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Sample records for specific molecular beacon

  1. Quantum Dot Molecular Beacons for DNA Detection

    Science.gov (United States)

    Cady, Nathaniel C.

    Molecular beacons have become an important fluorescent probe for sequence-specific DNA detection. To improve the sensitivity and robustness of molecular beacon assays, fluorescent semiconductor quantum dots (QDs) are now being used as the fluorescent moiety for molecular beacon synthesis. Multiple linkage strategies can be used for attaching molecular beacon DNA to QDs, and multiple quenchers, including gold particles, can be used for fluorescence quenching. Covalent attachment of QDs to DNA can be achieved through amide linkage, and affinity-based attachment can be achieved with streptavidin-biotin linkage. We have shown that these linkage strategies can be used to successfully create quantum dot molecular beacons that can be used in DNA detection assays with high specificity.

  2. Electrochemical molecular beacon biosensor for sequence-specific recognition of double-stranded DNA.

    Science.gov (United States)

    Miao, Xiangmin; Guo, Xiaoting; Xiao, Zhiyou; Ling, Liansheng

    2014-09-15

    Direct recognition of double-stranded DNA (dsDNA) was crucial to disease diagnosis and gene therapy, because DNA in its natural state is double stranded. Here, a novel sensor for the sequence-specific recognition of dsDNA was developed based on the structure change of ferrocene (Fc) redox probe modified molecular beacon (MB). For constructing such a sensor, gold nanoparticles (AuNPs) were initially electrochemical-deposited onto glass carbon electrode (GCE) surface to immobilize thiolated MB in their folded states with Au-S bond. Hybridization of MB with target dsDNA induced the formation of parallel triplex DNA and opened the stem-loop structure of it, which resulted in the redox probe (Fc) away from the electrode and triggered the decrease of current signals. Under optimal conditions, dsDNA detection could be realized in the range from 350 pM to 25 nM, with a detection limit of 275 pM. Moreover, the proposed method has good sequence-specificity for target dsDNA compared with single base pair mismatch and two base pairs mismatches. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. 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...... section gives initially an overview of the molecular beacon technology usability and working principle. Later on the mechanism of molecular beacon’s internalization by SLO treatment was theoretically and experimentally investigated to determine optimal transfection condition and actual cell loading....... Finally the problem of signal generation by molecular beacons was tackled by developing two new methods. It was demonstrated that by carefully design of interacting beacons with a new geometrical configuration, it is possible to induce among them both a linear and an avalanche reaction which improve...

  4. 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

  5. Detection of Toxoplasma gondii with a DNA molecular beacon probe

    Science.gov (United States)

    Zhou, Cun; Xu, Shichao; Yang, Juan; Zhang, Jimei; Dai, Zhao; Zheng, Guo; Sun, Bo; Sun, Shuqing; Feng, Teilin; Zi, Yan; Liang, Chu; Luo, Hao

    2009-07-01

    Toxoplasma gondii is a kind of microscopic parasite that may infect humans, and there are increasing concerns on the early detection of latent Toxoplasma gondii infection in recent years. This research highlights a new type of molecular beacon (MB) fluorescent probe for Toxoplasma DNA testing. We combined high-efficiency fluorescent inorganic core-shell quantum dots-CdTe/ZnS (as fluorescent energy donor) and BHQ-2 (energy acceptor) to the single-strand DNA of Toxoplasma gondii, and a molecular beacon sensing system based on fluorescence resonance energy transfer (FRET) was achieved. Core-shell quantum dots CdTe/ZnS was firstly prepared in aqueous solution, and the influencing factor of its fluorescent properties, including CdTe/Na2S/Zn(CH3COO)2 (v/v), dependence of reaction time, temperature, and pH, is investigated systematically. The synthesized quantum dots and molecular beacon were characterized by transmission electron microscopy (TEM), ultraviolet-visible spectrophotometer (UV-vis), fluorescent spectrophotometer (FS), respectively. The TEM results showed that CdTe/ZnS core-shell quantum dots is ~11nm in size, and the quantum dots is water-soluble well. The sensing ability of target DNA of assembled MB was investigated, and results showed that the target Toxoplasma gonddi DNA can be successfully detected by measuring the change of fluorescence intensity. The results showed that the current sensing probe will be a useful and convenient tool in Toxoplasma gondii early detection.

  6. Molecular beacon biosensors for DNA/RNA analysis

    Science.gov (United States)

    Fang, Xiaohong; Schuster, Sheldon; Liu, Xiaojing; Correll, Tiffany; Zhang, Peng; Tapec, Ruby; Santra, Swadeshmukul; Qhobosheanne, Monde; Lou, Jane H.; Tan, Weihong

    2000-03-01

    We have developed a variety of novel DNA biosensors using a new class of oligonucleotide probe, molecular beacon (MB). MB has the fluorescence signal transduction mechanism built within the molecules. It can report the presence of specific nucleic acids with high sensitivity and excellent selectivity. Biotinylated MBs have been designed and synthesized for immobilization onto silica surface through avidin-biotin binding. The effect of the avidin-biotin bridge on the MB hybridization has been studied. Our result shows that using streptavidin has less effect than using avidin in MB hybridization. Two kinds of fiber optical DNA sensors have been prepared and characterized: a fiber optic evanescent wave sensor and a submicrometer optical fiber sensor. The sensors are rapid,stable, highly selective, reproducible and regenerable. They have been applied to detect specific DNA and mRNA sequences and to the study of the DNA hybridization kinetics. Silica nanoparticles have also been used for MB immobilization in order to prepare a large quantity of nanometer sized DNA/RNA biosensors.

  7. 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.

  8. A novel strategy for human papillomavirus detection and genotyping with SybrGreen and molecular beacon polymerase chain reaction.

    Science.gov (United States)

    Szuhai, K; Sandhaus, E; Kolkman-Uljee, S M; Lemaître, M; Truffert, J C; Dirks, R W; Tanke, H J; Fleuren, G J; Schuuring, E; Raap, A K

    2001-11-01

    Human papillomaviruses (HPVs) play an important role in the pathogenesis of cervical cancer. For identification of the large number of different HPV types found in (pre)malignant lesions, a robust methodology is needed that combines general HPV detection with HPV genotyping. We have developed for formaldehyde-fixed samples a strategy that, in a homogeneous, real-time fluorescence polymerase chain reaction (PCR)-based assay, accomplishes general HPV detection by SybrGreen reporting of HPV-DNA amplicons, and genotyping of seven prevalent HPV types (HPV-6, -11, -16, -18, -31, -33, -45) by real-time molecular beacon PCR. The false-positive rate of the HPV SybrGreen-PCR was 4%, making it well suited as a prescreening, general HPV detection technology. The type specificity of the seven selected HPV molecular beacons was 100% and double infections were readily identified. The multiplexing capacity of the HPV molecular beacon PCR was analyzed and up to three differently labeled molecular beacons could be used in one PCR reaction without observing cross talk. The inherent quantitation capacities of real-time fluorescence PCR allowed the determination of average HPV copy number per cell. We conclude that the HPV SybrGreen-PCR in combination with the HPV molecular beacon PCR provides a robust, sensitive, and quantitative general HPV detection and genotyping methodology.

  9. Toxoplasma gondii DNA detection with a magnetic molecular beacon probe

    Science.gov (United States)

    Xu, Shichao; Yao, Cuicui; Wei, Shuoming; Zhang, Jimei; Dai, Zhao; Zheng, Guo; Sun, Bo; Han, Qing; Hu, Fei; Zhou, Hongming

    2008-12-01

    Toxoplasma Gondii infection is widespread in humans worldwide and reported infection rates range from 3%-70%, depending on the populations or geographic areas, and it has been recognized as a potential food safety hazard in our daily life. A magnetic molecular beacon probe (mMBP), based on theory of fluorescence resonance energy transfer (FRET), was currently reported to detect Toxoplasma Gondii DNA. Nano-sized Fe3O4 were primarily prepared by coprecipitation method in aqueous phase with NaOH as precipitator, and was used as magnetic core. The qualified coreshell magnetic quantum dots (mQDs), i.e. CdTe(symbol)Fe3O4, were then achieved by layer-by-layer method when mol ratio of Fe3O4/CdTe is 1/3, pH at 6.0, 30 °C, and reactant solution was refluxed for 30 min, the size of mQDs were determined to be 12-15 nm via transmission electron microscopy (TEM). Over 70% overlap between emission spectrum of mQDs and absorbance spectrum of BHQ-2 was observed, this result suggests the synthesized mQDs and BHQ-2 can be utilized as energy donor and energy acceptor, respectively. The sensing probe was fabricated and a stem-loop Toxoplasma Gondii DNA oligonucleotide was labeled with mQDs at the 5' end and BHQ-2 at 3' end, respectively. Target Toxoplasma gondii DNA was detected under conditions of 37 °C, hybridization for 2h, at pH8.0 in Tris-HCl buffer. About 30% recovery of fluorescence intensity was observed via fluorescence spectrum (FS) after the Toxoplasma gondii DNA was added, which suggested that the Toxoplasma Gondii DNA was successfully detected. Specificity investigation of the mMBP indicated that relative low recovery of fluorescence intensity was obtained when the target DNA with one-base pair mismatch was added, this result indicated the high specificity of the sensing probe. Our research simultaneously indicated that mMBP can be conveniently separated from the unhybridized stem-loop DNA and target DNA, which will be meaningful in DNA sensing and purification process.

  10. 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...

  11. Analytical performance of molecular beacons on surface immobilized gold nanoparticles of varying size and density.

    Science.gov (United States)

    Uddayasankar, Uvaraj; Krull, Ulrich J

    2013-11-25

    The high quenching efficiency of metal nanoparticles has facilitated its use as quenchers in molecular beacons. To optimize this system, a good understanding of the many factors that influence molecular beacon performance is required. In this study, molecular beacon performance was evaluated as a function of gold nanoparticle size and its immobilization characteristics. Gold nanoparticles of 4 nm, 15 nm and 87 nm diameter, were immobilized onto glass slides. Each size regime offered distinctive optical properties for fluorescence quenching of molecular dyes that were conjugated to oligonucleotides that were immobilized to the gold nanoparticles. Rigid double stranded DNA was used as a model to place fluorophores at different distances from the gold nanoparticles. The effect of particle size and also the immobilization density of nanoparticles was evaluated. The 4 nm and 87 nm gold nanoparticles offered the highest sensitivity in terms of the change in fluorescence intensity as a function of distance (3-fold improvement for Cy5). The optical properties of the molecular fluorophore was of significance, with Cy5 offering higher contrast ratios than Cy3 due to the red-shifted emission spectrum relative to the plasmon peak. A high density of gold nanoparticles reduced contrast ratios, indicating preference for a monolayer of immobilized nanoparticles when considering analytical performance. Molecular beacon probes were then used in place of the double stranded oligonucleotides. There was a strong dependence of molecular beacon performance on the length of a linker used for attachment to the nanoparticle surface. The optimal optical performance was obtained with 4 nm gold nanoparticles that were immobilized as monolayers of low density (5.7×10(11)particles cm(-2)) on glass surfaces. These nanoparticle surfaces offered a 2-fold improvement in analytical performance of the molecular beacons when compared to other nanoparticle sizes investigated. The principles developed

  12. Non-linear molecular pattern classification using molecular beacons with multiple targets.

    Science.gov (United States)

    Lee, In-Hee; Lee, Seung Hwan; Park, Tai Hyun; Zhang, Byoung-Tak

    2013-12-01

    In vitro pattern classification has been highlighted as an important future application of DNA computing. Previous work has demonstrated the feasibility of linear classifiers using DNA-based molecular computing. However, complex tasks require non-linear classification capability. Here we design a molecular beacon that can interact with multiple targets and experimentally shows that its fluorescent signals form a complex radial-basis function, enabling it to be used as a building block for non-linear molecular classification in vitro. The proposed method was successfully applied to solving artificial and real-world classification problems: XOR and microRNA expression patterns. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Visual detection of multidrug resistance gene in living cell using the molecular beacon imaging

    Science.gov (United States)

    Zhou, Qiumei; Ma, Yi; Gu, Yueqing

    2014-09-01

    A major problem in cancer treatment is the development of resistance to chemotherapeutic agents in tumor cells. Detection of effective prognostic biomarkers and targets are of crucial importance to the management of individualized therapies. However, quantitative analysis of the drug resistance gene had been difficult because of technical limitations. In this study, we designed and used a special hairpin deoxyribonucleic acid (DNA), which served as a beacon for detecting human drug resistance indicater. 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 hDAuNP beacons could be taken up by living cells with low inherent cytotoxicity and higher stability. hDAuNP beacon imaged by confocal laser scanning microscopy to detect the resistance gene expression. The detected fluorescence in MCF7and MCF7/ADR cells correlates with the specific drug resistance gene expression, which is consistent with the result from Q-PCR. Thus, this approach overcame many of the challenges of previous techniques by creating highly sensitive and effective intracellular probes for monitoring gene expression.

  14. 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

  15. Quantification of Salmonella Typhi in water and sediments by molecular-beacon based qPCR.

    Science.gov (United States)

    Rani, Neetika; Vajpayee, Poornima; Bhatti, Saurabh; Singh, Smriti; Shanker, Rishi; Gupta, Kailash Chand

    2014-10-01

    A molecular-beacon based qPCR assay targeting staG gene was designed for specific detection and quantification of S. Typhi and validated against water and sediment samples collected from the river Ganga, Yamuna and their confluence on two days during Mahakumbha mela 2012-2013 (a) 18 December, 2012: before six major religious holy dips (Makar Sankranti, Paush Poornima, Mauni Amavasya, Basant Panchami, Maghi Poornima and Mahashivratri) (b) 10 February, 2013: after the holy dip was taken by over 3,00,00,000 devotees led by ascetics of Hindu sects at Sangam on 'Mauni Amavasya' (the most auspicious day of ritualistic mass bathing). The assay could detect linearly lowest 1 genomic equivalent per qPCR and is highly sensitive and selective for S. Typhi detection in presence of non specific DNA from other bacterial strains including S. Paratyphi A and S. Typhimurium. It has been observed that water and sediment samples exhibit S. Typhi. The mass holy dip by devotees significantly affected the water and sediment quality by enhancing the number of S. Typhi in the study area. The qPCR developed in the study might be helpful in planning the intervention and prevention strategies for control of enteric fever outbreaks in endemic regions. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. 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.

  17. The use of nanocrystal quantum dot as fluorophore reporters in molecular beacon-based assays

    Science.gov (United States)

    Adegoke, Oluwasesan; Park, Enoch Y.

    2016-12-01

    The utilization of molecular beacon (MB) biosensor probes to detect nucleic acid targets has received enormous interest within the scientific community. This interest has been stimulated by the operational qualities of MB-based probes with respect to their unique sensitivity and specificity. The design of MB biosensors entails not only optimizing the sequence of the loop to hybridize with the nucleic acid target or optimization of the length of the stem to tune the sensitivity but also the selection of the appropriate fluorophore reporter to generate the signal transduction read-out upon hybridization of the probe with the target sequence. Traditional organic fluorescent dyes are mostly used for signal reporting in MB assays but their optical properties in comparison to semiconductor fluorescent quantum dot (Qdot) nanocrystals are at a disadvantage. This review highlights the progress made in exploiting Qdot as fluorophore reporters in MB-based assays with the aim of instigating further development in the field of Qdot-MB technology. The development reported to date indicates that unparalleled fluorescence signal reporting in MB-based assays can be achieved using well-constructed Qdot fluorophores.

  18. Early Detection of Breast Cancer Using Molecular Beacons

    National Research Council Canada - National Science Library

    Yang, Lily

    2004-01-01

    .... We also developed a procedure to detect both survivin and cyclin Dl gene expression simultaneously in single cancer cells, which increases the sensitivity and specificity of detection of cancer cells...

  19. Proteomics in reproductive biology: beacon for unraveling the molecular complexities.

    Science.gov (United States)

    Upadhyay, Rahul D; Balasinor, N H; Kumar, Anita V; Sachdeva, Geetanjali; Parte, Priyanka; Dumasia, Kushaan

    2013-01-01

    Proteomics, an interface of rapidly evolving advances in physics and biology, is rapidly developing and expanding its potential applications to molecular and cellular biology. Application of proteomics tools has contributed towards identification of relevant protein biomarkers that can potentially change the strategies for early diagnosis and treatment of several diseases. The emergence of powerful mass spectrometry-based proteomics technique has added a new dimension to the field of medical research in liver, heart diseases and certain forms of cancer. Most proteomics tools are also being used to study physiological and pathological events related to reproductive biology. There have been attempts to generate the proteomes of testes, sperm, seminal fluid, epididymis, oocyte, and endometrium from reproductive disease patients. Here, we have reviewed proteomics based investigations in humans over the last decade, which focus on delineating the mechanism underlying various reproductive events such as spermatogenesis, oogenesis, endometriosis, polycystic ovary syndrome, embryo development. The challenge is to harness new technologies like 2-DE, DIGE, MALDI-MS, SELDI-MS, MUDPIT, LC-MS etc., to a greater extent to develop widely applicable clinical tools in understanding molecular aspects of reproduction both in health and disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 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...

  1. Hybridization Efficiency of Molecular Beacons Bound to Gold Nanowires: Effect of Surface Coverage and Target Length

    Science.gov (United States)

    2010-01-01

    Surface-bound nucleic acid probes designed to adopt specific secondary structures are becoming increasingly important in a range of biosensing applications but remain less well characterized than traditional single-stranded probes, which are typically designed to avoid secondary structure. We report the hybridization efficiency for surface-immobilized hairpin DNA probes. Our probes are molecular beacons, carrying a 3′ dye moiety and a 5′ thiol for attachment to gold nanowires, which serve as both scaffolds for probe attachment and quenchers. Hybridization efficiency was dependent on probe surface coverage, reaching a maximum of ∼90% at intermediate coverages of (1−2) × 1012 probes/cm2 and dropping to ≤20% at higher or lower coverages. Fluorescence intensity did not track with the number of target molecules bound, and was highest for high probe coverage despite the lower bound targets per square centimeter. Backfilling with short thiolated oligoethylene glycol spacers increased hybridization efficiency at low hairpin probe coverages (∼(3−4) × 1011 probes/cm2), but not at higher probe coverages (1 × 1012/cm2). We also evaluated the effect of target length by adding up to 50 nonhybridizing nucleotides to the 3′ or 5′ end of the complementary target sequence. Additional nucleotides on the 3′ end of the complementary target sequence (i.e., the end near the nanowire surface) had a much greater impact on hybridization efficiency as compared to nucleotides added to the 5′ end. This work provides guidance in designing sensors in which surface-bound probes designed to adopt secondary structures are used to detect target sequences from solution. PMID:21038880

  2. 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.

  3. 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 R...... in living cells was demonstrated....

  4. 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

    Monitoring gene expression is an important tool for elucidating mechanisms of cellular function. In order to monitor gene expression during nerve cell development, molecular beacon (MB) probes targeting markers representing different stages of neuronal differentiation were designed and synthesized...... transfection. The cells will then each contain about 60,000 MBs. Gene expression was detected at different time points using fluorescence microscopy. Nestin and NeuN mRNA were expressed in approximately 35% of the LUHMES cells grown in growth medium, and in 80-90% of cells after differentiation. MAP2...... 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...

  5. Theranostic Properties of a Survivin-Directed Molecular Beacon in Human Melanoma Cells

    Science.gov (United States)

    Carpi, Sara; Fogli, Stefano; Giannetti, Ambra; Adinolfi, Barbara; Tombelli, Sara; Da Pozzo, Eleonora; Vanni, Alessia; Martinotti, Enrica; Martini, Claudia; Breschi, Maria Cristina; Pellegrino, Mario

    2014-01-01

    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. PMID:25501971

  6. Chitosan Combined with Molecular Beacon for Mir-155 Detection and Imaging in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hai-Zhen Zhu

    2014-09-01

    Full Text Available Lung cancer is the major cause of cancer-related deaths worldwide, thus developing effective methods for its early diagnosis is urgently needed. In recent years, microRNAs (miRNAs, miR have been reported to play important roles in carcinogenesis and have become potential biomarkers for cancer diagnosis and treatment. Molecular beacon (MB technology is a universal technology to detect DNA/RNA expression in living cells. As a natural polymers, chitosan (CS nanoparticles could be used as a carrier for safe delivery of nucleic acid. In this study, we developed a probe using nanoparticles of miR-155 MB self assembled with CS (CS-miR-155 MB to image the expression of miR-155 in cancer cells. Hybridization assay showed that the locked nucleic acid (LAN modified miR-155 MB could target miR-155 effectively and sensitively. The miR-155 MB self-assembly with CS nanoparticles formed stable complexes at the proper weight ratio. The CS nanoparticles showed higher fluorescence intensity and transfection efficiency than the lipid-based formulation transfection agent by confocal microscopy and flow cytometry analysis. The CS-MB complexes were found to be easily synthesized and exhibited strong enzymatic stability, efficient cellular uptake, high target selectivity and biocompatibility. The CS-MB complexes can also be applied in other cancers just by simply changing for a targeted miRNA highly expressed in those cancer cells. Therefore, it is a promising vehicle used for detecting miRNA expression in living cells.

  7. Photodynamic Molecular Beacons: An Image-Guided Therapeutic Approach to Breast Cancer Vertebral Metastases

    Science.gov (United States)

    2012-03-01

    spinal metastases are predominantly osteolytic (bone destructive), which is associated with an increase in osteo- clast activity.1 Metastasis disrupts...0.001). The distributions and shape of the cells are largely homogeneous after incubation with the beacons, suggesting minimal toxicity (SI Figure S3

  8. A tumor mRNA-mediated bi-photosensitizer molecular beacon as an efficient imaging and photosensitizing agent.

    Science.gov (United States)

    Gao, Yuan; Qiao, Guangming; Zhuo, Linhai; Li, Na; Liu, Ying; Tang, Bo

    2011-05-14

    A bi-photosensitizer molecular beacon (bi-PS MB) is assembled by coupling two PS molecules, respectively, onto the opposite ends of a single MB. The MB can be triggered by a tumor marker-survivin mRNA. Fluorescence and cytotoxic (1)O(2) generation occur effectively in breast cancer cells, but not in normal cells. Compared with a single-PS MB, a bi-PS MB exhibits much-enhanced properties in the signal-to-background ratio and (1)O(2) generation simultaneously. © The Royal Society of Chemistry 2011

  9. A multiplex protein-free lateral flow assay for detection of microRNAs based on unmodified molecular beacons.

    Science.gov (United States)

    Javani, Atefeh; Javadi-Zarnaghi, Fatemeh; Rasaee, Mohammad Javad

    2017-11-15

    Lateral flow assays (LFAs) have promising potentials for point-of-care applications. Recently, many LFAs have been reported that are based on hybridization of oligonucleotide strands. Mostly, biotinylated capture DNAs are immobilized on the surface of a nitrocellulose membrane via streptavidin interactions. During the assay, stable colorful complexes get formed that are visible by naked eyes. Here, we present an inexpensive and unique design of LFA that applies unmodified oligonucleotides at capture lines. The presented LFA do not utilize streptavidin or any other affinity protein. We employ structural switch of molecular beacons (MB) in combination with base stacking hybridization (BSH) phenomenon. The unique design of the reported LFA provided high selectivity for target oligonucleotides. We validated potential applications of the system for detection of DNA mimics of two microRNAs in multiplex assays. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. In vitro RNA release from a human rhinovirus monitored by means of a molecular beacon and chip electrophoresis.

    Science.gov (United States)

    Weiss, Victor U; Bliem, Christina; Gösler, Irene; Fedosyuk, Sofiya; Kratzmeier, Martin; Blaas, Dieter; Allmaier, Günter

    2016-06-01

    Liquid-phase electrophoresis either in the classical capillary format or miniaturized (chip CE) is a valuable tool for quality control of virus preparations and for targeting questions related to conformational changes of viruses during infection. We present an in vitro assay to follow the release of the RNA genome from a human rhinovirus (common cold virus) by using a molecular beacon (MB) and chip CE. The MB, a probe that becomes fluorescent upon hybridization to a complementary sequence, was designed to bind close to the 3' end of the viral genome. Addition of Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a well-known additive for reduction of bleaching and blinking of fluorophores in fluorescence microscopy, to the background electrolyte increased the sensitivity of our chip CE set-up. Hence, a fast, sensitive and straightforward method for the detection of viral RNA is introduced. Additionally, challenges of our assay will be discussed. In particular, we found that (i) desalting of virus preparations prior to analysis increased the recorded signal and (ii) the MB-RNA complex signal decreased with the time of virus storage at -70 °C. This suggests that 3'-proximal sequences of the viral RNA, if not the whole genome, underwent degradation during storage and/or freezing and thawing. In summary, we demonstrate, for two independent virus batches, that chip electrophoresis can be used to monitor MB hybridization to RNA released upon incubation of the native virus at 56 °C. Graphical Abstract Schematic of the study strategy: RNA released from HRV-A2 is detected by chip electrophoresis through the increase in fluorescence after genom complexation to a cognate molecular beacon.

  11. Rapid genetic typing of diarrheagenic Escherichia coli using a two-tube modified molecular beacon based multiplex real-time PCR assay and its clinical application.

    Science.gov (United States)

    Chen, Qingliang; Shi, Xiaolu; Li, Yinghui; Jiang, Yixiang; Lin, Yiman; Qiu, Yaqun; Li, Qingge; Hu, Qinghua

    2014-07-15

    Diarrheagenic Escherichia coli (DEC), including Enterotoxigenic E.coli (ETEC), Enteroaggregative E.coli (EAEC), Enteropathogenic E.coli (EPEC), Enterohemolysin E.coli (EHEC) and Enteroinvasive E.coli (EIEC) causes diarrhea or hemolytic uremic syndromes among infants and travelers around the world. A rapid, reliable and repeatable method is urgent for identifying DEC so as to provide the reference for responding to diarrheal disease outbreak and the treatment of the diarrheal patients associated with DEC. In this study, specific primers and modified molecular beacon probes of nine specific virulence genes, whose 5'end were added with homo tail sequence, were designed; and a two-tube modified molecular beacon based multiplex real-time PCR (rtPCR) assay for the identification of five Escherichia coli pathotypes, including ETEC, EAEC, EPEC, EHEC and EIEC was developed and optimized. Totally 102 bacterial strains, including 52 reference bacterial strains and 50 clinical strains were detected to confirm whether the target genes selected were specific. Then detection limits of the assay were tested. Lastly, the assay was applied to the detection of 11860 clinical samples to evaluate the specificity and sensitivity of the developed assay compared with the conventional PCR. The target genes were 100% specific as assessed on 102 bacterial strains since no cross-reactions were observed. The detection limits ranged from 88 CFU/mL (EHEC) to 880 CFU/mL (EPEC). Compared with the conventional PCR, the specificity and sensitivity of the multiplex rtPCR was 100% and over 99%, respectively. The coefficient of variation (CV) for each target gene ranged from 0.45% to 1.53%. 171 positive clinical samples were mostly identified as ETEC (n = 111, 64.9%) and EPEC (n = 38, 22.2%), which were the dominating pathotypes of DEC strains. The developed multiplex rtPCR assay for the identification of DEC was high sensitive and specific and could be applied to the rapid identification of

  12. 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.

  13. Determination of mutated genes in the presence of wild-type DNA by using molecular beacons as probe

    Science.gov (United States)

    Zhang, Yonghua; Ai, Junjie; Gu, Qiaorong; Gao, Qiang; Qi, Honglan; Zhang, Chengxiao

    2017-03-01

    Low-abundance mutations in the presence of wild-type DNA can be determined using molecular beacon (MB) as probe. A MB is generally used as DNA probe because it can distinguish single-base mismatched target DNA from fully matched target DNA. However, the probe can not determine low-abundance mutations in the presence of wild-type DNA. In this study, this limitation is addressed by enhancing the stability of unpaired base-containing dsDNA with a hydrogen-bonding ligand, which was added after hybridization of the MB to the target DNA. The ligand formed hydrogen bonds with unpaired bases and stabilized the unpaired base-containing dsDNA if target DNA is mutated one. As a result, more MBs were opened by the mutant genes in the presence of the ligand and a further increase in the fluorescence intensity was obtained. By contrast, fluorescence intensity did not change if target DNA is wild-type one. Consequent increase in the fluorescence intensity of the MB was regarded as a signal derived from mutant genes. The proposed method was applied in synthetic template systems to determine point mutation in DNA obtained from PCR analysis. The method also allows rapid and simple discrimination of a signal if it is originated in the presence of mutant gene or alternatively by a lower concentration of wild gene.

  14. A modified molecular beacons-based multiplex real-time PCR assay for simultaneous detection of eight foodborne pathogens in a single reaction and its application.

    Science.gov (United States)

    Hu, Qinghua; Lyu, Dongyue; Shi, Xiaolu; Jiang, Yixiang; Lin, Yiman; Li, Yinghui; Qiu, Yaqun; He, Lianhua; Zhang, Ran; Li, Qingge

    2014-03-01

    Foodborne disease outbreaks are often caused by one of the major pathogens. Early identification of the causal pathogen is crucial for disease control and prevention. We describe a real-time polymerase chain reaction (rtPCR) assay that can identify, in a single reaction, up to eight common foodborne bacterial pathogens, including Salmonella enterica subsp. enterica, Listeria monocytogenes, Escherichia coli O157, Vibrio parahaemolyticus, V. vulnificus, Campylobacter jejuni, Enterobacter sakazakii, and Shigella spp. This multiplex rtPCR assay takes advantage of modified molecular beacons and the multicolor combinational probe coding strategy to discriminate each pathogen and the homo-tag assisted non-dimer (HAND) system to prevent dimer formation. The detection limits of the assay ranged from 1.3×10(3) colony-forming units (CFU)/g stool (L. monocytogenes) to 1.6×10(4) CFU/g stool (Shigella spp.). The target genes were 100% specific as assessed on 986 reference strains covering 41 species since no cross-reactions were observed. The assay was applied to the detection of foodborne pathogens in 11,167 clinical samples and the results were compared with culture methods for further validation. The sensitivity and specificity of the rtPCR were 100% and 99%, respectively. When performed in a 96-well rtPCR system, more than 90 samples could be analyzed within 3 h. Given the high accuracy, sensitivity, specificity, and short turn-around time, the established assay could be used for the rapid and reliable identification of the causative pathogens responsible for a certain foodborne disease outbreak and rapid screening of these major foodborne pathogens in laboratory-based surveillance of outpatient clinical samples or even food samples.

  15. 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...

  16. 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

    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......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...

  17. 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

  18. Continuous monitoring of restriction endonuclease cleavage activity by universal molecular beacon light quenching coupled with real-time polymerase chain reaction.

    Science.gov (United States)

    Li, Xiaomin; Song, Chen; Zhao, Meiping; Li, Yuanzong

    2008-10-01

    We describe a method for sensitive monitoring of restriction endonuclease kinetics and activity by use of a universal molecular beacon (U-MB) coupled with real-time polymerase chain reaction (PCR). The method is used to monitor the progress of DNA cleavage in a sealed reaction tube and offers more accurate and high-throughput detection. The template has a universal tail hybridized with the U-MB and the remaining sequence is complementary to one of the restriction endonuclease digestion products. The U-MB is replaced by the extension of digested product and the fluorescence quenches. With this concept, one universal fluorescence probe can be used in different enzyme analytical systems. In the work described here, homogenous assays were performed with the restriction endonucleases AluI, EcoRI, XhoI, and SacI at smoothly controlled temperature. Cleavage efficiencies were determined, and the potential applications of this method were discussed. Furthermore, the AluI and EcoRI cleavage reactions were monitored online at varying substrate concentrations at the molecular level, and K(m), V(max), and K(cat) values were calculated. The results suggest that U-MB monitoring of restriction endonuclease assays based on real-time PCR will be very useful for high-throughput, sensitive, and precise assays for enzyme activity screening and evolutionary biotechnology analysis.

  19. 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.

  20. Real-time PCR with molecular beacons provides a highly accurate assay for detection of Tay-Sachs alleles in single cells.

    Science.gov (United States)

    Rice, John E; Sanchez, J Aquiles; Pierce, Kenneth E; Wangh, Lawrence J

    2002-12-01

    The results presented here provide the first single-cell genetic assay for Tay-Sachs disease based on real-time PCR. Individual lymphoblasts were lysed with an optimized lysis buffer and assayed using one pair of primers that amplifies both the wild type and 1278 + TATC Tay-Sachs alleles. The resulting amplicons were detected in real time with two molecular beacons each with a different colored fluorochrome. The kinetics of amplicon accumulation generate objective criteria by which to evaluate the validity of each reaction. The assay had an overall utility of 95%, based on the detection of at least one signal in 235 of the 248 attempted tests and an efficiency of 97%, as 7 of the 235 samples were excluded from further analysis for objective quantitative reasons. The accuracy of the assay was 99.1%, because 228 of 230 samples gave signals consistent with the genotype of the cells. Only two of the 135 heterozygous samples were allele drop-outs, a rate far lower than previously reported for single-cell Tay-Sachs assays using conventional methods of PCR. Copyright 2002 John Wiley & Sons, Ltd.

  1. 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.

  2. Molecular and cellular limits to somatosensory specificity

    Directory of Open Access Journals (Sweden)

    Viana Félix

    2008-04-01

    Full Text Available Abstract Animals detect environmental changes through sensory neural mechanisms that enable them to differentiate the quality, intensity and temporal characteristics of stimuli. The 'doctrine of specific nervous energies' postulates that the different sensory modalities experienced by humans result of the activation of specific nervous pathways. Identification of functional classes of sensory receptors provided scientific support to the concept that somatosensory modalities (touch, pain, temperature, kinesthesis are subserved by separate populations of sensory receptor neurons specialized in detecting innocuous and injurious stimuli of different quality (mechanical forces, temperature, chemical compounds. The identification of receptor proteins activated by different physicochemical stimuli, in particular ion channels of the Transient Receptor Potential (TRP superfamily, has put forward the concept that specificity of peripheral sensory receptor neurons is determined by their expression of a particular "molecular sensor" that confers to each functional type its selectivity to respond with a discharge of nerve impulses to stimuli of a given quality. Nonetheless, recent experimental data suggest that the various molecular sensors proposed as specific transducer molecules for stimuli of different quality are not as neatly associated with the distinct functional types of sensory receptors as originally proposed. First, many ion channel molecules initially associated to the transduction of only one particular form of energy are also activated by stimuli of different quality, implying a limited degree of specificity in their transducing capacities. Second, molecular sensors associated with a stimulus quality and hence to a sensory receptor type and ultimately to a sensory modality may be concomitantly expressed in sensory receptor neurons functionally defined as specific for another stimulus quality. Finally, activation of voltage gated channels

  3. 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...

  4. 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.

  5. 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.

  6. Molecular Recognition and Specific Interactions for Biosensing Applications

    Directory of Open Access Journals (Sweden)

    Dae Joon Kang

    2008-10-01

    Full Text Available Molecular recognition and specific interactions are reliable and versatile routes for site-specific and well-oriented immobilization of functional biomolecules on surfaces. The control of surface properties via the molecular recognition and specific interactions at the nanoscale is a key element for the nanofabrication of biosensors with high sensitivity and specificity. This review intends to provide a comprehensive understanding of the molecular recognition- and specific interaction-mediated biosensor fabrication routes that leads to biosensors with well-ordered and controlled structures on both nanopatterned surfaces and nanomaterials. Herein self-assembly of the biomolecules via the molecular recognition and specific interactions on nanoscaled surfaces as well as nanofabrication techniques of the biomolecules for biosensor architecture are discussed. We also describe the detection of molecular recognition- and specific interaction-mediated molecular binding as well as advantages of nanoscale detection.

  7. Contention Window Analysis for Beaconing in VANETs

    OpenAIRE

    Reinders, René; van Eenennaam, Martijn; Karagiannis, Georgios; Heijenk, Geert

    2011-01-01

    The recently standardised IEEE 802.11p Wireless Access in Vehicular Environment (WAVE) protocol is envisioned to be used for Vehicle-to-Vehicle and Vehicle-to-Infrastructure communications. We provide an analysis of 802.11p’s performance when used for the exchange of small status messages known as beacons. These beacons enable vehicles to establish a Cooperative Awareness from which many applications can draw their inputs. Applications have been proposed to increase safety, efficiency and com...

  8. Multiple beacons for supporting lunar landing navigation

    Science.gov (United States)

    Theil, Stephan; Bora, Leonardo

    2018-02-01

    The exploration and potential future exploitation of solar system bodies requires technologies for precise and safe landings. Current navigation systems for landing probes are relying on a combination of inertial and optical sensor measurements to determine the current flight state with respect to the target body and the desired landing site. With a future transition from single exploration missions to more frequent first exploration and then exploitation missions, the implementation and operation of these missions changes, since it can be expected that a ground infrastructure on the target body is available in the vicinity of the landing site. In a previous paper, the impact of a single ground-based beacon on the navigation performance was investigated depending on the type of radiometric measurements and on the location of the beacon with respect to the landing site. This paper extends this investigation on options for ground-based multiple beacons supporting the on-board navigation system. It analyzes the impact on the achievable navigation accuracy. For that purpose, the paper introduces briefly the existing navigation architecture based on optical navigation and its extension with radiometric measurements. The same scenario of lunar landing as in the previous paper is simulated. The results are analyzed and discussed. They show a single beacon at a large distance along the landing trajectory and multiple beacons close to the landing site can improve the navigation performance. The results show how large the landing area can be increased where a sufficient navigation performance is achieved using the beacons.

  9. 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...

  10. Molecular basis for gene-specific transactivation by nuclear receptors

    DEFF Research Database (Denmark)

    Jørgensen, Mads Aagaard; Siersbæk, Rasmus; Mandrup, Susanne

    2010-01-01

    Nuclear receptors (NRs) are key transcriptional regulators of metazoan physiology and metabolism. Different NRs bind to similar or even identical core response elements; however, they regulate transcription in a highly receptor- and gene-specific manner. These differences in gene activation can m...... on the recent advances in the molecular mechanisms responsible for receptor- and gene-specific transcriptional activation. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease....... most likely be accounted for by mechanisms involving receptor-specific interactions with DNA as well as receptor-specific interactions with protein complexes binding to adjacent and distant DNA sequences. Here, we review key molecular aspects of transactivation by NRs with special emphasis...

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

    Science.gov (United States)

    2007-05-01

    C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H.; Garnett, M. J.; Bottomley, W.; Davis, N.; Dicks, E.; Ewing, R.; Floyd , Y...Weissleder, R. Radiology, 1999, 213, 866-70. [98] Chen, J.; Tung, C. H.; Allport , J. R.; Chen, S.; Weissleder, R.; Huang, P. L. Circulation, 2005, 111

  12. Impacts of Fog Characteristics, Forward Illumination, and Warning Beacon Intensity Distribution on Roadway Hazard Visibility

    Directory of Open Access Journals (Sweden)

    John D. Bullough

    2016-01-01

    Full Text Available Warning beacons are critical for the safety of transportation, construction, and utility workers. These devices need to produce sufficient luminous intensity to be visible without creating glare to drivers. Published standards for the photometric performance of warning beacons do not address their performance in conditions of reduced visibility such as fog. Under such conditions light emitted in directions other than toward approaching drivers can create scattered light that makes workers and other hazards less visible. Simulations of visibility of hazards under varying conditions of fog density, forward vehicle lighting, warning beacon luminous intensity, and intensity distribution were performed to assess their impacts on visual performance by drivers. Each of these factors can influence the ability of drivers to detect and identify workers and hazards along the roadway in work zones. Based on the results, it would be reasonable to specify maximum limits on the luminous intensity of warning beacons in directions that are unlikely to be seen by drivers along the roadway, limits which are not included in published performance specifications.

  13. 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.

  14. 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.

  15. High molecular weight polypeptide bands specific for equine herpesvirus 4.

    Science.gov (United States)

    Zheng, M; Love, D N; Sabine, M

    1995-09-01

    Serum neutralisation (SN) and immunoblotting were used in attempts to distinguish between natural infections with the closely related viruses equine herpesvirus 1 (EHV-1) and equine herpes-virus 4 (EHV-4). Horse sera (n = 323) collected in 1990 from studs with no experience of EHV-1 abortions as well as 197 sera collected in 1992 from studs with a history of EHV-1 abortions were tested by SN. The two groups differed in the proportion with measurable EHV-1 antibody, the 1992 group being significantly higher. Both groups had high proportions with EHV-4 antibody and no serum had antibody to EHV-1 alone. Pools of positive sera were prepared as probes in immunoblots. High molecular weight (> 200 kDa) polypeptide bands specific for EHV-4 were detected. No bands specific for EHV-1 only were found. The specific EHV-4 polypeptides shared some properties with gp2 of EHV-1.

  16. 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.

  17. Determining Locations by Use of Networks of Passive Beacons

    Science.gov (United States)

    Okino, Clayton; Gray, Andrew; Jennings, Esther

    2009-01-01

    Networks of passive radio beacons spanning moderate-sized terrain areas have been proposed to aid navigation of small robotic aircraft that would be used to explore Saturn s moon Titan. Such networks could also be used on Earth to aid navigation of robotic aircraft, land vehicles, or vessels engaged in exploration or reconnaissance in situations or locations (e.g., underwater locations) in which Global Positioning System (GPS) signals are unreliable or unavailable. Prior to use, it would be necessary to pre-position the beacons at known locations that would be determined by use of one or more precise independent global navigation system(s). Thereafter, while navigating over the area spanned by a given network of passive beacons, an exploratory robot would use the beacons to determine its position precisely relative to the known beacon positions (see figure). If it were necessary for the robot to explore multiple, separated terrain areas spanned by different networks of beacons, the robot could use a long-haul, relatively coarse global navigation system for the lower-precision position determination needed during transit between such areas. The proposed method of precise determination of position of an exploratory robot relative to the positions of passive radio beacons is based partly on the principles of radar and partly on the principles of radio-frequency identification (RFID) tags. The robot would transmit radar-like signals that would be modified and reflected by the passive beacons. The distance to each beacon would be determined from the roundtrip propagation time and/or round-trip phase shift of the signal returning from that beacon. Signals returned from different beacons could be distinguished by means of their RFID characteristics. Alternatively or in addition, the antenna of each beacon could be designed to radiate in a unique pattern that could be identified by the navigation system. Also, alternatively or in addition, sets of identical beacons could

  18. Molecular diversity and host specificity of termite-associated Xylaria.

    Science.gov (United States)

    Guedegbe, Herbert J; Miambi, Edouard; Pando, Anne; Houngnandan, Pascal; Rouland-Lefevre, Corinne

    2009-01-01

    Studies have revealed that some Xylaria species were closely associated with fungus-growing termite nests. However this relationship rarely had been investigated and the host specificity of termite-associated Xylaria was not yet clearly established. Eighteen Xylaria rDNA-ITS sequences were obtained from fungus combs belonging to 11 Macrotermitinae species from eight regions. Low diversity was found between isolates, and nine sequences were retrieved. Termite-associated Xylaria were shown to be monophyletic, with three main clades, all including strains from various termite hosts and geographical localities. This new molecular study shows no species specificity with respect to fungus-growing termites, which suggests that there might be substrate specialization.

  19. 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...

  20. Molecular basis for the substrate specificity of quorum signal synthases.

    Science.gov (United States)

    Dong, Shi-Hui; Frane, Nicole D; Christensen, Quin H; Greenberg, E Peter; Nagarajan, Rajesh; Nair, Satish K

    2017-08-22

    In several Proteobacteria , LuxI-type enzymes catalyze the biosynthesis of acyl-homoserine lactones (AHL) signals using S -adenosyl-l-methionine and either cellular acyl carrier protein (ACP)-coupled fatty acids or CoA-aryl/acyl moieties as progenitors. Little is known about the molecular mechanism of signal biosynthesis, the basis for substrate specificity, or the rationale for donor specificity for any LuxI member. Here, we present several cocrystal structures of BjaI, a CoA-dependent LuxI homolog that represent views of enzyme complexes that exist along the reaction coordinate of signal synthesis. Complementary biophysical, structure-function, and kinetic analysis define the features that facilitate the unusual acyl conjugation with S -adenosylmethionine (SAM). We also identify the determinant that establishes specificity for the acyl donor and identify residues that are critical for acyl/aryl specificity. These results highlight how a prevalent scaffold has evolved to catalyze quorum signal synthesis and provide a framework for the design of small-molecule antagonists of quorum signaling.

  1. 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.

  2. 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.

  3. 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...

  4. 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.

  5. 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...

  6. Multiple systems for spatial learning: dead reckoning and beacon homing in rats.

    Science.gov (United States)

    Shettleworth, Sara J; Sutton, Jennifer E

    2005-04-01

    Rats homed with food in a large lighted arena. Without visual cues, they used dead reckoning. When a beacon indicated the home, rats could also use the beacon. Homing did not differ in 2 groups of rats, 1 provided with the beacon and 1 without it; tests without the beacon gave no evidence that beacon learning overshadowed dead reckoning (Experiment 1). When the beacon was at the home for 1 group and in random locations for another, there was again no evidence of cue competition (Experiment 2). Dead reckoning experience did not block acquisition of beacon homing (Experiment 3). Beacon learning and dead reckoning do not compete for predictive value but acquire information in parallel and are used hierarchically.

  7. 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

  8. 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/ .

  9. New St-chromosome-specific molecular markers for identifying ...

    Indian Academy of Sciences (India)

    specific marker. St-specific markers for wheat–Th. intermedium introgression lines. An introgression line Z148 was selected from the progeny of hybrid between wheat and wheat–Th. intermedium ssp. trichorophrum partial amphiploid (Yang et al. 2006). The chromosome constitution of Z148 was determined using the.

  10. Molecular evolution of the insect-specific flaviviruses.

    Science.gov (United States)

    Cook, Shelley; Moureau, Gregory; Kitchen, Andrew; Gould, Ernest A; de Lamballerie, Xavier; Holmes, Edward C; Harbach, Ralph E

    2012-02-01

    There has been an explosion in the discovery of 'insect-specific' flaviviruses and/or their related sequences in natural mosquito populations. Herein we review all 'insect-specific' flavivirus sequences currently available and conduct phylogenetic analyses of both the 'insect-specific' flaviviruses and available sequences of the entire genus Flavivirus. We show that there is no statistical support for virus-mosquito co-divergence, suggesting that the 'insect-specific' flaviviruses may have undergone multiple introductions with frequent host switching. We discuss potential implications for the evolution of vectoring within the family Flaviviridae. We also provide preliminary evidence for potential recombination events in the history of cell fusing agent virus. Finally, we consider priorities and guidelines for future research on 'insect-specific' flaviviruses, including the vast potential that exists for the study of biodiversity within a range of potential hosts and vectors, and its effect on the emergence and maintenance of the flaviviruses.

  11. Early Detection of Breast Cancer Using Molecular Beacons

    Science.gov (United States)

    2008-01-01

    DCIS tissues (Figure 6). Therefore, in addition to three tumor markers that were originally proposed for this study, we added HIF-1α and uPAR as...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...lab will only be given the ID number of each sample. All research results will be recorded using the ID numbers. The original experimental records

  12. New St-chromosome-specific molecular markers for identifying ...

    Indian Academy of Sciences (India)

    chromosome-specific PLUG and SCAR markers, and successfully used them to detect the St-chromosome in wheat–Th. intermedium introgression lines. Materials and methods. Plant materials. Wheat line ML13 was provided by International Maize and.

  13. 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.

  14. 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

  15. 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.

  16. 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)

  17. 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 <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 90% of the

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2015-06-01

    Full Text Available 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.

  20. 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/

  1. 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.

  2. 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.

  3. Hsp90-Tau complex reveals molecular basis for specificity in chaperone action

    NARCIS (Netherlands)

    Karagöz, G. Elif; Duarte, Afonso M.S.; Akoury, Elias; Ippel, Hans|info:eu-repo/dai/nl/115343415; Biernat, Jacek; Morán Luengo, Tania|info:eu-repo/dai/nl/369406036; Radli, Martina|info:eu-repo/dai/nl/375810420; Didenko, Tatiana|info:eu-repo/dai/nl/304829455; Nordhues, Bryce A.; Veprintsev, Dmitry B.; Dickey, Chad A.; Mandelkow, Eckhard; Zweckstetter, Markus; Boelens, Rolf|info:eu-repo/dai/nl/070151407; Madl, Tobias; Rüdiger, Stefan G.D.|info:eu-repo/dai/nl/314076662

    2014-01-01

    Protein folding in the cell relies on the orchestrated action of conserved families of molecular chaperones, the Hsp70 and Hsp90 systems. Hsp70 acts early and Hsp90 late in the folding path, yet the molecular basis of this timing is enigmatic, mainly because the substrate specificity of Hsp90 is

  4. 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.

  5. 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...

  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. 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.

  8. 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.

  9. 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...

  10. 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...

  11. Specific interactions and binding energies between thermolysin and potent inhibitors: molecular simulations based on ab initio molecular orbital method.

    Science.gov (United States)

    Hirakawa, Tatsuya; Fujita, Seiya; Ohyama, Tatsuya; Dedachi, Kenichi; Khan, Mahmud Tareq Hassan; Sylte, Ingebrigt; Kurita, Noriyuki

    2012-03-01

    Biochemical functions of the metalloprotease thermolysin (TLN) are controlled by various inhibitors. In a recent study we identified 12 compounds as TLN inhibitors by virtual screening and in vitro competitive binding assays. However, the specific interactions between TLN and these inhibitors have not been clarified. We here investigate stable structures of the solvated TLN-inhibitor complexes by classical molecular mechanics simulations and elucidate the specific interactions between TLN and these inhibitors at an electronic level by using ab initio fragment molecular orbital (FMO) calculations. The calculated binding energies between TLN and the inhibitors are qualitatively consistent with the experimental results, and the FMO results elucidate important amino acid residues of TLN for inhibitor binding. Based on the calculated results, we propose a novel potent inhibitor having a large binding affinity to TLN. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Targeted therapy in renal cell carcinoma: moving from molecular agents to specific immunotherapy.

    Science.gov (United States)

    Bedke, Jens; Gouttefangeas, Cécile; Singh-Jasuja, Harpreet; Stevanović, Stefan; Behnes, Carl-Ludwig; Stenzl, Arnulf

    2014-02-01

    Non-specific immunotherapy has been for a long time a standard treatment option for patients with metastatic renal cell carcinoma but was redeemed by specific targeted molecular therapies, namely the VEGF and mTOR inhibitors. After moving treatment for mRCC to specific molecular agents with a well-defined mode of action, immunotherapy still needs this further development to increase its accuracy. Nowadays, an evolution from a rather non-specific cytokine treatment to sophisticated targeted approaches in specific immunotherapy led to a re-launch of immunotherapy in clinical studies. Recent steps in the development of immunotherapy strategies are discussed in this review with a special focus on peptide vaccination which aims at a tumor targeting by specific T lymphocytes. In addition, different combinatory strategies with immunomodulating agents like cyclophosphamide or sunitinib are outlined, and the effects of immune checkpoint modulators as anti-CTLA-4 or PD-1 antibodies are discussed.

  13. Construction of PSCA-specific MR molecular probe and its immunological activity examination

    International Nuclear Information System (INIS)

    Ren Jing; Yang Yong; Wang Fang; Wei Guangquan; Zhang Rui; Yang Angang; Huan Yi

    2011-01-01

    Objective: To construct the PSCA-specific MR molecular probe 7F5@GoldMag, and to reveal its biochemical characteristics. Methods: The PSCA -specific MR molecular probe 7F5@GoldMag was constructed by noncovalent bond conjugating anti-human PSCA monoclonal antibody (mAb) 7F5 with ColdMag TM -CS nanoparticles, and the coupling efficiency was calculated. The specific binding capability for 7F5@GoldMag to prostate cancer cells was defined by using laser confocal microscopy, transmission electron microscope, and flow cytometry. Results: The PSCA-specific MR molecular probe (7F5@GoldMag) was successfully constructed. Flow cytometry results have shown that the positive rate of the binding was 92.1% at the mAb 7F5@GoldMag + PC-3 cells. Red fluorescence was observed in the membrane at the group of mAb 7F5@GoldMag + PC-3 cells by laser confocal microscopy. The results of transmission electron microscope showed that GoldMag nanoparticles were observed as punctuate black spots, which located near the membrane at mAb 7F5@GoldMag + PC-3 cells. Conclusion: The PSCA-specific MR molecular probe (7F5@GoldMag) constructed by conjugating anti-human PSCA mAb 7F5 with GoldMag TM -CS nanoparticles can specifically bind with PSCA-positive prostate cancer cells. (authors)

  14. 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.

  15. 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…

  16. Model-Based Localization and Tracking Using Bluetooth Low-Energy Beacons

    Directory of Open Access Journals (Sweden)

    F. Serhan Daniş

    2017-10-01

    Full Text Available We introduce a high precision localization and tracking method that makes use of cheap Bluetooth low-energy (BLE beacons only. We track the position of a moving sensor by integrating highly unreliable and noisy BLE observations streaming from multiple locations. A novel aspect of our approach is the development of an observation model, specifically tailored for received signal strength indicator (RSSI fingerprints: a combination based on the optimal transport model of Wasserstein distance. The tracking results of the entire system are compared with alternative baseline estimation methods, such as nearest neighboring fingerprints and an artificial neural network. Our results show that highly accurate estimation from noisy Bluetooth data is practically feasible with an observation model based on Wasserstein distance interpolation combined with the sequential Monte Carlo (SMC method for tracking.

  17. Model-Based Localization and Tracking Using Bluetooth Low-Energy Beacons.

    Science.gov (United States)

    Daniş, F Serhan; Cemgil, Ali Taylan

    2017-10-29

    We introduce a high precision localization and tracking method that makes use of cheap Bluetooth low-energy (BLE) beacons only. We track the position of a moving sensor by integrating highly unreliable and noisy BLE observations streaming from multiple locations. A novel aspect of our approach is the development of an observation model, specifically tailored for received signal strength indicator (RSSI) fingerprints: a combination based on the optimal transport model of Wasserstein distance. The tracking results of the entire system are compared with alternative baseline estimation methods, such as nearest neighboring fingerprints and an artificial neural network. Our results show that highly accurate estimation from noisy Bluetooth data is practically feasible with an observation model based on Wasserstein distance interpolation combined with the sequential Monte Carlo (SMC) method for tracking.

  18. 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)

  19. The tick (Acari: Ixodidae) fauna of Herald's Beacon Islet, Australia.

    Science.gov (United States)

    Kwak, Mackenzie L; Mintram, Kate

    2017-01-01

    A rare opportunity to travel to Herald's Beacon Islet with permission from the Australian government to collect ticks allowed for a survey of the tick fauna of the island to be undertaken for the first time. The avian fauna of the island, which serve as hosts, was also recorded and includes one new species record for the island. The seabird soft tick Ornithodoros capensis Neumann and the seabird hard tick Amblyomma loculosum Neumann were found to be present on the island. Images of the ticks present on the island are presented along with morphological characters for their identification.

  20. 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.

  1. Purification and molecular cloning of a new galactose-specific lectin ...

    Indian Academy of Sciences (India)

    Srinivas

    The mature protein was predicted to have 263 amino acid residues and. 28 963 Da in size. [Pinto L S, Nagano C S, Oliveira T M, Moura T R, Sampaio A H, Debray H, Pinto V P, Dellagostin O A and Cavada B S 2008 Purification and molecular cloning of a new galactose-specific lectin from Bauhinia variegata seeds; J. Biosci ...

  2. 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.

  3. 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.

  4. 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.

  5. Conformational proofreading: the impact of conformational changes on the specificity of molecular recognition.

    Directory of Open Access Journals (Sweden)

    Yonatan Savir

    Full Text Available To perform recognition, molecules must locate and specifically bind their targets within a noisy biochemical environment with many look-alikes. Molecular recognition processes, especially the induced-fit mechanism, are known to involve conformational changes. This raises a basic question: Does molecular recognition gain any advantage by such conformational changes? By introducing a simple statistical-mechanics approach, we study the effect of conformation and flexibility on the quality of recognition processes. Our model relates specificity to the conformation of the participant molecules and thus suggests a possible answer: Optimal specificity is achieved when the ligand is slightly off target; that is, a conformational mismatch between the ligand and its main target improves the selectivity of the process. This indicates that deformations upon binding serve as a conformational proofreading mechanism, which may be selected for via evolution.

  6. Molecular mechanism of substrate specificity in the bacterial neutral amino acid transporter LeuT.

    Science.gov (United States)

    Noskov, Sergei Y

    2008-12-01

    The recently published X-ray structure of LeuT, a Na(+)/Cl(-)-dependent neurotransmitter transporter, has provided fresh impetus to efforts directed at understanding the molecular principles governing specific neurotransmitter transport. The combination of the LeuT crystal structure with the results of molecular simulations enables the functional data on specific binding and transport to be related to molecular structure. All-atom FEP and molecular dynamics (MD) simulations of LeuT embedded in an explicit membrane were performed alongside a decomposition analysis to dissect the molecular determinants of the substrate specificity of LeuT. It was found that the ligand must be in a zwitterionic (ZW) form to bind tightly to the transporter. The theoretical results on the absolute binding-free energies for leucine, alanine, and glycine show that alanine can be a potent substrate for LeuT, although leucine is preferred, which is consistent with the recent experimental data (Singh et al., Nature 2007;448:952-956). Furthermore, LeuT displays robust specificity for leucine over glycine. Interestingly, the ability of LeuT to discriminate between substrates relies on the dynamics of residues that form its binding pocket (e.g., F253 and Q250) and the charged side chains (R30-D404) from a second coordination shell. The water-mediated R30-D404 salt bridge is thought to be part of the extracellular (EC) gate of LeuT. The introduction of a polar ligand such as glycine to the water-depleted binding pocket of LeuT gives rise to structural rearrangements of the R30-D404-Q250 hydrogen-bonding network and leads to increased hydration of the binding pocket. Conformational changes associated with the broken hydrogen bond between Q250 and R30 are shown to be important for tight and selective ligand binding to LeuT.

  7. 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.

  8. Atmospheric Beacons of Life from Exoplanets Around G and K Stars

    Science.gov (United States)

    Airapetian, Vladimir S.; Jackman, Charles H.; Mlynczak, Martin; Danchi, William; Hunt, Linda

    2017-01-01

    The current explosion in detection and characterization of thousands of extrasolar planets from the Kepler mission, the Hubble Space Telescope, and large ground-based telescopes opens a new era in searches for Earth-analog exoplanets with conditions suitable for sustaining life. As more Earth-sized exoplanets are detected in the near future, we will soon have an opportunity to identify habitale worlds. Which atmospheric biosignature gases from habitable planets can be detected with our current capabilities? The detection of the common biosignatures from nitrogen-oxygen rich terrestrial-type exoplanets including molecular oxygen (O2), ozone (O3), water vapor (H2O), carbon dioxide (CO2), nitrous oxide (N2O), and methane (CH4) requires days of integration time with largest space telescopes, and thus are very challenging for current instruments. In this paper we propose to use the powerful emission from rotational-vibrational bands of nitric oxide, hydroxyl and molecular oxygen as signatures of nitrogen, oxygen, and water rich atmospheres of terrestrial type exoplanets "highlighted" by the magnetic activity from young G and K main-sequence stars. The signals from these fundamental chemical prerequisites of life we call atmospheric "beacons of life" create a unique opportunity to perform direct imaging observations of Earth-sized exoplanets with high signal-to-noise and low spectral resolution with the upcoming NASA missions.

  9. 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.

  10. 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

    nodes, pretending to have a fake identity within the network. To prevent this attack we propose RAP, a challenge-response authentication protocol that is able to detect and prevent the beacon replay attack. The effectiveness of the protocol is formally verified using OFMC and ProVerif. Furthermore, we......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...

  11. Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides

    Science.gov (United States)

    Du, Yuzhe; Nomura, Yoshiko; Luo, Ningguang; Liu, Zhiqi; Lee, Jung-Eun; Khambay, Bhupinder; Dong, Ke

    2011-01-01

    Pyrethroid insecticides are classified as type I or type II based on their distinct symptomology and effects on sodium channel gating. Structurally, type II pyrethroids possess an α-cyano group at the phenylbenzyl alcohol position, which is lacking in type I pyrethroids. Both type I and type II pyrethroids inhibit deactivation consequently prolonging the opening of sodium channels. However, type II pyrethroids inhibit the deactivation of sodium channels to a greater extent than type I pyrethroids inducing much slower decaying of tail currents upon repolarization. The molecular basis of type II-specific action, however, is not known. Here we report the identification of a residue G1111 and two positively charged lysines immediately downstream of G1111 in the intracellular linker connecting domains II and III of the cockroach sodium channel that are specifically involved in the action of type II pyrethroids, but not in the action of type I pyrethroids. Deletion of G1111, a consequence of alternative splicing, reduced the sodium channel sensitivity to type II pyrethroids, but had no effect on channel sensitivity to type I pyrethroids. Interestingly, charge neutralization or charge reversal of two positively charged lysines (Ks) downstream of G1111 had a similar effect. These results provide the molecular insight into the type II-specific interaction of pyrethroids with the sodium channel at the molecular level. PMID:19022275

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways.

    Science.gov (United States)

    Khurana, Vikram; Peng, Jian; Chung, Chee Yeun; Auluck, Pavan K; Fanning, Saranna; Tardiff, Daniel F; Bartels, Theresa; Koeva, Martina; Eichhorn, Stephen W; Benyamini, Hadar; Lou, Yali; Nutter-Upham, Andy; Baru, Valeriya; Freyzon, Yelena; Tuncbag, Nurcan; Costanzo, Michael; San Luis, Bryan-Joseph; Schöndorf, David C; Barrasa, M Inmaculada; Ehsani, Sepehr; Sanjana, Neville; Zhong, Quan; Gasser, Thomas; Bartel, David P; Vidal, Marc; Deleidi, Michela; Boone, Charles; Fraenkel, Ernest; Berger, Bonnie; Lindquist, Susan

    2017-02-22

    Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson's disease. Genome-wide screens in yeast identified 332 genes that impact α-syn toxicity. To "humanize" this molecular network, we developed a computational method, TransposeNet. This integrates a Steiner prize-collecting approach with homology assignment through sequence, structure, and interaction topology. TransposeNet linked α-syn to multiple parkinsonism genes and druggable targets through perturbed protein trafficking and ER quality control as well as mRNA metabolism and translation. A calcium signaling hub linked these processes to perturbed mitochondrial quality control and function, metal ion transport, transcriptional regulation, and signal transduction. Parkinsonism gene interaction profiles spatially opposed in the network (ATP13A2/PARK9 and VPS35/PARK17) were highly distinct, and network relationships for specific genes (LRRK2/PARK8, ATXN2, and EIF4G1/PARK18) were confirmed in patient induced pluripotent stem cell (iPSC)-derived neurons. This cross-species platform connected diverse neurodegenerative genes to proteinopathy through specific mechanisms and may facilitate patient stratification for targeted therapy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  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. Comparative Methods for Molecular Determination of Host-Specificity Factors in Plant-Pathogenic Fungi

    Directory of Open Access Journals (Sweden)

    Nilam Borah

    2018-03-01

    Full Text Available Many plant-pathogenic fungi are highly host-specific. In most cases, host-specific interactions evolved at the time of speciation of the respective host plants. However, host jumps have occurred quite frequently, and still today the greatest threat for the emergence of new fungal diseases is the acquisition of infection capability of a new host by an existing plant pathogen. Understanding the mechanisms underlying host-switching events requires knowledge of the factors determining host-specificity. In this review, we highlight molecular methods that use a comparative approach for the identification of host-specificity factors. These cover a wide range of experimental set-ups, such as characterization of the pathosystem, genotyping of host-specific strains, comparative genomics, transcriptomics and proteomics, as well as gene prediction and functional gene validation. The methods are described and evaluated in view of their success in the identification of host-specificity factors and the understanding of their functional mechanisms. In addition, potential methods for the future identification of host-specificity factors are discussed.

  2. Multi-kW Uplink Fiber-Laser Beacon with Agile Signal Format Project

    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...

  3. Multi-kW Uplink Fiber-Laser Beacon with Agile Signal Format Project

    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...

  4. 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...

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

    CSIR Research Space (South Africa)

    Burke, Michael G

    2011-11-01

    Full Text Available -only Beacons for Mobile Robot Localisation Michael Burke Mobile Intelligent Autonomous Systems Council for Scientific and Industrial Research Pretoria, South Africa Email: michaelburke@ieee.org Nico Bos Dept. Electrical, Electronic and Computer...

  6. 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...

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

    Science.gov (United States)

    2011-10-20

    ... coders'' at Beacon Medical Services, LLC, Aurora, Colorado, states that ``our jobs were outsourced to... shift in production by such workers' firm or subdivision to a foreign country of articles like or...

  10. Sequence-Specific β-Peptide Synthesis by a Rotaxane-Based Molecular Machine.

    Science.gov (United States)

    De Bo, Guillaume; Gall, Malcolm A Y; Kitching, Matthew O; Kuschel, Sonja; Leigh, David A; Tetlow, Daniel J; Ward, John W

    2017-08-09

    We report on the synthesis and operation of a three-barrier, rotaxane-based, artificial molecular machine capable of sequence-specific β-homo (β 3 ) peptide synthesis. The machine utilizes nonproteinogenic β 3 -amino acids, a class of amino acids not generally accepted by the ribosome, particularly consecutively. Successful operation of the machine via native chemical ligation (NCL) demonstrates that even challenging 15- and 19-membered ligation transition states are suitable for information translation using this artificial molecular machine. The peptide-bond-forming catalyst region can be removed from the transcribed peptide by peptidases, artificial and biomachines working in concert to generate a product that cannot be made by either machine alone.

  11. Temporal mapping of photochemical reactions and molecular excited states with carbon specificity.

    Science.gov (United States)

    Wang, K; Murahari, P; Yokoyama, K; Lord, J S; Pratt, F L; He, J; Schulz, L; Willis, M; Anthony, J E; Morley, N A; Nuccio, L; Misquitta, A; Dunstan, D J; Shimomura, K; Watanabe, I; Zhang, S; Heathcote, P; Drew, A J

    2017-04-01

    Photochemical reactions are essential to a large number of important industrial and biological processes. A method for monitoring photochemical reaction kinetics and the dynamics of molecular excitations with spatial resolution within the active molecule would allow a rigorous exploration of the pathway and mechanism of photophysical and photochemical processes. Here we demonstrate that laser-excited muon pump-probe spin spectroscopy (photo-μSR) can temporally and spatially map these processes with a spatial resolution at the single-carbon level in a molecule with a pentacene backbone. The observed time-dependent light-induced changes of an avoided level crossing resonance demonstrate that the photochemical reactivity of a specific carbon atom is modified as a result of the presence of the excited state wavefunction. This demonstrates the sensitivity and potential of this technique in probing molecular excitations and photochemistry.

  12. Bluetooth Low Energy Beacon Performance and Utility in a Car Location Memory Aid Setting

    OpenAIRE

    Sætre, Karsten Andre Skogstad

    2018-01-01

    This project explores the usefulness and performance of BLE Bluetooth beacons. This is done through an experiment conducted in cooperation with a fellow student. The results reveal weaknesses in performance, but also potential. Within the constraints of those weaknesses I construct a memory aid prototype Android application, CaRemember, as a proof of concept in order to demonstrate a potentially useful use case that make use of BLE Bluetooth beacons.

  13. 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}

  14. Quick acquisition and recognition method for the beacon in deep space optical communications.

    Science.gov (United States)

    Wang, Qiang; Liu, Yuefei; Ma, Jing; Tan, Liying; Yu, Siyuan; Li, Changjiang

    2016-12-01

    In deep space optical communications, it is very difficult to acquire the beacon given the long communication distance. Acquisition efficiency is essential for establishing and holding the optical communication link. Here we proposed a quick acquisition and recognition method for the beacon in deep optical communications based on the characteristics of the deep optical link. To identify the beacon from the background light efficiently, we utilized the maximum similarity between the collecting image and the reference image for accurate recognition and acquisition of the beacon in the area of uncertainty. First, the collecting image and the reference image were processed by Fourier-Mellin. Second, image sampling and image matching were applied for the accurate positioning of the beacon. Finally, the field programmable gate array (FPGA)-based system was used to verify and realize this method. The experimental results showed that the acquisition time for the beacon was as fast as 8.1s. Future application of this method in the system design of deep optical communication will be beneficial.

  15. 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.

  16. An Adaptive Scheme for Robot Localization and Mapping with Dynamically Configurable Inter-Beacon Range Measurements

    Directory of Open Access Journals (Sweden)

    Arturo Torres-González

    2014-04-01

    Full Text Available 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.

  17. Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.

    Directory of Open Access Journals (Sweden)

    Haritz Irizar

    Full Text Available BACKGROUND: Although the most common clinical presentation of multiple sclerosis (MS is the so called Relapsing-Remitting MS (RRMS, the molecular mechanisms responsible for its progression are currently unknown. To tackle this problem, a whole-genome gene expression analysis has been performed on RRMS patients. RESULTS: The comparative analysis of the Affymetrix Human Gene 1.0 ST microarray data from peripheral blood leucocytes obtained from 25 patients in remission and relapse and 25 healthy subjects has revealed 174 genes altered in both remission and relapse, a high proportion of them showing what we have called "mirror pattern": they are upregulated in remission and downregulated in relapse or vice versa. The coexpression analysis of these genes has shown that they are organized in three female-specific and one male-specific modules. CONCLUSIONS: The interpretation of the modules of the coexpression network suggests that Epstein-Barr virus (EBV reactivation of B cells happens in MS relapses; however, qPCR expression data of the viral genes supports that hypothesis only in female patients, reinforcing the notion that different molecular processes drive disease progression in females and males. Besides, we propose that the "primed" state showed by neutrophils in women is an endogenous control mechanism triggered to keep EBV reactivation under control through vitamin B12 physiology. Finally, our results also point towards an important sex-specific role of non-coding RNA in MS.

  18. Fabrication and evaluation of a sequence-specific oligonucleotide miniarray for molecular genotyping

    Directory of Open Access Journals (Sweden)

    Iqbal J

    2008-01-01

    Full Text Available Purpose: Molecular genotyping relies on the identification of specific microbial DNA sequences. Accurate genotyping not only requires discrimination between low- and high-risk pathogens for effective diagnosis or disease management but also requires the identity of the specific strain or type of the microbe involved in pathogenesis. The majority of these assays require DNA amplification followed by genome identification either through sequencing or hybridization to specific oligonucleotide probes. We evaluated the use of a DNA microchip assay as a simple and easy-to-use procedure for genotyping. Methods: Various methodological parameters were optimized for single-base mismatch discrimination on a DNA microarray. The fabrication procedures involved substrate chemistry for immobilization. The effect of various buffers and features associated with oligonucleotide sequences were standardized. The assay was evaluated on a low-density genotyping chip containing the sequences of various (Human Papilloma Virus HPV subtypes. Results: The specific subtype was identified with high specificity by hybridization in miniaturized condition. Conclusions: The DNA microchip provides a rapid and cost-effective genotyping procedure for microbial organisms and can be implemented easily in any laboratory.

  19. 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...

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

    Directory of Open Access Journals (Sweden)

    Qi Wang

    2018-03-01

    Full Text Available 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.

  1. 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.

  2. Exploration of Deinococcus-Thermus molecular diversity by novel group-specific PCR primers

    Science.gov (United States)

    Theodorakopoulos, Nicolas; Bachar, Dipankar; Christen, Richard; Alain, Karine; Chapon, Virginie

    2013-01-01

    The deeply branching Deinococcus-Thermus lineage is recognized as one of the most extremophilic phylum of bacteria. In previous studies, the presence of Deinococcus-related bacteria in the hot arid Tunisian desert of Tataouine was demonstrated through combined molecular and culture-based approaches. Similarly, Thermus-related bacteria have been detected in Tunisian geothermal springs. The present work was conducted to explore the molecular diversity within the Deinococcus-Thermus phylum in these extreme environments. A set of specific primers was designed in silico on the basis of 16S rRNA gene sequences, validated for the specific detection of reference strains, and used for the polymerase chain reaction (PCR) amplification of metagenomic DNA retrieved from the Tataouine desert sand and Tunisian hot spring water samples. These analyses have revealed the presence of previously undescribed Deinococcus-Thermus bacterial sequences within these extreme environments. The primers designed in this study thus represent a powerful tool for the rapid detection of Deinococcus-Thermus in environmental samples and could also be applicable to clarify the biogeography of the Deinococcus-Thermus phylum. PMID:23996915

  3. The strong specific effect of coions on micellar growth from molecular-thermodynamic theory.

    Science.gov (United States)

    Koroleva, S V; Victorov, A I

    2014-09-07

    Viscoelastic solutions of ionic surfactants with an added salt exhibit a surprisingly strong dependence of their behavior on the nature of the added coion. We apply a recently proposed molecular-thermodynamic model to elucidate the effect of a coion's specificity on the aggregation of cationic and anionic surfactants. We show that micellar growth and branching are opposed by penetration of coions inside a micelle's corona leading to an increase of the aggregate's preferential curvature. These effects result from hydration/dehydration and dispersion attraction of coions and are only important at high salinity where electrostatic repulsion of coions from the micelle is screened and where branching of micelles and viscosity maxima are observed. At low and medium salinity, the coion plays a minor role; its effect on critical micelle concentration and sphere-to-rod transitions is insignificant. Our molecular-thermodynamic approach describes the specific effects of both counterions and coions and their different roles at different salinity levels based on a unified physical picture.

  4. Genome-wide functional analysis on the molecular mechanism of specifically biosynthesized fluorescence Eu complex.

    Science.gov (United States)

    Ye, Jing; Dong, Xiawei; Jiang, Xuerui; Jiang, Hui; Li, Chen-Zhong; Wang, Xuemei

    2017-09-22

    Fluorescence imaging as an attractive diagnostic technique is widely employed for early diagnosis of cancer. Self-biosynthesized fluorescent Eu complex in situ in Hela cells have realized specifically and accurately fluorescence imaging for cancer cells. But the molecular mechanism of the in situ biosynthesized process is still unclear. In order to reveal this mechanism, we have investigated whole-genome expression profiles with cDNA microarray, incubated with Eu solution in Hela cells for 24 h. Methylthiazoltetrazolium (MTT) assay and laser confocal fluorescence microscopy study showed the low cytotoxicity and specifically fluorescence imaging of Eu complex in Hela cells. It is observed that 563 up-regulated genes and 274 down-regulated genes were differentially expressed. Meanwhile, quantitative RT-PCR was utilized to measure the expression of some important genes, which validated the results of microarray data analysis. Besides, GO analysis showed that a wide range of differential expression functional genes involved in three groups, including cellular component, molecular function and cellular biological process. It was evident that some important biological pathways were apparently affected through KEGG pathway analysis, including focal adhesion pathway and PI3K (phosphatidylinositol 3' -kinase)-Akt signaling pathway, which can influence glycolytic metabolism and NAD(P)H-oxidases metabolic pathway.

  5. 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.

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

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    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.

  7. 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

  8. 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.

  9. Molecular inversion probe: a new tool for highly specific detection of plant pathogens.

    Science.gov (United States)

    Lau, Han Yih; Palanisamy, Ramkumar; Trau, Matt; Botella, Jose R

    2014-01-01

    Highly specific detection methods, capable of reliably identifying plant pathogens are crucial in plant disease management strategies to reduce losses in agriculture by preventing the spread of diseases. We describe a novel molecular inversion probe (MIP) assay that can be potentially developed into a robust multiplex platform to detect and identify plant pathogens. A MIP has been designed for the plant pathogenic fungus Fusarium oxysporum f.sp. conglutinans and the proof of concept for the efficiency of this technology is provided. We demonstrate that this methodology can detect as little as 2.5 ng of pathogen DNA and is highly specific, being able to accurately differentiate Fusarium oxysporum f.sp. conglutinans from other fungal pathogens such as Botrytis cinerea and even pathogens of the same species such as Fusarium oxysporum f.sp. lycopersici. The MIP assay was able to detect the presence of the pathogen in infected Arabidopsis thaliana plants as soon as the tissues contained minimal amounts of pathogen. MIP methods are intrinsically highly multiplexable and future development of specific MIPs could lead to the establishment of a diagnostic method that could potentially screen infected plants for hundreds of pathogens in a single assay.

  10. Mechanism Analysis of Selective Adsorption and Specific Recognition by Molecularly Imprinted Polymers of Ginsenoside Re

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2018-02-01

    Full Text Available In this article, the molecularly imprinted polymers (MIPs of ginsenoside Re (Re were synthesized by suspension polymerization with Re as the template molecule, methacrylic acid (MAA as the functional monomers, and ethyl glycol dimethacrylate (EGDMA as the crosslinker. The MIPs were characterized by Fourier transform infrared spectroscopy (FTIR, Field emission scanning electron microscopy (FESEM, and surface porosity detector, and the selective adsorption and specific recognition of MIPs were analyzed using the theory of kinetics and thermodynamics. The experimental results showed that compared with non-imprinted polymers (NIPs, MIPs had a larger specific surface area and special pore structure and that different from the Langmuir model of NIPs, the static adsorption isotherm of MIPs for Re was in good agreement with the Freundlich model based on the two adsorption properties of MIPs. The curves of the adsorption dynamics and the lines of kinetic correlation indicate that there was a fast and selective adsorption equilibrium for Re because of the affinity of MIPs to the template rather than its analogue of ginsenoside Rg1 (Rg1. The study of thermodynamics indicate that the adsorption was controlled by enthalpy and that MIPs had higher enthalpy and entropy than NIPs, which contributed to the specific recognition of MIPs.

  11. Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone.

    Science.gov (United States)

    Ito, Shinya; Nagata, Kazuhiro

    2017-02-01

    Hsp47, a collagen-specific molecular chaperone that localizes in the endoplasmic reticulum (ER), is indispensable for molecular maturation of collagen. Hsp47, which is encoded by the SERPINH1 gene, belongs to the serpin family and has the serpin fold; however, it has no serine protease inhibitory activity. Hsp47 transiently binds to procollagen in the ER, dissociates in the cis-Golgi or ER-Golgi intermediate compartment (ERGIC) in a pH-dependent manner, and is then transported back to the ER via its RDEL retention sequence. Hsp47 recognizes collagenous (Gly-Xaa-Arg) repeats on triple-helical procollagen and can prevent local unfolding and/or aggregate formation of procollagen. Gene disruption of Hsp47 in mice causes embryonic lethality due to impairments in basement membrane and collagen fibril formation. In Hsp47-knockout cells, the type I collagen triple helix forms abnormally, resulting in thin and frequently branched fibrils. Secretion of type I collagens is slow and plausible in making aggregates of procollagens in the ER of hsp47-knocked out fibroblasts, which are ultimately degraded by autophagy. Mutations in Hsp47 are causally associated with osteogenesis imperfecta. Expression of Hsp47 is strongly correlated with expression of collagens in multiple types of cells and tissues. Therefore, Hsp47 represents a promising target for treatment of collagen-related disorders, including fibrosis of the liver, lung, and other organs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Perfusion patterns of metastatic gastrointestinal stromal tumor lesions under specific molecular therapy

    Energy Technology Data Exchange (ETDEWEB)

    Schlemmer, Marcus [Department of Internal Medicine III, University Hospitals-Grosshadern, Ludwig Maximilians University Munich, Marchioninistr. 15, 81377 Munich (Germany); Sourbron, Steven P. [Institute of Clinical Radiology, University Hospitals-Grosshadern, Ludwig Maximilians University Munich, Marchioninistr. 15, 81377 Munich (Germany); Schinwald, Nicole [Department of Internal Medicine III, University Hospitals-Grosshadern, Ludwig Maximilians University Munich, Marchioninistr. 15, 81377 Munich (Germany); Nikolaou, Konstantin; Becker, Christoph R.; Reiser, Maximilian F. [Institute of Clinical Radiology, University Hospitals-Grosshadern, Ludwig Maximilians University Munich, Marchioninistr. 15, 81377 Munich (Germany); Berger, Frank, E-mail: Frank.Berger@med.uni-muenchen.de [Institute of Clinical Radiology, University Hospitals-Grosshadern, Ludwig Maximilians University Munich, Marchioninistr. 15, 81377 Munich (Germany)

    2011-02-15

    Rationale and objective: The aim of this pilot study was the evaluation of CT perfusion patterns in metastatic GIST lesions under specific molecular therapy with sunitinib or imatinib both in responders and non-responders. Patients and methods: 24 patients with metastatic GIST under tyrosine kinase inhibition were retrospectively evaluated. A total of 46 perfusion and venous phase CT scans were acquired. Volume of distribution, blood flow, blood volume, permeability and hepatic perfusion index measurements of metastatic lesions were carried out. Lesions were classified as 'good response' or 'poor response' to therapy, and perfusion parameters were compared for these two types of lesions. Results: 24 patients were evaluated. In the extrahepatic abdominal lesions (N = 15), good responders showed significant lower perfusion values than poor responders (volume of distribution: 3.3 {+-} 2.0 vs. 13.0 {+-} 1.8 ml/100 ml, p = 0.001). The same tendency was observed in intrahepatic lesions (N = 31) (liver volume of distribution: 2.1 {+-} 0.3 vs. 7.1 {+-} 1.3 ml/100 ml, p = 0.003); (hepatic perfusion index: 24.3 {+-} 7.9 vs. 76.1 {+-} 1.5%, p = 0.0001). Conclusion: Our data indicate that there are characteristic perfusion patterns of metastatic GIST lesions showing a good or poor response to molecular pharmacotherapy. Perfusion should be further evaluated in cross-sectional imaging studies as a possible biomarker for treatment response in targeted therapies of GIST.

  13. 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.

  14. BBUNS: Bluetooth Beacon-Based Underground Navigation System to Support Mine Haulage Operations

    Directory of Open Access Journals (Sweden)

    Jieun Baek

    2017-11-01

    Full Text Available A Bluetooth beacon-based underground navigation system (BBUNS was developed to identify the optimal haul road in an underground mine, track the locations of dump trucks, and display this information on mobile devices. A three-dimensional (3-D geographic information system (GIS database of the haul roads in an underground mine was constructed, and the travel time for each section was calculated. A GIS database was also constructed for 50 Bluetooth beacons that were installed along the haul roads. An Android-based BBUNS application was developed to visualize the current location of each dump truck and the optimal haul road to the destination on mobile devices, using the Bluetooth beacon system that was installed in the underground mine. Whenever the BBUNS recognized all of the Bluetooth beacons installed in the underground mine, it could provide the dump truck drivers with information on the current location and the two-dimensional (2-D and 3-D haul road properties. The operating time of each dump truck and the time spent on each unit task could be analyzed using recorded data on the times when Bluetooth beacon signals were recognized by the BBUNS. The underground mine navigation system that was developed in this study can contribute to the improvement of haul operation efficiency and productivity.

  15. 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.

  16. 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.

  17. Perlecan domain V therapy for stroke: a beacon of hope?

    Science.gov (United States)

    Bix, Gregory J

    2013-03-20

    The sad reality is that in the year 2012, people are still dying or suffering from the extreme morbidity of ischemic stroke. This tragedy is only compounded by the graveyard full of once promising new therapies. While it is indeed true that the overall mortality from stroke has declined in the United States, perhaps due to increased awareness of stroke symptoms by both the lay public and physicians, it is clear that better therapies are needed. In this regard, progress has been tremendously slowed by the simple fact that experimental models of stroke and the animals that they typically employ, rats and mice, do not adequately represent human stroke. Furthermore, the neuroprotective therapeutic approach, in which potential treatments are administered with the hope of preventing the spread of dying neurons that accompanies a stroke, typically fail for a number of reasons such as there is simply more brain matter to protect in a human than there is in a rodent! For this reason, there has been somewhat of a shift in stroke research away from neuroprotection and toward a neurorepair approach. This too may be problematic in that agents that might foster brain repair could be acutely deleterious or neurotoxic and vice versa, making the timing of treatment administration after stroke critical. Therefore, in our efforts to discover a new stroke therapy, we decided to focus on identifying brain repair elements that were (1) endogenously and actively generated in response to stroke in both human and experimental animal brains, (2) present acutely and chronically after ischemic stroke, suggesting that they could have a role in acute neuroprotection and chronic neurorepair, and (3) able to be administered peripherally and reach the site of stroke brain injury. In this review, I will discuss the evidence that suggests that perlecan domain V may be just that substance, a potential beacon of hope for stroke patients.

  18. Molecular basis for the specification of floral organs by APETALA3 and PISTILLATA.

    Science.gov (United States)

    Wuest, Samuel E; O'Maoileidigh, Diarmuid S; Rae, Liina; Kwasniewska, Kamila; Raganelli, Andrea; Hanczaryk, Katarzyna; Lohan, Amanda J; Loftus, Brendan; Graciet, Emmanuelle; Wellmer, Frank

    2012-08-14

    How different organs are formed from small sets of undifferentiated precursor cells is a key question in developmental biology. To understand the molecular mechanisms underlying organ specification in plants, we studied the function of the homeotic selector genes APETALA3 (AP3) and PISTILLATA (PI), which control the formation of petals and stamens during Arabidopsis flower development. To this end, we characterized the activities of the transcription factors that AP3 and PI encode throughout flower development by using perturbation assays as well as transcript profiling and genomewide localization studies, in combination with a floral induction system that allows a stage-specific analysis of flower development by genomic technologies. We discovered considerable spatial and temporal differences in the requirement for AP3/PI activity during flower formation and show that they control different sets of genes at distinct phases of flower development. The genomewide identification of target genes revealed that AP3/PI act as bifunctional transcription factors: they activate genes involved in the control of numerous developmental processes required for organogenesis and repress key regulators of carpel formation. Our results imply considerable changes in the composition and topology of the gene network controlled by AP3/PI during the course of flower development. We discuss our results in light of a model for the mechanism underlying sex-determination in seed plants, in which AP3/PI orthologues might act as a switch between the activation of male and the repression of female development.

  19. 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.

  20. 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.

  1. Preliminary Observations of Ionospheric Structures using Ground Receivers and the COSMIC Radio Beacon

    Science.gov (United States)

    Garner, T. W.; Gaussiran, T. L., II; Bust, G. S.

    2006-11-01

    With the launch of the Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC) satellite constellation, a new era has begun for low-Earth-orbiting (LEO) satellite beacon research has begun. Each COSMIC satellite carries a radio beacon that can emit at 1066, 400, and 150 MHz. Coherent Ionospheric Doppler Receivers (CIDR) deployed at mid-latitudes observe the electron content and phase scintillation in the 400 and 150 MHz channels. In addition to high (Alaska and Greenland) and low (Peru) latitude systems, CIDRs are deployed in Austin, Texas, a chain across southern New York, Millstone Hill, and Wallops Island. This study presents preliminary observations of different ionospheric structures using CIDR receivers and the COSMIC radio beacon.

  2. 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

  3. Gender-Specific Molecular and Clinical Features underlie Malignant Pleural Mesothelioma

    Science.gov (United States)

    Rienzo, Assunta De; Archer, Michael A.; Yeap, Beow Y.; Dao, Nhien; Sciaranghella, Daniele; Sideris, Antonios C.; Zheng, Yifan; Holman, Alexander G.; Wang, Yaoyu E.; Dal Cin, Paola S.; Fletcher, Jonathan A.; Rubio, Renee; Croft, Larry; Quackenbush, John; Sugarbaker, Peter E.; Munir, Kiara J.; Battilana, Jesse R.; Gustafson, Corinne E.; Chirieac, Lucian R.; Ching, Soo Meng; Wong, James; Tay, Liang Chung; Rudd, Stephen; Hercus, Robert; Sugarbaker, David J.; Richards, William G.; Bueno, Raphael

    2015-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (p<0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that non-epitheliod histology (p=0.037), whereas CDKN2A deletions occurred more frequently in non-epithelioid subtypes among men (p=0.021) and were correlated with shorter overall survival for the entire cohort (p=0.002) and for men (p=0.012). Furthermore, women were more likely to harbor TP53 mutations (p=0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in non-epithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM. PMID:26554828

  4. 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

  5. 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

  6. Theoretical analysis and experimental study of constraint boundary conditions for acquiring the beacon in satellite-ground laser communications

    Science.gov (United States)

    Yu, Siyuan; Wu, Feng; Wang, Qiang; Tan, Liying; Ma, Jing

    2017-11-01

    Acquisition and recognition for the beacon is the core technology of establishing the satellite optical link. In order to acquire the beacon correctly, the beacon image should be recognized firstly, excluding the influence of the background light. In this processing, many factors will influence the recognition precision of the beacon. This paper studies the constraint boundary conditions for acquiring the beacon from the perspective of theory and experiment, and as satellite-ground laser communications, an approach for obtaining the adaptive segmentation method is also proposed. Finally, the long distance laser communication experiment (11.16 km) verifies the validity of this method and the tracking error with the method is the least compared with the traditional approaches. The method helps to greatly improve the tracking precision in the satellite-ground laser communications.

  7. 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

  8. Molecular cloning and characterization of the ABA-specific glucosyltransferase gene from bean (Phaseolus vulgaris L.).

    Science.gov (United States)

    Palaniyandi, Sasikumar Arunachalam; Chung, Gyuhwa; Kim, Sang Hyon; Yang, Seung Hwan

    2015-04-15

    Levels of the plant hormone abscisic acid (ABA) are maintained in homeostasis by a balance of its biosynthesis, catabolism and conjugation. The detailed molecular and signaling events leading to strict homeostasis are not completely understood in crop plants. In this study, we obtained cDNA of an ABA-inducible, ABA-specific UDP-glucosyltransferase (ABAGT) from the bean plant (Phaseolus vulgaris L.) involved in conjugation of a glucose residue to ABA to form inactive ABA-glucose ester (ABA-GE) to examine its role during development and abiotic stress in bean. The bacterially expressed PvABAGTase enzyme showed ABA-specific glucosylation activity in vitro. A higher level of the PvABAGT transcript was observed in mature leaves, mature flowers, roots, seed coats and embryos as well as upon rehydration following a period of dehydration. Overexpression of 35S::PvABAGT in Arabidopsis showed reduced sensitivity to ABA compared with WT. The transgenic plants showed a high level of ABA-GE without significant decrease in the level of ABA compared with the wild type (WT) during dehydration stress. Upon rehydration, the levels of ABA and phaseic acid (PA) decreased in the WT and the PvABAGT-overexpressing lines with high levels of ABA-GE only in the transgenic plants. Our findings suggest that the PvABAGT gene could play a role in ABA homeostasis during development and stress responses in bean and its overexpression in Arabidopsis did not alter ABA homeostasis during dehydration stress. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. 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

  10. Molecular evolution constraints in the floral organ specification gene regulatory network module across 18 angiosperm genomes.

    Science.gov (United States)

    Davila-Velderrain, Jose; Servin-Marquez, Andres; Alvarez-Buylla, Elena R

    2014-03-01

    The gene regulatory network of floral organ cell fate specification of Arabidopsis thaliana is a robust developmental regulatory module. Although such finding was proposed to explain the overall conservation of floral organ types and organization among angiosperms, it has not been confirmed that the network components are conserved at the molecular level among flowering plants. Using the genomic data that have accumulated, we address the conservation of the genes involved in this network and the forces that have shaped its evolution during the divergence of angiosperms. We recovered the network gene homologs for 18 species of flowering plants spanning nine families. We found that all the genes are highly conserved with no evidence of positive selection. We studied the sequence conservation features of the genes in the context of their known biological function and the strength of the purifying selection acting upon them in relation to their placement within the network. Our results suggest an association between protein length and sequence conservation, evolutionary rates, and functional category. On the other hand, we found no significant correlation between the strength of purifying selection and gene placement. Our results confirm that the studied robust developmental regulatory module has been subjected to strong functional constraints. However, unlike previous studies, our results do not support the notion that network topology plays a major role in constraining evolutionary rates. We speculate that the dynamical functional role of genes within the network and not just its connectivity could play an important role in constraining evolution.

  11. Development of patient-specific molecular imaging phantoms using a 3D printer.

    Science.gov (United States)

    Gear, J I; Long, C; Rushforth, D; Chittenden, S J; Cummings, C; Flux, G D

    2014-08-01

    The aim of the study was to investigate rapid prototyping technology for the production of patient-specific, cost-effective liquid fillable phantoms directly from patient CT data. Liver, spleen, and kidney volumes were segmented from patient CT data. Each organ was converted to a shell and filling holes and leg supports were added using computer aided design software and prepared for printing. Additional fixtures were added to the liver to allow lesion inserts to be fixed within the structure. Phantoms were printed from an ultraviolet curable photopolymer using polyjet technology on an Objet EDEN 500V 3D printer. The final print material is a clear solid acrylic plastic which is watertight, rigid, and sufficiently durable to withstand multiple assembly and scanning protocols. Initial scans of the phantoms have been performed with Tc-99m SPECT and F-18 PET/CT. The organ geometry showed good correspondence with anatomical references. The methodology developed can be generally applied to other anatomical or geometrical phantoms for molecular imaging.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Torres G, E. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Gonzalez V, A. [UAEM, Facultad de Medicina, Toluca (Mexico); Murphy, C.A. de [INCMNSZ, Mexico D.F. (Mexico)

    2006-07-01

    Molecular imaging techniques directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochemical, biologic, diagnostic or therapeutic applications. {sup 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 {sup 99m}Tc-HYNlC-TOC and {sup 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 {sup 99m}Tc-HYNlC-TOC or {sup 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. {sup 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 {sup 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)

  13. 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)

  14. Increased amylosucrase activity and specificity, and identification of regions important for activity, specificity and stability through molecular evolution

    DEFF Research Database (Denmark)

    van der Veen, Bart A; Skov, Lars K; Potocki-Véronèse, Gabrielle

    2006-01-01

    , several variants are expected to be improved concerning activity and/or thermostability. Most of the amino acid substitutions observed in the totality of these improved variants are clustered around specific regions. The secondary sucrose-binding site and beta strand 7, connected to the important Asp393...

  15. 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…

  16. 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.

  17. 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.

  18. 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

  19. The Roles of Beaconing and Dead Reckoning in Human Virtual Navigation

    Science.gov (United States)

    Bodily, Kent D.; Daniel, Thomas A.; Sturz, Bradley R.

    2012-01-01

    Beaconing is a process in which the distance between a visual landmark and current position is reduced in order to return to a location. In contrast, dead reckoning is a process in which vestibular, kinesthetic and/or optic flow cues are utilized to update speed of movement, elapsed time of movement, and direction of movement to return to a…

  20. 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.

  1. 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.

  2. Preparation and evaluation of magnetic molecularly imprinted polymers for the specific enrichment of phloridzin.

    Science.gov (United States)

    Gao, Die; Wang, Dan-Dan; Fu, Qi-Feng; Wang, Lu-Jun; Zhang, Kai-Lian; Yang, Feng-Qing; Xia, Zhi-Ning

    2018-02-01

    In present study, magnetic molecularly imprinted polymers (MMIPs) were successfully prepared for specific recognition and selective enrichment of phloridzin from the leaves of Malus doumeri (Bois) A. Chev and rats' plasma. The magnetic Fe 3 O 4 were prepared by the solvothermal reaction method and followed by the modification of TEOS and functionalization with APTES. Using functionalized Fe 3 O 4 particles as the magnetic cores, phloridzin as template, ethylene glycol dimethacrylate (EGDMA) as cross-linker and 2,2-azobisisobutyonnitrile (AIBN) as initiator, the MMIPs were prepared through APTES to associate the template on the surface of the magnetic substrate. The structural features and morphological characterizations of MMIPs were performed by FT-IR, SEM, TEM, XRD, TGA and VSM. The adsorption experiments revealed that the MMIPs presented high selective recognition property to phloridzin. The selectivity experiment indicated that the adsorption capacity and selectivity of polymers to phloridzin was higher than that of baicalin and 2,3,5,4'-ttrahydroxy stilbene-2-O-β-D-glucoside. Furthermore, the MMIPs were employed as adsorbents for extraction and enrichment of phloridzin from the leaves of M. doumeri and rats' plasma. The recoveries of phloridzin in the leaves of M. doumeri ranged from 81.45% to 90.27%. The maximum concentration (C max ) of phloridzin in rats' plasma was detected as 12.19 ± 0.84μg/mL at about 15min after oral administration of phloridzin (200mg/kg). These results demonstrate that the prepared MMIPs are suitable for the selective adsorption of phloridzin from complex samples such as natural medical plants and biological samples. Copyright © 2017. Published by Elsevier B.V.

  3. 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

  4. Supplementary Material for: BEACON: automated tool for Bacterial GEnome Annotation ComparisON

    KAUST Repository

    Kalkatawi, Manal M.

    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/ .

  5. 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...

  6. 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

  7. Isolation, characterization and molecular cloning of Duplex-Specific Nuclease from the hepatopancreas of the Kamchatka crab

    Directory of Open Access Journals (Sweden)

    Vagner Laura L

    2008-05-01

    Full Text Available Abstract Background Nucleases, which are key components of biologically diverse processes such as DNA replication, repair and recombination, antiviral defense, apoptosis and digestion, have revolutionized the field of molecular biology. Indeed many standard molecular strategies, including molecular cloning, studies of DNA-protein interactions, and analysis of nucleic acid structures, would be virtually impossible without these versatile enzymes. The discovery of nucleases with unique properties has often served as the basis for the development of modern molecular biology methods. Thus, the search for novel nucleases with potentially exploitable functions remains an important scientific undertaking. Results Using degenerative primers and the rapid amplification of cDNA ends (RACE procedure, we cloned the Duplex-Specific Nuclease (DSN gene from the hepatopancreas of the Kamchatka crab and determined its full primary structure. We also developed an effective method for purifying functional DSN from the crab hepatopancreas. The isolated enzyme was highly thermostable, exhibited a broad pH optimum (5.5 – 7.5 and required divalent cations for activity, with manganese and cobalt being especially effective. The enzyme was highly specific, cleaving double-stranded DNA or DNA in DNA-RNA hybrids, but not single-stranded DNA or single- or double-stranded RNA. Moreover, only DNA duplexes containing at least 9 base pairs were effectively cleaved by DSN; shorter DNA duplexes were left intact. Conclusion We describe a new DSN from Kamchatka crab hepatopancreas, determining its primary structure and developing a preparative method for its purification. We found that DSN had unique substrate specificity, cleaving only DNA duplexes longer than 8 base pairs, or DNA in DNA-RNA hybrids. Interestingly, the DSN primary structure is homologous to well-known Serratia-like non-specific nucleases structures, but the properties of DSN are distinct. The unique substrate

  8. Specific volume-hole volume correlations in amorphous carbohydrates: effect of temperature, molecular weight, and water content.

    Science.gov (United States)

    Townrow, Sam; Roussenova, Mina; Giardiello, Maria-Isabelle; Alam, Ashraf; Ubbink, Job

    2010-02-04

    The specific volume and the nanostructure of the free volume of amorphous blends of maltose with a narrow molecular weight distribution maltopolymer were systematically studied as a function of temperature, water content, pressure, and blend composition. Correlations between the hole free volume and the specific volume were investigated in the glassy and rubbery phases and in solution using positron annihilation lifetime spectroscopy (PALS) and pressure-volume-temperature (PVT) measurements, with the aim to provide a consolidated mechanistic understanding of the relation between changes in molecular packing and at the molecular level and the behavior of the specific volume at the macrolevel. Both specific volume and hole volume show a linear dependence on the temperature, but with a slope which is higher in the rubbery state than in the glassy state. As a function of temperature, the hole volume and the specific volume are linearly related, with no discontinuity at the glass transition temperature (T(g)). In the glassy state, both the specific volume and the hole volume decrease nonlinearly with the addition of maltose to the maltopolymer matrix, due to a more efficient molecular packing. For variations in carbohydrate composition, a linear dependence between the hole volume and the specific volume was again observed. The role of water was found to be significantly more complex, with increasing water content causing an increase in density in both the glassy and rubbery phases indicating that water exists in a highly dispersed state with a significantly lower specific molar volume than in bulk water. At very low water contents, the hole volume and the specific volume both decrease with increasing water content, which suggests that water acts as both a hole filler and a plasticizer. In the glassy state at slightly higher water contents, the specific volume continues to slowly decrease, but the hole size passes through a minimum before it starts to increase. This

  9. The development of 7E chromosome-specific molecular markers for Thinopyrum elongatum based on SLAF-seq technology.

    Directory of Open Access Journals (Sweden)

    Shiqiang Chen

    Full Text Available Thinopyrum elongatum is an important relative of wheat, it is favored by many researchers for the disease resistant genes that exist in its E genome. Some studies have showed that the 7E chromosome of Th. elongatum contains resistance genes related to Fusarium head blight and wheat rust. Therefore, developing 7E chromosome-specific molecular markers linked to resistance genes will provide an important tool for exploring and using the resistant genes of Th. elongatum. In addition, it would greatly contribute in the effort to cultivate disease-resistant wheat varieties. Featured in high throughput, high-accuracy and low-cost, SLAF-seq technology has been widely used in molecular breeding, system evolution, and germplasm resource detection. Based on SLAF-seq, 518 specific fragments on the 7E chromosome of Th. elongatum were successfully amplified. A total of 135 primers were designed according to 135 randomly selected fragments, and 89 specific molecular markers of Th. elongatum were developed, with efficiencies up to 65.9%. These markers were all detected in a variety of materials, and they are all proved to be specific and stable. These markers can be used not only for detecting the 7E chromosome of Th. elongatum but also for providing an important theoretical and practical basis for wheat breeding by marker-assisted selection (MAS. This paper reports the first application of SLAF-seq technology with a high success rate in developing specific molecular markers for Th. elongatum, providing a strong case for the application of this new technology.

  10. Purification and molecular cloning of a new galactose-specific lectin ...

    Indian Academy of Sciences (India)

    SDS-PAGE showed that the lectin, named BVL, has a pattern similar to other lectins isolated from the same genus, Bauhinia purpurea agglutinin (BPA). The molecular mass of BVL subunit is 32 871 Da, determined by MALDI-TOF spectrometry. DNA extracted from B. variegata young leaves and primers designed according ...

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Electrical and Nonlinear Optical Studies of Specific Organic Molecular and Nonconjugated Conductive Polymeric Systems

    Science.gov (United States)

    Narayanan, Ananthakrishnan

    film of poly(beta-pinene) on bare multi-mode optical fiber and doping it with iodine. The doped fibers were of excellent optical quality. Two-photon absorption experiments were conducted using these waveguides and large changes in transmission upto 28% was observed in 15cm long fiber. More work needs to be done to confirm this result. This is a significant step in the direction of making these materials a viable choice for ultrafast (femtosecond time-scale) optical devices. To summarize, these works included detailed investigations of structural, electrical and nonlinear optical characteristics of specific molecular crystal films and nonconjugated conducting polymers.

  16. 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.

  17. 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.

  18. Creation of a Library Tour Application for Mobile Equipment using iBeacon Technology

    Directory of Open Access Journals (Sweden)

    Jonathan Bradley

    2016-04-01

    Full Text Available We describe the design, development, and deployment of a library tour application utilizing Bluetooth Low Energy devices know as iBeacons. The tour application will serve as library orientation for incoming students. The students visit stations in the library with mobile equipment running a special tour app. When the app detects a beacon nearby, it automatically plays a video that describes the current location. After the tour, students are assessed according to the defined learning objectives. Special attention is given to issues encountered during development, deployment, content creation, and testing of this application that depend on functioning hardware, and the necessity of appointing a project manager to limit scope, define priorities, and create an actionable plan for the experiment.

  19. 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.

  20. 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.

  1. 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 ...

  2. 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.)

  3. 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.

  4. 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

  5. Endometrial Serous Carcinoma: Its Molecular Characteristics and Histology-Specific Treatment Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Kentaro, E-mail: kn88@med.shimane-u.ac.jp [Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 6938501 (Japan); Nakayama, Naomi [Department of Biochemistry, Shimane University School of Medicine, Izumo 6938501 (Japan); Ishikawa, Masako; Miyazaki, Kohji [Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 6938501 (Japan)

    2012-08-07

    Endometrial cancer is the fourth most common malignancy in women, with most cases being classified as early stage endometrioid tumors that carry a favorable prognosis. The endometrial serous histological subtype (ESC), however, while only accounting for 10% of all endometrial cancers is responsible for a disproportionate number of deaths. Unlike the estrogen-dependent, well differentiated endometrioid tumors, which are commonly associated with a younger age of onset, ESCs are estrogen-independent and tend to present at an advanced stage and in older women. Treatment for ESC entails aggressive surgery and multimodal adjuvant therapy. In this review, we describe the clinical behavior, molecular aspects, and treatment strategies for ESC.

  6. Host specificity of North American Rhabdias spp. (Nematoda: Rhabdiasidae): combining field data and experimental infections with a molecular phylogeny.

    Science.gov (United States)

    Langford, Gabriel J; Janovy, John

    2013-04-01

    Lungworms of the cosmopolitan genus Rhabdias are among the most common parasites of amphibians and squamate reptiles. The present study used experimental infections, field studies, and a molecular phylogeny to determine the host specificity of 6 Rhabdias spp. that infect snakes and anurans from North America. The molecular phylogeny suggests Rhabdias ranae from Nebraska and Mississippi may represent separate, cryptic species. In addition, the phylogeny strongly supports separate clades for anuran and snake lungworms. Field studies and experimental infections indicate that snake lungworms are generalist snake parasites; however, laboratory experiments also suggest that lizards can be infected under some environmental conditions. Lungworms from anurans were found not to infect salamanders or reptiles, in nature or in the laboratory; anuran lungworm species ranged from strict host specificity, e.g., R. ranae from Nebraska, to relative generalist, e.g., Rhabdias joaquinensis from Nebraska. Overall, host specificity for species of Rhabdias does not provide support for the evolution of progressive specialization over time. For most species of lungworms, host specificity in nature appears to be limited by both ecological and physiological factors, which vary between species and their hosts. Furthermore, some lungworms, e.g., Rhabdias bakeri from Missouri, appear to be tracking host resources instead of host phylogenies, an example of ecological fitting.

  7. VNAR single-domain antibodies specific for BAFF inhibit B cell development by molecular mimicry.

    Science.gov (United States)

    Häsler, Julien; Flajnik, Martin F; Williams, Gareth; Walsh, Frank S; Rutkowski, J Lynn

    2016-07-01

    B cell-activating factor (BAFF) plays a dominant role in the B cell homeostasis. However, excessive BAFF promotes the development of autoreactive B-cells and several antibodies have been developed to block its activity. Bispecific antibodies with added functionality represent the next wave of biologics that may be more effective in the treatment of complex autoimmune disease. The single variable domain from the immunoglobulin new antigen receptor (VNAR) is one of the smallest antibody recognition units that could be combined with monospecific antibodies to develop bispecific agents. We isolated a panel of BAFF-binding VNARs with low nM potency from a semi-synthetic phage display library and examined their functional activity. The anti-BAFF VNARs blocked the binding of BAFF to all three of its receptors (BR3, TACI and BCMA) and the presence of the conserved DXL receptor motif found in the CDR3 regions suggests molecular mimicry as the mechanism of antagonism. One clone was formatted as an Fc fusion for functional testing and it was found to inhibit both mouse and human BAFF with equal potency ex vivo in a splenocyte proliferation assay. In mice, subchronic administration reduced the number of immature and transitional intermediates B cells and mature B cell subsets. These results indicate that VNAR single domain antibodies function as selective B-cell inhibitors and offer an alternative molecular format for targeting B-cell disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. 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

    , such as oxidized phospholipids and oxidized cholesteryl esters, and mediate a variety of immune responses, from expression of proinflammatory genes to excessive intracellular lipoprotein accumulation to atheroprotective humoral immunity. These insights may lead to improved understanding of inflammation......Oxidation reactions are vital parts of metabolism and signal transduction. However, they also produce reactive oxygen species, which damage lipids, proteins and DNA, generating "oxidation-specific" epitopes. In this review, we discuss the hypothesis that such common oxidation-specific epitopes...... 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...

  9. 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

  10. Molecular basis of sidekick-mediated cell-cell adhesion and specificity

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Kerry M.; Yamagata, Masahito; Jin, Xiangshu; Mannepalli, Seetha; Katsamba, Phinikoula S.; Ahlsén, Göran; Sergeeva, Alina P.; Honig, Barry; Sanes, Joshua R.; Shapiro, Lawrence

    2016-09-19

    Sidekick (Sdk) 1 and 2 are related immunoglobulin superfamily cell adhesion proteins required for appropriate synaptic connections between specific subtypes of retinal neurons. Sdks mediate cell-cell adhesion with homophilic specificity that underlies their neuronal targeting function. Here we report crystal structures of Sdk1 and Sdk2 ectodomain regions, revealing similar homodimers mediated by the four N-terminal immunoglobulin domains (Ig1–4), arranged in a horseshoe conformation. These Ig1–4 horseshoes interact in a novel back-to-back orientation in both homodimers through Ig1:Ig2, Ig1:Ig1 and Ig3:Ig4 interactions. Structure-guided mutagenesis results show that this canonical dimer is required for both Sdk-mediated cell aggregation (viatransinteractions) and Sdk clustering in isolated cells (viacisinteractions). Sdk1/Sdk2 recognition specificity is encoded across Ig1–4, with Ig1–2 conferring the majority of binding affinity and differential specificity. We suggest that competition betweencisandtransinteractions provides a novel mechanism to sharpen the specificity of cell-cell interactions.

  11. 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.

  12. 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.

  13. Molecular determinants for the complex binding specificity of the PDZ domain in PICK1

    DEFF Research Database (Denmark)

    Madsen, Kenneth L; Beuming, Thijs; Niv, Masha Y

    2005-01-01

    polarization. Our results showed that the PICK1 PDZ domain binds the type II sequence presented by the human dopamine transporter (-WLKV) with an almost 15-fold and >100-fold higher affinity than the type I sequences presented by protein kinase Calpha (-QSAV) and the beta(2)-adrenergic receptor (-DSLL......), respectively. Mutational analysis of Lys(83) in the alphaB1 position of the PDZ domain suggested that this residue mimics the function of hydrophobic residues present in this position in regular type II PDZ domains. The PICK1 PDZ domain was moreover found to prefer small hydrophobic residues in the C......-terminal P(0) position of the ligand. Molecular modeling predicted a rank order of (Val > Ile > Leu) that was verified experimentally with up to a approximately 16-fold difference in binding affinity between a valine and a leucine in P(0). The results define the structural basis for the unusual binding...

  14. Molecular beacon nanosensors for live cell detection and tracking differentiation and reprogramming

    DEFF Research Database (Denmark)

    Ilieva, Mirolyuba

    2013-01-01

    High-sensitive and high-affinity methods to measure gene expression inside living cells have proven to be invaluable in regards to understanding fundamental processes such as cell differentiation, reprogramming, regeneration and cancer genesis. One tool for transcription visualization on single...

  15. Activatable clinical fluorophore-quencher antibody pairs as dual molecular probes for the enhanced specificity of image-guided surgery

    Science.gov (United States)

    Obaid, Girgis; Spring, Bryan Q.; Bano, Shazia; Hasan, Tayyaba

    2017-12-01

    The emergence of fluorescently labeled therapeutic antibodies has given rise to molecular probes for image-guided surgery. However, the extraneous interstitial presence of an unbound and nonspecifically accumulated probe gives rise to false-positive detection of tumor tissue and margins. Thus, the concept of tumor-cell activation of smart probes provides a potentially superior mechanism of delineating tumor margins as well as small tumor deposits. The combination of molecular targeting with intracellular activation circumvents the presence of extracellular, nonspecific signals of targeted probe accumulation. Here, we present a demonstration of the clinical antibodies cetuximab (cet, anti-EGFR mAb) and trastuzumab (trast, anti-HER-2 mAb) conjugated to Alexa Fluor molecules and IRDye QC-1 quencher optimized at the ratio of 1∶2∶6 to provide the greatest degree of proteolytic fluorescence activation, synonymous with intracellular lysosomal degradation. The cet-AF-Q-C1 conjugate (1∶2∶6) provides up to 9.8-fold proteolytic fluorescence activation. By preparing a spectrally distinct, irrelevant sham IgG-AF-QC-1 conjugate, a dual-activatable probe approach is shown to enhance the specificity of imaging within an orthotopic AsPC-1 pancreatic cancer xenograft model. The dual-activatable approach warrants expedited clinical translation to improve the specificity of image-guided surgery by spectrally decomposing specific from nonspecific probe accumulation, binding, and internalization.

  16. 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.

  17. Joint effects of molecular structure and processing history on specific nucleation of isotactic polypropylene

    Czech Academy of Sciences Publication Activity Database

    Chvátalová, L.; Navrátilová, J.; Čermák, R.; Raab, Miroslav; Obadal, M.

    2009-01-01

    Roč. 42, č. 19 (2009), s. 7413-7417 ISSN 0024-9297 Institutional research plan: CEZ:AV0Z40500505 Keywords : specific beta nucleation * isotactic polypropylene * beta phase Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.539, year: 2009

  18. Highly specific spectroscopic photoacoustic molecular imaging of dynamic optical absorption shifts of an antibody-ICG contrast agent (Conference Presentation)

    Science.gov (United States)

    Wilson, Katheryne E.; Bachawal, Sunitha; Abou-Elkacem, Lotfi; Jensen, Kristen C.; Machtaler, Steven; Tian, Lu; Willmann, Juergen K.

    2017-03-01

    Improved techniques for breast cancer screening are critically needed as current methods lack diagnostic accuracy. Using spectroscopic photoacoustic (sPA) molecular imaging with a priori knowledge of optical absorption spectra allows suppression of endogenous background signal, increasing the overall sensitivity and specificity of the modality to exogenous contrast agents. Here, sPA imaging was used to monitor antibody-indocyanine green (ICG) conjugates as they undergo optical absorption spectrum shifts after cellular endocytosis and degradation to allow differentiation between normal murine mammary glands from breast cancer by enhancing molecular imaging signal from target (B7-H3)-bound antibody-ICG. First, B7-H3 was shown to have highly specific (AUC of 0.93) expression on both vascular endothelium and tumor stroma in malignant lesions through quantitative immunohistochemical staining of B7-H3 on 279 human samples (normal (n=53), benign lesions (11 subtypes, n=182), breast cancers (4 subtypes, n=97)), making B7-H3 a promising target for sPA imaging. Second, absorption spectra of intracellular and degraded B7-H3-ICG and Isotype control (Iso-ICG) were characterized through in vitro and in vivo experiments. Finally, a transgenic murine breast cancer model (FVB/N-Tg(MMTVPyMT)634Mul) was imaged, and sPA imaging in found a 3.01 (IQR 2.63, 3.38, Pcontrast agents, which have dynamic optical absorption spectra representative of molecular interactions, allows for highly specific sPA imaging of murine breast cancer.

  19. Understanding the specificity of human Galectin-8C domain interactions with its glycan ligands based on molecular dynamics simulations.

    Science.gov (United States)

    Kumar, Sonu; Frank, Martin; Schwartz-Albiez, Reinhard

    2013-01-01

    Human Galectin-8 (Gal-8) is a member of the galectin family which shares an affinity for β-galactosides. The tandem-repeat Gal-8 consists of a N- and a C-terminal carbohydrate recognition domain (N- and C-CRD) joined by a linker peptide of various length. Despite their structural similarity both CRDs recognize different oligosaccharides. While the molecular requirements of the N-CRD for high binding affinity to sulfated and sialylated glycans have recently been elucidated by crystallographic studies of complexes with several oligosaccharides, the binding specificities of the C-CRD for a different set of oligosaccharides, as derived from experimental data, has only been explained in terms of the three-dimensional structure for the complex C-CRD with lactose. In this study we performed molecular dynamics (MD) simulations using the recently released crystal structure of the Gal-8C-CRD to analyse the three-dimensional conditions for its specific binding to a variety of oligosaccharides as previously defined by glycan-microarray analysis. The terminal β-galactose of disaccharides (LacNAc, lacto-N-biose and lactose) and the internal β-galactose moiety of blood group antigens A and B (BGA, BGB) as well as of longer linear oligosaccharide chains (di-LacNAc and lacto-N-neotetraose) are interacting favorably with conserved amino acids (H53, R57, N66, W73, E76). Lacto-N-neotetraose and di-LacNAc as well as BGA and BGB are well accommodated. BGA and BGB showed higher affinity than LacNAc and lactose due to generally stronger hydrogen bond interactions and water mediated hydrogen bonds with α1-2 fucose respectively. Our results derived from molecular dynamics simulations are able to explain the glycan binding specificities of the Gal-8C-CRD in comparison to those of the Gal-8N -CRD.

  20. Understanding the specificity of human Galectin-8C domain interactions with its glycan ligands based on molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Sonu Kumar

    Full Text Available Human Galectin-8 (Gal-8 is a member of the galectin family which shares an affinity for β-galactosides. The tandem-repeat Gal-8 consists of a N- and a C-terminal carbohydrate recognition domain (N- and C-CRD joined by a linker peptide of various length. Despite their structural similarity both CRDs recognize different oligosaccharides. While the molecular requirements of the N-CRD for high binding affinity to sulfated and sialylated glycans have recently been elucidated by crystallographic studies of complexes with several oligosaccharides, the binding specificities of the C-CRD for a different set of oligosaccharides, as derived from experimental data, has only been explained in terms of the three-dimensional structure for the complex C-CRD with lactose. In this study we performed molecular dynamics (MD simulations using the recently released crystal structure of the Gal-8C-CRD to analyse the three-dimensional conditions for its specific binding to a variety of oligosaccharides as previously defined by glycan-microarray analysis. The terminal β-galactose of disaccharides (LacNAc, lacto-N-biose and lactose and the internal β-galactose moiety of blood group antigens A and B (BGA, BGB as well as of longer linear oligosaccharide chains (di-LacNAc and lacto-N-neotetraose are interacting favorably with conserved amino acids (H53, R57, N66, W73, E76. Lacto-N-neotetraose and di-LacNAc as well as BGA and BGB are well accommodated. BGA and BGB showed higher affinity than LacNAc and lactose due to generally stronger hydrogen bond interactions and water mediated hydrogen bonds with α1-2 fucose respectively. Our results derived from molecular dynamics simulations are able to explain the glycan binding specificities of the Gal-8C-CRD in comparison to those of the Gal-8N -CRD.

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

    Science.gov (United States)

    Villar, Emilie; Klopp, Christophe; Noirot, Céline; Novaes, Evandro; Kirst, Matias; Plomion, Christophe; Gion, Jean-Marc

    2011-11-02

    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. 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. 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 of biomass growth during the

  2. 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.)

  3. 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...... designed that can act as a forward primer in PCRs for any Perna species. Four reverse primers have also been designed, based on nad4 and intergenic spacer sequences, which yield species-specific products of different lengths when paired with the conserved forward primer. A further pair of primers has been...

  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

    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....

  5. 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.

  6. 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.

  7. Species-Specific Inactivation of Triosephosphate Isomerase from Trypanosoma brucei: Kinetic and Molecular Dynamics Studies

    Directory of Open Access Journals (Sweden)

    Alejandra Vázquez-Raygoza

    2017-11-01

    Full Text Available Human African Trypanosomiasis (HAT, a disease that provokes 2184 new cases a year in Sub-Saharan Africa, is caused by Trypanosoma brucei. Current treatments are limited, highly toxic, and parasite strains resistant to them are emerging. Therefore, there is an urgency to find new drugs against HAT. In this context, T. brucei depends on glycolysis as the unique source for ATP supply; therefore, the enzyme triosephosphate isomerase (TIM is an attractive target for drug design. In the present work, three new benzimidazole derivatives were found as TbTIM inactivators (compounds 1, 2 and 3 with an I50 value of 84, 82 and 73 µM, respectively. Kinetic analyses indicated that the three molecules were selective when tested against human TIM (HsTIM activity. Additionally, to study their binding mode in TbTIM, we performed a 100 ns molecular dynamics simulation of TbTIM-inactivator complexes. Simulations showed that the binding of compounds disturbs the structure of the protein, affecting the conformations of important domains such as loop 6 and loop 8. In addition, the physicochemical and drug-like parameters showed by the three compounds suggest a good oral absorption. In conclusion, these molecules will serve as a guide to design more potent inactivators that could be used to obtain new drugs against HAT.

  8. Diagnostic accuracy of specific IgE antibodies measurements in occupational airway allergy to high molecular weight agents

    Directory of Open Access Journals (Sweden)

    Joanna Zgorzelska-Kowalik

    2017-02-01

    Full Text Available Background: The performance of specific inhalation challenge test (SICT – reference method in diagnostics of occupational allergy – has some limitations due to health status of a particular patient. Therefore, it is extremely important to identify usefulness of other tests, and the evaluation of diagnostic accuracy of commercially available serum specific immunoglobulin E (sIgE kits to the most common high molecular weight agents has been launched. Material and Methods: The study group comprised 141 subjects – 110 bakers and 31 farmers – with suspicion of occupational airway allergy. All patients underwent evaluation of serum sIgE to occupational allergens with the use of Phadia and Allergopharma kits: in bakers to flour mix and α-amylase, in farmers to epithelium of cow, pig and feathers. Specific inhalation challenge test with workplace allergens performed in all subjects was a reference method for further analysis. Results: Serum specific IgE to flour mix had the highest sensitivity (Phadia – 95.6%, Allergopharma – 88.3%, while its specificity was relatively low (Phadia – 47.8%, Allergopharma – 25%. There were numerous discrepancies between the results of sIgE estimation for particular single allergens (k87, e4, e83, as well as for their mixtures (fx901, fx20, ex71, performed with the kits of both companies (Phadia vs. Allergopharma. Conclusions: Evaluation of serum specific IgE is characterized by inadequate sensitivity, specificity and predictive value to take the place of specific inhalation challenge test in diagnostics of occupational respiratory allergy. Med Pr 2017;68(1:31–43

  9. Many genes in fish have species-specific asymmetric rates of molecular evolution

    Directory of Open Access Journals (Sweden)

    Braasch Ingo

    2006-02-01

    Full Text Available Abstract Background Gene and genome duplication events increase the amount of genetic material that might then contribute to an increase in the genomic and phenotypic complexity of organisms during evolution. Thus, it has been argued that there is a relationship between gene copy number and morphological complexity and/or species diversity. This hypothesis implies that duplicated genes have subdivided or evolved novel functions compared to their pre-duplication proto-orthologs. Such a functional divergence might be caused by an increase in evolutionary rates in one ortholog, by changes in expression, regulatory evolution, insertion of repetitive elements, or due to positive Darwinian selection in one copy. We studied a set of 2466 genes that were present in Danio rerio, Takifugu rubripes, Tetraodon nigroviridis and Oryzias latipes to test (i for forces of positive Darwinian selection; (ii how frequently duplicated genes are retained, and (iii whether novel gene functions might have evolved. Results 25% (610 of all investigated genes show significantly smaller or higher genetic distances in the genomes of particular fish species compared to their human ortholog than their orthologs in other fish according to relative rate tests. We identified 49 new paralogous pairs of duplicated genes in fish, in which one of the paralogs is under positive Darwinian selection and shows a significantly higher rate of molecular evolution in one of the four fish species, whereas the other copy apparently did not undergo adaptive changes since it retained the original rate of evolution. Among the genes under positive Darwinian selection, we found a surprisingly high number of ATP binding proteins and transcription factors. Conclusion The significant rate difference suggests that the function of these rate-changed genes might be essential for the respective fish species. We demonstrate that the measurement of positive selection is a powerful tool to identify

  10. Selecting Tumor-Specific Molecular Targets in Pancreatic Adenocarcinoma: Paving the Way for Image-Guided Pancreatic Surgery.

    Science.gov (United States)

    de Geus, Susanna W L; Boogerd, Leonora S F; Swijnenburg, Rutger-Jan; Mieog, J Sven D; Tummers, Willemieke S F J; Prevoo, Hendrica A J M; Sier, Cornelis F M; Morreau, Hans; Bonsing, Bert A; van de Velde, Cornelis J H; Vahrmeijer, Alexander L; Kuppen, Peter J K

    2016-12-01

    The purpose of this study was to identify suitable molecular targets for tumor-specific imaging of pancreatic adenocarcinoma. The expression of eight potential imaging targets was assessed by the target selection criteria (TASC)-score and immunohistochemical analysis in normal pancreatic tissue (n = 9), pancreatic (n = 137), and periampullary (n = 28) adenocarcinoma. Integrin α v β 6 , carcinoembryonic antigen (CEA), epithelial growth factor receptor (EGFR), and urokinase plasminogen activator receptor (uPAR) showed a significantly higher (all p < 0.001) expression in pancreatic adenocarcinoma compared to normal pancreatic tissue and were confirmed by the TASC score as promising imaging targets. Furthermore, these biomarkers were expressed in respectively 88 %, 71 %, 69 %, and 67 % of the pancreatic adenocarcinoma patients. The results of this study show that integrin α v β 6 , CEA, EGFR, and uPAR are suitable targets for tumor-specific imaging of pancreatic adenocarcinoma.

  11. TAT-LHRH conjugated low molecular weight chitosan as a gene carrier specific for hepatocellular carcinoma cells

    Science.gov (United States)

    Liu, Lanxia; Dong, Xia; Zhu, Dunwan; Song, Liping; Zhang, Hailing; Leng, Xigang G

    2014-01-01

    To develop a chitosan-based nonviral gene carrier capable of delivering genes specifically into hepatoma cells, a bifunctional peptide composed of the TAT (transactivator of transcription) peptide and luteinizing hormone-releasing hormone (LHRH) was conjugated with low molecular weight chitosan, resulting in a TAT-LHRH-chitosan conjugate (TLC). TLC/DNA nanoparticles (TLCDNPs) were characterized by agarose gel retardation, atomic force microscopy, and dynamic light scattering analysis. In vitro targeting specificity and transfection efficiency were analyzed with a GE IN Cell Analyzer 2000 High-Content Cellular Analysis System. The results demonstrated that TLC had stronger DNA condensing power than unmodified chitosan, and that TLCDNPs were of roughly round shape with average diameter of 70–85 nm and zeta potential of +30 mV and were relatively stable in solution. The in vitro study demonstrated TLC was highly selective for hepatoma cells and essentially nontoxic. PMID:24959076

  12. 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.

  13. Molecular model of the specificity pocket of the hepatitis C virus protease: implications for substrate recognition.

    OpenAIRE

    Pizzi, E; Tramontano, A; Tomei, L; La Monica, N; Failla, C; Sardana, M; Wood, T; De Francesco, R

    1994-01-01

    We have built a model of the specificity pocket of the protease of hepatitis C virus on the basis of the known structures of trypsin-like serine proteases and of the conservation pattern of the protease sequences among various hepatitis C strains. The model allowed us to predict that the substrate of this protease should have a cysteine residue in position P1. This hypothesis was subsequently proved by N-terminal sequencing of two products of the protease. The success of this "blind" test inc...

  14. Molecular and Functional Characterization of ssDNA Aptamers that Specifically Bind Leishmania infantum PABP.

    Directory of Open Access Journals (Sweden)

    Natalia Guerra-Pérez

    Full Text Available A poly (A-binding protein from Leishmania infantum (LiPABP has been recently cloned and characterized in our laboratory. Although this protein shows a very high homology with PABPs from other eukaryotic organisms including mammals and other parasites, exist divergences along the sequence that convert them in potential diagnostic markers and/or therapeutics targets. Aptamers are oligonucleotide ligands that are selected in vitro by their affinity and specificity for the target as a consequence of the particular tertiary structure that they are able to acquire depending on their sequence. Development of high-affinity molecules with the ability to recognize specifically Leishmania proteins is essential for the progress of this kind of study.We have selected a ssDNA aptamer population against a recombinant 6xHIS-LiPABP protein (rLiPABP that is able to recognize the target with a low Kd. Cloning, sequencing and in silico analysis of the aptamers obtained from the population yielded three aptamers (ApPABP#3, ApPABP#7 and ApPABP#11 that significantly bound to PABP with higher affinity than the naïve population. These aptamers were analyzed by ELONA and slot blot to establish affinity and specificity for rLiPABP. Results demonstrated that the three aptamers have high affinity and specificity for the target and that they are able to detect an endogenous LiPABP (eLiPABP protein amount corresponding to 2500 L. infantum promastigotes in a significant manner. The functional analysis of the aptamers also revealed that ApPABP#11 disrupts the binding of both Myc-LiPABP and eLiPABP to poly (A in vitro. On the other hand, these aptamers are able to bind and purify LiPABP from complex mixes.Results presented here demonstrate that aptamers represent new reagents for characterization of LiPABP and that they can affect LiPABP activity. At this respect, the use of these aptamers as therapeutic tool affecting the physiological role of PABP has to be analyzed.

  15. Molecular evolution and species-specific expansion of the NAP members in plants.

    Science.gov (United States)

    Fan, Kai; Shen, Hao; Bibi, Noreen; Li, Feng; Yuan, Shuna; Wang, Ming; Wang, Xuede

    2015-08-01

    The NAP (NAC-Like, Activated by AP3 /PI) subfamily is one of the important plant-specific transcription factors, and controls many vital biological processes in plants. In the current study, 197 NAP proteins were identified from 31 vascular plants, but no NAP members were found in eight non-vascular plants. All NAP proteins were phylogenetically classified into two groups (NAP I and NAP II), and the origin time of the NAP I group might be relatively later than that of the NAP II group. Furthermore, species-specific gene duplications, caused by segmental duplication events, resulted in the expansion of the NAP subfamily after species-divergence. Different groups have different expansion rates, and the NAP group preference was found during the expansion in plants. Moreover, the expansion of NAP proteins may be related to the gain and loss of introns. Besides, functional divergence was limited after the gene duplication. Abscisic acid (ABA) might play an important role in leaf senescence, which is regulated by NAP subfamily. These results could lay an important foundation for expansion and evolutionary analysis of NAP subfamily in plants. © 2015 Institute of Botany, Chinese Academy of Sciences.

  16. [Molecular identification of Mentha haplocalyx and Mentha spicata with specific primers multi-PCR system].

    Science.gov (United States)

    Cao, Liang; Qin, Shuang-shuang; Yuan, Yuan; Zhu, Xiao-qi

    2014-01-01

    To screen specific SNPs loci of Mentha haplocalyx and Mentha spicata,and then specific primers were designed to identify the two species and their mixture rapidly. PsbA-trnH sequences of Mentha haplocalyx and Mentha spicata were obtained by PCR product sequencing and downloading from GenBank. SNPs in the psbA-trnH sequences of Mentha haplocalyx and Mentha spicata were found by ClustulW program and Bioedit software. Primers for authentication of the two species were designed according to the SNP loci, and PCR reaction system was optimized to identify the original plants. Multi-PCR reaction system was constructed. The 181 bp identification band for Mentha haplocalyx or(and) 288 bp identification band for Mentha spicata could be produced by a single PCR reaction,which showed good identification ability to the two species. The multi-PCR reaction system can be applied to identify Mentha haplocalyx and Mentha spicata as well as their mixture.

  17. 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.

  18. 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.

  19. 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.

  20. A molecular switch sensor for detection of PRSS1 genotype based on site-specific DNA cleavage of restriction endonuclease.

    Science.gov (United States)

    Liu, Qicai; Gao, Feng; Weng, Shaohuang; Peng, Huaping; Lin, Liqing; Zhao, Chengfei; Lin, Xinhua

    2015-01-01

    PRSS1 mutations or polymorphism in the peripheral blood of patients can be used as susceptible molecular markers to pancreatic cancer. A sensor for selective electrochemical detection of PRSS1 genotypes was developed based on site-specific DNA cleavage of restriction endonuclease EcoRI. A mercapto-modified hairpin probe was immobilized on a gold electrode. The probe's neck can be cleaved by EcoRI in the absence of rs10273639 C/C of PRSS1 genotype, but it cannot be cleaved in the presence of T/T. The difference in quantity of electric charge was monitored by biosensors before and after enzymatic cleavage. Electrochemical signals are generated by differential pulse voltammetry interrogation of methylene blue (MB) that quantitatively binds to surface-confined hairpin probe via electrostatic interactions. The results suggested this method had a good specificity in distinguishing PRSS1 genotypes. There was a good linear relationship between the charge and the logarithmic function of PRSS1 rs10273639 T/T type DNA concentration (current=120.6303+8.8512log C, R=0.9942). The detection limit was estimated at 0.5 fM. The molecular switch sensor has several advantages, and it is possible to qualitatively, quantitatively, and noninvasively detect PRSS1 genotypes in the blood of patients with pancreatic cancer. © 2015 by the Association of Clinical Scientists, Inc.

  1. Dipeptidyl peptidases 8 and 9: specificity and molecular characterization compared with dipeptidyl peptidase IV

    DEFF Research Database (Denmark)

    Bjelke, Jais R; Christensen, Jesper; Nielsen, Per F

    2006-01-01

    Dipeptidyl peptidases 8 and 9 have been identified as gene members of the S9b family of dipeptidyl peptidases. In the present paper, we report the characterization of recombinant dipeptidyl peptidases 8 and 9 using the baculovirus expression system. We have found that only the full-length variants...... of the two proteins can be expressed as active peptidases, which are 882 and 892 amino acids in length for dipeptidyl peptidase 8 and 9 respectively. We show further that the purified proteins are active dimers and that they show similar Michaelis-Menten kinetics and substrate specificity. Both cleave...... the peptide hormones glucagon-like peptide-1, glucagon-like peptide-2, neuropeptide Y and peptide YY with marked kinetic differences compared with dipeptidyl peptidase IV. Inhibition of dipeptidyl peptidases IV, 8 and 9 using the well-known dipeptidyl peptidase IV inhibitor valine pyrrolidide resulted...

  2. Molecular model of the specificity pocket of the hepatitis C virus protease: implications for substrate recognition.

    Science.gov (United States)

    Pizzi, E; Tramontano, A; Tomei, L; La Monica, N; Failla, C; Sardana, M; Wood, T; De Francesco, R

    1994-02-01

    We have built a model of the specificity pocket of the protease of hepatitis C virus on the basis of the known structures of trypsin-like serine proteases and of the conservation pattern of the protease sequences among various hepatitis C strains. The model allowed us to predict that the substrate of this protease should have a cysteine residue in position P1. This hypothesis was subsequently proved by N-terminal sequencing of two products of the protease. The success of this "blind" test increases our confidence in the overall correctness of our proposed alignment of the enzyme sequence with those of other proteases of known structure and constitutes a first step in the construction of a complete model of the viral protease domain.

  3. 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

  4. Molecular cloning and characterization of oocyte-specific Pat1a in Rana rugosa frogs.

    Science.gov (United States)

    Nakamura, Yoriko; Iwasaki, Takehiro; Umei, Yosuke; Saotome, Kazuhiro; Nakajima, Yukiko; Kitahara, Shoichi; Uno, Yoshinobu; Matsuda, Yoichi; Oike, Akira; Kodama, Maho; Nakamura, Masahisa

    2015-10-01

    The Pat1 gene is expressed in the immature oocytes of Xenopus, and is reportedly involved in regulating the translation of maternal mRNAs required for oocyte-maturation. However, it is still unknown when Pat1a first appears in the differentiating ovary of amphibians. To address this issue, we isolated the full-length Pat1a cDNA from the frog Rana rugosa and examined its expression in the differentiating ovary of this frog. Among eight different tissues examined, the Pat1a mRNA was detectable in only the ovary. When frozen sections from the ovaries of tadpoles at various stages of development were immunostained for Vasa-a germ cell-specific protein-and Pat1a, Vasa-immunopositive signals were observed in all of the germ cells, whereas Pat1a signals were confined to the growing oocytes (50-200 μm in diameter), and absent from small germ cells (<50 μm in diameter). Forty days after testosterone injection into tadpoles to induce female-to-male sex-reversal, Pat1a-immunoreactive oocytes had disappeared completely from the sex-reversed gonad, but Vasa-positive small germ cells persisted. Thus, Pat1a would be a good marker for identifying the sexual status of the sex-reversing gonad in amphibians. In addition, fluorescence in situ hybridization analysis showed Pat1a to have an autosomal locus, suggesting that Pat1a transcription is probably regulated by a tissue-specific transcription factor in R. rugosa. © 2015 Wiley Periodicals, Inc.

  5. 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.

  6. Decentralized Single-beacon Acoustic Navigation: Combined Communication and Navigation for Underwater Vehicles

    Science.gov (United States)

    2010-06-01

    navigation beacons. When the modem is in synchronous navigation ( SNV ) mode, as described in [39], the modem’s clock can be synchronized to a PPS signal using...In SNV mode, all transmitted messages are initiated by the modem within ± 10 µs of the rising edge of the PPS signal [39]. 3.3.2 PPSBoard The PPSBoard...reference for use subsea that can be synchronized to a GPS timing signal. In addition to supplying a PPS signal to the Micro- Modem to enable its SNV

  7. Optical Measurement of a Compressible Shear Layer Using a Laser-Induced Air Breakdown Beacon (Preprint)

    Science.gov (United States)

    2009-12-01

    Comrol Unil’ersity of NOire Dame. Notre Dame. IN. 46556 David Goorskei, Matthew R. Whiteley4 MZA Associates Corporation, Dayton. OH. 45459 David...Cavalieri s, and Eric J. Jumper6 Cenler for Flow Physics and Comrol University of NOire Dame. Noire Dame. IN. 46556 The aero-optic aberrations due to...wave fronts. th3t limit the ability of the beacon system to detect aero-optic aberrations that ha\\’e an amplitude below the noi5e level. Figure 3

  8. A mobile indoor positioning system based on iBeacon technology.

    Science.gov (United States)

    Lin, Xin-Yu; Ho, Te-Wei; Fang, Cheng-Chung; Yen, Zui-Shen; Yang, Bey-Jing; Lai, Feipei

    2015-01-01

    To increase the efficiency in the emergency room, the goal of this research is to implement a mobile-based indoor positioning system using mobile applications (APP) with the iBeacon solution based on the Bluetooth Low Energy (BLE) technology. We use the Received Signal Strength (RSS) based localization method to estimate the patients' locations. Our positioning algorithm achieves 97.22% (95% Confidence Interval = 95.90% - 98.55%) accuracy of classification. As the result, our mechanism is reliable enough to satisfy the need for medical staff to track the locations of their patients.

  9. 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

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

    Directory of Open Access Journals (Sweden)

    RUSTAMAJI RUSTAMAJI

    2016-02-01

    Full Text Available 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, detektor selubung, penguat audio, dan loud speaker. Frekuensi sinyal 37,5 kHz ± 1 kHz yang dikirim oleh pingers transmitter akan diterima oleh pingers receiver, dimana tahap pertama melewati rangkaian Band Pass Filter (BPF selanjutnya sinyal akan dideteksi oleh detektor selubung untuk mengambil kembali sinyal informasi yang berupa sinyal pulsa dengan lebar pulsa 10 milidetik dan interval 1 detik sebagai sinyal pingers yang nantinya mampu didengar oleh telinga manusia. Berdasarkan perancangan yang telah dibuat, output sinyal yang dihasilkan oleh prototipe pingers receiver tersebut memiliki lebar pulsa 14 milidetik dengan interval 1 detik. Kata kunci: pingers receiver, band pass filter (BPF, detektor selubung, loud speaker. ABSTRACT 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

  11. 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

  12. 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

  13. Molecular phylogeny of the mycorrhizal desert truffles (Terfezia and Tirmania), host specificity and edaphic tolerance.

    Science.gov (United States)

    Díez, Jesús; Manjón, José Luis; Martin, Francis

    2002-01-01

    Terfezia and Tirmania, so called desert truffles, are mycorrhizal fungi mostly endemic to arid and semi-arid areas of the Mediterranean Region, where they are associated with Helianthemum species. The aim of this work was to study the phylogenetic relationships in these pezizalean hypogeous fungi. The restriction fragment length polymorphism (RFLP) and DNA sequences of internal transcribed spacers (ITS) of the nuclear rDNA were studied for several morphological species, Terfezia arenaria, T. boudieri, T. claveryi, T. leptoderma, T. terfezioides (=Mattirolomyces terfezioides), Tirmania nivea and T. pinoyi. The sequences were analyzed with distance and parsimony methods. Phylogenetic analyses indicated a close genetic relationship between Tirmania and Terfezia. They may have arisen from a single evolutionary lineage of pezizalean fungi that developed the hypogeous habit as an adaptation to heat and drought in Mediterranean ecosystems. This analysis also supports the re-establishment of the genus Mattirolomyces. The genera Tirmania and Terfezia were monophyletic, and morphological species corresponded to phylogenetic species. The Tirmania clade comprises desert truffles with smooth spores and amyloid asci, which were found in deserts. The Terfezia clade grouped species found in semi-arid habitats having ornamented and spherical spores. These species are adapted to exploit different types of soil (either acid or basic soils) in association with specific hosts (either basophilous or acidophilous species). Although other factors might also play a role, host specialization and edaphic tolerances (fungus and/or host tolerances) might be the key in the species diversity of these genera.

  14. Cyanobacteria as source of marine bioactive compounds: Molecular specific detection based on Δ9 desaturase gene.

    Science.gov (United States)

    Ben Amor, Faten; Barkallah, Mohamed; Elleuch, Fatma; Karkouch, Nesrine; Dammak, Mouna; Baréa, Bruno; Villeneuve, Pierre; Abdelkafi, Slim; Fendri, Imen

    2017-12-01

    The blue-green microalga, Arthrospira sp., isolated from the sea of Kssour Essef in Mahdia (Tunisia), was purified and then identified both morphologically and genetically based on 16S rRNA gene sequence. Following physicochemical analysis, the prokaryotic microalga tested represented a competitive source of pigments and showed a considerable rate in protein (64%) which was confirmed by FTIR measurement. The lipid content (4%) was quantified by the gravimetric method and the intracellular lipid bodies were detected with the Nile red staining. Using gas chromatography coupled with flame ionization detector, the fatty acid profile revealed the presence of 27.4% and 32.88% of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), respectively. Given the richness of the isolated microalga in unsaturated fatty acids, we have developed a SYBR Green real time PCR method for the specific identification of Arthrospira sp. Δ9 desaturase gene. This current method will be of great value for carrying out high-throughput studies like cloning, heterologous expression and structure-function relationship analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Anti-metatype peptides, a molecular tool with high sensitivity and specificity to monitor small ligands.

    Science.gov (United States)

    Inaba, Junko; Nakamura, Shugo; Shimizu, Kentaro; Asami, Tadao; Suzuki, Yoshihito

    2009-05-01

    To develop a new immunological detection system of gibberellins (GAs), a class of phytohormones, peptides that interact with an antibody against GA4 in a GA4-dependent manner, were screened from phage display random peptide libraries. The biopanning procedure yielded peptides designated as anti-metatype peptides (AM-peps), which showed specific binding to the complex of the antibody and its ligand GA4; that is, the antibody could not be replaced with the other anti-GA4 antibody, and GA4 could not be replaced with GA1, another ligand of the antibody. Together with computational analyses such as analysis of structural propensity of the AM-peps and docking simulation of the AM-peps and the 8/E9-GA4 complex, it was suggested that AM-peps formed a helix in their central region and interacted with a part of the 8/E9-GA4 complex located in close proximity to the GA4 molecule. Based on the property of AM-peps to make a ternary complex with antibody and its ligand, a noncompetitive enzyme-linked immunosorbent assay (ELISA) system corresponding to sandwich ELISA was developed to detect GA4. GA4 as low as 30 pg, which could not be achieved by conventional competitive ELISA, could be detected by the new system, demonstrating the feasibility of this system.

  16. Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding

    Energy Technology Data Exchange (ETDEWEB)

    Aller, Stephen G.; Yu, Jodie; Ward, Andrew; Weng, Yue; Chittaboina, Srinivas; Zhuo, Rupeng; Harrell, Patina M.; Trinh, Yenphuong T.; Zhang, Qinghai; Urbatsch, Ina L.; Chang, Geoffrey; (Scripps); (TTU)

    2009-04-22

    P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of -6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding.

  17. Species-specific markers provide molecular genetic evidence for natural introgression of bullhead catfishes in Hungary

    Science.gov (United States)

    Béres, Beatrix; Kánainé Sipos, Dóra; Müller, Tamás; Staszny, Ádám; Farkas, Milán; Bakos, Katalin; Urbányi, Béla

    2017-01-01

    Since three bullhead catfish species were introduced to Europe in the late 19th century, they have spread to most European countries. In Hungary, the brown bullhead (Ameiurus nebulosus) was more widespread in the 1970s–1980s, but the black bullhead (Ameiurus melas) has gradually supplanted since their second introduction in 1980. The introgressive hybridization of the two species has been presumed based on morphological examinations, but it has not previously been supported by genetic evidence. In this study, 11 different Hungarian habitats were screened with a new species-specific nuclear genetic, duplex PCR based, marker system to distinguish the introduced catfish species, Ameiurus nebulosus, Ameiurus melas, and Ameiurus natalis, as well as the hybrids of the first two. More than 460 specimens were analyzed using the above markers and additional mitochondrial sequence analyses were also conducted on >25% of the individuals from each habitat sampled. The results showed that only 7.9% of the specimens from two habitats belonged to Ameiurus nebulosus, and 92.1% were classified as Ameiurus melas of all habitats, whereas the presence of Ameiurus natalis was not detected. Two specimens (>0.4%) showed the presence of both nuclear genomes and they were identified as hybrids of Ameiurus melas and Ameiurus nebulosus. An additional two individuals showed contradicting results from the nuclear and mitochondrial assays as a sign of a possible footprint of introgressive hybridization that might have happened two or more generations before. Surprisingly, the level of hybridization was much smaller than expected based on the analyses of the North American continent’s indigenous stock from the hybrid zones. This phenomenon has been observed in several invasive fish species and it is regarded as an added level of complexity in the management of their rapid adaptation. PMID:28265489

  18. In silico evidence for the species-specific conservation of mosquito retroposons: implications as a molecular biomarker

    Directory of Open Access Journals (Sweden)

    Byarugaba Wilson

    2009-07-01

    molecular biomarkers for mosquitoes, and as RST-specific monoclonal antibody (MAb-DDT immunoconjugates to enhance targeted toxicity. Conclusion We offer evidence to support the species-specific conservation of mosquito retroposons among lower taxa. Our findings suggest that retroposons may therefore constitute a unique biomarker for mosquito species that may be exploited in molecular entomology. Mosquito RST-specific MAbs may possibly permit synthesis of DDT immunoconjugates that could be used to achieve species-tailored toxicity.

  19. Distinct Subfamilies of Odorant Binding Proteins in Locust (Orthoptera, Acrididae: Molecular Evolution, Structural Variation, and Sensilla-Specific Expression

    Directory of Open Access Journals (Sweden)

    Xingcong Jiang

    2017-09-01

    Full Text Available Odorant binding proteins (OBPs play an important role in insect olfaction, facilitating transportation of odorant molecules in the sensillum lymph. While most of the researches are concentrated on Lepidopteran and Dipteran species, our knowledge about Orthopteran species is still very limited. In this study, we have investigated OBPs of the desert locust Schistocerca gregaria, a representative Orthopteran species. We have identified 14 transcripts from a S. gregaria antennal transcriptome encoding SgreOBPs, and recapitulated the phylogenetic relationship of SgreOBPs together with OBPs from three other locust species. Two conserved subfamilies of classic OBPs have been identified, named I-A and II-A, exhibiting both common and subfamily-specific amino acid motifs. Distinct evolutionary features were observed for subfamily I-A and II-A OBPs. Surface topology and interior cavity were elucidated for OBP members from the two subfamilies. Antennal topographic expression revealed distinct sensilla- and cellular- specific expression patterns for SgreOBPs from subfamily I-A and II-A. These findings give first insight into the repertoire of locust OBPs with respect to their molecular and evolutionary features as well as their expression in the antenna, which may serve as an initial step to unravel specific roles of distinct OBP subfamilies in locust olfaction.

  20. 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.

  1. Molecular profiling of 6,892 colorectal cancer samples suggests different possible treatment options specific to metastatic sites.

    Science.gov (United States)

    El-Deiry, Wafik S; Vijayvergia, Namrata; Xiu, Joanne; Scicchitano, Angelique; Lim, Bora; Yee, Nelson S; Harvey, Harold A; Gatalica, Zoran; Reddy, Sandeep

    2015-01-01

    Metastatic colorectal cancer (mCRC) carries a poor prognosis with an overall 5-year survival of 13.1%. Therapies guided by tumor profiling have suggested benefit in advanced cancer. We used a multiplatform molecular profiling (MP) approach to identify key molecular changes that may provide therapeutic options not typically considered in mCRC. We evaluated 6892 mCRC referred to Caris Life Sciences by MP including sequencing (Sanger/NGS), immunohistochemistry (IHC) and in-situ hybridization (ISH). mCRC metastases to liver, brain, ovary or lung (n = 1507) showed differential expression of markers including high protein expression of TOPO1 (52%) and/or low RRM1 (57%), TS (71%) and MGMT (39%), suggesting possible benefit from irinotecan, gemcitabine, 5FU/capecitabine and temozolomide, respectively. Lung metastases harbored a higher Her2 protein expression than the primary colon tumors (4% vs. 1.8%, p = 0.028). Brain and lung metastases had higher KRAS mutations than other sites (65% vs 59% vs 47%, respectively, p = 0.07, cancer versus colon cancer (10% and 3.3%, respectively). MP of 6892 CRCs identified significant differences between primary and metastatic sites and among BRAF/KRAS sub-types. Our findings are hypothesis generating and need to be examined in prospective studies. Specific therapies may be considered for different actionable targets in mCRC as revealed by MP.

  2. 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.

  3. 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.

  4. Molecularly imprinted polymer based on MWCNT-QDs as fluorescent biomimetic sensor for specific recognition of target protein

    International Nuclear Information System (INIS)

    Ding, Zhaoqiang; Annie Bligh, S.W.; Tao, Lei; Quan, Jing; Nie, Huali; Zhu, Limin; Gong, Xiao

    2015-01-01

    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 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 −7 –35.0 × 10 −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

  5. 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...... in the alpha-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the beta-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel....

  6. Cluster Study of Anion Specificity in Solutions: From Molecular-Like Species to Nano-Sized Droplets

    Science.gov (United States)

    Wang, Xue-Bin

    2015-03-01

    In this talk, I will present our cluster approach using size-selected, low-temperature photoelectron spectroscopy and ab initio calculations to study a variety of complex anion solvation across the Hofmeister series. Pronounced anion specific effects and rich solute-solvent, solvent-solvent interactions have been discovered en-route to solvation evolution from molecular-like species to nano-sized droplets. We found significant solute anisotropy effects in preferably selecting solvent network to align solute permanent dipole with the solvent electric field in hydrated neutral clusters. Thermodynamic advantage of organic acids in facilitating formation of bisulfate ion clusters, an important issue related to atmospheric chemistry and aerosol particle formation will also be discussed. This work was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences.

  7. 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.

  8. 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.

  9. Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles.

    Science.gov (United States)

    Förster, Yvonne; Schmidt, Johannes R; Wissenbach, Dirk K; Pfeiffer, Susanne E M; Baumann, Sven; Hofbauer, Lorenz C; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

    2016-01-01

    Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis.

  10. Systematic dissection and trajectory-scanning mutagenesis of the molecular interface that ensures specificity of two-component signaling pathways.

    Directory of Open Access Journals (Sweden)

    Emily J Capra

    2010-11-01

    Full Text Available Two-component signal transduction systems enable bacteria to sense and respond to a wide range of environmental stimuli. Sensor histidine kinases transmit signals to their cognate response regulators via phosphorylation. The faithful transmission of information through two-component pathways and the avoidance of unwanted cross-talk require exquisite specificity of histidine kinase-response regulator interactions to ensure that cells mount the appropriate response to external signals. To identify putative specificity-determining residues, we have analyzed amino acid coevolution in two-component proteins and identified a set of residues that can be used to rationally rewire a model signaling pathway, EnvZ-OmpR. To explore how a relatively small set of residues can dictate partner selectivity, we combined alanine-scanning mutagenesis with an approach we call trajectory-scanning mutagenesis, in which all mutational intermediates between the specificity residues of EnvZ and another kinase, RstB, were systematically examined for phosphotransfer specificity. The same approach was used for the response regulators OmpR and RstA. Collectively, the results begin to reveal the molecular mechanism by which a small set of amino acids enables an individual kinase to discriminate amongst a large set of highly-related response regulators and vice versa. Our results also suggest that the mutational trajectories taken by two-component signaling proteins following gene or pathway duplication may be constrained and subject to differential selective pressures. Only some trajectories allow both the maintenance of phosphotransfer and the avoidance of unwanted cross-talk.

  11. A high molecular weight melanoma-associated antigen-specific chimeric antigen receptor redirects lymphocytes to target human melanomas.

    Science.gov (United States)

    Burns, William R; Zhao, Yangbing; Frankel, Timothy L; Hinrichs, Christian S; Zheng, Zhili; Xu, Hui; Feldman, Steven A; Ferrone, Soldano; Rosenberg, Steven A; Morgan, Richard A

    2010-04-15

    Immunotherapy, particularly the adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL), is a very promising therapy for metastatic melanoma. Some patients unable to receive TIL have been successfully treated with autologous peripheral blood lymphocytes (PBL), genetically modified to express human leukocyte antigen (HLA) class I antigen-restricted, melanoma antigen-reactive T-cell receptors; however, substantial numbers of patients remain ineligible due to the lack of expression of the restricting HLA class I allele. We sought to overcome this limitation by designing a non-MHC-restricted, chimeric antigen receptor (CAR) targeting the high molecular weight melanoma-associated antigen (HMW-MAA), which is highly expressed on more than 90% of human melanomas but has a restricted distribution in normal tissues. HMW-MAA-specific CARs containing an antigen recognition domain based on variations of the HMW-MAA-specific monoclonal antibody 225.28S and a T-cell activation domain based on combinations of CD28, 4-1BB, and CD3zeta activation motifs were constructed within a retroviral vector to allow stable gene transfer into cells and their progeny. Following optimization of the HMW-MAA-specific CAR for expression and function in human PBL, these gene-modified T cells secreted cytokines, were cytolytic, and proliferated in response to HMW-MAA-expressing cell lines. Furthermore, the receptor functioned in both CD4(+) and CD8(+) cells, was non-MHC restricted, and reacted against explanted human melanomas. To evaluate this HMW-MAA-specific CAR in patients with metastatic melanoma, we developed a clinical-grade retroviral packaging line. This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies. (c)2010 AACR.

  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. Conserved Molecular Mechanism of TyrA Dehydrogenase Substrate Specificity Underlying Alternative Tyrosine Biosynthetic Pathways in Plants and Microbes

    Directory of Open Access Journals (Sweden)

    Craig A. Schenck

    2017-11-01

    Full Text Available L-Tyrosine (Tyr is an aromatic amino acid synthesized de novo in plants and microbes. In animals, Tyr must be obtained through their diet or synthesized from L-phenylalanine. In addition to protein synthesis, Tyr serves as the precursor of neurotransmitters (e.g., dopamine and epinephrine in animals and of numerous plant natural products, which serve essential functions in both plants and humans (e.g., vitamin E and morphine. Tyr is synthesized via two alternative routes mediated by a TyrA family enzyme, prephenate, or arogenate dehydrogenase (PDH/TyrAp or ADH/TyrAa, typically found in microbes and plants, respectively. Although ADH activity is also found in some bacteria, the origin of arogenate-specific TyrAa enzymes is unknown. We recently identified an acidic Asp222 residue that confers ADH activity in plant TyrAs. In this study, structure-guided phylogenetic analyses identified bacterial homologs, closely-related to plant TyrAs, that also have an acidic 222 residue and ADH activity. A more distant archaeon TyrA that preferred PDH activity had a non-acidic Gln, whose substitution to Glu introduced ADH activity. These results indicate that the conserved molecular mechanism operated during the evolution of arogenate-specific TyrAa in both plants and microbes.

  15. 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

  16. Measurements of Tilt and Focus for Sodium Beacon Adaptive Optics on the Starfire 3.5 Meter Telescope

    Science.gov (United States)

    2010-09-01

    beacon and natural guide star operation. This approach, and a more complicated approach, are described in detail by Link and Foucault [3]. They show these...Astronomical Telescopes and Instrumentation Conference, Glasgow, Scotland, 21–25 June 2004. 3. Link D. and Foucault B., "Investigation of focus control

  17. Impact of IEEE 1609.4 channel switching on the IEEE 802.11p beaconing performance

    NARCIS (Netherlands)

    van Eenennaam, Martijn; van de Venis, Anne; Karagiannis, Georgios

    2012-01-01

    The IEEE 802.11p Wireless Access in Vehicular Environment (WAVE) protocol can only transmit packets on one channel. To support multi-channel operations, channel switching procedures have been proposed in IEEE 1609.4. This paper provides an analysis of the beaconing performance of IEEE 802.11p when

  18. 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...

  19. Sporadic early-onset colorectal cancer is a specific sub-type of cancer: a morphological, molecular and genetics study.

    Directory of Open Access Journals (Sweden)

    Sylvain Kirzin

    Full Text Available Sporadic early onset colorectal carcinoma (EOCRC which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45-60 years were excluded to help define "young" and "old" groups. Thirty-nine cases of sporadic EOCRC (patients ≤ 45 years with microsatellite stable tumors were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p = 0.013. Genetic studies also showed the absence of BRAF mutations (p = 0.022 and the methylator phenotype (p = 0.005 in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p = 0.01. This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways including the

  20. 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

  1. Widespread, Juvenile Alteration of the Ferrar Dolerite in Beacon Valley, Antarctica

    Science.gov (United States)

    Salvatore, M. R.; Mustard, J. F.; Head, J. W.; Cooper, R. F.; Marchant, D. R.

    2011-12-01

    The hyper-arid and hypo-thermal conditions that are pervasive throughout the McMurdo Dry Valleys (MDV) result in slow, immature chemical alteration that is often shadowed by physical erosion and mass wasting processes. Beacon Valley is an exception to this model in that its surface is extremely stable and has been for at least several million years. This stability allows for chemical alteration to progress in the absence of extensive physical erosion. We have collected fourteen Ferrar Dolerite samples from the floor of central Beacon Valley and have analyzed them to assess the range and extent of chemical and mineralogical variations between the unaltered interiors and their altered surfaces. Surface rocks from Beacon Valley, Antarctica, exhibit a distinct red/brown weathering/alteration rind relative to their dark grey interiors as a result of in situ chemical alteration. The rind is readily visible in broken and cut rocks and is typically 0.5-10 mm in thickness. It shows a gradational transition to the unaltered interiors. Reflectance and emission spectroscopy both show distinct disparity between unaltered rock interiors and their corresponding surfaces related to the alteration rind. Interestingly, spectroscopic signatures of primary minerals are clearly present showing that the alteration process does not completely mask the primary rock constituents from remote sensing. Visible-near infrared spectra show distinct ferric absorptions between 0.3 and 1.0 μm indicating a significant increase in ferric iron. Emission spectroscopy shows distinct absorptions related to poorly crystalline alteration products suggesting a breakdown in mineral structure in the optically active zone. EPMA analyses and BSE imagery of the dolerite surfaces and the transition between altered and unaltered regions, however, do not show any obvious chemical or mineralogical variability. This result is supported by flux fusion and ICP-AES analyses that show no substantial chemical variations

  2. Detection of substrate binding of a collagen-specific molecular chaperone HSP47 in solution using fluorescence correlation spectroscopy.

    Science.gov (United States)

    Kitamura, Akira; Ishida, Yoshihito; Kubota, Hiroshi; Pack, Chan-Gi; Homma, Takayuki; Ito, Shinya; Araki, Kazutaka; Kinjo, Masataka; Nagata, Kazuhiro

    2018-02-26

    Heat shock protein 47 kDa (HSP47), an ER-resident and collagen-specific molecular chaperone, recognizes collagenous hydrophobic amino acid sequences (Gly-Pro-Hyp) and assists in secretion of correctly folded collagen. Elevated collagen production is correlated with HSP47 expression in various diseases, including fibrosis and keloid. HSP47 knockdown ameliorates liver fibrosis by inhibiting collagen secretion, and inhibition of the interaction of HSP47 with procollagen also prevents collagen secretion. Therefore, a high-throughput system for screening of drugs capable of inhibiting the interaction between HSP47 and collagen would aid the development of novel therapies for fibrotic diseases. In this study, we established a straightforward method for rapidly and quantitatively measuring the interaction between HSP47 and collagen in solution using fluorescence correlation spectroscopy (FCS). The diffusion rate of HSP47 labeled with Alexa Fluor 488 (HSP47-AF), a green fluorescent dye, decreased upon addition of type I or III collagen, whereas that of dye-labeled protein disulfide isomerase (PDI) or bovine serum albumin (BSA) did not, indicating that specific binding of HSP47 to collagen could be detected using FCS. Using this method, we calculated the dissociation constant of the interaction between HSP47 and collagen. The binding ratio between HSP47-AF and collagen did not change in the presence of sodium chloride, confirming that the interaction was hydrophobic in nature. In addition, we observed dissociation of collagen from HSP47 at low pH and re-association after recovery to neutral pH. These observations indicate that this system is appropriate for detecting the interaction between HSP47 and collagen, and could be applied to high-throughput screening for drugs capable of suppressing and/or curing fibrosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. 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

  4. Gene-expression Analysis Identifies Specific Patterns of Dysregulated Molecular Pathways and Genetic Subgroups of Human Hepatocellular Carcinoma.

    Science.gov (United States)

    Hass, Holger G; Vogel, Ulrich; Scheurlen, Michael; Jobst, Jürgen

    2016-10-01

    Hepatocellular carcinoma comprises of a group of heterogeneous tumors of different etiologies. The multistep process of liver carcinogenesis involves various genetic and phenotypic alterations. The molecular pathways and driver mutations involved are still under investigation. DNA micorarray technology was used to identify differentially expressed genes between human hepatocarcinoma and non-tumorous liver tissues to establish a unique specific gene-expression profile independent of the underlying liver disease. The validity of this global gene-expression profile was tested for its robustness against biopsies from other liver entities (cirrhotic and non-cirrhotic liver) by diagnosing HCC in blinded samples. Most of the consistently and strongly overexpressed genes were related to cell-cycle regulation and DNA replication [27 genes, e.g. cyclin B1, karyopherin alpha 2 (KPNA2), cyclin-dependent kinase 2 (CDC2)], G-protein depending signaling [e.g. Rac GTPase activating protein 1 (RACGAP1), Rab GTPase YPT1 homolog (RAB1), and ADP-ribosylation factor-like 2 (ARL2)] and extracellular matrix re-modelling or cytoskeleton structure [22 genes, e.g. serine proteinase inhibitor 1 kazal-type (SPINK1), osteopontin (OPN), secreted protein acidic and rich in cysteine (SPARC), collagen type 1 alpha2 (COL1A2), integrin alpha6 (ITGA6), and metalloproteinase 12 (MMP12)]. Furthermore, significantly differentially expressed genes (e.g. calcium-binding proteins, G-proteins, oncofetal proteins) in relation to tumor differentiation were detected using gene-expression analysis. It is suggested that these significantly dysregulated genes are highly specific and potentially utilizable as prognostic markers and may lead to a better understanding of human hepatocarcinogenesis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Instrumentation of Molecular Imaging on Site-Specific Targeting Fluorescent Peptide for Early Detection of Breast Cancer

    Science.gov (United States)

    Yu, Ping; Ma, Lixin

    2012-02-01

    In this work we developed two biomedical imaging techniques for early detection of breast cancer. Both image modalities provide molecular imaging capability to probe site-specific targeting dyes. The first technique, heterodyne CCD fluorescence mediated tomography, is a non-invasive biomedical imaging that uses fluorescent photons from the targeted dye on the tumor cells inside human breast tissue. The technique detects a large volume of tissue (20 cm) with a moderate resolution (1 mm) and provides the high sensitivity. The second technique, dual-band spectral-domain optical coherence tomography, is a high-resolution tissue imaging modality. It uses a low coherence interferometer to detect coherent photons hidden in the incoherent background. Due to the coherence detection, a high resolution (20 microns) is possible. We have finished prototype imaging systems for the development of both image modalities and performed imaging experiments on tumor tissues. The spectroscopic/tomographic images show contrasts of dense tumor tissues and tumor necrotic regions. In order to correlate the findings from our results, a diffusion-weighted magnetic resonance imaging (MRI) of the tumors was performed using a small animal 7-Telsa MRI and demonstrated excellent agreement.

  6. Molecularly organic/inorganic hybrid hollow mesoporous organosilica nanocapsules with tumor-specific biodegradability and enhanced chemotherapeutic functionality.

    Science.gov (United States)

    Huang, Ping; Chen, Yu; Lin, Han; Yu, Luodan; Zhang, Linlin; Wang, Liying; Zhu, Yufang; Shi, Jianlin

    2017-05-01

    Based on the intrinsic features of high stability and unique multifunctionality, inorganic nanoparticles have shown remarkable potentials in combating cancer, but their biodegradability and biocompatibility are still under debate. As a paradigm, this work successfully demonstrates that framework organic-inorganic hybridization can endow the inorganic mesoporous silica nanocarriers with unique tumor-sensitive biodegradability and high biocompatibility. Based on a "chemical homology" mechanism, molecularly organic-inorganic hybridized hollow mesoporous organosilica nanocapsules (HMONs) with high dispersity and sub-50 nm particle dimension were constructed in mass production. A physiologically active disulfide bond (SS) was directly incorporated into the silica framework, which could break up upon contacting the reducing microenvironment of tumor tissue and biodegrade accordingly. Such a tumor-specific biodegradability is also responsible for the tumor-responsive drug releasing by the fast biodegradation and disintegration of the framework. The ultrasmall particle size of HMONs guarantees their high accumulation into tumor tissue, thus causing the high chemotherapeutic outcome. This research provides a paradigm that framework organic-inorganic hybridization can endow the inorganic nanocarrier with unique biological effects suitable for biomedical application, benefiting the development of novel nanosystems with the unique bio-functionality and performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. In vitro Study of SPIONs-C595 as Molecular Imaging Probe for Specific Breast Cancer (MCF-7) Cells Detection

    Science.gov (United States)

    Moradi Khaniabadi, Pegah; Shahbazi-Gahrouei, Daryoush; Malik Shah Abdul Majid, Amin; Suhaimi Jaafar, Mohammad; Moradi Khaniabadi, Bita; Shahbazi-Gahrouei, Saghar

    2017-11-01

    Magnetic resonance imaging (MRI) plays an essential role in molecular imaging by delivering the contrast agent into targeted cancer cells. The aim of this study was to evaluate the C595 monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles (SPIONs-C595) for the detection of breast cancer cell (MCF-7). The conjugation of monoclonal antibody and nanoparticles was confirmed using X-ray diffraction, transmission electron microscopy, and photon correlation spectroscopy. The selectivity of the nanoprobe for breast cancer cells (MCF-7) was obtained by Prussian blue, atomic emission spectroscopy, and MRI relaxometry. The in vitro MRI showed that T2 relaxation time will be reduced 76% when using T2-weighed magnetic resonance images compared to the control group (untreated cells) at the dose of 200 μg Fe/ml, as the optimum dose. In addition, the results showed the high uptake of nanoprobe into MCF-7 cancer cells. The SPIONs-C595 nanoprobe has potential for the detection of specific breast cancer.

  8. 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.

  9. 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.

  10. Biogeography, Host Specificity, and Molecular Phylogeny of the Basidiomycetous Yeast Phaffia rhodozyma and Its Sexual Form, Xanthophyllomyces dendrorhous▿

    Science.gov (United States)

    Libkind, Diego; Ruffini, Alejandra; van Broock, Maria; Alves, Leonor; Sampaio, José Paulo

    2007-01-01

    Phaffia rhodozyma (sexual form, Xanthophyllomyces dendrorhous) is a basidiomycetous yeast that has been found in tree exudates in the Northern Hemisphere at high altitudes and latitudes. This yeast produces astaxanthin, a carotenoid pigment with biotechnological importance because it is used in aquaculture for fish pigmentation. We isolated X. dendrorhous from the Southern Hemisphere (Patagonia, Argentina), where it was associated with fruiting bodies of Cyttaria hariotii, an ascomycetous parasite of Nothofagus trees. We compared internal transcribed spacer (ITS)-based phylogenies of P. rhodozyma and its tree host (Betulaceae, Corneaceae, Fagaceae, and Nothofagaceae) and found them to be generally concordant, suggesting that different yeast lineages colonize different trees and providing an explanation for the phylogenetic distance observed between the type strains of P. rhodozyma and X. dendrorhous. We hypothesize that the association of Xanthophyllomyces with Cyttaria derives from a previous association of the yeast with Nothofagus, and the sister relationship between Nothofagaceae and Betulaceae plus Fagaceae correlates with the phylogeny of X. dendrorhous strains originating from these three plant families. The two most basal strains of X. dendrorhous are those isolated from Cornus, an ancestral genus in the phylogenetic analysis of the host trees. Thus, we question previous conclusions that P. rhodozyma and X. dendrorhous represent different species since the polymorphisms detected in the ITS and intergenic spacer sequences can be attributed to intraspecific variation associated with host specificity. Our study provides a deeper understanding of Phaffia biogeography, ecology, and molecular phylogeny. Such knowledge is essential for the comprehension of many aspects of the biology of this organism and will facilitate the study of astaxanthin production within an evolutionary and ecological framework. PMID:17189439

  11. Biogeography, host specificity, and molecular phylogeny of the basidiomycetous yeast Phaffia rhodozyma and its sexual form, Xanthophyllomyces dendrorhous.

    Science.gov (United States)

    Libkind, Diego; Ruffini, Alejandra; van Broock, Maria; Alves, Leonor; Sampaio, José Paulo

    2007-02-01

    Phaffia rhodozyma (sexual form, Xanthophyllomyces dendrorhous) is a basidiomycetous yeast that has been found in tree exudates in the Northern Hemisphere at high altitudes and latitudes. This yeast produces astaxanthin, a carotenoid pigment with biotechnological importance because it is used in aquaculture for fish pigmentation. We isolated X. dendrorhous from the Southern Hemisphere (Patagonia, Argentina), where it was associated with fruiting bodies of Cyttaria hariotii, an ascomycetous parasite of Nothofagus trees. We compared internal transcribed spacer (ITS)-based phylogenies of P. rhodozyma and its tree host (Betulaceae, Corneaceae, Fagaceae, and Nothofagaceae) and found them to be generally concordant, suggesting that different yeast lineages colonize different trees and providing an explanation for the phylogenetic distance observed between the type strains of P. rhodozyma and X. dendrorhous. We hypothesize that the association of Xanthophyllomyces with Cyttaria derives from a previous association of the yeast with Nothofagus, and the sister relationship between Nothofagaceae and Betulaceae plus Fagaceae correlates with the phylogeny of X. dendrorhous strains originating from these three plant families. The two most basal strains of X. dendrorhous are those isolated from Cornus, an ancestral genus in the phylogenetic analysis of the host trees. Thus, we question previous conclusions that P. rhodozyma and X. dendrorhous represent different species since the polymorphisms detected in the ITS and intergenic spacer sequences can be attributed to intraspecific variation associated with host specificity. Our study provides a deeper understanding of Phaffia biogeography, ecology, and molecular phylogeny. Such knowledge is essential for the comprehension of many aspects of the biology of this organism and will facilitate the study of astaxanthin production within an evolutionary and ecological framework.

  12. Molecularly imprinted polymers prepared using protein-conjugated cleavable monomers followed by site-specific post-imprinting introduction of fluorescent reporter molecules.

    Science.gov (United States)

    Suga, Yusuke; Sunayama, Hirobumi; Ooya, Tooru; Takeuchi, Toshifumi

    2013-10-04

    Molecularly imprinted polymers were prepared using a protein-conjugated disulfide cleavable monomer. After removing the protein by disulfide reduction, a thiol-reactive fluorophore was introduced into the thiol residue located only inside the imprinted cavity, resulting in specific transduction of the binding events into fluorescence spectral change.

  13. 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.

  14. Aspect Determination Using a Beacon with a Spiral Wave Front: Modeling and Performance Analysis in Operational Environments

    Science.gov (United States)

    2014-12-19

    the NSWC PCD Acoustic Test Facility in FY10 and at the Navy’s Dodge Pond facility operated by the Naval Undersea Warfare Center–Division Newport...minima shown in Fig. 15. The choice of minima will depend on the signal processing requirements of the beacon receiver, either mini - mizing the phase...surface it is also moving over these rods, leading to variation in amplitude. To mini - mize these effects, a sliding average is applied to the data

  15. 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.

  16. [Incomplete congruence between morphobiological characters and sex-specific molecular markers in Pacific salmons: 1. Analysis of discrepancy in five species of the genus Oncorhynchus].

    Science.gov (United States)

    Brykov, Vl A; Kukhlevskiĭ, A D; Podlesnykh, A V

    2010-07-01

    The congruence between molecular markers, identifying the presence of the Y chromosome, and secondary sexual characters was examined in Asian populations of five Pacific salmon species: pink salmon (Oncorhynchus gorbuscha), chum salmon (O. keta), sockeye salmon (O. nerka), chinook salmon (O. tschawytsha), and sima (O. masou). It was demonstrated that in all species examined, the presence or absence of sex-specific molecular markers was to a considerable degree congruent with secondary sexual characters, but in some cases, an incongruence was found. These findings suggested that the mechanism underlying this phenomenon was similar or identical in all species examined. Possible genetic and physiological explanations of this phenomenon are discussed.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Contrasting root associated fungi of three common oak-woodland plant species based on molecular identification: host specificity or non-specific amplification?

    Science.gov (United States)

    Douhan, Greg W; Petersen, Carolyn; Bledsoe, Caroline S; Rizzo, David M

    2005-07-01

    An increasingly popular approach used to identify arbuscular mycorrhizal (AM) fungi in planta is to amplify a portion of AM fungal small subunit ribosomal DNA (SSU-rDNA) from whole root DNA extractions using the primer pair AM1-NS31, followed by cloning and sequencing. We used this approach to study the AM fungal community composition of three common oak-woodland plant species: a grass (Cynosurus echinatus), blue oak (Quercus douglasii), and a forb (Torilis arvensis). Significant diversity of AM fungi were found in the roots of C. echinatus, which is consistent with previous studies demonstrating a high degree of AM fungal diversity from the roots of various hosts. In contrast, clones from Q. douglasii and T. arvensis were primarily from non-AM fungi of diverse origins within the Ascomycota and Basidiomycota. This work demonstrates that caution must be taken when using this molecular approach to determine in planta AM fungal diversity if non-sequence based methods such as terminal restriction fragment length polymorphisms, denaturing gradient gel electrophoresis, or temperature gradient gel electrophoresis are used.

  3. 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.

  4. Utilization of elongation factor Tu gene (tuf) sequencing and species-specific PCR (SS-PCR) for the molecular identification of Acetobacter species complex.

    Science.gov (United States)

    Huang, Chien-Hsun; Chang, Mu-Tzu; Huang, Lina; Chu, Wen-Shen

    2014-02-01

    The aim of this study was to use tuf gene as a molecular target for species discrimination in the Acetobacter genus, as well as to develop species-specific PCR method for direct species identification of Acetobacter aceti. The results showed that most Acetobacter species could be clearly distinguished, and the average sequence similarity for the tuf gene (89.5%) among type strains was significantly lower than that of the 16S rRNA gene sequence (98.0%). A pair of species-specific primers were designed and used to specifically identify A. aceti, but none of the other Acetobacter strains. Our data indicate that the phylogenetic relationships of most strains in the Acetobacter genus can be resolved using tuf gene sequencing, and the novel species-specific primer pair could be used to rapidly and accurately identify the species of A. aceti by the PCR based assay. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Experimental Analysis of Sublimation Dynamics for Buried Glacier Ice in Beacon Valley, Antarctica

    Science.gov (United States)

    Ehrenfeucht, S.; Dennis, D. P.; Marchant, D. R.

    2017-12-01

    The age of the oldest known buried ice in Beacon Valley, McMurdo Dry Valleys (MDV) Antarctica is a topic of active debate due to its implications for the stability of the East Antarctic Ice Sheet. Published age estimates range from as young as 300 ka to as old as 8.1 Ma. In the upland MDV, ablation occurs predominantly via sublimation. The relict ice in question (ancient ice from Taylor Glacier) lies buried beneath a thin ( 30-70 cm) layer of sublimation till, which forms as a lag deposit as underlying debris-rich ice sublimes. As the ice sublimates, the debris held within the ice accumulates slowly on the surface, creating a porous boundary between the buried-ice surface and the atmosphere, which in turn influences gas exchange between the ice and the atmosphere. Additionally, englacial debris adds several salt species that are ultimately concentrated on the ice surface. It is well documented the rate of ice sublimation varies as a function of overlying till thickness. However, the rate-limiting dynamics under varying environmental conditions, including the threshold thicknesses at which sublimation is strongly retarded, are not yet defined. To better understand the relationships between sublimation rate, till thickness, and long-term surface evolution, we build on previous studies by Lamp and Marchant (2017) and evaluate the role of till thickness as a control on ice loss in an environmental chamber capable of replicating the extreme cold desert conditions observed in the MDV. Previous work has shown that this relationship exhibits exponential decay behavior, with sublimation rate significantly dampened under less than 10 cm of till. In our experiments we pay particular attention to the effect of the first several cm of till in order to quantify the dynamics that govern the transition from bare ice to debris-covered ice. We also examine this transition for various forms of glacier ice, including ice with various salt species.

  6. A parallel approach for subwavelength molecular surgery using gene-specific positioned metal nanoparticles as laser light antennas.

    Science.gov (United States)

    Csaki, Andrea; Garwe, Frank; Steinbrück, Andrea; Maubach, Gunter; Festag, Grit; Weise, Anja; Riemann, Iris; König, Karsten; Fritzsche, Wolfgang

    2007-02-01

    An optical technique for the parallel manipulation of nanoscale structures with molecular resolution is presented. Bioconjugated metal nanoparticles are thereby positioned at the location of interest, such as, e.g., certain DNA sequences along metaphase chromosomes, prior to pulsed laser light irradiation of the whole sample. The nanoparticles are designed to absorb the introduced energy highly efficiently, in that way acting as nanoantenna. As result of the interaction, structural changes of the sample with subwavelength dimensions and nanoscale precision are observed at the location of the particles. The process leading to the nanolocalized destruction is caused by particle ablation as well as thermal damage of the surrounding material.

  7. [Identification of low-molecular weight prostate-specific antigen(PSA) and lactoferrin in the prostatic secretion of benign prostatic hyperplasia].

    Science.gov (United States)

    Xu, Ke-xin; Wang, Xiao-feng

    2006-12-18

    To investigate the expression of low-molecular-weight PSA(lw-PSA) and lactoferrin in the expressed prostatic secretion (EPS) from both benign prostatic hyperplasia (BPH) and normal prostate. Forty human EPS samples obtained from 20 BPH patients and 20 normal males were subjected to two-dimensional gel electrophoresis (2-DE). Mass spectrometry was performed to confirm the nature of the secreted proteins in EPS. One uniquely expressed protein in BPH was detected and mass spectrometry determined its nature as lw-PSA (molecular weight 10x10(3), pI 8.5-9.3). More importantly, Western blotting analysis also revealed that lw-PSA detected in BPH-EPS, but was undetectable in BPH-free EPS. In addition, up-regulation of Lactoferrin (molecular weight 35x10(3), pI 7-7.5) in BPH-EPS, as compared with BPH-free EPS, was also observed. More interestingly, lactoferrin was absent in prostate cancer tissues. Our results indicate lw-PSA may be produced specifically by BPH epithelium and it has a potential to be used as a specific biological marker for the diagnosis of BPH. In addition, benign prostatic epithelium can produce more lactoferrin while prostate cancer tissues go without its lactoferrin secretion.

  8. Metal Ion Coordination Essential for Specific Molecular Interactions of Butea monosperma Lectin: ITC and MD Simulation Studies.

    Science.gov (United States)

    Abhilash, J; Haridas, M

    2015-05-01

    Crystal structure of Butea monosperma seed lectin (BML) was analyzed and the metal ion geometry identified. In order to understand the role of metal ions for the structural stability and ligand binding, studies of demetallized protein were carried out. Binding of different ligands like GalNAc, lactose, and galactose onto native and demetallized protein was studied by isothermal titration calorimetry as well as molecular simulation methods. Molecular dynamics was applied to the structure after removing the coordinates of metal ions, to identify the effect of demetallization in silico. Docking studies of different sugar molecules as well as the fungal α-amylase was carried out and compared the interactions in the native and apo states. It was found that metal ions are important for the ligand binding with increased affinity. However, their absence did not make any alteration to the secondary structure. Though the metal ions were not coordinated to the loops contacting the α-amylase, the absence of metal ions reduced the protein-protein binding strength due to long-range changes in irregular structures of the lectin.

  9. Molecular distributions and compound-specific stable carbon isotopic compositions of lipids in wintertime aerosols from Beijing.

    Science.gov (United States)

    Ren, Lujie; Fu, Pingqing; He, Yue; Hou, Juzhi; Chen, Jing; Pavuluri, Chandra Mouli; Sun, Yele; Wang, Zifa

    2016-06-08

    Molecular distributions and stable carbon isotopic compositions (δ(13)C) of n-alkanes, fatty acids and n-alcohols were investigated in urban aerosols from Beijing, northern China to better understand the sources and long-range atmospheric transport of terrestrial organic matter during polluted and clear days in winter. n-Alkanes (C19-C36), fatty acids (C8-C32) and n-alcohols (C16-C32) detected in Beijing aerosols are characterized by the predominance of C23, C16 and C28, respectively. Carbon preference index (CPI) values of n-alkanes, the ratios of the sum of odd-numbered n-alkanes to the sum of even-numbered n-alkanes, are close to 1, indicating a heavy influence of fossil fuel combustion. Relatively higher ratios of C(18:0+16:0)/C(18:n+16:1) (fatty acids) on clear days than polluted days indicate that long-distance transport and/or photochemical aging are more significant during clear days. δ(13)C values of n-alkanes and low molecular weight fatty acids (C16:0, C18:0) ranged from -34.1 to -24.7% and -26.9 to -24.6%, respectively, which are generally heavier on polluted days than those on clear days. Such a wide range suggests that atmospheric lipids in Beijing aerosols originate from multiple sources and encounter complicated atmospheric processes during long-range transport in North China.

  10. 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.

  11. 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.

  12. Shape and Size Characteristics of Bedload Transported During Winter Storm Events in the Cwm Treweryn Stream, Brecon Beacons, South Wales

    OpenAIRE

    WALSH, TUNCER DEMİR & RORY PETER DOMINIC

    2005-01-01

    Bedload transport in the Cwm Treweryn stream, a tributary of the Usk in the Brecon Beacons, South Wales, was investigated during a wet winter period in early 1995 using basket-type bedload traps and the tracing of painted clasts. The Cwm Treweryn is a typical mountain stream of the region with its gravel-bedload, flashy regime, high gradient and pool-riffle sequences. In particular, the study explored - for a range of categories of clast size - the nature of any influence of clast shape on be...

  13. Neuronal cell fate specification by the molecular convergence of different spatio-temporal cues on a common initiator terminal selector gene.

    Directory of Open Access Journals (Sweden)

    Johannes Stratmann

    2017-04-01

    Full Text Available The extensive genetic regulatory flows underlying specification of different neuronal subtypes are not well understood at the molecular level. The Nplp1 neuropeptide neurons in the developing Drosophila nerve cord belong to two sub-classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1 neurons are specified by spatial cues; the Hox homeotic network and GATA factor grn, and temporal cues; the hb -> Kr -> Pdm -> cas -> grh temporal cascade. These spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp neurons that activate a common terminal selector feedforward cascade of col -> ap/eya -> dimm -> Nplp1. Here, we molecularly decode the specification of Nplp1 neurons, and find that the cis-regulatory organization of col functions as an integratory node for the different spatio-temporal combinatorial codes. These findings may provide a logical framework for addressing spatio-temporal control of neuronal sub-type specification in other systems.

  14. Molecular Basis of Allele-Specific Efficacy of a Blood-Stage Malaria Vaccine: Vaccine Development Implications

    Science.gov (United States)

    Ouattara, Amed; Takala-Harrison, Shannon; Thera, Mahamadou A.; Coulibaly, Drissa; Niangaly, Amadou; Saye, Renion; Tolo, Youssouf; Dutta, Sheetij; Heppner, D. Gray; Soisson, Lorraine; Diggs, Carter L.; Vekemans, Johan; Cohen, Joe; Blackwelder, William C.; Dube, Tina; Laurens, Matthew B.; Doumbo, Ogobara K.; Plowe, Christopher V.

    2013-01-01

    The disappointing efficacy of blood-stage malaria vaccines may be explained in part by allele-specific immune responses that are directed against polymorphic epitopes on blood-stage antigens. FMP2.1/AS02A, a blood-stage candidate vaccine based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, had allele-specific efficacy against clinical malaria in a phase II trial in Malian children. We assessed the cross-protective efficacy of the malaria vaccine and inferred which polymorphic amino acid positions in AMA1 were the targets of protective allele-specific immune responses. FMP2.1/AS02A had the highest efficacy against AMA1 alleles that were identical to the 3D7 vaccine-type allele at 8 highly polymorphic amino acid positions in the cluster 1 loop (c1L) but differed from 3D7 elsewhere in the molecule. Comparison of the incidence of vaccine-type alleles before and after vaccination in the malaria vaccine and control groups and examination of the patterns of allele change at polymorphic positions in consecutive malaria episodes suggest that the highly polymorphic amino acid position 197 in c1L was the most critical determinant of allele-specific efficacy. These results indicate that a multivalent AMA1 vaccine with broad efficacy could include only a limited set of key alleles of this extremely polymorphic antigen. PMID:23204168

  15. Mannose-specific interactions of Lactobacillus plantarum in the intestine : bacterial genes, molecular host responses and potential probiotic effects

    NARCIS (Netherlands)

    Pretzer, G.

    2008-01-01

    One potential mechanism by which probiotic microorganisms may exert beneficial health effects to the host is the inhibition of intestinal infections by competitive exclusion of pathogenic bacteria. This concept may also be applicable for mannose-specific adhesion to the epithelial surface, which has

  16. 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.

  17. 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...

  18. Proteotranscriptomic Analysis Reveals Stage Specific Changes in the Molecular Landscape of Clear-Cell Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Benjamin A Neely

    Full Text Available Renal cell carcinoma comprises 2 to 3% of malignancies in adults with the most prevalent subtype being clear-cell RCC (ccRCC. This type of cancer is well characterized at the genomic and transcriptomic level and is associated with a loss of VHL that results in stabilization of HIF1. The current study focused on evaluating ccRCC stage dependent changes at the proteome level to provide insight into the molecular pathogenesis of ccRCC progression. To accomplish this, label-free proteomics was used to characterize matched tumor and normal-adjacent tissues from 84 patients with stage I to IV ccRCC. Using pooled samples 1551 proteins were identified, of which 290 were differentially abundant, while 783 proteins were identified using individual samples, with 344 being differentially abundant. These 344 differentially abundant proteins were enriched in metabolic pathways and further examination revealed metabolic dysfunction consistent with the Warburg effect. Additionally, the protein data indicated activation of ESRRA and ESRRG, and HIF1A, as well as inhibition of FOXA1, MAPK1 and WISP2. A subset analysis of complementary gene expression array data on 47 pairs of these same tissues indicated similar upstream changes, such as increased HIF1A activation with stage, though ESRRA and ESRRG activation and FOXA1 inhibition were not predicted from the transcriptomic data. The activation of ESRRA and ESRRG implied that HIF2A may also be activated during later stages of ccRCC, which was confirmed in the transcriptional analysis. This combined analysis highlights the importance of HIF1A and HIF2A in developing the ccRCC molecular phenotype as well as the potential involvement of ESRRA and ESRRG in driving these changes. In addition, cofilin-1, profilin-1, nicotinamide N-methyltransferase, and fructose-bisphosphate aldolase A were identified as candidate markers of late stage ccRCC. Utilization of data collected from heterogeneous biological domains strengthened

  19. A novel strategy for human papillomavirus detection and genotyping with SybrGreen and molecular beacon polymerase chain reaction

    NARCIS (Netherlands)

    Szuhai, K; Sandhaus, E; Kolkman-Uljee, SM; Lemaitre, M; Truffert, JC; Dirks, RW; Tanke, HJ; Fleuren, GJ; Schuuring, E; Raap, AK

    2001-01-01

    Human papillomaviruses (HPVs) play an important role in the pathogenesis of cervical cancer. For identification of the large number of different HPV types found in (pre)malignant lesions, a robust methodology is needed that combines general HPV detection with HPV genotyping. We have developed for

  20. Tentacle probe sandwich assay in porous polymer monolith improves specificity, sensitivity and kinetics.

    Science.gov (United States)

    Satterfield, Brent C; Caplan, Michael R; West, Jay A A

    2008-11-01

    Nucleic acid sandwich assays improve low-density array analysis through the addition of a capture probe and a specific label, increasing specificity and sensitivity. Here, we employ photo-initiated porous polymer monolith (PPM) as a high-surface area substrate for sandwich assay analysis. PPMs are shown to enhance extraction efficiency by 20-fold from 2 microl of sample. We further compare the performance of labeled linear probes, quantum dot labeled probes, molecular beacons (MBs) and tentacle probes (TPs). Each probe technology was compared and contrasted with traditional hybridization methods using labeled sample. All probes demonstrated similar sensitivity and greater specificity than traditional hybridization techniques. MBs and TPs were able to bypass a wash step due to their 'on-off' signaling mechanism. TPs demonstrated reaction kinetics 37.6 times faster than MBs, resulting in the fastest assay time of 5 min. Our data further indicate TPs had the most sensitive detection limit (1 x 10(4) improvement) among all tested probes in these experiments. By matching the enhanced extraction efficiencies of PPM with the selectivity of TPs, we have created a format for improved sandwich assays.

  1. Molecular Serotype-Specific Identification of Non-type b Haemophilus influenzae by Loop-Mediated Isothermal Amplification

    Directory of Open Access Journals (Sweden)

    Chika Takano

    2017-10-01

    Full Text Available Over the past four decades, the incidence of meningitis caused by Haemophilus influenzae in children has decreased due to widespread vaccination against H. influenzae type b (Hib. The incidence of invasive diseases due to H. influenzae types not included in the vaccines, however, has increased. At present, there are a limited number of diagnostics available to detect non-type b H. influenzae. To address this issue, we developed a rapid, simple, and cost-effective method for detecting serotypes of H. influenzae. We designed LAMP primer sets based on published sequences for H. influenzae capsular types a, c, d, e, and f. The assay was evaluated to determine test reactivity, specificity, and sensitivity. To support its use in patients with suspected meningitis, we evaluated the detection limit of the non-Hib serotype specific LAMP assay using bacterial genomic DNA-spiked cerebrospinal fluid (CSF specimens. The reactivity and specificity of the LAMP assays were confirmed using six serotypes and non-typeable H. influenzae strains, plus eight strains of other Haemophilus species and non-Haemophilus genera. The detection limits of the LAMP assay for capsular types a, c, d, e, and f were 102, 102, 102, 103, and 10 copies per reaction, while those of the PCR assay were 104, 104, 103, 103, and 104 genome copies per reaction, respectively. Using DNA-spiked CSF specimens, the detection limit of the LAMP assay was equivalent to that using purified DNA as the template. However, the detection limit of the PCR was reduced from 103 to 104 genome copies per reaction for serotype d and from 103 to 105 genome copies per reaction for serotype e. To the best of our knowledge, this is the first report of a serotype-specific identification assay for H. influenzae using the LAMP method. Our results suggest the potential of LAMP methods for patients with suspected meningitis in resource-limited laboratories or public health surveillance systems.

  2. A catalytic and dual recycling amplification ATP sensor based on target-driven allosteric structure switching of aptamer beacons.

    Science.gov (United States)

    Peng, Ying; Li, Daxiu; Yuan, Ruo; Xiang, Yun

    2018-05-15

    Abnormal concentrations of ATP are associated with many diseases and cancers, and quantitative detection of ATP is thus of great importance for disease diagnosis and prognosis. In the present work, we report a new dual recycling amplification sensor integrated with catalytic hairpin assembly (CHA) to achieve high sensitivity for fluorescent detection of ATP. The association of the target ATP with the aptamer beacons causes the allosteric structure switching of the aptamer beacons to expose the toehold regions, which hybridize with and unfold the fluorescently quenched hairpin signal probes (HP1) to recycle the target ATP and to trigger CHA between HP1 and the secondary hairpin probes (HP2) to form HP1/HP2 duplexes. Due to the recycling amplification, the presence of ATP leads to the formation of many HP1/HP2 duplexes, generating dramatically amplified fluorescent signals for sensitive detection of ATP. Under optimal experimental conditions, our sensor linearly responds to ATP in the range from 25 to 600nM with a calculated detection limit of 8.2nM. Furthermore, the sensor shows a high selectivity and can also be used to detect ATP in human serums to realize its application for real samples. With the distinct advantage of significant signal amplification without the involvement of any nanomaterial and enzyme, the developed sensor thus holds great potential for simple and sensitive detection of different small molecules and proteins. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Design and Analysis of A Beacon-Less Routing Protocol for Large Volume Content Dissemination in Vehicular Ad Hoc Networks.

    Science.gov (United States)

    Hu, Miao; Zhong, Zhangdui; Ni, Minming; Baiocchi, Andrea

    2016-11-01

    Large volume content dissemination is pursued by the growing number of high quality applications for Vehicular Ad hoc NETworks(VANETs), e.g., the live road surveillance service and the video-based overtaking assistant service. For the highly dynamical vehicular network topology, beacon-less routing protocols have been proven to be efficient in achieving a balance between the system performance and the control overhead. However, to the authors' best knowledge, the routing design for large volume content has not been well considered in the previous work, which will introduce new challenges, e.g., the enhanced connectivity requirement for a radio link. In this paper, a link Lifetime-aware Beacon-less Routing Protocol (LBRP) is designed for large volume content delivery in VANETs. Each vehicle makes the forwarding decision based on the message header information and its current state, including the speed and position information. A semi-Markov process analytical model is proposed to evaluate the expected delay in constructing one routing path for LBRP. Simulations show that the proposed LBRP scheme outperforms the traditional dissemination protocols in providing a low end-to-end delay. The analytical model is shown to exhibit a good match on the delay estimation with Monte Carlo simulations, as well.

  4. 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)

  5. Molecular approaches identify known species, reveal cryptic species and verify host specificity of Chinese Philotrypesis (Hymenoptera: Pteromalidae).

    Science.gov (United States)

    Zhou, Mei-Jiao; Xiao, Jin-Hua; Bian, Sheng-Nan; Li, Yan-Wei; Niu, Li-Ming; Hu, Hao-Yuan; Wu, Wen-Shan; Murphy, Robert W; Huang, Da-Wei

    2012-07-01

    Philotrypesis, a major component of the fig wasp community (Hymenoptera: Pteromalidae), is a model taxon for studying male fighting and mating behaviour. Its extreme sexual dimorphism and male polymorphism render species identification uncertain and in-depth research on its ecology, behaviour and other evolutionary topics challenging. The fig wasps' enclosed habitat within the syconia makes their mating behaviour inaccessible, to the extent of matching conspecific females and males. In this study, we combine morphological and molecular analyses to identify species of Philotrypesis sampled from south China and to associate their extraordinarily dimorphic genders and labile male morphologies. Morphological evaluations of females identify 22 species and 28 male morphs. The mitochondrial cytochrome c oxidase I and nuclear internal transcribed spacer 2 data detect 21 species using females, and 15 species among the males. Most of the males match the species as delimited by females. Both markers reveal cryptic species in P. quadrisetosa on Ficus vasculosa. Most species of wasps live on one species of fig but three species co-occur in two hosts (F. microcarpa and F. benjamina), which indicates host switching. © 2012 Blackwell Publishing Ltd.

  6. 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

  7. 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.

  8. 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.

  9. Single photon simultaneous K-shell ionization and K-shell excitation. II. Specificities of hollow nitrogen molecular ions

    Energy Technology Data Exchange (ETDEWEB)

    Carniato, S., E-mail: stephane.carniato@upmc.fr; Selles, P.; Andric, L.; Palaudoux, J.; Penent, F.; Lablanquie, P. [Laboratoire de Chimie Physique-Matière et Rayonnement, UMR 7614, Sorbonne Universités, UPMC University of Paris 6, 11 rue Pierre et Marie Curie, 75231 Paris Cedex 05 (France); LCPMR(UMR 7614), CNRS, 11 rue Pierre et Marie Curie, 75231 Paris Cedex 05 (France); Žitnik, M.; Bučar, K. [Jozef Stefan Institute, P.O. Box 3000, SI-1001 Ljubljana (Slovenia); Nakano, M. [Department of Chemistry, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8551 (Japan); Photon Factory, Institute of Materials Structure Science, Tsukuba, Ibaraki 305-0801 (Japan); Hikosaka, Y. [Department of Environmental Science, Niigata University, Niigata 950-2181 (Japan); Ito, K. [Photon Factory, Institute of Materials Structure Science, Tsukuba, Ibaraki 305-0801 (Japan)

    2015-01-07

    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{sup −2} and core ionization-core excitation K{sup −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{sup −2}V spectrum is assigned to a K{sup −2}π{sup ∗} state mainly populated by the 1s→ lowest unoccupied molecular orbital dipolar excitation, as it is in the K{sup −1}V NEXAFS (Near-Edge X-ray Absorption Fine Structure) signals. Closer to the K{sup −2} threshold Rydberg resonances have been also identified, and among them a K{sup −2}σ{sup ∗} resonance characterized by a large amount of 2s/2p hybridization, and double K{sup −2}(2σ{sup ∗}/1π/3σ){sup −1}1π{sup ∗2} shake-up states. These resonances correspond in NEXAFS spectra to, respectively, the well-known σ{sup ∗} shape resonance and double excitation K{sup −1}(2σ{sup ∗}/1π/3σ){sup −1}1π{sup ∗2} resonances, all being positioned above the threshold.

  10. 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

  11. 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.

  12. Use of telomerase promoter mutations to mark specific molecular subsets with reciprocal clinical behavior in IDH mutant and IDH wild-type diffuse gliomas.

    Science.gov (United States)

    Akyerli, Cemaliye B; Yüksel, Şirin; Can, Özge; Erson-Omay, E Zeynep; Oktay, Yavuz; Coşgun, Erdal; Ülgen, Ege; Erdemgil, Yiğit; Sav, Aydın; von Deimling, Andreas; Günel, Murat; Yakıcıer, M Cengiz; Pamir, M Necmettin; Özduman, Koray

    2017-06-16

    OBJECTIVE Recent studies have established that hemispheric diffuse gliomas may be grouped into subsets on the basis of molecular markers; these subsets are loosely correlated with the histopathological diagnosis but are strong predictors of clinical tumor behavior. Based on an analysis of molecular and clinical parameters, the authors hypothesized that mutations of the telomerase promoter (TERTp-mut) mark separate oncogenic programs among isocitrate dehydrogenase 1 and/or 2 (IDH) mutant (IDH-mut) and IDH wild-type (IDH-wt) diffuse gliomas independent of histopathology or WHO grade. METHODS Four molecular subsets of the combined statuses of IDH and TERT-promoter mutations (double mutant, IDH only, TERT only, and double negative) were defined. Differences in age, anatomical location, molecular genetics, and survival rates in a surgical cohort of 299 patients with a total of 356 hemispheric diffuse gliomas (WHO Grade II, III, or IV) were analyzed. RESULTS TERTp-mut were present in 38.8% of IDH-mut and 70.2% of IDH-wt gliomas. The mutational status was stable in each patient at 57 recurrence events over a 2645-month cumulative follow-up period. Among patients with IDH-mut gliomas, those in the double-mutant subset had better survival and a lower incidence of malignant degeneration than those in the IDH-only subset. Of patients in the double-mutant subset, 96.3% were also positive for 1p/19q codeletions. All patients with 1p/19q codeletions had TERTp-mut. In patients with IDH-mut glioma, epidermal growth factor receptor or phosphatase and tensin homolog mutations were not observed, and copy-number variations were uncommon. Among IDH-wt gliomas, the TERT-only subset was associated with significantly higher age, higher Ki-67 labeling index, primary glioblastoma-specific oncogenic changes, and poor survival. The double-negative subset was genetically and biologically heterogeneous. Survival analyses (Kaplan-Meier, multivariate, and regression-tree analyses) confirmed that

  13. 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

  14. Increased sampling reveals novel lineages of Entamoeba: consequences of genetic diversity and host specificity for taxonomy and molecular detection.

    Science.gov (United States)

    Stensvold, C Rune; Lebbad, Marianne; Victory, Emma L; Verweij, Jaco J; Tannich, Egbert; Alfellani, Mohammed; Legarraga, Paulette; Clark, C Graham

    2011-07-01

    To expand the representation for phylogenetic analysis, ten additional complete Entamoeba small-subunit rRNA gene sequences were obtained from humans, non-human primates, cattle and a tortoise. For some novel sequences no corresponding morphological data were available, and we suggest that these organisms should be referred to as ribosomal lineages (RL) rather than being assigned species names at present. To investigate genetic diversity and host specificity of selected Entamoeba species, a total of 91 new partial small subunit rRNA gene sequences were obtained, including 49 from Entamoeba coli, 18 from Entamoeba polecki, and 17 from Entamoeba hartmanni. We propose a new nomenclature for significant variants within established Entamoeba species. Based on current data we propose that the uninucleated-cyst-producing Entamoeba infecting humans is called Entamoeba polecki and divided into four subtypes (ST1-ST4) and that Entamoeba coli is divided into two subtypes (ST1-ST2). New hosts for several species were detected and, while host specificity and genetic diversity of several species remain to be clarified, it is clear that previous reliance on cultivated material has given us a misleading and incomplete picture of variation within the genus Entamoeba. Copyright © 2010 Elsevier GmbH. All rights reserved.

  15. Specific labeling and assignment strategies of valine methyl groups for NMR studies of high molecular weight proteins

    International Nuclear Information System (INIS)

    Mas, Guillaume; Crublet, Elodie; Hamelin, Olivier; Gans, Pierre; Boisbouvier, Jérôme

    2013-01-01

    The specific protonation of valine and leucine methyl groups in proteins is typically achieved by overexpressing proteins in M9/D 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 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

  16. 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.

  17. Beyond molecular recognition: using a repulsive field to tune interfacial valency and binding specificity between adhesive surfaces.

    Science.gov (United States)

    Santore, Maria M; Zhang, Jun; Srivastava, Sudhanshu; Rotello, Vincent M

    2009-01-06

    Surface-bound biomolecular fragments enable "smart" materials to recognize cells and other particles in applications ranging from tissue engineering and medical diagnostics to colloidal and nanoparticle assembly. Such smart surfaces are, however, limited in their design to biomolecular selectivity. This feature article demonstrates, using a completely nonbiological model system, how specificity can be achieved for particle (and cell) binding, employing surface designs where immobilized nanoscale adhesion elements are entirely nonselective. Fundamental principles are illustrated by a model experimental system where 11 nm cationic nanoparticles on a planar negative silica surface interact with flowing negative silica microspheres having 1.0 and 0.5 microm diameters. In these systems, the interfacial valency, defined as the number of cross-bonds needed to capture flowing particles, is tunable through ionic strength, which alters the range of the background repulsion and therefore the effective binding strength of the adhesive elements themselves. At high ionic strengths where long-range electrostatic repulsions are screened, single surface-bound nanoparticles capture microspheres, defining the univalent regime. At low ionic strengths, competing repulsions weaken the effective nanoparticle adhesion so that multiple nanoparticles are needed for microparticle capture. This article discusses important features of the univalent regime and then illustrates how multivalency produces interfacial-scale selectivity. The arguments are then generalized, providing a possible explanation for highly specific cell binding in nature, despite the degeneracy of adhesion molecules and cell types. The mechanism for the valency-related selectivity is further developed in the context of selective flocculation in the colloidal literature. Finally, results for multivalent binding are contrasted with the current thinking for interfacial design and the presentation of adhesion moieties on

  18. 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.

  19. BEACON/MOD2A: a computer program for subcompartment analysis of nuclear reactor containment. A user's manual. [PWR

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. 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

  1. Molecular implication of PP2A and Pin1 in the Alzheimer's disease specific hyperphosphorylation of Tau.

    Directory of Open Access Journals (Sweden)

    Isabelle Landrieu

    Full Text Available Tau phosphorylation and dephosphorylation regulate in a poorly understood manner its physiological role of microtubule stabilization, and equally its integration in Alzheimer disease (AD related fibrils. A specific phospho-pattern will result from the balance between kinases and phosphatases. The heterotrimeric Protein Phosphatase type 2A encompassing regulatory subunit PR55/Bα (PP2A(T55α is a major Tau phosphatase in vivo, which contributes to its final phosphorylation state. We use NMR spectroscopy to determine the dephosphorylation rates of phospho-Tau by this major brain phosphatase, and present site-specific and kinetic data for the individual sites including the pS202/pT205 AT8 and pT231 AT180 phospho-epitopes.We demonstrate the importance of the PR55/Bα regulatory subunit of PP2A within this enzymatic process, and show that, unexpectedly, phosphorylation at the pT231 AT180 site negatively interferes with the dephosphorylation of the pS202/pT205 AT8 site. This inhibitory effect can be released by the phosphorylation dependent prolyl cis/trans isomerase Pin1. Because the stimulatory effect is lost with the dimeric PP2A core enzyme (PP2A(D or with a phospho-Tau T231A mutant, we propose that Pin1 regulates the interaction between the PR55/Bα subunit and the AT180 phospho-epitope on Tau.Our results show that phosphorylation of T231 (AT180 can negatively influence the dephosphorylation of the pS202/pT205 AT8 epitope, even without an altered PP2A pool. Thus, a priming dephosphorylation of pT231 AT180 is required for efficient PP2A(T55α-mediated dephosphorylation of pS202/pT205 AT8. The sophisticated interplay between priming mechanisms reported for certain Tau kinases and the one described here for Tau phosphatase PP2A(T55α may contribute to the hyperphosphorylation of Tau observed in AD neurons.

  2. Investigation of the molecular mechanism of the blue-light-specific excitation energy quenching in the plant antenna complex LHCII.

    Science.gov (United States)

    Gruszecki, Wieslaw I; Zubik, Monika; Luchowski, Rafal; Grudzinski, Wojciech; Gospodarek, Malgorzata; Szurkowski, Janusz; Gryczynski, Zygmunt; Gryczynski, Ignacy

    2011-03-15

    Excitation of the major photosynthetic antenna complex of plants, LHCII, with blue light (470nm) provides an advantage to plants, as it gives rise to chlorophyll a fluorescence lifetimes shorter than with excitation with red light (635nm). This difference is particularly pronounced in fluorescence emission wavelengths longer than 715nm. Illumination of LHCII preparation with blue light additionally induces fluorescence quenching, which develops on a minute timescale. This effect is much less efficient when induced by red light, despite the equalized energy absorbed in both the spectral regions. Simultaneous analysis of the fluorescence and photoacoustic signals in LHCII demonstrated that the light-driven fluorescence quenching is not associated with an increase in heat emission. Instead, a reversible light-induced conformational transformation of the protein takes place, as demonstrated by the FTIR technique. These findings are discussed in terms of the blue-light-specific excitation energy quenching in LHCII, which may have photoprotective applications. Copyright © 2010 Elsevier GmbH. All rights reserved.

  3. Molecular Characterization and Tissue-specific Expression of a Novel FKBP38 Gene in the Cashmere Goat (Capra hircus).

    Science.gov (United States)

    Zheng, X; Hao, X Y; Chen, Y H; Zhang, X; Yang, J F; Wang, Z G; Liu, D J

    2012-06-01

    As a member of a subclass of immunophilins, it is controversial that FKBP38 acts an upstream regulator of mTOR signaling pathway, which control the process of cell-growth, proliferation and differentiation. In order to explore the relationship between FKBP38 and mTOR in the Cashmere goat (Capra hircus) cells, a full-length cDNA was cloned (GenBank accession number JF714970) and expression pattern was analyzed. The cloned FKBP38 gene is 1,248 bp in length, containing an open reading frame (ORF) from nucleotide 13 to 1,248 which encodes 411 amino acids, and 12 nucleotides in front of the initiation codon. The full cDNA sequence shares 98% identity with cattle, 94% with horse and 90% with human. The putative amino acid sequence shows the higher homology which is 98%, 97% and 94%, correspondingly. The bioinformatics analysis showed that FKBP38 contained a FKBP_C domain, two TPR domains and a TM domain. Psite analysis suggested that the ORF encoding protein contained a leucine-zipper pattern and a Prenyl group binding site (CAAX box). Tissue-specific expression analysis was performed by semi-quantitative RT-PCR and showed that the FKBP38 expression was detected in all the tested tissues and the highest level of mRNA accumulation was detected in testis, suggesting that FKBP38 plays an important role in goat cells.

  4. 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.

  5. Molecular cloning, sequence analysis, prokaryotic expression, and function prediction of foot-specific peroxidase in Hydra magnipapillata Chinese strain.

    Science.gov (United States)

    Pan, H C; Yang, H Q; Zhao, F X; Qian, X C

    2014-08-28

    The cDNA sequence of foot-specific peroxidase PPOD1 from the Chinese strain of Hydra magnipapillata was cloned by reverse transcription-polymerase chain reaction. The cDNA sequence contained a coding region with an 873-bp open reading frame, a 31-bp 5'-untranslated region, and a 36-bp 3'-untranslated region. The structure prediction results showed that PPOD1 contains 10.34% of α-helix, 38.62% of extended strand, 12.41% of β-turn, and 38.62% of random coil. The structural core was α-helix at the N terminus. The GenBank protein blast server showed that PPOD1 contains 2 fascin-like domains. In addition, high-level PPOD1 activity was only present in the ectodermal epithelial cells located on the edge of the adhesive face of the basal disc, and that these cells extended lamellipodia and filopodia when the basal disc was tightly attached to a glass slide. The fascin-like domains of Hydra PPOD1 might contribute to the bundling of the actin filament of these cells, and hence, the formation of filopodia. In conclusion, these cells might play an important role in strengthening the adsorbability of the basal disc to substrates.

  6. 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.

  7. 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.

  8. 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

  9. Molecular Characterization and Tissue-specific Expression of a Novel FKBP38 Gene in the Cashmere Goat (

    Directory of Open Access Journals (Sweden)

    X. Zheng

    2012-06-01

    Full Text Available As a member of a subclass of immunophilins, it is controversial that FKBP38 acts an upstream regulator of mTOR signaling pathway, which control the process of cell-growth, proliferation and differentiation. In order to explore the relationship between FKBP38 and mTOR in the Cashmere goat (Capra hircus cells, a full-length cDNA was cloned (GenBank accession number JF714970 and expression pattern was analyzed. The cloned FKBP38 gene is 1,248 bp in length, containing an open reading frame (ORF from nucleotide 13 to 1,248 which encodes 411 amino acids, and 12 nucleotides in front of the initiation codon. The full cDNA sequence shares 98% identity with cattle, 94% with horse and 90% with human. The putative amino acid sequence shows the higher homology which is 98%, 97% and 94%, correspondingly. The bioinformatics analysis showed that FKBP38 contained a FKBP_C domain, two TPR domains and a TM domain. Psite analysis suggested that the ORF encoding protein contained a leucine-zipper pattern and a Prenyl group binding site (CAAX box. Tissue-specific expression analysis was performed by semi-quantitative RT-PCR and showed that the FKBP38 expression was detected in all the tested tissues and the highest level of mRNA accumulation was detected in testis, suggesting that FKBP38 plays an important role in goat cells.

  10. 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.

  11. 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

  12. Comparative analysis of detection limits and specificity of molecular diagnostic markers for three pathogens (Microsporidia, Nosema spp.) in the key pollinators Apis mellifera and Bombus terrestris.

    Science.gov (United States)

    Erler, Silvio; Lommatzsch, Stefanie; Lattorff, H Michael G

    2012-04-01

    Global pollinator decline has recently been discussed in the context of honey and bumble bee infections from various pathogens including viruses, bacteria, microsporidia and mites. The microsporidian pathogens Nosema apis, Nosema ceranae and Nosema bombi may in fact be major candidates contributing to this decline. Different molecular and non-molecular detection methods have been developed; however, a comparison, especially of the highly sensitive PCR based methods, is currently lacking. Here, we present the first comparative quantitative real-time PCR study of nine Nosema spp. primers within the framework of primer specificity and sensitivity. With the help of dilution series of defined numbers of spores, we reveal six primer pairs amplifying N. apis, six for N. bombi and four for N. ceranae. All appropriate primer pairs detected an amount of at least 10(4) spores, the majority of which were even as sensitive to detect such low amounts as 10(3) to ten spores. Species specificity of primers was observed for N. apis and N. bombi, but not for N. ceranae. Additionally, we did not find any significant correlation for the amplified fragments with PCR efficiency or the limit of detection. We discuss our findings on the background of false positive and negative results using quantitative real-time PCR. On the basis of these results, future research might be based on appropriate primer selection depending on the experimental needs. Primers may be selected on the basis of specificity or sensitivity. Pathogen species and load may be determined with higher precision enhancing all kinds of diagnostic studies.

  13. 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.

  14. Reconstructions of Climatic and Topographic Gradients in the Sierra Nevada during the early Eocene using compound-specific stable isotopes and organic molecular temperature proxies

    Science.gov (United States)

    Hren, M. T.; Pagani, M.; Brandon, M.; Erwin, D. M.

    2008-12-01

    Terrestrial sediments from the early Cenozoic provide important records of continental temperature gradients during periods of high global temperatures and PCO2, yet these records are often interpreted in terms of either climatic or orographic effects. As a result, linking models of past global climate with terrestrial temperature information is hampered by a lack of detailed information on paleoelevation. Organic molecular proxies provide new tools to help distinguish between climatic and orographic information in terrestrial sediments. For this study, we used organic molecular proxies to determine paleoelevation and paleotemperature gradients in the Sierra Nevada during the early Eocene warm period. Specifically, we analyzed the hydrogen and carbon isotopes of n-alkanes in bulk sediments and fossil angiosperm leaf cuticle in overbank deposits of major drainages of the Eocene Sierra Nevada to quantify the changes in the isotopic composition of leaf water that potentially reflect changes in paleoelevation. We coupled this data with paleotemperature measurements across this landscape using the MBT/CBT organic molecular temperature proxy, as well as thermodynamic models of the isotopic evolution of rainwater during orographic ascent. Hydrogen isotopes of n-alkanes systematically decrease by more than 30 per mil with distance from the Eocene shoreline and temperature data show a decrease of more than 8 degrees across this ancient range, with temperatures near the ocean margin exceeding 22 degrees. Isotopic and temperature data provide evidence for steep topography and high temperature lapse rates at the California margin during the early Eocene. These results support model estimates of temperature and relative humidity for the early Eocene based on a four time doubling of atmospheric CO2.

  15. Specific isotopic labelling: a tool to extend the limits of bio-molecular NMR; Le marquage isotopique specifique: un outil pour repousser les frontieres de la RMN biomoleculaire

    Energy Technology Data Exchange (ETDEWEB)

    Boisbouvier, J. [Centre National de la Recherche Scientifique (CNRS), 38 - Grenoble (France); Gans, P. [CEA Grenoble, Lab. de Resonance Magnetique Nucleaire, Institut de Biologie Structurale, 38 (France)

    2010-12-15

    Nuclear magnetic resonance spectroscopy is a method of choice to study the structural and dynamic properties of bio-macromolecules in solution at atomic resolution. However, standard NMR techniques are characterized by low sensitivity and are limited to biological objects of modest size. The development of new specific isotope labeling techniques has allowed the limits of bio-molecular NMR to be extended in recent years. Protocols have been developed to selectively incorporate {sup 13}CH{sub 3} labeled methyl groups in isoleucine, alanine, methionine, leucine and valine amino acids within otherwise perdeuterated proteins. These labeling schemes significantly improve the quality of NMR data and this gain in sensitivity and resolution allows the characterization of the structure and dynamics of molecular interactions within supramolecular complexes of up to 1 MDa. Moreover, the improvement in sensitivity allows detection of very weak interactions in proteins such as nOe between protons separated by more than 10 angstrom or scalar couplings of a few tenths or hundredths of a hertz. (authors)

  16. 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

  17. Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON.

    Directory of Open Access Journals (Sweden)

    Michael B Cook

    Full Text Available Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA. It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON allowed an in-depth assessment of these issues.Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA. We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted.Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ≥20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index.This analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients.

  18. How a Beacon Community Program in New Orleans Helped Create a Better Health Care System by Building Relationships before Technology.

    Science.gov (United States)

    Khurshid, Anjum; Brown, Lisanne

    2014-01-01

    In the aftermath of Hurricane Katrina, much of New Orleans' healthcare infrastructure was destroyed. Initial federal funding after the storm expanded primary care services and helped set up medical homes for New Orleans' large uninsured and underinsured population. Following that, the Beacon Community in New Orleans, charged with improving health care through the use of technology, decided the best way to accomplish those goals was to build community partnerships and introduce technology improvements based on their input and on their terms. The purpose of this paper is to describe how those partnerships were wrought, including the innovative use of a conceptual framework, and how they are being sustained; how different technologies were and are being introduced; and what the results have been so far. Past successful community experiences, as well as a proven conceptual framework, were used to help establish community partnerships and governance structures, as well as to demonstrate their linkages. This paper represents a compilation of reports and information from key Beacon leaders, staff and providers and their firsthand experiences in setting up those structures, as well as their conclusions. The community partnerships proved extremely successful in not only devising successful ways to introduce new technology into healthcare settings, but in sustaining those changes by creating a governance structure that has enough fluidity to adapt to changing circumstances. Building and developing community partnerships takes time and effort; however, these relationships are necessary and essential to introducing and sustaining new technologies in a healthcare setting and should be a first step for any organization looking to accomplish such goals.

  19. Molecular Tools to Monitor Microbial Contaminants During Long-Term Exploration Class Missions

    Science.gov (United States)

    Larios-Sanz, M.; Kourentzi, K.; Willson, R.; Pierson, D.; Fox, G.

    Microbial contaminants will inevitably accompany a human crew in our adventures into space. Humans constantly shed large numbers of microorganisms into the environment, and during spaceflight some normally benign microbes may become pathogenic. Concerns about microbial disease during Exploration Class human space missions are particularly important in light of the clinically significant changes that the immune system undergoes during spaceflight. Additionally, increased microbial burdens on closed air and water systems may lead to disease and become dangerous sources of contamination for replacement crews. These microbes might also become a serious threat to regenerative life support systems. The development of a robust system to detect, identify and monitor these contaminants i therefore critical. Wes are currently developing a monitoring system that employs 16S ribosomal RNA sequence information to identify bacterial contaminants at the genus and species level. Despite extensive secondary structure, a large number of regions on the 16S rRNA molecule have been successfully targeted. Probes specific for certain groups, such as "all bacteria", "Gram positives", "Gram negatives", and "enterics", as well as some targeting specific genera and species have been designed and optimized. A set of working probes is now being tested in a variety of solution assays that exploit new and exciting technologies such as molecular beacons and DNA microarrays.

  20. Molecular Identification and Typing of Putative Probiotic Indigenous Lactobacillus plantarum Strain Lp91 of Human Origin by Specific Primed-PCR Assays.

    Science.gov (United States)

    Kumar, Rajesh; Grover, Sunita; Batish, Virender Kumar

    2011-12-01

    In the present scenario, it is now well documented that probiotics confer health benefits to the host and the purported probiotic effects are highly strain specific. Hence, accurate genotypic identification is extremely important to link the strain to the specific health effect. With this aim, specific primed-PCR assays were developed and explored for the molecular identification and typing of a putative indigenous probiotic isolate Lp91 of human faecal origin. PCR with specific primers targeting 23S rRNA gene of genus Lactobacillus and 16S rRNA gene of species L. plantarum resulted positive for Lp91. In addition, BLAST analysis of 16S rRNA gene sequence of Lp91 and multiple sequence alignment of 16S rRNA gene variable (V2-V3) regions along with the reference sequences revealed it as L. plantarum with a sequence identity of more than 99%. Furthermore, resolution of 16S rRNA gene sequences was sufficient to infer a phylogenetic relationship amongst Lactobacillus species. In order to determine strain-level variations, randomly amplified polymorphic DNA (RAPD) banding profiles of Lp91 obtained with OPAA-01, OPAP-01 and OPBB-01 primers were compared with those of reference strains of Lactobacillus spp., and Lp91 could be delineated as a distinct strain. Apart from this, presence of probiotic markers viz. bile salt hydrolase (bsh) and collagen-binding protein (cbp) encoding genes in Lp91 genome could be attributed to its exploitation as a potential probiotic adjunct in the development of indigenous functional foods. Lactobacillus isolates/or strains from the gastrointestinal system, fermented products and other environmental niches could be identified and characterized by employing the PCR methods developed in this study; they are rapid, reproducible and more accurate than the conventional methods based on the fermentation profiles.

  1. Allele Specific Locked Nucleic Acid Quantitative PCR (ASLNAqPCR): An Accurate and Cost-Effective Assay to Diagnose and Quantify KRAS and BRAF Mutation

    Science.gov (United States)

    Morandi, Luca; de Biase, Dario; Visani, Michela; Cesari, Valentina; De Maglio, Giovanna; Pizzolitto, Stefano; Pession, Annalisa; Tallini, Giovanni

    2012-01-01

    The use of tyrosine kinase inhibitors (TKIs) requires the testing for hot spot mutations of the molecular effectors downstream the membrane-bound tyrosine kinases since their wild type status is expected for response to TKI therapy. We report a novel assay that we have called Allele Specific Locked Nucleic Acid quantitative PCR (ASLNAqPCR). The assay uses LNA-modified allele specific primers and LNA-modified beacon probes to increase sensitivity, specificity and to accurately quantify mutations. We designed primers specific for codon 12/13 KRAS mutations and BRAF V600E, and validated the assay with 300 routine samples from a variety of sources, including cytology specimens. All were analyzed by ASLNAqPCR and Sanger sequencing. Discordant cases were pyrosequenced. ASLNAqPCR correctly identified BRAF and KRAS mutations in all discordant cases and all had a mutated/wild type DNA ratio below the analytical sensitivity of the Sanger method. ASLNAqPCR was 100% specific with greater accuracy, positive and negative predictive values compared with Sanger sequencing. The analytical sensitivity of ASLNAqPCR is 0.1%, allowing quantification of mutated DNA in small neoplastic cell clones. ASLNAqPCR can be performed in any laboratory with real-time PCR equipment, is very cost-effective and can easily be adapted to detect hot spot mutations in other oncogenes. PMID:22558339

  2. 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)

  3. “Self” and “Non-Self” in the Control of Phytoalexin Biosynthesis: Plant Phospholipases A2 with Alkaloid-Specific Molecular Fingerprints

    Science.gov (United States)

    Heinze, Michael; Brandt, Wolfgang; Marillonnet, Sylvestre; Roos, Werner

    2015-01-01

    The overproduction of specialized metabolites requires plants to manage the inherent burdens, including the risk of self-intoxication. We present a control mechanism that stops the expression of phytoalexin biosynthetic enzymes by blocking the antecedent signal transduction cascade. Cultured cells of Eschscholzia californica (Papaveraceae) and Catharanthus roseus (Apocynaceae) overproduce benzophenanthridine alkaloids and monoterpenoid indole alkaloids, respectively, in response to microbial elicitors. In both plants, an elicitor-responsive phospholipase A2 (PLA2) at the plasma membrane generates signal molecules that initiate the induction of biosynthetic enzymes. The final alkaloids produced in the respective plant inhibit the respective PLA, a negative feedback that prevents continuous overexpression. The selective inhibition by alkaloids from the class produced in the “self” plant could be transferred to leaves of Nicotiana benthamiana via recombinant expression of PLA2. The 3D homology model of each PLA2 displays a binding pocket that specifically accommodates alkaloids of the class produced by the same plant, but not of the other class; for example, C. roseus PLA2 only accommodates C. roseus alkaloids. The interaction energies of docked alkaloids correlate with their selective inhibition of PLA2 activity. The existence in two evolutionary distant plants of phospholipases A2 that discriminate “self-made” from “foreign” alkaloids reveals molecular fingerprints left in signal enzymes during the evolution of species-specific, cytotoxic phytoalexins. PMID:25670767

  4. 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

  5. Molecular basis for specific viral RNA recognition and 2'-O-ribose methylation by the dengue virus nonstructural protein 5 (NS5).

    Science.gov (United States)

    Zhao, Yongqian; Soh, Tingjin Sherryl; Lim, Siew Pheng; Chung, Ka Yan; Swaminathan, Kunchithapadam; Vasudevan, Subhash G; Shi, Pei-Yong; Lescar, Julien; Luo, Dahai

    2015-12-01

    Dengue virus (DENV) causes several hundred million human infections and more than 20,000 deaths annually. Neither an efficacious vaccine conferring immunity against all four circulating serotypes nor specific drugs are currently available to treat this emerging global disease. Capping of the DENV RNA genome is an essential structural modification that protects the RNA from degradation by 5' exoribonucleases, ensures efficient expression of viral proteins, and allows escape from the host innate immune response. The large flavivirus nonstructural protein 5 (NS5) (105 kDa) has RNA methyltransferase activities at its N-terminal region, which is responsible for capping the virus RNA genome. The methyl transfer reactions are thought to occur sequentially using the strictly conserved flavivirus 5' RNA sequence as substrate (GpppAG-RNA), leading to the formation of the 5' RNA cap: G0pppAG-RNA → (m7)G0pppAG-RNA ("cap-0")→(m7)G0pppAm2'-O-G-RNA ("cap-1"). To elucidate how viral RNA is specifically recognized and methylated, we determined the crystal structure of a ternary complex between the full-length NS5 protein from dengue virus, an octameric cap-0 viral RNA substrate bearing the authentic DENV genomic sequence (5'-(m7)G0pppA1G2U3U4G5U6U7-3'), and S-adenosyl-l-homocysteine (SAH), the by-product of the methylation reaction. The structure provides for the first time, to our knowledge, a molecular basis for specific adenosine 2'-O-methylation, rationalizes mutagenesis studies targeting the K61-D146-K180-E216 enzymatic tetrad as well as residues lining the RNA binding groove, and offers previously unidentified mechanistic and evolutionary insights into cap-1 formation by NS5, which underlies innate immunity evasion by flaviviruses.

  6. 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.

  7. First molecular epidemiology of Entamoeba histolytica, E. dispar and E. moshkovskii infections in Yemen: different species-specific associated risk factors.

    Science.gov (United States)

    Al-Areeqi, Mona A; Sady, Hany; Al-Mekhlafi, Hesham M; Anuar, Tengku Shahrul; Al-Adhroey, Abdulelah H; Atroosh, Wahib M; Dawaki, Salwa; Elyana, Fatin Nur; Nasr, Nabil A; Ithoi, Init; Lau, Yee-Ling; Surin, Johari

    2017-04-01

    To investigate the molecular epidemiology of Entamoeba histolytica, E. dispar and E. moshkovskii infections among rural communities in Yemen. In a community-based study, faecal samples were collected from 605 participants and examined by wet mount, formalin-ether sedimentation, trichrome staining and nested multiplex PCR techniques. Demographic, socio-economic and environmental information was collected using a pre-tested questionnaire. Overall, 324 (53.6%) of the samples were positive for Entamoeba cysts and/or trophozoites by microscopic examination. Molecular analysis revealed that 20.2%, 15.7% and 18.2% of the samples were positive for E. histolytica, E. dispar and E. moshkovskii, respectively. Multivariate analysis showed different sets of species-specific risk factors among these communities. Educational level was identified as the significant risk factor for E. histolytica; age and gender were the significant risk factors for E. moshkovskii; and sources of drinking water and consumption of unwashed vegetables were the significant risk factors for E. dispar. Moreover, living in coastal/foothill areas and presence of other infected family members were risk factors for both E. histolytica and E. moshkovskii infections. The study reveals that Entamoeba spp. infection is highly prevalent among rural communities in Yemen, with E. histolytica, E. dispar and E. moshkovskii differentiated for the first time. Identifying and treating infected family members, providing health education pertinent to good personal and food hygiene practices and providing clean drinking water should be considered in developing a strategy to control intestinal parasitic infections in these communities, particularly in the coastal/foothill areas of the country. © 2017 John Wiley & Sons Ltd.

  8. 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.

  9. Carbon sources in suspended particles and surface sediments from the Beaufort Sea revealed by molecular lipid biomarkers and compound-specific isotope analysis

    Directory of Open Access Journals (Sweden)

    I. Tolosa

    2013-03-01

    Full Text Available Molecular lipid biomarkers (hydrocarbons, alcohols, sterols and fatty acids and compound-specific isotope analysis of suspended particulate organic matter (SPM and surface sediments of the Mackenzie Shelf and slope (southeast Beaufort Sea, Arctic Ocean were studied in summer 2009. The concentrations of the molecular lipid markers, characteristic of known organic matter sources, were grouped and used as proxies to evaluate the relative importance of fresh algal, detrital algal, fossil, C3 terrestrial plants, bacterial and zooplankton material in the organic matter (OM of this area. Fossil and detrital algal contributions were the major fractions of the freshwater SPM from the Mackenzie River with ~34% each of the total molecular biomarkers. Fresh algal, C3 terrestrial, bacterial and zooplanktonic components represented much lower percentages, 17, 10, 4 and 80%, with a minor contribution of fossil and C3 terrestrial biomarkers. Characterization of the sediments revealed a major sink of refractory algal material mixed with some fresh algal material, fossil hydrocarbons and a small input of C3 terrestrial sources. In particular, the sediments from the shelf and at the mouth of the Amundsen Gulf presented the highest contribution of detrital algal material (60–75%, whereas those from the slope contained the highest proportion of fossil (40% and C3 terrestrial plant material (10%. Overall, considering that the detrital algal material is marine derived, autochthonous sources contributed more than allochthonous sources to the OM lipid pool. Using the ratio of an allochthonous biomarker (normalized to total organic carbon, TOC found in the sediments to those measured at the river mouth water, we estimated that the fraction of terrestrial material preserved in the sediments accounted for 30–40% of the total carbon in the inner shelf sediments, 17% in the outer shelf and Amundsen Gulf and up to 25% in the slope sediments. These estimates are low

  10. Sequence-specific detection of different strains of LCMV in a single sample using tentacle probes.

    Science.gov (United States)

    Franco, Lina S; Holechek, Susan A; Caplan, Michael R; Blattman, Joseph N

    2017-10-13

    Virus infections often result in quasispecies of viral strains that can have dramatic impacts on disease outcomes. However, sequencing of viruses to determine strain composition is time consuming and often cost-prohibitive. Rapid, cost-effective methods are needed for accurate measurement of virus diversity to understand virus evolution and can be useful for experimental systems. We have developed a novel molecular method for sequence-specific detection of RNA virus genetic variants called Tentacle Probes. The probes are modified molecular beacons that have dramatically improved false positive rates and specificity in routine qPCR. To validate this approach, we have designed Tentacle Probes for two different strains of Lymphocytic Choriomeningitis Virus (LCMV) that differ by only 3 nucleotide substitutions, the parental Armstrong and the more virulent Clone-13 strain. One of these mutations is a missense mutation in the receptor protein GP1 that leads to the Armstrong strain to cause an acute infection and Clone-13 to cause a chronic infection instead. The probes were designed using thermodynamic calculations for hybridization between target or non-target sequences and the probe. Using this approach, we were able to distinguish these two strains of LCMV individually by a single nucleotide mutation. The assay showed high reproducibility among different concentrations of viral cDNA, as well as high specificity and sensitivity, especially for the Clone-13 Tentacle Probe. Furthermore, in virus mixing experiments we were able to detect less than 10% of Clone-13 cDNA diluted in Armstrong cDNA. Thus, we have developed a fast, cost-effective approach for identifying Clone-13 strain in a mix of other LCMV strains.

  11. Genome-wide analysis of the mouse lung transcriptome reveals novel molecular gene interaction networks and cell-specific expression signatures

    Directory of Open Access Journals (Sweden)

    Williams Robert W

    2011-05-01

    Full Text Available Abstract Background The lung is critical in surveillance and initial defense against pathogens. In humans, as in mice, individual genetic differences strongly modulate pulmonary responses to infectious agents, severity of lung disease, and potential allergic reactions. In a first step towards understanding genetic predisposition and pulmonary molecular networks that underlie individual differences in disease vulnerability, we performed a global analysis of normative lung gene expression levels in inbred mouse strains and a large family of BXD strains that are widely used for systems genetics. Our goal is to provide a key community resource on the genetics of the normative lung transcriptome that can serve as a foundation for experimental analysis and allow predicting genetic predisposition and response to pathogens, allergens, and xenobiotics. Methods Steady-state polyA+ mRNA levels were assayed across a diverse and fully genotyped panel of 57 isogenic strains using the Affymetrix M430 2.0 array. Correlations of expression levels between genes were determined. Global expression QTL (eQTL analysis and network covariance analysis was performed using tools and resources in GeneNetwork http://www.genenetwork.org. Results Expression values were highly variable across strains and in many cases exhibited a high heri-tability factor. Several genes which showed a restricted expression to lung tissue were identified. Using correlations between gene expression values across all strains, we defined and extended memberships of several important molecular networks in the lung. Furthermore, we were able to extract signatures of immune cell subpopulations and characterize co-variation and shared genetic modulation. Known QTL regions for respiratory infection susceptibility were investigated and several cis-eQTL genes were identified. Numerous cis- and trans-regulated transcripts and chromosomal intervals with strong regulatory activity were mapped. The Cyp1a1 P

  12. Breast-specific gamma-imaging: molecular imaging of the breast using 99mTc-sestamibi and a small-field-of-view gamma-camera.

    Science.gov (United States)

    Jones, Elizabeth A; Phan, Trinh D; Blanchard, Deborah A; Miley, Abbe

    2009-12-01

    Breast-specific gamma-imaging (BSGI), also known as molecular breast imaging, is breast scintigraphy using a small-field-of-view gamma-camera and (99m)Tc-sestamibi. There are many different types of breast cancer, and many have characteristics making them challenging to detect by mammography and ultrasound. BSGI is a cost-effective, highly sensitive and specific technique that complements other imaging modalities currently being used to identify malignant lesions in the breast. Using the current Society of Nuclear Medicine guidelines for breast scintigraphy, Legacy Good Samaritan Hospital began conducting BSGI, breast scintigraphy with a breast-optimized gamma-camera. In our experience, optimal imaging has been conducted in the Breast Center by a nuclear medicine technologist. In addition, the breast radiologists read the BSGI images in correlation with the mammograms, ultrasounds, and other imaging studies performed. By modifying the current Society of Nuclear Medicine protocol to adapt it to the practice of breast scintigraphy with these new systems and by providing image interpretation in conjunction with the other breast imaging studies, our center has found BSGI to be a valuable adjunctive procedure in the diagnosis of breast cancer. The development of a small-field-of-view gamma-camera, designed to optimize breast imaging, has resulted in improved detection capabilities, particularly for lesions less than 1 cm. Our experience with this procedure has proven to aid in the clinical work-up of many of our breast patients. After reading this article, the reader should understand the history of breast scintigraphy, the pharmaceutical used, patient preparation and positioning, imaging protocol guidelines, clinical indications, and the role of breast scintigraphy in breast cancer diagnosis.

  13. Extracellular self-DNA as a damage-associated molecular pattern (DAMP) that triggers self-specific immunity induction in plants.

    Science.gov (United States)

    Duran-Flores, Dalia; Heil, Martin

    2017-10-16

    Mammals sense self or non-self extracellular or extranuclear DNA fragments (hereinafter collectively termed eDNA) as indicators of injury or infection and respond with immunity. We hypothesised that eDNA acts as a damage-associated molecular pattern (DAMP) also in plants and that it contributes to self versus non-self discrimination. Treating plants and suspension-cultured cells of common bean (Phaseolus vulgaris) with fragmented self eDNA (obtained from other plants of the same species) induced early, immunity-related signalling responses such as H 2 O 2 generation and MAPK activation, decreased the infection by a bacterial pathogen (Pseudomonas syringae) and increased an indirect defence to herbivores (extrafloral nectar secretion). By contrast, non-self DNA (obtained from lima bean, Phaseolus lunatus, and Acacia farnesiana) had significantly lower or no detectable effects. Only fragments below a size of 700 bp were active, and treating the eDNA preparation DNAse abolished its inducing effects, whereas treatment with RNAse or proteinase had no detectable effect. These findings indicate that DNA fragments, rather than small RNAs, single nucleotides or proteins, accounted for the observed effects. We suggest that eDNA functions a DAMP in plants and that plants discriminate self from non-self at a species-specific level. The immune systems of plants and mammals share multiple central elements, but further work will be required to understand the mechanisms and the selective benefits of an immunity response that is triggered by eDNA in a species-specific manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Influence of specific intermolecular interactions on the thermal and dielectric properties of bulk polymers: atomistic molecular dynamics simulations of Nylon 6.

    Science.gov (United States)

    Lukasheva, N V; Tolmachev, D A; Nazarychev, V M; Kenny, J M; Lyulin, S V

    2017-01-04

    Specific intermolecular interactions, in particular H-bonding, have a strong influence on the structural, thermal and relaxation characteristics of polymers. We report here the results of molecular dynamics simulations of Nylon 6 which provides an excellent example for the investigation of such an influence. To demonstrate the effect of proper accounting for H-bonding on bulk polymer properties, the AMBER99sb force field is used with two different parametrization approaches leading to two different sets of partial atomic charges. The simulations allowed the study of the thermal and dielectric properties in a wide range of temperatures and cooling rates. The feasibility of the use of the three methods for the estimation of the glass transition temperature not only from the temperature dependence of structural characteristics such as density, but also by using the electrostatic energy and dielectric constant is demonstrated. The values of glass transition temperatures obtained at different cooling rates are practically the same for the three methods. By proper accounting for partial charges in the simulations, a reasonable agreement between the results of our simulations and experimental data for the density, thermal expansion coefficient, static dielectric constant and activation energy of γ and β relaxations is obtained demonstrating the validity of the modeling approach reported.

  15. Solvation Mechanism of Task-Specific Ionic Liquids in Water: A Combined Investigation Using Classical Molecular Dynamics and Density Functional Theory.

    Science.gov (United States)

    Yuvaraj, Surya V J; Zhdanov, Ravil K; Belosludov, Rodion V; Belosludov, Vladimir R; Subbotin, Oleg S; Kanie, Kiyoshi; Funaki, Kenji; Muramatsu, Atsushi; Nakamura, Takashi; Kawazoe, Yoshiyuki

    2015-10-08

    The solvation behavior of task-specific ionic liquids (TSILs) containing a common, L-histidine derived imidazolium cation [C20H28N3O3](+) and different anions, bromide-[Br](-) and bis(trifluoromethylsulfonyl)amide-[NTF2](-), in water is examined, computationally. These amino acid functionalized ionic liquids (ILs) are taken into account because of their ability to react with rare earth metal salts. It has been noted that the TSIL with [Br](-) is more soluble than its counterpart TSIL with [NTF2](-), experimentally. In this theoretical work, the combined classical molecular dynamics (CMD) and density functional theory (DFT) calculations are performed to study the behavior of the bulk phase of these two TSILs in the vicinity of water (H2O) molecules with different concentrations. Initially, all the constructed systems are equilibrated using the CMD method. The final structures of the equilibrated systems are extracted for DFT calculations. Under CMD operation, the radial distribution function (RDF) plots and viscosity of TSILs are analyzed to understand the effect of water on TSILs. In the DFT regime, binding energy per H2O, charge transfer, charge density mapping, and electronic density of states (EDOS) analyses are done. The CMD results along with the DFT results are consolidated to support the hydrophilic and hydrophobic nature of the TSILs. Interestingly, we have found a strong correlation between the viscosity and the EDOS results that leads to an understanding of the hydration properties of the TSILs.

  16. The Molecular Switch of Telomere Phages: High Binding Specificity of the PY54 Cro Lytic Repressor to a Single Operator Site

    Science.gov (United States)

    Hammerl, Jens Andre; Roschanski, Nicole; Lurz, Rudi; Johne, Reimar; Lanka, Erich; Hertwig, Stefan

    2015-01-01

    Temperate bacteriophages possess a molecular switch, which regulates the lytic and lysogenic growth. The genomes of the temperate telomere phages N15, PY54 and ϕKO2 harbor a primary immunity region (immB) comprising genes for the prophage repressor, the lytic repressor and a putative antiterminator. The roles of these products are thought to be similar to those of the lambda proteins CI, Cro and Q, respectively. Moreover, the gene order and the location of several operator sites in the prototype telomere phage N15 and in ϕKO2 are also reminiscent of lambda-like phages. By contrast, in silico analyses revealed the presence of only one operator (OR3) in PY54. The purified PY54 Cro protein was used for EMSA studies demonstrating that it exclusively binds to a 16-bp palindromic site (OR3) upstream of the prophage repressor gene. The OR3 operator sequences of PY54 and ϕKO2/N15 only differ by their peripheral base pairs, which are responsible for Cro specificity. PY54 cI and cro transcription is regulated by highly active promoters initiating the synthesis of a homogenious species of leaderless mRNA. The location of the PY54 Cro binding site and of the identified promoters suggests that the lytic repressor suppresses cI transcription but not its own synthesis. The results indicate an unexpected diversity of the growth regulation mechanisms in lambda-related phages. PMID:26043380

  17. Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study

    Directory of Open Access Journals (Sweden)

    Dahl R

    2013-10-01

    Full Text Available Ronald Dahl,1 Dalal Jadayel,2 Vijay KT Alagappan,3 Hungta Chen,3 Donald Banerji31Department of Dermatology, Allergy Centre, Odense University Hospital, Odense, Denmark; 2Novartis Horsham Research Centre, Horsham, UK; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAIntroduction: The BEACON study evaluated the efficacy and safety of QVA149, a once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist (LABA indacaterol and long-acting muscarinic antagonist (LAMA glycopyrronium (NVA237, in development for the treatment of patients with chronic obstructive pulmonary disease (COPD, compared with the free-dose concurrent administration of indacaterol plus glycopyrronium (IND+GLY.Methods: In this multicenter, double-blind, parallel group study, patients with stage II or stage III COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] 2010 were randomized (1:1 to once-daily QVA149 (110 µg indacaterol/50 µg glycopyrronium or concurrent administration of indacaterol (150 µg and glycopyrronium (50 µg via the Breezhaler® device (Novartis AG, Basel, Switzerland for 4 weeks. The primary endpoint was to evaluate the noninferiority of QVA149 as compared with concurrent administration of IND+GLY, for trough forced expiratory volume in 1 second (FEV1 after 4 weeks of treatment. The other assessments included FEV1 area under the curve from 0 to 4 hours (AUC0–4 hours at day 1 and week 4, symptom scores, rescue medication use, safety, and tolerability over the 4-week study period.Results: Of 193 patients randomized, 187 (96.9% completed the study. Trough FEV1 at week 4 for QVA149 and IND+GLY was 1.46 L ± 0.02 and 1.46 L ± 0.18, respectively. The FEV1 AUC0–4 hours at day 1 and week 4 were similar between the two treatment groups. Both treatment groups had a similar reduction in symptom scores and rescue medication use for the 4-week treatment period. Overall, 25.6% of patients in QVA149 group

  18. Inhibition of p38 MAPK activity leads to cell type-specific effects on the molecular circadian clock and time-dependent reduction of glioma cell invasiveness.

    Science.gov (United States)

    Goldsmith, Charles S; Kim, Sam Moon; Karunarathna, Nirmala; Neuendorff, Nichole; Gerard Toussaint, L; Earnest, David J; Bell-Pedersen, Deborah

    2018-01-10

    The circadian clock is the basis for biological time keeping in eukaryotic organisms. The clock mechanism relies on biochemical signaling pathways to detect environmental stimuli and to regulate the expression of clock-controlled genes throughout the body. MAPK signaling pathways function in both circadian input and output pathways in mammals depending on the tissue; however, little is known about the role of p38 MAPK, an established tumor suppressor, in the mammalian circadian system. Increased expression and activity of p38 MAPK is correlated with poor prognosis in cancer, including glioblastoma multiforme; however, the toxicity of p38 MAPK inhibitors limits their clinical use. Here, we test if timed application of the specific p38 MAPK inhibitor VX-745 reduces glioma cell invasive properties in vitro. The levels and rhythmic accumulation of active phosphorylated p38 MAPK in different cell lines were determined by western blots. Rhythmic luciferase activity from clock gene luciferase reporter cells lines was used to test the effect of p38 MAPK inhibition on clock properties as determined using the damped sine fit and Levenberg-Marquardt algorithm. Nonlinear regression and Akaike's information criteria were used to establish rhythmicity. Boyden chamber assays were used to measure glioma cell invasiveness following time-of-day-specific treatment with VX-745. Significant differences were established using t-tests. We demonstrate the activity of p38 MAPK cycles under control of the clock in mouse fibroblast and SCN cell lines. The levels of phosphorylated p38 MAPK were significantly reduced in clock-deficient cells, indicating that the circadian clock plays an important role in activation of this pathway. Inhibition of p38 MAPK activity with VX-745 led to cell-type-specific period changes in the molecular clock. In addition, phosphorylated p38 MAPK levels were rhythmic in HA glial cells, and high and arrhythmic in invasive IM3 glioma cells. We show that inhibition of

  19. Comparison of mapped and measured total ionospheric electron content using global positioning system and beacon satellite observations

    International Nuclear Information System (INIS)

    Lanyi, G.E.; Roth, T.

    1988-01-01

    Total ionospheric electron contents (TEC) were measured by global positioning system (GPS) dual-frequency receivers developed by the Jet Propulsion Laboratory. The measurements included P-code (precise ranging code) and carrier phase data for six GPS satellites during multiple five-hour observing sessions. A set of these GPS TEC measurements were mapped from the GPS lines of sight to the line of sight of a Faraday beacon satellite by statistically fitting the TEC data to a simple model of the ionosphere. The mapped GPS TEC values were compared with the Faraday rotation measurements. Because GPS transmitter offsets are different for each satellite and because some GPS receiver offsets were uncalibrated, the sums of the satellite and receiver offsets were estimated simultaneously with the TEC in a least squares procedure. The accuracy of this estimation procedure is evaluated indicating that the error of the GPS-determined line of sight TEC can be at or below 1 x 10 to the 16th el/sq cm. Consequently, the current level of accuracy is comparable to the Faraday rotation technique; however, GPS provides superior sky coverage. 15 references

  20. Location-Enhanced Activity Recognition in Indoor Environments Using Off the Shelf Smart Watch Technology and BLE Beacons.

    Science.gov (United States)

    Filippoupolitis, Avgoustinos; Oliff, William; Takand, Babak; Loukas, George

    2017-05-27

    Activity recognition in indoor spaces benefits context awareness and improves the efficiency of applications related to personalised health monitoring, building energy management, security and safety. The majority of activity recognition frameworks, however, employ a network of specialised building sensors or a network of body-worn sensors. As this approach suffers with respect to practicality, we propose the use of commercial off-the-shelf devices. In this work, we design and evaluate an activity recognition system composed of a smart watch, which is enhanced with location information coming from Bluetooth Low Energy (BLE) beacons. We evaluate the performance of this approach for a variety of activities performed in an indoor laboratory environment, using four supervised machine learning algorithms. Our experimental results indicate that our location-enhanced activity recognition system is able to reach a classification accuracy ranging from 92% to 100%, while without location information classification accuracy it can drop to as low as 50% in some cases, depending on the window size chosen for data segmentation.

  1. Location-Enhanced Activity Recognition in Indoor Environments Using Off the Shelf Smart Watch Technology and BLE Beacons

    Directory of Open Access Journals (Sweden)

    Avgoustinos Filippoupolitis

    2017-05-01

    Full Text Available Activity recognition in indoor spaces benefits context awareness and improves the efficiency of applications related to personalised health monitoring, building energy management, security and safety. The majority of activity recognition frameworks, however, employ a network of specialised building sensors or a network of body-worn sensors. As this approach suffers with respect to practicality, we propose the use of commercial off-the-shelf devices. In this work, we design and evaluate an activity recognition system composed of a smart watch, which is enhanced with location information coming from Bluetooth Low Energy (BLE beacons. We evaluate the performance of this approach for a variety of activities performed in an indoor laboratory environment, using four supervised machine learning algorithms. Our experimental results indicate that our location-enhanced activity recognition system is able to reach a classification accuracy ranging from 92% to 100%, while without location information classification accuracy it can drop to as low as 50% in some cases, depending on the window size chosen for data segmentation.

  2. Molecular insights into the specific recognition between the RNA binding domain qRRM2 of hnRNP F and G-tract RNA: A molecular dynamics study.

    Science.gov (United States)

    Wang, Lingyun; Yan, Feng

    2017-12-09

    Heterogeneous nuclear ribonucleoprotein F (hnRNP F) controls the expression of various genes through regulating the alternative splicing of pre-mRNAs in the nucleus. It uses three quasi-RNA recognition motifs (qRRMs) to recognize G-tract RNA which contains at least three consecutive guanines. The structures containing qRRMs of hnRNP F in complex with G-tract RNA have been determined by nuclear magnetic resonance (NMR) spectroscopy, shedding light on the recognition mechanism of qRRMs with G-tract RNA. However, knowledge of the recognition details is still lacking. To investigate how qRRMs specifically bind with G-tract RNA and how the mutations of any guanine to an adenine in the G-tract affect the binding, molecular dynamics simulations with binding free energy analysis were performed based on the NMR structure of qRRM2 in complex with G-tract RNA. Simulation results demonstrate that qRRM2 binds strongly with G-tract RNA, but any mutation of the G-tract leads to a drastic reduction of the binding free energy. Further comparisons of the energetic components reveal that van der Waals and non-polar interactions play essential roles in the binding between qRRM2 and G-tract RNA, but the interactions are weakened by the effect of RNA mutations. Structural and dynamical analyses indicate that when qRRM2 binds with G-tract RNA, both qRRM2 and G-tract maintain stabilized structures and dynamics; however, the stability is disrupted by the mutations of the G-tract. These results provide novel insights into the recognition mechanism of qRRM2 with G-tract RNA that are not elucidated by the NMR technique. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Fine epitope specificity of anti-erythropoietin antibodies reveals molecular mimicry with HIV-1 p17 protein: a pathogenetic mechanism for HIV-1-related anemia.

    Science.gov (United States)

    Tsiakalos, Aristotelis; Routsias, John G; Kordossis, Theodore; Moutsopoulos, Haralampos M; Tzioufas, Athanasios G; Sipsas, Nikolaos V

    2011-09-15

    Circulating autoantibodies to endogenous erythropoietin (anti-Epo) are detected in human immunodeficiency virus type 1 (HIV-1)-infected patients and represent a risk factor for anemia. The aim of this study was to map the B-cell epitopes on the Epo molecule. Serum samples from HIV-1-positive patients and healthy individuals were tested against overlapping peptides covering the entire sequence of Epo. Serum samples from anti-Epo-positive patients exhibited significant binding to Epo epitopes spanning the following sequences: amino acids 1-20 (Ep1), amino acids 54-72 (Ep5), and amino acids 147-166 (Ep12). Structural analysis of erythropoietin revealed that the immunodominant epitopes, Ep1 and Ep12, comprise the interaction interface with Epo receptor (EpoR). Autoantibodies binding to this specific region are anticipated to inhibit the Epo-EpoR interaction, resulting in blunted erythropoiesis; this phenomenon is indicated by the significantly higher Epo levels and lower hemoglobin levels of anti-Ep1-positive patients compared with anti-Ep1-negative individuals. The region corresponding to the Ep1 epitope exhibited a 63% sequence homology with the ³⁴LVCASRELERFAVNPGLLE⁵² fragment of the HIV-1 p17 matrix protein. These results suggest that the main body of anti-Epo is directed against a functional domain of Epo, and that the presence of anti-Epo can be considered to be a result of a molecular mimicry mechanism, which is caused by the similarity between the Ep1 region and the p17 protein.

  4. Specific sequestering agents for the actinides. 2. A ligand field effect in the crystal and molecular structures of tetrakis(catecholato)uranate(IV) and -thorate(IV)

    International Nuclear Information System (INIS)

    Sofen, S.R.; Abu-Dari, K.; Freyberg, D.P.; Raymond, K.N.

    1978-01-01

    The structures of the title compounds, Na 4 [M(C 6 H 4 O 2 ) 4 ] 21H 2 O,M = Th, U, have been determined by single-crystal x-ray diffraction methods using counter data. These isostructural tetrakis(catecholato) complexes are structural archetypes for actinide-specific macrocyclic sequestering agents. The complexes have D/sub 2d/ molecular symmetry. The M--O bond lengths are 2.417(3) and 2.421(3) A for Th and 2.362(3) and 2.389(4) A for U. The ring O--M--O bond angles are 66.8(1) 0 for Th and 67.7(1) 0 for U. The difference in M--O bond lengths for the uranium complex [0.027(5) A] vs. a difference of 0.004(4) A in the thorium complex is attributed to a ligand field effect of the 5f 2 electronic configuration of U(IV) vs. 5f 0 for Th(IV). Green crystals of the uranium complex, obtained from basic aqueous solution, conform to the space group I anti 4 with a = 14.659(3) and c = 9.984(4) A. For 3660 independent data with F 0 2 > 3 sigma(F 0 2 ) full-matrix least-squares refinement with anisotropic thermal parameters for all nonhydrogen atoms converged to unweighted and weighted R factors of 3.8 and 4.5%, respectively. The colorless thorium compound, also obtained from basic aqueous solution, has a = 14.709(4) and c = 9.978(3) A. For 5038 independent data refinement as above converged to unweighted and weighted R factors of 4.3 and 5.3%, respectively. 3 figures, 8 tables

  5. A Network of AOPs for reduced thyroid hormone synthesis derived from inhibition of Thyroperoxidase - A common Molecular Initiating Event Leading to Species-Specific Indices of Adversity.

    Science.gov (United States)

    This collection of 3 AOPs describe varying outcomes of adversity dependent upon species in response to inhibition of thyroperoxidase (TPO) during development. Chemical inhibition of TPO, the molecular-initiating event (MIE), results in decreased thyroid hormone (TH) synthesis, a...

  6. Molecular ferromagnetism

    International Nuclear Information System (INIS)

    Epstein, A.J.

    1990-01-01

    This past year has been one of substantial advancement in both the physics and chemistry of molecular and polymeric ferromagnets. The specific heat studies of (DMeFc)(TCNE) have revealed a cusp at the three-dimensional ferromagnetic transition temperature with a crossover to primarily 1-D behavior at higher temperatures. This paper discusses these studies

  7. Molecular Star

    Indian Academy of Sciences (India)

    This report describes the making of a self-assembled coordination architecture that is named as a 'molecular star' since it resembles the shape of a star; more specifically a five-pointed star. This work has been already published in Chemistry- A European Jour- nal in the September 2017 issue and was featured in the cover.

  8. [Incomplete congruence between morphobiological characters and sex-specific molecular markers in Pacific salmons: II. Population and temporal variability of the phenomenon].

    Science.gov (United States)

    Brykov, V A; Kukhlevskiĭ, A D; Podlesnykh, A V

    2010-11-01

    The congruence between secondary sexual characters and molecular markers, linked to the Y chromosome was examined in Asian populations of five Pacific salmon species of the genus Oncorhynchus. Our results support the existence of discrepancy between secondary sexual characters and sex-linked molecular markers in all species examined, which suggests the existence of similar or identical mechanism responsible for this phenomenon in Pacific salmons. Clinal latitudinal directional variation of the character confirmed the possibility that this phenomenon could be adaptively important, including its importance for regulation of the population number. In addition to natural factors affecting the degree of discrepancy between morphobiological characters and molecular markers in the Pacific salmon populations, anthropogenic factors, in particular intense fishery of certain population or population group, is also important.

  9. Glu-Ureido-Based Inhibitors of Prostate-Specific Membrane Antigen: Lessons Learned During the Development of a Novel Class of Low-Molecular-Weight Theranostic Radiotracers

    Czech Academy of Sciences Publication Activity Database

    Kopka, K.; Benesova, M.; Bařinka, Cyril; Haberkorn, U.; Babich, J.

    2017-01-01

    Roč. 58, Suppl. 2 (2017), s. 17-26 ISSN 0161-5505 Institutional support: RVO:86652036 Keywords : small-molecule PSMA inhibitors * theranostic PSMA radioligands * PSMA radiotracers Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 6.646, year: 2016

  10. Ward-Specific Rates of Nasal Cocolonization with Methicillin-Susceptible and -Resistant Staphylococcus spp. and Potential Impact on Molecular Methicillin-Resistant Staphylococcus aureus Screening Tests

    Science.gov (United States)

    Rasigade, Jean-Philippe; Lustig, Sebastien; Lhoste, Yannick; Valour, Florent; Guerin, Claude; Aubrun, Frederic; Tigaud, Sylvestre; Laurent, Frederic

    2013-01-01

    We report that the rates of nasal cocolonization with methicillin-susceptible Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci can vary widely between patients admitted to different wards within a single hospital. Such cocolonization can greatly influence the performance of molecular methicillin-resistant S. aureus (MRSA) screening tests depending on the methods used and targets selected. PMID:23658254

  11. Pan-cancer subtyping in a 2D-map shows substructures that are driven by specific combinations of molecular characteristics

    NARCIS (Netherlands)

    Taskesen, E.; Huisman, S.M.H.; Mahfouz, A.M.E.T.A.; Krijthe, J.H.; de Ridder, J.; van de Stolpe, A; van den Akker, E.B.; Verhaegh, Wim; Reinders, M.J.T.

    2016-01-01

    The use of genome-wide data in cancer research, for the identification of groups of patients with similar molecular characteristics, has become a standard approach for applications in therapy-response, prognosis-prediction, and drug-development. To progress in these applications, the trend is to

  12. Molecular and biological characterization of Tomato mottle mosaic virus and development of reverse transcription-polymerase chain reaction for species-specific detection

    Science.gov (United States)

    Tomato mottle mosaic virus (ToMMV) was first identified in 2013 as a novel tobamovirus infecting tomatoes in Mexico. In just a few years, ToMMV has been identified in several countries around the world, including the United States. In the present study, we characterized the molecular, serological an...

  13. iBodies: modular synthetic antibody mimetics based on hydrophilic polymers decorated with functional moieties as tools for molecular recognition, imaging and specific drug delivery

    Czech Academy of Sciences Publication Activity Database

    Šácha, Pavel; Dvořáková, Petra; Knedlík, Tomáš; Schimer, Jiří; Šubr, Vladimír; Ulbrich, Karel; Bušek, P.; Navrátil, Václav; Sedlák, František; Majer, Pavel; Šedo, A.; Konvalinka, Jan

    2017-01-01

    Roč. 284, Suppl 1 (2017), s. 340 ISSN 1742-464X. [FEBS Congress /42./ From Molecules to Cells and Back. 10.09.2017-14.09.2017, Jerusalem] Institutional support: RVO:61388963 ; RVO:61389013 Keywords : antibody mimetics * molecular recognition * polymer conjugates Subject RIV: CE - Biochemistry

  14. Combined Pharmacological and Genetic Manipulations Unlock Unprecedented Temporal Elasticity and Reveal Phase-Specific Modulation of the Molecular Circadian Clock of the Mouse Suprachiasmatic Nucleus.

    Science.gov (United States)

    Patton, Andrew P; Chesham, Johanna E; Hastings, Michael H

    2016-09-07

    The suprachiasmatic nucleus (SCN) is the master circadian oscillator encoding time-of-day information. SCN timekeeping is sustained by a cell-autonomous transcriptional-translational feedback loop, whereby expression of the Period and Cryptochrome genes is negatively regulated by their protein products. This loop in turn drives circadian oscillations in gene expression that direct SCN electrical activity and thence behavior. The robustness of SCN timekeeping is further enhanced by interneuronal, circuit-level coupling. The aim of this study was to combine pharmacological and genetic manipulations to push the SCN clockwork toward its limits and, by doing so, probe cell-autonomous and emergent, circuit-level properties. Circadian oscillation of mouse SCN organotypic slice cultures was monitored as PER2::LUC bioluminescence. SCN of three genetic backgrounds-wild-type, short-period CK1ε(Tau/Tau) mutant, and long-period Fbxl3(Afh/Afh) mutant-all responded reversibly to pharmacological manipulation with period-altering compounds: picrotoxin, PF-670462 (4-[1-Cyclohexyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2-pyrimidinamine dihydrochloride), and KNK437 (N-Formyl-3,4-methylenedioxy-benzylidine-gamma-butyrolactam). This revealed a remarkably wide operating range of sustained periods extending across 25 h, from ≤17 h to >42 h. Moreover, this range was maintained at network and single-cell levels. Development of a new technique for formal analysis of circadian waveform, first derivative analysis (FDA), revealed internal phase patterning to the circadian oscillation at these extreme periods and differential phase sensitivity of the SCN to genetic and pharmacological manipulations. For example, FDA of the CK1ε(Tau/Tau) mutant SCN treated with the CK1ε-specific inhibitor PF-4800567 (3-[(3-Chlorophenoxy)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride) revealed that period acceleration in the mutant is due to inappropriately phased

  15. An Indoor Location-Based Control System Using Bluetooth Beacons for IoT Systems.

    Science.gov (United States)

    Huh, Jun-Ho; Seo, Kyungryong

    2017-12-19

    The indoor location-based control system estimates the indoor position of a user to provide the service he/she requires. The major elements involved in the system are the localization server, service-provision client, user application positioning technology. The localization server controls access of terminal devices (e.g., Smart Phones and other wireless devices) to determine their locations within a specified space first and then the service-provision client initiates required services such as indoor navigation and monitoring/surveillance. The user application provides necessary data to let the server to localize the devices or allow the user to receive various services from the client. The major technological elements involved in this system are indoor space partition method, Bluetooth 4.0, RSSI (Received Signal Strength Indication) and trilateration. The system also employs the BLE communication technology when determining the position of the user in an indoor space. The position information obtained is then used to control a specific device(s). These technologies are fundamental in achieving a "Smart Living". An indoor location-based control system that provides services by estimating user's indoor locations has been implemented in this study (First scenario). The algorithm introduced in this study (Second scenario) is effective in extracting valid samples from the RSSI dataset but has it has some drawbacks as well. Although we used a range-average algorithm that measures the shortest distance, there are some limitations because the measurement results depend on the sample size and the sample efficiency depends on sampling speeds and environmental changes. However, the Bluetooth system can be implemented at a relatively low cost so that once the problem of precision is solved, it can be applied to various fields.

  16. An Indoor Location-Based Control System Using Bluetooth Beacons for IoT Systems

    Directory of Open Access Journals (Sweden)

    Jun-Ho Huh

    2017-12-01

    Full Text Available The indoor location-based control system estimates the indoor position of a user to provide the service he/she requires. The major elements involved in the system are the localization server, service-provision client, user application positioning technology. The localization server controls access of terminal devices (e.g., Smart Phones and other wireless devices to determine their locations within a specified space first and then the service-provision client initiates required services such as indoor navigation and monitoring/surveillance. The user application provides necessary data to let the server to localize the devices or allow the user to receive various services from the client. The major technological elements involved in this system are indoor space partition method, Bluetooth 4.0, RSSI (Received Signal Strength Indication and trilateration. The system also employs the BLE communication technology when determining the position of the user in an indoor space. The position information obtained is then used to control a specific device(s. These technologies are fundamental in achieving a “Smart Living”. An indoor location-based control system that provides services by estimating user’s indoor locations has been implemented in this study (First scenario. The algorithm introduced in this study (Second scenario is effective in extracting valid samples from the RSSI dataset but has it has some drawbacks as well. Although we used a range-average algorithm that measures the shortest distance, there are some limitations because the measurement results depend on the sample size and the sample efficiency depends on sampling speeds and environmental changes. However, the Bluetooth system can be implemented at a relatively low cost so that once the problem of precision is solved, it can be applied to various fields.

  17. The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions | Office of Cancer Genomics

    Science.gov (United States)

    We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children’s Oncology Group (COG) AML trials. The COG–National Cancer Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases.

  18. Proposal for novel curcumin derivatives as potent inhibitors against Alzheimer's disease: Ab initio molecular simulations on the specific interactions between amyloid-beta peptide and curcumin

    Science.gov (United States)

    Ota, Shintaro; Fujimori, Mitsuki; Ishimura, Hiromi; Shulga, Sergiy; Kurita, Noriyuki

    2017-10-01

    Accumulation of amyloid-β (Aβ) peptides in a brain is closely related with the pathogenesis of Alzheimer's disease. To suppress the production of Aβ peptides, we propose novel curcumin derivatives and investigate their binding properties with the amyloid precursor protein (APP), using protein-ligand docking as well as ab initio molecular simulations. Our proposed derivative (curcumin XIV) is found to have a large binding energy with APP and interacts strongly with the cleavage site Ala19 by secretase. It is thus expected that curcumin XIV can protect APP from the secretase attack and be a potent inhibitor against the production of Aβ peptides.

  19. Molecular Detection of Neuron-Specific ELAV-Like-Positive Cells in the Peripheral Blood of Patients with Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Vito D’Alessandro

    2008-01-01

    Full Text Available Background: n-ELAV (neuronal-Embryonic Lethal, Abnormal Vision-like genes belong to a family codifying for onconeural RNA-binding proteins. Anti-Hu-antibodies (anti-Hu-Ab are typically associated with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN, and low titres of anti-Hu-Ab, were found in newly diagnosed Small Cell Lung Cancer (SCLC. The aim of this study is to develop a sensitive and quantitative molecular real-time PCR assay to detect SCLC cells in peripheral blood (PB through nELAV-like transcripts quantification.

  20. Predicting fecal sources in waters with diverse pollution loads using general and molecular host-specific indicators and applying machine learning methods

    OpenAIRE

    Casanovas Massana, Arnau; Gómez Doñate, Marta; Sánchez, David; Belanche Muñoz, Luis Antonio; Muniesa, Maite; Blanch, Anicet R.

    2015-01-01

    In this study we use a machine learning software (Ichnaea) to generate predictive models for water samples with different concentrations of fecal contamination (point source, moderate and low). We applied several MST methods (host-specific Bacteroides phages, mitochondrial DNA genetic markers, Bifidobacterium adolescentis and Bifidobacterium dentium markers, and bifidobacterial host-specific qPCR), and general indicators (Escherichia colt, enterococci and somatic coliphages) to evaluate the s...

  1. Molecular evolution of myoglobin in the Tibetan Plateau endemic schizothoracine fish (Cyprinidae, Teleostei) and tissue-specific expression changes under hypoxia.

    Science.gov (United States)

    Qi, Delin; Chao, Yan; Zhao, Yongli; Xia, Mingzhe; Wu, Rongrong

    2018-04-01

    Myoglobin (Mb) is an oxygen-binding hemoprotein that was once thought to be exclusively expressed in oxidative myocytes of skeletal and cardiac muscle where it serves in oxygen storage and facilitates intracellular oxygen diffusion. In this study, we cloned the coding sequence of the Mb gene from four species, representing three groups, of the schizothoracine fish endemic to the Qinghai-Tibetan Plateau (QTP), then conducted molecular evolution analyses. We also investigated tissue expression patterns of Mb and the expression response to moderate and severe hypoxia at the mRNA and protein levels in a representative of the highly specialized schizothoracine fish species, Schizopygopsis pylzovi. Molecular evolution analyses showed that Mb from the highly specialized schizothoracine fish have undergone positive selection and one positively selected residue (81L) was identified, which is located in the F helix, close to or in contact with the heme. We present tentative evidence that the Mb duplication event occurred in the ancestor of the schizothoracine and Cyprininae fish (common carp and goldfish), and that the Mb2 paralog was subsequently lost in the schizothoracine fish. In S. pylzovi, Mb mRNA is expressed in various tissues with the exception of the intestine and gill, but all such tissues, including the liver, muscle, kidney, brain, eye, and skin, expressed very low levels of Mb mRNA (Tibetan Plateau fish.

  2. Man Overboard Beacon

    National Research Council Canada - National Science Library

    Frank, Thomas A

    2005-01-01

    .... A battery powers the multiple indicators contained in the housing, which include a high intensity strobe light to provide a visual indication, an x-band radar patch antenna to transmit a radar signal...

  3. Beacons of Sound

    DEFF Research Database (Denmark)

    Knakkergaard, Martin

    2018-01-01

    The chapter discusses expectations and imaginations vis-à-vis the concert hall of the twenty-first century. It outlines some of the central historical implications of western culture’s haven for sounding music. Based on the author’s study of the Icelandic concert-house Harpa, the chapter considers...... how these implications, together with the prime mover’s visions, have been transformed as private investors and politicians took over. The chapter furthermore investigates the objectives regarding musical sound and the far-reaching demands concerning acoustics that modern concert halls are required...

  4. Opportunistic Beacon Networks

    NARCIS (Netherlands)

    Türkes, Okan

    2016-01-01

    Modern society is surrounded by an ample spectrum of personal mobile devices with short-range wireless communication support. This ubiquity creates an immense potential of new concepts for people-centric ad hoc networks that can be applied to every personal and social dimension of life. The last

  5. Characterization of Bile Salt Hydrolase from Lactobacillus gasseri FR4 and Demonstration of Its Substrate Specificity and Inhibitory Mechanism Using Molecular Docking Analysis

    Directory of Open Access Journals (Sweden)

    Rizwana Parveen Rani

    2017-05-01

    Full Text Available Probiotic bacteria are beneficial to the health of poultry animals, thus are used as alternative candidates for antibiotics used as growth promoters (AGPs. However, they also reduce the body weight gain due to innate bile salt hydrolase (BSH activity. Hence, the addition of a suitable BSH inhibitor along with the probiotic feed can decrease the BSH activity. In this study, a BSH gene (981 bp encoding 326-amino acids was identified from the genome of Lactobacillus gasseri FR4 (LgBSH. The LgBSH-encoding gene was cloned and purified using an Escherichia coli BL21 (DE3 expression system, and its molecular weight (37 kDa was confirmed by SDS–PAGE and a Western blot analysis. LgBSH exhibited greater hydrolysis toward glyco-conjugated bile salts compared to tauro-conjugated bile salts. LgBSH displayed optimal activity at 52°C at a pH of 5.5, and activity was further increased by several reducing agents (DTT, surfactants (Triton X-100 and Tween 80, and organic solvents (isopropanol, butanol, and acetone. Riboflavin and penicillin V, respectively, inhibited LgBSH activity by 98.31 and 97.84%. A homology model of LgBSH was predicted using EfBSH (4WL3 as a template. Molecular docking analysis revealed that the glycocholic acid had lowest binding energy of -8.46 kcal/mol; on the other hand, inhibitors, i.e., riboflavin and penicillin V, had relatively higher binding energies of -6.25 and -7.38 kcal/mol, respectively. Our results suggest that L. gasseri FR4 along with riboflavin might be a potential alternative to AGPs for poultry animals.

  6. A cost-effective protocol for the parallel production of libraries of 13CH3-specifically labeled mutants for NMR studies of high molecular weight proteins.

    Science.gov (United States)

    Crublet, Elodie; Kerfah, Rime; Mas, Guillaume; Noirclerc-Savoye, Marjolaine; Lantez, Violaine; Vernet, Thierry; Boisbouvier, Jerome

    2014-01-01

    There is increasing interest in applying NMR spectroscopy to the study of large protein assemblies. Development of methyl-specific labeling protocols combined with improved NMR spectroscopy enable nowadays studies of proteins complexes up to 1 MDa. For such large complexes, the major interest lies in obtaining structural, dynamic and interaction information in solution, which requires sequence-specific resonance assignment of NMR signals. While such analysis is quite standard for small proteins, it remains one of the major bottlenecks when the size of the protein increases. Here, we describe implementation and latest improvements of SeSAM, a fast and user-friendly approach for assignment of methyl resonances in large proteins using mutagenesis. We have improved culture medium to boost the production of methyl-specifically labeled proteins, allowing us to perform small-scale parallel production and purification of a library of (13)CH3-specifically labeled mutants. This optimized protocol is illustrated by assignment of Alanine, Isoleucine, and Valine methyl groups of the homododecameric aminopeptidase PhTET2. We estimated that this improved method allows assignment of ca. 100 methyl cross-peaks in 2 weeks, including 4 days of NMR time and less than 2 k€ of isotopic materials.

  7. Molecular cloning, purification, and characterization of a novel polyMG-specific alginate lyase responsible for alginate MG block degradation in Stenotrophomas maltophilia KJ-2

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Su In; Kim, Hee Sook [Kyungsung Univ., Busan (Korea, Republic of). Dept. of Food Science and Biotechnology; Choi, Sung Hee; Lee, Eun Yeol [Kyung Hee Univ., Gyeonggi-do (Korea, Republic of). Dept. of Chemical Engineering

    2012-09-15

    A gene for a polyMG-specific alginate lyase possessing a novel structure was identified and cloned from Stenotrophomas maltophilia KJ-2 by using PCR with homologous nucleotide sequences-based primers. The recombinant alginate lyase consisting of 475 amino acids was purified on Ni-Sepharose column and exhibited the highest activity at pH 8 and 40 C. Interestingly, the recombinant alginate lyase was expected to have a similar catalytic active site of chondroitin B lyase but did not show chondroitin lyase activity. In the test of substrate specificity, the recombinant alginate lyase preferentially degraded the glycosidic bond of polyMG-block than polyM-block and polyG-block. The chemical structures of the degraded alginate oligosaccharides were elucidated to have mannuronate (M) at the reducing end on the basis of NMR analysis, supporting that KJ-2 polyMG-specific alginate lyase preferably degraded the glycosidic bond in M-G linkage than that in G-M linkage. The KJ-2 polyMG-specific alginate lyase can be used in combination with other alginate lyases for a synergistic saccharification of alginate. (orig.)

  8. Molecular analysis of the role of two aromatic aminotransferases and a broad-specificity aspartate aminotransferase in the aromatic amino acid metabolism of Pyrococcus furiosus

    NARCIS (Netherlands)

    Ward, D.E.; Vos, de W.M.; Oost, van der J.

    2002-01-01

    The genes encoding aromatic aminotransferase II (AroAT II) and aspartate aminotransferase (AspAT) from Pyrococcus furiosus have been identified, expressed in Escherichia coli and the recombinant proteins characterized. The AroAT II enzyme was specific for the transamination reaction of the aromatic

  9. RENAL SPECIFIC DELIVERY OF SULFAMETHOXAZOLE IN THE RAT BY COUPLING TO THE LOW-MOLECULAR-WEIGHT PROTEIN LYSOZYME VIA AN ACID-SENSITIVE LINKER

    NARCIS (Netherlands)

    FRANSSEN, EJF; MOOLENAAR, F; DEZEEUW, D; MEIJER, DKF

    1992-01-01

    Sulfamethoxazole (SM) was converted to a renal specific drug targeting preparation by coupling the drug to egg-white lysozyme via an acid-sensitive cis-aconityl linker (1:1). Due to this chemical manipulation SM was rapidly distributed to the kidney. Both in vitro and in vivo data indicate that SM

  10. Molecular detection and species-specific identification of medically important Aspergillus species by real-time PCR in experimental invasive pulmonary aspergillosis.

    Science.gov (United States)

    Walsh, Thomas J; Wissel, Mark C; Grantham, Kevin J; Petraitiene, Ruta; Petraitis, Vidmantas; Kasai, Miki; Francesconi, Andrea; Cotton, Margaret P; Hughes, Johanna E; Greene, Lora; Bacher, John D; Manna, Pradip; Salomoni, Martin; Kleiboeker, Steven B; Reddy, Sushruth K

    2011-12-01

    Diagnosis of invasive pulmonary aspergillosis (IPA) remains a major challenge to clinical microbiology laboratories. We developed rapid and sensitive quantitative PCR (qPCR) assays for genus- and species-specific identification of Aspergillus infections by use of TaqMan technology. In order to validate these assays and understand their potential diagnostic utility, we then performed a blinded study of bronchoalveolar lavage (BAL) fluid specimens from well-characterized models of IPA with the four medically important species. A set of real-time qPCR primers and probes was developed by utilizing unique ITS1 regions for genus- and species-specific detection of the four most common medically important Aspergillus species (Aspergillus fumigatus, A. flavus, A. niger, and A. terreus). Pan-Aspergillus and species-specific qPCRs with BAL fluid were more sensitive than culture for detection of IPA caused by A. fumigatus in untreated (P < 0.0007) and treated (P ≤ 0.008) animals, respectively. For infections caused by A. terreus and A. niger, culture and PCR amplification from BAL fluid yielded similar sensitivities for untreated and treated animals. Pan-Aspergillus PCR was more sensitive than culture for detection of A. flavus in treated animals (P = 0.002). BAL fluid pan-Aspergillus and species-specific PCRs were comparable in sensitivity to BAL fluid galactomannan (GM) assay. The copy numbers from the qPCR assays correlated with quantitative cultures to determine the pulmonary residual fungal burdens in lung tissue. Pan-Aspergillus and species-specific qPCR assays may improve the rapid and accurate identification of IPA in immunocompromised patients.

  11. Identification of Molecular Markers Associated with Alteration of Receptor-Binding Specificity in a Novel Genotype of Highly Pathogenic Avian Influenza A(H5N1) Viruses Detected in Cambodia in 2013

    Science.gov (United States)

    Rith, Sareth; Davis, C. Todd; Duong, Veasna; Sar, Borann; Horm, Srey Viseth; Chin, Savuth; Ly, Sovann; Laurent, Denis; Richner, Beat; Oboho, Ikwo; Jang, Yunho; Davis, William; Thor, Sharmi; Balish, Amanda; Iuliano, A. Danielle; Sorn, San; Holl, Davun; Sok, Touch; Seng, Heng; Tarantola, Arnaud; Tsuyuoka, Reiko; Parry, Amy; Chea, Nora; Allal, Lotfi; Kitsutani, Paul; Warren, Dora; Prouty, Michael; Horwood, Paul; Widdowson, Marc-Alain; Lindstrom, Stephen; Villanueva, Julie; Donis, Ruben; Cox, Nancy

    2014-01-01

    Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to the absence of the mutations in poultry/environmental samples, suggested that the mutations occurred during human infection and did not transmit further. PMID:25210193

  12. Analysis of the condition of the SNAP 7-E acoustic beacon installation after 64 months at 2,650 fathoms. Final report Nov 1970--May 1971

    Energy Technology Data Exchange (ETDEWEB)

    Jenkins, J.F.

    1972-02-01

    An isotopic generator powered acoustic beacon installation was recovered after 64 months of exposure to the seawater and bottom sediments at 2,650 fathoms of depth in the Atlantic Ocean south of Bermuda. An analysis of the deterioration of the components of the installation showed that the basic steel support structure and the isotopic generator housing suffered only minimal attack. The lifetimes of these elements are projected to exceed ten years at this site. Stainless steel components of the installation were severely corroded and the use of stainless steel is not recommended. The bottom environment in this location was found to be a typical and similar installations at other sites would have significantly shorter lifetimes.

  13. Synthesis and characterization of novel molecularly imprinted polymer - coated Mn-doped ZnS quantum dots for specific fluorescent recognition of cocaine.

    Science.gov (United States)

    Chantada-Vázquez, María Pilar; Sánchez-González, Juan; Peña-Vázquez, Elena; Tabernero, María Jesús; Bermejo, Ana María; Bermejo-Barrera, Pilar; Moreda-Piñeiro, Antonio

    2016-01-15

    Mn-doped ZnS quantum dots (QDs) coated with a molecularly imprinted polymer (MIP) material selective toward cocaine and its metabolites have been prepared and applied to cocaine (COC) and metabolites assessment by spectrofluorimetry. Ultrasound irradiation (37kHz) was novelty used for performing the Mn-doped ZnS QDs synthesis as well as for preparing the QD based MIP-coated composite by precipitation polymerization (imprinting process). This fact allowed the synthesis to be accomplished in four hours. In addition, the use of ultrasound irradiation during MIP-QDs synthesis increased the homogeneity of the QDs size, and reduced nanoparticles agglomeration. MIP was synthesized using COC as a template molecule, ethylene dimethacrylate (EDMA) as a functional monomer, divinylbenzene (DVB) as a cross-linker, and 2,2'-azobisisobutyronitrile (AIBN) as an initiator. The fluorescence of MIP-coated QDs was quenched by the template (COC) and also by metabolites from COC such as benzoylecgonine (BZE), and ecgonine methyl ester (EME). Quenching was not observed when performing experiments with non-imprinted polymer (NIP)-coated QDs; and also, fluorescence quenching of MIP-coated QDs was not observed by other drugs of abuse and metabolites (heroin and cannabis abuse). This fact indicates that the prepared material recognize only COC (template) and metabolites. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Molecular portrait-based correlation between primary canine mammary tumor and its lymph node metastasis: possible prognostic-predictive models and/or stronghold for specific treatments?

    Directory of Open Access Journals (Sweden)

    Beha Germana

    2012-11-01

    Full Text Available Abstract Background This study aimed to evaluate the relationship between the molecular phenotype of the primary mammary tumor and its related lymph node metastasis in the dog to develop prognostic-predictive models and targeted therapeutic options. Results Twenty mammary tumor samples and their lymph node metastases were selected and stained by immunohistochemistry with anti-estrogen receptor (ER, -progesterone receptor (PR, -human epidermal growth factor receptor 2 (c-erbB-2, -cytokeratin 5/6 (CK 5/6, -cytokeratin 14 (CK14, -cytokeratin 19 (CK 19 and -protein 63 (p63 antibodies. Four phenotypes (luminal A, luminal B, c-erbB2 overexpressing and basal-like were diagnosed in primary tumors and five (luminal A, luminal B, c-erbB-2 overexpressing, basal-like and normal-like in the lymph node metastases. Phenotypic concordance was found in 13 of the 20 cases (65%, and seven cases (35% showed discordance with different lymph node phenotypic profile from the primary tumor. Conclusions The phenotype of the primary tumor assumes a predictive-therapeutic role only in concordant cases, meaning that both the primary tumor and its lymph node metastasis should be evaluated at the same time. A treatment plan based only on the primary tumor phenotype could lead to therapeutic failures if the phenotype of the lymph node metastasis differs from that of the primary tumor.

  15. Molecular analysis of the early interaction between the grapevine flower and Botrytis cinerea reveals that prompt activation of specific host pathways leads to fungus quiescence.

    Science.gov (United States)

    Haile, Zeraye Mehari; Pilati, Stefania; Sonego, Paolo; Malacarne, Giulia; Vrhovsek, Urska; Engelen, Kristof; Tudzynski, Paul; Zottini, Michela; Baraldi, Elena; Moser, Claudio

    2017-08-01

    Grape quality and yield can be impaired by bunch rot, caused by the necrotrophic fungus Botrytis cinerea. Infection often occurs at flowering, and the pathogen stays quiescent until fruit maturity. Here, we report a molecular analysis of the early interaction between B. cinerea and Vitis vinifera flowers, using a controlled infection system, confocal microscopy and integrated transcriptomic and metabolic analysis of the host and the pathogen. Flowers from fruiting cuttings of the cultivar Pinot Noir were infected with green fluorescent protein (GFP)-labelled B. cinerea and studied at 24 and 96 hours post-inoculation (h.p.i.). We observed that penetration of the epidermis by B. cinerea coincided with increased expression of genes encoding cell-wall-degrading enzymes, phytotoxins and proteases. Grapevine responded with a rapid defence reaction involving 1193 genes associated with the accumulation of antimicrobial proteins, polyphenols, reactive oxygen species and cell wall reinforcement. At 96 h.p.i., the reaction appears largely diminished both in the host and in the pathogen. Our data indicate that the defence responses of the grapevine flower collectively are able to restrict invasive fungal growth into the underlying tissues, thereby forcing the fungus to enter quiescence until the conditions become more favourable to resume pathogenic development. © 2017 John Wiley & Sons Ltd.

  16. Molecular cloning of tissue-specific transcripts of a transketolase-related gene: Implications for the evolution of new vertebrate genes

    Energy Technology Data Exchange (ETDEWEB)

    Coy, J.F.; Duebel, S.; Kioschis, P.; Delius, H.; Poustka, A. [Deutsches Krebsforschungszentrum, Heidelberg (Germany)] [and others

    1996-03-05

    As part of a systematic search for differentially expressed genes, we have isolated a novel transketolase-related gene (TKR) (HGMW-approved symbol TKT), located between the green color vision pigment gene (GCP) and the ABP-280 filamin gene (FLN1) in Xq28. Transcripts encoding tissue-specific protein isoforms could be isolated. Comparison with known transketolases (TK) demonstrated a TKR-specific deletion mutating one thiamine binding site. Genomic sequencing of the TKR gene revealed the presence of a pseudoexon as well as the acquisition of a tissue-specific spliced exon compared to TK. Since it has been postulated that the vertebrate genome arose by two cycles of tetraploidization from a cephalochordate genome, this could represent an example of the modulation of the function of a preexisting transketolase gene by gene duplication. Thiamine defiency is closely involved with two neurological disorders, Beriberi and Wernicke-Korsakoff syndromes, and in both of these conditions TK with altered activity are found. We discuss the possible involvement of TKR in explaining the observed variant transketolase forms. 34 refs., 4 figs., 1 tab.

  17. Predicting fecal sources in waters with diverse pollution loads using general and molecular host-specific indicators and applying machine learning methods.

    Science.gov (United States)

    Casanovas-Massana, Arnau; Gómez-Doñate, Marta; Sánchez, David; Belanche-Muñoz, Lluís A; Muniesa, Maite; Blanch, Anicet R

    2015-03-15

    In this study we use a machine learning software (Ichnaea) to generate predictive models for water samples with different concentrations of fecal contamination (point source, moderate and low). We applied several MST methods (host-specific Bacteroides phages, mitochondrial DNA genetic markers, Bifidobacterium adolescentis and Bifidobacterium dentium markers, and bifidobacterial host-specific qPCR), and general indicators (Escherichia coli, enterococci and somatic coliphages) to evaluate the source of contamination in the samples. The results provided data to the Ichnaea software, that evaluated the performance of each method in the different scenarios and determined the source of the contamination. Almost all MST methods in this study determined correctly the origin of fecal contamination at point source and in moderate concentration samples. When the dilution of the fecal pollution increased (below 3 log10 CFU E. coli/100 ml) some of these indicators (bifidobacterial host-specific qPCR, some mitochondrial markers or B. dentium marker) were not suitable because their concentrations decreased below the detection limit. Using the data from source point samples, the software Ichnaea produced models for waters with low levels of fecal pollution. These models included some MST methods, on the basis of their best performance, that were used to determine the source of pollution in this area. Regardless the methods selected, that could vary depending on the scenario, inductive machine learning methods are a promising tool in MST studies and may represent a leap forward in solving MST cases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. A Novel Algorithm for Determining the Contextual Characteristics of Movement Behaviors by Combining Accelerometer Features and Wireless Beacons: Development and Implementation.

    Science.gov (United States)

    Magistro, Daniele; Sessa, Salvatore; Kingsnorth, Andrew P; Loveday, Adam; Simeone, Alessandro; Zecca, Massimiliano; Esliger, Dale W

    2018-04-20

    Unfortunately, global efforts to promote "how much" physical activity people should be undertaking have been largely unsuccessful. Given the difficulty of achieving a sustained lifestyle behavior change, many scientists are reexamining their approaches. One such approach is to focus on understanding the context of the lifestyle behavior (ie, where, when, and with whom) with a view to identifying promising intervention targets. The aim of this study was to develop and implement an innovative algorithm to determine "where" physical activity occurs using proximity sensors coupled with a widely used physical activity monitor. A total of 19 Bluetooth beacons were placed in fixed locations within a multilevel, mixed-use building. In addition, 4 receiver-mode sensors were fitted to the wrists of a roving technician who moved throughout the building. The experiment was divided into 4 trials with different walking speeds and dwelling times. The data were analyzed using an original and innovative algorithm based on graph generation and Bayesian filters. Linear regression models revealed significant correlations between beacon-derived location and ground-truth tracking time, with intraclass correlations suggesting a high goodness of fit (R 2 =.9780). The algorithm reliably predicted indoor location, and the robustness of the algorithm improved with a longer dwelling time (>100 s; error location of an individual within an indoor environment. This novel implementation of "context sensing" will facilitate a wealth of new research questions on promoting healthy behavior change, the optimization of patient care, and efficient health care planning (eg, patient-clinician flow, patient-clinician interaction). ©Daniele Magistro, Salvatore Sessa, Andrew P Kingsnorth, Adam Loveday, Alessandro Simeone, Massimiliano Zecca, Dale W Esliger. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 20.04.2018.

  19. Molecular analysis of myelodysplastic syndrome with isolated deletion of the long arm of chromosome 5 reveals a specific spectrum of molecular mutations with prognostic impact: a study on 123 patients and 27 genes

    Science.gov (United States)

    Meggendorfer, Manja; Haferlach, Claudia; Kern, Wolfgang; Haferlach, Torsten

    2017-01-01

    The only cytogenetic aberration defining a myelodysplastic syndrome subtype is the deletion of the long arm of chromosome 5, which, along with morphological features, leads to the diagnosis of myelodysplastic syndrome with isolated deletion of the long arm of chromosome 5. These patients show a good prognosis and respond to treatment such as lenalidomide, but some cases progress to acute myeloid leukemia; however, the molecular mutation pattern is rarely characterized. Therefore, we investigated a large cohort of 123 myelodysplastic syndrome patients with isolated deletion of the long arm of chromosome 5, diagnosed following the World Health Organization classifications 2008 and 2016, by sequencing 27 genes. A great proportion of patients showed no or only one mutation. Only seven genes showed mutation frequencies >5% (SF3B1, DNMT3A, TP53, TET2, CSNK1A1, ASXL1, JAK2). However, the pattern of recurrently mutated genes was comparable to other myelodysplastic syndrome subtypes by comparison to a reference cohort, except that of TP53 which was significantly more often mutated in myelodysplastic syndrome with isolated deletion of the long arm of chromosome 5. As expected, SF3B1 was frequently mutated and correlated with ring sider-oblasts, while JAK2 mutations correlated with elevated platelet counts. Surprisingly, SF3B1 mutations led to significantly worse prognosis within cases with isolated deletion of the long arm of chromosome 5, but showed a comparable outcome to other myelodysplastic syndrome subtypes with SF3B1 mutation. However, addressing genetic stability in follow-up cases might suggest different genetic mechanisms for progression to secondary acute myeloid leukemia compared to overall myelodysplastic syndrome patients. PMID:28642303

  20. 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

    Here we present an optimized readout format for detection of the circularized products from a DNA-based sensor for measurement of DNA-modifying enzymes including DNA Topoisomerase I. The basic design of the DNA-sensor relies on the use of a substrate that can be circularized by the activity of DN...

  1. Assessment of the sensitivity and specificity of serological (IFAT) and molecular (direct-PCR) techniques for diagnosis of leishmaniasis in lagomorphs using a Bayesian approach.

    Science.gov (United States)

    de la Cruz, María Luisa; Pérez, Andres; Domínguez, Mercedes; Moreno, Inmaculada; García, Nerea; Martínez, Irene; Navarro, Alejandro; Domínguez, Lucas; Álvarez, Julio

    2016-08-01

    Leishmaniasis, caused by Leishmania infantum , is a vector-borne zoonotic disease that is endemic to the Mediterranean basin. The potential of rabbits and hares to serve as competent reservoirs for the disease has recently been demonstrated, although assessment of the importance of their role on disease dynamics is hampered by the absence of quantitative knowledge on the accuracy of diagnostic techniques in these species. A Bayesian latent-class model was used here to estimate the sensitivity and specificity of the Immuno-fluorescence antibody test (IFAT) in serum and a Leishmania -nested PCR (Ln-PCR) in skin for samples collected from 217 rabbits and 70 hares from two different populations in the region of Madrid, Spain. A two-population model, assuming conditional independence between test results and incorporating prior information on the performance of the tests in other animal species obtained from the literature, was used. Two alternative cut-off values were assumed for the interpretation of the IFAT results: 1/50 for conservative and 1/25 for sensitive interpretation. Results suggest that sensitivity and specificity of the IFAT were around 70-80%, whereas the Ln-PCR was highly specific (96%) but had a limited sensitivity (28.9% applying the conservative interpretation and 21.3% with the sensitive one). Prevalence was higher in the rabbit population (50.5% and 72.6%, for the conservative and sensitive interpretation, respectively) than in hares (6.7% and 13.2%). Our results demonstrate that the IFAT may be a useful screening tool for diagnosis of leishmaniasis in rabbits and hares. These results will help to design and implement surveillance programmes in wild species, with the ultimate objective of early detecting and preventing incursions of the disease into domestic and human populations.

  2. Unilateral testicular tumour associated to congenital adrenal hyperplasia: Failure of specific tumoral molecular markers to discriminate between adrenal rest and leydigioma.

    Science.gov (United States)

    Fenichel, P; Bstandig, B; Roger, C; Chevallier, D; Michels, J-F; Sadoul, J-L; Hieronimus, S; Brucker-Davis, F

    2008-11-01

    Testicular adrenal rest tumours are frequently associated with congenital adrenal hyperplasia (CAH). These ACTH-dependent tumours cannot be easily distinguished histologically from Leydig-cell tumours. We report the case of a 30-year-old man who was explored for infertility, azoospermia and unilateral testicular tumour. High levels of 17-OH progesterone and ACTH, low cortisol and undetectable gonadotropins levels, associated to bilateral adrenal hyperplasia, led to the diagnosis of CAH by 21-OH deficiency with a composite heterozygoty. The testicular tumour was first considered as adrenal rest. However, histological analysis of this unilateral painful tumour showed a steroid-hormone-secreting cell proliferation with atypical and frequent mitosis. To discriminate between a benign adrenal rest tumour and a possible malignant leydigioma, tumoral expression of specific gene products was analyzed by RT-PCR. No 11-beta-hydroxylase nor ACTH receptor mRNAs could be found in the tumour, which did not behave like usual adrenal rest cells. For this unilateral testicular tumour, the lack of adrenal-specific markers associated with a high rate of mitosis and pleiomorphism supported a leydigian origin with malignant potential. However, lack of tumoral LH-R mRNA expression and a tumour-free 3-year follow-up led us to retain the diagnosis of adrenal rest tumour with loss of adrenal gene expression and progressive autonomous behaviour.

  3. Specificity and selectivity of HypC chaperonins and endopeptidases in the molecular assembly machinery of [NiFe] hydrogenases of Thiocapsa roseopersicina

    Energy Technology Data Exchange (ETDEWEB)

    Maroti, Gergely [BayGen Institute, Bay Zoltan Foundation for Applied Research, Derkovics fasor 2, Szeged 6726 (Hungary); Rakhely, Gabor; Kovacs, Kornel L. [Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt. 62., Szeged 6726 (Hungary); Department of Biotechnology, University of Szeged, Koezep fasor 52., Szeged 6726 (Hungary); Maroti, Judit [Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt. 62., Szeged 6726 (Hungary); Doroghazi, Emma [Department of Biotechnology, University of Szeged, Koezep fasor 52., Szeged 6726 (Hungary); Klement, Eva; Medzihradszky, Katalin F. [Proteomics Research Group, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt. 62., Szeged 6726 (Hungary)

    2010-04-15

    The purple photosynthetic bacterium, Thiocapsa roseopersicina harbours at least three functional [NiFe] hydrogenases. Two of them are attached to the periplasmic membrane (HynSL, HupSL), while the third one is apparently localized in the cytoplasm (HoxEFUYH). Two hypC-type genes, coding for putative small maturation proteins, were found and their roles were studied by activity measurements performed with hypC mutants. Protein-protein interaction experiments confirmed that each HypC-type protein participates in the maturation of at least two [NiFe] hydrogenase large subunits via direct interaction. Endopeptidases perform the last step of the complex [NiFe] hydrogenase maturation process. A separate endopeptidase (HynD, HupD, HoxW) cleaves off the C-terminus of each large subunit and they are strictly specific for their corresponding hydrogenases. The results demonstrate a sophisticated assembly of these functionally active redox metalloenzymes through specific and selective protein-protein interactions and imply some diversity in the hydrogenase assembly machinery among the various microbes. (author)

  4. Crystal Structure of the Homo sapiens Kynureninase-3-Hydroxyhippuric Acid Inhibitor Complex: Insights into the Molecular Basis Of Kynureninase Substrate Specificity

    Energy Technology Data Exchange (ETDEWEB)

    Lima,Santiago; Kumar,Sunil; Gawandi,Vijay; Momany,Cory; Phillips,Robert S.; (Georgia)

    2009-02-23

    Homo sapiens kynureninase is a pyridoxal-5'-phosphate dependent enzyme that catalyzes the hydrolytic cleavage of 3-hydroxykynurenine to yield 3-hydroxyanthranilate and L-alanine as part of the tryptophan catabolic pathway leading to the de novo biosynthesis of NAD{sup +}. This pathway results in quinolinate, an excitotoxin that is an NMDA receptor agonist. High levels of quinolinate have been correlated with the etiology of neurodegenerative disorders such as AIDS-related dementia and Alzheimer's disease. We have synthesized a novel kynureninase inhibitor, 3-hydroxyhippurate, cocrystallized it with human kynureninase, and solved the atomic structure. On the basis of an analysis of the complex, we designed a series of His-102, Ser-332, and Asn-333 mutants. The H102W/N333T and H102W/S332G/N333T mutants showed complete reversal of substrate specificity between 3-hydroxykynurenine and L-kynurenine, thus defining the primary residues contributing to substrate specificity in kynureninases.

  5. Molecular distribution and compound-specific stable carbon isotopic composition of dicarboxylic acids, oxocarboxylic acids and α-dicarbonyls in PM2.5 from Beijing, China

    Science.gov (United States)

    Zhao, Wanyu; Kawamura, Kimitaka; Yue, Siyao; Wei, Lianfang; Ren, Hong; Yan, Yu; Kang, Mingjie; Li, Linjie; Ren, Lujie; Lai, Senchao; Li, Jie; Sun, Yele; Wang, Zifa; Fu, Pingqing

    2018-02-01

    This study investigates the seasonal variation, molecular distribution and stable carbon isotopic composition of diacids, oxocarboxylic acids and α-dicarbonyls to better understand the sources and formation processes of fine aerosols (PM2.5) in Beijing. The concentrations of total dicarboxylic acids varied from 110 to 2580 ng m-3, whereas oxoacids (9.50-353 ng m-3) and dicarbonyls (1.50-85.9 ng m-3) were less abundant. Oxalic acid was found to be the most abundant individual species, followed by succinic acid or occasionally by terephthalic acid (tPh), a plastic waste burning tracer. Ambient concentrations of phthalic acid (37.9 ± 27.3 ng m-3) and tPh (48.7 ± 51.1 ng m-3) were larger in winter than in other seasons, illustrating that fossil fuel combustion and plastic waste incineration contribute more to wintertime aerosols. The year-round mass concentration ratios of malonic acid to succinic acid (C3 / C4) were relatively low by comparison with those in other urban aerosols and remote marine aerosols. The values were less than or equal to unity in Beijing, implying that the degree of photochemical formation of diacids in Beijing is insignificant. Moreover, strong correlation coefficients of major oxocarboxylic acids and α-dicarbonyls with nss-K+ suggest that biomass burning contributes significantly to these organic acids and related precursors. The mean δ13C value of succinic acid is the highest among all species, with values of -17.1 ± 3.9 ‰ (winter) and -17.1 ± 2.0 ‰ (spring), while malonic acid is more enriched in 13C than others in autumn (-17.6 ± 4.6 ‰) and summer (-18.7 ± 4.0 ‰). The δ13C values of major species in Beijing aerosols are generally lower than those in the western North Pacific atmosphere, the downwind region, which indicates that stable carbon isotopic compositions of diacids depend on their precursor sources in Beijing. Therefore, our study demonstrates that in addition to photochemical oxidation, high abundances of diacids

  6. Functional characterization of the Mycobacterium abscessus genome coupled with condition specific transcriptomics reveals conserved molecular strategies for host adaptation and persistence.

    Science.gov (United States)

    Miranda-CasoLuengo, Aleksandra A; Staunton, Patrick M; Dinan, Adam M; Lohan, Amanda J; Loftus, Brendan J

    2016-08-05

    Mycobacterium abscessus subsp. abscessus (MAB) is a highly drug resistant mycobacterium and the most common respiratory pathogen among the rapidly growing non-tuberculous mycobacteria. MAB is also one of the most deadly of the emerging cystic fibrosis (CF) pathogens requiring prolonged treatment with multiple antibiotics. In addition to its "mycobacterial" virulence genes, the genome of MAB harbours a large accessory genome, presumably acquired via lateral gene transfer including homologs shared with the CF pathogens Pseudomonas aeruginosa and Burkholderia cepacia. While multiple genome sequences are available there is little functional genomics data available for this important pathogen. We report here the first multi-omics approach to characterize the primary transcriptome, coding potential and potential regulatory regions of the MAB genome utilizing differential RNA sequencing (dRNA-seq), RNA-seq, Ribosome profiling and LC-MS proteomics. In addition we attempt to address the genomes contribution to the molecular systems that underlie MAB's adaptation and persistence in the human host through an examination of MABs transcriptional response to a number of clinically relevant conditions. These include hypoxia, exposure to sub-inhibitory concentrations of antibiotics and growth in an artificial sputum designed to mimic the conditions within the cystic fibrosis lung. Our integrated map provides the first comprehensive view of the primary transcriptome of MAB and evidence for the translation of over one hundred new short open reading frames (sORFs). Our map will act as a resource for ongoing functional genomics characterization of MAB and our transcriptome data from clinically relevant stresses informs our understanding of MAB's adaptation to life in the CF lung. MAB's adaptation to growth in artificial CF sputum highlights shared metabolic strategies with other CF pathogens including P. aeruginosa and mirrors the transcriptional responses that lead to persistence in

  7. Molecularly imprinted sensor based on Russian Matryoshka structured molecules for enhanced specific identification and double amplification in ultra-trace Tb3+ determination.

    Science.gov (United States)

    Li, Jianping; Yang, Bin; Pan, Hongcheng; Xu, Guobao

    2018-06-30

    The selective and sensitive detection of rare earth elements is thought to be difficult because the concentration of those elements in the sample is commonly at a low level and they normally have severe mutual interference which is caused by homologous chemical properties. In this study, a novel molecularly imprinted polymer (MIP) sensor was fabricated for highly sensitive and selective determination of ultra-trace Tb 3+ . The Tb 3+ -ethylenediaminetetraacetic acid complex (Tb-EDTA) as the template molecule was incorporated into mono-6-mercapto-β-cyclodextrin (mono-6-SH-β-CD) to form a Russian Matryoshka (RM)-structured molecule (CD/Tb-EDTA). Titanium isopropoxide was utilized in vapor sol-gel polymerization to construct MIP membrane. Moreover, the selectivity of the RM MIP sensor was remarkably enhanced by the "triple-selectivity" recognition of EDTA-to-Tb 3+ , β-CD-to-(Tb-EDTA), and 3D cavity-to-(CD/Tb-EDTA), while the sensitivity of the MIP sensor was significantly improved by ECL signal enhancement based on double amplification, in other words, the electrochemiluminescence resonance energy transfer (ECL-RET) between the ECL donor of CD/Tb-EDTA and the ECL acceptor of Ru(bpy) 3 2+ , and the ECL enhancement by the co-reactant of CD/Tb-EDTA on Ru(bpy) 3 Cl 2 . When the imprinted cavities were occupied by Tb-EDTA during rebinding, the host-guest inclusion structured complex was formed and the ECL intensities produced by the Ru(bpy) 3 Cl 2 ECL system increased with increasing concentration of Tb-EDTA. The proposed sensor was used for quantitative analysis of Tb 3+ with concentrations ranging from 8.00 × 10 -13 mol/L to 4.00 × 10 -9 mol/L and successfully applied to detect Tb 3+ in seawater samples. The detection limit of the sensor was found to be 3.90 × 10 -13 mol/L (DL = 3δ b /K), which is lower than previously reported values. Thus, the fabricated sensor is feasible for practical applications. Copyright © 2018 Elsevier B.V. All rights

  8. Molecular distribution and compound-specific stable carbon isotopic composition of dicarboxylic acids, oxocarboxylic acids and α-dicarbonyls in PM2.5 from Beijing, China

    Directory of Open Access Journals (Sweden)

    W. Zhao

    2018-02-01

    Full Text Available This study investigates the seasonal variation, molecular distribution and stable carbon isotopic composition of diacids, oxocarboxylic acids and α-dicarbonyls to better understand the sources and formation processes of fine aerosols (PM2.5 in Beijing. The concentrations of total dicarboxylic acids varied from 110 to 2580 ng m−3, whereas oxoacids (9.50–353 ng m−3 and dicarbonyls (1.50–85.9 ng m−3 were less abundant. Oxalic acid was found to be the most abundant individual species, followed by succinic acid or occasionally by terephthalic acid (tPh, a plastic waste burning tracer. Ambient concentrations of phthalic acid (37.9 ± 27.3 ng m−3 and tPh (48.7 ± 51.1 ng m−3 were larger in winter than in other seasons, illustrating that fossil fuel combustion and plastic waste incineration contribute more to wintertime aerosols. The year-round mass concentration ratios of malonic acid to succinic acid (C3 ∕ C4 were relatively low by comparison with those in other urban aerosols and remote marine aerosols. The values were less than or equal to unity in Beijing, implying that the degree of photochemical formation of diacids in Beijing is insignificant. Moreover, strong correlation coefficients of major oxocarboxylic acids and α-dicarbonyls with nss-K+ suggest that biomass burning contributes significantly to these organic acids and related precursors. The mean δ13C value of succinic acid is the highest among all species, with values of −17.1 ± 3.9 ‰ (winter and −17.1 ± 2.0 ‰ (spring, while malonic acid is more enriched in 13C than others in autumn (−17.6 ± 4.6 ‰ and summer (−18.7 ± 4.0 ‰. The δ13C values of major species in Beijing aerosols are generally lower than those in the western North Pacific atmosphere, the downwind region, which indicates that stable carbon isotopic compositions of diacids depend on their precursor sources in Beijing. Therefore, our

  9. Molecular characterization and chromosomal distribution of a species-specific transcribed centromeric satellite repeat from the olive fruit fly, Bactrocera oleae.

    Directory of Open Access Journals (Sweden)

    Konstantina T Tsoumani

    Full Text Available Satellite repetitive sequences that accumulate in the heterochromatin consist a large fraction of a genome and due to their properties are suggested to be implicated in centromere function. Current knowledge of heterochromatic regions of Bactrocera oleae genome, the major pest of the olive tree, is practically nonexistent. In our effort to explore the repetitive DNA portion of B. oleae genome, a novel satellite sequence designated BoR300 was isolated and cloned. The present study describes the genomic organization, abundance and chromosomal distribution of BoR300 which is organized in tandem, forming arrays of 298 bp-long monomers. Sequence analysis showed an AT content of 60.4%, a CENP-B like-motif and a high curvature value based on predictive models. Comparative analysis among randomly selected monomers demonstrated a high degree of sequence homogeneity (88%-97% of BoR300 repeats, which are present at approximately 3,000 copies per haploid genome accounting for about 0.28% of the total genomic DNA, based on two independent qPCR approaches. In addition, expression of the repeat was also confirmed through RT-PCR, by which BoR300 transcripts were detected in both sexes. Fluorescence in situ hybridization (FISH of BoR300 on mitotic metaphases and polytene chromosomes revealed signals to the centromeres of two out of the six chromosomes which indicated a chromosome-specific centromeric localization. Moreover, BoR300 is not conserved in the closely related Bactrocera species tested and it is also absent in other dipterans, but it's rather restricted to the B. oleae genome. This feature of species-specificity attributed to BoR300 satellite makes it a good candidate as an identification probe of the insect among its relatives at early development stages.

  10. Molecular evidence of Opisthorchis viverrini in infected bithyniid snails in the Lao People's Democratic Republic by specific hybridization probe-based real-time fluorescence resonance energy transfer PCR method.

    Science.gov (United States)

    Sri-Aroon, Pusadee; Intapan, Pewpan M; Lohachit, Chantima; Phongsasakulchoti, Phunthira; Thanchomnang, Tongjit; Lulitanond, Viraphong; Hiscox, Alexandra; Phompida, Samlane; Sananikhom, Pany; Maleewong, Wanchai; Brey, Paul T

    2011-04-01

    Naturally occurring bithyniid snails, Bithynia siamensis goniomphalos (Prosobranchia: Bithyniidae), and their intermediate hosts were sampled from Khammouane Province, the Lao People's Democratic Republic, and the prevalence of the carcinogenic human liver fluke, Opisthorchis viverrini, was examined. The presence of O. viverrini cercariae in snails was examined by cercarial shedding test and then confirmed by specific hybridization probe-based real-time fluorescence resonance energy transfer (FRET) PCR method. The real-time FRET PCR method is based on a fluorescence melting curve analysis of a hybrid between an amplicon produced from the pOV-A6 specific sequence (Genbank accession no. S80278), a 162-bp repeated sequence specific to O. viverrini, and specific fluorophore-labeled probes. Mean melting temperature of O. viverrini DNA from the cercariae and each of two positive snails by shedding test was 66.3 ± 0.1. The O. viverrini infection rate in snails was 2.47% (2/81) by cercarial shedding test but was 8.52% (4/47) by real-time FRET PCR method. The real-time FRET PCR method is rapid and effective in examining a large number of snail samples simultaneously. Validation using molecular evidence from this procedure provides another tool for surveying the prevalence of O. viverrini-infected snails in Southeast Asian countries.

  11. Intense habitat-specific fisheries-induced selection at the molecular Pan I locus predicts imminent collapse of a major cod fishery.

    Science.gov (United States)

    Arnason, Einar; Hernandez, Ubaldo Benitez; Kristinsson, Kristján

    2009-05-27

    Predation is a powerful agent in the ecology and evolution of predator and prey. Prey may select multiple habitats whereby different genotypes prefer different habitats. If the predator is also habitat-specific the prey may evolve different habitat occupancy. Drastic changes can occur in the relation of the predator to the evolved prey. Fisheries exert powerful predation and can be a potent evolutionary force. Fisheries-induced selection can lead to phenotypic changes that influence the collapse and recovery of the fishery. However, heritability of the phenotypic traits involved and selection intensities are low suggesting that fisheries-induced evolution occurs at moderate rates at decadal time scales. The Pantophysin I (Pan I) locus in Atlantic cod (Gadus morhua), representing an ancient balanced polymorphism predating the split of cod and its sister species, is under an unusual mix of balancing and directional selection including current selective sweeps. Here we show that Pan I alleles are highly correlated with depth with a gradient of 0.44% allele frequency change per meter. AA fish are shallow-water and BB deep-water adapted in accordance with behavioral studies using data storage tags showing habitat selection by Pan I genotype. AB fish are somewhat intermediate although closer to AA. Furthermore, using a sampling design covering space and time we detect intense habitat-specific fisheries-induced selection against the shallow-water adapted fish with an average 8% allele frequency change per year within year class. Genotypic fitness estimates (0.08, 0.27, 1.00 of AA, AB, and BB respectively) predict rapid disappearance of shallow-water adapted fish. Ecological and evolutionary time scales, therefore, are congruent. We hypothesize a potential collapse of the fishery. We find that probabilistic maturation reaction norms for Atlantic cod at Iceland show declining length and age at maturing comparable to changes that preceded the collapse of northern cod at

  12. Genome-Wide Comprehensive Analysis the Molecular Phylogenetic Evaluation and Tissue-Specific Expression of SABATH Gene Family in Salvia miltiorrhiza

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2017-12-01

    Full Text Available The plant SABATH gene family is a group of O-methyltransferases (O-MTs, which belongs to the S-adenosyl-l-methionine-dependent methyltransferases (SAM-MTs. The resulting reaction products of SABATH genes play an important role in various processes of plant development. In this study, a total of 30 SABATH genes were detected in Salvia miltiorrhiza, which is an important medicinal plant, widely used to treat cardiovascular disease. Multiple sequence alignment and phylogenetic analyses showed that SmSABATH genes could be classified into three groups. The ratios of non-synonymous (Ka and synonymous (Ks substitution rates of 11 pairs paralogous of SmSABATH genes revealed that the SmSABATH genes had gone through purifying selection. Positive selection analyses using site models and branch-site models indicated that SmSABATH genes had undergone selective pressure for adaptive evolution. Functional divergence analyses suggested that the SmSABATH subgroup genes were divergent in terms of functions and positive selection sites that contributed to a functional divergence among the subgroups that were detected. Tissue-specific expression showed that the SABATH gene family in S. miltiorrhiza was primarily expressed in stems and leaves.

  13. Insights into the molecular mechanism of action of Celastraceae sesquiterpenes as specific, non-transported inhibitors of human P-glycoprotein.

    Science.gov (United States)

    Muñoz-Martínez, Francisco; Reyes, Carolina P; Pérez-Lomas, Antonio L; Jiménez, Ignacio A; Gamarro, Francisco; Castanys, Santiago

    2006-01-01

    Dihydro-beta-agarofuran sesquiterpenes from Celastraceae have been recently shown to bind to human P-glycoprotein (Pgp), functioning as specific, mixed-type inhibitors of its drug transport activity, as well as multidrug resistance (MDR) modulators in vitro. However, nothing is known about whether such compounds are themselves transported by Pgp, or whether they affect Pgp expression as well as its activity, or about the location of their binding site within the protein. We performed transport experiments with a newly synthesized fluorescent sesquiterpene derivative, which retains the anti-Pgp activity of its natural precursor. This probe was poorly transported by Pgp, MRP1, MRP2 and BCRP transporters, compared with classical MDR substrates. Moreover, Pgp did not confer cross-resistance to the most potent dihydro-beta-agarofurans, which did not affect Pgp expression levels in several MDR cell lines. Finally, we observed competitive and non-competitive interactions between one of such dihydro-beta-agarofurans (Mama12) and classical Pgp modulators such as cyclosporin A, verapamil, progesterone, vinblastine and GF120918. These findings suggest that multidrug ABC transporters do not confer resistance to dihydro-beta-agarofurans and could not affect their absorption and biodistribution in the body. Moreover, we mapped their binding site(s) within Pgp, which may prove useful for the rational design of improved modulators based on the structure of dihydro-beta-agarofurans.

  14. Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)

    Science.gov (United States)

    Obaid, Girgis; Wang, Yucheng; Kuriakose, Jerrin; Broekgaarden, Mans; Alkhateeb, Ahmed; Bulin, Anne-Laure; Hui, James; Tsourkas, Andrew; Hasan, Tayyaba

    2016-03-01

    Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for `click' conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody's Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody's optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond

  15. Improving the molecular diagnosis of Chlamydia psittaci and Chlamydia abortus infection with a species-specific duplex real-time PCR.

    Science.gov (United States)

    Opota, Onya; Jaton, Katia; Branley, James; Vanrompay, Daisy; Erard, Veronique; Borel, Nicole; Longbottom, David; Greub, Gilbert

    2015-10-01

    Chlamydia psittaci and Chlamydia abortus are closely related intracellular bacteria exhibiting different tissue tropism that may cause severe but distinct infection in humans. C. psittaci causes psittacosis, a respiratory zoonotic infection transmitted by birds. C. abortus is an abortigenic agent in small ruminants, which can also colonize the human placenta and lead to foetal death and miscarriage. Infections caused by C. psittaci and C. abortus are underestimated mainly due to diagnosis difficulties resulting from their strict intracellular growth. We developed a duplex real-time PCR to detect and distinguish these two bacteria in clinical samples. The first PCR (PCR1) targeted a sequence of the 16S-23S rRNA operon allowing the detection of both C. psittaci and C. abortus. The second PCR (PCR2) targeted the coding DNA sequence CPSIT_0607 unique to C. psittaci. The two PCRs showed 100 % detection for ≥ 10 DNA copies per reaction (1000 copies ml(- 1)). Using a set of 120 samples, including bacterial reference strains, clinical specimens and infected cell culture material, we monitored 100 % sensitivity and 100 % specificity for the detection of C. psittaci and C. abortus for PCR1. When PCR1 was positive, PCR2 could discriminate C. psittaci from C. abortus with a positive predictive value of 100 % and a negative predictive value of 88 %. In conclusion, this new duplex PCR represents a low-cost and time-saving method with high-throughput potential, expected to improve the routine diagnosis of psittacosis and pregnancy complication in large-scale screening programs and also during outbreaks.

  16. ERIC-PCR fingerprinting-based community DNA hybridization to pinpoint genome-specific fragments as molecular markers to identify and track populations common to healthy human guts.

    Science.gov (United States)

    Wei, Guifang; Pan, Li; Du, Huimin; Chen, Junyi; Zhao, Liping

    2004-10-01

    Bacterial populations common to healthy human guts may play important roles in human health. A new strategy for discovering genomic sequences as markers for these bacteria was developed using Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR fingerprinting. Structural features within microbial communities are compared with ERIC-PCR followed by DNA hybridization to identify genomic fragments shared by samples from healthy human individuals. ERIC-PCR profiles of fecal samples from 12 diseased or healthy human and piglet subjects demonstrated stable, unique banding patterns for each individual tested. Sequence homology of DNA fragments in bands of identical size was examined between samples by hybridization under high stringency conditions with DIG-labeled ERIC-PCR products derived from the fecal sample of one healthy child. Comparative analysis of the hybridization profiles with the original agarose fingerprints identified three predominant bands as signatures for populations associated with healthy human guts with sizes of 500, 800 and 1000 bp. Clone library profiling of the three bands produced 17 genome fragments, three of which showed high similarity only with regions of the Bacteroides thetaiotaomicron genome, while the remainder were orphan sequences. Association of these sequences with healthy guts was validated by sequence-selective PCR experiments, which showed that a single fragment was present in all 32 healthy humans and 13 healthy piglets tested. Two fragments were present in the healthy human group and in 18 children with non-infectious diarrhea but not in eight children with infectious diarrhea. Genome fragments identified with this novel strategy may be used as genome-specific markers for dynamic monitoring and sequence-guided isolation of functionally important bacterial populations in complex communities such as human gut microflora.

  17. Deoxyhypusine hydroxylase from Plasmodium vivax, the neglected human malaria parasite: molecular cloning, expression and specific inhibition by the 5-LOX inhibitor zileuton.

    Directory of Open Access Journals (Sweden)

    Veronika Anyigoh Atemnkeng

    Full Text Available Primaquine, an 8-aminoquinoline, is the only drug which cures the dormant hypnozoites of persistent liver stages from P. vivax. Increasing resistance needs the discovery of alternative pathways as drug targets to develop novel drug entities. Deoxyhypusine hydroxylase (DOHH completes hypusine biosynthesis in eukaryotic initiation factor (eIF-5A which is the only cellular protein known to contain the unusual amino acid hypusine. Modified EIF-5A is important for proliferation of the malaria parasite. Here, we present the first successful cloning and expression of DOHH from P. vivax causing tertiary malaria. The nucleic acid sequence of 1041 bp encodes an open reading frame of 346 amino acids. Histidine tagged expression of P. vivax DOHH detected a protein of 39.01 kDa in E. coli. The DOHH protein from P. vivax shares significant amino acid identity to the simian orthologues from P. knowlesi and P. yoelii strain H. In contrast to P. falciparum only four E-Z-type HEAT-like repeats are present in P. vivax DOHH with different homology to phycocyanin lyase subunits from cyanobacteria and in proteins participating in energy metabolism of Archaea and Halobacteria. However, phycocyanin lyase activity is absent in P. vivax DOHH. The dohh gene is present as a single copy gene and transcribed throughout the whole erythrocytic cycle. Specific inhibition of recombinant P. vivax DOHH is possible by complexing the ferrous iron with zileuton, an inhibitor of mammalian 5-lipoxygenase (5-LOX. Ferrous iron in the active site of 5-LOX is coordinated by three conserved histidines and the carboxylate of isoleucine(673. Zileuton inhibited the P. vivax DOHH protein with an IC50 of 12,5 nmol determined by a relative quantification by GC/MS. By contrast, the human orthologue is only less affected with an IC50 of 90 nmol suggesting a selective iron-complexing strategy for the parasitic enzyme.

  18. Relationship of Parental Genetic Distance with Heterosis and Specific Combining Ability in Sesame (Sesamum indicum L.) Based on Phenotypic and Molecular Marker Analysis.

    Science.gov (United States)

    Pandey, Sarita K; Dasgupta, Tapash; Rathore, Abhishek; Vemula, Anilkumar

    2018-01-10

    The genetic distance analysis for selection of suitable parents has been established and effectively used in many crops; however, there is dearth of conclusive report of relationship of genetic distance analysis with heterosis in sesame. In the present study, an attempt was made to estimate the associations of genetic distances using SSR (GDSSR), seed-storage protein profiling (GDSDS) and agro-morphological traits (GDMOR) with hybrid performance. Seven parents were selected from 60 exotic and Indian genotypes based on genetic distance from clustering pattern based on SSR, seed-storage protein, morphological traits and per se performance. For combining ability analysis, 7 parents and 21 crosses generated from 7 × 7 half diallel evaluated at two environments in a replicated field trial during pre-kharif season of 2013. Compared with the average parents yield (12.57 g plant -1 ), eight hybrids had a significant (P < 0.01) yield advantage across environments, with averages of 26.94 and 29.99% for better-parent heterosis (BPH) and mid-parent heterosis (MPH), respectively, across environments. Highly significant positive correlation was observed between specific combining ability (SCA) and per se performance (0.97), while positive non-significant correlation of BPH with GDSSR (0.048), and non-significant negative correlations with GDMOR (- 0.01) and GDSDS (- 0.256) were observed. The linear regressions of SCA on MPH, BPH and per se performance of F 1 s were significant with R 2 value of 0.88, 0.84 and 0.95 respectively. The present findings revealed a weak association of GDSSR with F 1 's performance; however, SCA has appeared as an important factor in the determination of heterosis and per se performance of the hybrids. The present findings also indicated that parental divergence in the intermediate group would likely produce high heterotic crosses in sesame.

  19. Whole-Genome Re-Alignment Facilitates Development of Specific Molecular Markers for Races 1 and 4 of Xanthomonas campestris pv. campestris, the Cause of Black Rot Disease in Brassica oleracea

    Directory of Open Access Journals (Sweden)

    Mehede Hassan Rubel

    2017-11-01

    Full Text Available Black rot, caused by Xanthomonas campestris pv. campestris (Xcc, is a seed borne disease of Brassicaceae. Eleven pathogenic races have been identified based on the phenotype interaction pattern of differential brassica cultivars inoculated with different strains. Race 1 and 4 are the two most frequent races found in Brassica oleracea crops. In this study, a PCR molecular diagnostic tool was developed for the identification of Xcc races 1 and 4 of this pathogen. Whole genomic sequences of races 1, 3, 4 and 9 and sequences of three other Xanthomonas pathovars/species (X. campestris pv. incanae (Xci, X. campestris pv. raphani (Xcr and X. euvesicatoria (Xev were aligned to identify variable regions among races. To develop specific markers for races 1 and 4, primers were developed from a region where sequences were dissimilar in other races. Sequence-characterized amplified regions (SCAR and insertion or deletion of bases (InDel were used to develop each specific set of primers. The specificity of the selected primers was confirmed by PCR tests using genomic DNA of seven different Xcc races, two strains of X. campestris pathovars and other species of bacteria. Bacterial samples of the races 1 and 4 isolates were collected from artificially inoculated cabbage leaves to conduct bio-PCR. Bio-PCR successfully detected the two Xcc isolates. By using our race-specific markers, a potential race 1 strain from the existing Korean Xcc collection was identified. The Xcc race 1 and 4-specific markers developed in this study are novel and can potentially be used for rapid detection of Xcc races through PCR.

  20. Solid-phase extraction based on a molecularly imprinted polymer nanoshell at the surface of silica nanospheres for the specific enrichment and identification of alkaloids from Crinum asiaticum L. var. sinicum.

    Science.gov (United States)

    Yang, Ruixiang; Zhu, Dong; Wen, Hongmei; Fu, Anchen; Zhao, Zihan; Dai, Guoying; Miao, Zhaoyi; Hu, Yue

    2017-03-01

    A molecularly imprinted nanoshell on the surface of silica nanospheres was prepared for specific enrichment and identification of alkaloids from Crinum asiaticum L. var. sinicum. The nanoshell was synthesized by surface polymerization using lycorine as the template, acrylamide as the functional monomer, ethylene glycol dimethacrylate as the cross-linker, 2',2-azobisisobutyronitrile as the initiator and acetonitrile as the pore-forming agent. The core-shell nanospheres were characterized by transmission electron microscopy and infrared spectroscopy, and the results show that the nanoshell layer was homogeneously attached to the surface of vinyl-modified SiO 2 nanospheres. The adsorption capacity of the nanospheres was estimated by binding equilibrium and adsorption kinetics experiments. The maximum adsorption amount of lycorine on the nanospheres was 6.68 μmol/g and the imprinting factor was nearly 2.5, indicating a good imprinting effect. The nanospheres were successfully applied in solid-phase extraction for lycorine from Crinum asaticum L. var. sinicum and detection of target molecule in rat metabolites. The average recoveries of lycorine in Crinum asaticum L. var. sinicum extraction and rat metabolites were 93.5 ± 0.6% (n = 3) and 91.6 ± 1.9% (n = 3), respectively. This work provides a simple approach for the fabrication of a molecularly imprinted nanoshell at the surface of silica nanospheres-based solid-phase extraction for drug analysis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Multimodality cardiovascular molecular imaging technology.

    Science.gov (United States)

    O'Donnell, Matthew; McVeigh, Elliot R; Strauss, H William; Tanaka, Atsushi; Bouma, Brett E; Tearney, Guillermo J; Guttman, Michael A; Garcia, Ernest V

    2010-05-01

    Cardiovascular molecular imaging is a new discipline that integrates scientific advances in both functional imaging and molecular probes to improve our understanding of the molecular basis of the cardiovascular system. These advances are driven by in vivo imaging of molecular processes in animals, usually small animals, and are rapidly moving toward clinical applications. Molecular imaging has the potential to revolutionize the diagnosis and treatment of cardiovascular disease. The 2 key components of all molecular imaging systems are the molecular contrast agents and the imaging system providing spatial and temporal localization of these agents within the body. They must deliver images with the appropriate sensitivity and specificity to drive clinical applications. As work in molecular contrast agents matures and highly sensitive and specific probes are developed, these systems will provide the imaging technologies required for translation into clinical tools. This is the promise of molecular medicine.

  2. Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician's choice: Results from the randomised phase III BEACON trial.

    Science.gov (United States)

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

    2017-05-01

    Health-related quality of life (HRQoL) enhances understanding of treatment effects that impact clinical decision-making. Although the primary end-point was not achieved, the BEACON (BrEAst Cancer Outcomes with NKTR-102) trial established etirinotecan pegol, a long-acting topoisomerase-1 (TOP1) inhibitor, as a promising therapeutic for patients with advanced/metastatic breast cancer (MBC) achieving clinically meaningful benefits in median overall survival (OS) for patients with stable brain metastases, with liver metastases or ≥ 2 sites of metastatic disease compared to treatment of physician's choice (TPC). Reported herein are the findings from the preplanned secondary end-point of HRQoL. HRQoL, assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (version 3.0) supplemented by the breast cancer-specific Quality of Life Questionnaire (QLQ-BR23), was evaluated post randomisation in 733 of 852 patients with either anthracycline-, taxane- and capecitabine-pretreated locally recurrent or MBC randomised to etirinotecan pegol (n = 378; 145 mg/m 2 every 3 weeks (q3wk)) or single-agent TPC (n = 355). Patients completed assessments at screening, every 8 weeks (q8wk) during treatment, and end-of-treatment. Changes from baseline were analysed, and the proportions of patients achieving differences (≥5 points) in HRQoL scores were compared. Differences were seen favouring etirinotecan pegol up to 32 weeks for global health status (GHS) and physical functioning scales (P adverse event profiles; etirinotecan pegol was associated with worsening gastrointestinal symptoms whereas TPC was associated with worsened dyspnoea and other systemic side-effects. Analysis of GHS and physical functioning at disease progression showed a decline in HRQoL in both treatment arms, with a mean change from baseline of -9.4 and -10.8 points, respectively. There was evidence of benefit associated with etirinotecan

  3. Molecular characterization of Lepidopteran specific Bacillus ...

    African Journals Online (AJOL)

    Bacillus thuringiensis (Bt) strains pathogenic to Lepidopteran insects and native to hilly zone soils of Karnataka (India) were explored. 19 strains were isolated from the soils and identified by morphological and microscopic characters. Toxicity level of the Bt isolates was tested by treating third Instar larvae of silkworm ...

  4. Molecular characterization of Lepidopteran specific Bacillus ...

    African Journals Online (AJOL)

    Guest

    2013-05-15

    May 15, 2013 ... Department of Plant Biotechnology, University of Agricultural Sciences, GKVK Campus, Bangalore, India. Accepted 24 April, 2013. Bacillus thuringiensis (Bt) strains pathogenic to Lepidopteran insects and native to hilly zone soils of. Karnataka ... In one of the isolates (Bt9), the cry gene was not detected.

  5. Molecular characterization and temporal expression analyses indicate that the MIC (Meloidogyne Induced Cotton) gene family represents a novel group of root-specific defense-related genes in upland cotton (Gossypium hirsutum L.).

    Science.gov (United States)

    Wubben, Martin J; Callahan, Franklin E; Hayes, Russel W; Jenkins, Johnie N

    2008-06-01

    The molecular events underlying the resistance of Upland cotton (Gossypium hirsutum L.) to the root-knot nematode (RKN) are largely unknown. In this report, we further characterize the previously identified MIC3 gene including the identification of 14 related MIC cDNAs in nematode-infected roots of allotetraploid cotton that show >85% identity with MIC3. A time-course analysis of RKN infection in resistant and susceptible cotton lines showed that maximum MIC transcript accumulation occurred immediately prior to the phenotypic manifestation of resistance. MIC expression was not induced by mechanical wounding or by virulent reniform nematode infection. MIC expression was undetectable in cotton leaves undergoing a hypersensitive response to Xanthomonas campestris. A time-course analysis of defense gene expression (PR10, ERF5, CDNS, LOX1, POD4, POD8) in resistant and susceptible cotton roots showed that RKN infection specifically elicits the induction of MIC in resistant roots and not other common defense-signaling pathways. These results suggest that cotton resistance to RKN involves novel defense-signaling pathways and further supports the idea that the MIC genes are intimately involved in this resistance response and represent a group of root-specific defense-related genes in cotton.

  6. A novel enzyme-linked immunosorbent assay for detection of Escherichia coli O157:H7 using immunomagnetic and beacon gold nanoparticles

    Science.gov (United States)

    2014-01-01

    This paper presents a functional nanoparticle-enhanced enzyme-linked immunosorbent assay (FNP-ELISA) for detection of enterohemorrhagic Escherichia coli (EHEC) O157:H7. Immunomagnetic nanoparticles (IMMPs) conjugated with monoclonal anti-O157:H7 antibody were used to capture E. coli O157:H7. Beacon gold nanoparticles (B-GNPs) coated with polyclonal anti-O157:H7 and biotin single-stranded DNA (B-DNA) were then subjective to immunoreaction with E. coli O157:H7, which was followed by streptavidin-horseradish peroxidase (Strep-HRP) conjugated with B-GNPs based on a biotin-avidin system. The solutions containing E. coli O157:H7, IMMPs, B-GNPs, and Strep-HRP were collected for detecting color change. The signal was significantly amplified with detection limits of 68 CFU mL-1 in PBS and 6.8 × 102 to 6.8 × 103 CFU mL-1 in the food samples. The FNP-ELISA method developed in this study was two orders of magnitude more sensitive than immunomagnetic separation ELISA (IMS-ELISA) and four orders of magnitude more sensitive than C-ELISA. The entire detection process of E. coli O157:H7 lasted only 3 h, and thus FNP-ELISA is considered as a time-saving method. PMID:24864164

  7. Effect of a Dual Charge on the DNA-Conjugated Redox Probe on DNA Sensing by Short Hairpin Beacons Tethered to Gold Electrodes.

    Science.gov (United States)

    Kékedy-Nagy, László; Shipovskov, Stepan; Ferapontova, Elena E

    2016-08-16

    Charges of redox species can critically affect both the interfacial state of DNA and electrochemistry of DNA-conjugated redox labels and, as a result, the electroanalytical performance of those systems. Here, we show that the kinetics of electron transfer (ET) between the gold electrode and methylene blue (MB) label conjugated to a double-stranded (ds) DNA tethered to gold strongly depend on the charge of the MB molecule, and that affects the performance of genosensors exploiting MB-labeled hairpin DNA beacons. Positively charged MB binds to dsDNA via electrostatic and intercalative/groove binding, and this binding allows the DNA-mediated electrochemistry of MB intercalated into the duplex and, as a result, a complex mode of the electrochemical signal change upon hairpin hybridization to the target DNA, dominated by the "on-off" signal change mode at nanomolar levels of the analyzed DNA. When MB bears an additional carboxylic group, the negative charge provided by this group prevents intimate interactions between MB and DNA, and then the ET in duplexes is limited by the diffusion of the MB-conjugated dsDNA (the phenomenon first shown in Farjami , E. ; Clima , L. ; Gothelf , K. ; Ferapontova , E. E. Anal. Chem. 2011 , 83 , 1594 ) providing the robust "off-on" nanomolar DNA sensing. Those results can be extended to other intercalating redox probes and are of strategic importance for design and development of electrochemical hybridization sensors exploiting DNA nanoswitchable architectures.

  8. Molecular characterization and expression analysis of four fish-specific CC chemokine receptors CCR4La, CCR4Lc1, CCR4Lc2 and CCR11 in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Qi, Zhitao; Holland, Jason W; Jiang, Yousheng; Secombes, Christopher J; Nie, Pin; Wang, Tiehui

    2017-09-01

    The chemokine and chemokine receptor networks regulate leukocyte trafficking, inflammation, immune cell differentiation, cancer and other biological processes. Comparative immunological studies have revealed that both chemokines and their receptors have expanded greatly in a species/lineage specific way. Of the 10 human CC chemokine receptors (CCR1-10) that bind CC chemokines, orthologues only to CCR6, 7, 9 and 10 are present in teleost fish. In this study, four fish-specific CCRs, termed as CCR4La, CCR4Lc1, CCR4Lc2 and CCR11, with a close link to human CCR1-5 and 8, in terms of amino acid homology and syntenic conservation, have been identified and characterized in rainbow trout (Oncorhynchus mykiss). These CCRs were found to possess the conserved features of the G protein-linked receptor family, including an extracellular N-terminal, seven TM domains, three extracellular loops and three intracellular loops, and a cytoplasmic carboxyl tail with multiple potential serine/threonine phosphorylation sites. Four cysteine residues known to be involved in forming two disulfide bonds are present in the extracellular domains and a DRY motif is present in the second intracellular loop. Signaling mediated by these receptors might be regulated by N-glycosylation, tyrosine sulfation, S-palmitoylation, a PDZ ligand motif and di-leucine motifs. Studies of intron/exon structure revealed distinct fish-specific CCR gene organization in different fish species/lineages that might contribute to the diversification of the chemokine ligand-receptor networks in different fish lineages. Fish-specific trout CCRs are highly expressed in immune tissues/organs, such as thymus, spleen, head kidney and gills. Their expression can be induced by the pro-inflammatory cytokines, IL-1β, IL-6 and IFNγ, by the pathogen associated molecular patterns, PolyIC and peptidoglycan, and by bacterial infection. These data suggest that fish-specific CCRs are likely to have an important role in immune

  9. Magnetismo Molecular (Molecular Magentism)

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Mario S [Universidade Federal Fluminense, Brasil; Moreira Dos Santos, Antonio F [ORNL

    2010-07-01

    The new synthesis processes in chemistry open a new world of research, new and surprising materials never before found in nature can now be synthesized and, as a wonderful result, observed a series of physical phenomena never before imagined. Among these are many new materials the molecular magnets, the subject of this book and magnetic properties that are often reflections of the quantum behavior of these materials. Aside from the wonderful experience of exploring something new, the theoretical models that describe the behavior these magnetic materials are, in most cases, soluble analytically, which allows us to know in detail the physical mechanisms governing these materials. Still, the academic interest in parallel this subject, these materials have a number of properties that are promising to be used in technological devices, such as in computers quantum magnetic recording, magnetocaloric effect, spintronics and many other devices. This volume will journey through the world of molecular magnets, from the structural description of these materials to state of the art research.

  10. Molecular hematology

    National Research Council Canada - National Science Library

    Provan, Drew; Gribben, John

    2010-01-01

    ... The molecular basis of hemophilia, 219 Paul LF Giangrande 4 The genetics of acute myeloid leukemias, 42 Carolyn J Owen & Jude Fitzgibbon 19 The molecular basis of von Willebrand disease, 233 Luciano Baronc...

  11. Molecular nuclear imaging of tumoral angio genesis using a rgd-containing tracer, Raft-RGD, targeted at the neo vessel-specific integrin αvβ3

    International Nuclear Information System (INIS)

    Sancey, L.

    2006-06-01

    Tumoral neo-angio genesis targeting is currently a major field of research for the diagnostic and treatment of solid tumors. Endothelial cells from neo vessels over express several specific markers such as the α v β 3 integrin, which binds RGD (-Arg-Gly-Asp-)- containing peptides. We evaluated the potential of a novel radiotracer - RAFT-RGD - for the molecular nuclear imaging of neo vessels. In vitro, the coupling of 4 c(RGDfK) to the RAFT platform resulted in an increased cellular uptake of the tracer by α v β 3 positive cells when compared to c(RGDfK). Furthermore, RAFTRGD has a higher affinity than c(RGDfK) and similar properties for angio genesis inhibition. In vivo, both α v β 3 positive and negative tumors were visible by non invasive whole body planar and tomographic imaging from 30 min to 24 h post-injection, using a gamma camera dedicated to small animal imaging. Despite a lack of significant contrast improvement compare with c(RGDfK), RAFT-RGD could represent a promising tracer for tumoral angio genesis since it could provide invaluable information about tumor development and treatment efficacy in Nuclear Medicine departments. Furthermore, thanks to its chemical structure, RAFT-RGD can be labelled with a variety of radioisotopes including γ and β - emitters, allowing interesting therapeutical applications such as internal targeted radiotherapy. (author)

  12. Theoretical molecular biophysics

    CERN Document Server

    Scherer, Philipp O J

    2017-01-01

    This book gives an introduction to molecular biophysics. It starts from material properties at equilibrium related to polymers, dielectrics and membranes. Electronic spectra are developed for the understanding of elementary dynamic processes in photosynthesis including proton transfer and dynamics of molecular motors. Since the molecular structures of functional groups of bio-systems were resolved, it has become feasible to develop a theory based on the quantum theory and statistical physics with emphasis on the specifics of the high complexity of bio-systems. This introduction to molecular aspects of the field focuses on solvable models. Elementary biological processes provide as special challenge the presence of partial disorder in the structure which does not destroy the basic reproducibility of the processes. Apparently the elementary molecular processes are organized in a way to optimize the efficiency. Learning from nature by means exploring the relation between structure and function may even help to b...

  13. MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium.

    Directory of Open Access Journals (Sweden)

    Matthew F Buas

    Full Text Available Incidence of esophageal adenocarcinoma (EA has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett's esophagus (BE, such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON genome-wide association study (GWAS of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs that potentially affect the biogenesis or biological activity of microRNAs (miRNAs, small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes; miRNA gene loci (234 SNPs, 210 genes; and miRNA-targeted mRNAs (177 SNPs, 158 genes. Nominal associations (P0.50, and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity. This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.

  14. BlueDetect: An iBeacon-Enabled Scheme for Accurate and Energy-Efficient Indoor-Outdoor Detection and Seamless Location-Based Service

    Directory of Open Access Journals (Sweden)

    Han Zou

    2016-02-01

    Full Text Available The location and contextual status (indoor or outdoor is fundamental and critical information for upper-layer applications, such as activity recognition and location-based services (LBS for individuals. In addition, optimizations of building management systems (BMS, such as the pre-cooling or heating process of the air-conditioning system according to the human traffic entering or exiting a building, can utilize the information, as well. The emerging mobile devices, which are equipped with various sensors, become a feasible and flexible platform to perform indoor-outdoor (IO detection. However, power-hungry sensors, such as GPS and WiFi, should be used with caution due to the constrained battery storage on mobile device. We propose BlueDetect: an accurate, fast response and energy-efficient scheme for IO detection and seamless LBS running on the mobile device based on the emerging low-power iBeacon technology. By leveraging the on-broad Bluetooth module and our proposed algorithms, BlueDetect provides a precise IO detection service that can turn on/off on-board power-hungry sensors smartly and automatically, optimize their performances and reduce the power consumption of mobile devices simultaneously. Moreover, seamless positioning and navigation services can be realized by it, especially in a semi-outdoor environment, which cannot be achieved by GPS or an indoor positioning system (IPS easily. We prototype BlueDetect on Android mobile devices and evaluate its performance comprehensively. The experimental results have validated the superiority of BlueDetect in terms of IO detection accuracy, localization accuracy and energy consumption.

  15. BlueDetect: An iBeacon-Enabled Scheme for Accurate and Energy-Efficient Indoor-Outdoor Detection and Seamless Location-Based Service.

    Science.gov (United States)

    Zou, Han; Jiang, Hao; Luo, Yiwen; Zhu, Jianjie; Lu, Xiaoxuan; Xie, Lihua

    2016-02-22

    The location and contextual status (indoor or outdoor) is fundamental and critical information for upper-layer applications, such as activity recognition and location-based services (LBS) for individuals. In addition, optimizations of building management systems (BMS), such as the pre-cooling or heating process of the air-conditioning system according to the human traffic entering or exiting a building, can utilize the information, as well. The emerging mobile devices, which are equipped with various sensors, become a feasible and flexible platform to perform indoor-outdoor (IO) detection. However, power-hungry sensors, such as GPS and WiFi, should be used with caution due to the constrained battery storage on mobile device. We propose BlueDetect: an accurate, fast response and energy-efficient scheme for IO detection and seamless LBS running on the mobile device based on the emerging low-power iBeacon technology. By leveraging the on-broad Bluetooth module and our proposed algorithms, BlueDetect provides a precise IO detection service that can turn on/off on-board power-hungry sensors smartly and automatically, optimize their performances and reduce the power consumption of mobile devices simultaneously. Moreover, seamless positioning and navigation services can be realized by it, especially in a semi-outdoor environment, which cannot be achieved by GPS or an indoor positioning system (IPS) easily. We prototype BlueDetect on Android mobile devices and evaluate its performance comprehensively. The experimental results have validated the superiority of BlueDetect in terms of IO detection accuracy, localization accuracy and energy consumption.

  16. Magnetic resonance molecular imaging in cancer research

    International Nuclear Information System (INIS)

    Wu Peihong; Wang Guohui

    2005-01-01

    The magnetic resonance (MR) molecular imaging can be defined as the in vivo characterization and measurement of biologic processes at the molecular and gene level by the means of MR imaging science. The purpose of molecular imaging is to diagnose tumor more early and specifically and monitor the anti-tumor therapy response. The present researches of molecular imaging focus on the specific MR molecular probes, molecular imaging of tumor angiogenesis, genetic imaging, and magnetic resonance spectroscopic imaging, and so on. Because of it has high spatial resolution and functional imaging, the MR molecular imaging will play an important role in the tumor diagnosis and treatment in 21 century. (authors)

  17. Synergetics of molecular systems

    CERN Document Server

    Lupichev, Lev N; Kadantsev, Vasiliy N

    2014-01-01

    Synergetics is the quantitative study of multicomponent systems that exhibit nonlinear dynamics and cooperativity. This book specifically considers basic models of the nonlinear dynamics of molecular systems and discusses relevant applications in biological physics and the polymer sciences.Emphasis is placed on specific solutions to the dynamical equations that correspond to the coherent formation of spatial-temporal structures, such as solitons, kinks and breathers, in particular. The emergence of these patterns in molecular structures provides a variety of information on their structural pro

  18. Host specificity, molecular phylogeny and morphological differences of Phyllodistomum pseudofolium Nybelin, 1926 and Phyllodistomum angulatum Linstow, 1907 (Trematoda: Gorgoderidae) with notes on Eurasian ruffe as final host for Phyllodistomum spp.

    Science.gov (United States)

    Stunžėnas, Virmantas; Petkevičiūtė, Romualda; Poddubnaya, Larisa G; Stanevičiūtė, Gražina; Zhokhov, Alexander E

    2017-06-06

    Host-specificity patterns are not well-defined for trematodes of the genus Phyllodistomum Braun, 1899. The Eurasian ruffe, Gymnocephalus cernuus L., has been recorded as a definitive host for Phyllodistomum folium (Olfers, 1816), P. angulatum Linstow, 1907 and P. megalorchis Nybelin, 1926 and as the type-host for P. pseudofolium Nybelin (1926). A wide range of other host fishes have been recorded for these species as well. All present host records have been based on light microscopy and the life-cycles of P. pseudofolium, P. angulatum and P. megalorchis are unknown. The validity of P. pseudofolium and P. megalorchis require verification. In this study, rDNA sequences generated from adult Phyllodistomum spp., as well as from larval stages developing in Pisidium amnicum Müller, were analysed to establish the real number of Phyllodistomum species utilizing G. cernuus, and to associate larvae with the corresponding adult forms. Phylogenetic analyses of adult and larval stages of Phyllodistomum spp. based on ITS2 and partial 28S rDNA data allowed the confirmation of the validity of P. pseudofolium. A macrocercous cercaria, known as Phyllodistomum sp. from P. amnicum is genetically identical to adult P. pseudofolium. Phyllodistomum megalorchis obtained from its type-host, Lota lota L., showed no genetic differences from P. angulatum parasitizing Sander lucioperca L. In our analysis, P. pseudofolium, P. angulatum and P. macrocotyle formed a highly supported clade despite the fact that these species appear to be associated with distinct patterns of first intermediate host identity and cercarial morphology. Some morphological differences between gravid specimens of P. pseudofolium and P. angulatum were observed and their SEM tegumental surface topography is described. The results lead us to the perception that macroevolutionary host switching in the genus Phyllodistomum is independent of host phylogeny. This study suggests strict host-specificity (oioxeny) for P

  19. Molecular beams

    International Nuclear Information System (INIS)

    Ramsey, N.F.

    1985-01-01

    This book is a timeless and rather complete theoretical and experimental treatment of electric and magnetic resonance molecular-beam experiments for studying the radio frequency spectra of atoms and molecules. The theory of interactions of the nucleus with atomic and molecular fields is extensively presented. Measurements of atomic and nuclear magnetic moments, electric multipole moments, and atomic fine and hyperfine structure are detailed. Useful but somewhat outdated chapters on gas kinetics, molecular beam design, and experimental techniques are also included

  20. Molecular pharmacognosy.

    Science.gov (United States)

    Huang, LuQi; Xiao, PeiGen; Guo, LanPing; Gao, WenYuan

    2010-06-01

    This article analyzes the background and significance of molecular pharmacognosy, including the molecular identification of medicinal raw materials, phylogenetic evolution of medicinal plants and animals, evaluation and preservation of germplasm resources for medicinal plants and animals, etiology of endangerment and protection of endangered medicinal plants and animals, biosynthesis and bioregulation of active components in medicinal plants, and characteristics and the molecular bases of top-geoherbs.

  1. Mesoporous molecular sieve catalysts

    DEFF Research Database (Denmark)

    Højholt, Karen Thrane

    This thesis deals with a very specific class of molecular sieves known as zeolites. Zeolites are a class of crystalline aluminosilicates characterised by pores or cavities of molecular dimensions as part of their crystal structure. In this work zeolites were modified for the use and understanding...... of different catalytic applications. Primarily the zeolites were modified regarding the porosity and the introduction of metals to the framework. The obtained materials were used as solid acid catalysts, as an inert matrix for stabilising metal nanoparticles and as an anchoring material for molecular metal....... Furthermore, preliminary work was done using mesoporous ZSM-5 zeolites as support material for anchoring molecular CoMo6 species for the application as potential bi-functional catalyst in simultaneous hydrodesulfurisation (HDS) and hydrocracking. HDS activity tests revealed that the anchoring improved...

  2. Description and analysis of assistance in science teaching reform: The reports of Maine's Beacon Center science facilitators and the teachers they help

    Science.gov (United States)

    Kesselheim, Craig

    This study describes the assistance relationship between teachers engaged in school-based science education reform and the full-time facilitators hired to provide their training and support. The model which supplied these facilitators to Maine's "Beacon Center" schools was unique in combining three important design factors: content expertise, the duration of their time on site, and the intensity of the assistance provided. Participant perceptions regarding the usefulness of facilitators' assistance were studied, as were the reported impacts of facilitators' assistance on science teaching practices. Participants in the study were three science facilitators and fourteen teachers. Interviewing was the primary method of data gathering, although daily logs from facilitators also provided essential information. Seven categories of assistance were indicated by participants. Among these were several which assisted teachers' efforts to deliver innovative practices in classroom science. Other categories included one which added to teachers' capacities and one which promoted and guided overall efforts. The seven categories occurred at all three sites, although there were unique patterns in the frequency with which each kind occurred at a site. Factors were described at each site which appear to have affected the forms of assistance which facilitators provided. Teacher perceptions of what made facilitator assistance useful were grouped into two broad categories. Assistance was most useful when it possessed a feature of immediate application or "implementability." Another perception of teachers' related to professional growth value of assistance, including such areas as confidence and content knowledge. Three impacts of facilitator assistance on teachers' practice were also reported in this study: More time spent on science; shifts in science teaching philosophy or instructional preferences; participation in systems-level changes in science teaching. The implications of this

  3. Molecular dynamics

    NARCIS (Netherlands)

    Bergstra, J.A.; Bethke, I.

    2002-01-01

    Molecular dynamics is a model for the structure and meaning of object based programming systems. In molecular dynamics the memory state of a system is modeled as a fluid consisting of a collection of molecules. Each molecule is a collection of atoms with bindings between them. A computation is

  4. Molecular Modeling

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 9; Issue 5. Molecular Modeling: A Powerful Tool for Drug Design and Molecular Docking. Rama Rao Nadendla. General Article Volume 9 Issue 5 May 2004 pp 51-60. Fulltext. Click here to view fulltext PDF. Permanent link:

  5. Molecular motors

    National Research Council Canada - National Science Library

    Schliwa, M

    2003-01-01

    ... and entitled Primitive Motile Systems in Cell Biology, the field has moved from the phenomenological to the mechanistic and from the largely structural to the primarily molecular. We have come to appreciate that at every level of complexity the cell operates through molecular machines. Some of these machines are single molecules that car...

  6. Self-Assembling Molecular Logic Gates Based on DNA Crossover Tiles.

    Science.gov (United States)

    Campbell, Eleanor A; Peterson, Evan; Kolpashchikov, Dmitry M

    2017-07-05

    DNA-based computational hardware has attracted ever-growing attention due to its potential to be useful in the analysis of complex mixtures of biological markers. Here we report the design of self-assembling logic gates that recognize DNA inputs and assemble into crossover tiles when the output signal is high; the crossover structures disassemble to form separate DNA stands when the output is low. The output signal can be conveniently detected by fluorescence using a molecular beacon probe as a reporter. AND, NOT, and OR logic gates were designed. We demonstrate that the gates can connect to each other to produce other logic functions. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Molecular Descriptors

    Science.gov (United States)

    Consonni, Viviana; Todeschini, Roberto

    In the last decades, several scientific researches have been focused on studying how to encompass and convert - by a theoretical pathway - the information encoded in the molecular structure into one or more numbers used to establish quantitative relationships between structures and properties, biological activities, or other experimental properties. Molecular descriptors are formally mathematical representations of a molecule obtained by a well-specified algorithm applied to a defined molecular representation or a well-specified experimental procedure. They play a fundamental role in chemistry, pharmaceutical sciences, environmental protection policy, toxicology, ecotoxicology, health research, and quality control. Evidence of the interest of the scientific community in the molecular descriptors is provided by the huge number of descriptors proposed up today: more than 5000 descriptors derived from different theories and approaches are defined in the literature and most of them can be calculated by means of dedicated software applications. Molecular descriptors are of outstanding importance in the research fields of quantitative structure-activity relationships (QSARs) and quantitative structure-property relationships (QSPRs), where they are the independent chemical information used to predict the properties of interest. Along with the definition of appropriate molecular descriptors, the molecular structure representation and the mathematical tools for deriving and assessing models are other fundamental components of the QSAR/QSPR approach. The remarkable progress during the last few years in chemometrics and chemoinformatics has led to new strategies for finding mathematical meaningful relationships between the molecular structure and biological activities, physico-chemical, toxicological, and environmental properties of chemicals. Different approaches for deriving molecular descriptors here reviewed and some of the most relevant descriptors are presented in

  8. Molecular geometry

    CERN Document Server

    Rodger, Alison

    1995-01-01

    Molecular Geometry discusses topics relevant to the arrangement of atoms. The book is comprised of seven chapters that tackle several areas of molecular geometry. Chapter 1 reviews the definition and determination of molecular geometry, while Chapter 2 discusses the unified view of stereochemistry and stereochemical changes. Chapter 3 covers the geometry of molecules of second row atoms, and Chapter 4 deals with the main group elements beyond the second row. The book also talks about the complexes of transition metals and f-block elements, and then covers the organometallic compounds and trans

  9. Identifying Anomalous Port-Specific Network Behavior

    Science.gov (United States)

    2010-05-01

    Backscatter 4.3 6.2 1.3 Connection Attempt 4.3 7.6 3.3 User Non-Web activity 3.9 22.0 11.9 SYN flood 3.6 9.0 4.4 Beaconing (Non-443) 3.6 20.5 5.0 Large...flagged events are composed of suspicious events such as beaconing (keep- alives on non-standard ports), SYN floods , scanning, and large data...systems. A port is an integer value between 0 and 65535 that represents a logical connection place for Transmission Control Protocol ( TCP ) and User

  10. Molecular ecology of aquatic microbes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    Abstracts of reports are presented from a meeting on Molecular Ecology of Aquatic Microbes. Topics included: opportunities offered to aquatic ecology by molecular biology; the role of aquatic microbes in biogeochemical cycles; characterization of the microbial community; the effect of the environment on aquatic microbes; and the targeting of specific biological processes.

  11. Molecular Electronics

    DEFF Research Database (Denmark)

    Jennum, Karsten Stein

    This thesis includes the synthesis and characterisation of organic compounds designed for molecular electronics. The synthesised organic molecules are mainly based on two motifs, the obigo(phenyleneethynylenes) (OPE)s and tetrathiafulvalene (TTF) as shown below. These two scaffolds (OPE and TTF......) are chemically merged together to form cruciform-like structures that are an essential part of the thesis. The cruciform molecules were subjected to molecular conductance measurements to explore their capability towards single-crystal field-effect transistors (Part 1), molecular wires, and single electron...... transistors (Part 2). The synthetic protocols rely on stepwise Sonogashira coupling reactions. Conductivity studies on various OPE-based molecular wires reveal that mere OPE compounds have a higher electrical resistance compared to the cruciform based wires (up to 9 times higher). The most spectacular result...

  12. Molecular sciences

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    The research in molecular sciences summarized includes photochemistry, radiation chemistry, geophysics, electromechanics, heavy-element oxidizers , heavy element chemistry collisions, atoms, organic solids. A list of publications is included

  13. Cardiovascular Molecular Imaging

    International Nuclear Information System (INIS)

    Lee, Kyung Han

    2009-01-01

    Molecular imaging strives to visualize processes in living subjects at the molecular level. Monitoring biochemical processes at this level will allow us to directly track biological processes and signaling events that lead to pathophysiological abnormalities, and help make personalized medicine a reality by allowing evaluation of therapeutic efficacies on an individual basis. Although most molecular imaging techniques emerged from the field of oncology, they have now gradually gained acceptance by the cardiovascular community. Hence, the availability of dedicated high-resolution small animal imaging systems and specific targeting imaging probes is now enhancing our understanding of cardiovascular diseases and expediting the development of newer therapies. Examples include imaging approaches to evaluate and track the progress of recent genetic and cellular therapies for treatment of myocardial ischemia. Other areas include in vivo monitoring of such key molecular processes as angiogenesis and apoptosis. Cardiovascular molecular imaging is already an important research tool in preclinical experiments. The challenge that lies ahead is to implement these techniques into the clinics so that they may help fulfill the promise of molecular therapies and personalized medicine, as well as to resolve disappointments and controversies surrounding the field

  14. Specific phobia.

    Science.gov (United States)

    Silverman, Wendy K; Moreno, Jacqueline

    2005-10-01

    This article describes specific phobia of childhood and its clinical presentation, discusses issues related to the differential diagnosis of specific phobia, considers the issue of comorbidity among phobic and anxiety disorders and developmental trends in the manifestation of fears, summarizes the epidemiology, causes, and course of specific phobia, and presents assessment and treatment issues. Finally, a case study is offered that serves to illuminate the major topics outlined in the article.

  15. The ANTARES optical beacon system

    NARCIS (Netherlands)

    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.; 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.; Compere, 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.; Hernandez-Rey, J. J.; Hoessl, J.; Hoffman, C.; Hogenbirk, J.; Hubbard, J. R.; Jaquet, 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.; Van Suu, A. Le; Lefevre, D.; Legou, T.; Lelaizant, G.; Lim, G.; Lo Presti, D.; Löhner, H.; Loucatos, S.; Louis, F.; Lucarelli, F.; Lyashuk, V.; Marcelin, M.; Margiotta, A.; Masullo, R.; Mazeas, 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.; Rethore, 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.; Wijnker, G.; Huberts, P. de Witt; Wobbe, G.; de Wolf, E.; Yao, A-F.; Zaborov, D.; Zaccone, H.; Zornoza, J. D.; Zuniga, J.; van Wijk, R.

    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

  16. Underwater Acoustic Beacon Location System

    Science.gov (United States)

    2016-12-23

    distance is the predicted detection range R based on consideration of Equations (1) and (2) together with the parameters for SL, NL, DI, DT and alpha ...R nvnv nvnv ia               cossin0 sincos0 0012 (12) [0091] Finally, the positions on the seafloor 500 in the array...numerical values of the beam pattern projected onto the seafloor are divided by the sum of all of the (non- zero ) numerical values projected onto the

  17. Beacons of the Experience Economy

    DEFF Research Database (Denmark)

    Delica, Kristian Nagel

    2014-01-01

    This essay outlines the boundaries among various interests in the library sector; among positions that prioritize libraries as aesthetically appealing junctions of the experience economy versus positions that prioritize the library as a community forum. The main emphasis is placed on developments...... in the Danish library sector with the additional inclusion of international examples....

  18. Targeted molecular imaging

    International Nuclear Information System (INIS)

    Kim, E. Edmund

    2003-01-01

    Molecular imaging aims to visualize the cellular and molecular processes occurring in living tissues, and for the imaging of specific molecules in vivo, the development of reporter probes and dedicated imaging equipment is most important. Reporter genes can be used to monitor the delivery and magnitude of therapeutic gene transfer, and the time variation involved. Imaging technologies such as micro-PET, SPECT, MRI and CT, as well as optical imaging systems, are able to non-invasively detect, measure, and report the simultaneous expression of multiple meaningful genes. It is believed that recent advances in reporter probes, imaging technologies and gene transfer strategies will enhance the effectiveness of gene therapy trials

  19. Molecular imaging in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Schober, Otmar; Riemann, Burkhard (eds.) [Universitaetsklinikum Muenster (Germany). Klinik fuer Nuklearmedizin

    2013-02-01

    Considers in detail all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. Examines technological issues and probe design. Discusses preclinical studies in detail, with particular attention to multimodality imaging. Presents current clinical use of PET/CT, SPECT/CT, and optical imagingWritten by acknowledged experts. The impact of molecular imaging on diagnostics, therapy, and follow-up in oncology is increasing significantly. The process of molecular imaging includes key biotarget identification, design of specific molecular imaging probes, and their preclinical evaluation, e.g., in vivo using small animal studies. A multitude of such innovative molecular imaging probes have already entered clinical diagnostics in oncology. There is no doubt that in future the emphasis will be on multimodality imaging in which morphological, functional, and molecular imaging techniques are combined in a single clinical investigation that will optimize diagnostic processes. This handbook addresses all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. The first section is devoted to technology and probe design, and examines a variety of PET and SPECT tracers as well as multimodality probes. Preclinical studies are then discussed in detail, with particular attention to multimodality imaging. In the third section, diverse clinical applications are presented, and the book closes by looking at future challenges. This handbook will be of value to all who are interested in the revolution in diagnostic oncology that is being brought about by molecular imaging.

  20. Molecular fountain.

    Energy Technology Data Exchange (ETDEWEB)

    Strecker, Kevin E.; Chandler, David W.

    2009-09-01

    A molecular fountain directs slowly moving molecules against gravity to further slow them to translational energies that they can be trapped and studied. If the molecules are initially slow enough they will return some time later to the position from which they were launched. Because this round trip time can be on the order of a second a single molecule can be observed for times sufficient to perform Hz level spectroscopy. The goal of this LDRD proposal was to construct a novel Molecular Fountain apparatus capable of producing dilute samples of molecules at near zero temperatures in well-defined user-selectable, quantum states. The slowly moving molecules used in this research are produced by the previously developed Kinematic Cooling technique, which uses a crossed atomic and molecular beam apparatus to generate single rotational level molecular samples moving slowly in the laboratory reference frame. The Kinematic Cooling technique produces cold molecules from a supersonic molecular beam via single collisions with a supersonic atomic beam. A single collision of an atom with a molecule occurring at the correct energy and relative velocity can cause a small fraction of the molecules to move very slowly vertically against gravity in the laboratory. These slowly moving molecules are captured by an electrostatic hexapole guiding field that both orients and focuses the molecules. The molecules are focused into the ionization region of a time-of-flight mass spectrometer and are ionized by laser radiation. The new molecular fountain apparatus was built utilizing a new design for molecular beam apparatus that has allowed us to miniaturize the apparatus. This new design minimizes the volumes and surface area of the machine allowing smaller pumps to maintain the necessary background pressures needed for these experiments.

  1. Peptide binding specificity of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Sandhu, N.; Duus, K.; Jorgensen, C.S.

    2007-01-01

    Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length and composit...

  2. Molecular machines open cell membranes.

    Science.gov (United States)

    García-López, Víctor; Chen, Fang; Nilewski, Lizanne G; Duret, Guillaume; Aliyan, Amir; Kolomeisky, Anatoly B; Robinson, Jacob T; Wang, Gufeng; Pal, Robert; Tour, James M

    2017-08-30

    Beyond the more common chemical delivery strategies, several physical techniques are used to open the lipid bilayers of cellular membranes. These include using electric and magnetic fields, temperature, ultrasound or light to introduce compounds into cells, to release molecular species from cells or to selectively induce programmed cell death (apoptosis) or uncontrolled cell death (necrosis). More recently, molecular motors and switches that can change their conformation in a controlled manner in response to external stimuli have been used to produce mechanical actions on tissue for biomedical applications. Here we show that molecular machines can drill through cellular bilayers using their molecular-scale actuation, specifically nanomechanical action. Upon physical adsorption of the molecular motors onto lipid bilayers and subsequent activation of the motors using ultraviolet light, holes are drilled in the cell membranes. We designed molecular motors and complementary experimental protocols that use nanomechanical action to induce the diffusion of chemical species out of synthetic vesicles, to enhance the diffusion of traceable molecular machines into and within live cells, to induce necrosis and to introduce chemical species into live cells. We also show that, by using molecular machines that bear short peptide addends, nanomechanical action can selectively target specific cell-surface recognition sites. Beyond the in vitro applications demonstrated here, we expect that molecular machines could also be used in vivo, especially as their design progresses to allow two-photon, near-infrared and radio-frequency activation.

  3. Molecular machines open cell membranes

    Science.gov (United States)

    García-López, Víctor; Chen, Fang; Nilewski, Lizanne G.; Duret, Guillaume; Aliyan, Amir; Kolomeisky, Anatoly B.; Robinson, Jacob T.; Wang, Gufeng; Pal, Robert; Tour, James M.

    2017-08-01

    Beyond the more common chemical delivery strategies, several physical techniques are used to open the lipid bilayers of cellular membranes. These include using electric and magnetic fields, temperature, ultrasound or light to introduce compounds into cells, to release molecular species from cells or to selectively induce programmed cell death (apoptosis) or uncontrolled cell death (necrosis). More recently, molecular motors and switches that can change their conformation in a controlled manner in response to external stimuli have been used to produce mechanical actions on tissue for biomedical applications. Here we show that molecular machines can drill through cellular bilayers using their molecular-scale actuation, specifically nanomechanical action. Upon physical adsorption of the molecular motors onto lipid bilayers and subsequent activation of the motors using ultraviolet light, holes are drilled in the cell membranes. We designed molecular motors and complementary experimental protocols that use nanomechanical action to induce the diffusion of chemical species out of synthetic vesicles, to enhance the diffusion of traceable molecular machines into and within live cells, to induce necrosis and to introduce chemical species into live cells. We also show that, by using molecular machines that bear short peptide addends, nanomechanical action can selectively target specific cell-surface recognition sites. Beyond the in vitro applications demonstrated here, we expect that molecular machines could also be used in vivo, especially as their design progresses to allow two-photon, near-infrared and radio-frequency activation.

  4. Molecular modeling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-01-01

    Full Text Available The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and the exponential growth of the knowledge of protein structures have made it possible for organic compounds to be tailored to decrease the harmful side effects and increase the potency. This article provides a detailed description of the techniques employed in molecular modeling. Molecular modeling is a rapidly developing discipline, and has been supported by the dramatic improvements in computer hardware and software in recent years.

  5. Molecular physics

    CERN Document Server

    Demtröder, Wolfgang

    2008-01-01

    The richly illustrated book comprehensively explains the important principles of diatomic and polyatomic molecules and their spectra in two separate, distinct parts. The first part concentrates on the theoretical aspects of molecular physics, such as the vibration, rotation, electronic states, potential curves, and spectra of molecules. The different methods of approximation for the calculation of electronic wave functions and their energy are also covered. The introduction of basics terms used in group theory and their meaning in molecular physics enables an elegant description of polyatomic

  6. Molecular pathways

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine Terra

    2014-01-01

    that 45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection...... of fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases. Clin Cancer Res; 20(14); 3637-43. ©2014 AACR....

  7. Nanomechanical molecular devices made of DNA origami.

    Science.gov (United States)

    Kuzuya, Akinori; Ohya, Yuichi

    2014-06-17

    CONSPECTUS: Eight years have passed since the striking debut of the DNA origami technique ( Rothemund, P. W. K. Nature 2006 , 440 , 297 - 302 ), in which long single-stranded DNA is folded into a designed nanostructure, in either 2D or 3D, with the aid of many short staple strands. The number of proposals for new design principles for DNA origami structures seems to have already reached a peak. It is apparent that DNA origami study is now entering the second phase of creating practical applications. The development of functional nanomechanical molecular devices using the DNA origami technique is one such application attracting significant interest from researchers in the field. Nanomechanical DNA origami devices, which maintain the characteristics of DNA origami structures, have various advantages over conventional DNA nanomachines. Comparatively high assembly yield, relatively large size visible via atomic force microscopy (AFM) or transmission electron microscopy (TEM), and the capability to assemble multiple functional groups with precision using multiple staple strands are some of the advantages of the DNA origami technique for constructing sophisticated molecular devices. This Account describes the recent developments of such nanomechanical DNA origami devices and reviews the emerging target of DNA origami studies. First, simple "dynamic" DNA origami structures with transformation capability, such as DNA origami boxes and a DNA origami hatch with structure control, are briefly summarized. More elaborate nanomechanical DNA origami devices are then reviewed. The first example describes DNA origami pinching devices that can be used as "single-molecule" beacons to detect a variety of biorelated molecules, from metal ions at the size of a few tens of atomic mass number units to relatively gigantic proteins with a molecular mass greater than a hundred kilodaltons, all on a single platform. Clamshell-like DNA nanorobots equipped with logic gates can discriminate

  8. Phylogenetic molecular function annotation

    International Nuclear Information System (INIS)

    Engelhardt, Barbara E; Jordan, Michael I; Repo, Susanna T; Brenner, Steven E

    2009-01-01

    It is now easier to discover thousands of protein sequences in a new microbial genome than it is to biochemically characterize the specific activity of a single protein of unknown function. The molecular functions of protein sequences have typically been predicted using homology-based computational methods, which rely on the principle that homologous proteins share a similar function. However, some protein families include groups of proteins with different molecular functions. A phylogenetic approach for predicting molecular function (sometimes called 'phylogenomics') is an effective means to predict protein molecular function. These methods incorporate functional evidence from all members of a family that have functional characterizations using the evolutionary history of the protein family to make robust predictions for the uncharacterized proteins. However, they are often difficult to apply on a genome-wide scale because of the time-consuming step of reconstructing the phylogenies of each protein to be annotated. Our automated approach for function annotation using phylogeny, the SIFTER (Statistical Inference of Function Through Evolutionary Relationships) methodology, uses a statistical graphical model to compute the probabilities of molecular functions for unannotated proteins. Our benchmark tests showed that SIFTER provides accurate functional predictions on various protein families, outperforming other available methods.

  9. Molecular Origami

    Indian Academy of Sciences (India)

    Molecular Origami. Modular Construction of Platonic Solids as Models for Reversible ... by Nature using a modular protocol wherein each of the mod- ules holds latent ... The Design Principle. All the designs can be made from thick square sheets of the size. 20 cm x 20 cm (readily available A4 size photocopy paper, from.

  10. Molecular gastronomy

    Science.gov (United States)

    This, Hervé

    2005-01-01

    For centuries, cooks have been applying recipes without looking for the mechanisms of the culinary transformations. A scientific discipline that explores these changes from raw ingredients to eating the final dish, is developing into its own field, termed molecular gastronomy. Here, one of the founders of the discipline discusses its aims and importance.

  11. Molecular farming

    NARCIS (Netherlands)

    Merck, K.B.; Vereijken, J.M.

    2006-01-01

    Molecular Farming is a new and emerging technology that promises relatively cheap and flexible production of large quantities of pharmaceuticals in genetically modified plants. Many stakeholders are involved in the production of pharmaceuticals in plants, which complicates the discussion on the

  12. Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

    Science.gov (United States)

    Lee, Roy E; Henricks, Walter H; Sirintrapun, Sahussapont J

    2016-03-01

    Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

  13. Expedient multi-step synthesis of organometallic complexes of Tc and Re in high effective specific activity. A new platform for the production of molecular imaging and therapy agents.

    Science.gov (United States)

    Causey, Patrick W; Besanger, Travis R; Schaffer, Paul; Valliant, John F

    2008-09-15

    For over thirty years, instant labeling kits which involve no purification steps have been the only method used to prepare (99m)Tc radiopharmaceuticals for clinical studies. To address the limitations imposed by instant kits, which is hindering the development of molecularly targeted Tc- and Re-based imaging and therapy agents, a new strategy for the rapid multistep synthesis and purification of organometallic technetium-based molecular probes and corresponding rhenium-based therapeutic analogues was developed. Beginning with MO4(-) (M = (99m)Tc, (186/188)Re), the carbonyl precursor [M(CO)3(H2O)3](+) was synthesized in 3 min in quantitative yield in a microwave reactor. A dipicolyl ligand was added and the chelate complex was formed in high yield in 2 min using microwave heating at 150 degrees C. This was followed by a new purification strategy to remove unlabeled ligand which entailed using a copper resin/C18 solid phase extraction protocol giving the desired product in greater than 78% decay corrected yield (dcy). Conversion to the corresponding succinimidyl active ester was achieved following a 5 min microwave irradiation at 120 degrees C and C18 solid phase extraction purification in 60% dcy. A series of amides were prepared subsequently by microwave heating at 120 degrees C for 5 min producing the desired targets in greater than 86% dcy. The reported method represents a move away from traditional instant kits toward more versatile platform synthesis and purification technologies that are better suited for producing modern molecular imaging and therapy agents.

  14. Molecular Rotors as Switches

    Directory of Open Access Journals (Sweden)

    Kang L. Wang

    2012-08-01

    Full Text Available The use of a functional molecular unit acting as a state variable provides an attractive alternative for the next generations of nanoscale electronics. It may help overcome the limits of conventional MOSFETd due to their potential scalability, low-cost, low variability, and highly integratable characteristics as well as the capability to exploit bottom-up self-assembly processes. This bottom-up construction and the operation of nanoscale machines/devices, in which the molecular motion can be controlled to perform functions, have been studied for their functionalities. Being triggered by external stimuli such as light, electricity or chemical reagents, these devices have shown various functions including those of diodes, rectifiers, memories, resonant tunnel junctions and single settable molecular switches that can be electronically configured for logic gates. Molecule-specific electronic switching has also been reported for several of these device structures, including nanopores containing oligo(phenylene ethynylene monolayers, and planar junctions incorporating rotaxane and catenane monolayers for the construction and operation of complex molecular machines. A specific electrically driven surface mounted molecular rotor is described in detail in this review. The rotor is comprised of a monolayer of redox-active ligated copper compounds sandwiched between a gold electrode and a highly-doped P+ Si. This electrically driven sandwich-type monolayer molecular rotor device showed an on/off ratio of approximately 104, a read window of about 2.5 V, and a retention time of greater than 104 s. The rotation speed of this type of molecular rotor has been reported to be in the picosecond timescale, which provides a potential of high switching speed applications. Current-voltage spectroscopy (I-V revealed a temperature-dependent negative differential resistance (NDR associated with the device. The analysis of the device