited number of markers of low sensitivity and specificity which belong mostly to extracellular matrix proteins. Also, for clinical use of human skeletal (mesenchymal) stem cells (hMSC) in bone regeneration......, there is a need to identify predictive markers for in vivo bone forming capacity. Thus, we employed Illumina RNA sequencing (RNASeq) to examine changes in gene expression across 8 time points between 0-12 days of ex vivo OB differentiation of hMSC. We identified a subset of expressed genes as potentially...

  14. Genetic and Molecular Mechanisms Underlying Symbiotic Specificity in Legume-Rhizobium Interactions.

    Science.gov (United States)

    Wang, Qi; Liu, Jinge; Zhu, Hongyan

    2018-01-01

    Legumes are able to form a symbiotic relationship with nitrogen-fixing soil bacteria called rhizobia. The result of this symbiosis is to form nodules on the plant root, within which the bacteria can convert atmospheric nitrogen into ammonia that can be used by the plant. Establishment of a successful symbiosis requires the two symbiotic partners to be compatible with each other throughout the process of symbiotic development. However, incompatibility frequently occurs, such that a bacterial strain is unable to nodulate a particular host plant or forms nodules that are incapable of fixing nitrogen. Genetic and molecular mechanisms that regulate symbiotic specificity are diverse, involving a wide range of host and bacterial genes/signals with various modes of action. In this review, we will provide an update on our current knowledge of how the recognition specificity has evolved in the context of symbiosis signaling and plant immunity.

  15. Mycobacterium tuberculosis strains exhibit differential and strain-specific molecular signatures in pulmonary epithelial cells.

    Science.gov (United States)

    Mvubu, Nontobeko Eunice; Pillay, Balakrishna; Gamieldien, Junaid; Bishai, William; Pillay, Manormoney

    2016-12-01

    Although pulmonary epithelial cells are integral to innate and adaptive immune responses during Mycobacterium tuberculosis infection, global transcriptomic changes in these cells remain largely unknown. Changes in gene expression induced in pulmonary epithelial cells infected with M. tuberculosis F15/LAM4/KZN, F11, F28, Beijing and Unique genotypes were investigated by RNA sequencing (RNA-Seq). The Illumina HiSeq 2000 platform generated 50 bp reads that were mapped to the human genome (Hg19) using Tophat (2.0.10). Differential gene expression induced by the different strains in infected relative to the uninfected cells was quantified and compared using Cufflinks (2.1.0) and MeV (4.0.9), respectively. Gene expression varied among the strains with the total number of genes as follows: F15/LAM4/KZN (1187), Beijing (1252), F11 (1639), F28 (870), Unique (886) and H37Rv (1179). A subset of 292 genes was commonly induced by all strains, where 52 genes were down-regulated while 240 genes were up-regulated. Differentially expressed genes were compared among the strains and the number of induced strain-specific gene signatures were as follows: F15/LAM4/KZN (138), Beijing (52), F11 (255), F28 (55), Unique (186) and H37Rv (125). Strain-specific molecular gene signatures associated with functional pathways were observed only for the Unique and H37Rv strains while certain biological functions may be associated with other strain signatures. This study demonstrated that strains of M. tuberculosis induce differential gene expression and strain-specific molecular signatures in pulmonary epithelial cells. Specific signatures induced by clinical strains of M. tuberculosis can be further explored for novel host-associated biomarkers and adjunctive immunotherapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Trypanosoma equiperdum Low Molecular Weight Proteins As Candidates for Specific Serological Diagnosis of Dourine

    Directory of Open Access Journals (Sweden)

    Mirella Luciani

    2018-03-01

    Full Text Available The diagnosis of dourine can be difficult because the clinical signs of this disease in horses are similar to those of surra, caused by Trypanosoma evansi. Moreover, T. equiperdum and T. evansi are closely related and, so far, they cannot be distinguished using serological tests. In a previous work, the T. equiperdum protein pattern recognized by antibodies from dourine-infected horses and the humoral immune response kinetics were investigated by immunoblotting assay; a total of 20 sera from naturally and experimentally infected horses and from healthy animals were tested. Immunoblotting analysis showed that antibodies from infected horses specifically bind T. equiperdum low molecular weight proteins (from 16 to 35 kDa, which are not recognized by antibodies from uninfected horses. In this work, we tested other 615 sera (7 from naturally infected horses and 608 sera from healthy horses and donkeys: results confirmed the data obtained previously. In addition, six SDS-PAGE bands with molecular weight ranging from 10 to 37 kDa were analyzed by mass spectrometry, in order to identify immunogenic proteins that could be used as biomarkers for the diagnosis of dourine. A total of 167 proteins were identified. Among them, 37 were found unique for T. equiperdum. Twenty-four of them could represent possible candidate diagnostic antigens for the development of serological tests specific for T. equiperdum.

  17. Weak beacon detection for air-to-ground optical wireless link establishment.

    Science.gov (United States)

    Han, Yaoqiang; Dang, Anhong; Tang, Junxiong; Guo, Hong

    2010-02-01

    In an air-to-ground free-space optical communication system, strong background interference seriously affects the beacon detection, which makes it difficult to establish the optical link. In this paper, we propose a correlation beacon detection scheme under strong background interference conditions. As opposed to traditional beacon detection schemes, the beacon is modulated by an m-sequence at the transmitting terminal with a digital differential matched filter (DDMF) array introduced at the receiving end to detect the modulated beacon. This scheme is capable of suppressing both strong interference and noise by correlation reception of the received image sequence. In addition, the DDMF array enables each pixel of the image sensor to have its own DDMF of the same structure to process its received image sequence in parallel, thus it makes fast beacon detection possible. Theoretical analysis and an outdoor experiment have been demonstrated and show that the proposed scheme can realize fast and effective beacon detection under strong background interference conditions. Consequently, the required beacon transmission power can also be reduced dramatically.

  18. Beacon Editor: Capturing Signal Transduction Pathways Using the Systems Biology Graphical Notation Activity Flow Language.

    Science.gov (United States)

    Elmarakeby, Haitham; Arefiyan, Mostafa; Myers, Elijah; Li, Song; Grene, Ruth; Heath, Lenwood S

    2017-12-01

    The Beacon Editor is a cross-platform desktop application for the creation and modification of signal transduction pathways using the Systems Biology Graphical Notation Activity Flow (SBGN-AF) language. Prompted by biologists' requests for enhancements, the Beacon Editor includes numerous powerful features for the benefit of creation and presentation.

  19. 46 CFR 169.555 - Emergency position indicating radio beacon (EPIRB).

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Emergency position indicating radio beacon (EPIRB). 169.555 Section 169.555 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS... Emergency position indicating radio beacon (EPIRB). (a) Each vessel certificated for exposed waters must...

  20. 46 CFR 169.831 - Emergency position indicating radio beacon (EPIRB).

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Emergency position indicating radio beacon (EPIRB). 169.831 Section 169.831 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS... radio beacon (EPIRB). The master shall ensure that— (a) The EPIRB required in § 169.555 of this...

  1. What Happened to the Beacon Schools? Policy Reform and Educational Equity

    Science.gov (United States)

    Smith, Emma

    2015-01-01

    This paper considers the impact of the Beacon schools initiative on the social and academic characteristics of secondary schools in England. The Beacon schools programme ran from 1998 to 2004 and epitomised the (then) Labour government's focus on school improvement through diversity, collaboration and partnership. This paper looks at variation in…

  2. 46 CFR 169.744 - Emergency position indicating radio beacon (EPIRB).

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Emergency position indicating radio beacon (EPIRB). 169.744 Section 169.744 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS... position indicating radio beacon (EPIRB). Each EPIRB must be marked with the vessel's name. ...

  3. Detecting and Preventing Beacon Replay Attacks in Receiver-Initiated MAC Protocols for Energy Efficient WSNs

    DEFF Research Database (Denmark)

    Di Mauro, Alessio; Fafoutis, Xenofon; Mödersheim, Sebastian Alexander

    2013-01-01

    In receiver-initiated MAC protocols for Wireless Sensor Networks (WSNs), communication is initiated by the receiver of the data through beacons containing the receiver's identity. In this paper, we consider the case of a network intruder that captures and replays such beacons towards legitimate...

  4. Beacon- and Schema-Based Method for Recognizing Algorithms from Students' Source Code

    Science.gov (United States)

    Taherkhani, Ahmad; Malmi, Lauri

    2013-01-01

    In this paper, we present a method for recognizing algorithms from students programming submissions coded in Java. The method is based on the concept of "programming schemas" and "beacons". Schemas are high-level programming knowledge with detailed knowledge abstracted out, and beacons are statements that imply specific…

  5. Het effect van beacons in de ByAmfi Store gemeten, geanalyseerd en ontmaskerd

    NARCIS (Netherlands)

    Moes, Anne; van Vliet, Harry

    2015-01-01

    Volgens meerdere marketeers zijn beacons ‘the next big thing’; en grote retailers als de Bijenkorf zetten beacons al in. Klanten kopen namelijk steeds meer via internet, en winkels zoeken daarom naar manieren om een beleving te bieden, zodat klanten naar de winkel blijven komen.

  6. Probing the molecular determinants of aniline dioxygenase substrate specificity by saturation mutagenesis.

    Science.gov (United States)

    Ang, Ee L; Obbard, Jeffrey P; Zhao, Huimin

    2007-02-01

    Aniline dioxygenase is a multicomponent Rieske nonheme-iron dioxygenase enzyme isolated from Acinetobacter sp. strain YAA. Saturation mutagenesis of the substrate-binding pocket residues, which were identified using a homology model of the alpha subunit of the terminal dioxygenase (AtdA3), was used to probe the molecular determinants of AtdA substrate specificity. The V205A mutation widened the substrate specificity of aniline dioxygenase to include 2-isopropylaniline, for which the wild-type enzyme has no activity. The V205A mutation also made 2-isopropylaniline a better substrate for the enzyme than 2,4-dimethylaniline, a native substrate of the wild-type enzyme. The I248L mutation improved the activity of aniline dioxygenase against aniline and 2,4-dimethylaniline approximately 1.7-fold and 2.1-fold, respectively. Thus, it is shown that the alpha subunit of the terminal dioxygenase indeed plays a part in the substrate specificity as well as the activity of aniline dioxygenase. Interestingly, the equivalent residues of V205 and I248 have not been previously reported to influence the substrate specificity of other Rieske dioxygenases. These results should facilitate future engineering of the enzyme for bioremediation and industrial applications.

  7. Formation of target-specific binding sites in enzymes: solid-phase molecular imprinting of HRP

    Science.gov (United States)

    Czulak, J.; Guerreiro, A.; Metran, K.; Canfarotta, F.; Goddard, A.; Cowan, R. H.; Trochimczuk, A. W.; Piletsky, S.

    2016-05-01

    Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike complex protein engineering approaches commonly employed to generate affinity proteins, the method proposed can be used to produce protein-based ligands in a short time period using native protein molecules. These affinity materials are potentially useful tools especially for assays since they combine the catalytic properties of enzymes (for signaling) and molecular recognition properties of antibodies. We demonstrate this concept in an ELISA-format assay where HRP imprinted with vancomycin and ampicillin replaced traditional enzyme-antibody conjugates for selective detection of templates at micromolar concentrations. This approach can potentially provide a fast alternative to raising antibodies for targets that do not require high assay sensitivities; it can also find uses as a biochemical research tool, as a possible replacement for immunoperoxidase-conjugates.Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike

  8. ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations.

    Directory of Open Access Journals (Sweden)

    Benfeard Williams

    2015-10-01

    Full Text Available The increased risk of developing Alzheimer's disease (AD is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD.

  9. Molecular Subtyping of Primary Prostate Cancer Reveals Specific and Shared Target Genes of Different ETS Rearrangements

    Directory of Open Access Journals (Sweden)

    Paula Paulo

    2012-07-01

    Full Text Available This work aimed to evaluate whether ETS transcription factors frequently involved in rearrangements in prostate carcinomas (PCa, namely ERG and ETV1, regulate specific or shared target genes. We performed differential expression analysis on nine normal prostate tissues and 50 PCa enriched for different ETS rearrangements using exon-level expression microarrays, followed by in vitro validation using cell line models. We found specific deregulation of 57 genes in ERG-positive PCa and 15 genes in ETV1-positive PCa, whereas deregulation of 27 genes was shared in both tumor subtypes. We further showed that the expression of seven tumor-associated ERG target genes (PLA1A, CACNA1D, ATP8A2, HLA-DMB, PDE3B, TDRD1, and TMBIM1 and two tumor-associated ETV1 target genes (FKBP10 and GLYATL2 was significantly affected by specific ETS silencing in VCaP and LNCaP cell line models, respectively, whereas the expression of three candidate ERG and ETV1 shared targets (GRPR, KCNH8, and TMEM45B was significantly affected by silencing of either ETS. Interestingly, we demonstrate that the expression of TDRD1, the topmost overexpressed gene of our list of ERG-specific candidate targets, is inversely correlated with the methylation levels of a CpG island found at -66 bp of the transcription start site in PCa and that TDRD1 expression is regulated by direct binding of ERG to the CpG island in VCaP cells. We conclude that ETS transcription factors regulate specific and shared target genes and that TDRD1, FKBP10, and GRPR are promising therapeutic targets and can serve as diagnostic markers for molecular subtypes of PCa harboring specific fusion gene rearrangements.

  10. Uncertainty analysis for the BEACON-COLSS core monitoring system application

    International Nuclear Information System (INIS)

    Morita, T.; Boyd, W.A.; Seong, K.B.

    2005-01-01

    This paper will cover the measurement uncertainty analysis of BEACON-COLSS core monitoring system. The uncertainty evaluation is made by using a BEACON-COLSS simulation program. By simulating the BEACON on-line operation for analytically generated reactor conditions, accuracy of the 'Measured' results can be evaluated by comparing to analytically generated 'Truth'. The DNB power margin is evaluated based on the Combustion Engineering's Modified Statistical Combination of Uncertainties (MSCU) using the CETOPD code for the DNBR calculation. A BEACON-COLSS simulation program for the uncertainty evaluation function has been established for plant applications. Qualification work has been completed for two Combustion Engineering plants. Results of the BEACON-COLSS measured peaking factors and DNBR power margin are plant type dependent and are applicable to reload cores as long as the core geometry and detector layout are unchanged. (authors)

  11. Potential effects of the introduction of the discrete address beacon system data link on air/ground information transfer problems

    Science.gov (United States)

    Grayson, R. L.

    1981-01-01

    This study of Aviation Safety Reporting System reports suggests that benefits should accure from implementation of discrete address beacon system data link. The phase enhanced terminal information system service is expected to provide better terminal information than present systems by improving currency and accuracy. In the exchange of air traffic control messages, discrete address insures that only the intended recipient receives and acts on a specific message. Visual displays and printer copy of messages should mitigate many of the reported problems associated with voice communications. The problems that remain unaffected include error in addressing the intended recipient and messages whose content is wrong but are otherwise correct as to format and reasonableness.

  12. Oral keratinocyte stem/progenitor cells: specific markers, molecular signaling pathways and potential uses.

    Science.gov (United States)

    Calenic, Bogdan; Greabu, Maria; Caruntu, Constantin; Tanase, Cristiana; Battino, Maurizio

    2015-10-01

    Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self-renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor-cell subpopulations have been categorized based on combinations of positive and/or negative membrane-surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self-renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem-cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem-cell-derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Determination of BEACON Coupling Coefficients using data from Xenon transient

    International Nuclear Information System (INIS)

    Bozic, M.; Kurincic, B.

    2007-01-01

    NEK uses BEACO TM code (BEACO TM - Westinghouse Best Estimate Analyzer for Core Operating Nuclear) for core monitoring, analysis and core behaviour prediction. Coupling Coefficients determine relationship between core response and excore instrumentation. Measured power distribution using incore moveable detectors during Xenon transient with sufficient power axial offset change is the most important data for further analysis. Classic methodology and BEACO TM Conservative methodology using established Coupling Coefficients are compared on NPP Krsko case. BEACON TM Conservative methodology with predefined Coupling Coefficients is used as a surveillance tool for verification of relationship between core and excore instrumentation during power operation. (author)

  14. Beacon-teknologi - fremtidens kundebehandling eller en trussel for personvernet?

    OpenAIRE

    Jyrkinen, Anna; Kamås, Kamilla

    2016-01-01

    Smarttelefoner har blitt en naturlig del av våre liv. Alt man gjør på smarttelefonen, blir lagret som såkalte “big data”. Dette er verdifull informasjon for bedrifter, da de får mer detaljert bilde av hva forbrukere ser, eller holder på med i det virkelige liv. Det kan oppstå et dilemma ved hvor langt selskapene er villige til å strekke seg, for å samle inn informasjon om sine kunder. Beacons er en ny teknologiform og fungerer via små apparater som kommuniserer med kunder gjenn...

  15. Deep sea AUV navigation using multiple acoustic beacons

    Science.gov (United States)

    Ji, Da-xiong; Song, Wei; Zhao, Hong-yu; Liu, Jian

    2016-04-01

    Navigation is a critical requirement for the operation of Autonomous Underwater Vehicles (AUVs). To estimate the vehicle position, we present an algorithm using an extended Kalman filter (EKF) to integrate dead-reckoning position with acoustic ranges from multiple beacons pre-deployed in the operating environment. Owing to high latency, variable sound speed multipath transmissions and unreliability in acoustic measurements, outlier recognition techniques are proposed as well. The navigation algorithm has been tested by the recorded data of deep sea AUV during field operations in a variety of environments. Our results show the improved performance over prior techniques based on position computation.

  16. Facile Fabrication of Animal-Specific Positioning Molds For Multi-modality Molecular Imaging

    International Nuclear Information System (INIS)

    Park, Jeong Chan; Oh, Ji Eun; Woo, Seung Tae

    2008-01-01

    Recently multi-modal imaging system has become widely adopted in molecular imaging. We tried to fabricate animal-specific positioning molds for PET/MR fusion imaging using easily available molding clay and rapid foam. The animal-specific positioning molds provide immobilization and reproducible positioning of small animal. Herein, we have compared fiber-based molding clay with rapid foam in fabricating the molds of experimental animal. The round bottomed-acrylic frame, which fitted into microPET gantry, was prepared at first. The experimental mice was anesthetized and placed on the mold for positioning. Rapid foam and fiber-based clay were used to fabricate the mold. In case of both rapid foam and the clay, the experimental animal needs to be pushed down smoothly into the mold for positioning. However, after the mouse was removed, the fabricated clay needed to be dried completely at 60 .deg. C in oven overnight for hardening. Four sealed pipe tips containing [ 18 F]FDG solution were used as fiduciary markers. After injection of [ 18 F]FDG via tail vein, microPET scanning was performed. Successively, MRI scanning was followed in the same animal. Animal-specific positioning molds were fabricated using rapid foam and fiber-based molding clay for multimodality imaging. Functional and anatomical images were obtained with microPET and MRI, respectively. The fused PET/MR images were obtained using freely available AMIDE program. Animal-specific molds were successfully prepared using easily available rapid foam, molding clay and disposable pipet tips. Thanks to animal-specific molds, fusion images of PET and MR were co-registered with negligible misalignment

  17. Molecular characterization of host-specific biofilm formation in a vertebrate gut symbiont.

    Directory of Open Access Journals (Sweden)

    Steven A Frese

    Full Text Available Although vertebrates harbor bacterial communities in their gastrointestinal tract whose composition is host-specific, little is known about the mechanisms by which bacterial lineages become selected. The goal of this study was to characterize the ecological processes that mediate host-specificity of the vertebrate gut symbiont Lactobacillus reuteri, and to systematically identify the bacterial factors that are involved. Experiments with monoassociated mice revealed that the ability of L. reuteri to form epithelial biofilms in the mouse forestomach is strictly dependent on the strain's host origin. To unravel the molecular basis for this host-specific biofilm formation, we applied a combination of transcriptome analysis and comparative genomics and identified eleven genes of L. reuteri 100-23 that were predicted to play a role. We then determined expression and importance of these genes during in vivo biofilm formation in monoassociated mice. This analysis revealed that six of the genes were upregulated in vivo, and that genes encoding for proteins involved in epithelial adherence, specialized protein transport, cell aggregation, environmental sensing, and cell lysis contributed to biofilm formation. Inactivation of a serine-rich surface adhesin with a devoted transport system (the SecA2-SecY2 pathway completely abrogated biofilm formation, indicating that initial adhesion represented the most significant step in biofilm formation, likely conferring host specificity. In summary, this study established that the epithelial selection of bacterial symbionts in the vertebrate gut can be both specific and highly efficient, resulting in biofilms that are exclusively formed by the coevolved strains, and it allowed insight into the bacterial effectors of this process.

  18. Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity

    DEFF Research Database (Denmark)

    Miller, Yury I; Choi, Soo-Ho; Wiesner, Philipp

    2011-01-01

    are a major target of innate immunity, recognized by a variety of "pattern recognition receptors" (PRRs). By analogy with microbial "pathogen-associated molecular patterns" (PAMPs), we postulate that host-derived, oxidation-specific epitopes can be considered to represent "danger (or damage......)-associated molecular patterns" (DAMPs). We also argue that oxidation-specific epitopes present on apoptotic cells and their cellular debris provided the primary evolutionary pressure for the selection of such PRRs. Furthermore, because many PAMPs on microbes share molecular identity and/or mimicry with oxidation...

  19. Thermodynamic Molecular Switch in Sequence-Specific Hydrophobic Interaction: Two Computational Models Compared

    Directory of Open Access Journals (Sweden)

    Paul Chun

    2003-01-01

    Full Text Available We have shown in our published work the existence of a thermodynamic switch in biological systems wherein a change of sign in ΔCp°(Treaction leads to a true negative minimum in the Gibbs free energy change of reaction, and hence, a maximum in the related Keq. We have examined 35 pair-wise, sequence-specific hydrophobic interactions over the temperature range of 273–333 K, based on data reported by Nemethy and Scheraga in 1962. A closer look at a single example, the pair-wise hydrophobic interaction of leucine-isoleucine, will demonstrate the significant differences when the data are analyzed using the Nemethy-Scheraga model or treated by the Planck-Benzinger methodology which we have developed. The change in inherent chemical bond energy at 0 K, ΔH°(T0 is 7.53 kcal mol-1 compared with 2.4 kcal mol-1, while ‹ts› is 365 K as compared with 355 K, for the Nemethy-Scheraga and Planck-Benzinger model, respectively. At ‹tm›, the thermal agitation energy is about five times greater than ΔH°(T0 in the Planck-Benzinger model, that is 465 K compared to 497 K in the Nemethy-Scheraga model. The results imply that the negative Gibbs free energy minimum at a well-defined ‹ts›, where TΔS° = 0 at about 355 K, has its origin in the sequence-specific hydrophobic interactions, which are highly dependent on details of molecular structure. The Nemethy-Scheraga model shows no evidence of the thermodynamic molecular switch that we have found to be a universal feature of biological interactions. The Planck-Benzinger method is the best known for evaluating the innate temperature-invariant enthalpy, ΔH°(T0, and provides for better understanding of the heat of reaction for biological molecules.

  20. Molecular dynamics investigations of BioH protein substrate specificity for biotin synthesis.

    Science.gov (United States)

    Xue, Qiao; Cui, Ying-Lu; Zheng, Qing-Chuan; Zhang, Hong-Xing

    2016-05-01

    BioH, an enzyme of biotin synthesis, plays an important role in fatty acid synthesis which assembles the pimelate moiety. Pimeloyl-acyl carrier protein (ACP) methyl ester, which is long known to be a biotin precursor, is the physiological substrate of BioH. Azelayl methyl ester, which has a longer chain than pimeloyl methyl ester, conjugated to ACP is also indeed accepted by BioH with very low rate of hydrolysis. To date, the substrate specificity for BioH and the molecular origin for the experimentally observed rate changes of hydrolysis by the chain elongation have remained elusive. To this end, we have investigated chain elongation effects on the structures by using the fully atomistic molecular dynamics simulations combined with binding free energy calculations. The results indicate that the substrate specificity is determined by BioH together with ACP. The added two methylenes would increase the structural flexibility by protein motions at the interface of ACP and BioH, instead of making steric clashes with the side chains of the BioH hydrophobic cavity. On the other hand, the slower hydrolysis of azelayl substrate is suggested to be associated with the loose of contacts between BioH and ACP, and with the lost electrostatic interactions of two ionic/hydrogen bonding networks at the interface of the two proteins. The present study provides important insights into the structure-function relationships of the complex of BioH with pimeloyl-ACP methyl ester, which could contribute to further understanding about the mechanism of the biotin synthetic pathway, including the catalytic role of BioH.

  1. Molecular Evolution of the Substrate Specificity of Chloroplastic Aldolases/Rubisco Lysine Methyltransferases in Plants.

    Science.gov (United States)

    Ma, Sheng; Martin-Laffon, Jacqueline; Mininno, Morgane; Gigarel, Océane; Brugière, Sabine; Bastien, Olivier; Tardif, Marianne; Ravanel, Stéphane; Alban, Claude

    2016-04-04

    Rubisco and fructose-1,6-bisphosphate aldolases (FBAs) are involved in CO2 fixation in chloroplasts. Both enzymes are trimethylated at a specific lysine residue by the chloroplastic protein methyltransferase LSMT. Genes coding LSMT are present in all plant genomes but the methylation status of the substrates varies in a species-specific manner. For example, chloroplastic FBAs are naturally trimethylated in both Pisum sativum and Arabidopsis thaliana, whereas the Rubisco large subunit is trimethylated only in the former species. The in vivo methylation status of aldolases and Rubisco matches the catalytic properties of AtLSMT and PsLSMT, which are able to trimethylate FBAs or FBAs and Rubisco, respectively. Here, we created chimera and site-directed mutants of monofunctional AtLSMT and bifunctional PsLSMT to identify the molecular determinants responsible for substrate specificity. Our results indicate that the His-Ala/Pro-Trp triad located in the central part of LSMT enzymes is the key motif to confer the capacity to trimethylate Rubisco. Two of the critical residues are located on a surface loop outside the methyltransferase catalytic site. We observed a strict correlation between the presence of the triad motif and the in vivo methylation status of Rubisco. The distribution of the motif into a phylogenetic tree further suggests that the ancestral function of LSMT was FBA trimethylation. In a recent event during higher plant evolution, this function evolved in ancestors of Fabaceae, Cucurbitaceae, and Rosaceae to include Rubisco as an additional substrate to the archetypal enzyme. Our study provides insight into mechanisms by which SET-domain protein methyltransferases evolve new substrate specificity. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  2. Microscopic Analysis of Corn Fiber Using Corn Starch- and Cellulose-Specific Molecular Probes

    Energy Technology Data Exchange (ETDEWEB)

    Porter, S. E.; Donohoe, B. S.; Beery, K. E.; Xu, Q.; Ding, S.-Y.; Vinzant, T. B.; Abbas, C. A.; Himmel, M. E.

    2007-09-01

    Ethanol is the primary liquid transportation fuel produced from renewable feedstocks in the United States today. The majority of corn grain, the primary feedstock for ethanol production, has been historically processed in wet mills yielding products such as gluten feed, gluten meal, starch, and germ. Starch extracted from the grain is used to produce ethanol in saccharification and fermentation steps; however the extraction of starch is not 100% efficient. To better understand starch extraction during the wet milling process, we have developed fluorescent probes that can be used to visually localize starch and cellulose in samples using confocal microscopy. These probes are based on the binding specificities of two types of carbohydrate binding modules (CBMs), which are small substrate-specific protein domains derived from carbohydrate degrading enzymes. CBMs were fused, using molecular cloning techniques, to a green fluorescent protein (GFP) or to the red fluorescent protein DsRed (RFP). Using these engineered probes, we found that the binding of the starch-specific probe correlates with starch content in corn fiber samples. We also demonstrate that there is starch internally localized in the endosperm that may contribute to the high starch content in corn fiber. We also surprisingly found that the cellulose-specific probe did not bind to most corn fiber samples, but only to corn fiber that had been hydrolyzed using a thermochemical process that removes the residual starch and much of the hemicellulose. Our findings should be of interest to those working to increase the efficiency of the corn grain to ethanol process.

  3. Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone.

    Science.gov (United States)

    Pickett, Julie E; Thompson, John M; Sadowska, Agnieszka; Tkaczyk, Christine; Sellman, Bret R; Minola, Andrea; Corti, Davide; Lanzavecchia, Antonio; Miller, Lloyd S; Thorek, Daniel Lj

    2018-01-01

    Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA). Specificity and affinity were assessed in vitro. We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging tool for detecting infection via immunoPET imaging in an in vivo mouse model of prosthetic joint infection (PJI). In vitro and ex vivo binding of the anti-LTA mAb to pathogenic bacteria was measured with Octet, ELISA, and flow cytometry. The in vivo PJI mouse model was assessed using traditional imaging modalities, including positron emission tomography (PET) with [ 18 F]FDG and [ 18 F]NaF as well as X-ray computed tomography (CT), before being evaluated with the zirconium-89-labeled antibody specific for LTA ([ 89 Zr]SAC55). The anti-LTA mAb exhibited specific binding in vitro to LTA-expressing bacteria. Results from imaging showed that our model could reliably simulate infection at the surgical site by bioluminescent imaging, conventional PET tracer imaging, and bone morphological changes by CT. One day following injection of both the radiolabeled anti-LTA and isotype control antibodies, the anti-LTA antibody demonstrated significantly greater ( P  infected prosthesis sites over either the same antibody at sterile prosthesis sites or of control non-specific antibody at infected prosthesis sites. Taken together, the radiolabeled anti-LTA mAb, [ 89 Zr]SAC55, may serve as a valuable diagnostic molecular imaging probe to help distinguish between sterile inflammation and infection in the setting of PJI. Future studies are needed to determine whether these findings will translate to human PJI.

  4. Overview of on-line core monitoring system BEACON

    International Nuclear Information System (INIS)

    Dai Qing; Chen Xiaosong

    2013-01-01

    After more than 20 years of development, key technologies embedded with such system have reached a certain degree of maturity among some foreign countries. However, domestically, there is no comparable system yet. Through in-depth research and analysis on the most widely used core monitoring system in the world, BEACON, it's hope that this will provide guidance on our independent development of the first core monitoring system in China. Excore detectors, core outlet thermocouples and incore movable detectors are used to provide measure data on the status of the core for BEACON. Under the assumption of nodal homogeneity, an effective fast group model is used to solve the diffusion equation, followed by core-wise interpolation by Green's function. Finally, reconstruction of a calculated core is fitted with measured data using the surface spline function. The most significant technological advances are core monitoring during unstable core conditions, the use of nodal expansion method to improve accuracy and the adoption of single point calibration to increase the period of recalibration for the whole core. (authors)

  5. Water absorption length measurement with the ANTARES optical beacon system

    International Nuclear Information System (INIS)

    Yepes-Ramirez, Harold

    2011-01-01

    ANTARES is a neutrino telescope located in the Mediterranean Sea with the aim of detecting high energy neutrinos of extra-terrestrial origin. It consists of a three dimensional array on 12 detection lines of photomultiplier tubes (PMTs) able to detect the Cherenkov light induced by muons produced in the interaction of neutrinos with the surrounding water and seabed. To reach the best angular resolution, good time and positioning calibrations are required. The propagation of Cherenkov photons strongly depends on the optical properties of the sea water, which has an impact on the reconstruction efficiency. The determination of the optical parameters, as the absorption and scattering lengths, is crucial to calculate properly the effective area and the angular resolution of the detector. The ANTARES optical beacon system consists of pulsed and fast, well controlled light sources distributed throughout the detector to carry out in situ the relative time calibration of the detector components. In this contribution we show some results on the sea water optical properties and their stability measured with the optical beacon system.

  6. Design and implementation of Bluetooth beacon in mobile payment system

    Science.gov (United States)

    Han, Tiantian; Ding, Lei

    2017-08-01

    The current line of payment means, mainly in the following ways, cash payment, credit card payment, WeChat Alipay sweep payment. There are many inconvenience in Cash payment, large amounts of cash inconvenience to carry, count the money to spend time and effort, true and false banknotes difficult to distinguish, ticket settlement easy to go wrong. Credit card payment is relatively time-consuming, and WeChat Alipay sweep payment need to sweep. Therefore, the design of a convenient, fast payment to meet the line to pay the demand is particularly important. Based on the characteristics of BLE Bluetooth wireless communication technology, this paper designs a kind of payment method based on Bluetooth beacon. Through the Bluetooth beacon broadcast consumption, consumers only need to open the relevant APP in the Android client, and you can get Bluetooth via mobile phone Bluetooth the amount of consumption of the standard broadcast, in accordance with the corresponding payment platform to complete the payment process, which pay less time to improve the efficiency of payment.

  7. Molecular Modeling of Peroxidase and Polyphenol Oxidase: Substrate Specificity and Active Site Comparison

    Directory of Open Access Journals (Sweden)

    Lalida Shank

    2010-09-01

    Full Text Available Peroxidases (POD and polyphenol oxidase (PPO are enzymes that are well known to be involved in the enzymatic browning reaction of fruits and vegetables with different catalytic mechanisms. Both enzymes have some common substrates, but each also has its specific substrates. In our computational study, the amino acid sequence of grape peroxidase (ABX was used for the construction of models employing homology modeling method based on the X-ray structure of cytosolic ascorbate peroxidase from pea (PDB ID:1APX, whereas the model of grape polyphenol oxidase was obtained directly from the available X-ray structure (PDB ID:2P3X. Molecular docking of common substrates of these two enzymes was subsequently studied. It was found that epicatechin and catechin exhibited high affinity with both enzymes, even though POD and PPO have different binding pockets regarding the size and the key amino acids involved in binding. Predicted binding modes of substrates with both enzymes were also compared. The calculated docking interaction energy of trihydroxybenzoic acid related compounds shows high affinity, suggesting specificity and potential use as common inhibitor to grape ascorbate peroxidase and polyphenol oxidase.

  8. [Molecular authentication of Jinyinhua formula granule by using allele-specific PCR].

    Science.gov (United States)

    Jiang, Chao; Tu, Li-Chan; Yuan, Yuan; Huang, Lu-Qi; Gao, Wei; Jin, Yan

    2017-07-01

    Traditional authentication method is hard to identify herb's authenticity of traditional Chinese medicine(TCM) formula granules because they have lost all their morphological characteristics. In this study, a new allele-specific PCR method was established for identifying the authentication of Jinyinhua formula granule (made from Lonicerae Japonicae Flos) based on an SNP site in trnL-trnF fragment. Genomic DNA was successfully extracted from Lonicerae Japonicae Flos and its formula granules by using an improved spin column method and then PCR was performed with the designed primer. Approximately 110 bp specific bands was obtained only in the authentic Lonicerae Japonicae Flos and its formula granules, while no bands were found in fake mixed products. In addition, the PCR product sequence was proved from Lonicerae Japonicae Flos trnL-trnF sequence by using BLAST method. Therefore, DNA molecular authentication method could make up the limitations of character identification method and microscopic identification, and quickly identify herb's authenticity of TCM formula granules, with enormous potential for market supervision and quality control. Copyright© by the Chinese Pharmaceutical Association.

  9. The PP1 binding code: a molecular-lego strategy that governs specificity.

    Science.gov (United States)

    Heroes, Ewald; Lesage, Bart; Görnemann, Janina; Beullens, Monique; Van Meervelt, Luc; Bollen, Mathieu

    2013-01-01

    Ser/Thr protein phosphatase 1 (PP1) is a single-domain hub protein with nearly 200 validated interactors in vertebrates. PP1-interacting proteins (PIPs) are ubiquitously expressed but show an exceptional diversity in brain, testis and white blood cells. The binding of PIPs is mainly mediated by short motifs that dock to surface grooves of PP1. Although PIPs often contain variants of the same PP1 binding motifs, they differ in the number and combination of docking sites. This molecular-lego strategy for binding to PP1 creates holoenzymes with unique properties. The PP1 binding code can be described as specific, universal, degenerate, nonexclusive and dynamic. PIPs control associated PP1 by interference with substrate recruitment or access to the active site. In addition, some PIPs have a subcellular targeting domain that promotes dephosphorylation by increasing the local concentration of PP1. The diversity of the PP1 interactome and the properties of the PP1 binding code account for the exquisite specificity of PP1 in vivo. © 2012 The Authors Journal compilation © 2012 FEBS.

  10. Power-Efficient Beacon Recognition Method Based on Periodic Wake-Up for Industrial Wireless Devices.

    Science.gov (United States)

    Song, Soonyong; Lee, Donghun; Jang, Ingook; Choi, Jinchul; Son, Youngsung

    2018-04-17

    Energy harvester-integrated wireless devices are attractive for generating semi-permanent power from wasted energy in industrial environments. The energy-harvesting wireless devices may have difficulty in their communication with access points due to insufficient power supply for beacon recognition during network initialization. In this manuscript, we propose a novel method of beacon recognition based on wake-up control to reduce instantaneous power consumption in the initialization procedure. The proposed method applies a moving window for the periodic wake-up of the wireless devices. For unsynchronized wireless devices, beacons are always located in the same positions within each beacon interval even though the starting offsets are unknown. Using these characteristics, the moving window checks the existence of the beacon associated withspecified resources in a beacon interval, checks again for neighboring resources at the next beacon interval, and so on. This method can reduce instantaneous power and generates a surplus of charging time. Thus, the proposed method alleviates the problems of power insufficiency in the network initialization. The feasibility of the proposed method is evaluated using computer simulations of power shortage in various energy-harvesting conditions.

  11. DNA aptamer beacon assay for C-telopeptide and handheld fluorometer to monitor bone resorption.

    Science.gov (United States)

    Bruno, John Gordon; Carrillo, Maria P; Phillips, Taylor; Hanson, Douglas; Bohmann, Jonathan A

    2011-09-01

    A novel DNA aptamer beacon is described for quantification of a 26-amino acid C-telopeptide (CTx) of human type I bone collagen. One aptamer sequence and its reverse complement dominated the aptamer pool (31.6% of sequenced clones). Secondary structures of these aptamers were examined for potential binding pockets. Three-dimensional computer models which analyzed docking topologies and binding energies were in agreement with empirical fluorescence experiments used to select one candidate loop for beacon assay development. All loop structures from the aptamer finalists were end-labeled with TYE 665 and Iowa Black quencher for comparison of beacon fluorescence levels as a function of CTx concentration. The optimal beacon, designated CTx 2R-2h yielded a low ng/ml limit of detection using a commercially available handheld fluorometer. The CTx aptamer beacon bound full-length 26-amino acid CTx peptide, but not a shorter 8-amino acid segment of CTx peptide which is a common target for commercial CTx ELISA kits. The prototype assay was shown to detect CTx peptide from human urine after creatinine and urea were removed by size-exclusion chromatography to prevent nonspecific denaturing of the aptamer beacon. This work demonstrates the potential of aptamer beacons to be utilized for rapid and sensitive bone health monitoring in a handheld or point-of-care format.

  12. Molecular cloning of a seed specific multifunctional RFO synthase/ galactosylhydrolase in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Roman eGangl

    2015-09-01

    Full Text Available Stachyose is among the raffinose family oligosaccharides one of the major water-soluble carbohydrates next to sucrose in seeds of a number of plant species. Especially in leguminous seeds, e.g. chickpea, stachyose is reported as the major component. In contrast to their ambiguous potential as essential source of carbon for germination, raffinose family oligosaccharides are indigestible for humans and can contribute to diverse abdominal disorders.In the genome of Arabidopsis thaliana, six putative raffinose synthase genes are reported, whereas little is known about these putative raffinose synthases and their biochemical characteristics or their contribution to the raffinose family oligosaccharide physiology in A. thaliana.In this paper, we report on the molecular cloning, functional expression in Escherichia coli and purification of recombinant AtRS4 from A. thaliana and the biochemical characterisation of the putative stachyose synthase (AtSTS, At4g01970 as a raffinose and high affinity stachyose synthase (Km for raffinose 259.2 ± 21.15 µM as well as stachyose and galactinol specific galactosylhydrolase. A T-DNA insertional mutant in the AtRS4 gene was isolated. Only sqPCR from WT siliques showed a specific transcriptional AtRS4 PCR product. Metabolite measurements in seeds of ΔAtRS4 mutant plants revealed a total loss of stachyose in ΔAtRS4 mutant seeds. We conclude that AtRS4 is the only stachyose synthase in the genome of A. thaliana that AtRS4 represents a key regulation mechanism in the raffinose family oligosaccharide physiology of A. thaliana due to its multifunctional enzyme activity and that AtRS4 is possibly the second seed specific raffinose synthase beside AtRS5, which is responsible for Raf-accumulation under abiotic stress.

  13. Molecular Diagnosis of Brettanomyces bruxellensis’ Sulfur Dioxide Sensitivity Through Genotype Specific Method

    Directory of Open Access Journals (Sweden)

    Marta Avramova

    2018-06-01

    Full Text Available The yeast species Brettanomyces bruxellensis is associated with important economic losses due to red wine spoilage. The most common method to prevent and/or control B. bruxellensis spoilage in winemaking is the addition of sulfur dioxide into must and wine. However, recently, it was reported that some B. bruxellensis strains could be tolerant to commonly used doses of SO2. In this work, B. bruxellensis response to SO2 was assessed in order to explore the relationship between SO2 tolerance and genotype. We selected 145 isolates representative of the genetic diversity of the species, and from different fermentation niches (roughly 70% from grape wine fermentation environment, and 30% from beer, ethanol, tequila, kombucha, etc.. These isolates were grown in media harboring increasing sulfite concentrations, from 0 to 0.6 mg.L-1 of molecular SO2. Three behaviors were defined: sensitive strains showed longer lag phase and slower growth rate and/or lower maximum population size in presence of increasing concentrations of SO2. Tolerant strains displayed increased lag phase, but maximal growth rate and maximal population size remained unchanged. Finally, resistant strains showed no growth variation whatever the SO2 concentrations. 36% (52/145 of B. bruxellensis isolates were resistant or tolerant to sulfite, and up to 43% (46/107 when considering only wine isolates. Moreover, most of the resistant/tolerant strains belonged to two specific genetic groups, allowing the use of microsatellite genotyping to predict the risk of sulfur dioxide resistance/tolerance with high reliability (>90%. Such molecular diagnosis could help the winemakers to adjust antimicrobial techniques and efficient spoilage prevention with minimal intervention.

  14. Specificity of molecular interactions in transient protein-protein interaction interfaces.

    Science.gov (United States)

    Cho, Kyu-il; Lee, KiYoung; Lee, Kwang H; Kim, Dongsup; Lee, Doheon

    2006-11-15

    In this study, we investigate what types of interactions are specific to their biological function, and what types of interactions are persistent regardless of their functional category in transient protein-protein heterocomplexes. This is the first approach to analyze protein-protein interfaces systematically at the molecular interaction level in the context of protein functions. We perform systematic analysis at the molecular interaction level using classification and feature subset selection technique prevalent in the field of pattern recognition. To represent the physicochemical properties of protein-protein interfaces, we design 18 molecular interaction types using canonical and noncanonical interactions. Then, we construct input vector using the frequency of each interaction type in protein-protein interface. We analyze the 131 interfaces of transient protein-protein heterocomplexes in PDB: 33 protease-inhibitors, 52 antibody-antigens, 46 signaling proteins including 4 cyclin dependent kinase and 26 G-protein. Using kNN classification and feature subset selection technique, we show that there are specific interaction types based on their functional category, and such interaction types are conserved through the common binding mechanism, rather than through the sequence or structure conservation. The extracted interaction types are C(alpha)-- H...O==C interaction, cation...anion interaction, amine...amine interaction, and amine...cation interaction. With these four interaction types, we achieve the classification success rate up to 83.2% with leave-one-out cross-validation at k = 15. Of these four interaction types, C(alpha)--H...O==C shows binding specificity for protease-inhibitor complexes, while cation-anion interaction is predominant in signaling complexes. The amine ... amine and amine...cation interaction give a minor contribution to the classification accuracy. When combined with these two interactions, they increase the accuracy by 3.8%. In the case of

  15. Andrographis paniculata transcriptome provides molecular insights into tissue-specific accumulation of medicinal diterpenes.

    Science.gov (United States)

    Garg, Anchal; Agrawal, Lalit; Misra, Rajesh Chandra; Sharma, Shubha; Ghosh, Sumit

    2015-09-02

    Kalmegh (Andrographis paniculata) has been widely exploited in traditional medicine for the treatment of infectious diseases and health disorders. Ent-labdane-related diterpene (ent-LRD) specialized (i.e., secondary) metabolites of kalmegh such as andrographolide, neoandrographolide and 14-deoxy-11,12-didehydroandrographolide, are known for variety of pharmacological activities. However, due to the lack of genomic and transcriptomic information, underlying molecular basis of ent-LRDs biosynthesis has remained largely unknown. To identify candidate genes of the ent-LRD biosynthetic pathway, we performed comparative transcriptome analysis using leaf and root tissues that differentially accumulate ent-LRDs. De novo assembly of Illumina HiSeq2000 platform-generated paired-end sequencing reads resulted into 69,011 leaf and 64,244 root transcripts which were assembled into a total of 84,628 unique transcripts. Annotation of these transcripts to the Uniprot, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active Enzymes (CAZy) databases identified candidate transcripts of the ent-LRD biosynthetic pathway. These included transcripts that encode enzymes of the plastidial 2C-methyl-D-erythritol-4-phosphate pathway which provides C5 isoprenoid precursors for the ent-LRDs biosynthesis, geranylgeranyl diphosphate synthase, class II diterpene synthase (diTPS), cytochrome P450 monooxygenase and glycosyltransferase. Three class II diTPSs (ApCPS1, ApCPS2 and ApCPS3) that showed distinct tissue-specific expression profiles and are phylogenetically related to the dicotyledon ent-copalyl diphosphate synthases, are identified. ApCPS1, ApCPS2 and ApCPS3 encode for 832-, 817- and 797- amino acids proteins of 55-63 % identity, respectively. Spatio-temporal patterns of transcripts and ent-LRDs accumulation are consistent with the involvement of ApCPS1 in general (i.e., primary) metabolism for the biosynthesis of phytohormone gibberellin, ApCPS2 in leaf specialized ent

  16. Tight Bounds for Beacon-Based Coverage in Simple Rectilinear Polygons

    KAUST Repository

    Bae, Sang Won; Shin, Chan-Su; Vigneron, Antoine E.

    2016-01-01

    We establish tight bounds for beacon-based coverage problems. In particular, we show that $$\\lfloor \\frac{n}{6} \\rfloor $$⌊n6⌋ beacons are always sufficient and sometimes necessary to cover a simple rectilinear polygon P with n vertices. When P is monotone and rectilinear, we prove that this bound becomes $$\\lfloor \\frac{n+4}{8} \\rfloor $$⌊n+48⌋. We also present an optimal linear-time algorithm for computing the beacon kernel of P.

  17. Tight Bounds for Beacon-Based Coverage in Simple Rectilinear Polygons

    KAUST Repository

    Bae, Sang Won

    2016-03-21

    We establish tight bounds for beacon-based coverage problems. In particular, we show that $$\\\\lfloor \\\\frac{n}{6} \\ floor $$⌊n6⌋ beacons are always sufficient and sometimes necessary to cover a simple rectilinear polygon P with n vertices. When P is monotone and rectilinear, we prove that this bound becomes $$\\\\lfloor \\\\frac{n+4}{8} \\ floor $$⌊n+48⌋. We also present an optimal linear-time algorithm for computing the beacon kernel of P.

  18. Anticancer efficacy of the metabolic blocker 3-bromopyruvate: specific molecular targeting.

    Science.gov (United States)

    Ganapathy-Kanniappan, Shanmugasundaram; Kunjithapatham, Rani; Geschwind, Jean-Francois

    2013-01-01

    The anticancer efficacy of the pyruvate analog 3-bromopyruvate has been demonstrated in multiple tumor models. The chief principle underlying the antitumor effects of 3-bromopyruvate is its ability to effectively target the energy metabolism of cancer cells. Biochemically, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been identified as the primary target of 3-bromopyruvate. Its inhibition results in the depletion of intracellular ATP, causing cell death. Several reports have also demonstrated that in addition to GAPDH inhibition, the induction of cellular stress also contributes to 3-bromopyruvate treatment-dependent apoptosis. Furthermore, recent evidence shows that 3-bromopyruvate is taken up selectively by tumor cells via the monocarboxylate transporters (MCTs) that are frequently overexpressed in cancer cells (for the export of lactate produced during aerobic glycolysis). The preferential uptake of 3-bromopyruvate via MCTs facilitates selective targeting of tumor cells while leaving healthy and non-malignant tissue untouched. Taken together, the specificity of molecular (GAPDH) targeting and selective uptake by tumor cells, underscore the potential of 3-bromopyruvate as a potent and promising anticancer agent. In this review, we highlight the mechanistic characteristics of 3-bromopyruvate and discuss its potential for translation into the clinic.

  19. Molecular recognition of malachite green by hemoglobin and their specific interactions: insights from in silico docking and molecular spectroscopy.

    Science.gov (United States)

    Peng, Wei; Ding, Fei; Peng, Yu-Kui; Sun, Ying

    2014-01-01

    Malachite green is an organic compound that can be widely used as a dyestuff for various materials; it has also emerged as a controversial agent in aquaculture. Since malachite green is proven to be carcinogenic and mutagenic, it may become a hazard to public health. For this reason, it is urgently required to analyze this controversial dye in more detail. In our current research, the interaction between malachite green and hemoglobin under physiological conditions was investigated by the methods of molecular modeling, fluorescence spectroscopy, circular dichroism (CD) as well as hydrophobic ANS displacement experiments. From the molecular docking, the central cavity of hemoglobin was assigned to possess high-affinity for malachite green, this result was corroborated by time-resolved fluorescence and hydrophobic ANS probe results. The recognition mechanism was found to be of static type, or rather the hemoglobin-malachite green complex formation occurred via noncovalent interactions such as π-π interactions, hydrogen bonds and hydrophobic interactions with an association constant of 10(4) M(-1). Moreover, the results also show that the spatial structure of the biopolymer was changed in the presence of malachite green with a decrease of the α-helix and increase of the β-sheet, turn and random coil suggesting protein damage, as derived from far-UV CD and three-dimensional fluorescence. Results of this work will help to further comprehend the molecular recognition of malachite green by the receptor protein and the possible toxicological profiles of other compounds, which are the metabolites and ramifications of malachite green.

  20. Biokinetics and dosimetry of target-specific radiopharmaceuticals for molecular imaging and therapy

    International Nuclear Information System (INIS)

    Ferro F, G.; Torres G, E.; Gonzalez V, A.; Murphy, C.A. de

    2006-01-01

    Molecular imaging techniques directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochemical, biologic, diagnostic or therapeutic applications. 99m Tc-HYNlC-TOC has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. Therapies using radiolabeled anti-CD20 have demonstrated their efficacy in patients with B-cell non Hodgkin's Iymphoma (NHL). The aim of this study was to establish biokinetic models for 99m Tc-HYNlC-TOC and 188 Re-anti-CD20 prepared from Iyophilized kits, and to evaluate their dosimetry as target-specific radiopharmaceuticals. Whole-body images were acquired at different times after 99m Tc-HYNlC-TOC or 188 Re-anti-CD20 administration obtained from instant freeze-dried kit formulations with radiochemical purities > 95 %. Regions of interest (ROls) were drawn around source organs on each time frame. The cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate time-activity curves in each organ, to adjust the biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. 99m Tc-HYNlC-TOC images showed an average tumor/blood (heart) ratio of 4.3 ± 0.7 in receptor-positive tumors at 1 h and the mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv. Results showed that after administration of 7 GBq of 188 Re-anti-CD20 the absorbed dose to whole body would be 0.7 Gy (0.1 mGy/MBq) which is the indicated dose for non Hodgkin's Iymphome therapies. (Author)

  1. Design and Implementation of Distress Prevention System using a Beacon

    Directory of Open Access Journals (Sweden)

    Lee Imsu

    2016-01-01

    Full Text Available It was proven that human accidents due to mountain climbing occupy large proportion of recently occurred man-made disasters. This paper designed and implemented an application that tells users about a variety of accidents that frequently occur in mountain and shows dynamic information about mountain climbing. It designed ‘distress prevention system using beacon’. When using beacon, it can dynamically express information without using GPS. It has advantage of supporting BLE and has little Smartphone battery consumption. The application was developed based on Android as a prototype. We expect that the application developed in this paper can contribute to the protection of precious lives by helping quick rescue in case of emergency such as distress. Manager of mountain can control data regarding the mountain climbing accident where the related functions are provided through view and user authority setup in DBMS.

  2. Beacons of discovery the worldwide science of particle physics

    CERN Document Server

    International Committee for Future Accelerators (ICFA)

    2011-01-01

    To discover what our world is made of and how it works at the most fundamental level is the challenge of particle physics. The tools of particle physics—experiments at particle accelerators and underground laboratories, together with observations of space—bring opportunities for discovery never before within reach. Thousands of scientists from universities and laboratories around the world collaborate to design, build and use unique detectors and accelerators to explore the fundamental physics of matter, energy, space and time. Together, in a common world-wide program of discovery, they provide a deep understanding of the world around us and countless benefits to society. Beacons of Discovery presents a vision of the global science of particle physics at the dawn of a new light on the mystery and beauty of the universe.

  3. BEACON: An application of nodal methods for operational support

    International Nuclear Information System (INIS)

    Boyd, W.A.; Nguyen, T.Q.

    1992-01-01

    A practical application of nodal methods is on-line plant operational support. However, to enable plant personnel to take full advantage of a nodal model to support plant operations, (a) a core nodal model must always be up to date with the current core history and conditions, (b) the nodal methods must be fast enough to allow numerous core calculations to be performed in minutes to support engineering decisions, and (c) the system must be easily accessible to engineering personnel at the reactor, their offices, or any other location considered appropriate. A core operational support package developed by Westinghouse called BEACON (best estimate analysis of core operations - nuclear) has been installed at several plants. Results from these plants and numerous in-core flux maps analyzed have demonstrated the accuracy of the model and the effectiveness of the methodology

  4. Seamless Guidance System Combining GPS, BLE Beacon, and NFC Technologies

    Directory of Open Access Journals (Sweden)

    Rung-Shiang Cheng

    2016-01-01

    Full Text Available Users rely increasingly on Location-Based Services (LBS and automated navigation/guidance systems nowadays. However, while such services are easily implemented in outdoor environments using Global Positioning System (GPS technology, a requirement still exists for accurate localization and guidance schemes in indoor settings. Accordingly, the present study proposes a system based on GPS, Bluetooth Low Energy (BLE beacons, and Near Field Communication (NFC technology. Through establishing graphic information and the design of algorithm, this study develops a guidance system for indoors and outdoors on smart phones, wishing to give user perfect smart life through this system. The proposed system is implemented on a smart phone and evaluated on a student campus environment. The experimental results confirm the ability of the proposed app to switch automatically from an outdoor mode to an indoor mode and to guide the user to requested target destination via the shortest possible route.

  5. NPP Grassland: Beacon Hill, U.K., 1972-1993, R1

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set contains two ASCII text files, one providing productivity measurements for a chalk grassland on Beacon Hill, West Sussex, U.K. (50.92 N, -0.85 W) and...

  6. Evaluation of light-emitting diode beacon light fixtures : final report.

    Science.gov (United States)

    2009-12-01

    Rotating beacons containing filament light sources have long been used on highway maintenance trucks : to indicate the presence of the truck to other drivers. Because of advances in light-emitting diode (LED) : technologies, flashing lights containin...

  7. Multi-kW Uplink Fiber-Laser Beacon with Agile Signal Format, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration —  Laser beacons with scalable powers are needed for ground to deep-space optical communication uplinks. They serve as absolute reference for tracking of spacecraft...

  8. Multi-kW Uplink Fiber-Laser Beacon with Agile Signal Format, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Uplink Laser Beacons for deep-space communication, can benefit greatly from migration to the 1010-1030nm wavelengths, via use of Silicon-APDs on the spacecraft...

  9. BEACON: A Summary Framework to Overcome Potential Reimbursement Hurdles.

    Science.gov (United States)

    Dunlop, William C N; Mullins, C Daniel; Pirk, Olaf; Goeree, Ron; Postma, Maarten J; Enstone, Ashley; Heron, Louise

    2016-10-01

    To provide a framework for addressing payers' criteria during the development of pharmaceuticals. A conceptual framework was presented to an international health economic expert panel for discussion. A structured literature search (from 2010 to May 2015), using the following databases in Ovid: Medline(®) and Medline(®) In-Process (PubMed), Embase (Ovid), EconLit (EBSCOhost) and the National Health Service Economic Evaluation Database (NHS EED), and a 'grey literature' search, were conducted to identify existing criteria from the payer perspective. The criteria assessed by existing frameworks and guidelines were collated; the most commonly reported criteria were considered for inclusion in the framework. A mnemonic was conceived as a memory aide to summarise these criteria. Overall, 41 publications were identified as potentially relevant to the objective. Following further screening, 26 were excluded upon full-text review on the basis of no framework presented (n = 13), redundancy (n = 11) or abstract only (n = 2). Frameworks that captured criteria developed for or utilised by the pharmaceutical industry (n = 5) and reimbursement guidance (n = 10) were reviewed. The most commonly identified criteria-unmet need/patient burden, safety, efficacy, quality-of-life outcomes, environment, evidence quality, budget impact and comparator-were incorporated into the summary framework. For ease of communication, the following mnemonic was developed: BEACON (Burden/target population, Environment, Affordability/value, Comparator, Outcomes, Number of studies/quality of evidence). The BEACON framework aims to capture the 'essence' of payer requirements by addressing the most commonly described criteria requested by payers regarding the introduction of a new pharmaceutical.

  10. Remote tracking of a magnetic receiver using low frequency beacons

    International Nuclear Information System (INIS)

    Sheinker, Arie; Ginzburg, Boris; Salomonski, Nizan; Frumkis, Lev; Kaplan, Ben-Zion

    2014-01-01

    Low frequency magnetic fields feature high penetration ability, which allows communication, localization, and tracking in environments where radio or acoustic waves are blocked or distorted by multipath interferences. In the present work, we propose a method for tracking a magnetic receiver using beacons of low frequency magnetic field, where the receiver includes a tri-axial search-coil magnetometer. Measuring the beacons’ magnetic fields and calculating the total-field signals enables localization without restrictions on magnetometer orientation, allowing on-the-move tracking. The total-field signals are used by a global search method, e.g., simulated annealing (SA) algorithm, to localize the receiver. The magnetic field produced by each beacon has a dipole structure and is governed by the beacon’s position and magnetic moment. We have investigated two different methods for estimating beacons’ magnetic moments prior to localization. The first method requires directional measurements, whereas for the second method the total-field signal is used. Effectiveness of these methods has been proved in numerous field tests. In the present work, we introduce a method for tracking a moving receiver by successive localizations. Using previous localization as a starting point of the search method for the next localization can reduce execution time and chances for divergence. The proposed method has been tested using numerous computer simulations. Successful system operation has been verified in field conditions. The good tracking capability together with simple implementation makes the proposed method attractive for real-time, low power field applications, such as mobile robots navigation. (paper)

  11. Improving adherence to the Epic Beacon ambulatory workflow.

    Science.gov (United States)

    Chackunkal, Ellen; Dhanapal Vogel, Vishnuprabha; Grycki, Meredith; Kostoff, Diana

    2017-06-01

    Computerized physician order entry has been shown to significantly improve chemotherapy safety by reducing the number of prescribing errors. Epic's Beacon Oncology Information System of computerized physician order entry and electronic medication administration was implemented in Henry Ford Health System's ambulatory oncology infusion centers on 9 November 2013. Since that time, compliance to the infusion workflow had not been assessed. The objective of this study was to optimize the current workflow and improve the compliance to this workflow in the ambulatory oncology setting. This study was a retrospective, quasi-experimental study which analyzed the composite workflow compliance rate of patient encounters from 9 to 23 November 2014. Based on this analysis, an intervention was identified and implemented in February 2015 to improve workflow compliance. The primary endpoint was to compare the composite compliance rate to the Beacon workflow before and after a pharmacy-initiated intervention. The intervention, which was education of infusion center staff, was initiated by ambulatory-based, oncology pharmacists and implemented by a multi-disciplinary team of pharmacists and nurses. The composite compliance rate was then reassessed for patient encounters from 2 to 13 March 2015 in order to analyze the effects of the determined intervention on compliance. The initial analysis in November 2014 revealed a composite compliance rate of 38%, and data analysis after the intervention revealed a statistically significant increase in the composite compliance rate to 83% ( p < 0.001). This study supports a pharmacist-initiated educational intervention can improve compliance to an ambulatory, oncology infusion workflow.

  12. Perancangan Prototipe Receiver Beacon Black Box Locator Acoustic 37,5 kHz Pingers

    OpenAIRE

    RUSTAMAJI RUSTAMAJI; PAULINE RAHMIATI; SARAH PERMATASARI

    2016-01-01

    ABSTRAK Ketika suatu pesawat terbang mengalami kecelakaan terjatuh ke dalam air, maka lokasi keberadaannya dapat dideteksi oleh alat yang disebut receiver beacon black box locator acoustic (pingers receiver). Pingers receiver berfungsi untuk menerima sinyal dengan frekuensi 37,5 kHz ± 1 kHz dari pingers transmitter atau Underwater Locator Beacon (ULB) yang berada pada black box pesawat. Dalam penelitian ini dibuat perancangan pingers receiver yang tersusun dari rangkaian Band Pass Filter (BPF...

  13. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.

    Science.gov (United States)

    Cortés, Javier; Rugo, Hope S; Awada, Ahmad; Twelves, Chris; Perez, Edith A; Im, Seock-Ah; Gómez-Pardo, Patricia; Schwartzberg, Lee S; Diéras, Veronique; Yardley, Denise A; Potter, David A; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol; Hoch, Ute; Tagliaferri, Mary; Hannah, Alison L; O'Shaughnessy, Joyce

    2017-09-01

    Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

  14. Molecular diagnostic for boll weevil (Coleoptera: Curculionidae) based on amplification of three species-specific microsatellites.

    Science.gov (United States)

    Kim, Kyung Seok; Szendrei, Zsofia; Rodriguez-Saona, Cesar; Mulder, Phillip G; Sappington, Thomas W

    2009-04-01

    The boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), is a serious pest of cultivated cotton, Gossypium hirsutum L., in the Americas, and reinfestation of zones from which they have been eradicated is of perpetual concern. Extensive arrays of pheromone traps monitor for reintroductions, but occasionally the traps collect nontarget weevils that can be misidentified by scouts. For example, the congeneric pepper weevil, Anthonomus eugenii Cano, and other superficially similar weevils are attracted to components of the boll weevil lure or trap color. Although morphologically distinguishable by trained personnel, the potential for misidentification is compounded when captured weevils are dismembered or partially consumed by ants or ground beetles that sometimes feed on them in the traps. Because misidentification can have expensive consequences, a molecular diagnostic tool would be of great value to eradication managers. We demonstrate that a cocktail of three primer pairs in a single polymerase chain reaction (PCR) amplify species-specific microsatellites that unambiguously distinguish the boll weevil from three other weevil species tested, including pepper weevil; cranberry weevil, Anthonomus eugenii musculus Say; and pecan weevil, Curculio caryae Horn. However, it does not distinguish the boll weevil from the subspecific "thurberia" weevil. A universal internal transcribed spacer primer pair included in the cocktail cross-amplifies DNA from all species, serving as a positive control. Furthermore, the diagnostic primers amplified the target microsatellites from various boll weevil adult body parts, indicating that the PCR technology using the primer cocktail is sensitive enough to positively identify a boll weevil even when the body is partly degraded.

  15. TU-F-CAMPUS-T-03: Enhancing the Tumor Specific Radiosensitization Using Molecular Targeted Gold Nanorods

    International Nuclear Information System (INIS)

    Diagaradjane, P; Deorukhkar, A; Sankaranarayanapillai, M; Singh, P; Manohar, N; Tailor, R; Cho, S; Goodrich, G; Krishnan, S

    2015-01-01

    Purpose: Gold nanoparticle (GNP) mediated radiosensitization has gained significant attention in recent years. However, the widely used passive targeting strategy requires high concentration of GNPs to induce the desired therapeutic effect, thus dampening the enthusiasm for clinical translation. The purpose of this study is to utilize a molecular targeting strategy to minimize the concentration of GNPs injected while simultaneously enhancing the tumor specific radiosensitization for an improved therapeutic outcome. Methods: Cetuximab (antibody specific to the epidermal growth factor receptor that is over-expressed in tumors) conjugated gold nanorods (cGNRs) was used for the tumor targeting. The binding affinity, internalization, and in vitro radiosensitization were evaluated using dark field microscopy, transmission electron microscopy, and clonogenic cell survival assay, respectively. In vivo biodistribution in tumor (HCT116-colorectal cancer cells) bearing mice were quantified using inductively coupled plasma mass spectrometry. In vivo radiosensitization potential was tested using 250-kVp x-rays and clinically relevant 6-MV radiation beams. Results: cGNRs displayed excellent cell-surface binding and internalization (∼31,000 vs 12,000/cell) when compared to unconjugated GNRs (pGNRs). In vitro, the dose enhancement factor at 10% survival (DEF10) was estimated as 1.06 and 1.17, respectively for both 250-kVp and 6-MV beams. In vivo biodistribution analysis revealed enhanced uptake of cGNRs in tumor (1.3 µg/g of tumor tissue), which is ∼1000-fold less than the reported values using passive targeting strategy. Nonetheless, significant radiosensitization was observed in vivo with cGNRs when compared to pGNRs, when irradiated with 250-kVp (tumor volume doubling time 35 days vs 25 days; p=0.002) and 6 MV (17 days vs 13 days; p=0.0052) beams. Conclusion: The enhanced radiosensitization effect observed with very low intratumoral concentrations of gold and megavoltage x

  16. TU-F-CAMPUS-T-03: Enhancing the Tumor Specific Radiosensitization Using Molecular Targeted Gold Nanorods

    Energy Technology Data Exchange (ETDEWEB)

    Diagaradjane, P [M.D. Anderson Cancer Center, Houston, TX (United States); Deorukhkar, A; Sankaranarayanapillai, M; Singh, P [The UT MD Anderson Cancer Center, Houston, TX (United States); Manohar, N; Tailor, R; Cho, S [UT MD Anderson Cancer Center, Houston, TX (United States); Goodrich, G [Nanospectra Biosciences Inc, Houston, TX (United States); Krishnan, S [The University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Gold nanoparticle (GNP) mediated radiosensitization has gained significant attention in recent years. However, the widely used passive targeting strategy requires high concentration of GNPs to induce the desired therapeutic effect, thus dampening the enthusiasm for clinical translation. The purpose of this study is to utilize a molecular targeting strategy to minimize the concentration of GNPs injected while simultaneously enhancing the tumor specific radiosensitization for an improved therapeutic outcome. Methods: Cetuximab (antibody specific to the epidermal growth factor receptor that is over-expressed in tumors) conjugated gold nanorods (cGNRs) was used for the tumor targeting. The binding affinity, internalization, and in vitro radiosensitization were evaluated using dark field microscopy, transmission electron microscopy, and clonogenic cell survival assay, respectively. In vivo biodistribution in tumor (HCT116-colorectal cancer cells) bearing mice were quantified using inductively coupled plasma mass spectrometry. In vivo radiosensitization potential was tested using 250-kVp x-rays and clinically relevant 6-MV radiation beams. Results: cGNRs displayed excellent cell-surface binding and internalization (∼31,000 vs 12,000/cell) when compared to unconjugated GNRs (pGNRs). In vitro, the dose enhancement factor at 10% survival (DEF10) was estimated as 1.06 and 1.17, respectively for both 250-kVp and 6-MV beams. In vivo biodistribution analysis revealed enhanced uptake of cGNRs in tumor (1.3 µg/g of tumor tissue), which is ∼1000-fold less than the reported values using passive targeting strategy. Nonetheless, significant radiosensitization was observed in vivo with cGNRs when compared to pGNRs, when irradiated with 250-kVp (tumor volume doubling time 35 days vs 25 days; p=0.002) and 6 MV (17 days vs 13 days; p=0.0052) beams. Conclusion: The enhanced radiosensitization effect observed with very low intratumoral concentrations of gold and megavoltage x

  17. An adaptive scheme for robot localization and mapping with dynamically configurable inter-beacon range measurements.

    Science.gov (United States)

    Torres-González, Arturo; Martinez-de Dios, Jose Ramiro; Ollero, Anibal

    2014-04-25

    This work is motivated by robot-sensor network cooperation techniques where sensor nodes (beacons) are used as landmarks for range-only (RO) simultaneous localization and mapping (SLAM). This paper presents a RO-SLAM scheme that actuates over the measurement gathering process using mechanisms that dynamically modify the rate and variety of measurements that are integrated in the SLAM filter. It includes a measurement gathering module that can be configured to collect direct robot-beacon and inter-beacon measurements with different inter-beacon depth levels and at different rates. It also includes a supervision module that monitors the SLAM performance and dynamically selects the measurement gathering configuration balancing SLAM accuracy and resource consumption. The proposed scheme has been applied to an extended Kalman filter SLAM with auxiliary particle filters for beacon initialization (PF-EKF SLAM) and validated with experiments performed in the CONET Integrated Testbed. It achieved lower map and robot errors (34% and 14%, respectively) than traditional methods with a lower computational burden (16%) and similar beacon energy consumption.

  18. Supporting Beacon and Event-Driven Messages in Vehicular Platoons through Token-Based Strategies.

    Science.gov (United States)

    Balador, Ali; Uhlemann, Elisabeth; Calafate, Carlos T; Cano, Juan-Carlos

    2018-03-23

    Timely and reliable inter-vehicle communications is a critical requirement to support traffic safety applications, such as vehicle platooning. Furthermore, low-delay communications allow the platoon to react quickly to unexpected events. In this scope, having a predictable and highly effective medium access control (MAC) method is of utmost importance. However, the currently available IEEE 802.11p technology is unable to adequately address these challenges. In this paper, we propose a MAC method especially adapted to platoons, able to transmit beacons within the required time constraints, but with a higher reliability level than IEEE 802.11p, while concurrently enabling efficient dissemination of event-driven messages. The protocol circulates the token within the platoon not in a round-robin fashion, but based on beacon data age, i.e., the time that has passed since the previous collection of status information, thereby automatically offering repeated beacon transmission opportunities for increased reliability. In addition, we propose three different methods for supporting event-driven messages co-existing with beacons. Analysis and simulation results in single and multi-hop scenarios showed that, by providing non-competitive channel access and frequent retransmission opportunities, our protocol can offer beacon delivery within one beacon generation interval while fulfilling the requirements on low-delay dissemination of event-driven messages for traffic safety applications.

  19. Supporting Beacon and Event-Driven Messages in Vehicular Platoons through Token-Based Strategies

    Directory of Open Access Journals (Sweden)

    Ali Balador

    2018-03-01

    Full Text Available Timely and reliable inter-vehicle communications is a critical requirement to support traffic safety applications, such as vehicle platooning. Furthermore, low-delay communications allow the platoon to react quickly to unexpected events. In this scope, having a predictable and highly effective medium access control (MAC method is of utmost importance. However, the currently available IEEE 802.11p technology is unable to adequately address these challenges. In this paper, we propose a MAC method especially adapted to platoons, able to transmit beacons within the required time constraints, but with a higher reliability level than IEEE 802.11p, while concurrently enabling efficient dissemination of event-driven messages. The protocol circulates the token within the platoon not in a round-robin fashion, but based on beacon data age, i.e., the time that has passed since the previous collection of status information, thereby automatically offering repeated beacon transmission opportunities for increased reliability. In addition, we propose three different methods for supporting event-driven messages co-existing with beacons. Analysis and simulation results in single and multi-hop scenarios showed that, by providing non-competitive channel access and frequent retransmission opportunities, our protocol can offer beacon delivery within one beacon generation interval while fulfilling the requirements on low-delay dissemination of event-driven messages for traffic safety applications.

  20. Accelerated Adoption of Advanced Health Information Technology in Beacon Community Health Centers.

    Science.gov (United States)

    Jones, Emily; Wittie, Michael

    2015-01-01

    To complement national and state-level HITECH Act programs, 17 Beacon communities were funded to fuel community-wide use of health information technology to improve quality. Health centers in Beacon communities received supplemental funding. This article explores the association between participation in the Beacon program and the adoption of electronic health records. Using the 2010-2012 Uniform Data System, trends in health information technology adoption among health centers located within and outside of Beacon communities were explored using differences in mean t tests and multivariate logistic regression. Electronic health record adoption was widespread and rapidly growing in all health centers, especially quality improvement functionalities: structured data capture, order and results management, and clinical decision support. Adoption lagged for functionalities supporting patient engagement, performance measurement, care coordination, and public health. The use of advanced functionalities such as care coordination grew faster in Beacon health centers, and Beacon health centers had 1.7 times higher odds of adopting health records with basic safety and quality functionalities in 2010-2012. Three factors likely underlie these findings: technical assistance, community-wide activation supporting health information exchange, and the layering of financial incentives. Additional technical assistance and community-wide activation is needed to support the use of functionalities that are currently lagging. © Copyright 2015 by the American Board of Family Medicine.

  1. Quantitative Molecular Imaging with a Single Gd-Based Contrast Agent Reveals Specific Tumor Binding and Retention in Vivo.

    Science.gov (United States)

    Johansen, Mette L; Gao, Ying; Hutnick, Melanie A; Craig, Sonya E L; Pokorski, Jonathan K; Flask, Chris A; Brady-Kalnay, Susann M

    2017-06-06

    Magnetic resonance imaging (MRI) has become an indispensable tool in the diagnosis and treatment of many diseases, especially cancer. However, the poor sensitivity of MRI relative to other imaging modalities, such as PET, has hindered the development and clinical use of molecular MRI contrast agents that could provide vital diagnostic information by specifically locating a molecular target altered in the disease process. This work describes the specific and sustained in vivo binding and retention of a protein tyrosine phosphatase mu (PTPμ)-targeted, molecular magnetic resonance (MR) contrast agent with a single gadolinium (Gd) chelate using a quantitative MRI T 1 mapping technique in glioma xenografts. Quantitative T 1 mapping is an imaging method used to measure the longitudinal relaxation time, the T 1 relaxation time, of protons in a magnetic field after excitation by a radiofrequency pulse. T 1 relaxation times can in turn be used to calculate the concentration of a gadolinium-containing contrast agent in a region of interest, thereby allowing the retention or clearance of an agent to be quantified. In this context, retention is a measure of molecular contrast agent binding. Using conventional peptide chemistry, a PTPμ-targeted peptide was linked to a chelator that had been conjugated to a lysine residue. Following complexation with Gd, this PTPμ-targeted molecular contrast agent containing a single Gd ion showed significant tumor enhancement and a sustained increase in Gd concentration in both heterotopic and orthotopic tumors using dynamic quantitative MRI. This single Gd-containing PTPμ agent was more effective than our previous version with three Gd ions. Differences between nonspecific and specific agents, due to specific tumor binding, can be determined within the first 30 min after agent administration by examining clearance rates. This more facile chemistry, when combined with quantitative MR techniques, allows for widespread adoption by academic

  2. Evaluation of molecular markers for Phytophthora ramorum detection and identification: Testing for specificity using a standardized library of isolates

    Science.gov (United States)

    F.N. Martin; M.D. Coffey; K. Zeller; R.C. Hamelin; P. Tooley; M. Garbelotto; K.J.D. Hughes; T. Kubisiak; G.J. Bilodeau; L. Levy; C. Blomquist; P.H. Berger

    2009-01-01

    Given the importance of Phytophthora ramorum from a regulatory standpoint, it is imperative that molecular markers for pathogen detection are fully tested to evaluate their specificity in detection of the pathogen. In an effort to evaluate 11 reported diagnostic techniques, we assembled a standardized DNA library using accessions from the World...

  3. Lipidomic Adaptations in White and Brown Adipose Tissue in Response to Exercise Demonstrate Molecular Species-Specific Remodeling

    Directory of Open Access Journals (Sweden)

    Francis J. May

    2017-02-01

    Full Text Available Exercise improves whole-body metabolic health through adaptations to various tissues, including adipose tissue, but the effects of exercise training on the lipidome of white adipose tissue (WAT and brown adipose tissue (BAT are unknown. Here, we utilize MS/MSALL shotgun lipidomics to determine the molecular signatures of exercise-induced adaptations to subcutaneous WAT (scWAT and BAT. Three weeks of exercise training decrease specific molecular species of phosphatidic acid (PA, phosphatidylcholines (PC, phosphatidylethanolamines (PE, and phosphatidylserines (PS in scWAT and increase specific molecular species of PC and PE in BAT. Exercise also decreases most triacylglycerols (TAGs in scWAT and BAT. In summary, exercise-induced changes to the scWAT and BAT lipidome are highly specific to certain molecular lipid species, indicating that changes in tissue lipid content reflect selective remodeling in scWAT and BAT of both phospholipids and glycerol lipids in response to exercise training, thus providing a comprehensive resource for future studies of lipid metabolism pathways.

  4. Development of Thinopyrum ponticum-specific molecular markers and FISH probes based on SLAF-seq technology.

    Science.gov (United States)

    Liu, Liqin; Luo, Qiaoling; Teng, Wan; Li, Bin; Li, Hongwei; Li, Yiwen; Li, Zhensheng; Zheng, Qi

    2018-05-01

    Based on SLAF-seq, 67 Thinopyrum ponticum-specific markers and eight Th. ponticum-specific FISH probes were developed, and these markers and probes could be used for detection of alien chromatin in a wheat background. Decaploid Thinopyrum ponticum (2n = 10x = 70) is a valuable gene reservoir for wheat improvement. Identification of Th. ponticum introgression would facilitate its transfer into diverse wheat genetic backgrounds and its practical utilization in wheat improvement. Based on specific-locus-amplified fragment sequencing (SLAF-seq) technology, 67 new Th. ponticum-specific molecular markers and eight Th. ponticum-specific fluorescence in situ hybridization (FISH) probes have been developed from a tiny wheat-Th. ponticum translocation line. These newly developed molecular markers allowed the detection of Th. ponticum DNA in a variety of materials specifically and steadily at high throughput. According to the hybridization signal pattern, the eight Th. ponticum-specific probes could be divided into two groups. The first group including five dispersed repetitive sequence probes could identify Th. ponticum chromatin more sensitively and accurately than genomic in situ hybridization (GISH). Whereas the second group having three tandem repetitive sequence probes enabled the discrimination of Th. ponticum chromosomes together with another clone pAs1 in wheat-Th. ponticum partial amphiploid Xiaoyan 68.

  5. Suitability and use of two molecular markers to track race-specific ...

    African Journals Online (AJOL)

    Molecular markers linked to resistance to different races of S. gesneriodes have been identified. It was desirable to demonstrate the applicability and efficiency for use in ... The two marker data set were significantly correlated with the phenotypic data (r=0.95). Based on the tight linkage with the resistant locus, 61RM2 was ...

  6. Interlaboratory variation in the detection of HPA-specific alloantibodies and in molecular HPA typing

    NARCIS (Netherlands)

    Allen, D.; Ouwehand, W. H.; de Haas, M.; Kekomaki, R.; Kaplan, C.; Metcalfe, P.

    2007-01-01

    Platelet immunology quality assurance exercises have been organized by National Institute for Biological Standards and Control since 1991 and, as of 2006, 35 laboratories participate in the serology section. Molecular human platelet antigen (HPA) typing has been included in the exercises since 1998

  7. Source-specific sewage pollution detection in urban river waters using pharmaceuticals and personal care products as molecular indicators.

    Science.gov (United States)

    Kiguchi, Osamu; Sato, Go; Kobayashi, Takashi

    2016-11-01

    Source-specific elucidation of domestic sewage pollution caused by various effluent sources in an urban river water, as conducted for this study, demands knowledge of the relation between concentrations of pharmaceuticals and personal care products (PPCPs) as molecular indicators (caffeine, carbamazepine, triclosan) and water quality concentrations of total nitrogen (T-N) and total phosphorous (T-P). River water and wastewater samples from the Asahikawa River Basin in northern Japan were analyzed using derivatization-gas chromatography/mass spectrometry. Caffeine, used as an indicator of domestic sewage in the Asahikawa River Basin, was more ubiquitous than either carbamazepine or triclosan (92-100 %). Its concentration was higher than any target compound used to assess the basin: caffeine, caffeine concentrations detected in wastewater effluents and the strongly positive mutual linear correlation between caffeine and T-N or T-P (R 2  > 0.759) reflect the contribution of septic tank system effluents to the lower Asahikawa River Basin. Results of relative molecular indicators in combination with different molecular indicators (caffeine/carbamazepine and triclosan/carbamazepine) and cluster analysis better reflect the contribution of sewage than results obtained using concentrations of respective molecular indicators and cluster analysis. Relative molecular indicators used with water quality parameters (e.g., caffeine/T-N ratio) in this study provide results more clearly, relatively, and quantitatively than results obtained using molecular indicators alone. Moreover, the caffeine/T-N ratio reflects variations of caffeine flux from effluent sources. These results suggest strongly relative molecular indicators are also useful indicators, reflecting differences in spatial contributions of domestic sources for PPCPs in urban areas.

  8. Molecular property diagnostic suite (MPDS): Development of disease-specific open source web portals for drug discovery.

    Science.gov (United States)

    Nagamani, S; Gaur, A S; Tanneeru, K; Muneeswaran, G; Madugula, S S; Consortium, Mpds; Druzhilovskiy, D; Poroikov, V V; Sastry, G N

    2017-11-01

    Molecular property diagnostic suite (MPDS) is a Galaxy-based open source drug discovery and development platform. MPDS web portals are designed for several diseases, such as tuberculosis, diabetes mellitus, and other metabolic disorders, specifically aimed to evaluate and estimate the drug-likeness of a given molecule. MPDS consists of three modules, namely data libraries, data processing, and data analysis tools which are configured and interconnected to assist drug discovery for specific diseases. The data library module encompasses vast information on chemical space, wherein the MPDS compound library comprises 110.31 million unique molecules generated from public domain databases. Every molecule is assigned with a unique ID and card, which provides complete information for the molecule. Some of the modules in the MPDS are specific to the diseases, while others are non-specific. Importantly, a suitably altered protocol can be effectively generated for another disease-specific MPDS web portal by modifying some of the modules. Thus, the MPDS suite of web portals shows great promise to emerge as disease-specific portals of great value, integrating chemoinformatics, bioinformatics, molecular modelling, and structure- and analogue-based drug discovery approaches.

  9. Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements

    Science.gov (United States)

    McJimpsey, Erica L.

    2016-01-01

    The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves. PMID:26911983

  10. Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements

    Science.gov (United States)

    McJimpsey, Erica L.

    2016-02-01

    The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves.

  11. Detailed Source-Specific Molecular Composition of Ambient Aerosol Organic Matter Using Ultrahigh Resolution Mass Spectrometry and 1H NMR

    Directory of Open Access Journals (Sweden)

    Amanda S. Willoughby

    2016-06-01

    Full Text Available Organic aerosols (OA are universally regarded as an important component of the atmosphere that have far-ranging impacts on climate forcing and human health. Many of these impacts are related to OA molecular characteristics. Despite the acknowledged importance, current uncertainties related to the source apportionment of molecular properties and environmental impacts make it difficult to confidently predict the net impacts of OA. Here we evaluate the specific molecular compounds as well as bulk structural properties of total suspended particulates in ambient OA collected from key emission sources (marine, biomass burning, and urban using ultrahigh resolution mass spectrometry (UHR-MS and proton nuclear magnetic resonance spectroscopy (1H NMR. UHR-MS and 1H NMR show that OA within each source is structurally diverse, and the molecular characteristics are described in detail. Principal component analysis (PCA revealed that (1 aromatic nitrogen species are distinguishing components for these biomass burning aerosols; (2 these urban aerosols are distinguished by having formulas with high O/C ratios and lesser aromatic and condensed aromatic formulas; and (3 these marine aerosols are distinguished by lipid-like compounds of likely marine biological origin. This study provides a unique qualitative approach for enhancing the chemical characterization of OA necessary for molecular source apportionment.

  12. Modified beacon probe assisted dual signal amplification for visual detection of microRNA.

    Science.gov (United States)

    Sun, Xiuwei; Ying, Na; Ju, Chuanjing; Li, Zhongyi; Xu, Na; Qu, Guijuan; Liu, Wensen; Wan, Jiayu

    2018-04-21

    In a recent study, we reported a novel assay for the detection of microRNA-21 based on duplex-specific nuclease (DSN)-assisted isothermal cleavage and hybridization chain reaction (HCR) dual signal amplification. The Fam modified double-stranded DNA products were generated after the HCR, another biotin modified probe was digested by DSN and released from the magnetic beads after the addition of the target miRNA. The released sequence was then combined with HCR products to form a double-tagging dsDNA, which can be recognized by the lateral flow strips. In this study, we introduced a 2-OMethyl-RNA modified beacon probe (2-OMe-MB) to make some improvements based on the previous study. Firstly, the substitution of modified probe combined on magnetic beads avoids the fussy washing steps for the separation of un-reacted probes. Furthermore, the modification of 2-OMe on the stem of the probe avoided the unnecessary cleavage by DSN, which greatly reduce the background signal. Compared to the previous work, these improvements save us a lot of steps but possess the comparable sensitivity and selectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Practical Fingerprinting Localization for Indoor Positioning System by Using Beacons

    Directory of Open Access Journals (Sweden)

    Santosh Subedi

    2017-01-01

    Full Text Available Recent developments in the fields of smartphones and wireless communication technologies such as beacons, Wi-Fi, and ultra-wideband have made it possible to realize indoor positioning system (IPS with a few meters of accuracy. In this paper, an improvement over traditional fingerprinting localization is proposed by combining it with weighted centroid localization (WCL. The proposed localization method reduces the total number of fingerprint reference points over the localization space, thus minimizing both the time required for reading radio frequency signals and the number of reference points needed during the fingerprinting learning process, which eventually makes the process less time-consuming. The proposed positioning has two major steps of operation. In the first step, we have realized fingerprinting that utilizes lightly populated reference points (RPs and WCL individually. Using the location estimated at the first step, WCL is run again for the final location estimation. The proposed localization technique reduces the number of required fingerprint RPs by more than 40% compared to normal fingerprinting localization method with a similar localization estimation error.

  14. Species detection using HyBeacon(®) probe technology: Working towards rapid onsite testing in non-human forensic and food authentication applications.

    Science.gov (United States)

    Dawnay, Nick; Hughes, Rebecca; Court, Denise Syndercombe; Duxbury, Nicola

    2016-01-01

    Identifying individual species or determining species' composition in an unknown sample is important for a variety of forensic applications. Food authentication, monitoring illegal trade in endangered species, forensic entomology, sexual assault case work and counter terrorism are just some of the fields that can require the detection of the biological species present. Traditional laboratory based approaches employ a wide variety of tools and technologies and exploit a number of different species specific traits including morphology, molecular differences and immuno-chemical analyses. A large number of these approaches require laboratory based apparatus and results can take a number of days to be returned to investigating authorities. Having a presumptive test for rapid identification could lead to savings in terms of cost and time and allow sample prioritisation if confirmatory testing in a laboratory is required later. This model study describes the development of an assay using a single HyBeacon(®) probe and melt curve analyses allowing rapid screening and authentication of food products labelled as Atlantic cod (Gadus morhua). Exploiting melt curve detection of species specific SNP sites on the COI gene the test allows detection of a target species (Atlantic cod) and closely related species which may be used as substitutes. The assay has been designed for use with the Field Portable ParaDNA system, a molecular detection platform for non-expert users. The entire process from sampling to result takes approximately 75min. Validation studies were performed on both single source genomic DNA, mixed genomic DNA and commercial samples. Data suggests the assay has a lower limit of detection of 31 pg DNA. The specificity of the assay to Atlantic cod was measured by testing highly processed food samples including frozen, defrosted and cooked fish fillets as well as fish fingers, battered fish fillet and fish pie. Ninety-six (92.7%) of all Atlantic cod food products

  15. Accurate beacon positioning method for satellite-to-ground optical communication.

    Science.gov (United States)

    Wang, Qiang; Tong, Ling; Yu, Siyuan; Tan, Liying; Ma, Jing

    2017-12-11

    In satellite laser communication systems, accurate positioning of the beacon is essential for establishing a steady laser communication link. For satellite-to-ground optical communication, the main influencing factors on the acquisition of the beacon are background noise and atmospheric turbulence. In this paper, we consider the influence of background noise and atmospheric turbulence on the beacon in satellite-to-ground optical communication, and propose a new locating algorithm for the beacon, which takes the correlation coefficient obtained by curve fitting for image data as weights. By performing a long distance laser communication experiment (11.16 km), we verified the feasibility of this method. Both simulation and experiment showed that the new algorithm can accurately obtain the position of the centroid of beacon. Furthermore, for the distortion of the light spot through atmospheric turbulence, the locating accuracy of the new algorithm was 50% higher than that of the conventional gray centroid algorithm. This new approach will be beneficial for the design of satellite-to ground optical communication systems.

  16. A spiral wave front beacon for underwater navigation: transducer prototypes and testing.

    Science.gov (United States)

    Dzikowicz, Benjamin R; Hefner, Brian T

    2012-05-01

    Transducers for acoustic beacons which can produce outgoing signals with wave fronts whose horizontal cross sections are circular or spiral are studied experimentally. A remote hydrophone is used to determine its aspect relative to the transducers by comparing the phase of the circular signal to the phase of the spiral signal. The transducers for a "physical-spiral" beacon are made by forming a strip of 1-3 piezocomposite transducer material around either a circular or spiral backing. A "phased-spiral" beacon is made from an array of transducer elements which can be driven either in phase or staggered out of phase so as to produce signals with either a circular or spiral wave front. Measurements are made to study outgoing signals and their usefulness in determining aspect angle. Vertical beam width is also examined and phase corrections applied when the hydrophone is out of the horizontal plane of the beacon. While numerical simulations indicate that the discontinuity in the physical-spiral beacon introduces errors into the measured phase, damping observed at the ends of the piezocomposite material is a more significant source of error. This damping is also reflected in laser Doppler vibrometer measurements of the transducer's surface velocity.

  17. Adaptive Beaconing in Mobility Aware Clustering Based MAC Protocol for Safety Message Dissemination in VANET

    Directory of Open Access Journals (Sweden)

    Nishu Gupta

    2017-01-01

    Full Text Available Majority of research contributions in wireless access in vehicular environment (WAVE/IEEE 802.11p standard focus on life critical safety-related applications. These applications require regular status update of vehicle’s position referred to as beaconing. Periodic beaconing in vehicle to vehicle communication leads to severe network congestion in the communication channel. The condition worsens under high vehicular density where it impacts reliability and upper bound latency of safety messages. In this paper, WAVE compliant enhancement to the existing IEEE 802.11p protocol is presented which targets prioritized delivery of safety messages while simultaneously provisioning the dissemination of nonsafety messages. Proposed scheme relies on dynamic generation of beacons to mitigate channel congestion and inefficient bandwidth utilization by reducing transmission frequency of beacons. Through the use of clustering mechanism, different beaconing frequencies and different data transmission rates are assigned to prioritize vehicular mobility. Through extensive simulation results, the performance of the proposed approach is evaluated in terms of a wide range of quality of service (QoS parameters for two different transmission ranges. Results show that the proposed protocol provides significant enhancement and stability of the clustered topology in vehicular ad hoc network over existing standard and other protocols with similar applications.

  18. Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

    Science.gov (United States)

    San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

    2014-12-01

    Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

  19. First-in-Human Ultrasound Molecular Imaging With a VEGFR2-Specific Ultrasound Molecular Contrast Agent (BR55) in Prostate Cancer: A Safety and Feasibility Pilot Study.

    Science.gov (United States)

    Smeenge, Martijn; Tranquart, François; Mannaerts, Christophe K; de Reijke, Theo M; van de Vijver, Marc J; Laguna, M Pilar; Pochon, Sibylle; de la Rosette, Jean J M C H; Wijkstra, Hessel

    2017-07-01

    BR55, a vascular endothelial growth factor receptor 2 (VEGFR2)-specific ultrasound molecular contrast agent (MCA), has shown promising results in multiple preclinical models regarding cancer imaging. In this first-in-human, phase 0, exploratory study, we investigated the feasibility and safety of the MCA for the detection of prostate cancer (PCa) in men using clinical standard technology. Imaging with the MCA was performed in 24 patients with biopsy-proven PCa scheduled for radical prostatectomy using a clinical ultrasound scanner at low acoustic power. Safety monitoring was done by physical examination, blood pressure and heart rate measurements, electrocardiogram, and blood sampling. As first-in-human study, MCA dosing and imaging protocol were necessarily fine-tuned along the enrollment to improve visualization. Imaging data were correlated with radical prostatectomy histopathology to analyze the detection rate of ultrasound molecular imaging with the MCA. Imaging with MCA doses of 0.03 and 0.05 mL/kg was adequate to obtain contrast enhancement images up to 30 minutes after administration. No serious adverse events or clinically meaningful changes in safety monitoring data were identified during or after administration. BR55 dosing and imaging were fine-tuned in the first 12 patients leading to 12 subsequent patients with an improved MCA dosing and imaging protocol. Twenty-three patients underwent radical prostatectomy. A total of 52 lesions were determined to be malignant by histopathology with 26 (50%) of them seen during BR55 imaging. In the 11 patients that were scanned with the improved protocol and underwent radical prostatectomy, a total of 28 malignant lesions were determined: 19 (68%) were seen during BR55 ultrasound molecular imaging, whereas 9 (32%) were not identified. Ultrasound molecular imaging with BR55 is feasible with clinical standard technology and demonstrated a good safety profile. Detectable levels of the MCA can be reached in patients

  20. A Measurement Study of BLE iBeacon and Geometric Adjustment Scheme for Indoor Location-Based Mobile Applications

    Directory of Open Access Journals (Sweden)

    Jeongyeup Paek

    2016-01-01

    Full Text Available Bluetooth Low Energy (BLE and the iBeacons have recently gained large interest for enabling various proximity-based application services. Given the ubiquitously deployed nature of Bluetooth devices including mobile smartphones, using BLE and iBeacon technologies seemed to be a promising future to come. This work started off with the belief that this was true: iBeacons could provide us with the accuracy in proximity and distance estimation to enable and simplify the development of many previously difficult applications. However, our empirical studies with three different iBeacon devices from various vendors and two types of smartphone platforms prove that this is not the case. Signal strength readings vary significantly over different iBeacon vendors, mobile platforms, environmental or deployment factors, and usage scenarios. This variability in signal strength naturally complicates the process of extracting an accurate location/proximity estimation in real environments. Our lessons on the limitations of iBeacon technique lead us to design a simple class attendance checking application by performing a simple form of geometric adjustments to compensate for the natural variations in beacon signal strength readings. We believe that the negative observations made in this work can provide future researchers with a reference on how well of a performance to expect from iBeacon devices as they enter their system design phases.

  1. atpE gene as a new useful specific molecular target to quantify Mycobacterium in environmental samples

    Science.gov (United States)

    2013-01-01

    Background The environment is the likely source of many pathogenic mycobacterial species but detection of mycobacteria by bacteriological tools is generally difficult and time-consuming. Consequently, several molecular targets based on the sequences of housekeeping genes, non-functional RNA and structural ribosomal RNAs have been proposed for the detection and identification of mycobacteria in clinical or environmental samples. While certain of these targets were proposed as specific for this genus, most are prone to false positive results in complex environmental samples that include related, but distinct, bacterial genera. Nowadays the increased number of sequenced genomes and the availability of software for genomic comparison provide tools to develop novel, mycobacteria-specific targets, and the associated molecular probes and primers. Consequently, we conducted an in silico search for proteins exclusive to Mycobacterium spp. genomes in order to design sensitive and specific molecular targets. Results Among the 3989 predicted proteins from M. tuberculosis H37Rv, only 11 proteins showed 80% to 100% of similarity with Mycobacterium spp. genomes, and less than 50% of similarity with genomes of closely related Corynebacterium, Nocardia and Rhodococcus genera. Based on DNA sequence alignments, we designed primer pairs and a probe that specifically detect the atpE gene of mycobacteria, as verified by quantitative real-time PCR on a collection of mycobacteria and non-mycobacterial species. The real-time PCR method we developed was successfully used to detect mycobacteria in tap water and lake samples. Conclusions The results indicate that this real-time PCR method targeting the atpE gene can serve for highly specific detection and precise quantification of Mycobacterium spp. in environmental samples. PMID:24299240

  2. Efficient Beacon Collision Resolution Procedure for IEEE 802.15.4 /Zigbee Wireless Personal Area Networks

    Directory of Open Access Journals (Sweden)

    Bassam A. Zafar

    2017-04-01

    Full Text Available While IEEE 802.15.4/Zigbee is a promising technology for Wireless Personal Area Networks, several transmission problems are not yet resolved. In particular, the problem of beacon transmission interferences is causing the device connection loss to the network. In order to resolve this problem, we present a new distributed and reactive procedure for beacon collision resolution. It is an extension of the alignment procedure to reorganize randomly the beacon transmission time when a collision has occurred. The detail of the proposed procedure will be fully described and analyzed. The performance of our approach is performed by simulations. The results show that our approach reduces the collision probability and the device disconnections consequently.

  3. A beacon interval shifting scheme for interference mitigation in body area networks.

    Science.gov (United States)

    Kim, Seungku; Kim, Seokhwan; Kim, Jin-Woo; Eom, Doo-Seop

    2012-01-01

    This paper investigates the issue of interference avoidance in body area networks (BANs). IEEE 802.15 Task Group 6 presented several schemes to reduce such interference, but these schemes are still not proper solutions for BANs. We present a novel distributed TDMA-based beacon interval shifting scheme that reduces interference in the BANs. A design goal of the scheme is to avoid the wakeup period of each BAN coinciding with other networks by employing carrier sensing before a beacon transmission. We analyze the beacon interval shifting scheme and investigate the proper back-off length when the channel is busy. We compare the performance of the proposed scheme with the schemes presented in IEEE 802.15 Task Group 6 using an OMNeT++ simulation. The simulation results show that the proposed scheme has a lower packet loss, energy consumption, and delivery-latency than the schemes of IEEE 802.15 Task Group 6.

  4. Development of satellite position location system for aircraft and boat distress beacons

    Science.gov (United States)

    Kahle, D. R.

    1982-01-01

    An international satellite system for the detection and location of distress beacons carried on aircraft and vessels is in its technical checkout phase. User demonstration and evaluation (D&E) will start in early 1983 and continue for two years. The D&E phase and a subsequent transition period will form the basis for improved search and rescue operations for the 1980's and beyond. The system, called COSPAS/SARSAT, has international participation involving the U.S., Canada, and France as SARSAT members and joint participation with the Soviet Union's COSPAS Project. Norway and the U.K. have recently joined as investigators. Average position location error of the satellite aided processing is expected to be from 10-20KM for the existing 121.5/243 MHz distress beacons and from 2-5KM for experimental beacons transmitting in the 406 MHz band.

  5. High hydrostatic pressure specifically affects molecular dynamics and shape of low-density lipoprotein particles

    Science.gov (United States)

    Golub, M.; Lehofer, B.; Martinez, N.; Ollivier, J.; Kohlbrecher, J.; Prassl, R.; Peters, J.

    2017-04-01

    Lipid composition of human low-density lipoprotein (LDL) and its physicochemical characteristics are relevant for proper functioning of lipid transport in the blood circulation. To explore dynamical and structural features of LDL particles with either a normal or a triglyceride-rich lipid composition we combined coherent and incoherent neutron scattering methods. The investigations were carried out under high hydrostatic pressure (HHP), which is a versatile tool to study the physicochemical behavior of biomolecules in solution at a molecular level. Within both neutron techniques we applied HHP to probe the shape and degree of freedom of the possible motions (within the time windows of 15 and 100 ps) and consequently the flexibility of LDL particles. We found that HHP does not change the types of motion in LDL, but influences the portion of motions participating. Contrary to our assumption that lipoprotein particles, like membranes, are highly sensitive to pressure we determined that LDL copes surprisingly well with high pressure conditions, although the lipid composition, particularly the triglyceride content of the particles, impacts the molecular dynamics and shape arrangement of LDL under pressure.

  6. Molecular dynamics of conformation-specific dopamine transporter-inhibitor complexes.

    Science.gov (United States)

    Jean, Bernandie; Surratt, Christopher K; Madura, Jeffry D

    2017-09-01

    The recreational psychostimulant cocaine inhibits dopamine reuptake from the synapse, resulting in excessive stimulation of postsynaptic dopamine receptors in brain areas associated with reward and addiction. Cocaine binds to and stabilizes the outward- (extracellular-) facing conformation of the dopamine transporter (DAT) protein, while the low abuse potential DAT inhibitor benztropine prefers the inward- (cytoplasmic-) facing conformation. A correlation has been previously postulated between psychostimulant abuse potential and preference for the outward-facing DAT conformation. The 3β-aryltropane cocaine analogs LX10 and LX11, however, differ only in stereochemistry and share a preference for the outward-facing DAT, yet are reported to vary widely in abuse potential in an animal model. In search of the molecular basis for DAT conformation preference, complexes of cocaine, benztropine, LX10 or LX11 bound to each DAT conformation were subjected to 100ns of all-atom molecular dynamics simulation. Results were consistent with previous findings from cysteine accessibility assays used to assess an inhibitor's DAT conformation preference. The respective 2β- and 2α-substituted phenyltropanes of LX10 and LX11 interacted with hydrophobic regions of the DAT S1 binding site that were inaccessible to cocaine. Solvent accessibility measurements also revealed subtle differences in inhibitor positioning within a given DAT conformation. This work serves to advance our understanding of the conformational selectivity of DAT inhibitors and suggests that MD may be useful in antipsychostimulant therapeutic design. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Synthesis and Surface-Specific Analysis of Molecular Constituents Relevant to Biogenic Secondary Organic Aerosol Material

    Science.gov (United States)

    Be, A. G.; Upshur, M. A.; Chase, H. M.; Geiger, F.; Thomson, R. J.

    2017-12-01

    Secondary organic aerosol (SOA) particles formed from the oxidation of biogenic volatile organic compounds (BVOCs) remain a principal, yet elusive, class of airborne particulate matter that impacts the Earth's radiation budget. Given the characteristic molecular complexity comprising biogenic SOA particles, chemical information selective to the gas-aerosol interface may be valuable in the investigation of such systems, as surface considerations likely dictate the phenomena driving particle evolution mechanisms and climate effects. In particular, cloud activation processes may be parameterized using the surface tension depression that coincides with partitioning of surface-active organic species to the gas-droplet interface. However, the extent to which surface chemical processes, such as cloud droplet condensation, are influenced by the chemical structure and reactivity of individual surface-active molecules in SOA particles is largely unknown. We seek to study terpene-derived organic species relevant to the surfaces of biogenic SOA particles via synthesis of putative oxidation products followed by analysis using surface-selective physicochemical measurements. Using dynamic surface tension measurements, considerable differences are observed in the surface tension depression of aqueous pendant droplets that contain synthetically prepared ozonolysis products derived from abundant terpene precursors. Furthermore, sum frequency generation spectroscopy is utilized for comparison of the surface vibrational spectral responses of synthesized reference compounds with those observed for laboratory aerosol toward probing the surface composition of SOA material. Such ongoing findings highlight the underlying importance of molecular structure and reactivity when considering the surface chemistry of biogenic terpene-derived atmospheric aerosols.

  8. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism

    OpenAIRE

    Parikshak, Neelroop N.; Luo, Rui; Zhang, Alice; Won, Hyejung; Lowe, Jennifer K.; Chandran, Vijayendran; Horvath, Steve; Geschwind, Daniel H.

    2013-01-01

    Genetic studies have identified dozens of autism spectrum disorder (ASD) susceptibility genes, raising two critical questions: 1) do these genetic loci converge on specific biological processes, and 2) where does the phenotypic specificity of ASD arise, given its genetic overlap with intellectual disability (ID)? To address this, we mapped ASD and ID risk genes onto co-expression networks representing developmental trajectories and transcriptional profiles representing fetal and adult cortica...

  9. Development of an aptamer beacon for detection of interferon-gamma.

    Science.gov (United States)

    Tuleuova, Nazgul; Jones, Caroline N; Yan, Jun; Ramanculov, Erlan; Yokobayashi, Yohei; Revzin, Alexander

    2010-03-01

    Traditional antibody-based affinity sensing strategies employ multiple reagents and washing steps and are unsuitable for real-time detection of analyte binding. Aptamers, on the other hand, may be designed to monitor binding events directly, in real-time, without the need for secondary labels. The goal of the present study was to design an aptamer beacon for fluorescence resonance energy transfer (FRET)-based detection of interferon-gamma (IFN-gamma)--an important inflammatory cytokine. Variants of DNA aptamer modified with biotin moieties and spacers were immobilized on avidin-coated surfaces and characterized by surface plasmon resonance (SPR). The SPR studies showed that immobilization of aptamer via the 3' end resulted in the best binding IFN-gamma (K(d) = 3.44 nM). This optimal aptamer variant was then used to construct a beacon by hybridizing fluorophore-labeled aptamer with an antisense oligonucleotide strand carrying a quencher. SPR studies revealed that IFN-gamma binding with an aptamer beacon occurred within 15 min of analyte introduction--suggesting dynamic replacement of the quencher-complementary strand by IFN-gamma molecules. To further highlight biosensing applications, aptamer beacon molecules were immobilized inside microfluidic channels and challenged with varying concentration of analyte. Fluorescence microscopy revealed low fluorescence in the absence of analyte and high fluorescence after introduction of IFN-gamma. Importantly, unlike traditional antibody-based immunoassays, the signal was observed directly upon binding of analyte without the need for multiple washing steps. The surface immobilized aptamer beacon had a linear range from 5 to 100 nM and a lower limit of detection of 5 nM IFN-gamma. In conclusion, we designed a FRET-based aptamer beacon for monitoring of an inflammatory cytokine-IFN-gamma. In the future, this biosensing strategy will be employed to monitor dynamics of cytokine production by the immune cells.

  10. Results from the northern New Mexico satellite-beacon radio interferometer

    International Nuclear Information System (INIS)

    Carlos, R.; Jacobson, A.; Massey, R.; Wu, G.

    1994-01-01

    An interferometer described in the Boston, 1992, meeting of the Beacon Satellite Symposium has been in full operation for over a year now. It consists of four autonomous stations; three are in a triangle 70 km on a side and one is in the center. The stations receive the VHF beacons from two geosynchronous satellites, GOES-2 and ATS-3. The phases of the beacons are tracked at each station by referring them to an extremely stable rubidium oscillator. The studies of the two satellites are virtually separate experiments. The received phase of the beacon is retarded by the increased Total-Electron-Content of the dense regions of waves in the ionosphere. By comparing the phase history at four spatially separated stations, the authors can determine the two-dimensional propagation vector of the waves. This array is optimal for wavelengths of 70--300 km (periods of 300--3,000 seconds). Since the measurement is of the phase of the signal rather than the difference between the O-mode and X-mode phases, and since the beacons are in the VHF rather than in the L-band of GPS beacons, the array is very sensitive. It has a noise level of 10 13 electrons/m 2 , or 10 -4 of the normal daytime TEC. This has been verified by operating two stations in the same location, so that they saw the same ionosphere. The first interesting results from a year's study is that the authors do not see the same TID's when looking at the two satellites. One conclusion they draw is that they do not see evidence of ionospheric winds

  11. Time-Resolved Nucleic Acid Hybridization Beacons Utilizing Unimolecular and Toehold-Mediated Strand Displacement Designs.

    Science.gov (United States)

    Massey, Melissa; Ancona, Mario G; Medintz, Igor L; Algar, W Russ

    2015-12-01

    Nucleic acid hybridization probes are sought after for numerous assay and imaging applications. These probes are often limited by the properties of fluorescent dyes, prompting the development of new probes where dyes are paired with novel or nontraditional luminescent materials. Luminescent terbium complexes are an example of such a material, and these complexes offer several unique spectroscopic advantages. Here, we demonstrate two nonstem-loop designs for light-up nucleic acid hybridization beacons that utilize time-resolved Förster resonance energy transfer (TR-FRET) between a luminescent Lumi4-Tb cryptate (Tb) donor and a fluorescent reporter dye, where time-resolved emission from the dye provides an analytical signal. Both designs are based on probe oligonucleotides that are labeled at their opposite termini with Tb and a fluorescent reporter dye. In one design, a probe is partially blocked with a quencher dye-labeled oligonucleotide, and target hybridization is signaled through toehold-mediated strand displacement and loss of a competitive FRET pathway. In the other design, the intrinsic folding properties of an unblocked probe are utilized in combination with a temporal mechanism for signaling target hybridization. This temporal mechanism is based on a recently elucidated "sweet spot" for TR-FRET measurements and exploits distance control over FRET efficiencies to shift the Tb lifetime within or outside the time-gated detection window for measurements. Both the blocked and unblocked beacons offer nanomolar (femtomole) detection limits, response times on the order of minutes, multiplexing through the use of different reporter dyes, and detection in complex matrices such as serum and blood. The blocked beacons offer better mismatch selectivity, whereas the unblocked beacons are simpler in design. The temporal mechanism of signaling utilized with the unblocked beacons also plays a significant role with the blocked beacons and represents a new and effective

  12. Experience and evaluation of advanced on-line core monitoring system 'BEACON' at IKATA site

    International Nuclear Information System (INIS)

    Fujitsuka, Nobumichi; Tanouchi, Hideyuki; Imamura, Yasuhiro; Mizobuchil, Daisuke

    1997-01-01

    Shikoku Electric Power Company installed BEACON core monitoring system into IKATA unit 3 in May 1994. During its first cycle of core operation, various operational data were obtained including data of some anomalous reactor conditions introduced for the test objective of the plant start-up. This paper presents the evaluation of the BEACON system capability based on this experience. The system functions such as core monitoring and anomaly detection, prediction of future reactor conditions and increased efficiency of core management activities are discussed. Our future plan to utilize the system is also presented. (authors)

  13. Code Development and Analysis Program: developmental checkout of the BEACON/MOD2A code

    International Nuclear Information System (INIS)

    Ramsthaler, J.A.; Lime, J.F.; Sahota, M.S.

    1978-12-01

    A best-estimate transient containment code, BEACON, is being developed by EG and G Idaho, Inc. for the Nuclear Regulatory Commission's reactor safety research program. This is an advanced, two-dimensional fluid flow code designed to predict temperatures and pressures in a dry PWR containment during a hypothetical loss-of-coolant accident. The most recent version of the code, MOD2A, is presently in the final stages of production prior to being released to the National Energy Software Center. As part of the final code checkout, seven sample problems were selected to be run with BEACON/MOD2A

  14. Optimal placement of range-only beacons for mobile robot localisation

    CSIR Research Space (South Africa)

    Burke, Michael G

    2011-11-01

    Full Text Available of the Euclidean distance between the position estimate (x; y; z) and the largest orthogo- nal standard deviations in 3D space, and is an improvement on the GDOP metric as it considers both off-diagonal covariance terms and individual beacon noise. The beacon... is the Euclidean distance between an accessed node and a goal. This results in the shortest route to a goal being determined. The cost of traversing to a node is typically the distance between nodes. However, by replacing this cost with the uncertainty metric...

  15. Alignment independent 3D-QSAR, quantum calculations and molecular docking of Mer specific tyrosine kinase inhibitors as anticancer drugs.

    Science.gov (United States)

    Shiri, Fereshteh; Pirhadi, Somayeh; Ghasemi, Jahan B

    2016-03-01

    Mer receptor tyrosine kinase is a promising novel cancer therapeutic target in many human cancers, because abnormal activation of Mer has been implicated in survival signaling and chemoresistance. 3D-QSAR analyses based on alignment independent descriptors were performed on a series of 81 Mer specific tyrosine kinase inhibitors. The fractional factorial design (FFD) and the enhanced replacement method (ERM) were applied and tested as variable selection algorithms for the selection of optimal subsets of molecular descriptors from a much greater pool of such regression variables. The data set was split into 65 molecules as the training set and 16 compounds as the test set. All descriptors were generated by using the GRid INdependent descriptors (GRIND) approach. After variable selection, GRIND were correlated with activity values (pIC50) by PLS regression. Of the two applied variable selection methods, ERM had a noticeable improvement on the statistical parameters of PLS model, and yielded a q (2) value of 0.77, an [Formula: see text] of 0.94, and a low RMSEP value of 0.25. The GRIND information contents influencing the affinity on Mer specific tyrosine kinase were also confirmed by docking studies. In a quantum calculation study, the energy difference between HOMO and LUMO (gap) implied the high interaction of the most active molecule in the active site of the protein. In addition, the molecular electrostatic potential energy at DFT level confirmed results obtained from the molecular docking. The identified key features obtained from the molecular modeling, enabled us to design novel kinase inhibitors.

  16. Alignment independent 3D-QSAR, quantum calculations and molecular docking of Mer specific tyrosine kinase inhibitors as anticancer drugs

    Directory of Open Access Journals (Sweden)

    Fereshteh Shiri

    2016-03-01

    Full Text Available Mer receptor tyrosine kinase is a promising novel cancer therapeutic target in many human cancers, because abnormal activation of Mer has been implicated in survival signaling and chemoresistance. 3D-QSAR analyses based on alignment independent descriptors were performed on a series of 81 Mer specific tyrosine kinase inhibitors. The fractional factorial design (FFD and the enhanced replacement method (ERM were applied and tested as variable selection algorithms for the selection of optimal subsets of molecular descriptors from a much greater pool of such regression variables. The data set was split into 65 molecules as the training set and 16 compounds as the test set. All descriptors were generated by using the GRid INdependent descriptors (GRIND approach. After variable selection, GRIND were correlated with activity values (pIC50 by PLS regression. Of the two applied variable selection methods, ERM had a noticeable improvement on the statistical parameters of PLS model, and yielded a q2 value of 0.77, an rpred2 of 0.94, and a low RMSEP value of 0.25. The GRIND information contents influencing the affinity on Mer specific tyrosine kinase were also confirmed by docking studies. In a quantum calculation study, the energy difference between HOMO and LUMO (gap implied the high interaction of the most active molecule in the active site of the protein. In addition, the molecular electrostatic potential energy at DFT level confirmed results obtained from the molecular docking. The identified key features obtained from the molecular modeling, enabled us to design novel kinase inhibitors.

  17. Model-specific selection of molecular targets for heart failure gene therapy

    Science.gov (United States)

    Katz, Michael G.; Fargnoli, Anthony S.; Tomasulo, Catherine E.; Pritchette, Louella A.; Bridges, Charles R.

    2013-01-01

    Heart failure (HF) is a complex multifaceted problem of abnormal ventricular function and structure. In recent years, new information has been accumulated allowing for a more detailed understanding of the cellular and molecular alterations that are the underpinnings of diverse causes of HF, including myocardial ischemia, pressure-overload, volume-overload or intrinsic cardiomyopathy. Modern pharmacological approaches to treat HF have had a significant impact on the course of the disease, although they do not reverse the underlying pathological state of the heart. Therefore gene-based therapy holds a great potential as a targeted treatment for cardiovascular diseases. Here, we survey the relative therapeutic efficacy of genetic modulation of β-adrenergic receptor signaling, Ca2+ handling proteins and angiogenesis in the most common extrinsic models of HF. PMID:21954055

  18. Association between glioma susceptibility loci and tumour pathology defines specific molecular etiologies.

    Science.gov (United States)

    Di Stefano, Anna Luisa; Enciso-Mora, Victor; Marie, Yannick; Desestret, Virginie; Labussière, Marianne; Boisselier, Blandine; Mokhtari, Karima; Idbaih, Ahmed; Hoang-Xuan, Khe; Delattre, Jean-Yves; Houlston, Richard S; Sanson, Marc

    2013-05-01

    Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at 7 loci influencing glioma risk: rs2736100 (TERT), rs11979158 and rs2252586 (EGFR), rs4295627 (CCDC26), rs4977756 (CDKN2A/CDKN2B), rs498872 (PHLDB1), and rs6010620 (RTEL1). We studied the relationship among these 7 glioma-risk SNPs and characteristics of tumors from 1374 patients, including grade, IDH (ie IDH1 or IDH2) mutation, EGFR amplification, CDKN2A-p16-INK4a homozygous deletion, 9p and 10q loss, and 1p-19q codeletion. rs2736100 (TERT) and rs6010620 (RTEL1) risk alleles were associated with high-grade disease, EGFR amplification, CDKN2A-p16-INK4a homozygous deletion, and 9p and 10q deletion; rs4295627 (CCDC26) and rs498872 (PHLDB1) were associated with low-grade disease, IDH mutation, and 1p-19q codeletion. In contrast, rs4977756 (CDKN2A/B), rs11979158 (EGFR), and to a lesser extent, rs2252586 (EGFR) risk alleles were independent of tumor grade and genetic profile. Adjusting for tumor grade showed a significant association between rs2736100 and IDH status (P = .01), 10q loss (P = .02); rs4295627 and 1p-19q codeletion (P = .04), rs498872 and IDH (P = .02), 9p loss (P = .04), and 10q loss (P = .02). Case-control analyses stratified into 4 molecular classes (defined by 1p-19q status, IDH mutation, and EGFR amplification) showed an association of rs4295627 and rs498872 with IDH-mutated gliomas (P RTEL1, CCDC26, and PHLDB1 variants were associated with different genetic profiles that annotate distinct molecular pathways. Our findings provide further insight into the biological basis of glioma etiology.

  19. A molecular assay for sensitive detection of pathogen-specific T-cells.

    Directory of Open Access Journals (Sweden)

    Victoria O Kasprowicz

    Full Text Available Here we describe the development and validation of a highly sensitive assay of antigen-specific IFN-γ production using real time quantitative PCR (qPCR for two reporters--monokine-induced by IFN-γ (MIG and the IFN-γ inducible protein-10 (IP10. We developed and validated the assay and applied it to the detection of CMV, HIV and Mycobacterium tuberculosis (MTB specific responses, in a cohort of HIV co-infected patients. We compared the sensitivity of this assay to that of the ex vivo RD1 (ESAT-6 and CFP-10-specific IFN-γ Elispot assay. We observed a clear quantitative correlation between the two assays (P<0.001. Our assay proved to be a sensitive assay for the detection of MTB-specific T cells, could be performed on whole blood samples of fingerprick (50 uL volumes, and was not affected by HIV-mediated immunosuppression. This assay platform is potentially of utility in diagnosis of infection in this and other clinical settings.

  20. RNA-Seq reveals genotype-specific molecular responses to water deficit in eucalyptus

    Science.gov (United States)

    2011-01-01

    Background In a context of climate change, phenotypic plasticity provides long-lived species, such as trees, with the means to adapt to environmental variations occurring within a single generation. In eucalyptus plantations, water availability is a key factor limiting productivity. However, the molecular mechanisms underlying the adaptation of eucalyptus to water shortage remain unclear. In this study, we compared the molecular responses of two commercial eucalyptus hybrids during the dry season. Both hybrids differ in productivity when grown under water deficit. Results Pyrosequencing of RNA extracted from shoot apices provided extensive transcriptome coverage - a catalog of 129,993 unigenes (49,748 contigs and 80,245 singletons) was generated from 398 million base pairs, or 1.14 million reads. The pyrosequencing data enriched considerably existing Eucalyptus EST collections, adding 36,985 unigenes not previously represented. Digital analysis of read abundance in 14,460 contigs identified 1,280 that were differentially expressed between the two genotypes, 155 contigs showing differential expression between treatments (irrigated vs. non irrigated conditions during the dry season), and 274 contigs with significant genotype-by-treatment interaction. The more productive genotype displayed a larger set of genes responding to water stress. Moreover, stress signal transduction seemed to involve different pathways in the two genotypes, suggesting that water shortage induces distinct cellular stress cascades. Similarly, the response of functional proteins also varied widely between genotypes: the most productive genotype decreased expression of genes related to photosystem, transport and secondary metabolism, whereas genes related to primary metabolism and cell organisation were over-expressed. Conclusions For the most productive genotype, the ability to express a broader set of genes in response to water availability appears to be a key characteristic in the maintenance

  1. Behavior of specific heat and self diffusion coefficient of sodium near transition temperature: a molecular dynamics study

    International Nuclear Information System (INIS)

    Ahmed, N.; Khan, G.

    1990-09-01

    In this report the author used of a very useful technique of simulation and applied it to successfully for determining the various properties of sodium, both in liquid and solid phase near transition point. As a first step the determination of specific heat and diffusion coefficient have been carried out. In liquid state the molecular dynamics (MD) values calculated matched the experimental data. But in solid state the diffusion coefficient obtained were not consistent with the one expected for a solid, rather the values obtained suggested that sodium remained in liquid state even below the melting point. (A.B.)

  2. A Molecular Toolbox to Engineer Site-Specific DNA Replication Perturbation.

    Science.gov (United States)

    Larsen, Nicolai B; Hickson, Ian D; Mankouri, Hocine W

    2018-01-01

    Site-specific arrest of DNA replication is a useful tool for analyzing cellular responses to DNA replication perturbation. The E. coli Tus-Ter replication barrier can be reconstituted in eukaryotic cells as a system to engineer an unscheduled collision between a replication fork and an "alien" impediment to DNA replication. To further develop this system as a versatile tool, we describe a set of reagents and a detailed protocol that can be used to engineer Tus-Ter barriers into any locus in the budding yeast genome. Because the Tus-Ter complex is a bipartite system with intrinsic DNA replication-blocking activity, the reagents and protocols developed and validated in yeast could also be optimized to engineer site-specific replication fork barriers into other eukaryotic cell types.

  3. The Role of System-Specific Molecular Chaperones in the Maturation of Molybdoenzymes in Bacteria

    Directory of Open Access Journals (Sweden)

    Meina Neumann

    2011-01-01

    Full Text Available Biogenesis of prokaryotic molybdoenzymes is a complex process with the final step representing the insertion of a matured molybdenum cofactor (Moco into a folded apoenzyme. Usually, specific chaperones of the XdhC family are required for the maturation of molybdoenzymes of the xanthine oxidase family in bacteria. Enzymes of the xanthine oxidase family are characterized to contain an equatorial sulfur ligand at the molybdenum center of Moco. This sulfur ligand is inserted into Moco while bound to the XdhC-like protein and before its insertion into the target enzyme. In addition, enzymes of the xanthine oxidase family bind either the molybdopterin (Mo-MPT form of Moco or the modified molybdopterin cytosine dinucleotide cofactor (MCD. In both cases, only the matured cofactor is inserted by a proofreading process of XdhC. The roles of these specific XdhC-like chaperones during the biogenesis of enzymes of the xanthine oxidase family in bacteria are described.

  4. A Molecular Toolbox to Engineer Site-Specific DNA Replication Perturbation

    DEFF Research Database (Denmark)

    Larsen, Nicolai B; Hickson, Ian D; Mankouri, Hocine W

    2018-01-01

    " impediment to DNA replication. To further develop this system as a versatile tool, we describe a set of reagents and a detailed protocol that can be used to engineer Tus-Ter barriers into any locus in the budding yeast genome. Because the Tus-Ter complex is a bipartite system with intrinsic DNA replication......Site-specific arrest of DNA replication is a useful tool for analyzing cellular responses to DNA replication perturbation. The E. coli Tus-Ter replication barrier can be reconstituted in eukaryotic cells as a system to engineer an unscheduled collision between a replication fork and an "alien......-blocking activity, the reagents and protocols developed and validated in yeast could also be optimized to engineer site-specific replication fork barriers into other eukaryotic cell types....

  5. Chemical modification of DNA: Molecular specificity studied by tandem mass spectrometry and liquid chromatography

    International Nuclear Information System (INIS)

    Chang, Ching-jer; Cooks, R.G.; Chae, Whi-Gun; Wood, J.M.

    1989-01-01

    Chemical modifications of DNA in vitro could be directly studied by C-13 NMR and P-31 NMR, which eliminated all degradation and separation processes. The prospects of utilized the NMR method in the in vitro experiments are limited because of the inherent low sensitivity of NMR and low level of DNA modification. We have developed a reverse-phase ion-paired HPLC method to study DNA modifications by methylating agents. The structural specificity of HPLC is significantly enhanced by conjunction with the specificity of enzymic transformations. The HPLC studies have also revealed the limitation of HPLC method for simultaneous determination of many minor modified nucleosides. This problem has been overcome by tandem mass spectrometry. In conjunction with the resolving power of HPLC in separating isomers, desorption chemical ionization tandem mass spectrometry has been utilized in the determination of the modified nucleosides at the picomole level using stable-isotope labeled compounds as internal references

  6. Molecular interactions and trafficking of influenza A virus polymerase proteins analyzed by specific monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, Leslie A.; Aggarwal, Shilpa; Bussey, Kendra A.; Desmet, Emily A.; Kim, Baek; Takimoto, Toru, E-mail: toru_takimoto@urmc.rochester.edu

    2012-04-25

    The influenza polymerase complex composed of PA, PB1 and PB2, plays a key role in viral replication and pathogenicity. Newly synthesized components must be translocated to the nucleus, where replication and transcription of viral genomes take place. Previous studies suggest that while PB2 is translocated to the nucleus independently, PA and PB1 subunits could not localize to the nucleus unless in a PA-PB1 complex. To further determine the molecular interactions between the components, we created a panel of 16 hybridoma cell lines, which produce monoclonal antibodies (mAbs) against each polymerase component. We showed that, although PB1 interacts with both PA and PB2 individually, nuclear localization of PB1 is enhanced only when co-expressed with PA. Interestingly, one of the anti-PA mAbs reacted much more strongly with PA when co-expressed with PB1. These results suggest that PA-PB1 interactions induce a conformational change in PA, which could be required for its nuclear translocation.

  7. Towards a molecular identification and classification system of lepidopteran-specific baculoviruses

    International Nuclear Information System (INIS)

    Lange, Martin; Wang Hualin; Hu Zhihong; Jehle, Johannes A.

    2004-01-01

    Virus genomics provides novel approaches for virus identification and classification. Based on the comparative analyses of sequenced lepidopteran-specific baculovirus genomes, degenerate oligonucleotides were developed that allow the specific amplification of several regions of the genome using polymerase chain reaction (PCR) followed by DNA sequencing. The DNA sequences within the coding regions of three highly conserved genes, namely polyhedrin/granulin (polh/gran), late expression factor 8 (lef-8), and late expression factor 9 (lef-9), were targeted for amplification. The oligonucleotides were tested on viral DNAs isolated from historical field samples, and amplification products were generated from 12 isolated nucleopolyhedrovirus (NPV) and 8 granulovirus (GV) DNAs. The PCR products were cloned or directly sequenced, and phylogenetic trees were inferred from individual and combined data sets of these three genes and compared to a phylogeny, which includes 22 baculoviruses using a combined data set of 30 core genes. This method allows a fast and reliable detection and identification of lepidopteran-specific NPVs and GVs. Furthermore, a strong correlation of the base composition of these three genome areas with that of the complete virus genome was observed and used to predict the base composition of uncharacterized baculovirus genomes. These analyses suggested that GVs have a significantly higher AT content than NPVs

  8. Estrone specific molecularly imprinted polymeric nanospheres: synthesis, characterization and applications for electrochemical sensor development.

    Science.gov (United States)

    Congur, Gulsah; Senay, Hilal; Turkcan, Ceren; Canavar, Ece; Erdem, Arzum; Akgol, Sinan

    2013-06-28

    The aim of this study is (i) to prepare estrone-imprinted nanospheres (nano-EST-MIPs) and (ii) to integrate them into the electrochemical sensor as a recognition layer. N-methacryloyl-(l)-phenylalanine (MAPA) was chosen as the complexing monomer. Firstly, estrone (EST) was complexed with MAPA and the EST-imprinted poly(2-hyroxyethylmethacrylate-co-N-methacryloyl-(l)-phenylalanine) [EST-imprinted poly(HEMA-MAPA)] nanospheres were synthesized by surfactant- free emulsion polymerization method. The specific surface area of the EST-imprinted poly(HEMA-MAPA) nanospheres was found to be 1275 m2/g with a size of 163.2 nm in diameter. According to the elemental analysis results, the nanospheres contained 95.3 mmole MAPA/g nanosphere. The application of EST specific MIP nanospheres for the development of an electrochemical biosensor was introduced for the first time in our study by using electrochemical impedance spectroscopy (EIS) technique. This nano-MIP based sensor presented a great specificity and selectivity for EST.

  9. Molecular evolution of a chordate specific family of G protein-coupled receptors

    Directory of Open Access Journals (Sweden)

    Leese Florian

    2011-08-01

    Full Text Available Abstract Background Chordate evolution is a history of innovations that is marked by physical and behavioral specializations, which led to the development of a variety of forms from a single ancestral group. Among other important characteristics, vertebrates obtained a well developed brain, anterior sensory structures, a closed circulatory system and gills or lungs as blood oxygenation systems. The duplication of pre-existing genes had profound evolutionary implications for the developmental complexity in vertebrates, since mutations modifying the function of a duplicated protein can lead to novel functions, improving the evolutionary success. Results We analyzed here the evolution of the GPRC5 family of G protein-coupled receptors by comprehensive similarity searches and found that the receptors are only present in chordates and that the size of the receptor family expanded, likely due to genome duplication events in the early history of vertebrate evolution. We propose that a single GPRC5 receptor coding gene originated in a stem chordate ancestor and gave rise by duplication events to a gene family comprising three receptor types (GPRC5A-C in vertebrates, and a fourth homologue present only in mammals (GPRC5D. Additional duplications of GPRC5B and GPRC5C sequences occurred in teleost fishes. The finding that the expression patterns of the receptors are evolutionarily conserved indicates an important biological function of these receptors. Moreover, we found that expression of GPRC5B is regulated by vitamin A in vivo, confirming previous findings that linked receptor expression to retinoic acid levels in tumor cell lines and strengthening the link between the receptor expression and the development of a complex nervous system in chordates, known to be dependent on retinoic acid signaling. Conclusions GPRC5 receptors, a class of G protein-coupled receptors with unique sequence characteristics, may represent a molecular novelty that helped non

  10. Molecular characterization of two sub-family specific monoclonal antibodies to meningococcal Factor H binding protein

    Directory of Open Access Journals (Sweden)

    C. Lo Passo

    2018-04-01

    Full Text Available Factor H binding protein (FHbp is a component of two licensed vaccines for prevention of sepsis and meningitis caused by serogroup B meningococci. FHbp binds human Factor H (FH, which contributes to evasion of host immunity and FHbp sequence variants can be classified into two sub-families. Antibodies against FHbp elicit complement-mediated killing and can inhibit recruitment of FH to the bacterial surface. We report epitope mapping studies of two murine IgG mAbs, designated JAR 31 and JAR 36, isolated from a mouse immunized with FHbp in sub-family A, which is present in ∼30–40% of invasive isolates. In the present study, we tested the reactivity of mAbs JAR 31 and JAR 36 with seven natural FHbp sequence variants from different phylogenic groups. We screened bacteriophage-displayed peptide libraries to identify amino acid residues contributing to the JAR 36 epitope. Based on the reactivities of mAbs JAR 31 and JAR 36 with the seven FHbp variants, and the frequent occurrences of aspartate (D and lysine (K residues in the JAR 36-bound phage peptides, we selected six residues in the carboxyl-terminal region of FHbp for replacement with alanine (A. The D201A and K203A substitutions respectively eliminated and decreased binding of mAbs JAR 31 and JAR 36 to FHbp. These substitutions did not affect binding of the control mAb JAR 33 or of human FH. JAR 31 or JAR 36 mediated cooperative complement-mediated bactericidal activity with other anti-FHbp mAbs. The identification of two amino acid residues involved in the epitopes recognized by these anti-FHbp mAbs may contribute to a more complete understanding of the spatial requirements for cooperative anti-FHbp mAb bactericidal activity. Keywords: Biochemistry, Immunology, Microbiology, Molecular biology

  11. The first Malay database toward the ethnic-specific target molecular variation.

    Science.gov (United States)

    Halim-Fikri, Hashim; Etemad, Ali; Abdul Latif, Ahmad Zubaidi; Merican, Amir Feisal; Baig, Atif Amin; Annuar, Azlina Ahmad; Ismail, Endom; Salahshourifar, Iman; Liza-Sharmini, Ahmad Tajudin; Ramli, Marini; Shah, Mohamed Irwan; Johan, Muhammad Farid; Hassan, Nik Norliza Nik; Abdul-Aziz, Noraishah Mydin; Mohd Noor, Noor Haslina; Nur-Shafawati, Ab Rajab; Hassan, Rosline; Bahar, Rosnah; Zain, Rosnah Binti; Yusoff, Shafini Mohamed; Yusoff, Surini; Tan, Soon Guan; Thong, Meow-Keong; Wan-Isa, Hatin; Abdullah, Wan Zaidah; Mohamed, Zahurin; Abdul Latiff, Zarina; Zilfalil, Bin Alwi

    2015-04-30

    The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb). Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register ). This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background.

  12. Pro j 2 is mesquite profilin: molecular characteristics and specific IgE binding activity.

    Science.gov (United States)

    Ali-Sadeghi, Hosein; Khodadadi, Ali; Amini, Akram; Assarehzadegan, Mohammad-Ali; Sepahi, Najmeh; Zarinhadideh, Farnoosh

    2015-06-01

    Pollens from mesquite (Prosopis juliflora) are potent allergen responsible in causing immediate hypersensitivity reactions in susceptible people in tropical countries. This study aimed to clone, express and purify the mesquite pollen profilin (Pro j 2) as well as evaluating its nucleotide sequence homology in order to predict allergenic cross-reactivity with profilins of common allergenic plants. Immunoblotting assay and specific ELISA were applied to determine the immunoreactivity of sera from 35 patients who were allergic to mesquite pollen. The mesquite profilin-coding sequence was cloned into PTZ57R/T vector and amplified. The cDNA of mesquite pollen profilin was then expressed in Escherichia coli using pET-21b (+) vector and puri?ed by one-step Ni2+ a?nity chromatography. IgE binding capacity of the recombinant mesquite profiling (rPro j 2) was analyzed by specific ELISA, immunoblotting, and inhibition assays. cDNA nucleotide sequencing revealed an open reading frame of 399bp encoding for 133 amino acids which belongs to the profilin family. Seventeen patients (17/35, 48.57%) had significant specific IgE level for rPro j 2. Immunodetection and inhibition assays indicated that puri?ed rPro j 2 might be similar as that in the crude extract. Pro j 2, as a new allergen from mesquite pollen, was produced in E. coli with an IgE-reactivity similar to that of its natural counterpart. The amino acid sequences homology analysis of mesquite profilin and several profilin molecules from other plants showed high degree of cross-reactivity among plant-derived profilins from unrelated families.

  13. Of arrows and flows. Causality, determination, and specificity in the Central Dogma of molecular biology.

    Science.gov (United States)

    Fantini, Bernardino

    2006-01-01

    From its first proposal, the Central Dogma had a graphical form, complete with arrows of different types, and this form quickly became its standard presentation. In different scientific contexts, arrows have different meanings and in this particular case the arrows indicated the flow of information among different macromolecules. A deeper analysis illustrates that the arrows also imply a causal statement, directly connected to the causal role of genetic information. The author suggests a distinction between two different kinds of causal links, defined as 'physical causality' and 'biological determination', both implied in the production of biological specificity.

  14. Geologic map of the Beacon Rock quadrangle, Skamania County, Washington

    Science.gov (United States)

    Evarts, Russell C.; Fleck, Robert J.

    2017-06-06

    The Beacon Rock 7.5′ quadrangle is located approximately 50 km east of Portland, Oregon, on the north side of the Columbia River Gorge, a scenic canyon carved through the axis of the Cascade Range by the Columbia River. Although approximately 75,000 people live within the gorge, much of the region remains little developed and is encompassed by the 292,500-acre Columbia River Gorge National Scenic Area, managed by a consortium of government agencies “to pro­tect and provide for the enhancement of the scenic, cultural, recreational and natural resources of the Gorge and to protect and support the economy of the Columbia River Gorge area.” As the only low-elevation corridor through the Cascade Range, the gorge is a critical regional transportation and utilities corridor (Wang and Chaker, 2004). Major state and national highways and rail lines run along both shores of the Columbia River, which also provides important water access to ports in the agricultural interior of the Pacific Northwest. Transmission lines carry power from hydroelectric facilities in the gorge and farther east to the growing urban areas of western Oregon and Washington, and natural-gas pipelines transect the corridor (Wang and Chaker, 2004). These lifelines are highly vulnerable to disruption by earthquakes, landslides, and floods. A major purpose of the work described here is to identify and map geologic hazards, such as faults and landslide-prone areas, to provide more accurate assessments of the risks associated with these features.The steep canyon walls of the map area reveal exten­sive outcrops of Miocene flood-basalt flows of the Columbia River Basalt Group capped by fluvial deposits of the ances­tral Columbia River, Pliocene lavas erupted from the axis of the Cascade arc to the east, and volcanic rocks erupted from numerous local vents. The Columbia River Basalt Group unconformably rests on a sequence of late Oligocene and early Miocene rocks of the ancestral Cascade volcanic arc

  15. Structural and biochemical studies of a fluoroacetyl-CoA-specific thioesterase reveal a molecular basis for fluorine selectivity.

    Science.gov (United States)

    Weeks, Amy M; Coyle, Scott M; Jinek, Martin; Doudna, Jennifer A; Chang, Michelle C Y

    2010-11-02

    We have initiated a broad-based program aimed at understanding the molecular basis of fluorine specificity in enzymatic systems, and in this context, we report crystallographic and biochemical studies on a fluoroacetyl-coenzyme A (CoA) specific thioesterase (FlK) from Streptomyces cattleya. Our data establish that FlK is competent to protect its host from fluoroacetate toxicity in vivo and demonstrate a 10(6)-fold discrimination between fluoroacetyl-CoA (k(cat)/K(M) = 5 × 10⁷ M⁻¹ s⁻¹) and acetyl-CoA (k(cat)/K(M) = 30 M⁻¹ s⁻¹) based on a single fluorine substitution that originates from differences in both substrate reactivity and binding. We show that Thr 42, Glu 50, and His 76 are key catalytic residues and identify several factors that influence substrate selectivity. We propose that FlK minimizes interaction with the thioester carbonyl, leading to selection against acetyl-CoA binding that can be recovered in part by new C═O interactions in the T42S and T42C mutants. We hypothesize that the loss of these interactions is compensated by the entropic driving force for fluorinated substrate binding in a hydrophobic binding pocket created by a lid structure, containing Val 23, Leu 26, Phe 33, and Phe 36, that is not found in other structurally characterized members of this superfamily. We further suggest that water plays a critical role in fluorine specificity based on biochemical and structural studies focused on the unique Phe 36 "gate" residue, which functions to exclude water from the active site. Taken together, the findings from these studies offer molecular insights into organofluorine recognition and design of fluorine-specific enzymes.

  16. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.

    Science.gov (United States)

    Boldt, Karsten; van Reeuwijk, Jeroen; Lu, Qianhao; Koutroumpas, Konstantinos; Nguyen, Thanh-Minh T; Texier, Yves; van Beersum, Sylvia E C; Horn, Nicola; Willer, Jason R; Mans, Dorus A; Dougherty, Gerard; Lamers, Ideke J C; Coene, Karlien L M; Arts, Heleen H; Betts, Matthew J; Beyer, Tina; Bolat, Emine; Gloeckner, Christian Johannes; Haidari, Khatera; Hetterschijt, Lisette; Iaconis, Daniela; Jenkins, Dagan; Klose, Franziska; Knapp, Barbara; Latour, Brooke; Letteboer, Stef J F; Marcelis, Carlo L; Mitic, Dragana; Morleo, Manuela; Oud, Machteld M; Riemersma, Moniek; Rix, Susan; Terhal, Paulien A; Toedt, Grischa; van Dam, Teunis J P; de Vrieze, Erik; Wissinger, Yasmin; Wu, Ka Man; Apic, Gordana; Beales, Philip L; Blacque, Oliver E; Gibson, Toby J; Huynen, Martijn A; Katsanis, Nicholas; Kremer, Hannie; Omran, Heymut; van Wijk, Erwin; Wolfrum, Uwe; Kepes, François; Davis, Erica E; Franco, Brunella; Giles, Rachel H; Ueffing, Marius; Russell, Robert B; Roepman, Ronald

    2016-05-13

    Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine.

  17. Molecular Simulations of Sequence-Specific Association of Transmembrane Proteins in Lipid Bilayers

    Science.gov (United States)

    Doxastakis, Manolis; Prakash, Anupam; Janosi, Lorant

    2011-03-01

    Association of membrane proteins is central in material and information flow across the cellular membranes. Amino-acid sequence and the membrane environment are two critical factors controlling association, however, quantitative knowledge on such contributions is limited. In this work, we study the dimerization of helices in lipid bilayers using extensive parallel Monte Carlo simulations with recently developed algorithms. The dimerization of Glycophorin A is examined employing a coarse-grain model that retains a level of amino-acid specificity, in three different phospholipid bilayers. Association is driven by a balance of protein-protein and lipid-induced interactions with the latter playing a major role at short separations. Following a different approach, the effect of amino-acid sequence is studied using the four transmembrane domains of the epidermal growth factor receptor family in identical lipid environments. Detailed characterization of dimer formation and estimates of the free energy of association reveal that these helices present significant affinity to self-associate with certain dimers forming non-specific interfaces.

  18. Molecular basis of the specific subcellular localization of the C2-like domain of 5-lipoxygenase.

    Science.gov (United States)

    Kulkarni, Shilpa; Das, Sudipto; Funk, Colin D; Murray, Diana; Cho, Wonhwa

    2002-04-12

    The activation of 5-lipoxygenase (5-LO) involves its calcium-dependent translocation to the nuclear envelope, where it catalyzes the two-step transformation of arachidonic acid into leukotriene A(4), leading to the synthesis of various leukotrienes. To understand the mechanism by which 5-LO is specifically targeted to the nuclear envelope, we studied the membrane binding properties of the amino-terminal domain of 5-LO, which has been proposed to have a C2 domain-like structure. The model building, electrostatic potential calculation, and in vitro membrane binding studies of the isolated C2-like domain of 5-LO and selected mutants show that this Ca(2+)-dependent domain selectively binds zwitterionic phosphatidylcholine, which is conferred by tryptophan residues (Trp(13), Trp(75), and Trp(102)) located in the putative Ca(2+)-binding loops. The spatiotemporal dynamics of the enhanced green fluorescence protein-tagged C2-like domain of 5-LO and mutants in living cells also show that the phosphatidylcholine selectivity of the C2-like domain accounts for the specific targeting of 5-LO to the nuclear envelope. Together, these results show that the C2-like domain of 5-LO is a genuine Ca(2+)-dependent membrane-targeting domain and that the subcellular localization of the domain is governed in large part by its membrane binding properties.

  19. Molecular Imaging Agents Specific for the Annulus Fibrosus of the Intervertebral Disk

    Directory of Open Access Journals (Sweden)

    Summer L. Gibbs-Strauss

    2010-05-01

    Full Text Available Low back pain is a prevalent medical condition that is difficult to diagnose and treat. Current imaging methods are unable to correlate pain reliably with spinal structures, and surgical removal of painful damaged or degenerating disks is technically challenging. A contrast agent specific for the intervertebral disk could assist in the detection, diagnosis, and surgical treatment of low back pain. The styryl pyridinium (FM fluorophores were characterized and structure-activity relationships between chemical structure and in vivo uptake were established. Two novel FM fluorophores with improved optical properties for imaging the intervertebral disks were synthesized and evaluated in mice, rats, and pigs. After a single systemic injection, eight of eight FM fluorophores provided high-contrast imaging of the trigeminal ganglia, whereas six of eight provided high-contrast imaging of the dorsal root ganglia. Unexpectedly, three of eight FM fluorophores provided high-contrast imaging of annulus fibrosus tissue of the intervertebral disks, confirmed histologically. We present the first known contrast agent specific for the intervertebral disks and identify the chemical structural motif that mediates uptake. FM fluorophores could be used for image-guided surgery to assist in the removal of intervertebral disk and lay the foundation for derivatives for magnetic resonance imaging and positron emission tomography.

  20. Characteristics of Sucrose Transport through the Sucrose-Specific Porin ScrY Studied by Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Liping eSun

    2016-02-01

    Full Text Available Sucrose-specific porin (ScrY is a transmembrane protein that allows for the uptake of sucrose under growth-limiting conditions. The crystal structure of ScrY was resolved before by X-ray crystallography, both in its uncomplexed form and with bound sucrose. However, little is known about the molecular characteristics of the transport mechanism of ScrY. To date, there has not yet been any clear demonstration for sucrose transport through the ScrY.Here, the dynamics of the ScrY trimer embedded in a phospholipid bilayer as well as the characteristics of sucrose translocation were investigated by means of atomistic molecular dynamics (MD simulations. The potential of mean force (PMF for sucrose translocation through the pore showed two main energy barriers within the constriction region of ScrY. Energy decomposition allowed to pinpoint three aspartic acids as key residues opposing the passage of sucrose, all located within the L3 loop. Mutation of two aspartic acids to uncharged residues resulted in an accordingly modified electrostatics and decreased PMF barrier. The chosen methodology and results will aid in the design of porins with modified transport specificities.

  1. ClassBeacons: designing distributed visualization of teachers’ physical proximity in the classroom.

    NARCIS (Netherlands)

    An, P.; Bakker, S.; Ordanovski, S.; Taconis, R.; Eggen, J.H.

    2018-01-01

    Pengcheng An, Saskia Bakker, Sara Ordanovski, Ruurd Taconis, Berry Eggen. 2018 (accepted at Oct 2017). ClassBeacons: designing distributed visualization of teachers’ physical proximity in the classroom. In Proceedings of Tangible and Embodied Interaction, TEI 2018, Mar 18-21, 2018,

  2. Pedestrian hybrid beacon crosswalk system (PHB) or high-intensity activated crosswalk (HAWK).

    Science.gov (United States)

    2014-11-01

    The Pedestrian Hybrid Beacon Crosswalk (PHB) is a type of traffic control system, used to aid : pedestrians safely crossing the street and to regulate traffic flow. This study examines the : success of the first PHB installed in the state of Vermont....

  3. Improved fixation quality provided by a Bessel beacon in an adaptive optics system.

    Science.gov (United States)

    Lambert, Andrew J; Daly, Elizabeth M; Dainty, Christopher J

    2013-07-01

    We investigate whether a structured probe beam that creates the beacon for use in a retinal imaging adaptive optics system can provide useful side effects. In particular we investigate whether a Bessel beam that is seen by the subject as a set of concentric rings has a dampening effect on fixation variations of the subject under observation. This calming effect would allow longer periods of observation, particularly for patients with abnormal fixation. An experimental adaptive optics system developed for retinal imaging is used to monitor the fluctuations in aberrations for artificial and human subjects. The probe beam is alternated between a traditional beacon and one provided by a Bessel beam created by SLM. Time-frequency analysis is used to indicate the differences in power and time variation during fixation depending on whether the Bessel beam or the traditional beacon is employed. Comparison is made with the response for an artificial eye to discount systemic variations. Significant evidence is accrued to indicate the reduced fluctuations in fixation when the Bessel beam is employed to create the beacon. © 2013 The Authors Ophthalmic & Physiological Optics © 2013 The College of Optometrists.

  4. The Effects of a Rectangular Rapid-Flashing Beacon on Vehicle Speed

    Science.gov (United States)

    VanWagner, Michelle; Van Houten, Ron; Betts, Brian

    2011-01-01

    In 2008, nearly 31% of vehicle fatalities were related to failure to adhere to safe vehicle speeds (National Highway Traffic Safety Administration [NHTSA], 2009). The current study evaluated the effect of a rectangular rapid-flashing beacon (RRFB) triggered by excessive speed on vehicle speed using a combined alternating treatments and reversal…

  5. Beacon-Based Service Publishing Framework in Multiservice Wi-Fi Hotspots

    Directory of Open Access Journals (Sweden)

    Di Sorte Dario

    2007-01-01

    Full Text Available In an expected future multiaccess and multiservice IEEE 802.11 environment, the problem of providing users with useful service-related information to support a correct rapid network selection is expected to become a very important issue. A feasible short-term 802.11-tailored working solution, compliant with existing equipment, is to publish service information encoded within the SSID information element within beacon frames. This makes it possible for an operator to implement service publishing in 802.11 networks while waiting for a standardized mechanism. Also, this straightforward approach has allowed us to evaluate experimentally the performance of a beacon-based service publishing solution. In fact, the main focus of the paper is indeed to present a quantitative comparison of service discovery times between the legacy scenario, where the user is forced to associate and authenticate with a network point of access to check its service offer, and the enhanced scenario where the set of service-related information is broadcasted within beacons. These discovery times are obtained by processing the results of a measurement campaign performed in a multiaccess/service 802.11 environment. This analysis confirms the effectiveness of the beacon-based approach. We also show that the cost in terms of wireless bandwidth consumption of such solution is low.

  6. Application of the BEACON-TSM system to the operation of PWR reactors

    International Nuclear Information System (INIS)

    Lozano, J. A.; Mildrum, C.; Serrano, J. F.

    2011-01-01

    BEACON-TSM is an advanced system of the operation support of PWR reactors that combines the capabilities of an advanced nodal neutronic model and the measures of the instrumentation available in plant to determine, accurately and continuously, the distribution of power in the core and the available margins to the limits of the beak factors.

  7. Beacon signal in transcranial color coded ultrasound: A sign for brain death

    Directory of Open Access Journals (Sweden)

    Mehmet Akif Topçuoğlu

    2014-04-01

    Full Text Available A widely under-recognized brain-death confirming transcranial ultrasonography pattern resembling the red-blue beacon signal was demonstrated. Familiarity to this distinct and characteristic ultrasonic pattern seems to be important in the perspective of point-of-care neurological ultrasound use and knobology.

  8. A Beacon Transmission Power Control Algorithm Based on Wireless Channel Load Forecasting in VANETs.

    Science.gov (United States)

    Mo, Yuanfu; Yu, Dexin; Song, Jun; Zheng, Kun; Guo, Yajuan

    2015-01-01

    In a vehicular ad hoc network (VANET), the periodic exchange of single-hop status information broadcasts (beacon frames) produces channel loading, which causes channel congestion and induces information conflict problems. To guarantee fairness in beacon transmissions from each node and maximum network connectivity, adjustment of the beacon transmission power is an effective method for reducing and preventing channel congestion. In this study, the primary factors that influence wireless channel loading are selected to construct the KF-BCLF, which is a channel load forecasting algorithm based on a recursive Kalman filter and employs multiple regression equation. By pre-adjusting the transmission power based on the forecasted channel load, the channel load was kept within a predefined range; therefore, channel congestion was prevented. Based on this method, the CLF-BTPC, which is a transmission power control algorithm, is proposed. To verify KF-BCLF algorithm, a traffic survey method that involved the collection of floating car data along a major traffic road in Changchun City is employed. By comparing this forecast with the measured channel loads, the proposed KF-BCLF algorithm was proven to be effective. In addition, the CLF-BTPC algorithm is verified by simulating a section of eight-lane highway and a signal-controlled urban intersection. The results of the two verification process indicate that this distributed CLF-BTPC algorithm can effectively control channel load, prevent channel congestion, and enhance the stability and robustness of wireless beacon transmission in a vehicular network.

  9. Some measurements of total electron content made with the ATS-6 radio beacon

    International Nuclear Information System (INIS)

    Davies, K.; Degenhardt, W.; Hartmann, G.K.

    1978-01-01

    The paper deals with some measurements made with the radio beacon on board the ATS-6 satellite in the American and European sectors. Measurements of the slant electron content, the Faraday content, and the plasmaspheric (or residual) content, made under different geographic and geomagnetic conditions, are discussed and compared

  10. A Beacon Transmission Power Control Algorithm Based on Wireless Channel Load Forecasting in VANETs.

    Directory of Open Access Journals (Sweden)

    Yuanfu Mo

    Full Text Available In a vehicular ad hoc network (VANET, the periodic exchange of single-hop status information broadcasts (beacon frames produces channel loading, which causes channel congestion and induces information conflict problems. To guarantee fairness in beacon transmissions from each node and maximum network connectivity, adjustment of the beacon transmission power is an effective method for reducing and preventing channel congestion. In this study, the primary factors that influence wireless channel loading are selected to construct the KF-BCLF, which is a channel load forecasting algorithm based on a recursive Kalman filter and employs multiple regression equation. By pre-adjusting the transmission power based on the forecasted channel load, the channel load was kept within a predefined range; therefore, channel congestion was prevented. Based on this method, the CLF-BTPC, which is a transmission power control algorithm, is proposed. To verify KF-BCLF algorithm, a traffic survey method that involved the collection of floating car data along a major traffic road in Changchun City is employed. By comparing this forecast with the measured channel loads, the proposed KF-BCLF algorithm was proven to be effective. In addition, the CLF-BTPC algorithm is verified by simulating a section of eight-lane highway and a signal-controlled urban intersection. The results of the two verification process indicate that this distributed CLF-BTPC algorithm can effectively control channel load, prevent channel congestion, and enhance the stability and robustness of wireless beacon transmission in a vehicular network.

  11. Analysis and Enhancement of IEEE 802.15.4e DSME Beacon Scheduling Model

    Directory of Open Access Journals (Sweden)

    Kwang-il Hwang

    2014-01-01

    Full Text Available In order to construct a successful Internet of things (IoT, reliable network construction and maintenance in a sensor domain should be supported. However, IEEE 802.15.4, which is the most representative wireless standard for IoT, still has problems in constructing a large-scale sensor network, such as beacon collision. To overcome some problems in IEEE 802.15.4, the 15.4e task group proposed various different modes of operation. Particularly, the IEEE 802.15.4e deterministic and synchronous multichannel extension (DSME mode presents a novel scheduling model to solve beacon collision problems. However, the DSME model specified in the 15.4e draft does not present a concrete design model but a conceptual abstract model. Therefore, in this paper we introduce a DSME beacon scheduling model and present a concrete design model. Furthermore, validity and performance of DSME are evaluated through experiments. Based on experiment results, we analyze the problems and limitations of DSME, present solutions step by step, and finally propose an enhanced DSME beacon scheduling model. Through additional experiments, we prove the performance superiority of enhanced DSME.

  12. Scheduled MAC in Beacon Overlay Networks for Underwater Localization and Time-Synchronization

    NARCIS (Netherlands)

    van Kleunen, W.A.P.; Meratnia, Nirvana; Havinga, Paul J.M.

    2011-01-01

    In this article we introduce a MAC protocol designed for underwater localization and time-synchronisation. The MAC protocol assumes a network of static reference nodes and allows blind nodes to be localized by listening-only to the beacon messages. Such a system is known to be very scalable. We show

  13. Molecular detection and variability of Strawberry vein banding virus

    Czech Academy of Sciences Publication Activity Database

    Hanzlíková-Vašková, Dana; Špak, Josef

    2004-01-01

    Roč. 656, - (2004), 33-38 ISSN 0567-7572 Grant - others:EU EU QLR5-1999-1553 Institutional research plan: CEZ:AV0Z5051902 Keywords : AmpliDet RNA * caulimovirus * molecular beacon * nucleic acid sequence based amplification * PCR, SVBV * CaM Subject RIV: EE - Microbiology, Virology

  14. The retinal specific CD147 Ig0 domain: from molecular structure to biological activity

    Science.gov (United States)

    Redzic, Jasmina S.; Armstrong, Geoffrey S.; Isern, Nancy. G.; Jones, David N.M.; Kieft, Jeffrey S.; Eisenmesser, Elan Zohar

    2011-01-01

    CD147 is a type I transmembrane protein that is involved in inflammatory diseases, cancer progression, and multiple human pathogens utilize CD147 for efficient infection. In several cancers, CD147 expression is so high that it is now used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified, differing in their number of immunoglobulin (Ig)-like domains. These include CD147 Ig1-Ig2 that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 that is retinal specific and implicated in retinoblastoma. However, little is known in regard to the retinal specific CD147 Ig0 domain despite its potential role in retinoblastoma. We present the first crystal structure of the human CD147 Ig0 domain and show that the CD147 Ig0 domain is a crystallographic dimer with an I-type domain structure, which is maintained in solution. Furthermore, we have utilized our structural data together with mutagenesis to probe the biological activity of CD147-containing proteins both with and without the CD147 Ig0 domain within several model cell lines. Our findings reveal that the CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 domain has its own receptor distinct from that of the other CD147 Ig-like domains, CD147 Ig1-Ig2. Finally, we show that the CD147 Ig0 dimer is the functional unit required for activity and can be disrupted by a single point mutation. PMID:21620857

  15. The retinal specific CD147 Ig0 domain: from molecular structure to biological activity

    Energy Technology Data Exchange (ETDEWEB)

    Redzic, Jasmina S.; Armstrong, Geoffrey S.; Isern, Nancy G.; Jones, David N.M.; Kieft, Jeffrey S.; Eisenmesser, Elan Z.

    2011-06-18

    CD147 is a type I transmembrane protein that is involved in inflammatory diseases, cancer progression, and multiple human pathogens utilize CD147 for efficient infection. In several cancers, CD147 expression is so high that it is now used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified, differing in their number of immunoglobulin (Ig)-like domains. These include CD147 Ig1-Ig2 that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 that is retinal specific and implicated in retinoblastoma. However, little is known in regard to the retinal specific CD147 Ig0 domain despite its potential role in retinoblastoma. Thus, here we have extensively characterized the CD147 Ig0 domain by elucidating its three-dimensional structure through crystallography and its solution behavior through several biophysical methods that include nuclear magnetic resonance. Furthermore, we have utilized this data together with mutagenesis to probe the biological activity of CD147-containing proteins both with and without the CD147 Ig0 domain within several model cell lines. Our findings reveal that the CD147 Ig0 domain is a potent stimulator of interleukin-6, which is a well-known contributor to retinoblastoma and suggest that the CD147 Ig0 domain has its own receptor distinct from that of the other CD147 Ig-like domains, CD147 Ig1-Ig2. Furthermore, we show that the CD147 Ig0 dimer is the functional unit required for activity and can be disrupted by a single point mutation.

  16. State-specific Multi-reference Perturbation Theories with Relaxed Coefficients: Molecular Applications

    Directory of Open Access Journals (Sweden)

    Debashis Mukherjee

    2002-06-01

    Full Text Available Abstract: We present in this paper two new versions of Rayleigh-Schr¨odinger (RS and the Brillouin-Wigner (BW state-specific multi-reference perturbative theories (SSMRPT which stem from our state-specific multi-reference coupled-cluster formalism (SS-MRCC, developed with a complete active space (CAS. They are manifestly sizeextensive and are designed to avoid intruders. The combining coefficients cμ for the model functions φμ are completely relaxed and are obtained by diagonalizing an effective operator in the model space, one root of which is the target eigenvalue of interest. By invoking suitable partitioning of the hamiltonian, very convenient perturbative versions of the formalism in both the RS and the BW forms are developed for the second order energy. The unperturbed hamiltonians for these theories can be chosen to be of both Mφller-Plesset (MP and Epstein-Nesbet (EN type. However, we choose the corresponding Fock operator fμ for each model function φμ, whose diagonal elements are used to define the unperturbed hamiltonian in the MP partition. In the EN partition, we additionally include all the diagonal direct and exchange ladders. Our SS-MRPT thus utilizes a multi-partitioning strategy. Illustrative numerical applications are presented for potential energy surfaces (PES of the ground (1Σ+ and the first delta (1Δ states of CH+ which possess pronounced multi-reference character. Comparison of the results with the corresponding full CI values indicates the efficacy of our formalisms.

  17. Molecular and functional characterization of riboflavin specific transport system in rat brain capillary endothelial cells

    Science.gov (United States)

    Patel, Mitesh; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K.

    2012-01-01

    Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-Riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with Km and Vmax values of 19 ± 3 µM and 0.235 ± 0.012 picomoles/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca++/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-Riboflavin. Apical and baso-lateral uptake of [3H]-Riboflavin clearly indicate that riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. Blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. PMID:22683359

  18. Elucidating the evolutionary conserved DNA-binding specificities of WRKY transcription factors by molecular dynamics and in vitro binding assays

    Science.gov (United States)

    Brand, Luise H.; Fischer, Nina M.; Harter, Klaus; Kohlbacher, Oliver; Wanke, Dierk

    2013-01-01

    WRKY transcription factors constitute a large protein family in plants that is involved in the regulation of developmental processes and responses to biotic or abiotic stimuli. The question arises how stimulus-specific responses are mediated given that the highly conserved WRKY DNA-binding domain (DBD) exclusively recognizes the ‘TTGACY’ W-box consensus. We speculated that the W-box consensus might be more degenerate and yet undetected differences in the W-box consensus of WRKYs of different evolutionary descent exist. The phylogenetic analysis of WRKY DBDs suggests that they evolved from an ancestral group IIc-like WRKY early in the eukaryote lineage. A direct descent of group IIc WRKYs supports a monophyletic origin of all other group II and III WRKYs from group I by loss of an N-terminal DBD. Group I WRKYs are of paraphyletic descent and evolved multiple times independently. By homology modeling, molecular dynamics simulations and in vitro DNA–protein interaction-enzyme-linked immunosorbent assay with AtWRKY50 (IIc), AtWRKY33 (I) and AtWRKY11 (IId) DBDs, we revealed differences in DNA-binding specificities. Our data imply that other components are essentially required besides the W-box-specific binding to DNA to facilitate a stimulus-specific WRKY function. PMID:23975197

  19. Molecular analysis of volatile metabolites released specifically by staphylococcus aureus and pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Filipiak Wojciech

    2012-06-01

    Full Text Available Abstract Background The routinely used microbiological diagnosis of ventilator associated pneumonia (VAP is time consuming and often requires invasive methods for collection of human specimens (e.g. bronchoscopy. Therefore, it is of utmost interest to develop a non-invasive method for the early detection of bacterial infection in ventilated patients, preferably allowing the identification of the specific pathogens. The present work is an attempt to identify pathogen-derived volatile biomarkers in breath that can be used for early and non- invasive diagnosis of ventilator associated pneumonia (VAP. For this purpose, in vitro experiments with bacteria most frequently found in VAP patients, i.e. Staphylococcus aureus and Pseudomonas aeruginosa, were performed to investigate the release or consumption of volatile organic compounds (VOCs. Results Headspace samples were collected and preconcentrated on multibed sorption tubes at different time points and subsequently analyzed with gas chromatography mass spectrometry (GC-MS. As many as 32 and 37 volatile metabolites were released by S. aureus and P. aeruginosa, respectively. Distinct differences in the bacteria-specific VOC profiles were found, especially with regard to aldehydes (e.g. acetaldehyde, 3-methylbutanal, which were taken up only by P. aeruginosa but released by S. aureus. Differences in concentration profiles were also found for acids (e.g. isovaleric acid, ketones (e.g. acetoin, 2-nonanone, hydrocarbons (e.g. 2-butene, 1,10-undecadiene, alcohols (e.g. 2-methyl-1-propanol, 2-butanol, esters (e.g. ethyl formate, methyl 2-methylbutyrate, volatile sulfur compounds (VSCs, e.g. dimethylsulfide and volatile nitrogen compounds (VNCs, e.g. 3-methylpyrrole. Importantly, a significant VOC release was found already 1.5 hours after culture start, corresponding to cell numbers of ~8*106 [CFUs/ml]. Conclusions The results obtained provide strong evidence that the detection and perhaps even

  20. Molecular characterization of a complex site-specific radiation-induced DNA double-strand break

    International Nuclear Information System (INIS)

    Datta, K.; Dizdaroglu, M.; Jaruga, P.; Neumann, R.D.; Winters, T.A.

    2003-01-01

    Radiation lethality is a function of radiation-induced DNA double-strand breaks (DSB). Current models propose the lethality of a DSB to be a function of its structural complexity. We present here for the first time a map of damage associated with a site-specific double-strand break produced by decay of 125 I in a plasmid bound by a 125 I-labeled triplex forming oligonucleotide ( 125 I-TFO). The E. coli DNA repair enzymes, endonuclease IV (endo IV), endonuclease III (endo III), and formamidopyrimidine-DNA glycosylase (Fpg), which recognize AP sites, and pyrimidine and purine base damage respectively, were used as probes in this study. 125 I-TFO bound plasmid was incubated with and without DMSO at -80 deg C for 1 month. No significant difference in DSB yield was observed under these conditions. A 32 base pair fragment from the upstream side of the decay site was isolated by restriction digestion and enzymatically probed to identify damage sites. Endo IV treatment of the 5'-end labeled upper strand indicated clustering of AP sites within 3 bases downstream and 7 bases upstream of the targeted base. Also, repeated experiments consistently detected an AP site 4 bases upstream of the 125 Itarget base. This was further supported by complementary results with the 3'-end labeled upper strand. Endo IV analysis of the lower strand also shows clustering of AP sites near the DSB end. Endo III and Fpg probing demonstrated that base damage is also clustered near the targeted break site. DSBs produced in the absence of DMSO displayed a different pattern of enzyme sensitive damage than those produced in the presence of DMSO. Identification of specific base damage types within the restriction fragment containing the DSB end was achieved with GC/MS. Base damage consisted of 8-hydroguanine, 8-hydroxyadenine, and 5-hydroxycytosine. These lesions were observed at relative yields of 8-hydroguanine and 5-hydroxycytosine to 8-hydroxyadenine of 7.4:1 and 4.7:1, respectively, in the absence

  1. Supplementary Material for: BEACON: automated tool for Bacterial GEnome Annotation ComparisON

    KAUST Repository

    Kalkatawi, Manal M.; Alam, Intikhab; Bajic, Vladimir B.

    2015-01-01

    Abstract Background Genome annotation is one way of summarizing the existing knowledge about genomic characteristics of an organism. There has been an increased interest during the last several decades in computer-based structural and functional genome annotation. Many methods for this purpose have been developed for eukaryotes and prokaryotes. Our study focuses on comparison of functional annotations of prokaryotic genomes. To the best of our knowledge there is no fully automated system for detailed comparison of functional genome annotations generated by different annotation methods (AMs). Results The presence of many AMs and development of new ones introduce needs to: a/ compare different annotations for a single genome, and b/ generate annotation by combining individual ones. To address these issues we developed an Automated Tool for Bacterial GEnome Annotation ComparisON (BEACON) that benefits both AM developers and annotation analysers. BEACON provides detailed comparison of gene function annotations of prokaryotic genomes obtained by different AMs and generates extended annotations through combination of individual ones. For the illustration of BEACONâ s utility, we provide a comparison analysis of multiple different annotations generated for four genomes and show on these examples that the extended annotation can increase the number of genes annotated by putative functions up to 27 %, while the number of genes without any function assignment is reduced. Conclusions We developed BEACON, a fast tool for an automated and a systematic comparison of different annotations of single genomes. The extended annotation assigns putative functions to many genes with unknown functions. BEACON is available under GNU General Public License version 3.0 and is accessible at: http://www.cbrc.kaust.edu.sa/BEACON/ .

  2. O'nyong nyong virus molecular determinants of unique vector specificity reside in non-structural protein 3.

    Directory of Open Access Journals (Sweden)

    Kali D Saxton-Shaw

    Full Text Available O'nyong nyong virus (ONNV and Chikungunya virus (CHIKV are two closely related alphaviruses with very different infection patterns in the mosquito, Anopheles gambiae. ONNV is the only alphavirus transmitted by anopheline mosquitoes, but specific molecular determinants of infection of this unique vector specificity remain unidentified. Fifteen distinct chimeric viruses were constructed to evaluate both structural and non-structural regions of the genome and infection patterns were determined through artificial infectious feeds in An. gambiae with each of these chimeras. Only one region, non-structural protein 3 (nsP3, was sufficient to up-regulate infection to rates similar to those seen with parental ONNV. When ONNV non-structural protein 3 (nsP3 replaced nsP3 from CHIKV virus in one of the chimeric viruses, infection rates in An. gambiae went from 0% to 63.5%. No other single gene or viral region addition was able to restore infection rates. Thus, we have shown that a non-structural genome element involved in viral replication is a major element involved in ONNV's unique vector specificity.

  3. Love Wave Sensor for Prostate-Specific Membrane Antigen Detection Based on Hydrophilic Molecularly-Imprinted Polymer

    Directory of Open Access Journals (Sweden)

    Pingping Tang

    2018-05-01

    Full Text Available Prostate-specific membrane antigen (PSMA is a biomarker for prostate cancer (PCa, and a specific and reliable detection technique of PSMA is urgently required for PCa early diagnosis. A Love wave sensor has been widely studied for real-time sensing and highly sensitive applications, but the sensing unit needs special handling for selective detection purpose. In this study, we prepared a versatile Love wave sensor functionalized with molecularly-imprinted polymers (MIP, PSMA as the template molecule. To enhance the specific template bindings of MIP in pure aqueous solutions, facile reversible addition/fragmentation chain transfer (RAFT precipitation polymerization (RAFTPP was used to produce surface hydrophilic polymer brushes on MIP. The presence of hydrophilic polymer brushes on MIP improved its surface hydrophilicity and significantly reduced their hydrophobic interactions with template molecules in pure aqueous media. In detection process, the acoustic delay-line is confederative to a microfluidic chip and inserted in an oscillation loop. The real-time resonance frequency of the MIP-based Love wave sensor to different concentrations of PSMA was investigated. The limit of detection (LOD for this Love SAW sensor was 0.013 ng mL−1, which demonstrates that this sensor has outstanding performance in terms of the level of detection.

  4. Preparation of a molecularly imprinted sensor based on quartz crystal microbalance for specific recognition of sialic acid in human urine.

    Science.gov (United States)

    Qiu, Xiuzhen; Xu, Xian-Yan; Chen, Xuncai; Wu, Yiyong; Guo, Huishi

    2018-05-08

    A novel molecularly imprinted quartz crystal microbalance (QCM) sensor was successfully prepared for selective determination of sialic acid (SA) in human urine samples. To obtain the QCM sensor, we first modified the gold surface of the QCM chip by self-assembling of allylmercaptane to introduce polymerizable double bonds on the chip surface. Then, SA molecularly imprinted polymer (MIP) nanofilm was attached to the modified QCM chip surface. For comparison, we have also characterized the nonmodified and improved surfaces of the QCM sensor by using atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy. We then tested the selectivity and detection limit of the imprinted QCM sensor via a series of adsorption experiments. The results show a linear response in the range of 0.025-0.50 μmol L -1 for sialic acid. Moreover, the limit of detection (LOD) of the prepared imprinted QCM sensor was found to be 1.0 nmol L -1 for sialic acid, and high recovery values range from 87.6 to 108.5% with RSD sensor was developed and used to detect sialic acid in human urine samples. Graphical abstract Specific recognition of sialic acid by the MIP-QCM sensor system.

  5. Evaluation of molecular species of prostate-specific antigen complexed with immunoglobulin M in prostate cancer and benign prostatic hyperplasia.

    Science.gov (United States)

    Goč, Sanja; Janković, Miroslava

    2013-01-01

    This study was aimed at defining molecular species of prostate-specific antigen (PSA) in immune complexes with immunoglobulin M (IgM). Having in mind the oligoreactivity of IgM and its preference for carbohydrate antigens, there is the possibility that it can selectively recognize known PSA glycoisoforms. PSA-IgM complexes and free PSA fractions were separated from the sera of subjects with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) by gel filtration and subjected to on-chip immunoaffinity and ion-exchange chromatography. PSA-immunoreactive species were detected using surface-enhanced laser desorption/ionization time of flight mass spectrometry. The obtained spectra were analyzed for protein and glycan composition. The general pattern of the molecular species of PCa PSA and BPH PSA found in complexes with IgM was similar. It comprised major peaks at 17 kDa and minor peaks at 28 kDa, corresponding to the entire mature glycosylated PSA. The main difference was the presence of incompletely glycosylated 26.8 kDa species, having putative paucimannosidic structures, observed in PCa PSA-IgM, but not in BPH PSA-IgM. Characteristic PCa PSA-IgM glycoforms pose the question of the possible role of glycosylation as a framework for immune surveillance and may be of interest in light of recent data indicating mannose-containing glycans as cancer biomarker.

  6. Evaluation of Molecular Species of Prostate-Specific Antigen Complexed with Immunoglobulin M in Prostate Cancer and Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Sanja Goč

    2013-01-01

    Full Text Available This study was aimed at defining molecular species of prostate-specific antigen (PSA in immune complexes with immunoglobulin M (IgM. Having in mind the oligoreactivity of IgM and its preference for carbohydrate antigens, there is the possibility that it can selectively recognize known PSA glycoisoforms. PSA-IgM complexes and free PSA fractions were separated from the sera of subjects with prostate cancer (PCa and benign prostatic hyperplasia (BPH by gel filtration and subjected to on-chip immunoaffinity and ion-exchange chromatography. PSA-immunoreactive species were detected using surface-enhanced laser desorption/ionization time of flight mass spectrometry. The obtained spectra were analyzed for protein and glycan composition. The general pattern of the molecular species of PCa PSA and BPH PSA found in complexes with IgM was similar. It comprised major peaks at 17 kDa and minor peaks at 28 kDa, corresponding to the entire mature glycosylated PSA. The main difference was the presence of incompletely glycosylated 26.8 kDa species, having putative paucimannosidic structures, observed in PCa PSA-IgM, but not in BPH PSA-IgM. Characteristic PCa PSA-IgM glycoforms pose the question of the possible role of glycosylation as a framework for immune surveillance and may be of interest in light of recent data indicating mannose-containing glycans as cancer biomarker.

  7. Molecularly imprinted polymer based on MWCNT-QDs as fluorescent biomimetic sensor for specific recognition of target protein

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Zhaoqiang [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Annie Bligh, S.W. [Department of Life Sciences, Faculty of Science and Technology, University of Westminster, 115 New Cavendish Street, London W1W 6UW (United Kingdom); Tao, Lei; Quan, Jing [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Nie, Huali, E-mail: niehuali@dhu.edu.cn [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Zhu, Limin, E-mail: lzhu@dhu.edu.cn [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Gong, Xiao [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China)

    2015-03-01

    A novel molecularly imprinted optosensing material based on multi-walled carbon nanotube-quantum dots (MWCNT-QDs) has been designed and synthesized for its high selectivity, sensitivity and specificity in the recognition of a target protein bovine serum albumin (BSA). Molecularly imprinted polymer coated MWCNT-QDs using BSA as the template (BMIP-coated MWCNT-QDs) exhibits a fast mass-transfer speed with a response time of 25 min. It is found that the BSA as a target protein can significantly quench the luminescence of BMIP-coated MWCNT-QDs in a concentration-dependent manner that is best described by a Stern–Volmer equation. The K{sub SV} for BSA is much higher than bovine hemoglobin and lysozyme, implying a highly selective recognition of the BMIP-coated MWCNT-QDs to BSA. Under optimal conditions, the relative fluorescence intensity of BMIP-coated MWCNT-QDs decreases linearly with the increasing target protein BSA in the concentration range of 5.0 × 10{sup −7}–35.0 × 10{sup −7} M with a detection limit of 80 nM. - Highlights: • A novel fluorescent biomimetic sensor based on MWCNT-QDs was designed. • The sensor exhibited a fast mass-transfer speed with a response time of 25 min. • The sensor possessed a highly selective recognition to BSA.

  8. A small-molecule compound inhibits a collagen-specific molecular chaperone and could represent a potential remedy for fibrosis.

    Science.gov (United States)

    Ito, Shinya; Ogawa, Koji; Takeuchi, Koh; Takagi, Motoki; Yoshida, Masahito; Hirokawa, Takatsugu; Hirayama, Shoshiro; Shin-Ya, Kazuo; Shimada, Ichio; Doi, Takayuki; Goshima, Naoki; Natsume, Tohru; Nagata, Kazuhiro

    2017-12-08

    Fibrosis can disrupt tissue structure and integrity and impair organ function. Fibrosis is characterized by abnormal collagen accumulation in the extracellular matrix. Pharmacological inhibition of collagen secretion therefore represents a promising strategy for the management of fibrotic disorders, such as liver and lung fibrosis. Hsp47 is an endoplasmic reticulum (ER)-resident collagen-specific molecular chaperone essential for correct folding of procollagen in the ER. Genetic deletion of Hsp47 or inhibition of its interaction with procollagen interferes with procollagen triple helix production, which vastly reduces procollagen secretion from fibroblasts. Thus, Hsp47 could be a potential and promising target for the management of fibrosis. In this study, we screened small-molecule compounds that inhibit the interaction of Hsp47 with collagen from chemical libraries using surface plasmon resonance (BIAcore), and we found a molecule AK778 and its cleavage product Col003 competitively inhibited the interaction and caused the inhibition of collagen secretion by destabilizing the collagen triple helix. Structural information obtained with NMR analysis revealed that Col003 competitively binds to the collagen-binding site on Hsp47. We propose that these structural insights could provide a basis for designing more effective therapeutic drugs for managing fibrosis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. BEACON/MOD: a computer program for thermal-hydraulic analysis of nuclear reactor containments - user's manual

    International Nuclear Information System (INIS)

    Broadus, C.R.; Doyle, R.J.; James, S.W.; Lime, J.F.; Mings, W.J.

    1980-04-01

    The BEACON code is a best-estimate, advanced containment code designed to perform a best-estimate analysis of the flow of a mixture of air, water, and steam in a nuclear reactor containment system under loss-of-coolant accident conditions. The code can simulate two-component, two-phase fluid flow in complex geometries using a combination of two-dimensional, one-dimensional, and lumped-parameter representations for the various parts of the system. The current version of BEACON, which is designated BEACON/MOD3, contains mass and heat transfer models for wall film and wall conduction. It is suitable for the evaluation of short-term transients in dry-containment systems. This manual describes the models employed in BEACON/MOD3 and specifies code implementation requirements. It provides application information for input data preparation and for output data interpretation

  10. BEACON/MOD2A analysis of the Arkansas-1 reactor cavity during a hypothetical hot leg break

    International Nuclear Information System (INIS)

    Ramsthaler, J.A.

    1979-01-01

    As part of the evaluation of the new MOD2A version of the BEACON code, the Arkansas-1 reactor cavity was modeled during a hypothetical loss-of-coolant accident. Results of the BEACON analysis were compared with results obtained previously with the COMPARE containment code. Studies were also made investigating some of the BEACON interphasic, timestep control, and wall heat transfer options to assure that these models were working properly and to observe their effects on the results. Descriptions of the Arkansas-1 reactor cavity, initial assumptions during the hypothetical LOCA, and methods of modeling with BEACON are presented. Some of the problems encountered in accurately modeling the penetrations surrounding the hot and cold leg pipes are also discussed

  11. Traveling-Wave Tube Amplifier Second Harmonic as Millimeter-Wave Beacon Source for Atmospheric Propagation Studies

    Science.gov (United States)

    Simons, Rainee N.; Wintucky, Edwin G.

    2014-01-01

    This paper presents the design and test results of a CW millimeter-wave satellite beacon source, based on the second harmonic from a traveling-wave tube amplifier and utilizes a novel waveguide multimode directional coupler. A potential application of the beacon source is for investigating the atmospheric effects on Q-band (37-42 GHz) and V/W-band (71- 76 GHz) satellite-to-ground signals.

  12. The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

    International Nuclear Information System (INIS)

    Ronchetti, D; Todoerti, K; Tuana, G; Agnelli, L; Mosca, L; Lionetti, M; Fabris, S; Colapietro, P; Miozzo, M; Ferrarini, M; Tassone, P; Neri, A

    2012-01-01

    Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may have a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM) by profiling purified malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCLs) and 4 normal controls. Overall, a global sno/scaRNAs downregulation was found in MMs and, even more, in sPCLs compared with normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the translocation/cyclin D4 (TC4) MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by an imprinting center at 15q11, which, however, resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information to the bio-molecular complexity of plasma cell dyscrasias

  13. Automated synthesis with HPLC purification of 18F-FMISO as specific molecular imaging probe of tumor hypoxia

    International Nuclear Information System (INIS)

    Wang Mingwei; Zhang Yingjian; Zhang Yongping

    2012-01-01

    An improved automated synthesis of 1-H-1-(3-[ 18 F] fluoro-2-hydroxypropyl)-2-nitro-imidazole ( 18 F-FMISO), a specific molecular imaging probe of tumor hypoxia, was developed using an upgraded Explora GN module integrated with Explora LC for HPLC purification in this study. The radiochemical synthesis of 18 F-FMISO was started with precursor 1-( 2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-tosyl-propanediol (NITTP) and included nucleophilic [ 18 F] radio-fluorination at 120℃ for 5 min and hydrolysis at 130℃ for 8 min. The automated synthesis of 18 F-FMISO, presenting fast, reliable and multi-run features, could be completed with the total synthesis time of less than 65 min and radiochemical yield of 25%∼35% (without decay correction). The quality control of 18 F-FMISO was identical with the radiopharmaceutical requirements, especially the radiochemical purity of greater than 99% and high chemical purity and specific activity own to HPLC purification. (authors)

  14. Phylogeny and molecular signatures (conserved proteins and indels that are specific for the Bacteroidetes and Chlorobi species

    Directory of Open Access Journals (Sweden)

    Lorenzini Emily

    2007-05-01

    Full Text Available Abstract Background The Bacteroidetes and Chlorobi species constitute two main groups of the Bacteria that are closely related in phylogenetic trees. The Bacteroidetes species are widely distributed and include many important periodontal pathogens. In contrast, all Chlorobi are anoxygenic obligate photoautotrophs. Very few (or no biochemical or molecular characteristics are known that are distinctive characteristics of these bacteria, or are commonly shared by them. Results Systematic blast searches were performed on each open reading frame in the genomes of Porphyromonas gingivalis W83, Bacteroides fragilis YCH46, B. thetaiotaomicron VPI-5482, Gramella forsetii KT0803, Chlorobium luteolum (formerly Pelodictyon luteolum DSM 273 and Chlorobaculum tepidum (formerly Chlorobium tepidum TLS to search for proteins that are uniquely present in either all or certain subgroups of Bacteroidetes and Chlorobi. These studies have identified > 600 proteins for which homologues are not found in other organisms. This includes 27 and 51 proteins that are specific for most of the sequenced Bacteroidetes and Chlorobi genomes, respectively; 52 and 38 proteins that are limited to species from the Bacteroidales and Flavobacteriales orders, respectively, and 5 proteins that are common to species from these two orders; 185 proteins that are specific for the Bacteroides genus. Additionally, 6 proteins that are uniquely shared by species from the Bacteroidetes and Chlorobi phyla (one of them also present in the Fibrobacteres have also been identified. This work also describes two large conserved inserts in DNA polymerase III (DnaE and alanyl-tRNA synthetase that are distinctive characteristics of the Chlorobi species and a 3 aa deletion in ClpB chaperone that is mainly found in various Bacteroidales, Flavobacteriales and Flexebacteraceae, but generally not found in the homologs from other organisms. Phylogenetic analyses of the Bacteroidetes and Chlorobi species is also

  15. Prostate-specific membrane antigen targeted protein contrast agents for molecular imaging of prostate cancer by MRI

    Science.gov (United States)

    Pu, Fan; Salarian, Mani; Xue, Shenghui; Qiao, Jingjuan; Feng, Jie; Tan, Shanshan; Patel, Anvi; Li, Xin; Mamouni, Kenza; Hekmatyar, Khan; Zou, Juan; Wu, Daqing; Yang, Jenny J.

    2016-06-01

    Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high resolution has yet to be achieved due to the lack of contrast agents with significantly improved relaxivity for sensitivity, targeting capabilities and metal selectivity. We have previously reported our creation of a novel class of protein Gd3+ contrast agents, ProCA32, which displayed significantly improved relaxivity while exhibiting strong Gd3+ binding selectivity over physiological metal ions. In this study, we report our effort in further developing biomarker-targeted protein MRI contrast agents for molecular imaging of PSMA. Among three PSMA targeted contrast agents engineered with addition of different molecular recognition sequences, ProCA32.PSMA exhibits a binding affinity of 1.1 +/- 0.1 μM for PSMA while the metal binding affinity is maintained at 0.9 +/- 0.1 × 10-22 M. In addition, ProCA32.PSMA exhibits r1 of 27.6 mM-1 s-1 and r2 of 37.9 mM-1 s-1 per Gd (55.2 and 75.8 mM-1 s-1 per molecule r1 and r2, respectively) at 1.4 T. At 7 T, ProCA32.PSMA also has r2 of 94.0 mM-1 s-1 per Gd (188.0 mM-1 s-1 per molecule) and r1 of 18.6 mM-1 s-1 per Gd (37.2 mM-1 s-1 per molecule). This contrast capability enables the first MRI enhancement dependent on PSMA expression levels in tumor bearing mice using both T1 and T2-weighted MRI at 7 T. Further development of these PSMA-targeted contrast agents are expected to be used for the precision imaging of prostate cancer at an early stage and to monitor disease progression and staging, as well as determine the effect of therapeutic treatment by non-invasive evaluation of the PSMA level using MRI.Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high

  16. Purification and heterogeneity of human kininogen. Use of DEAE-chromatography, molecular sieving and antibody specific immunosorbents.

    Science.gov (United States)

    Hamberg, U; Elg, P; Nissinen, E; Stelwagen, P

    1975-01-01

    Various methods of preparing human kininogen were investigated with an aim to limit the immunoreactive contaminant proteins to permit purification by immunosorption. A five-step procedure is described giving 7.5% yield of highly purified kininogen (pharmacological purity 14--20) from pooled human plasma, and containing approximately 30% alpha-2HS-glycoprotein and 2.8% albumin. Alpha-2HS could not be removed by polyacrylamide gel electrophoresis or isoelectric focusing in column. Analysis of heterogeneity of kininogen after chromatography on DEAE-Sephadex using various linear gradients and gel filtration on Sephadex G-100 suggested that a minor component may be an aggregate, not included in the yield. It remains uncertain whether this component derives from an occasionally observed high molecular form of active kininogen in the primary purification steps in the 7-12 S sieve fractions from Sephadex G-200, and excluded from further purification by pooling. Purification with immunosorbents was investigated using batch operations with antibody specific polymers prepared with antisera insolubilized with ethylchloroformate. It was found that the adsorption-desorption procedure was favourable for immunization purposes in producing highly specific immunologically pure kininogen. The kininogen obtained by this method or by the removal of contaminant alpha-2HS and albumin with the corresponding antibody specific polymers gave similar heterogenous patterns by polyacrylamide gel electrophoresis, indicating a main band of kininogen and several faintly stained bands which responded only to anti-kininogen. With 200 mug of the kininogen protein purified by immunosorption using monospecific antiserum the kininogen precipitation titre was 1:8 after 6--8 weeks in rabbits. With a polymer prepared with 4 ml anti-kininogen serum (1:8) and incubated with 800 mug highly purified kininogen approximately half the protein was desorbed with 2 M and 3 M sodium iodide in the first adsorption

  17. Substrate Specificity of Cysteine Proteases Beyond the S2 Pocket: Mutagenesis and Molecular Dynamics Investigation of Fasciola hepatica Cathepsins L

    Directory of Open Access Journals (Sweden)

    Ileana Corvo

    2018-04-01

    Full Text Available Cysteine proteases are widespread in all life kingdoms, being central to diverse physiological processes based on a broad range of substrate specificity. Paralogous Fasciola hepatica cathepsin L proteases are essential to parasite invasion, tissue migration and reproduction. In spite of similarities in their overall sequence and structure, these enzymes often exhibit different substrate specificity. These preferences are principally determined by the amino acid composition of the active site's S2 subsite (pocket of the enzyme that interacts with the substrate P2 residue (Schetcher and Berger nomenclature. Although secreted FhCL1 accommodates aliphatic residues in the S2 pocket, FhCL2 is also efficient in cleaving proline in that position. To understand these differences, we engineered the FhCL1 S2 subsite at three amino acid positions to render it identical to that present in FhCL2. The substitutions did not produce the expected increment in proline accommodation in P2. Rather, they decreased the enzyme's catalytic efficiency toward synthetic peptides. Nonetheless, a change in the P3 specificity was associated with the mutation of Leu67 to Tyr, a hinge residue between the S2 and S3 subsites that contributes to the accommodation of Gly in S3. Molecular dynamic simulations highlighted changes in the spatial distribution and secondary structure of the S2 and S3 pockets of the mutant FhCL1 enzymes. The reduced affinity and catalytic efficiency of the mutant enzymes may be due to a narrowing of the active site cleft that hinders the accommodation of substrates. Because the variations in the enzymatic activity measured could not be exclusively allocated to those residues lining the active site, other more external positions might modulate enzyme conformation, and, therefore, catalytic activity.

  18. Structure Prediction, Molecular Dynamics Simulation and Docking Studies of D-Specific Dehalogenase from Rhizobium sp. RC1

    Directory of Open Access Journals (Sweden)

    Ismaila Yada Sudi

    2012-11-01

    Full Text Available Currently, there is no three-dimensional structure of D-specific dehalogenase (DehD in the protein database. We modeled DehD using ab initio technique, performed molecular dynamics (MD simulation and docking of D-2-chloropropionate (D-2CP, D-2-bromopropionate (D-2BP, monochloroacetate (MCA, monobromoacetate (MBA, 2,2-dichloropropionate (2,2-DCP, d,l-2,3-dichloropropionate (d,l-2,3-DCP, and 3-chloropropionate (3-CP into the DehD active site. The sequences of DehD and D-2-haloacid dehalogenase (HadD from Pseudomonas putida AJ1 have 15% sequence similarity. The model had 80% of the amino acid residues in the most favored region when compared to the crystal structure of DehI from Pseudomonas putida PP3. Docking analysis revealed that Arg107, Arg134 and Tyr135 interacted with D-2CP, and Glu20 activated the water molecule for hydrolytic dehalogenation. Single residue substitutions at 25–30 °C showed that polar residues of DehD were stable when substituted with nonpolar residues and showed a decrease in activity within the same temperature range. The molecular dynamics simulation of DehD and its variants showed that in R134A variant, Arg107 interacted with D-2CP, while in Y135A, Gln221 and Arg231 interacted with D-2CP. It is our emphatic belief that the new model will be useful for the rational design of DehDs with enhanced potentials.

  19. Visually Detecting the Variation of miR-301a Expression Using Gold Nanoparticle Beacon.

    Science.gov (United States)

    Zhang, Ying; Li, Kai; Li, Dandan; Li, Changfeng; Zhang, Bin

    2018-02-01

    It is well known that microRNA-301a plays an important role in many diseases, as well as is overexpressed in human colon cancer and affects the process of tumorigenesis. Determination of the miR-301a expression provides insight into the mechanism of tumor progression. In this study, we designed a special hairpin deoxyribonucleic acid (DNA) for miR-301a to functionalize gold nanoparticles, which served as a beacon for detecting miR-301a expression. A-quenching efficiency up to 90% was achieved. The beacon we designed in this study can monitor the precise variation of miR-301a expression in vivo. The strategy reported in this study is a promising approach for the measurement of miRNA in living cells. Moreover, it has a great potential in the study of drug screening and discovery.

  20. Multi-Band Multi-Tone Tunable Millimeter-Wave Frequency Synthesizer For Satellite Beacon Transmitter

    Science.gov (United States)

    Simons, Rainee N.; Wintucky, Edwin G.

    2016-01-01

    This paper presents the design and test results of a multi-band multi-tone tunable millimeter-wave frequency synthesizer, based on a solid-state frequency comb generator. The intended application of the synthesizer is in a satellite beacon transmitter for radio wave propagation studies at K-band (18 to 26.5 GHz), Q-band (37 to 42 GHz), and E-band (71 to 76 GHz). In addition, the architecture for a compact beacon transmitter, which includes the multi-tone synthesizer, polarizer, horn antenna, and power/control electronics, has been investigated for a notional space-to-ground radio wave propagation experiment payload on a small satellite. The above studies would enable the design of robust high throughput multi-Gbps data rate future space-to-ground satellite communication links.

  1. Design of a K/Q-Band Beacon Receiver for the Alphasat TDP#5 Experiment

    Science.gov (United States)

    Morse, Jacquelynne R.

    2014-01-01

    This paper describes the design and performance of a coherent KQ-band (2040 GHz) beacon receiver developed at NASA Glenn Research Center (GRC) that will be installed at the Politecnico di Milano (POLIMI) for use in the Alphasat Technology Demonstration Payload 5 (TDP5) beacon experiment. The goal of this experiment is to characterize rain fade attenuation at 40 GHz to improve the performance of existing statistical rain attenuation models in the Q-band. The ground terminal developed by NASA GRC utilizes an FFT-based frequency estimation receiver capable of characterizing total path attenuation effects due to gaseous absorption, clouds, rain, and scintillation. The receiver system has been characterized in the lab and demonstrates a system dynamic range performance of better than 58 dB at 1 Hz and better than 48 dB at 10 Hz rates.

  2. Nanosecond-level time synchronization of AERA using a beacon reference transmitter and commercial airplanes

    Directory of Open Access Journals (Sweden)

    Huege Tim

    2017-01-01

    Full Text Available Radio detection of cosmic-ray air showers requires time synchronization of detectors on a nanosecond level, especially for advanced reconstruction algorithms based on the wavefront curvature and for interferometric analysis approaches. At the Auger Engineering Radio Array, the distributed, autonomous detector stations are time-synchronized via the Global Positioning System which, however, does not provide sufficient timing accuracy. We thus employ a dedicated beacon reference transmitter to correct for eventby-event clock drifts in our offline data analysis. In an independent cross-check of this “beacon correction” using radio pulses emitted by commercial airplanes, we have shown that the combined timing accuracy of the two methods is better than 2 nanoseconds.

  3. Nanosecond-level time synchronization of AERA using a beacon reference transmitter and commercial airplanes

    Science.gov (United States)

    Huege, Tim

    2017-03-01

    Radio detection of cosmic-ray air showers requires time synchronization of detectors on a nanosecond level, especially for advanced reconstruction algorithms based on the wavefront curvature and for interferometric analysis approaches. At the Auger Engineering Radio Array, the distributed, autonomous detector stations are time-synchronized via the Global Positioning System which, however, does not provide sufficient timing accuracy. We thus employ a dedicated beacon reference transmitter to correct for eventby-event clock drifts in our offline data analysis. In an independent cross-check of this "beacon correction" using radio pulses emitted by commercial airplanes, we have shown that the combined timing accuracy of the two methods is better than 2 nanoseconds.

  4. Effectiveness of allergen-specific immunotherapy with pollen allergens in children from the viewpoint of molecular allergology

    Directory of Open Access Journals (Sweden)

    S.M. Nedelska

    2017-03-01

    Full Text Available Background. Allergen-specific immunotherapy as elimination procedures is the only method of treatment and prevention of allergic disorders formation and exacerbation of clinical symptoms. One of the approaches to molecular diagnosis is choice of allergen for allergen-specific immunotherapy (ASIT. The purpose of our study was to identify possible reasons of failure of ASIT with pollen allergens (predominantly weeds in children with seasonal allergic rhinitis (hay fever and/or bronchial asthma based on studying hypersensitivity to the allergens, analysis of anamnestic data. Materials and methods. Allergy skin prick tests were conducted to 192 children (middle age 9.8 ± 2.7 years with the seasonal symptoms of rhinitis and/or bronchial asthma according to standard methodology with pollen allergens of Immunolog Ltd (Vinnytsia. We evaluated positive results as 5 mm and higher diameter of papula/hyperemia. The anamnestic survey was carried out in 52 patients by means of the questionnaire that contained questions about cross allergy (pollen-food, oral allergy syndrome, concomitant pathology of upper respiratory tract and effectiveness of АSІТ, which is elaborated by us. Results. The skin prick tests show that in 192 patients, who have hay fever, ragweed, sunflower sensibilization predominates (56 and 58 %, correspondingly. About 10–20 % of children are sensitive to cereals (ryegrass, fescue. To the allergens of poplar, acacia, couch-grass, oak, mint, nettle, walnut, the positive reactions of prick tests were observed in 3–7 children, that is 1.5–3.6 %. According to our results, 23 % of patients had sensibilization to 5 and more pollen allergens. 52 % of children had concomitant food allergy, 15 % of patients have reactions of the lips, oral cavity when using certain products, mostly tomatoes, nuts, seeds (they were diagnosed oral allergy syndrome. Also, one third of children have varying degrees of adenoid hypertrophy, tonsils hypertrophy

  5. Increased dose near the skin due to electromagnetic surface beacon transponder.

    Science.gov (United States)

    Ahn, Kang-Hyun; Manger, Ryan; Halpern, Howard J; Aydogan, Bulent

    2015-05-08

    The purpose of this study was to evaluate the increased dose near the skin from an electromagnetic surface beacon transponder, which is used for localization and tracking organ motion. The bolus effect due to the copper coil surface beacon was evaluated with radiographic film measurements and Monte Carlo simulations. Various beam incidence angles were evaluated for both 6 MV and 18 MV experimentally. We performed simulations using a general-purpose Monte Carlo code MCNPX (Monte Carlo N-Particle) to supplement the experimental data. We modeled the surface beacon geometry using the actual mass of the glass vial and copper coil placed in its L-shaped polyethylene terephthalate tubing casing. Film dosimetry measured factors of 2.2 and 3.0 enhancement in the surface dose for normally incident 6 MV and 18 MV beams, respectively. Although surface dose further increased with incidence angle, the relative contribution from the bolus effect was reduced at the oblique incidence. The enhancement factors were 1.5 and 1.8 for 6 MV and 18 MV, respectively, at an incidence angle of 60°. Monte Carlo simulation confirmed the experimental results and indicated that the epidermal skin dose can reach approximately 50% of the dose at dmax at normal incidence. The overall effect could be acceptable considering the skin dose enhancement is confined to a small area (~ 1 cm2), and can be further reduced by using an opposite beam technique. Further clinical studies are justified in order to study the dosimetric benefit versus possible cosmetic effects of the surface beacon. One such clinical situation would be intact breast radiation therapy, especially large-breasted women.

  6. Beaconing Performance in IEEE 802.11p Vehicular Networks: the Effect of Radio Channel Congestion

    OpenAIRE

    Librino, Francesco; Renda, Maria Elena; Santi, Paolo

    2013-01-01

    In this paper, we study the performance of the beaconing mechanism underlying active safety vehicular applications in presence of different levels of channel congestion. The importance of this study lies in the fact that channel congestion is considered a major factor influencing communication performance in vehicular networks, and that ours is the first investigation of the effects of congestion based on extensive, real-world measurements. The results of our study reveal that congestion has ...

  7. Beacon: A three-dimensional structural analysis code for bowing history of fast breeder reactor cores

    International Nuclear Information System (INIS)

    Miki, K.

    1979-01-01

    The core elements of an LMFBR are bowed due to radial gradients of both temperature and neutron flux in the core. Since all hexagonal elements are multiply supported by adjacent elements or the restraint system, restraint forces and bending stresses are induced. In turn, these forces and stresses are relaxed by irradiation enhanced creep of the material. The analysis of the core bowing behavior requires a three-dimensional consideration of the mechanical interactions among the core elements, because the core consists of different kinds of elements and of fuel assemblies with various burnup histories. A new computational code BEACON has been developed for analyzing the bowing behavior of an LMFBR's core in three dimensions. To evaluate mechanical interactions among core elements, the code uses the analytical method of the earlier SHADOW code. BEACON analyzes the mechanical interactions in three directions, which form angles of 60 0 with one another. BEACON is applied to the 60 0 sector of a typical LMFBR's core for analyzing the bowing history during one equilibrium cycle. 120 core elements are treated, assuming the boundary condition of rotational symmetry. The application confirms that the code can be an effective tool for parametric studies as well as for detailed structural analysis of LMFBR's core. (orig.)

  8. Magnetic resonance beacon to detect intracellular microRNA during neurogenesis.

    Science.gov (United States)

    Lee, Jonghwan; Jin, Yeon A; Ko, Hae Young; Lee, Yong Seung; Heo, Hyejung; Cho, Sujeong; Kim, Soonhag

    2015-02-01

    Magnetic resonance imaging (MRI) offers great spatial resolution for viewing deep tissues and anatomy. We developed a self-assembling signal-on magnetic fluorescence nanoparticle to visualize intracellular microRNAs (miRNAs or miRs) during neurogenesis using MRI. The self-assembling nanoparticle (miR124a MR beacon) was aggregated by the incubation of three different oligonucleotides: a 3' adaptor, a 5' adaptor, and a linker containing miR124a-binding sequences. The T2-weighted magnetic resonance (MR) signal of the self-assembled nanoparticle was quenched when miR124a was absent from test tubes or was minimally expressed in cells and tissues. When miR124a was present in test tubes or highly expressed in vitro and in vivo during P19 cell neurogenesis, it hybridized with the miR124a MR beacon, causing the linker to detach, resulting in increased signal-on MRI intensity. This MR beacon can be used as a new imaging probe to monitor the miRNA-mediated regulation of cellular processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Sparse Localization with a Mobile Beacon Based on LU Decomposition in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Chunhui Zhao

    2015-09-01

    Full Text Available Node localization is the core in wireless sensor network. It can be solved by powerful beacons, which are equipped with global positioning system devices to know their location information. In this article, we present a novel sparse localization approach with a mobile beacon based on LU decomposition. Our scheme firstly translates node localization problem into a 1-sparse vector recovery problem by establishing sparse localization model. Then, LU decomposition pre-processing is adopted to solve the problem that measurement matrix does not meet the re¬stricted isometry property. Later, the 1-sparse vector can be exactly recovered by compressive sensing. Finally, as the 1-sparse vector is approximate sparse, weighted Cen¬troid scheme is introduced to accurately locate the node. Simulation and analysis show that our scheme has better localization performance and lower requirement for the mobile beacon than MAP+GC, MAP-M, and MAP-MN schemes. In addition, the obstacles and DOI have little effect on the novel scheme, and it has great localization performance under low SNR, thus, the scheme proposed is robust.

  10. Different low-molecular-mass organic acids specifically control leaching of arsenic and lead from contaminated soil.

    Science.gov (United States)

    Ash, Christopher; Tejnecký, Václav; Borůvka, Luboš; Drábek, Ondřej

    2016-04-01

    Low-molecular-mass organic acids (LMMOA) are of key importance for mobilisation and fate of metals in soil, by functioning as ligands that increase the amount of dissolved metal in solution or by dissociation of metal binding minerals. Column leaching experiments were performed on soil polluted with As and Pb, in order to determine the specificity of LMMOA related release for individual elements, at varying organic acid concentrations. Acetic, citric and oxalic acids were applied in 12h leaching experiments over a concentration range (0.5-25 mM) to soil samples that represent organic and mineral horizons. The leaching of As followed the order: oxalic>citric>acetic acid in both soils. Arsenic leaching was attributed primarily to ligand-enhanced dissolution of mineral oxides followed by As released into solution, as shown by significant correlation between oxalic and citric acids and content of Al and Fe in leaching solutions. Results suggest that subsurface mineral soil layers are more vulnerable to As toxicity. Leaching of Pb from both soils followed the order: citric>oxalic>acetic acid. Mineral soil samples were shown to be more susceptible to leaching of Pb than samples characterised by a high content of organic matter. The leaching efficiency of citric acid was attributed to formation of stable complexes with Pb ions, which other acids are not capable of. Results obtained in the study are evidence that the extent of As and Pb leaching in contaminated surface and subsurface soil depends significantly on the types of carboxylic acid involved. The implications of the type of acid and the specific element that can be mobilised become increasingly significant where LMMOA concentrations are highest, such as in rhizosphere soil. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Molecular characterization of Babesia peircei and Babesia ugwidiensis provides insight into the evolution and host specificity of avian piroplasmids

    Directory of Open Access Journals (Sweden)

    Michael J. Yabsley

    2017-12-01

    Full Text Available There are 16 recognized species of avian-infecting Babesia spp. (Piroplasmida: Babesiidae. While the classification of piroplasmids has been historically based on morphological differences, geographic isolation and presumed host and/or vector specificities, recent studies employing gene sequence analysis have provided insight into their phylogenetic relationships and host distribution and specificity. In this study, we analyzed the sequences of the 18S rRNA gene and ITS-1 and ITS-2 regions of two Babesia species from South African seabirds: Babesia peircei from African penguins (Spheniscus demersus and Babesia ugwidiensis from Bank and Cape cormorants (Phalacrocorax neglectus and P. capensis, respectively. Our results show that avian Babesia spp. are not monophyletic, with at least three distinct phylogenetic groups. B. peircei and B. ugwidiensis are closely related, and fall within the same phylogenetic group as B. ardeae (from herons Ardea cinerea, B. poelea (from boobies Sula spp. and B. uriae (from murres Uria aalge. The validity of B. peircei and B. ugwidiensis as separate species is corroborated by both morphological and genetic evidence. On the other hand, our results indicate that B. poelea might be a synonym of B. peircei, which in turn would be a host generalist that infects seabirds from multiple orders. Further studies combining morphological and molecular methods are warranted to clarify the taxonomy, phylogeny and host distribution of avian piroplasmids. Keywords: Africa, Babesia, Piroplasmida, Phalacrocoracidae, Spheniscidae, Tick-borne pathogen

  12. Probing specific molecular processes and intermediates by time-resolved Fourier transform infrared spectroscopy: application to the bacteriorhodopsin photocycle.

    Science.gov (United States)

    Lórenz-Fonfría, Víctor A; Kandori, Hideki; Padrós, Esteve

    2011-06-23

    We present a general approach for probing the kinetics of specific molecular processes in proteins by time-resolved Fourier transform infrared (IR) spectroscopy. Using bacteriorhodopsin (bR) as a model we demonstrate that by appropriately monitoring some selected IR bands it is possible obtaining the kinetics of the most important events occurring in the photocycle, namely changes in the chromophore and the protein backbone conformation, and changes in the protonation state of the key residues implicated in the proton transfers. Besides confirming widely accepted views of the bR photocycle, our analysis also sheds light into some disputed issues: the degree of retinal torsion in the L intermediate to respect the ground state; the possibility of a proton transfer from Asp85 to Asp212; the relationship between the protonation/deprotonation of Asp85 and the proton release complex; and the timing of the protein backbone dynamics. By providing a direct way to estimate the kinetics of photocycle intermediates the present approach opens new prospects for a robust quantitative kinetic analysis of the bR photocycle, which could also benefit the study of other proteins involved in photosynthesis, in phototaxis, or in respiratory chains.

  13. Tracking neuronal marker expression inside living differentiating cells using molecular beacons

    DEFF Research Database (Denmark)

    Ilieva, Mirolyuba; Della Vedova, Paolo; Hansen, Ole

    2013-01-01

    and tyrosine hydroxylase mRNAs were expressed 2 and 3 days post induction of differentiation, respectively. Oct 4 was not detected with MB in these cells and signal was not increased over time suggesting that MB are generally stable inside the cells. The gene expression changes measured using MBs were...... confirmed using qRT-PCR. These results suggest that MBs are simple to use sensors inside living cell, and particularly useful for studying dynamic gene expression in heterogeneous cell populations....

  14. Next Generation Sensors for Contaminants in Water: Catalytic DNA as a Molecular Beacon

    Science.gov (United States)

    2006-11-01

    Bohn, P. W., 1998: Electric Field Induced Permeability Modulation in Pure and Mixed Langmuir - Blodgett Multilayers of Hemicyanine Dyes and...c) the magnitude of κa. Because κ is controlled by solution ionic strength, control of flow in these nanometer channels is exceptionally versatile...added. Finally, the sensor can be extremely rugged -- in particular, it is insensitive to episodic loss of liquid analyte stream, so it can survive

  15. Molecular beacon nanosensors for live cell detection and tracking differentiation and reprogramming

    DEFF Research Database (Denmark)

    Ilieva, Mirolyuba

    2013-01-01

    open to closed state within living cells. Using MBs targeting pluripotent stem cell markers we demonstrated reverse into a more immature state of LUHMES induced by neurosphere-like growth conditions. Moreover, we have been able to trace localisation of this particular population during differentiation...... in separation of fluorophore from quencher and thereby emission of a fluorescent signal that can be detected. In this project the usability and applicability of MBs for live cell detection and tracing of gene expression was demonstrated. MBs library targeting gene markers for pluripotent stem cells as well...... and thus demonstrate the usability of MBs for monitoring cell behaviour within 3D clusters. Finally, MBs detection of expression of human pluripotent markers after reprograming of adult somatic cells with plasmid codding for mouse transcription factors was demonstrated. In conclusion, the method of using...

  16. Photodynamic Molecular Beacons: An Image-Guided Therapeutic Approach to Breast Cancer Vertebral Metastases

    Science.gov (United States)

    2012-03-01

    uptake. Prog Clin Biol Res. 1984;; 170: 629-­36. 14. Wilson BC, Firnau G, Jeeves WP, Brown KL, Burns-­McCormick DM . Chromatographic analysis and...Photosensitizer-­conjugated human serum albumin nanoparticles for effective photodynamic therapy. Theranostics. 2011;; 1: 230-­9. 24. Ferreira CL, Yapp DT, Crisp

  17. Apportioning sources of organic matter in streambed sediments: An integrated molecular and compound-specific stable isotope approach

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Richard J., E-mail: Richard.J.Cooper@uea.ac.uk [School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ (United Kingdom); Pedentchouk, Nikolai; Hiscock, Kevin M.; Disdle, Paul [School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ (United Kingdom); Krueger, Tobias [IRI THESys, Humboldt University, 10099 Berlin (Germany); Rawlins, Barry G. [British Geological Survey, Keyworth, Nottingham NG12 5GG (United Kingdom)

    2015-07-01

    We present a novel application for quantitatively apportioning sources of organic matter in streambed sediments via a coupled molecular and compound-specific isotope analysis (CSIA) of long-chain leaf wax n-alkane biomarkers using a Bayesian mixing model. Leaf wax extracts of 13 plant species were collected from across two environments (aquatic and terrestrial) and four plant functional types (trees, herbaceous perennials, and C{sub 3} and C{sub 4} graminoids) from the agricultural River Wensum catchment, UK. Seven isotopic (δ{sup 13}C{sub 27}, δ{sup 13}C{sub 29}, δ{sup 13}C{sub 31}, δ{sup 13}C{sub 27–31}, δ{sup 2}H{sub 27}, δ{sup 2}H{sub 29}, and δ{sup 2}H{sub 27–29}) and two n-alkane ratio (average chain length (ACL), carbon preference index (CPI)) fingerprints were derived, which successfully differentiated 93% of individual plant specimens by plant functional type. The δ{sup 2}H values were the strongest discriminators of plants originating from different functional groups, with trees (δ{sup 2}H{sub 27–29} = − 208‰ to − 164‰) and C{sub 3} graminoids (δ{sup 2}H{sub 27–29} = − 259‰ to − 221‰) providing the largest contrasts. The δ{sup 13}C values provided strong discrimination between C{sub 3} (δ{sup 13}C{sub 27–31} = − 37.5‰ to − 33.8‰) and C{sub 4} (δ{sup 13}C{sub 27–31} = − 23.5‰ to − 23.1‰) plants, but neither δ{sup 13}C nor δ{sup 2}H values could uniquely differentiate aquatic and terrestrial species, emphasizing a stronger plant physiological/biochemical rather than environmental control over isotopic differences. ACL and CPI complemented isotopic discrimination, with significantly longer chain lengths recorded for trees and terrestrial plants compared with herbaceous perennials and aquatic species, respectively. Application of a comprehensive Bayesian mixing model for 18 streambed sediments collected between September 2013 and March 2014 revealed considerable temporal variability in the

  18. Nanosilica-based molecularly imprinted polymer nanoshell for specific recognition and determination of rhodamine B in red wine and beverages.

    Science.gov (United States)

    Long, Zerong; Xu, Weiwei; Lu, Yi; Qiu, Hongdeng

    2016-09-01

    A new and facile rhodamine B (RhB)-imprinted polymer nanoshell coating for SiO2 nanoparticles was readily prepared by a combination of silica gel modification and molecular surface imprinting. The RhB-imprinted polymers (RhB-MIPs) were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and UV-vis spectroscopy; the binding properties and selectivity of these MIPs were investigated in detail. The uniformly imprinted nanoparticles displayed a rather thin shell thickness (23nm) with highly effective recognition sites, showing homogenous distribution and monolayer adsorption. The maximum MIP adsorption capacity (Qm) was as high as 45.2mgg(-1), with an adsorption equilibrium time of about 15min at ambient temperature. Dynamic rebinding experiments showed that chemical adsorption is crucial for RhB binding to RhB-MIPs. The adsorption isotherm for RhB-MIPs binding could also be described by the Langmuir equation at different temperatures and pH values. Increasing temperature led to an enhanced Qm, a decreased dissociation constant (K'd), and a more negative free energy (ΔG), indicating that adsorption is favored at higher temperatures. Moreover, the adsorption capacity of RhB was remarkably affected by pH. At pH>7, the adsorption of RhB was driven by hydrogen bonding interactions, while at pH<7 electrostatic forces were dominant. Additionally, the MIPs also showed specific recognition of RhB from the standard mixture solution containing five structurally analogs. This method was also successfully employed to determine RhB content in red wine and beverages using three levels of spiking, with recoveries in the range of 91.6-93.1% and relative standard deviations lower than 4.1%. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Molecular and compound-specific hydrogen isotope analyses of insoluble organic matter from different carbonaceous chondrite groups

    Science.gov (United States)

    Wang, Yi; Huang, Yongsong; Alexander, Conel M. O.'D.; Fogel, Marilyn; Cody, George

    2005-07-01

    We have conducted the first systematic analyses of molecular distribution and δD values of individual compounds in pyrolysates of insoluble organic matter (IOM) from different carbonaceous chondrite groups, using flash pyrolysis coupled to gas chromatography-mass spectrometry and compound-specific D/H analysis. IOM samples from six meteorites of different classifications, Elephant Moraine (EET) 92042 (CR2), Orgueil (CI1), Allan Hills (ALH) 83100 (CM1/2), Murchison (CM2), ALH 85013 (CM2), and Tagish Lake (C2) were isolated and studied. Except for the pyrolysate of Tagish Lake IOM, pyrolysates of all five meteorite IOM samples were dominated by an extensive series of aromatic (C 1 to C 7 alkyl-substituted benzenes, C 0 to C 2 alkyl-substituted naphthalenes), with aliphatic (straight chain and branched C 10 to C 15 alkanes) hydrocarbons and several S- and O- containing compounds (C 1 to C 2 alkylthiophenes, benzothiophene, benzaldehyde) being also present. The strong similarity in the pyrolysates of different carbonaceous chondrites suggests certain common characteristics in the formation mechanisms of IOM from different meteorites. The Tagish Lake IOM sample is unique in that its pyrolysate lacks most of the alkyl-substituted aromatic hydrocarbons detected in other meteorite IOM samples, suggesting distinctively different formation processes. Both bulk δD values of meteorite IOMs and weighted-average δD values of individual compounds in pyrolysates show a decreasing trend: CR2 > CI1 > CM2 > C2 (Tagish Lake), with the EET 92042 (CR2) IOM having the highest δD values (˜2000‰ higher than other samples). We attribute the high D contents in the IOM to primitive interstellar organic sources.

  20. Hairpin DNA-Templated Silver Nanoclusters as Novel Beacons in Strand Displacement Amplification for MicroRNA Detection.

    Science.gov (United States)

    Zhang, Jingpu; Li, Chao; Zhi, Xiao; Ramón, Gabriel Alfranca; Liu, Yanlei; Zhang, Chunlei; Pan, Fei; Cui, Daxiang

    2016-01-19

    MicroRNA (miRNA) biomarkers display great potential for cancer diagnosis and prognosis. The development of rapid and specific methods for miRNA detection has become a hotspot. Herein, hairpin DNA-templated silver nanoclusters (AgNCs/HpDNA) were prepared and integrated into strand-displacement amplification (SDA) as a novel beacon for miRNA detection. The light-up platform was established based on guanine (G)-rich fluorescence enhancement that essentially converted the excitation/emission pair of AgNCs/HpDNAs from a shorter wavelength to a longer wavelength, and then achieved fluorescent enhancement at longer wavelength. On the basis of the validation of the method, the single and duplex detection were conducted in two plasma biomarkers (miR-16-5p and miR-19b-3p) for the diagnosis of gastric cancer. The probe (AgNCs/RED 16(7s)C) utilized for miR-16-5p detection adopted a better conformation with high specificity to recognize single-base mismatches by producing dramatically opposite signals (increase or decrease at 580 nm ex/640 nm em) while the probe (AgNCs/GRE 19b(5s)C) for miR-19b-3p generated dual signals (increase at 490 nm ex/570 nm em and decrease at 430 nm ex/530 nm em) with bright fluorescence in one reaction during the amplification, but unexpectedly was partially digested. This is for the first time to allow the generation of enhanced fluorescent AgNCs and the target recognition integrated into a single process, which offers great opportunity for specific miRNA detection in an easy and rapid way.

  1. Creating a Connected Community: Lessons Learned from the Western New York Beacon Community

    Science.gov (United States)

    Maloney, Nancy; Heider, Arvela R.; Rockwood, Amy; Singh, Ranjit

    2014-01-01

    Introduction: Secure exchange of clinical data among providers has the potential to improve quality, safety, efficiency, and reduce duplication. Many communities are experiencing challenges in building effective health information exchanges (HIEs). Previous studies have focused on financial and technical issues regarding HIE development. This paper describes the Western New York (WNY) HIE growth and lessons learned about accelerating progress to become a highly connected community. Methods: HEALTHeLINK, with funding from the Office of the National Coordinator for Health Information Technology (ONC) under the Beacon Community Program, expanded HIE usage in eight counties. The communitywide transformation process used three main drivers: (1) a communitywide Electronic Health Record (EHR) adoption program; (2) clinical transformation partners; and (3) HIE outreach and infrastructure development. Results: ONC Beacon Community funding allowed WNY to achieve a new level in the use of interoperable HIE. Electronic delivery of results into the EHR expanded from 23 practices in 2010 to 222 practices in 2013, a tenfold increase. There were more than 12.5 million results delivered electronically (HL7 messages) to 222 practices’ EHRs via the HIE in 2013. Use of a secure portal and Virtual Health Record (VHR) to access reports (those not delivered directly to the EHR) also increased significantly, from 13,344 report views in 2010 to over 600,000 in 2013. Discussion and Conclusion: The WNY Beacon successfully expanded the sharing of clinical information among different sources of data and providers, creating a highly connected community to improve the quality and continuity of care. Technical, organizational, and community lessons described in this paper should prove beneficial to others as they pursue efforts to create connected communities. PMID:25848618

  2. Performance of the NASA Beacon Receiver for the Alphasat Aldo Paraboni TDP5 Propagation Experiment

    Science.gov (United States)

    Nessel, James; Morse, Jacquelynne; Zemba, Michael; Riva, Carlo; Luini, Lorenzo

    2015-01-01

    NASA Glenn Research Center (GRC) and the Politecnico di Milano (POLIMI) have initiated a joint propagation campaign within the framework of the Alphasat propagation experiment to characterize rain attenuation, scintillation, and gaseous absorption effects of the atmosphere in the 40 gigahertz band. NASA GRC has developed and installed a K/Q-band (20/40 gigahertz) beacon receiver at the POLIMI campus in Milan, Italy, which receives the 20/40 gigahertz signals broadcast from the Alphasat Aldo Paraboni Technology Demonstration Payload (TDP) no. 5 beacon payload. The primary goal of these measurements is to develop a physical model to improve predictions of communications systems performance within the Q-band. Herein, we describe the design and preliminary performance of the NASA propagation terminal, which has been installed and operating in Milan since June 2014. The receiver is based upon a validated Fast Fourier Transform (FFT) I/Q digital design approach utilized in other operational NASA propagation terminals, but has been modified to employ power measurement via a frequency estimation technique and to coherently track and measure the amplitude of the 20/40 gigahertz beacon signals. The system consists of a 1.2-meter K-band and a 0.6-meter Q-band Cassegrain reflector employing synchronous open-loop tracking to track the inclined orbit of the Alphasat satellite. An 8 hertz sampling rate is implemented to characterize scintillation effects, with a 1-hertz measurement bandwidth dynamic range of 45 decibels. A weather station with an optical disdrometer is also installed to characterize rain drop size distribution for correlation with physical based models.

  3. Preliminary Results of the NASA Beacon Receiver for Alphasat Aldo Paraboni TDP5 Propagation Experiment

    Science.gov (United States)

    Nessel, James; Morse, Jacquelynne; Zemba, Michael; Riva, Carlo; Luini, Lorenzo

    2014-01-01

    NASA Glenn Research Center (GRC) and the Politecnico di Milano (POLIMI) have initiated a joint propagation campaign within the framework of the Alphasat propagation experiment to characterize rain attenuation, scintillation, and gaseous absorption effects of the atmosphere in the 40 GHz band. NASA GRC has developed and installed a K/Q-band (20/40 GHz) beacon receiver at the POLIMI campus in Milan, Italy, which receives the 20/40 GHz signals broadcast from the Alphasat Aldo Paraboni TDP#5 beacon payload. The primary goal of these measurements is to develop a physical model to improve predictions of communications systems performance within the Q-band. Herein, we describe the design and preliminary performance of the NASA propagation terminal, which has been installed and operating in Milan since May 2014. The receiver is based upon a validated Fast Fourier Transform (FFT) I/Q digital design approach utilized in other operational NASA propagation terminals, but has been modified to employ power measurement via a frequency estimation technique and to coherently track and measure the amplitude of the 20/40 GHz beacon signals. The system consists of a 1.2-m K-band and a 0.6-m Qband Cassegrain reflector employing synchronous open-loop tracking to track the inclined orbit of the Alphasat satellite. An 8 Hz sampling rate is implemented to characterize scintillation effects, with a 1-Hz measurement bandwidth dynamic range of 45 dB. A weather station with an optical disdrometer is also installed to characterize rain drop size distribution for correlation with physical based models.

  4. Molecular cloning, characterization and functional analysis of a novel juvenile-specific cathepsin L of Fasciola gigantica.

    Science.gov (United States)

    Sansri, Veerawat; Changklungmoa, Narin; Chaichanasak, Pannigan; Sobhon, Prasert; Meemon, Krai

    2013-10-01

    Cathepsin L proteases are a major class of endopeptidases expressed at a high level in Fasciola parasites. Several isoforms of cathepsin L were detected and they may perform different functions during the parasite development. In this study, a complete cDNA encoding a cathepsin L protease was cloned from a newly excysted juvenile (NEJ) cDNA library of Fasciola gigantica and named FgCatL1H. It encoded a 326 amino acid preproenzyme which shared 62.8-83.1% and 39.5-42.9% identity to Fasciola spp. and mammalian cathepsins L, respectively. All functionally important residues previously described for cathepsin L were conserved in FgCatL1H. Phylogenetic analysis demonstrated that FgCatL1H belonged to a distinct group, clade 4, with respect to adult and other juvenile Fasciola cathepsin L genes. FgCatL1H expression was detected by RT-PCR, using gene specific primers, in metacercariae and NEJ, and the expression gradually decreased in advanced developmental stages. A recombinant proFgCatL1H (rproFgCatL1H) was expressed in the yeast Pichia pastoris, affinity purified, and found to migrate in SDS-PAGE at approximately 47.6 and 38.3kDa in glycosylated and deglycosylated forms, respectively. The molecular mass of the activated mature rFgCatL1H in glycosylated form was approximately 40.7kDa. Immunoblotting and immunohistochemistry using rabbit antibodies against rproFgCatL1H showed that FgCatL1H was predominantly expressed in epithelial cells of the digestive tract of metacercariae, NEJs and juveniles of F. gigantica. FgCatL1H could cleave the synthetic fluorogenic substrate Z-Phe-Arg-MCA preferentially over Z-Gly-Pro-Arg-MCA at an optimum pH of 6.5. It also showed hydrolytic activity against native substrates, including type I collagen, laminin, and immunoglobulin G (IgG) in vitro, suggesting possible roles in host tissue migration and immune evasion. Therefore, the FgCatL1H is a possible target for vaccine and chemotherapy for controlling F. gigantica infection. Copyright

  5. The use of low frequency HF beacons to derive layer shape

    International Nuclear Information System (INIS)

    Heron, M.L.; Davies, K.

    1978-01-01

    The ATS-6 with its coherent multifrequency channels and various calibrations has brought the technology of beacon experiments to the point where the experimental accuracy exceeds that of some of the approximations used to derive total electron content. For example, the magnetic field term in the Faraday rotation experiment used to be given a mean value corresponding to about 50 km above the F layer peak. Another quantity that depends on profile shape is also available with present experiment, namely the refraction or second order term for carrier phase, modulation phase, or Faraday rotation. Some theoretical and experimental results are presented on these problems

  6. Developing children’s palliative care in Africa through beacon centres: lessons learnt

    Science.gov (United States)

    2013-01-01

    Much progress has been made in the provision of palliative care across sub-Saharan Africa, however much still remains to be done, particularly in the area of children’s palliative care (CPC). The Beacon Centres programme was set up in 2009, aimed at improving access to CPC in South Africa, Uganda and Tanzania through more and better-trained health professionals and CPC clinical services of a high standard. Having identified sites in each country to develop into CPC Beacon Centres, Navigators were identified who would be the ‘champions’ for CPC in those sites and lead a programme of training, mentorship and support. Five navigators (2 in Uganda and Tanzania and 1 in South Africa) were trained between September and December 2009. Following this they undertook CPC needs assessments at the 3 centres and set up and delivered a six-month CPC training programme, providing mentorship and support to students to enable them to integrate CPC into their workplaces. To date, 188 participants have commenced the six-month course, with 80 having completed it. CPC has been integrated into the activities of the centres and a CPC virtual resource centre set up in South Africa. The achievements from the Beacon project have been great and the work of the navigators immense, but as in all projects it has not been without its challenges. Lessons learnt include issues around: the focus of the project; the length and nature of the training; assessment; accreditation; the choice of navigators; mentoring; administrative support; co-ordination; the choice of project sites; and the integration of CPC into services. The need for CPC is not going to go away and it is therefore important that models of scaling-up are found that are not only practical, feasible, affordable and sustainable, but that focus on the outcome of improved CPC for all those who need it. It is hoped that the lessons shared from the Beacon Project will help in developing and implementing such models. PMID:23419095

  7. The Southeastern Minnesota Beacon Project for Community-driven Health Information Technology: Origins, Achievements, and Legacy.

    Science.gov (United States)

    Chute, Christopher G; Hart, Lacey A; Alexander, Alex K; Jensen, Daniel W

    2014-01-01

    The Southeastern (SE) Minnesota Beacon organized all the health care providers, county public health organizations, and school districts in the deployment and integration of health information exchange (HIE) and targeted health communication around childhood asthma and diabetes. The community cooperated to establish a clinical data repository for all residents in the 11-county region. Through this community of practice approach that involved traditional and nontraditional providers, the SE Minnesota Beacon was able to realize unique applications of this technology. This manuscript overviews the associated organization and infrastructure of this community collaboration. The Office of the National Coordinator for Health Information Technology (ONC), as part of the American Recovery and Reinvestment Act of 2009 (ARRA) stimulus, established 17 projects throughout the United States targeting the introduction and meaningful use of health information technology (HIT). These 17 communities were intended to serve as an example of what could be accomplished. The SE Minnesota Beacon is one of these communities. The community ultimately opted for peer-to-peer HIE, using Nationwide Health Information Network (NwHIN) Connect software. The clinical data repository was established using the infrastructure developed by the Regenstrief Institute, which operated as a trusted third party. As an extension to HIE, the consortium of county public health departments created a patient data portal for use by school nurses and parents. Childhood asthma was addressed by creating, exchanging, and maintaining an "asthma action plan" for each affected child, shared throughout the community, including through the patient portal. Diabetes management introduced patient treatment decision tools and patient quality of life measures, facilitating care. Influenza vaccination was enhanced by large-scale community reporting in partnership with the state vaccination registry. The methodology and

  8. In situ exposure to non-directional beacons for air traffic control.

    Science.gov (United States)

    Joseph, Wout; Goeminne, Francis; Vermeeren, Günter; Verloock, Leen; Martens, Luc

    2012-04-01

    In situ electromagnetic field exposure of workers and the general public due to non-directional beacons (NDB) for air traffic control is assessed and characterized. For occupational exposure, the maximal measured electric field value is 881.6 V/m and the maximal magnetic field value is 9.1 A/m. The maximum electric fields exceed the International Commission on Non-Ionizing Radiation Protection (ICNIRP) reference levels at all seven NDB sites, and the magnetic fields at two of the seven NDB sites (occupational exposure). Recommendations and compliance distances for workers and the general public are provided. © 2012 Wiley Periodicals, Inc.

  9. Observability analysis of 2D single-beacon navigation in the presence of constant currents for two classes of maneuvers

    Digital Repository Service at National Institute of Oceanography (India)

    Crasta, N.; Bayat, M.; Aguiar, A.P.; Pascoal, A.M.

    . In particular, xc = 0 represents a circular motion about the beacon with radius v ω−1. The following result characterizes set of indistinguishable states for the system (5.1)-(5.2) subject to input class Ucir. Proposition 5.6. Consider the system (5...) = npi + 0.5 (−1)n pi, n ∈ Z. Notice also that under this condition the motion is a circular motion around the beacon. The following corollary follows from propositions 5.3 and 5.6. Corollary 5.8. Consider x0 ∈ M. Then (4.1)-(4.2) is observable...

  10. An extreme vertices mixture design approach to the optimisation of 1,2,3-trichlorobenzene specific molecularly imprinted polymers.

    Science.gov (United States)

    Cleland, Dougal; McCluskey, Adam

    2013-07-28

    Traditional approaches to molecularly imprinted polymer (MIP) design and optimisation typically afford a template (T) : functional monomer (FM) : crosslinker (CL) ratio of 1 : 2 : 20 to 1 : 4 : 20. This approach for 1,2,3-trichlorobenzene (7) as template gave a styrene based MIP (MIP(STY)) with an imprinting factor (IF) = 1.3. An extreme vertices mixture design (EVMD) approach was applied, and in two design cycles, 15 total experimental points, the optimum composition for MIP(STY) was determined as 0.40 : 0.05 : 0.55 (T : FM : CL) with IF = 2.8. Refinements gave optimum T : FM : CL ratios for the functional monomers: 4-vinylpyridine (4VP, 0.40 : 0.02 : 0.58); 2,4,6-trimethylstyrene (TMS, 0.40 : 0.02 : 0.58) and 2,3,4,5,6-pentafluorostyrene (PFS, 0.30 : 0.12 : 0.58) with IF = 2.8, 2.8 and 3.7 respectively. These ratios deviated significantly from the traditional MIP synthesis ratio. The low levels of FM for all MIPs, except for MIP(PFS), suggest that imprinting was more consistent with T-CL, than FM-T, interactions. Analysis of the specific interactions and removal (SR) of 7 with these MIPs revealed that the SR with MIP(STY) increased from 36% at 0.02 STY to 48% at 0.13 STY; with MIP(TMS) SR increased from 38% at 0.02 TMS to 42% at 0.10 TMS; and with MIP(PFS) SR increased from 34% at 0.02 PFS to 56% at 0.14 PFS. MIP(4VP) saw a decline in SR with increasing FM, with the highest SR was 35% at 0.02 4VP. This is consistent with changes in the non-specific interactions between 7 and the MIPs. Increasing the proportion of PFS produced the largest increase in imprinting of 7 demonstrated by the highest SR (56%) and highest IF (3.7). The application of an EVMD approach resulted in the IF of MIP(STY) increased from 1.3 to 2.8. The highest IF achieved by this study was 3.7 for MIP(PFS) in proportions of 0.30 : 0.12 : 0.48 (T : FM : CL).

  11. Novel primer specific false terminations during DNA sequencing reactions: danger of inaccuracy of mutation analysis in molecular diagnostics

    Science.gov (United States)

    Anwar, R; Booth, A; Churchill, A J; Markham, A F

    1996-01-01

    The determination of nucleotide sequence is fundamental to the identification and molecular analysis of genes. Direct sequencing of PCR products is now becoming a commonplace procedure for haplotype analysis, and for defining mutations and polymorphism within genes, particularly for diagnostic purposes. A previously unrecognised phenomenon, primer related variability, observed in sequence data generated using Taq cycle sequencing and T7 Sequenase sequencing, is reported. This suggests that caution is necessary when interpreting DNA sequence data. This is particularly important in situations where treatment may be dependent on the accuracy of the molecular diagnosis. Images PMID:16696096

  12. Molecular Allergen-Specific IgE Assays as a Complement to Allergen Extract-Based Sensitization Assessment

    NARCIS (Netherlands)

    Aalberse, Rob C.; Aalberse, Joost A.

    2015-01-01

    Molecular allergen-based component-resolved diagnostic IgE antibody tests have emerged in the form of singleplex assays and multiplex arrays. They use both native and recombinant allergen molecules, sometimes in combination with each other, to supplement allergen extract-based IgE antibody analyses.

  13. Molecular discrimination of Perna (Mollusca: Bivalvia) species using the polymerase chain reaction and species-specific mitochondrial primers

    DEFF Research Database (Denmark)

    Blair, D.; Waycott, M.; Byrne, L.

    2006-01-01

    This work was prompted by the need to be able to identify the invasive mussel species, Perna viridis, in tropical Australian seas using techniques that do not rely solely on morphology. DNA-based molecular methods utilizing a polymerase chain reaction (PCR) approach were developed to distinguish...

  14. Sex specific molecular responses of quick-to-court protein in Indian malarial vector Anopheles culicifacies: conflict of mating versus blood feeding behaviour

    Directory of Open Access Journals (Sweden)

    Tanwee Das De

    2017-07-01

    Full Text Available Understanding the molecular basis of mosquito behavioural complexity plays a central role in designing novel molecular tools to fight against their vector-borne diseases. Although the olfactory system plays an important role in guiding and managing many behavioural responses including feeding and mating, but the sex-specific regulation of olfactory responses remain poorly investigated. From our ongoing transcriptomic data annotation of olfactory tissue of blood fed adult female An. culicifacies mosquitoes; we have identified a 383 bp long unique transcript encoding a Drosophila homolog of the quick-to-court protein. Previously this was shown to regulate courtship behaviour in adult male Drosophila. A comprehensive in silico analysis of the quick-to-court (qtc gene of An. culicifacies (Ac-qtc predicts a 1536 bp single copy gene encoding 511 amino acid protein, having a high degree of conservation with other insect homologs. The age-dependent increased expression of putative Ac-qtc correlated with the maturation of the olfactory system, necessary to meet the sex-specific conflicting demand of mating (mate finding versus host-seeking behavioural responses. Sixteen to eighteen hours of starvation did not alter Ac-qtc expression in both sexes, however, blood feeding significantly modulated its response in the adult female mosquitoes, confirming that it may not be involved in sugar feeding associated behavioural regulation. Finally, a dual behavioural and molecular assay indicated that natural dysregulation of Ac-qtc in the late evening might promote the mating events for successful insemination. We hypothesize that Ac-qtc may play a unique role to regulate the sex-specific conflicting demand of mosquito courtship behaviour versus blood feeding behaviour in the adult female mosquitoes. Further elucidation of this molecular mechanism may provide further information to evaluate Ac-qtc as a key molecular target for mosquito-borne disease management.

  15. Preliminary Statistics from the NASA Alphasat Beacon Receiver in Milan, Italy

    Science.gov (United States)

    Nessel, James; Zemba, Michael; Morse, Jacquelynne; Luini, Lorenzo; Riva, Carlo

    2015-01-01

    NASA Glenn Research Center (GRC) and the Politecnico di Milano (POLIMI) have initiated a joint propagation campaign within the framework of the Alphasat propagation experiment to characterize rain attenuation, scintillation, and gaseous absorption effects of the atmosphere in the 40 gigahertz band. NASA GRC has developed and installed a K/Q-band (20/40 gigahertz) beacon receiver at the POLIMI campus in Milan, Italy, which receives the 20/40 gigahertz signals broadcast from the Alphasat Aldo Paraboni TDP no. 5 beacon payload. The primary goal of these measurements is to develop a physical model to improve predictions of communications systems performance within the Q-band. Herein, we provide an overview of the design and data calibration procedure, and present 6 months of preliminary statistics of the NASA propagation terminal, which has been installed and operating in Milan since May 2014. The Q-band receiver has demonstrated a dynamic range of 40 decibels at an 8-hertz sampling rate. A weather station with an optical disdrometer is also installed to characterize rain drop size distribution for correlation with physical based models.

  16. Performance Evaluation of Beacon-Enabled Mode for IEEE 802.15.4 Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    M. Udin Harun Al Rasyid

    2013-12-01

    Full Text Available IEEE 802.15.5 standard support structure of star and peer-to-peer network formation. Strating from these, the cluster tree network can be built as a special case of peer-to-peer network to increse coverage area. In this paper, we provide an performance evaluation of beacon- enabled mode for IEEE 802.15.4 wireless sensor network on star and cluster topology in order to get the maximum result to apply the appropriate topology model as needed. We conduct analysis on each topology model by using the numbers of nodes from 10 nodes to 100 nodes to analyze throughput, delay, energy consumption, and probability success packet by using NS2 simulator. The simulation results show that the throughput and the probability of success packet of cluster topology are higher than that of star topology, and the energy consumption of cluster topology is lesser than that of star topology. However, cluster topology increases the delay more than star topology. Keywords: IEEE 802.15.4, wireless sensor network, beacon-enabled mode, topology, csma/ca

  17. Secure Utilization of Beacons and UAVs in Emergency Response Systems for Building Fire Hazard.

    Science.gov (United States)

    Seo, Seung-Hyun; Choi, Jung-In; Song, Jinseok

    2017-09-25

    An intelligent emergency system for hazard monitoring and building evacuation is a very important application area in Internet of Things (IoT) technology. Through the use of smart sensors, such a system can provide more vital and reliable information to first-responders and also reduce the incidents of false alarms. Several smart monitoring and warning systems do already exist, though they exhibit key weaknesses such as a limited monitoring coverage and security, which have not yet been sufficiently addressed. In this paper, we propose a monitoring and emergency response method for buildings by utilizing beacons and Unmanned Aerial Vehicles (UAVs) on an IoT security platform. In order to demonstrate the practicability of our method, we also implement a proof of concept prototype, which we call the UAV-EMOR (UAV-assisted Emergency Monitoring and Response) system. Our UAV-EMOR system provides the following novel features: (1) secure communications between UAVs, smart sensors, the control server and a smartphone app for security managers; (2) enhanced coordination between smart sensors and indoor/outdoor UAVs to expand real-time monitoring coverage; and (3) beacon-aided rescue and building evacuation.

  18. Temporal change of EIA asymmetry revealed by a beacon receiver network in Southeast Asia

    Science.gov (United States)

    Watthanasangmechai, Kornyanat; Yamamoto, Mamoru; Saito, Akinori; Maruyama, Takashi; Yokoyama, Tatsuhiro; Nishioka, Michi; Ishii, Mamoru

    2015-05-01

    To reveal the temporal change of the equatorial ionization anomaly (EIA) asymmetry, a multipoint satellite-ground beacon experiment was conducted along the meridional plane of the Thailand-Indonesia sector. The observation includes one station near the magnetic equator and four stations at off-equator latitudes. This is the first EIA asymmetry study with high spatial resolution using GNU Radio Beacon Receiver (GRBR) observations in Southeast Asia. GRBR-total electron contents (TECs) from 97 polar-orbit satellite passes in March 2012 were analyzed in this study. Successive passes captured rapid evolution of EIA asymmetry, especially during geomagnetic disturbances. The penetrating electric fields that occur during geomagnetic disturbed days are not the cause of the asymmetry. Instead, high background TEC associated with an intense electric field empowers the neutral wind to produce severe asymmetry of the EIA. Such rapid evolution of EIA asymmetry was not seen during nighttime, when meridional wind mainly controlled the asymmetric structures. Additional data are necessary to identify the source of the variations, i.e., atmospheric waves. Precisely capturing the locations of the crests and the evolution of the asymmetry enhances understanding of the temporal change of EIA asymmetry at the local scale and leads to a future local modeling for TEC prediction in Southeast Asia.

  19. Perancangan Prototipe Receiver Beacon Black Box Locator Acoustic 37,5 kHz Pingers

    Directory of Open Access Journals (Sweden)

    RUSTAMAJI RUSTAMAJI

    2016-01-01

    When an aircraft caught in an accident and crashes into the water, its location can be detected using a device called a receiver beacon black box locator acoustic (pingers receiver. The pingers receiver functioned as a reciever signal with 37,5 kHz ± 1 kHz frequency from trnasmitter pingers or Underwater Locator Beacon (ULB which is on air plane black blox. In this research made design pingers receiver composed of a series of  Band Pass Filter (BPF, envelope detector, audio amplifier, and loud speaker. The signal of 37,5 kHz ± 1 kHz  frequency sent by pingers transmitter will bereceived by pingers receiver, after which the signal will be processed by the Band Pass Filter (BPF circuit before being detected by envelope detector for take back the signal information which like pulse signal with 10ms width and 1 second interval as pingers signal tha can  be to  be heard by human ear. Based on the  design that  was made, the signal ouput generated by the prototype has a 14 ms width with 1 second interval. Keywords: pingers receiver, band pass filter (BPF, envelope detector, loud speaker.

  20. Fish allergy in patients with parvalbumin-specific immunoglobulin E depends on parvalbumin content rather than molecular differences in the protein among fish species.

    Science.gov (United States)

    Kobayashi, Ayako; Kobayashi, Yukihiro; Shiomi, Kazuo

    2016-10-01

    Allergenic characteristics of purified parvalbumins from different fish species have not been thoroughly investigated. We revealed that purified parvalbumins from nine different fish species have identical IgE-reactivities and high cross-reactivities. We also showed that fish allergenicity is associated with the parvalbumin content of the fish species, rather than species-specific differences in the molecular characteristics of the individual parvalbumin proteins.

  1. Indication for a chiral phase in the molecular magnetic chain Gd(hfac)3NiTiPr by specific heat and μ+SR measurements

    International Nuclear Information System (INIS)

    Lascialfari, A.; Ullu, R.; Affronte, M.; Cinti, F.; Caneschi, A.; Gatteschi, D.; Rovai, D.; Pini, M.G.; Rettori, A.

    2004-01-01

    Specific heat and muon spin relaxation (μ + SR) measurements performed in the molecular magnetic chain Gd(hfac) 3 NiTiPr provide indication for the onset, at T 0 =2.08 K, of a phase with chiral order in the absence of long-range helical order. Specific heat data (probing the chirality-chirality correlation function) show a peak at T 0 that disappears upon application of a 5 T magnetic field, while μ + SR data (probing the spin-spin correlation function) do not present any anomaly at T 0 nor oscillations in the asymmetry curve below T 0

  2. Structural and Biochemical Studies of a Fluoroacetyl-CoA-Specific Thioesterase Reveal a Molecular Basis for Fluorine Selectivity†,‡

    OpenAIRE

    Weeks, Amy M.; Coyle, Scott M.; Jinek, Martin; Doudna, Jennifer A.; Chang, Michelle C. Y.

    2010-01-01

    We have initiated a broad-based program aimed at understanding the molecular basis of fluorine specificity in enzymatic systems, and in this context, we report crystallographic and biochemical studies on a fluoroacetyl-coenzyme A (CoA) specific thioesterase (FlK) from Streptomyces cattleya. Our data establish that FlK is competent to protect its host from fluoroacetate toxicity in vivo and demonstrate a 106-fold discrimination between fluoroacetyl-CoA(kcat/KM=5×107M−1 s−1) and acetyl-CoA(kcat...

  3. 75 FR 20364 - Public Buildings Service; Key Largo Beacon Annex Site; Key Largo, FL; Transfer of Property

    Science.gov (United States)

    2010-04-19

    ... GENERAL SERVICES ADMINISTRATION [Wildlife Order 187; 4-D-FL-1218] Public Buildings Service; Key Largo Beacon Annex Site; Key Largo, FL; Transfer of Property Pursuant to section 2 of Public Law 537, 80th Congress, approved May 19, 1948 (16 U.S.C. 667c), notice is hereby given that: 1. The General...

  4. Guiding Math Students to Campus Services: An Impact Evaluation of the Beacon Program at South Texas College

    Science.gov (United States)

    Visher, Mary; Butcher, Kristin F.; Cerna, Oscar S.

    2011-01-01

    This research rigorously evaluates whether a low-cost intervention can improve students' performance in developmental math. The "Beacon Mentoring Program" was developed at South Texas College by professors, administrators, and staff at the college. Surveys of students revealed that many did not have someone on campus whom they felt they…

  5. Beacon Charter School Needs a School: A Case of Capital Outlay of Charters in a Public District

    Science.gov (United States)

    Wronowski, Meredith L.

    2017-01-01

    The case study presented below is a representation of a real-world, ongoing situation involving a public school district's capital outlay for charter schools within its boundaries. One particular charter, Beacon Charter School, was promised a permanent building by the public school district that also acts as its authorizer. However, recent events…

  6. BEACON/MOD2A: a computer program for subcompartment analysis of nuclear reactor containment. A user's manual

    International Nuclear Information System (INIS)

    Wells, R.A.

    1979-03-01

    The BEACON code is a Best Estimate Advanced Containment code which being developed by EG and G, Idaho, Inc., at the Idaho National Engineering Laboratory. The program is designed to perform a best estimate analysis of the flow of a mixture of air, water, and steam in a nuclear reactor containment system under loss-of-coolant accident conditions. The code can simulate two-component, two-phase fluid flow in complex geometries using a combination of two-dimensional, one-dimensional, and lumped-parameter representations for the various parts of the system. The current version of BEACON, which is designated BEACON/MOD2A, contains mass and heat transfer models for wall film and for wall conduction. It is suitable for the evaluation of short term transients in PWR dry containment systems. This manual describes the models employed in BEACON/MOD2A and specifies code implementation requirements. It provides application information for input data preparation and for output data interpretation

  7. Certain laws governing the influence of high molecular polymer additives on specific electrical conductivity and viscosity of zincate alkaline solution

    Energy Technology Data Exchange (ETDEWEB)

    Dmitrenko, V.Ye.; Toropetsera, T.N.; Zubov, M.S.

    1983-01-01

    A study was made of the influence of polymer additives of different nature: polyelectrolyte, copolymer of ethylene with maleic anhydride, polymethacrylic acid and nonpolyectrolyte copolymer of vinyl alcohol with vinyleneglycol and polyvinyleneglycol on specific electrical conductance and viscosity of the zincate alkaline solution. It is indicated that with an increase in the content of additives, the specific conductance of the solution diminishes according to a linear law, while the viscosity rises. The additives of polyelectrolyte nature reduce more strongly the specific conductance and increase the viscosity than the nonpolyelectrolyte additives. From a comparison of the data on specific conductance and viscosity the following conclusion is drawn: the more the polymer ''structures'' the zincate alkaline solution, the more strongly it reduces its specific electrical conductance.

  8. Beacon of Hope? Lessons Learned from Efforts to Reduce Civilian Deaths from Police Shootings in an Australian State.

    Science.gov (United States)

    Saligari, Jessica; Evans, Richard

    2016-04-01

    In the 1990s, the police service in Victoria, Australia, faced a crisis of community confidence due to a spate of civilian deaths from police shootings. In that decade, twice as many civilians died at the hands of the police in Victoria than in every other Australian state combined. Most of those killed were mentally ill and affected by drugs and alcohol, and were rarely a serious threat except to themselves. The problem was also almost entirely an urban phenomenon. Shootings in rural communities, where mentally ill people were more likely to be personally known to local police, were (and remain) almost unknown. The large number of fatalities was recognised as a serious threat to public confidence, and Victoria Police introduced a ground-breaking training programme, Operation Beacon. Operating procedures and weapons training were fundamentally changed, to focus on de-escalation of conflict and avoiding or minimising police use of force. In the short term, Operation Beacon was successful. Shooting incidents were dramatically reduced. However, during the first decade of the new century, the number of civilians being killed again increased. This article examines Operation Beacon, both as a successful model for reducing civilian deaths at the hand of police and as a cautionary tale for police reform. We argue that the lessons of Operation Beacon have been gradually forgotten and that old habits and attitudes resurfaced. Fatal shootings of mentally ill civilians can be prevented, but if success is to be other than temporary, the Beacon philosophy must be continually reemphasised by police management.

  9. New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1

    DEFF Research Database (Denmark)

    Korolkova, Yuliya V; Bocharov, Eduard V; Angelo, Kamilla

    2002-01-01

    The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 shares the common molecular scaffold with other short scorpion toxins. The toxin spatial structure...... resolved by NMR consists of a short alpha-helix and a triple-stranded antiparallel beta-sheet. By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K+ (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located...

  10. Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

    National Research Council Canada - National Science Library

    Worsham, Maria J; Raju, Usha; Chase, Gary; Lu, Mei

    2004-01-01

    .... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

  11. Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

    National Research Council Canada - National Science Library

    Worsham, Maria J; Raju, Usha; Lu, Mei

    2006-01-01

    .... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

  12. Molecular identification of Malaysian Chrysomya megacephala (Fabricius) and Chrysomya rufifacies (Macquart) using life stage specific mitochondrial DNA.

    Science.gov (United States)

    Kavitha, R; Tan, T C; Lee, H L; Nazni, W A; Sofian, A M

    2013-06-01

    DNA identification of blow fly species can be a very useful tool in forensic entomology. One of the potential benefits that mitochondrial DNA (mtDNA) has offered in the field of forensic entomology is species determination. Conventional identification methods have limitations for sibling and closely related species of blow fly and stage and quality of the specimen used. This could be overcome by DNA-based identification methods using mitochondrial DNA which does not demand intact or undamaged specimens. Mitochondrial DNA is usually isolated from whole blow fly and legs. Alternate sources for mitochondrial DNA isolation namely, egg, larva, puparium and empty puparium were explored in this study. The sequence of DNA obtained for each sample for every life cycle stage was 100% identical for a particular species, indicating that the egg, 1st instar, 2nd instar, 3rd instar, pupa, empty puparium and adult from the same species and obtained from same generation will exhibit similar DNA sequences. The present study also highlighted the usefulness of collecting all life cycle stages of blow fly during crime scene investigation with proper preservation and subsequent molecular analysis. Molecular identification provides a strong basis for species identification and will prove an invaluable contribution to forensic entomology as an investigative tool in Malaysia.

  13. Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex.

    Science.gov (United States)

    Fame, Ryann M; Dehay, Colette; Kennedy, Henry; Macklis, Jeffrey D

    2017-03-01

    Callosal projection neurons (CPN) interconnect the neocortical hemispheres via the corpus callosum and are implicated in associative integration of multimodal information. CPN have undergone differential evolutionary elaboration, leading to increased diversity of cortical neurons-and more extensive and varied connections in neocortical gray and white matter-in primates compared with rodents. In mouse, distinct sets of genes are enriched in discrete subpopulations of CPN, indicating the molecular diversity of rodent CPN. Elements of rodent CPN functional and organizational diversity might thus be present in the further elaborated primate cortex. We address the hypothesis that genes controlling mouse CPN subtype diversity might reflect molecular patterns shared among mammals that arose prior to the divergence of rodents and primates. We find that, while early expression of the examined CPN-enriched genes, and postmigratory expression of these CPN-enriched genes in deep layers are highly conserved (e.g., Ptn, Nnmt, Cited2, Dkk3), in contrast, the examined genes expressed by superficial layer CPN show more variable levels of conservation (e.g., EphA3, Chn2). These results suggest that there has been evolutionarily differential retraction and elaboration of superficial layer CPN subpopulations between mouse and macaque, with independent derivation of novel populations in primates. Together, these data inform future studies regarding CPN subpopulations that are unique to primates and rodents, and indicate putative evolutionary relationships. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Considerations for Community-Based mHealth Initiatives: Insights From Three Beacon Communities

    Science.gov (United States)

    2013-01-01

    Mobile health (mHealth) is gaining widespread attention for its potential to engage patients in their health and health care in their daily lives. Emerging evidence suggests that mHealth interventions can be used effectively to support behavior change, but numerous challenges remain when implementing these programs at the community level. This paper provides an overview of considerations when implementing community-based mHealth initiatives, based on the experiences of three Beacon Communities across the United States that have launched text messaging (short message service, SMS) pilot programs aimed at diabetes risk reduction and disease management. The paper addresses lessons learned and suggests strategies to overcome challenges related to developing text message content, conducting marketing and outreach, enrolling participants, engaging providers, evaluating program effectiveness, and sustaining and scaling the programs. PMID:24128406

  15. ATS-6 radio beacon electron content measurements at Ootacamund, India, October 1975-July 1976

    International Nuclear Information System (INIS)

    Bouwer, S.D.; Davies, K.; Donnelly, R.F.; Grubb, R.N.; Jones, J.E.

    1980-03-01

    An atlas of total slant-path columnar electron content data measured between the ATS-6 satellite and Ootacamund, India, a site near the magnetic Equator is presented. Although these measurements were taken during a solar minimum, the general level of flare and geomagnetic activity that occurred during the observation period is summarized. These total content (N(T)) data were derived from the modulation phase (group delay) of a carrier signal transmitted from the geostationary satellite's Radio Beacon Experiment. This atlas contains two data sets: (1) N(T) as 2-min subsamples digitally recorded between 2 October 1975 and 28 January 1976 corrected for ATS-6 pitch maneuvers and (2) N(T) as 15-min subsamples chart recorded between 21 October 1975 and 22 July 1976 but uncorrected for changes in satellite orientation

  16. Considerations for community-based mHealth initiatives: insights from three Beacon Communities.

    Science.gov (United States)

    Abebe, Nebeyou A; Capozza, Korey L; Des Jardins, Terrisca R; Kulick, David A; Rein, Alison L; Schachter, Abigail A; Turske, Scott A

    2013-10-15

    Mobile health (mHealth) is gaining widespread attention for its potential to engage patients in their health and health care in their daily lives. Emerging evidence suggests that mHealth interventions can be used effectively to support behavior change, but numerous challenges remain when implementing these programs at the community level. This paper provides an overview of considerations when implementing community-based mHealth initiatives, based on the experiences of three Beacon Communities across the United States that have launched text messaging (short message service, SMS) pilot programs aimed at diabetes risk reduction and disease management. The paper addresses lessons learned and suggests strategies to overcome challenges related to developing text message content, conducting marketing and outreach, enrolling participants, engaging providers, evaluating program effectiveness, and sustaining and scaling the programs.

  17. Molecular-Level Thermodynamic Switch Controls Chemical Equilibrium in Sequence-Specific Hydrophobic Interaction of 35 Dipeptide Pairs

    OpenAIRE

    Chun, Paul W.

    2003-01-01

    Applying the Planck-Benzinger methodology, the sequence-specific hydrophobic interactions of 35 dipeptide pairs were examined over a temperature range of 273–333 K, based on data reported by Nemethy and Scheraga in 1962. The hydrophobic interaction in these sequence-specific dipeptide pairs is highly similar in its thermodynamic behavior to that of other biological systems. The results imply that the negative Gibbs free energy change minimum at a well-defined stable temperature, 〈Ts〉, where t...

  18. Evaluation of a rectangular rapid flashing beacon system at the Belmont Ridge Road and W&OD Trail mid-block crosswalk.

    Science.gov (United States)

    2015-05-01

    On April 8, 2013, the Virginia Department of Transportation (VDOT) installed a Rectangular Rapid Flashing Beacon : (RRFB) system at Belmont Ridge Road in Loudoun County that included two units at the Washington and Old Dominion : (W&OD) Trail crossin...

  19. Energy optimization for upstream data transfer in 802.15.4 beacon-enabled star formulation

    Science.gov (United States)

    Liu, Hua; Krishnamachari, Bhaskar

    2008-08-01

    Energy saving is one of the major concerns for low rate personal area networks. This paper models energy consumption for beacon-enabled time-slotted media accessing control cooperated with sleeping scheduling in a star network formulation for IEEE 802.15.4 standard. We investigate two different upstream (data transfer from devices to a network coordinator) strategies: a) tracking strategy: the devices wake up and check status (track the beacon) in each time slot; b) non-tracking strategy: nodes only wake-up upon data arriving and stay awake till data transmitted to the coordinator. We consider the tradeoff between energy cost and average data transmission delay for both strategies. Both scenarios are formulated as optimization problems and the optimal solutions are discussed. Our results show that different data arrival rate and system parameters (such as contention access period interval, upstream speed etc.) result in different strategies in terms of energy optimization with maximum delay constraints. Hence, according to different applications and system settings, different strategies might be chosen by each node to achieve energy optimization for both self-interested view and system view. We give the relation among the tunable parameters by formulas and plots to illustrate which strategy is better under corresponding parameters. There are two main points emphasized in our results with delay constraints: on one hand, when the system setting is fixed by coordinator, nodes in the network can intelligently change their strategies according to corresponding application data arrival rate; on the other hand, when the nodes' applications are known by the coordinator, the coordinator can tune the system parameters to achieve optimal system energy consumption.

  20. Molecular mechanism of strict substrate specificity of an extradiol dioxygenase, DesB, derived from Sphingobium sp. SYK-6.

    Directory of Open Access Journals (Sweden)

    Keisuke Sugimoto

    Full Text Available DesB, which is derived from Sphingobium sp. SYK-6, is a type II extradiol dioxygenase that catalyzes a ring opening reaction of gallate. While typical extradiol dioxygenases show broad substrate specificity, DesB has strict substrate specificity for gallate. The substrate specificity of DesB seems to be required for the efficient growth of S. sp. SYK-6 using lignin-derived aromatic compounds. Since direct coordination of hydroxyl groups of the substrate to the non-heme iron in the active site is a critical step for the catalytic reaction of the extradiol dioxygenases, the mechanism of the substrate recognition and coordination of DesB was analyzed by biochemical and crystallographic methods. Our study demonstrated that the direct coordination between the non-heme iron and hydroxyl groups of the substrate requires a large shift of the Fe (II ion in the active site. Mutational analysis revealed that His124 and His192 in the active site are essential to the catalytic reaction of DesB. His124, which interacts with OH (4 of the bound gallate, seems to contribute to proper positioning of the substrate in the active site. His192, which is located close to OH (3 of the gallate, is likely to serve as the catalytic base. Glu377' interacts with OH (5 of the gallate and seems to play a critical role in the substrate specificity. Our biochemical and structural study showed the substrate recognition and catalytic mechanisms of DesB.

  1. Genetic and molecular characterization of leaf rust resistance in two durum landraces against the durum- specific Puccinia triticina races

    Science.gov (United States)

    The Portuguese durum landraces, Aus26582 and Aus26579, showed resistance against two very different durum-specific Puccinia triticina (Pt) races CA 1.2 and ETH 12.5-2 collected from California and Ethiopia, respectively. Aus26582 and Aus26579 were crossed with a susceptible landrace Bansi to develop...

  2. MO-FG-BRA-06: Electromagnetic Beacon Insertion in Lung Cancer Patients and Resultant Surrogacy Errors for Dynamic MLC Tumour Tracking

    Energy Technology Data Exchange (ETDEWEB)

    Hardcastle, N; Booth, J; Caillet, V; Haddad, C; Crasta, C [Royal North Shore Hospital, St. Leonards, NSW (Australia); O’Brien, R; Keall, P [University of Sydney, Sydney, NSW (Australia); Szymura, K [Royal North Shore Hospital, Sydney, NSW (Australia)

    2016-06-15

    Purpose: To assess endo-bronchial electromagnetic beacon insertion and to quantify the geometric accuracy of using beacons as a surrogate for tumour motion in real-time multileaf collimator (MLC) tracking of lung tumours. Methods: The LIGHT SABR trial is a world-first clinical trial in which the MLC leaves move with lung tumours in real time on a standard linear accelerator. Tracking is performed based on implanted electromagnetic beacons (CalypsoTM, Varian Medical Systems, USA) as a surrogate for tumour motion. Five patients have been treated and have each had three beacons implanted endo-bronchially under fluoroscopic guidance. The centre of mass (C.O.M) has been used to adapt the MLC in real-time. The geometric error in using the beacon C.O.M as a surrogate for tumour motion was measured by measuring the tumour and beacon C.O.M in all phases of the respiratory cycle of a 4DCT. The surrogacy error was defined as the difference in beacon and tumour C.O.M relative to the reference phase (maximum exhale). Results: All five patients have had three beacons successfully implanted with no migration between simulation and end of treatment. Beacon placement relative to tumour C.O.M varied from 14 to 74 mm and in one patient spanned two lobes. Surrogacy error was measured in each patient on the simulation 4DCT and ranged from 0 to 3 mm. Surrogacy error as measured on 4DCT was subject to artefacts in mid-ventilation phases. Surrogacy error was a function of breathing phase and was typically larger at maximum inhale. Conclusion: Beacon placement and thus surrogacy error is a major component of geometric uncertainty in MLC tracking of lung tumours. Surrogacy error must be measured on each patient and incorporated into margin calculation. Reduction of surrogacy error is limited by airway anatomy, however should be taken into consideration when performing beacon insertion and planning. This research is funded by Varian Medical Systems via a collaborative research agreement.

  3. MO-FG-BRA-06: Electromagnetic Beacon Insertion in Lung Cancer Patients and Resultant Surrogacy Errors for Dynamic MLC Tumour Tracking

    International Nuclear Information System (INIS)

    Hardcastle, N; Booth, J; Caillet, V; Haddad, C; Crasta, C; O’Brien, R; Keall, P; Szymura, K

    2016-01-01

    Purpose: To assess endo-bronchial electromagnetic beacon insertion and to quantify the geometric accuracy of using beacons as a surrogate for tumour motion in real-time multileaf collimator (MLC) tracking of lung tumours. Methods: The LIGHT SABR trial is a world-first clinical trial in which the MLC leaves move with lung tumours in real time on a standard linear accelerator. Tracking is performed based on implanted electromagnetic beacons (CalypsoTM, Varian Medical Systems, USA) as a surrogate for tumour motion. Five patients have been treated and have each had three beacons implanted endo-bronchially under fluoroscopic guidance. The centre of mass (C.O.M) has been used to adapt the MLC in real-time. The geometric error in using the beacon C.O.M as a surrogate for tumour motion was measured by measuring the tumour and beacon C.O.M in all phases of the respiratory cycle of a 4DCT. The surrogacy error was defined as the difference in beacon and tumour C.O.M relative to the reference phase (maximum exhale). Results: All five patients have had three beacons successfully implanted with no migration between simulation and end of treatment. Beacon placement relative to tumour C.O.M varied from 14 to 74 mm and in one patient spanned two lobes. Surrogacy error was measured in each patient on the simulation 4DCT and ranged from 0 to 3 mm. Surrogacy error as measured on 4DCT was subject to artefacts in mid-ventilation phases. Surrogacy error was a function of breathing phase and was typically larger at maximum inhale. Conclusion: Beacon placement and thus surrogacy error is a major component of geometric uncertainty in MLC tracking of lung tumours. Surrogacy error must be measured on each patient and incorporated into margin calculation. Reduction of surrogacy error is limited by airway anatomy, however should be taken into consideration when performing beacon insertion and planning. This research is funded by Varian Medical Systems via a collaborative research agreement.

  4. Comprehensive molecular diagnosis of 67 Chinese Usher syndrome probands: high rate of ethnicity specific mutations in Chinese USH patients.

    Science.gov (United States)

    Jiang, Lichun; Liang, Xiaofang; Li, Yumei; Wang, Jing; Zaneveld, Jacques Eric; Wang, Hui; Xu, Shan; Wang, Keqing; Wang, Binbin; Chen, Rui; Sui, Ruifang

    2015-09-04

    Usher syndrome (USH) is the most common disease causing combined deafness and blindness. It is predominantly an autosomal recessive genetic disorder with occasionally digenic cases. Molecular diagnosis of USH patients is important for disease management. Few studies have tried to find the genetic cause of USH in Chinese patients. This study was designed to determine the mutation spectrum of Chinese USH patients. We applied next generation sequencing to characterize the mutation spectrum in 67 independent Chinese families with at least one member diagnosed with USH. Blood was collected at Peking Union Medical College Hospital. This cohort is one of the largest USH cohorts reported. We utilized customized panel and whole exome sequencing, variant analysis, Sanger validation and segregation tests to find disease causing mutations in these families. We identified biallelic disease causing mutations in known USH genes in 70 % (49) of our patients. As has been previously reported, MYO7A is the most frequently mutated gene in our USH type I patients while USH2A is the most mutated gene in our USH type II patients. In addition, we identify mutations in CLRN1, DFNB31, GPR98 and PCDH15 for the first time in Chinese USH patients. Together, mutations in CLRN1, DNFB31, GPR98 and PCDH15 account for 11.4 % of disease in our cohort. Interestingly, although the spectrum of disease genes is quite similar between our Chinese patient cohort and other patient cohorts from different (and primarily Caucasian) ethnic backgrounds, the mutations themselves are dramatically different. In particular, 76 % (52/68) of alleles found in this study have never been previously reported. Interestingly, we observed a strong enrichment for severe protein truncating mutations expected to have severe functional consequence on the protein in USH II patients compared to the reported mutation spectrum in RP patients, who often carry partial protein truncating mutations. Our study provides the first

  5. Molecular phylogeny of mangroves IV. nature and extent of intra-specific genetic variation and species diversity in mangroves

    International Nuclear Information System (INIS)

    Parida, A.; Parani, M.; Lakshmi, M.; Elango, S.; Ram, N.; Anuratha, C.S.

    1998-01-01

    Mangroves occupy estuarine ecosystems in the tropical regions of the world. Despite their highly productive nature and the protective roles they play in the coastal region, the ecosystem as a whole is under severe threat due to various climatic and anthropogenic factors. Therefore, the need for conservation of mangroves is widely emphasised. However, information on existing genetic diversity based on which a strategy for genetic conservation is to be drawn is not available for mangroves. This is primarily because conventional genetic analysis is difficult in these species for various reasons. Therefore, as an aid to our on-going conservation programme, efforts were made to assess the nature and extent of diversity in a number of mangrove species of the Indian coast using molecular markers. The nature and extent of intra-population diversity in sixteen mangrove species and detailed analysis of inter-population genetic polymorphism in four species, Acanthus ilicifolius, Excoecaria agallocha, Avicennia spp and Rhizophora (species and hybrid), is reported in the present communication. (author)

  6. Molecular phylogeny of mangroves IV. nature and extent of intra-specific genetic variation and species diversity in mangroves

    Energy Technology Data Exchange (ETDEWEB)

    Parida, A; Parani, M; Lakshmi, M; Elango, S; Ram, N; Anuratha, C S [M.S. Swaminathan Research Foundation, Taramani, Madras (India)

    1998-10-01

    Mangroves occupy estuarine ecosystems in the tropical regions of the world. Despite their highly productive nature and the protective roles they play in the coastal region, the ecosystem as a whole is under severe threat due to various climatic and anthropogenic factors. Therefore, the need for conservation of mangroves is widely emphasised. However, information on existing genetic diversity based on which a strategy for genetic conservation is to be drawn is not available for mangroves. This is primarily because conventional genetic analysis is difficult in these species for various reasons. Therefore, as an aid to our on-going conservation programme, efforts were made to assess the nature and extent of diversity in a number of mangrove species of the Indian coast using molecular markers. The nature and extent of intra-population diversity in sixteen mangrove species and detailed analysis of inter-population genetic polymorphism in four species, Acanthus ilicifolius, Excoecaria agallocha, Avicennia spp and Rhizophora (species and hybrid), is reported in the present communication. (author) 25 refs, 2 figs, 2 tabs

  7. Single photon simultaneous K-shell ionization and K-shell excitation. II. Specificities of hollow nitrogen molecular ions

    International Nuclear Information System (INIS)

    Carniato, S.; Selles, P.; Andric, L.; Palaudoux, J.; Penent, F.; Lablanquie, P.; Žitnik, M.; Bučar, K.; Nakano, M.; Hikosaka, Y.; Ito, K.

    2015-01-01

    The formalism developed in the companion Paper I is used here for the interpretation of spectra obtained recently on the nitrogen molecule. Double core-hole ionization K −2 and core ionization-core excitation K −2 V processes have been observed by coincidence electron spectroscopy after ionization by synchrotron radiation at different photon energies. Theoretical and experimental cross sections reported on an absolute scale are in satisfactory agreement. The evolution with photon energy of the relative contribution of shake-up and conjugate shake-up processes is discussed. The first main resonance in the K −2 V spectrum is assigned to a K −2 π ∗ state mainly populated by the 1s→ lowest unoccupied molecular orbital dipolar excitation, as it is in the K −1 V NEXAFS (Near-Edge X-ray Absorption Fine Structure) signals. Closer to the K −2 threshold Rydberg resonances have been also identified, and among them a K −2 σ ∗ resonance characterized by a large amount of 2s/2p hybridization, and double K −2 (2σ ∗ /1π/3σ) −1 1π ∗2 shake-up states. These resonances correspond in NEXAFS spectra to, respectively, the well-known σ ∗ shape resonance and double excitation K −1 (2σ ∗ /1π/3σ) −1 1π ∗2 resonances, all being positioned above the threshold

  8. Application of second derivative spectroscopy for increasing molecular specificity of Fourier transform infrared spectroscopic imaging of articular cartilage.

    Science.gov (United States)

    Rieppo, L; Saarakkala, S; Närhi, T; Helminen, H J; Jurvelin, J S; Rieppo, J

    2012-05-01

    Fourier transform infrared (FT-IR) spectroscopic imaging is a promising method that enables the analysis of spatial distribution of biochemical components within histological sections. However, analysis of FT-IR spectroscopic data is complicated since absorption peaks often overlap with each other. Second derivative spectroscopy is a technique which enhances the separation of overlapping peaks. The objective of this study was to evaluate the specificity of the second derivative peaks for the main tissue components of articular cartilage (AC), i.e., collagen and proteoglycans (PGs). Histological bovine AC sections were measured before and after enzymatic removal of PGs. Both formalin-fixed sections (n = 10) and cryosections (n = 6) were investigated. Relative changes in the second derivative peak heights caused by the removal of PGs were calculated for both sample groups. The results showed that numerous peaks, e.g., peaks located at 1202 cm(-1) and 1336 cm(-1), altered less than 5% in the experiment. These peaks were assumed to be specific for collagen. In contrast, two peaks located at 1064 cm(-1) and 1376 cm(-1) were seen to alter notably, approximately 50% or more. These peaks were regarded to be specific for PGs. The changes were greater in cryosections than formalin-fixed sections. The results of this study suggest that the second derivative spectroscopy offers a practical and more specific method than routinely used absorption spectrum analysis methods to obtain compositional information on AC with FT-IR spectroscopic imaging. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  9. Phylogenetic Analysis and Molecular Characterization of Xanthium sibiricum Using DNA Barcoding, PCR-RFLP, and Specific Primers.

    Science.gov (United States)

    Tomasello, Salvatore; Heubl, Günther

    2017-07-01

    The fruits of Xanthium sibiricum have been widely used in traditional Chinese medicine for the treatment of nasal sinusitis and headaches. The genus Xanthium (cocklebur) is a taxonomically complex genus. Different taxonomic concepts have been proposed, some including several species, others lumping the different taxa in a few extremely polymorphic species. Due to the morphological similarities between species, the correct authentication of X. sibiricum is very difficult. Therefore, we established a polymerase chain reaction-restriction fragment length polymorphism method and diagnostic PCR based on nuclear internal transcribed spacer and chloroplast trnQ-rps16 barcodes to differentiate X. sibirium from related species.Results from the phylogenetic analyses based on sequence information from four marker regions (plastidal psbA-trnH and trnQ-rps16 and nuclear ITS and D35 ) support those taxonomic concepts accepting a reduced number of species, as four to five major clades are revealed in the phylogenetic reconstructions. X. sibiricum , together with some accessions from closely related taxa, is always supported as monophyletic, constituting a well-defined genetic entity. Allele-specific primer pairs for ITS and trnQ-rps16 were designed to amplify diagnostic products from the genomic DNA of X. sibiricum . Specific PCR in combination with digestion using the restriction enzyme Mse I allowed for the identification of X. sibiricum by producing specific restriction patterns. The results demonstrate that the applied techniques provide effective and accurate authentication of X. sibiricum . Georg Thieme Verlag KG Stuttgart · New York.

  10. Microwave-assisted RAFT polymerization of well-constructed magnetic surface molecularly imprinted polymers for specific recognition of benzimidazole residues

    Science.gov (United States)

    Chen, Fangfang; Wang, Jiayu; Chen, Huiru; Lu, Ruicong; Xie, Xiaoyu

    2018-03-01

    Magnetic nanoparticles have been widely used as support core for fast separation, which could be directly separated from complicated matrices using an external magnet in few minutes. Surface imprinting based on magnetic core has shown favorable adsorption and separation performance, including good adsorption capacity, fast adsorption kinetics and special selectivity adsorption. Reversible addition-fragmentation chain transfer (RAFT) is an ideal choice for producing well-defined complex architecture with mild reaction conditions. We herein describe the preparation of well-constructed magnetic molecularly imprinted polymers (MMIPs) for the recognition of benzimidazole (BMZ) residues via the microwave-assisted RAFT polymerization. The merits of RAFT polymerization assisting with microwave heating allowed successful and more efficient preparation of well-constructed imprinted coats. Moreover, the polymerization time dramatically shortened and was just 1/24th of the time taken by conventional heating. The results indicated that a uniform nanoscale imprinted layer was formed on the Fe3O4 core successfully, and enough saturation magnetization of MMIPs (16.53 emu g-1) was got for magnetic separation. The desirable adsorption capacity (30.18 μmol g-1) and high selectivity toward template molecule with a selectivity coefficient (k) of 13.85 of MMIPs were exhibited by the adsorption isothermal assay and competitive binding assay, respectively. A solid phase extraction enrichment approach was successfully established for the determination of four BMZ residues from apple samples using MMIPs coupled to HPLC. Overall, this study provides a versatile approach for highly efficient fabrication of well-constructed MMIPs for enrichment and determination of target molecules from complicated samples.

  11. Structure of human Rad51 protein filament from molecular modeling and site-specific linear dichroism spectroscopy

    KAUST Repository

    Reymer, A.

    2009-07-08

    To get mechanistic insight into the DNA strand-exchange reaction of homologous recombination, we solved a filament structure of a human Rad51 protein, combining molecular modeling with experimental data. We build our structure on reported structures for central and N-terminal parts of pure (uncomplexed) Rad51 protein by aid of linear dichroism spectroscopy, providing angular orientations of substituted tyrosine residues of Rad51-dsDNA filaments in solution. The structure, validated by comparison with an electron microscopy density map and results from mutation analysis, is proposed to represent an active solution structure of the nucleo-protein complex. An inhomogeneously stretched double-stranded DNA fitted into the filament emphasizes the strategic positioning of 2 putative DNA-binding loops in a way that allows us speculate about their possibly distinct roles in nucleo-protein filament assembly and DNA strand-exchange reaction. The model suggests that the extension of a single-stranded DNA molecule upon binding of Rad51 is ensured by intercalation of Tyr-232 of the L1 loop, which might act as a docking tool, aligning protein monomers along the DNA strand upon filament assembly. Arg-235, also sitting on L1, is in the right position to make electrostatic contact with the phosphate backbone of the other DNA strand. The L2 loop position and its more ordered compact conformation makes us propose that this loop has another role, as a binding site for an incoming double-stranded DNA. Our filament structure and spectroscopic approach open the possibility of analyzing details along the multistep path of the strand-exchange reaction.

  12. Molecular characterization and phylogenetic analysis of two novel regio-specific flavonoid prenyltransferases from Morus alba and Cudrania tricuspidata.

    Science.gov (United States)

    Wang, Ruishan; Chen, Ridao; Li, Jianhua; Liu, Xiao; Xie, Kebo; Chen, Dawei; Yin, Yunze; Tao, Xiaoyu; Xie, Dan; Zou, Jianhua; Yang, Lin; Dai, Jungui

    2014-12-26

    and Molecular Biology, Inc.

  13. Molecular cloning and tissue-specific expression analysis of mouse spinesin, a type II transmembrane serine protease 5

    International Nuclear Information System (INIS)

    Watanabe, Yoshihisa; Okui, Akira; Mitsui, Shinichi; Kawarabuki, Kentaro; Yamaguchi, Tatsuyuki; Uemura, Hidetoshi; Yamaguchi, Nozomi

    2004-01-01

    We have previously reported novel serine proteases isolated from cDNA libraries of the human and mouse central nervous system (CNS) by PCR using degenerate oligodeoxyribonucleotide primers designed on the basis of the serine protease motifs, AAHC and DSGGP. Here we report a newly isolated serine protease from the mouse CNS. This protease is homologous (77.9% identical) to human spinesin type II transmembrane serine protease 5. Mouse spinesin (m-spinesin) is also composed of (from the N-terminus) a short cytoplasmic domain, a transmembrane domain, a stem region containing a scavenger-receptor-like domain, and a serine protease domain, as is h-spinesin. We also isolated type 1, type 2, and type 3 variant cDNAs of m-spinesin. Full-length spinesin (type 4) and type 3 contain all the domains, whereas type 1 and type 2 variants lack the cytoplasmic, transmembrane, and scavenger-receptor-like domains. Subcellular localization of the variant forms was analyzed using enhanced green fluorescent protein (EGFP) fusion proteins. EGFP-type 4 fusion protein was predominantly localized to the ER, Golgi apparatus, and plasma membrane, whereas EGFP-type 1 was localized to the cytoplasm, reflecting differential classification of m-spinesin variants into transmembrane and cytoplasmic types. We analyzed the distribution of m-spinesin variants in mouse tissues, using RT-PCR with variant-specific primer sets. Interestingly, transmembrane-type spinesin, types 3 and 4, was specifically expressed in the spinal cord, whereas cytoplasmic type, type 1, was expressed in multiple tissues, including the cerebrum and cerebellum. Therefore, m-spinesin variants may have distinct biological functions arising from organ-specific variant expression

  14. Indication for a chiral phase in the molecular magnetic chain Gd(hfac){sub 3}NiTiPr by specific heat and {mu}{sup +}SR measurements

    Energy Technology Data Exchange (ETDEWEB)

    Lascialfari, A.; Ullu, R.; Affronte, M.; Cinti, F.; Caneschi, A.; Gatteschi, D.; Rovai, D.; Pini, M.G. E-mail: mgpini@ifac.cnr.it; Rettori, A

    2004-05-01

    Specific heat and muon spin relaxation ({mu}{sup +}SR) measurements performed in the molecular magnetic chain Gd(hfac){sub 3}NiTiPr provide indication for the onset, at T{sub 0}=2.08 K, of a phase with chiral order in the absence of long-range helical order. Specific heat data (probing the chirality-chirality correlation function) show a peak at T{sub 0} that disappears upon application of a 5 T magnetic field, while {mu}{sup +}SR data (probing the spin-spin correlation function) do not present any anomaly at T{sub 0} nor oscillations in the asymmetry curve below T{sub 0}.

  15. Molecular cytogenetic analysis of Inv Dup(15) chromosomes, using probes specific for the Pradar-Willi/Angelman syndrome region: Clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Leana-Cox, J. (Univ. of Maryland School of Medicine, Baltimore, MD (United States)); Jenkins, L. (Kaiser Permanente Medical Group, San Jose, CA (United States)); Palmer, C.G.; Plattner, R. (Indiana School of Medicine, Indianapolis, IN (United States)); Sheppard, L. (Palo Verde Laboratory, Inc., Chandler, AZ (United States)); Flejter, W.L. (Univ. of Michigan, Ann Arbor, MI (United States)); Zackowski, J. (Univ. of Florida Health Science Center, Gainsville, FL (United States)); Tsien, F. (Tulane Univ. School of Medicine, New Orleans, LA (United States)); Schwartz, S. (Case Western Reserve Univ., Cleveland, OH (United States))

    1994-05-01

    Twenty-seven cases of inverted duplications of chromosome 15 (inv dup[15]) were investigated by FISH with two DNA probes specific for the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on proximal 15q. Sixteen of the marker chromosomes displayed two copies of each probe, while in the remaining 11 markers no hybridization was observed. A significant association was found between the presence of this region and an abnormal phenotype (P<.01). This is the largest study to date of inv dup(15) chromosomes, that uses molecular cytogenetic methods and is the first to report a significant association between the presence of a specific chromosomal region in such markers and an abnormal phenotype. 30 refs., 1 fig., 4 tabs.

  16. Molecular organization in bacterial cell membranes. Specific labelling and topological distribution of glycoproteins and proteins in Streptomyces albus membranes

    Energy Technology Data Exchange (ETDEWEB)

    Larraga, V; Munoz, E [Consejo Superior de Investigaciones Cientificas, Madrid (Spain). Instituto de Biologia Celular

    1975-05-01

    The paper reports about an investigation into the question of the specific labelling and topological distribution of glycoproteins and proteins in Streptomyces albus membranes. The method of sample preparation is described: Tritium labelling of glycoproteins in protoplasts and membranes, iodination of proteins, trypsin treatment and polyacrylamide gel electrophoresis. The findings suggest an asymmetrical distribution of the glycoproteins in membranes and a weak accessibility to iodine label. A structural model of the plasma membranes of Streptomyces albus is proposed similar to the general 'fluid mosaic' model of Singer and Nicholson.

  17. Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection

    Directory of Open Access Journals (Sweden)

    Chinestra Patrick

    2008-03-01

    Full Text Available Abstract Background The Rho GTPases A, B and C proteins, members of the Rho family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation and have recently been implicated in tumorigenesis. Although overexpression of Rho GTPases has been correlated with tumorigenesis, only their GTP-bound forms are able to activate the signalling pathways implicated in tumorigenesis. Thus, the focus of much recent research has been to identify biological tools capable of quantifying the level of cellular GTP-bound Rho, or determining the subcellular location of activation. However useful, these tools used to study the mechanism of Rho activation still have limitations. The aim of the present work was to employ phage display to identify a conformationally-specific single chain fragment variable (scFv that recognizes the active, GTP-bound, form of Rho GTPases and is able to discriminate it from the inactive, GDP-bound, Rho in endogenous settings. Results After five rounds of phage selection using a constitutively activated mutant of RhoB (RhoBQ63L, three scFvs (A8, C1 and D11 were selected for subsequent analysis. Further biochemical characterization was pursued for the single clone, C1, exhibiting an scFv structure. C1 was selective for the GTP-bound form of RhoA, RhoB, as well as RhoC, and failed to recognize GTP-loaded Rac1 or Cdc42, two other members of the Rho family. To enhance its production, soluble C1 was expressed in fusion with the N-terminal domain of phage protein pIII (scFv C1-N1N2, it appeared specifically associated with GTP-loaded recombinant RhoA and RhoB via immunoprecipitation, and endogenous activated Rho in HeLa cells as determined by immunofluorescence. Conclusion We identified an antibody, C1-N1N2, specific for the GTP-bound form of RhoB from a phage library, and confirmed its specificity towards GTP-bound RhoA and RhoC, as well as RhoB. The success of C1-N1N2 in discriminating activated

  18. Molecularly imprinted electrochemical sensing interface based on in-situ-polymerization of amino-functionalized ionic liquid for specific recognition of bovine serum albumin.

    Science.gov (United States)

    Wang, Yanying; Han, Miao; Liu, Guishen; Hou, Xiaodong; Huang, Yina; Wu, Kangbing; Li, Chunya

    2015-12-15

    A molecularly imprinted polymer film was in situ polymerized on a carboxyl functionalized multi-walled carbon nanotubes modified glassy carbon electrode surface under room temperature. This technique provides a promising imprinting approach for protein in an aqueous solution using 3-(3-aminopropyl)-1-vinylimidazolium tetrafluoroborate ionic liquid as functional monomer, N, N'-methylenebisacrylamide as crossing linker, ammonium persulfate and N,N,N',N'-tetramethylethylenediamine as initiator, and bovine serum albumin (BSA) as template. The molecularly imprinted polymerized ionic liquid film shows enhanced accessibility, high specificity and sensitivity towards BSA. Electrochemical sensing performance of the imprinted sensor was thoroughly investigated using K3Fe[CN]6/K4Fe[CN]6 as electroactive probes. Under optimal conditions, the current difference before and after specific recognition of BSA was found linearly related to its concentration in the range from 1.50×10(-9) to 1.50×10(-6) mol L(-1). The detection limit was calculated to be 3.91×10(-10) mol L(-1) (S/N=3). The practical application of the imprinted sensor was demonstrated by determining BSA in liquid milk samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Design of a K/Q-Band Beacon Receiver for the Alphasat Technology Demonstration Payload (TDP) #5 Experiment

    Science.gov (United States)

    Morse, Jacquelynne R.

    2014-01-01

    This paper describes the design and performance of a coherent KQ-band (2040 GHz) beacon receiver developed at NASA Glenn Research Center (GRC) that will be installed at the Politecnico di Milano (POLIMI) for use in the Alphasat Technology Demonstration Payload 5 (TDP5) beacon experiment. The goal of this experiment is to characterize rain fade attenuation at 40 GHz to improve the performance of existing statistical rain attenuation models in the Q-band. The ground terminal developed by NASA GRC utilizes an FFT-based frequency estimation receiver capable of characterizing total path attenuation effects due to gaseous absorption, clouds, rain, and scintillation. The receiver system has been characterized in the lab and demonstrates a system dynamic range performance of better than 58 dB at 1 Hz and better than 48 dB at 10 Hz rates.

  20. Safety, efficacy, and molecular mechanism of claudin-1-specific peptides to enhance blood-nerve-barrier permeability.

    Science.gov (United States)

    Sauer, Reine-Solange; Krug, Susanne M; Hackel, Dagmar; Staat, Christian; Konasin, Natalia; Yang, Shaobing; Niedermirtl, Benedikt; Bosten, Judith; Günther, Ramona; Dabrowski, Sebastian; Doppler, Kathrin; Sommer, Claudia; Blasig, Ingolf E; Brack, Alexander; Rittner, Heike L

    2014-07-10

    The blood-nerve barrier consists of the perineurium and endoneurial vessels. The perineurial barrier is composed of a basal membrane and a layer of perineurial cells sealed by tight junction proteins preventing e.g. application of analgesics for selective regional pain control. One of the barrier-sealing proteins in the blood-nerve barrier is claudin-1. Therefore, the claudin-1-peptidomimetics (C1C2), derived from the first extracellular loop (ECL1) on claudin-1 was developed. In this study, we further evaluated the expression of tight junction proteins in the perineurium in Wistar rats and characterized the specificity, in vivo applicability, mechanism of action as well as the biocompatibility of C1C2. In the perineurium, claudin-19, tricellulin and ZO-1, but no claudin-2, 3, 8 and -11 were expressed. C1C2 specifically bound to the ECL1 of claudin-1 and fluorescent 5,6-carboxytetramethylrhodamine-C1C2 was rapidly internalized. Opening the perineurium with C1C2 reduced the mRNA and protein expression of claudin-1 and increased small and macromolecule permeability into the peripheral nerve. Application of C1C2 facilitated regional analgesia using μ-opioid receptor agonists like DAMGO or morphine without motor impairment in naïve rats as well as rats with hind paw inflammation. In contrast the control peptide C2C2 derived from ECL1 on claudin-2 did neither open the barrier nor facilitated opioid-mediated regional analgesia. C1C2 delivery was well tolerated and caused no morphological and functional nerve damage. C1C2 effects could be reversed by interference with the wnt-signal-transduction pathway, specifically the homeobox transcription factor cdx2, using a glycogen-synthase-kinase-3 inhibitor. In summary, we describe the composition of and a pathway to open the perineurial barrier employing a peptide to deliver hydrophilic substances to the peripheral nerve. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Specific labeling and assignment strategies of valine methyl groups for NMR studies of high molecular weight proteins

    Energy Technology Data Exchange (ETDEWEB)

    Mas, Guillaume; Crublet, Elodie [Univ. Grenoble Alpes, Institut de Biologie Structurale (IBS) (France); Hamelin, Olivier [CNRS (France); Gans, Pierre; Boisbouvier, Jérôme, E-mail: jerome.boisbouvier@ibs.fr [Univ. Grenoble Alpes, Institut de Biologie Structurale (IBS) (France)

    2013-09-28

    The specific protonation of valine and leucine methyl groups in proteins is typically achieved by overexpressing proteins in M9/D{sub 2}O medium supplemented with either labeled α-ketoisovalerate for the labeling of the four prochiral methyl groups or with 2-acetolactate for the stereospecific labeling of the valine and leucine side chains. However, when these labeling schemes are applied to large protein assemblies, significant overlap between the correlations of the valine and leucine methyl groups occurs, hampering the analysis of 2D methyl-TROSY spectra. Analysis of the leucine and valine biosynthesis pathways revealed that the incorporation of labeled precursors in the leucine pathway can be inhibited by the addition of exogenous l-leucine-d{sub 10}. We exploited this property to label stereospecifically the pro-R and pro-S methyl groups of valine with minimal scrambling to the leucine residues. This new labeling protocol was applied to the 468 kDa homododecameric peptidase TET2 to decrease the complexity of its NMR spectra. All of the pro-S valine methyl resonances of TET2 were assigned by combining mutagenesis with this innovative labeling approach. The assignments were transferred to the pro-R groups using an optimally labeled sample and a set of triple resonance experiments. This improved labeling scheme enables us to overcome the main limitation of overcrowding in the NMR spectra of prochiral methyl groups, which is a prerequisite for the site-specific measurement of the structural and dynamic parameters or for the study of interactions in very large protein assemblies.

  2. Gene expression profiling, pathway analysis and subtype classification reveal molecular heterogeneity in hepatocellular carcinoma and suggest subtype specific therapeutic targets.

    Science.gov (United States)

    Agarwal, Rahul; Narayan, Jitendra; Bhattacharyya, Amitava; Saraswat, Mayank; Tomar, Anil Kumar

    2017-10-01

    A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis. The differential gene expression analysis using non-parametric Wilcoxon test revealed a total of 479 up-regulated and 91 down-regulated genes in HCC compared to controls. The list of top differentially expressed genes mainly consists of tumor/cancer associated genes, such as AFP, THBS4, LCN2, GPC3, NUF2, etc. The genes over-expressed in HCC were mainly associated with cell cycle pathways. In total, 59 kinases associated genes were found over-expressed in HCC, including TTK, MELK, BUB1, NEK2, BUB1B, AURKB, PLK1, CDK1, PKMYT1, PBK, etc. Overall four distinct HCC subtypes were predicted using consensus clustering method. Each subtype was unique in terms of gene expression, pathway enrichment and median survival. Conclusively, this study has exposed a number of interesting genes which can be exploited in future as potential markers of HCC, diagnostic as well as prognostic and subtype classification may guide for improved and specific therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Hardware Implementation of A Non-RLL Soft-decoding Beacon-based Visible Light Communication Receiver

    OpenAIRE

    Nguyen, Duc-Phuc; Le, Dinh-Dung; Tran, Thi-Hong; Huynh, Huu-Thuan; Nakashima, Yasuhiko

    2018-01-01

    Visible light communication (VLC)-based beacon systems, which usually transmit identification (ID) information in small-size data frames are applied widely in indoor localization applications. There is one fact that flicker of LED light should be avoid in any VLC systems. Current flicker mitigation solutions based on run-length limited (RLL) codes suffer from reduced code rates, or are limited to hard-decoding forward error correction (FEC) decoders. Recently, soft-decoding techniques of RLL-...

  4. Role of DNA conformation & energetic insights in Msx-1-DNA recognition as revealed by molecular dynamics studies on specific and nonspecific complexes.

    Science.gov (United States)

    Kachhap, Sangita; Singh, Balvinder

    2015-01-01

    In most of homeodomain-DNA complexes, glutamine or lysine is present at 50th position and interacts with 5th and 6th nucleotide of core recognition region. Molecular dynamics simulations of Msx-1-DNA complex (Q50-TG) and its variant complexes, that is specific (Q50K-CC), nonspecific (Q50-CC) having mutation in DNA and (Q50K-TG) in protein, have been carried out. Analysis of protein-DNA interactions and structure of DNA in specific and nonspecific complexes show that amino acid residues use sequence-dependent shape of DNA to interact. The binding free energies of all four complexes were analysed to define role of amino acid residue at 50th position in terms of binding strength considering the variation in DNA on stability of protein-DNA complexes. The order of stability of protein-DNA complexes shows that specific complexes are more stable than nonspecific ones. Decomposition analysis shows that N-terminal amino acid residues have been found to contribute maximally in binding free energy of protein-DNA complexes. Among specific protein-DNA complexes, K50 contributes more as compared to Q50 towards binding free energy in respective complexes. The sequence dependence of local conformation of DNA enables Q50/Q50K to make hydrogen bond with nucleotide(s) of DNA. The changes in amino acid sequence of protein are accommodated and stabilized around TAAT core region of DNA having variation in nucleotides.

  5. A case study of pediatric asthma alerts from the beacon community program in cincinnati: technology is just the first step.

    Science.gov (United States)

    Trudnak, Tara; Mansour, Mona; Mandel, Keith; Sauers, Hadley; Pandzik, Gerry; Donisi, Carl; Fairbrother, Gerry

    2014-01-01

    The Beacon Community in Cincinnati, Ohio was an innovative, community-wide initiative to use technology to transform care. One important feature was the development of regional alerts to notify practices when patients were hospitalized or seen in the emergency department. The purpose of this paper is to describe the way in which technology engages the improvement process, and to describe the early stages of learning how to use technology to enhance quality improvement. We interviewed key Beacon leaders as well as providers and office staff in selected practices. We also collected preliminary data from practices that reflected handling of alerts, including the number of asthma related alerts received and followed up. Regional alerts, supplied by the community-wide health information exchange, were a significant addition to the quality improvement effort in that they enabled practices to identify and follow up with additional children at risk. An important finding was the substantial effort at the practice level to integrate technology into ongoing patient care. Developing the technology for community wide alerts represented a significant endeavor in the Cincinnati Beacon Community. However, the technology was just the first step. Despite extra effort and time required on the part of individual practices, they reported that the value of having alerts was high. Hospital and ED visits represent some of the most costly aspects of care, and an efficient process for intervening with children using these costly services was seen as of significant value.

  6. A Specific Peptide with Calcium-Binding Capacity from Defatted Schizochytrium sp. Protein Hydrolysates and the Molecular Properties.

    Science.gov (United States)

    Cai, Xixi; Yang, Qian; Lin, Jiaping; Fu, Nanyan; Wang, Shaoyun

    2017-03-29

    Marine microorganisms have been proposed as a new kind of protein source. Efforts are needed in order to transform the protein-rich biological wastes left after lipid extraction into value-added bio-products. Thus, the utilization of protein recovered from defatted Schizochytrium sp. by-products presents an opportunity. A specific peptide Tyr-Leu (YL) with calcium-binding capacity was purified from defatted Schizochytrium sp. protein hydrolysates through gel filtration chromatography and RP-HPLC. The calcium-binding activity of YL reached 126.34 ± 3.40 μg/mg. The calcium-binding mechanism was investigated through ultraviolet, fluorescence and infrared spectroscopy. The results showed that calcium ions could form dative bonds with carboxyl oxygen atoms and amino nitrogen atoms as well as the nitrogen and oxygen atoms of amide bonds. YL-Ca exhibited excellent thermal stability and solubility, which was beneficial for its absorption and transport in the basic intestinal tract of the human body. Moreover, the cellular uptake of calcium in Caco-2 cells showed that YL-Ca could enhance calcium uptake efficiency and protect calcium ions against precipitation caused by dietary inhibitors such as tannic acid, oxalate, phytate and metal ions. The findings indicate that the by-product of Schizochytrium sp. is a promising source for making peptide-calcium bio-products as algae-based functional supplements for human beings.

  7. A Specific Peptide with Calcium-Binding Capacity from Defatted Schizochytrium sp. Protein Hydrolysates and the Molecular Properties

    Directory of Open Access Journals (Sweden)

    Xixi Cai

    2017-03-01

    Full Text Available Marine microorganisms have been proposed as a new kind of protein source. Efforts are needed in order to transform the protein-rich biological wastes left after lipid extraction into value-added bio-products. Thus, the utilization of protein recovered from defatted Schizochytrium sp. by-products presents an opportunity. A specific peptide Tyr-Leu (YL with calcium-binding capacity was purified from defatted Schizochytrium sp. protein hydrolysates through gel filtration chromatography and RP-HPLC. The calcium-binding activity of YL reached 126.34 ± 3.40 μg/mg. The calcium-binding mechanism was investigated through ultraviolet, fluorescence and infrared spectroscopy. The results showed that calcium ions could form dative bonds with carboxyl oxygen atoms and amino nitrogen atoms as well as the nitrogen and oxygen atoms of amide bonds. YL-Ca exhibited excellent thermal stability and solubility, which was beneficial for its absorption and transport in the basic intestinal tract of the human body. Moreover, the cellular uptake of calcium in Caco-2 cells showed that YL-Ca could enhance calcium uptake efficiency and protect calcium ions against precipitation caused by dietary inhibitors such as tannic acid, oxalate, phytate and metal ions. The findings indicate that the by-product of Schizochytrium sp. is a promising source for making peptide-calcium bio-products as algae-based functional supplements for human beings.

  8. Cloning and molecular analyses of a gibberellin 20-oxidase gene expressed specifically in developing seeds of watermelon.

    Science.gov (United States)

    Kang, H G; Jun, S H; Kim, J; Kawaide, H; Kamiya, Y; An, G

    1999-10-01

    To understand the biosynthesis and functional role of gibberellins (GAs) in developing seeds, we isolated Cv20ox, a cDNA clone from watermelon (Citrullus lanatus) that shows significant amino acid homology with GA 20-oxidases. The complementary DNA clone was expressed in Escherichia coli as a fusion protein, which oxidized GA(12) at C-20 to the C(19) compound GA(9), a precursor of bioactive GAs. RNA-blot analysis showed that the Cv20ox gene was expressed specifically in developing seeds. The gene was strongly expressed in the integument tissues, and it was also expressed weakly in inner seed tissues. In parthenocarpic fruits induced by 1-(2-chloro-4-pyridyl)-3-phenylurea treatment, the expression pattern of Cv20ox did not change, indicating that the GA 20-oxidase gene is expressed primarily in the maternal cells of developing seeds. The promoter of Cv20ox was isolated and fused to the beta-glucuronidase (GUS) gene. In a transient expression system, beta-glucuronidase staining was detectable only in the integument tissues of developing watermelon seeds.

  9. Cloning and Molecular Analyses of a Gibberellin 20-Oxidase Gene Expressed Specifically in Developing Seeds of Watermelon1

    Science.gov (United States)

    Kang, Hong-Gyu; Jun, Sung-Hoon; Kim, Junyul; Kawaide, Hiroshi; Kamiya, Yuji; An, Gynheung

    1999-01-01

    To understand the biosynthesis and functional role of gibberellins (GAs) in developing seeds, we isolated Cv20ox, a cDNA clone from watermelon (Citrullus lanatus) that shows significant amino acid homology with GA 20-oxidases. The complementary DNA clone was expressed in Escherichia coli as a fusion protein, which oxidized GA12 at C-20 to the C19 compound GA9, a precursor of bioactive GAs. RNA-blot analysis showed that the Cv20ox gene was expressed specifically in developing seeds. The gene was strongly expressed in the integument tissues, and it was also expressed weakly in inner seed tissues. In parthenocarpic fruits induced by 1-(2-chloro-4-pyridyl)-3-phenylurea treatment, the expression pattern of Cv20ox did not change, indicating that the GA 20-oxidase gene is expressed primarily in the maternal cells of developing seeds. The promoter of Cv20ox was isolated and fused to the β-glucuronidase (GUS) gene. In a transient expression system, β-glucuronidase staining was detectable only in the integument tissues of developing watermelon seeds. PMID:10517828

  10. Bulked segregant analysis of the pirarucu (Arapaima gigas) genome for identification of sex-specific molecular markers.

    Science.gov (United States)

    Almeida, I G; Ianella, P; Faria, M T; Paiva, S R; Caetano, A R

    2013-12-04

    Arapaima gigas (Osteoglossidae) is one of the largest fish species in the Amazon Basin, attaining lengths of over 2.5 m and weights of over 100 kg. Its flesh is prized, and it has great potential for production in aquaculture systems. However, live pirarucu cannot be reliably sexed visually, even after sexual development, since this species does not have clear external sexual dimorphism. Simple and inexpensive methods for sexing immature pirarucu based on DNA markers would facilitate production of this species in commercial operations. We analyzed A. gigas male and female DNA pools with 566 RAPD primers, generating 2609 fragments, with an estimated 1341 segregating polymorphic markers, and an estimated average spacing of 714 kb, which corresponds to less than 0.1% of the species' genome. Two putative sex-specific fragments were initially identified in bulked samples; but they were not confirmed in a study of individual male and female samples. We suggest that A. gigas has developed a non-chromosomal system of sex determination or, alternatively, that the species has undergone a recent loss of the chromosome carrying the sex-determining locus.

  11. Growth arrest specific gene 2 in tilapia (Oreochromis niloticus): molecular characterization and functional analysis under low-temperature stress.

    Science.gov (United States)

    Yang, ChangGeng; Wu, Fan; Lu, Xing; Jiang, Ming; Liu, Wei; Yu, Lijuan; Tian, Juan; Wen, Hua

    2017-07-17

    Growth arrest specific 2 (gas2) gene is a component of the microfilament system that plays a major role in the cell cycle, regulation of microfilaments, and cell morphology during apoptotic processes. However, little information is available on fish gas2. In this study, the tilapia (Oreochromis niloticus) gas2 gene was cloned and characterized for the first time. The open reading frame was 1020 bp, encoding 340 amino acids; the 5'-untranslated region (UTR) was 140 bp and the 3'-UTR was 70 bp, with a poly (A) tail. The highest promoter activity occurred in the regulatory region (-3000 to -2400 bp). The Gas2-GFP fusion protein was distributed within the cytoplasm. Quantitative reverse transcription-polymerase chain reaction and western blot analyses revealed that gas2 gene expression levels in the liver, muscle, and brain were clearly affected by low temperature stress. The results of gas2 RNAi showed decreased expression of the gas2 and P53 genes. These results suggest that the tilapia gas2 gene may be involved in low temperature stress-induced apoptosis.

  12. Molecular diversity of tuliposide B-converting enzyme in tulip (Tulipa gesneriana): identification of the root-specific isozyme.

    Science.gov (United States)

    Nomura, Taiji; Ueno, Ayaka; Ogita, Shinjiro; Kato, Yasuo

    2017-06-01

    6-Tuliposide B (PosB) is a glucose ester accumulated in tulip (Tulipa gesneriana) as a major secondary metabolite. PosB serves as the precursor of the antimicrobial lactone tulipalin B (PaB), which is formed by PosB-converting enzyme (TCEB). The gene TgTCEB1, encoding a TCEB, is transcribed in tulip pollen but scarcely transcribed in other tissues (e.g. roots) even though those tissues show high TCEB activity. This led to the prediction of the presence of a TCEB isozyme with distinct tissue specificity. Herein, we describe the identification of the TgTCEB-R gene from roots via native enzyme purification; this gene is a paralog of TgTCEB1. Recombinant enzyme characterization verified that TgTCEB-R encodes a TCEB. Moreover, TgTCEB-R was localized in tulip plastids, as found for pollen TgTCEB1. TgTCEB-R is transcribed almost exclusively in roots, indicating a tissue preference for the transcription of TCEB isozyme genes.

  13. Insight into the substrate specificity change caused by the Y227H mutation of α-glucosidase III from the European honeybee (Apis mellifera through molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Pratchaya Pramoj Na Ayutthaya

    Full Text Available Honey from the European honeybee, Apis mellifera, is produced by α-glucosidases (HBGases and is widely used in food, pharmaceutical, and cosmetic industries. Categorized by their substrate specificities, HBGases have three isoforms: HBGase I, II and III. Previous experimental investigations showed that wild-type HBGase III from Apis mellifera (WT preferred sucrose to maltose as a substrate, while the Y227H mutant (MT preferred maltose to sucrose. This mutant can potentially be used for malt hydrolysis because it can efficiently hydrolyze maltose. In this work, to elucidate important factors contributing to substrate specificity of this enzyme and gain insight into how the Y227H mutation causes substrate specificity change, WT and MT homology models were constructed, and sucrose/maltose was docked into active sites of the WT and MT. AMBER14 was employed to perform three independent molecular dynamics runs for these four complexes. Based on the relative binding free energies calculated by the MM-GBSA method, sucrose is better than maltose for WT binding, while maltose is better than sucrose for MT binding. These rankings support the experimentally observed substrate specificity that WT preferred sucrose to maltose as a substrate, while MT preferred maltose to sucrose, suggesting the importance of binding affinity for substrate specificity. We also found that the Y227H mutation caused changes in the proximities between the atoms necessary for sucrose/maltose hydrolysis that may affect enzyme efficiency in the hydrolysis of sucrose/maltose. Moreover, the per-residue binding free energy decomposition results show that Y227/H227 may be a key residue for preference binding of sucrose/maltose in the WT/MT active site. Our study provides important and novel insight into the binding of sucrose/maltose in the active site of Apis mellifera HBGase III and into how the Y227H mutation leads to the substrate specificity change at the molecular level. This

  14. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution.

    Directory of Open Access Journals (Sweden)

    Amanda Tse

    Full Text Available Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib and promiscuous (Bosutinib, Dasatinib kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations

  15. 99mTc-labeling and evaluation of a HYNIC modified small-molecular inhibitor of prostate-specific membrane antigen

    International Nuclear Information System (INIS)

    Xu, Xiaoping; Zhang, Jianping; Hu, Silong; He, Simin; Bao, Xiao; Ma, Guang; Luo, Jianmin; Cheng, Jingyi; Zhang, Yingjian

    2017-01-01

    Introduction: Prostate-specific membrane antigen (PSMA) is a well-established target in the development of radiopharmaceuticals for the diagnosis and therapy of prostate cancer (PCa). In this study, we evaluated a novel 99m Tc-labeled small molecular inhibitor of PSMA. Methods: This new small-molecular inhibitor of PSMA, 6-hydrazinonicotinate-Aminocaproic acid-Lysine-Urea-Glutamate (HYNIC-ALUG) was radiolabeled by 99m Tc and was evaluated both in vitro and in vivo using PCa models (PC-3 and LNCaP). Radiation dosimetry was assessed in mice. Results: 99m Tc-HYNIC-ALUG showed excellent stability in different media. A cell assay preliminarily displayed its specificity for PSMA. The inhibitor showed good pharmacokinetics making it suitable for in vivo imaging. PC-3-derived tumors showed no obvious radioactive uptake; however, the LNCaP-derived tumors showed very high radioactive uptake which was significantly decreased by the selective PSMA inhibitor 2-PMPA. Biodistribution in LNCaP xenografts showed an optimum tumor-to-blood ratio of 24.23 ± 3.54 at 2 h. Tumor uptake was also decreased in the inhibition experiment with 2-PMPA (19.45 ± 2.14%ID/g versus 1.42 ± 0.15%ID/g at 2 h). The effective dose of the 99m Tc-HYNIC-ALUG was 8.4E-04 mSv/MBq. Conclusions: A new 99m Tc-labeled PSMA inhibitor with specific accumulation in PSMA-positive tumors and low background in other organs was synthesized. The radiopharmaceutical also showed very low radiation dosimetry. This agent may significantly improve the diagnosis, staging, and subsequent monitoring of therapeutic effects in PCa patients.

  16. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution

    Science.gov (United States)

    Tse, Amanda; Verkhivker, Gennady M.

    2015-01-01

    Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib) and promiscuous (Bosutinib, Dasatinib) kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations of key mediating

  17. Molecular characterization of a phloem-specific gene encoding the filament protein, phloem protein 1 (PP1), from Cucurbita maxima.

    Science.gov (United States)

    Clark, A M; Jacobsen, K R; Bostwick, D E; Dannenhoffer, J M; Skaggs, M I; Thompson, G A

    1997-07-01

    Sieve elements in the phloem of most angiosperms contain proteinaceous filaments and aggregates called P-protein. In the genus Cucurbita, these filaments are composed of two major proteins: PP1, the phloem filament protein, and PP2, the phloem lactin. The gene encoding the phloem filament protein in pumpkin (Cucurbita maxima Duch.) has been isolated and characterized. Nucleotide sequence analysis of the reconstructed gene gPP1 revealed a continuous 2430 bp protein coding sequence, with no introns, encoding an 809 amino acid polypeptide. The deduced polypeptide had characteristics of PP1 and contained a 15 amino acid sequence determined by N-terminal peptide sequence analysis of PP1. The sequence of PP1 was highly repetitive with four 200 amino acid sequence domains containing structural motifs in common with cysteine proteinase inhibitors. Expression of the PP1 gene was detected in roots, hypocotyls, cotyledons, stems, and leaves of pumpkin plants. PP1 and its mRNA accumulated in pumpkin hypocotyls during the period of rapid hypocotyl elongation after which mRNA levels declined, while protein levels remained elevated. PP1 was immunolocalized in slime plugs and P-protein bodies in sieve elements of the phloem. Occasionally, PP1 was detected in companion cells. PP1 mRNA was localized by in situ hybridization in companion cells at early stages of vascular differentiation. The developmental accumulation and localization of PP1 and its mRNA paralleled the phloem lactin, further suggesting an interaction between these phloem-specific proteins.

  18. Molecular Detection of Antimicrobial Resistance

    Science.gov (United States)

    Fluit, Ad C.; Visser, Maarten R.; Schmitz, Franz-Josef

    2001-01-01

    The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art. PMID:11585788

  19. Contributions of molecular size, charge distribution, and specific amino acids to the iron-binding capacity of sea cucumber (Stichopus japonicus) ovum hydrolysates.

    Science.gov (United States)

    Sun, Na; Cui, Pengbo; Jin, Ziqi; Wu, Haitao; Wang, Yixing; Lin, Songyi

    2017-09-01

    This study investigated the contributions of molecular size, charge distribution and specific amino acids to the iron-binding capacity of sea cucumber (Stichopus japonicus) ovum hydrolysates (SCOHs), and further explored their iron-binding sites. It was demonstrated that enzyme type and degree of hydrolysis (DH) significantly influenced the iron-binding capacity of the SCOHs. The SCOHs produced by alcalase at a DH of 25.9% possessed the highest iron-binding capacity at 92.1%. As the hydrolysis time increased, the molecular size of the SCOHs decreased, the negative charges increased, and the hydrophilic amino acids were exposed to the surface, facilitating iron binding. Furthermore, the Fourier transform infrared spectra, combined with amino acid composition analysis, revealed that iron bound to the SCOHs primarily through interactions with carboxyl oxygen of Asp, guanidine nitrogen of Arg or nitrogen atoms in imidazole group of His. The formed SCOHs-iron complexes exhibited a fold and crystal structure with spherical particles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of 4q and 14q in Wilms tumor.

    Science.gov (United States)

    Williams, Richard D; Al-Saadi, Reem; Natrajan, Rachael; Mackay, Alan; Chagtai, Tasnim; Little, Suzanne; Hing, Sandra N; Fenwick, Kerry; Ashworth, Alan; Grundy, Paul; Anderson, James R; Dome, Jeffrey S; Perlman, Elizabeth J; Jones, Chris; Pritchard-Jones, Kathy

    2011-12-01

    Anaplasia in Wilms tumor, a distinctive histology characterized by abnormal mitoses, is associated with poor patient outcome. While anaplastic tumors frequently harbour TP53 mutations, little is otherwise known about their molecular biology. We have used array comparative genomic hybridization (aCGH) and cDNA microarray expression profiling to compare anaplastic and favorable histology Wilms tumors to determine their common and differentiating features. In addition to changes on 17p, consistent with TP53 deletion, recurrent anaplasia-specific genomic loss and under-expression were noted in several other regions, most strikingly 4q and 14q. Further aberrations, including gain of 1q and loss of 16q were common to both histologies. Focal gain of MYCN, initially detected by high resolution aCGH profiling in 6/61 anaplastic samples, was confirmed in a significant proportion of both tumor types by a genomic quantitative PCR survey of over 400 tumors. Overall, these results are consistent with a model where anaplasia, rather than forming an entirely distinct molecular entity, arises from the general continuum of Wilms tumor by the acquisition of additional genomic changes at multiple loci. Copyright © 2011 Wiley Periodicals, Inc.

  1. Specific Molecular Signatures for Type II Crustins in Penaeid Shrimp Uncovered by the Identification of Crustin-Like Antimicrobial Peptides in Litopenaeus vannamei

    Science.gov (United States)

    Barreto, Cairé; Coelho, Jaqueline da Rosa; Yuan, Jianbo; Xiang, Jianhai; Perazzolo, Luciane Maria

    2018-01-01

    Crustins form a large family of antimicrobial peptides (AMPs) in crustaceans composed of four sub-groups (Types I-IV). Type II crustins (Type IIa or “Crustins” and Type IIb or “Crustin-like”) possess a typical hydrophobic N-terminal region and are by far the most representative sub-group found in penaeid shrimp. To gain insight into the molecular diversity of Type II crustins in penaeids, we identified and characterized a Type IIb crustin in Litopenaeus vannamei (Crustin-like Lv) and compared Type II crustins at both molecular and transcriptional levels. Although L. vannamei Type II crustins (Crustin Lv and Crustin-like Lv) are encoded by separate genes, they showed a similar tissue distribution (hemocytes and gills) and transcriptional response to the shrimp pathogens Vibrio harveyi and White spot syndrome virus (WSSV). As Crustin Lv, Crustin-like Lv transcripts were found to be present early in development, suggesting a maternal contribution to shrimp progeny. Altogether, our in silico and transcriptional data allowed to conclude that (1) each sub-type displays a specific amino acid signature at the C-terminal end holding both the cysteine-rich region and the whey acidic protein (WAP) domain, and that (2) shrimp Type II crustins evolved from a common ancestral gene that conserved a similar pattern of transcriptional regulation. PMID:29337853

  2. Molecular Diagnostics

    OpenAIRE

    Choe, Hyonmin; Deirmengian, Carl A.; Hickok, Noreen J.; Morrison, Tiffany N.; Tuan, Rocky S.

    2015-01-01

    Orthopaedic infections are complex conditions that require immediate diagnosis and accurate identification of the causative organisms to facilitate appropriate management. Conventional methodologies for diagnosis of these infections sometimes lack accuracy or sufficient rapidity. Current molecular diagnostics are an emerging area of bench-to-bedside research in orthopaedic infections. Examples of promising molecular diagnostics include measurement of a specific biomarker in the synovial fluid...

  3. Comparative mRNA and microRNA expression profiling of three genitourinary cancers reveals common hallmarks and cancer-specific molecular events.

    Directory of Open Access Journals (Sweden)

    Xianxin Li

    Full Text Available Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA in a single type of cancer.Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis.Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of 'key' miRNAs may result in the global aberration of one or more pathways or processes as a whole.This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or

  4. Space Weather Operation at KASI With Van Allen Probes Beacon Signals

    Science.gov (United States)

    Lee, Jongkil; Kim, Kyung-Chan; Giuseppe, Romeo; Ukhorskiy, Sasha; Sibeck, David; Kessel, Ramona; Mauk, Barry; Giles, Barbara; Gu, Bon-Jun; Lee, Hyesook; Park, Young-Deuk; Lee, Jaejin

    2018-02-01

    The Van Allen Probes (VAPs) are the only modern National Aeronautics and Space Administration (NASA) spacecraft broadcasting real-time data on the Earth's radiation belts for space weather operations. Since 2012, the Korea Astronomy and Space Science Institute (KASI) has contributed to the receipt of these data via a 7 m satellite-tracking antenna and used these beacon data for space weather operations. An approximately 15 min period is required from measurement to acquisition of Level-1 data. In this paper, we demonstrate the use of VAP data for monitoring space weather conditions at geostationary orbit (GEO) by highlighting the Saint Patrick's Day storm of 2015. During that storm, Probe-A observed a significant increase in the relativistic electron flux at 3 RE. Those electrons diffused outward resulting in a large increase of the electron flux >2 MeV at GEO, which potentially threatened satellite operations. Based on this study, we conclude that the combination of VAP data and National Oceanic and Atmospheric Administration-Geostationary Operational Environmental Satellite (NOAA-GOES) data can provide improved space environment information to geostationary satellite operators. In addition, the findings obtained indicate that more data-receiving sites would be necessary and data connections improved if this or a similar system were to be used as an operational data service.

  5. The Inversion of Ionospheric/plasmaspheric Electron Density From GPS Beacon Observations

    Science.gov (United States)

    Zou, Y. H.; Xu, J. S.; Ma, S. Y.

    It is a space-time 4-D tomography to reconstruct ionospheric/ plasmaspheric elec- tron density, Ne, from ground-based GPS beacon measurements. The mathematical foundation of such inversion is studied in this paper and some simulation results of reconstruction for GPS network observation are presented. Assuming reasonably a power law dependence of NE on time with an index number of 1-3 during one ob- servational time of GPS (60-90min.), 4-D inversion in consideration is reduced to a 3-D cone-beam tomography with incomplete projections. To see clearly the effects of the incompleteness on the quality of reconstruction for 3-D condition, we deduced theoretically the formulae of 3-D parallel-beam tomography. After establishing the mathematical basis, we adopt linear temporal dependence of NE and voxel elemental functions to perform simulation of NE reconstruction with the help of IRI90 model. Reasonable time-dependent 3-D images of ionosphere/ plasmasphere electron density distributions are obtained when taking proper layout of the GPS network and allowing variable resolutions in vertical.

  6. Learning from Health Information Exchange Technical Architecture and Implementation in Seven Beacon Communities

    Science.gov (United States)

    McCarthy, Douglas B.; Propp, Karen; Cohen, Alexander; Sabharwal, Raj; Schachter, Abigail A.; Rein, Alison L.

    2014-01-01

    As health care providers adopt and make “meaningful use” of health information technology (health IT), communities and delivery systems must set up the infrastructure to facilitate health information exchange (HIE) between providers and numerous other stakeholders who have a role in supporting health and care. By facilitating better communication and coordination between providers, HIE has the potential to improve clinical decision-making and continuity of care, while reducing unnecessary use of services. When implemented as part of a broader strategy for health care delivery system and payment reform, HIE capability also can enable the use of analytic tools needed for population health management, patient engagement in care, and continuous learning and improvement. The diverse experiences of seven communities that participated in the three-year federal Beacon Community Program offer practical insight into factors influencing the technical architecture of exchange infrastructure and its role in supporting improved care, reduced cost, and a healthier population. The case studies also document challenges faced by the communities, such as significant time and resources required to harmonize variations in the interpretation of data standards. Findings indicate that their progress developing community-based HIE strategies, while driven by local needs and objectives, is also influenced by broader legal, policy, and market conditions. PMID:25848591

  7. The Keys to Governance and Stakeholder Engagement: The Southeast Michigan Beacon Community Case Study

    Science.gov (United States)

    Des Jardins, Terrisca R.

    2014-01-01

    Community-based health information exchanges (HIEs) and efforts to consolidate and house data are growing, given the advent of Accountable Care Organizations (ACOs) under the Affordable Care Act and other similar population health focused initiatives. The Southeast Michigan Beacon Community (SEMBC) can be looked to as one case study that offers lessons learned, insights on challenges faced and accompanying workarounds related to governance and stakeholder engagement. The SEMBC case study employs an established Data Warehouse Governance Framework to identify and explain the necessary governance and stakeholder engagement components, particularly as they relate to community-wide data sharing and data warehouses or repositories. Perhaps the biggest lesson learned through the SEMBC experience is that community-based work is hard. It requires a great deal of community leadership, collaboration and resources. SEMBC found that organizational structure and guiding principles needed to be continually revisited and nurtured in order to build the relationships and trust needed among stakeholder organizations. SEMBC also found that risks and risk mitigation tactics presented challenges and opportunities at the outset and through the duration of the three year pilot period. Other communities across the country embarking on similar efforts need to consider realistic expectations about community data sharing infrastructures and the accompanying and necessary governance and stakeholder engagement fundamentals. PMID:25848612

  8. Observations of inner plasmasphere irregularities with a satellite-beacon radio-interferometer array

    International Nuclear Information System (INIS)

    Jacobson, A.R.; Hoogeveen, G.; Carlos, R.C.; Wu, G.; Fejer, B.G.; Kelley, M.C.

    1996-01-01

    A radio-interferometer array illuminated by 136-MHz beacons of several geosynchronous satellites has been used to study small (≥10 13 m -2 ) transient disturbances in the total electron content along the lines of sight to the satellites. High-frequency (f>3 mHz) electron content oscillations are persistently observed, particularly during night and particularly during geomagnetically disturbed periods. The oscillations move across the array plane at speeds in the range 200 endash 2000 m/s, with propagation azimuths that are strongly peaked in lobes toward the western half-plane. Detailed analysis of this azimuth behavior, involving comparison between observations on various satellite positions, indicates compellingly that the phase oscillations originate in radio refraction due to geomagnetically aligned plasma density perturbations in the inner plasmasphere. The motion of the phase perturbations across the array plane is caused by EXB drift of the plasma medium in which the irregularities are embedded. We review the statistics of 2.5 years of around-the-clock data on the local time, magnetic disturbance, seasonal, and line-of-sight variations of these observed irregularities. We compare the irregularities close-quote inferred electrodynamic drifts to what is known about midlatitude plasma drift from incoherent scatter. Finally, we show in detail how the observation of these irregularities provides a unique and complementary monitor of inner plasmasphere irregularity incidence and zonal drift.copyright 1996 American Geophysical Union

  9. Outage Probability Analysis in Power-Beacon Assisted Energy Harvesting Cognitive Relay Wireless Networks

    Directory of Open Access Journals (Sweden)

    Ngoc Phuc Le

    2017-01-01

    Full Text Available We study the performance of the secondary relay system in a power-beacon (PB assisted energy harvesting cognitive relay wireless network. In our system model, a secondary source node and a relay node first harvest energy from distributed PBs. Then, the source node transmits its data to the destination node with the help of the relay node. Also, fading coefficients of the links from the PBs to the source node and relay node are assumed independent but not necessarily identically distributed (i.n.i.d Nakagami-m random variables. We derive exact expressions for the power outage probability and the channel outage probability. Based on that, we analyze the total outage probability of the secondary relay system. Asymptotic analysis is also performed, which provides insights into the system behavior. Moreover, we evaluate impacts of the primary network on the performance of the secondary network with respect to the tolerant interference threshold at the primary receiver as well as the interference introduced by the primary transmitter at the secondary source and relay nodes. Simulation results are provided to validate the analysis.

  10. Learning from health information exchange technical architecture and implementation in seven beacon communities.

    Science.gov (United States)

    McCarthy, Douglas B; Propp, Karen; Cohen, Alexander; Sabharwal, Raj; Schachter, Abigail A; Rein, Alison L

    2014-01-01

    As health care providers adopt and make "meaningful use" of health information technology (health IT), communities and delivery systems must set up the infrastructure to facilitate health information exchange (HIE) between providers and numerous other stakeholders who have a role in supporting health and care. By facilitating better communication and coordination between providers, HIE has the potential to improve clinical decision-making and continuity of care, while reducing unnecessary use of services. When implemented as part of a broader strategy for health care delivery system and payment reform, HIE capability also can enable the use of analytic tools needed for population health management, patient engagement in care, and continuous learning and improvement. The diverse experiences of seven communities that participated in the three-year federal Beacon Community Program offer practical insight into factors influencing the technical architecture of exchange infrastructure and its role in supporting improved care, reduced cost, and a healthier population. The case studies also document challenges faced by the communities, such as significant time and resources required to harmonize variations in the interpretation of data standards. Findings indicate that their progress developing community-based HIE strategies, while driven by local needs and objectives, is also influenced by broader legal, policy, and market conditions.

  11. The keys to governance and stakeholder engagement: the southeast michigan beacon community case study.

    Science.gov (United States)

    Des Jardins, Terrisca R

    2014-01-01

    Community-based health information exchanges (HIEs) and efforts to consolidate and house data are growing, given the advent of Accountable Care Organizations (ACOs) under the Affordable Care Act and other similar population health focused initiatives. The Southeast Michigan Beacon Community (SEMBC) can be looked to as one case study that offers lessons learned, insights on challenges faced and accompanying workarounds related to governance and stakeholder engagement. The SEMBC case study employs an established Data Warehouse Governance Framework to identify and explain the necessary governance and stakeholder engagement components, particularly as they relate to community-wide data sharing and data warehouses or repositories. Perhaps the biggest lesson learned through the SEMBC experience is that community-based work is hard. It requires a great deal of community leadership, collaboration and resources. SEMBC found that organizational structure and guiding principles needed to be continually revisited and nurtured in order to build the relationships and trust needed among stakeholder organizations. SEMBC also found that risks and risk mitigation tactics presented challenges and opportunities at the outset and through the duration of the three year pilot period. Other communities across the country embarking on similar efforts need to consider realistic expectations about community data sharing infrastructures and the accompanying and necessary governance and stakeholder engagement fundamentals.

  12. VLC-beacon detection with an under-sampled ambient light sensor

    Science.gov (United States)

    Green, Jacob; Pérez-Olivas, Huetzin; Martínez-Díaz, Saúl; García-Márquez, Jorge; Domínguez-González, Carlos; Santiago-Montero, Raúl; Guan, Hongyu; Rozenblat, Marc; Topsu, Suat

    2017-08-01

    LEDs will replace in a near future the current worldwide lighting mainly due to their low production-cost and energy-saving assets. Visible light communications (VLC) will turn gradually the existing lighting network into a communication network. Nowadays VLC transceivers can be found in some commercial centres in Europe; some of them broadcast continuously an identification tag that contains its coordinate position. In such a case, the transceiver acts as a geolocation beacon. Nevertheless, mobile transceivers represent a challenge in the VLC communication chain, as smartphones have not integrated yet a VLC customized detection stage. In order to make current smartphones capable to detect VLC broadcasted signals, their Ambient Light Sensor (ALS) is adapted as a VLC detector. For this to be achieved, lighting transceivers need to adapt their modulation scheme. For instance, frequencies representing start bit, 1, and 0 logic values can be set to avoid flicker from illumination and to permit detecting the under-sampled signal. Decoding the signal requires a multiple steps real-time signal processing as shown here.

  13. Gold nanoparticle-based beacon to detect STAT5b mRNA expression in living cells: a case optimized by bioinformatics screen.

    Science.gov (United States)

    Deng, Dawei; Li, Yang; Xue, Jianpeng; Wang, Jie; Ai, Guanhua; Li, Xin; Gu, Yueqing

    2015-01-01

    Messenger RNA (mRNA), a single-strand ribonucleic acid with functional gene information is usually abnormally expressed in cancer cells and has become a promising biomarker for the study of tumor progress. Hairpin DNA-coated gold nanoparticle (hDAuNP) beacon containing a bare gold nanoparticle (AuNP) as fluorescence quencher and thiol-terminated fluorescently labeled stem-loop-stem oligonucleotide sequences attached by Au-S bond is currently a new nanoscale biodiagnostic platform capable of mRNA detection, in which the design of the loop region sequence is crucial for hybridizing with the target mRNA. Hence, in this study, to improve the sensitivity and selectivity of hDAuNP beacon simultaneously, the loop region of hairpin DNA was screened by bioinformatics strategy. Here, signal transducer and activator of transcription 5b (STAT5b) mRNA was selected and used as a practical example. The results from the combined characterizations using optical techniques, flow cytometry assay, and cell microscopic imaging showed that after optimization, the as-prepared hDAuNP beacon had higher selectivity and sensitivity for the detection of STAT5b mRNA in living cells, as compared with our previous beacon. Thus, the bioinformatics method may be a promising new strategy for assisting in the designing of the hDAuNP beacon, extending its application in the detection of mRNA expression and the resultant mRNA-based biological processes and disease pathogenesis.

  14. Genetics and molecular mapping of genes for race-specific all-stage resistance and non-race-specific high-temperature adult-plant resistance to stripe rust in spring wheat cultivar Alpowa.

    Science.gov (United States)

    Lin, F; Chen, X M

    2007-05-01

    Stripe rust, caused by Puccinia striiformis f. sp. tritici, is one of the most widespread and destructive wheat diseases worldwide. Growing resistant cultivars is the preferred control of the disease. The spring wheat cultivar 'Alpowa' has both race-specific, all-stage resistance and non-race-specific, high-temperature adult-plant (HTAP) resistances to stripe rust. To identify genes for the stripe rust resistances, Alpowa was crossed with 'Avocet Susceptible' (AVS). Seedlings of the parents, and F(1), F(2) and F(3) progeny were tested with races PST-1 and PST-21 of P. striiformis f. sp. tritici under controlled greenhouse conditions. Alpowa has a single partially dominant gene, designated as YrAlp, conferring all-stage resistance. Resistance gene analog polymorphism (RGAP) and simple sequence repeat (SSR) techniques were used to identify molecular markers linked to YrAlp. A linkage group of five RGAP markers and two SSR markers was constructed for YrAlp using 136 F(3) lines. Amplification of a set of nulli-tetrasomic Chinese Spring lines with RGAP markers Xwgp47 and Xwgp48 and the two SSR markers indicated that YrAlp is located on the short arm of chromosome 1B. To map quantitative trait loci (QTLs) for the non-race-specific HTAP resistance, the parents and 136 F(3) lines were tested at two sites near Pullman and one site near Mount Vernon, Washington, under naturally infected conditions. A major HTAP QTL was consistently detected across environments and was located on chromosome 7BL. Because of its chromosomal location and the non-race-specific nature of the HTAP resistance, this gene is different from previously described genes for adult-plant resistance, and is therefore designated Yr39. The gene contributed to 64.2% of the total variation of relative area under disease progress curve (AUDPC) data and 59.1% of the total variation of infection type data recorded at the heading-flowering stages. Two RGAP markers, Xwgp36 and Xwgp45 with the highest R (2) values

  15. Electrochemical immunoassay for the prostate specific antigen using a reduced graphene oxide functionalized with a high molecular-weight silk peptide

    International Nuclear Information System (INIS)

    Wang, Yanying; Qu, Ying; Li, Chunya; Wu, Kangbing; Liu, Guishen; Hou, Xiaodong; Huang, Yina; Wu, Wangze

    2015-01-01

    High molecular-weight silk peptide (SP) was used to functionalize the surface of nanosheets of reduced graphene oxide (rGO). The SP-rGO nanocomposite was then mixed with mouse anti-human prostate specific antigen monoclonal antibody (anti-PSA) and coated onto a glassy carbon electrode to fabricate an immunosensor. By using the hexacyanoferrate redox system as electroactive probe, the immunosensor was characterized by voltammetry and electrochemical impedance spectroscopy. The peak current, measured at the potential of 0.24 V (vs. SCE), is distinctly reduced after binding prostate specific antigen (PSA). Response (measured by differential pulse voltammetry) is linearly related to PSA concentration in the range from 0.1 to 5.0 ng · mL −1 and from 5.0 to 80.0 ng∙mL −1 , and the detection limit is 53 pg∙mL −1 (at an SNR of 3). The immunosensor was successfully applied to the determination of PSA in clinical serum samples, and the results were found to agree well with those obtained with an enzyme-linked immunosorbent assay. (author)

  16. Routinely automated production of 3'-deoxy-3'-[18F] fluorothymidine as a specific molecular imaging probe of tumor cell proliferation

    International Nuclear Information System (INIS)

    Wang Mingwei; Zhang Yingjian; Zhang Yongping

    2011-01-01

    This work was aimed at developing a routine for automated production of 3'-deoxy-3'-[ 18 F]fluorothymidine ( 18 F-FLT), a specific molecular imaging probe of tumor cell proliferation, using one-pot two-step strategy and an upgraded Explora GN module integrated with a semi-preparative HPLC system. Firstly, the nucleophilic [ 18 F] radiofluorination of precursor BDNT with activated 18 F ion was carried out at 120 degree C for 5 min to yield the labeled intermediate 18 F-BDFT. Secondly, the acidic hydrolysis of 18 F-BDFT was run at 110 degree C for 5 min to produce 18 F-FLT after addition of HCl, and 18 F-FLT was purified by HPLC. This automated production of 18 F-FLT is of fast, reliable and multi-run features, being completed within 65 min with radiochemical yield of 15%-25% (without decay correction). The quality control of 18 F-FLT was identical with the radiopharmaceutical requirements, especiallly the radiochemical purity of greater than 99% and high chemical purity and specific activity own to HPLC purification. (authors)

  17. Molecular characterization and specific detection of Anaplasma species (AP-sd) in sika deer and its first detection in wild brown bears and rodents in Hokkaido, Japan.

    Science.gov (United States)

    Moustafa, Mohamed Abdallah Mohamed; Lee, Kyunglee; Taylor, Kyle; Nakao, Ryo; Sashika, Mariko; Shimozuru, Michito; Tsubota, Toshio

    2015-12-01

    A previously undescribed Anaplasma species (herein referred to as AP-sd) has been detected in sika deer, cattle and ticks in Japan. Despite being highly similar to some strains of A. phagocytophilum, AP-sd has never been detected in humans. Its ambiguous epidemiology and the lack of tools for its specific detection make it difficult to understand and interpret the prevalence of this Anaplasma species. We developed a method for specific detection, and examined AP-sd prevalence in Hokkaido wildlife. Our study included 250 sika deer (Cervus nippon yesoensis), 13 brown bears (Ursus arctos yesoensis) and 252 rodents including 138 (Apodemus speciosus), 45 (Apodemus argenteus), 42 (Myodes rufocanus) and 27 (Myodes rutilus) were collected from Hokkaido island, northern Japan, collected during 2010 to 2015. A 770 bp and 382 bp segment of the 16S rRNA and gltA genes, respectively, were amplified by nested PCR. Results were confirmed by cloning and sequencing of the positive PCR products. A reverse line blot hybridization (RLB) based on the 16S rRNA gene was then developed for the specific detection of AP-sd. The prevalence of AP-sd by nested PCR in sika deer was 51% (128/250). We detected this Anaplasma sp. for the first time in wild brown bears and rodents with a prevalence of 15% (2/13) and 2.4% (6/252), respectively. The sequencing results of the 16S rRNA and gltA gene amplicons were divergent from the selected A. phagocytophilum sequences in GenBank. Using a newly designed AP-sd specific probe for RLB has enabled us to specifically detect this Anaplasma species. Besides sika deer and cattle, wild brown bears and rodents were identified as potential reservoir hosts for AP-sd. This study provided a high throughput molecular method that specifically detects AP-sd, and which can be used to investigate its ecology and its potential as a threat to humans in Japan. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. No gold standard estimation of the sensitivity and specificity of two molecular diagnostic protocols for Trypanosoma brucei spp. in Western Kenya.

    Directory of Open Access Journals (Sweden)

    Barend Mark de Clare Bronsvoort

    2010-01-01

    Full Text Available African animal trypanosomiasis is caused by a range of tsetse transmitted protozoan parasites includingTrypanosoma vivax, Trypanosoma congolense and Trypansoma brucei. In Western Kenya and other parts of East Africa two subspecies of T. brucei, T.b. brucei and the zoonoticT.b. rhodesiense, co-circulate in livestock. A range of polymerase chain reactions (PCR have been developed as important molecular diagnostic tools for epidemiological investigations of T. brucei s.l. in the animal reservoir and of its zoonotic potential. Quantification of the relative performance of different diagnostic PCRs is essential to ensure comparability of studies. This paper describes an evaluation of two diagnostic test systems for T. brucei using a T. brucei s.l. specific PCR [1] and a single nested PCR targeting the Internal Transcribed Spacer (ITS regions of trypanosome ribosomal DNA [2]. A Bayesian formulation of the Hui-Walter latent class model was employed to estimate their test performance in the absence of a gold standard test for detecting T.brucei s.l. infections in ear-vein blood samples from cattle, pig, sheep and goat populations in Western Kenya, stored on Whatman FTA cards. The results indicate that the system employing the T. brucei s.l. specific PCR (Se1=0.760 had a higher sensitivity than the ITS-PCR (Se2=0.640; both have high specificity (Sp1=0.998; Sp2=0.997. The true prevalences for livestock populations were estimated (pcattle=0.091, ppigs=0.066, pgoats=0.005, psheep=0.006, taking into account the uncertainties in the specificity and sensitivity of the two test systems. Implications of test performance include the required survey sample size; due to its higher sensitivity and specificity, the T. brucei s.l. specific PCR requires a consistently smaller sample size than the ITS-PCR for the detection of T. brucei s.l. However the ITS-PCR is able to simultaneously screen samples for other pathogenic trypanosomes and may thus be, overall, a better

  19. Prussian blue mediated amplification combined with signal enhancement of ordered mesoporous carbon for ultrasensitive and specific quantification of metolcarb by a three-dimensional molecularly imprinted electrochemical sensor.

    Science.gov (United States)

    Yang, Yukun; Cao, Yaoyu; Wang, Xiaomin; Fang, Guozhen; Wang, Shuo

    2015-02-15

    In this work, we presented a three-dimensional (3D) molecularly imprinted electrochemical sensor (MIECS) with novel strategy for ultrasensitive and specific quantification of metolcarb based on prussian blue (PB) mediated amplification combined with signal enhancement of ordered mesoporous carbon. The molecularly imprinted polymers were synthesized by electrochemically induced redox polymerization of para aminobenzoic acid (p-ABA) in the presence of template metolcarb. Ordered mesoporous carbon material (CMK-3) was introduced to enhance the electrochemical response by improving the structure of the modified electrodes and facilitating charge transfer processes of PB which was used as an inherent electrochemical active probe. The modification process for the working electrodes of the MIECS was characterized by scanning electron microscope (SEM) and cyclic voltammetry (CV), and several important parameters controlling the performance of the MIECS were investigated and optimized in detail. The MIECS with 3D structure had the advantages of ease of preparation, high porous surface structure, speedy response, ultrasensitivity, selectivity, reliable stability, good reproducibility and repeatability. Under the optimal conditions, the MIECS offered an excellent current response for metolcarb in the linear response range of 5.0 × 10(-10)-1.0 × 10(-4) mol L(-1) and the limit of detection (LOD) was calculated to be 9.3 × 10 (-11)mol L(-1) (S/N = 3). The proposed MIECS has been successfully applied for the determination of metolcarb in real samples with satisfactory recoveries. Furthermore, the construction route of this ultrasensitive 3D MIECS may provide a guideline for the determination of non-electroactive analytes in environmental control and food safety. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Computational docking, molecular dynamics simulation and subsite structure analysis of a maltogenic amylase from Bacillus lehensis G1 provide insights into substrate and product specificity.

    Science.gov (United States)

    Manas, Nor Hasmaliana Abdul; Bakar, Farah Diba Abu; Illias, Rosli Md

    2016-06-01

    Maltogenic amylase (MAG1) from Bacillus lehensis G1 displayed the highest hydrolysis activity on β-cyclodextrin (β-CD) to produce maltose as a main product and exhibited high transglycosylation activity on malto-oligosaccharides with polymerization degree of three and above. These substrate and product specificities of MAG1 were elucidated from structural point of view in this study. A three-dimensional structure of MAG1 was constructed using homology modeling. Docking of β-CD and malto-oligosaccharides was then performed in the MAG1 active site. An aromatic platform in the active site was identified which is responsible in substrate recognition especially in determining the enzyme's preference toward β-CD. Molecular dynamics (MD) simulation showed MAG1 structure is most stable when docked with β-CD and least stable when docked with maltose. The docking analysis and MD simulation showed that the main subsites for substrate stabilization in the active site are -2, -1, +1 and +2. A bulky residue, Trp359 at the +2 subsite was identified to cause steric interference to the bound linear malto-oligosaccharides thus prevented it to occupy subsite +3, which can only be reached by a highly bent glucose molecule such as β-CD. The resulted modes of binding from docking simulation show a good correlation with the experimentally determined hydrolysis pattern. The subsite structure generated from this study led to a possible mode of action that revealed how maltose was mainly produced during hydrolysis. Furthermore, maltose only occupies subsite +1 and +2, therefore could not be hydrolyzed or transglycosylated by the enzyme. This important knowledge has paved the way for a novel structure-based molecular design for modulation of its catalytic activities. Copyright © 2016 Elsevier Inc. All rights reserved.